WELCOME, EVERYONE, TO THE 15th MEETING OF THE BRAIN NEUROETHICS WORKING GROUP, NEWG FOR SHORT. I WANT TO ESPECIALLY EXTEND A WARM WELCOME TO OUR WORKING GROUP CO-CHAIRS, DOCTORS NINA FARAHANY AND CHRISTINE GRADY, AS WELL AS ALL THE MEMBERS OF THE WORKING GROUP AND OUR INVITED SPEAKERS AND PANELISTS WHO ARE JOINING US TODAY. I'M ANDREA BECKEL-MITCHENER, DEPUTY DIRECTOR OF NIH BRAIN INITIATIVE, DESIGNATED FEDERAL OFFICIAL FOR TODAY'S MEETING. MOST OF YOU KNOW, THE NEUROETHICS WORKING GROUP IS NOT A FORMAL ADVISORY GROUP, LIKE "BRAIN"'S MULTI-COUNCIL WORKING GROUP. THE NEWG IS A WORKING GROUP OF THE ADVISORY COUNCILS OF THE TEN NIH INSTITUTES THAT PARTICIPATE IN THE BRAIN INITIATIVE, AND NEWG WAS ESTABLISHED BECAUSE OF THE NEED FOR INPUT ON NEUROETHICS CONSIDERATIONS RELATED TO THE RESEARCH SUPPORTED THROUGH THE BRAIN INITIATIVE. SO, THE NEWG WILL DELIBERATE ON ETHICAL QUESTIONS THAT COME UP IN THE CONTEXT OF BRAIN INITIATIVE RESEARCH AND CAN OFFER POINTS TO CONSIDER. TODAY WE ONCE AGAIN HAVE A VIRTUAL MEETING, AND SLIGHTLY ABRIDGED FORMAT, BUT WE'RE HOPEFUL WE'LL BE ABLE TO MEET IN PERSON AGAIN SOON. WE'LL TODAY HAVE AN UPDATE FROM THE "BRAIN" DIRECTOR ON THE NIH BRAIN INITIATIVE, WE'LL BEGIN WITH THAT, FOLLOWING THAT SPENDING TIME THINKING ABOUT HEALTH-RELATED TECHNOLOGIES THAT AFFECT THE BRAIN. FIRST BY HEARING ABOUT TWO RECENT CASE STUDIES, AFTER THE BREAK WE'LL BE LOOKING FORWARD TO THE DISCUSSION TO THINK ABOUT THE STARTING PLACE, IF ANY, FOR NEWG ENGAGEMENT ON HEALTH-RELATED APPLICATIONS OF TECHNOLOGIES THAT MAY AFFECT THE BRAIN. AND AS USUAL WE'LL WRAP UP THE OPEN SESSION BY HEARING ANY UPDATES FROM NEWG MEMBERS ON WHAT EVERYONE HAS BEEN UP TO IN THE NEUROETHICS SPACE. BEFORE WE GET STARTED A FEW HOUSEKEEPING ITEMS. THIS OPEN SESSION IS LIVE TO TO ARCHIVE LATER ON THE WEBSITES. PLEASE MUTE YOUR LINE AND TURN OFF YOUR VIDEO WHEN NOT SPEAKING. DURING DISCUSSIONS, FOR NEWG MEMBERS, PLEASE TURN ON YOUR VIDEO AND USE THE RAISE-HAND OPTION IF YOU HAVE QUESTIONS OR COMMENTS, YOU'LL BE CALLED ON UPON TO UNMUTE IN TURN. OPT FOR THE RAISE-HAND FUTURE SO VIDEOCAST ATTENDEES CAN HEAR AND SEE THE QUESTIONS. WE KNOW EVERYONE IS BUSY. WE REALLY APPRECIATE YOUR TIME AND VALUE YOUR INPUT TODAY. FINALLY, NONE OF THIS CAN HAPPEN WITHOUT THE FABULOUS TEAM HERE INCLUDING STAFF FROM ACROSS THE BRAIN INSTITUTES AS WELL AS COLLEAGUES HELPING WITH THE BROADCAST. I ESPECIALLY WANT TO THANK DR. NINA HSU, COMMITTEE SPECIALIST, WITH DR. SASKIA HENDRIKS, CONSULTANT, AND DR. JOHN NGAI, BRAIN DIRECTOR, FOR HIS SUPPORT OF NEUROETHICS BROADLY. I'M GOING TO TURN IT OVER TO ONE OF THE CO-CHAIRS, DR. GRADY. IT IS ALL YOURS. >>THANK YOU, AND WELCOME. I EXTEND MY THANK YOU AND WELCOME TO THE MEMBERS OF THE NEWG AND OUR INVITED SPEAKERS AS WELL. THANK YOU FOR BEING HERE TODAY. I KNOW EVERYBODY'S BUSY. WE HAVE A FULL AGENDA, AN EXCITING AGENDA. I THINK I'M REALLY LOOKING FORWARD TO OUR DISCUSSIONS AND DELIBERATIONS TODAY. BUT FIRST I JUST WANT TO TAKE A MINUTE TO RECOGNIZE THAT THIS IS THE FIRST MEETING OF THE NEUROETHICS WORKING GROUP WITH NINA FARAHANY AS OUR CO-CHAIR, AND I WANT TO RECOGNIZE PUBLICLY IT IS WONDERFUL TO HAVE HER AS A CO-CHAIR. WE'RE ALL VERY FORTUNATE. AS MANY OF YOU KNOW NINA IS THE ROBINSON O. EVERETT DISTINGUISHED PROFESSOR OF LAW AND PHILOSOPHY AT DUKE UNIVERSITY LAW SCHOOL, IMMEDIATE PAST PRESIDENT OF NEUROETHICS SOCIETY AND WEARS OTHER HATS IN ADDITION TO HER WORK WITH US WITH THE NEUROETHICS WORKING GROUP. TODAY SHE'S GOING TO LEAD OUR FIRST DISCUSSION ON THE VARIOUS HEALTH-RELATED WAYS THE BRAIN CAN BE AFFECTED. BUT BEFORE WE DO THAT, I'M GOING TO TURN IT OVER TO JOHN NGAI, THE BRAIN DIRECTOR, TO GIVE US HIS UPDATE ON BRAIN INITIATIVE. THANK YOU, JOHN. >>THANKS VERY MUCH, CHRISTINE. WELCOME TO ALL. DELIGHTED TO HAVE YOU ALL HERE. ALSO WELCOMING OUR NEWG CO-CHAIR, DR. NINA FARAHANY. THE LUNAR NEW YEAR IS OFF TO A ROCKY START BUT I WISH YOU ALL A HAPPIER AND PROSPEROUS YEAR OF THE RABBIT. SO LET'S SEE IF I CAN DO THIS CORRECTLY. I JUST HAVE A FEW BRIEF COMMENTS AS CRITICAL CONDITION -- CHRISTINE SAID, WE HAVE A PACKED AGENDA. ARE WE SEEING THE CORRECT SCREEN, FOLKS? YES, NO? >>YES, LOOKS GOOD. >>PERFECT. >>A QUICK UPDATE, OF WHAT'S HAPPENING IN AND AROUND NEUROETHICS AND BRAIN, I WANT TO CALL YOUR ATTENTION TO THIS CALL FOR SUPPLEMENT APPLICATIONS, NOT FROM THE BRAIN INITIATIVE PER SE, BUT FROM THE NIH'S OFFICE OF SCIENCE POLICY OUT OF THE OFFICE OF DIRECTOR, WHICH IS SEEKENING APPLICATIONS FOR SUPPLEMENTS TO CURRENTLY FUNDED AWARDS, INCLUDING BRAIN INITIATIVE FUNDED AWARDS, WHERE THE AIM IS ENHANCE IMPACT OF CURRENTLY FUNDED PROJECTS INTEGRATING BIOETHICS PERSPECTIVES AND APPROACHES INTO THEM. HERE AT BRAIN WE FUND ALL KINDS OF DIFFERENT PROJECTS THAT COULD BE HIGHLY RELEVANT FOR SUCH A SUPPLEMENT. WE'VE TALKED HERE AND ELSEWHERE ABOUT THE ETHICAL IMPLICATIONS OF ACCESS AND USE OF EMERGING AND LEADING EDGE NEUROTECHNOLOGIES, HOW THEY RELATE TO IMPORTANT ISSUES OF INFORMED CONSENT. ONE EXAMPLE, WE'VE TALKED ABOUT THE BARRIERS TO ACCESS THAT INVOLVE VARIOUS FACTORS INCLUDING CULTURAL DIFFERENCES AND SOCIOECONOMIC FACTORS. WE ALSO HAVE TALKED ABOUT RESEARCH ON LONG-TERM OBLIGATIONS, OR POST OR CONTINUING OBLIGATIONS AND I'LL TOUCH ON THAT IN A MOMENT IN A DIFFERENT CONTEXT, AND VERY IMPORTANT CROSSING SUBJECTS, THE ISSUE OF WHAT IT MEANS TO START COLLECTING OR TO BE COLLECTING HUMAN NEURAL DATA AND WHAT CAN WE DO TO ASSURE SAFETY AND PRIVACY AND GUARD AGAINST UNINTENDED USES. SO THESE ARE ROLLING SUBMISSION APPLICATIONS, REVIEW WILL TAKE PLACE SOON SO THESE ARE DUE FEBRUARY 17. YOU DON'T HAVE A WHOLE LOT OF TIME BUT IF YOU'RE INTERESTED I WOULD DEFINITELY LOOK INTO THIS. THE IDEA IS SUPPORT RESEARCH ABOUT BOTH ETHICAL ISSUES TO DEVELOP OR SUPPORT AND EVIDENCE BASE TO INFORM FUTURE POLICY DECISIONS OR BE USED TO DEVELOP OTHER AUGMENT BIOETHICS RESEARCH CAPACITY. HERE AT BRAIN WE DO SUPPORT SCHOLARLY WORK IN THE NEUROETHICS FIELD. CHALLENGES IN MANY AREAS OF WHAT WE DO, THIS IS REALLY A GREAT OPPORTUNITY FOR SOME OF OUR BRAIN INVESTIGATORS. WE'RE INTERESTED AT NIH IN MAKING AN INVESTMENT IN INTEGRATING BIOET ETHICS RESEARCH TO FACILITATE PUBLIC ENGAGEMENT AND PARTICIPATION BUILDING THERE'S WITH THE RESEARCH ENTERPRISE. TAKE A LOOK AT THAT IF YOU'RE INTERESTED. FOR YOU FOLKS WITH CURRENTLY FUNDED BRAIN GRANTS THIS IS A GREAT OPPORTUNITY TO SUPPLEMENT YOUR WORK. IT HAS TO BE WITHIN THE SCOPE OF THE GENERAL SCOPE OF THE CURRENT AWARDS AS WITH ANY SUPPLEMENT TYPE OF PROJECT, BUT REALLY COULD BE A GREAT OPPORTUNITY TO EXPAND YOUR PROJECT IN AN INTERESTING AND VERY IMPORTANT WAY. I MENTIONED CONTINUING TRIAL RESPONSIBILITIES, THIS IS AN ISSUE AROUND WHAT HAPPENS AFTER A TRIAL IS OVER OR SOMETHING HAPPENS WHERE THE MANUFACTURERS OR FOLKS THAT ARE PARTICIPATING IN THE STUDIES AS RESEARCHERS ARE NO LONGER AVAILABLE. AND PARTICULARLY ACUTE CASE OF POST TRIAL RESPONSIBILITIES INVOLVES SO CALLED INTRACRANIAL APPROACHES WHERE WE'RE ACTUALLY PLACING ELECTRODES AND SUCH IN PEOPLE'S BRAINS. WE HELD A WORKSHOP, OH GOSH, ALREADY BACK IN MAY OF 2022, AND WE BROUGHT IN WHAT WE FELT WERE ALL THE STAKE HOLDERS WHO NEEDED TO BE INVOLVED IN THIS DISCUSSION ABOUT HOW TO CARE FOR OUR PATIENTS, OUR HUMAN PARTNERS, IN THESE ENDEAVORS. AND WE INCLUDED DEVICE MANUFACTURERS, INVESTIGATORS, THE RESEARCHERS THEMSELVES AND THE SURGEONS, ALSO FOLKS FROM THE REGULATORY SIDE, PATIENT ADVOCATES. I MEAN, THE PATIENTS AND ADVOCATES, THE MOST IMPORTANT VOICE IN THE ROOM ARGUABLY COMES FROM THE FOLKS BEING TESTED WITH THESE NEW DEVICES AND TREATMENTS. AND THEIR CAREGIVERS AND FAMILIES. INSURANCE PROVIDERS, WE HAD FOLKS FROM DIFFERENT FEDERAL AGENCIES, REALLY TO SEE HOW BEST TO COVER THE RESPONSIBILITIES THAT WE HAVE FOR THESE PATIENTS AND RESEARCH PARTICIPANTS, AND THERE WAS A CONSENSUS THAT THERE WAS A NEED, LESS OF A CONSENSUS ABOUT WHO ACTUALLY WOULD BE RESPONSIBLE FOR THESE DIFFERENT POST-TRIAL OR CONTINUING TRIAL NEEDS, BUT I THINK WE MADE GRADE HEADWAY IN IDENTIFYING THE ISSUES. WE I THINK CAME TO -- AT LEAST I CAME TO THE CONCLUSION THAT WE NEEDED TO MOVE THE NEEDLE SOMEWHAT, IF NOT TO PERFECTION AT LEAST TOWARD PERFECTION. RIGHT NOW THE CONVERSATIONS ARE ONGOING. WE HAVE FORMED -- WE MEANING THE OFFICE OF SCIENCE POLICY, OFFICE OF EXTRAMURAL RESEARCH AT NIH, HAS ACTUALLY FORMED A WORKING GROUP TO REALLY EXAMINE WHAT WE CAN AND CANNOT DO TO MAKE THIS A BETTER SITUATION SO THAT WE CAN ASSURE THAT THE FOLKS WHO PARTICIPATE IN THESE TRIALS ARE PROPERLY CARED FOR TO THE BEST OF OUR ABILITIES. STAY TUNED. WE'RE WORKING ON THIS LONG PROCESS. IT'S A COMPLEX SET OF ISSUES THAT NOT ONLY INVOLVE INVASIVE BRAIN IMPLANTS BUT ALSO REALLY IN PRINCIPAL ALSO AFFECTS MANY OTHER KINDS OF CLINICAL TRIALS. STAY TUNED. WE'RE HARD AT WORK ON THIS AND APPRECIATE INPUT FROM ALL THE STAKEHOLDERS WE'VE RECEIVED SO FAR. I THOUGHT I WOULD TOUCH VERY, VERY BRIEFLY ON SOME COOL SCIENCE THAT HAS ETHICAL IMPLICATIONS IN THE BRAIN SPACE, AS IT WERE. I DON'T KNOW THAT WE'LL HAVE MUCH TIME TO DIVE IN. THE SECOND CASE I'LL TALK ABOUT ACTUALLY IS VERY MUCH RELEVANT TO THE DISCUSSION WE'LL HAVE IN A MOMENT. HERE IS JUST A PAPER FROM THE DEVORE AND KUZUM LOOKING AT ORGANOIDS IMPLANTED INTO ADULT STAGE MICE. THERE ARE A COUPLE COOL THINGS. ONE IS THAT THEY DID IT AND USED VARIOUS MEASURES TO SHOW THAT THESE HUMAN-DERIVED BRAIN ORGANOIDS COULD ACTUALLY INCORPORATE INTO A MOUSE BRAIN AND BECOME PART OF THE LOCAL NETWORK, AND THE OTHER COOL THING WAS TECHNOLOGY I BELIEVED DEVELOPED BY THE DEVORE LAB WHERE THEY DEVELOPED THIS OPTICALLY CLEAR ELECTRODE THEY COULD PLACE OVER THE IMPLANT INCLUDING PART OF THE SURROUNDING TISSUE, SO THEY COULD ACTUALLY LOOK TO SEE HOW WELL THIS ORGANOID IMPLANT COULD INCORPORATE INTO THE RECIPIENT BRAIN PHYSIOLOGICALLY, ELECTRICALLY, AND COMPARE IT TO THE SURROUNDING TISSUE. SO, TECHNICAL INNOVATIONS FROM THE BIOLOGY SIDE AS WELL AS TECHNOLOGY -- ELECTROPHYSIOLOGICAL TECHNOLOGY SIDE WITH GRAPHINE MICROELECTRODES, SHOWING THE ORGANOIDS INCORPORATE FUNCTIONALLY INTO SURROUNDING TISSUE, AND ACTUALLY VASCULARIZED AND SHOW OTHER FEATURES OF INTEGRATION BASED ON BIOCHEMICAL MARKERS. NOW, IT'S NOT PERFECT. BUT IT'S ACTUALLY SHOWING -- THIS COULD BE A GREAT SYSTEM FOR UNDERSTANDING HOW THESE ORGANOIDS CAN FUNCTION AND MAYBE ONE DAY BE USED FOR LOCAL REPAIR. NOW, THESE WERE IMPLANTED INTO THE CORTEX, RESPONDING TO VISUAL STIMULI PROBABLY FROM LOCAL CONDUCTIVITY, NOT INPUT FROM SENSOR STREAM THROUGH THE THALAMUS, THESE WERE PLACED INTO ADULT MICE WHERE IT'S SHOWN IN SEPARATE STUDIES THAT LOCAL NEUROGENESIS PROBABLY ALSO ONLY INVOLVES LOCAL INTERACTIONS. IT'S IMPORTANT TO NOTE A SIMILAR STUDY FROM SERGIO'S LAB AT STANFORD CAME OUT END OF LAST YEAR WHICH LOOKED AT THE INCORPORATION OF HUMAN ORGANOIDS INTO NOW NEONATAL BRANDS, THEY INCORPORATE INTO THE CIRCUIT, IN THAT CASE THEY DO RECEIVE INPUT FROM THE THALAMUS AS THIS PART OF THE CORTEX NORMALLY WOULD, BUT VERY IMPORTANTLY WHAT THEY DID SHOW UNTIL THESE ORGANOIDS WERE IMPLANTED INTO A HOST RECIPIENT, IN THAT CASE A RAT, THEY DID NOT SHOW FULL MATURATION OF THE NEURONS OR OTHER CELLS. ORGANOIDS ARE A GREAT MODEL SYSTEM FOR STUDYING HUMAN BRAIN TISSUE AND HUMAN BRAIN CELL TYPES, BUT WE STILL ARE NOT AT THE STAGE WHERE THEY SERVE AS A PERFECT MODEL. THERE'S NO SUCH THING AS PERFECT MODEL, BUT A PERFECT MODEL FOR THE MATURE STATE. WE HAVE A WAYS TO GO BUT CAN HOPEFULLY LEARN GREAT LESSONS FROM THE ORGANIZE TO BE A POWERFUL SYSTEM FOR UNDERSTANDING THE HUMAN BIOLOGY OF THE BRAIN. SO CLOSER TO OUR DISCUSSION THAT'S COMING UP IS THIS PILOT STUDY, LOOKING AT THE USE OF ADAPTIVE OR RESPONSIVE DBS FOR EATING CONTROL. HERE IS A CASE STUDY SHOWING TWO PATIENTS WHO HAD LOSS OF CONTROL EATING THAT RESULTED IN BINGE EATING DISORDER. WHAT THEY DID HERE IS THEY RECORDED FROM THE NUCLEUS ACCUMBENS OF THE TWO PATIENTS AND IDENTIFIED PHYSIOLOGIC SIGNATURED THAT PRECEDED BINGE EAT AND COULD SEE INCREASE IN POWER OF LOW FREQUENC OSCILLATION AND USE THAT AS TRIGGER TO STIMULATE IN THE NUCLEUS ACCUMBENS AND SHOW IN THESE TWO PATIENTS INCREASE IN SELF-CONTROL FOR BINGE EATING BUT NOT NORMAL EATING, ALSO WEIGHT LOSS WHERE THEY DIDN'T ACTUALLY INSTRUCT THE PATIENTS TO GO THROUGH OTHER STRATEGIES FOR WEIGHT LOSS. AGAIN, JUST A CASE STUDY WITH TWO PATIENTS, THEY KNOW THE CHALLENGES IN TRAINING THE PATIENTS IN THE SETTING IN THE LAB VERSUS REAL WORLD SETTING, AND THIS IS AN ISSUE WITH THESE ADAPTIVE DBS STUDIES, BUT ARE REALLY MAYBE POINTING THE WAY TO POWER OF USING THESE KINDS OF NEUROMODULATORY APPROACHES, PERSONALIZED NEUROMODULATORY APPROACHES, TO AFFECT INDIVIDUALS WITH SUCH DISORDERS. NOW, THIS IS OPENS YOU WILL A WHOLE HOST OF ETHICAL CONSIDERATIONS ABOUT HOW WE AFFECT THE BRAIN, WITH THESE NEUROMODULATION TECHNIQUES, WHETHER THEY BE INVASIVE IN THE CASE HERE WITH USING DEEP BRAIN STIMULATION, OR NON-INVASIVELY AS WE'LL SEE USING OTHER TECHNIQUES INCLUDING AS WE'LL ALSO LEARN IN A BIT VIRTUAL REALITY. SO THIS WILL BE SURE A TOPIC OF GREAT DISCUSSION IN THE NEXT HOUR OR SO. BEFORE WE GET THERE I JUST WANT TO REMIND EVERYBODY TO SAVE THE DATE FOR THE 9th ANNUAL BRAIN INITIATIVE MEETING, WHICH IS SCHEDULED FOR JUNE 12 AND 13. YOU'LL SEE AN INITIAL ANNOUNCEMENT I HOPE SOON ONCE WE GET THE PAPERWORK STRAIGHTENED OUT. SO THIS IS NOT ETCHED IN STONE BUT IF YOU USE A VERY DARK TYPE 1 PENCIL TO PUT IN YOUR CALENDAR, PLEASE MARK THE DATE OF JUNE 12 AND 13, MORE INFORMATION FORTHCOMING, AND YOU CAN LEARN MORE ABOUT THE BRAIN INITIATIVE AT THIS WEBSITE OR USE THIS SNAZZY NEW QR CODE. I WILL STOP THERE. I DON'T KNOW IF WE HAVE TIME FOR QUESTIONS BUT OTHERWISE I'LL TURN IT OVER TO THE CO-CHAIR, PROFESSOR FARAHANY. >>WE HAVE TWO MINUTES, JOHN, IF THERE ARE QUESTIONS BEFORE WE TRANSITION. ALL RIGHT. SEEING NONE, AT THIS MOMENT, WHICH I'M SURE WILL COME LATER WE'LL TRANSITION OVER. I WANT TO INTRODUCE THE SESSION AND MOTIVATION BEHIND THE SESSION TODAY. SO, WE WANTED TO FRAME THE CONVERSATION TODAY AROUND PERSUADING, ALTERING OR MANIPULATING THE BRAIN. WHAT IS THE LINE BETWEEN THEM AND HOW WE MIGHT AS NEWG ENGAGE WITH THESE ISSUES THAT WE'LL DISCUSS AT 2:00 P.M. EVERYTHING WE DO IMPACTS THE BRAIN, WHETHER IT'S FROM THIS CONVERSATION THAT WE'RE HAVING TOGETHER TO DIFFERENT INTERVENTIONS THAT MIGHT BE UNDERTAKEN. WHETHER IT IS IN THE MORE FOCUSED NEUROSIDE FROM NEURO FEEDBACK TO DIRECT STIMULATION, WE WANTED TO FRAME THE CONVERSATION TODAY MORE AROUND THE EFFECTS ON THE BRAIN, RATHER THAN NECESSARILY THE MODE OF INTERVENTION. AND WE WANTED TO INCLUDE WITHIN OUR CONVERSATION AND BRAINSTORMING WHERE AND HOW NEWG MIGHT ENGAGE IN THIS SPACE, THE BROADER CONSUMER-BASED DEVICES AND INTERVENTIONS THAT ARE LIKELY TO HAVE WIDER-SCALE ADOPTION AND IMPACT TO MORE TARGETED AND SELECTED INTERVENTIONS. IN SOME WAYS THE PRESENTATIONS THAT WILL FOLLOW ARE REALLY JUST A STARTING POINT FOR THINKING ABOUT THE SPECTRUM OF INTERVENTIONS THAT WE MIGHT THINK ABOUT, FROM A HEALTH-RELATED PERSPECTIVE FOR THE BRAIN, WHETHER THAT'S IMMERSIVE VIRTUAL REALITY IN A HEALTH-RELATED CONTEXT TO DIRECT STIMULATION OR INTERVENTION WITH THE BRAIN FOR TREATMENT. I'LL SAY I JUST GOT BACK FROM A TRIP LAST WEEK IN SWITZERLAND WHERE THE CONFERENCE AT THE WORLD ECONOMIC FORUM WAS VERY DEEPLY ENGAGED, THERE WERE MANY SESSIONS ON THE METAVERSE, VIRTUAL REALITY, SO I THINK THINKING ABOUT THIS IN A BROAD CONTEXT, THINKING ABOUT THE IMPLICATIONS AND APPLICATIONS IN A BROAD CONTEXT PARTICULARLY WHERE A LOT OF GLOBAL LEADERS SEE THE FUTURE COMING IS ONE OF THE TOUCH POINTS FOR OUR CONVERSATION. I'VE DONE A DEEP DIVE RECENTLY FOR A BOOK I'VE WRITTEN THAT LOOKS AT THE ISSUES ON MANIPULATION OF THE BRAIN, PERSUASION OF THE BRAIN. I'VE LOOKED AT ISSUES RANGING FROM DISINFORMATION AND MISINFORMATION TO APPEALING TO HUERISTICS OR SHORTCUTS IN THE BRAIN TO NEUROMARKETING TECHNIQUES FOR THE BRAIN OR ATTEMPTING TO INCUBATE DREAMS. WHAT WAS REALLY CLEAR TO ME IN THE DEEP DIVE I DID IS THAT THERE'S A SIGNIFICANT DIVERSITY OF THOUGHT ON HOW TO THINK ABOUT THESE ISSUES FROM A PHILOSOPHICAL PERSPECTIVE, FROM A LEGAL PERSPECTIVE, OR FROM A REGULATORY PERSPECTIVE. SOME OF THE CONCERNS THAT ACADEMICS AND OTHERS HAVE FOCUSED ON AS WE THINK ABOUT INTERVENTIONS IN THE BRAIN ARE HIDDEN INFLUENCES IN THE BRAIN. BUT THAT TURNS OUT TO BE A PRETTY DIFFICULT IF NOT UNTENABLE LINE AS A LOT OF THE MORE RECENT SCHOLARSHIPS SUGGEST THAT A LOT OF THE WAYS THAT ARE ATTEMPTING TO PERSUADE OR CHANGE THE BRAIN AREN'T HIDDEN BUT QUITE AAPPARENT, NEVERTHELESS MAY COMPROMISE AUTONOMY, DIGNITY, OR WELL-BEING OF THE INDIVIDUAL. MORE RECENT SCHOLARSHIP PARTICULARLY FROM BEHAVIORAL ECONOMICS, FOR EXAMPLE, RECOGNIZES THAT MANY INFLUENCES ON THE BRAIN ARE NOT HITTEN, ONE OF THE CONCERNS SHOULD BE INTENTION TO CAUSE HARM, IMPACTING THE BRAIN IN NEGATIVE WAYS. AND QUESTIONS ABOUT AUTONOMY AND CONSENT ARE PARAMOUNT IN MANY CONVERSATIONS. TODAY WE WANT TO FOCUS ON HEALTH-RELATED MODULATION OF THE BRAIN PRESUMABLY FOCUS INTENTIONALLY BENEFICIAL IMPACTS ON THE BRAIN SO THE QUESTION OF HARM WOULD BE PUT TO THE SIDE. BUT MAY NEVERTHELESS RAISE COMPLEX ETHICAL ISSUES FOR WHICH GUIDANCE OR DIRECTION FOR RESEARCHERS, CORPORATIONS, AND GOVERNING BODIES MAY BE A SIGNIFICANT VALUE. WE WANTED TO OFFER A SPECTRUM IN THE CONVERSATION AND PRESENTATIONS THAT WILL FOLLOW OF DIFFERENT WAYS OF IMPACTING THE BRAIN, FROM ENGAGING WITH IT FOR EXAMPLE THROUGH DEEP DISTRACTION, SO WE'VE LOT ABOUT CORPORATIONS USING IMMERSION TO ENGAGE THE BRAIN BUT WHAT ABOUT BENEFICIAL USES OF DOING SAME ACTIVATIONS IN THE BRAIN IN SURGICAL CONTEXTS OR IN OTHER CONTEXTS. WE ALSO WANTED TO LOOK AT WHAT WE SORT OF SAW AS OPPOSITE END OF THE SPECTRUM, WHICH IS MORE DIRECT INTERVENTIONS TO REWIRE OR CHANGE THE FUNCTIONING OF THE HUMAN BRAIN. WHILE THIS IS STARTING PLACE AND HOW WE WERE THINKING ABOUT A WAY TO DESIGN THE SPECTRUM OF THE CONVERSATION THAT WE MIGHT ENGAGE WITH, WE ALSO RECOGNIZED THIS MIGHT NOT BE THE WAY IN WHICH NEWG WOULD WANT TO SEGMENT THE WORLD AS WE THINK ABOUT MODULATION OF THE BRAIN OR THE RIGHT WAY TO THINK ABOUT IT. THE QUESTION IS WHETHER OR NOT SOMETHING LIKE IMPLANTED VERSUS WEARABLE TECHNOLOGY MAKES A DIFFERENCE, WHETHER OR NOT DIRECT VERSUS INDIRECT INTERVENTIONS ON THE BRAIN MAKE A DIFFERENCE, IF THOSE ARE USEFUL WAYS FOR US TO THINK ABOUT IT. AS WE TURN AFTER THIS CONVERSATION, WHAT I'D LIKE YOU TO KEEP IN MIND AS YOU HEAR THE PRESENTATIONS IS THINKING WHAT IS THE UNIQUE AND TARGETED VALUE ADD THAT NEWG COULD PROVIDE. AS YOU HEARD, THIS IS MY FIRST OPPORTUNITY TO SERVE AS CO-CHAIR. I'M DELIGHTED TO HAVE THE OPPORTUNITY TO DO SO. ONE OF THE THINGS I HOPE TO BRING IN MY ROLE AS CO-CHAIR IS A FOCUS AT THE BEGINNING OF EACH OF THESE CONVERSATIONS, REALLY DECIDING WHAT IS IT WE HOPE IS THE OUTPUT OR THE PRODUCT OF THE ENGAGEMENT. IT COULD BE A WORKSHOP THAT WE HOPE TO THEN HAVE PROCEEDINGS THAT FOLLOW FROM. IT COULD BE THAT WE HOPE WE WOULD HAVE TARGETED GUIDANCE THAT WE WOULD PROVIDE TO RESEARCHERS TO CORPORATIONS TO OTHER GOVERNING BODIES. IT COULD BE THAT WE HOPE THERE'S A WHITE PAPER OR ACADEMIC COLLABORATION THAT COULD BE BORN OUT OF IT. BUT AS YOU HEAR THE PRESENTATIONS THAT FOLLOW, I'D LOVE FOR YOU TO REALLY FOCUS ON THAT QUESTION, WHICH IS, WHAT IS THE RIGHT WAY FOR NEWG TO ENGAGE WITH THESE QUESTIONS AND WHAT IS THE INTENDED OUTPUT OR PRODUCT THAT WE LOPE TO HAVE AS A RESULT OF THESE CONVERSATIONS, AND IS THERE UTILITY TO OUR ENGAGING WITH THESE QUESTIONS UNIQUE OR DISTINCT FROM ACADEMIC OR OTHER ENGAGEMENT THAT HAS ALREADY OCCURRED ON THESE ISSUES. SO, WITH NO FURTHER ADO, I WILL HAND IT OVER TO CHRISTINE TO INTRODUCE OUR SPEAKERS FOR THE FOLLOWING CONVERSATION, AND, AGAIN, I'M DELIGHTED TO SERVE IN THIS ROLE. IT'S AN HONOR TO SERVE ALONGSIDE CHRISTINE AND AN HONOR TO BE GIVEN THE OPPORTUNITY TO SERVE IN THIS CAPACITY AND I LOOK FORWARD TO SERVING AS CO-CHAIR OF NEWG. >>THANK YOU, SHE'S GIVEN US A LOT TO THINK ABOUT. WE'RE PLEASED TO HAVE TWO SPEAKERS TO GET US STARTED ON THIS DISCUSSION TODAY. I'LL INTRODUCE EACH ONE SEPARATELY AND LET THE FIRST SPEAK AND THEN GO TO THE SECOND SPEAKER. FIRST SPEAKER IS DR. ANDREW CRYSTAL FROM UNIVERSITY OF CALIFORNIA IN SAN FRANCISCO. DR. KRYSTAL IS THE RAY AND DAGMAR DOLBY DISTINGUISHED PROFESSOR IN PSYCHOLOGY AND NEUROLOGY AT UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, DIRECTOR OF UCSF LABORATORIES AND VICE CLAIRE -- VICE CHAIR N RESEARCH FOR PSYCHIATRY. I WONDER WHEN HE SLEEPS. HE FOCUSES ON DEVELOPMENT OF BIOMARKERS FOR MOOD AND SLEEP DISORDERS AND THEIR APPLICATION IN DEVELOPMENT OF NOVEL AND PERSONALIZED TREATMENTS FOR THESE CONDITIONS. TODAY HE'S GOING TO SPEAK TO US ABOUT CLOSED-LOOP NEUROMODULATION IN AN INDIVIDUAL WITH TREATMENT-RESISTANT DEPRESSION. WELCOME, DR. KRYSTAL. THANK YOU FOR JOINING US. >>THANK YOU VERY MUCH. IT'S WONDERFUL TO HAVE THE OPPORTUNITY TO BE ABLE TO TALK WITH YOU TODAY. I REALLY APPRECIATE IT. LET ME FIRST GET MY SLIDES UP. I'M PRESENTING THIS WORK ON BEHALF OF A SUBSTANTIAL TEAM OF WHICH I'VE NOT BEEN ABLE TO LIST ALL THE MEMBERS ON THIS SLIDE WHO HAVE BEEN JUST SPECTACULAR TO WORK WITH AND A GREAT OPPORTUNITY FOR ME. I WANT TO START BY RAISING THE QUESTION ABOUT HOW CHALLENGING IT IS TO DEVELOP A DEEP BRAIN STIMULATION TREATMENT FOR DEPRESSION. WHEN WE WORK WITH THE CONDITION WHERE IT'S NOT RESOLVED WHERE THE PATHOLOGY IS LOCATED IN THE BRAIN, IT LEAVES OPEN THE QUESTION OF WHERE SHOULD YOU STIMULATE, I THINK THAT IS NOT CLEAR BASED ON THE EXPERIENCE WE'VE HAD TO DATE. THERE ARE MANY, MANY STUDIES CARRIED OUT THAT ALL POINT TO DIFFERENT REGIONS OF THE BRAIN. SO IT SUGGESTS POSSIBILITY THAT THERE IS HETEROGENEITY AMONG PEOPLE. AND THAT'S BUILT INTO THE DIAGNOSTIC STRUCTURE OF THIS CONDITION. THE DSM DIAGNOSIS REQUIRES THAT A PERSON HAVE FIVE OUT OF NINE POSSIBLE SYMPTOMS, AND SO YOU COULD HAVE TWO PEOPLE WHO HAVE DEPRESSION AND HAVE ONLY ONE SYMPTOM IN COMMON. AND WE SEE HUGE VARIATIONS. SOME PEOPLE SLEEP TOO LITTLE, TOO MUCH, EAT TOO LITTLE, EAT MORE THAN USUAL. IT'S QUITE VARIED. WE DON'T KNOW IF THESE ARE TRUE PATHOLOGICAL PHENOTYPES BUT IT'S VERY CLEAR THERE'S -- THERE'S A LOT OF VARIETY IN THE PATIENTS AND RESULTS OF STUDIES WHICH SUGGEST THAT THIS IS LIKELY TO BE THE CASE. ANOTHER POINT IS THAT SO FAR THERE HAVE BEEN A NUMBER OF EFFORTS THAT HAVE TRIED TO DO DIRECT BRAIN STIMULATION AND THESE HAVE ALL INVOLVED CONTINUOUS STIMULATION WHERE ELECTRICAL STIMULUS IS TURNED ON, LEFT ON DAY AND NIGHT FOR DAYS TO YEARS. AND TO ME SOME IMPORTANT QUESTIONS EMERGE FROM WORKING WITH PATIENTS WITH DEPRESSION FOR ALMOST 40 YEARS, PEOPLE HAVE SYMPTOMS THAT VARY QUITE A BIT, EVEN THOSE WITH VERY SEVERE TREATMENT RESISTANT DEPRESSION, AND IT'S NOT CLEAR WHAT IT'S DOING WHEN YOU STIMULATE WHEN PEOPLE DON'T HAVE SYMPTOMS. WHAT'S IT DOING WHEN PEOPLE ARE ASLEEP? THESE QUESTIONS HAVE NOT REALLY BEEN DRILLED DOWN ON VERY DEEPLY AND WE DON'T HAVE GREAT UNDERSTANDING OF IT. TO ME, IT RAISES POSSIBILITY YOU COULD HAVE PRODUCTIVE NEURAL ADAPTATION THAT LIMIT HOW EFFECTIVE TREATMENTS CAN BE. THERE'S ANOTHER CHALLENGE, HOW DO YOU DOSE THE TREATMENTS? THE HISTORY OF DEPRESSION HAS PRIMARILY DOMINATED BY TREATMENTS THAT TAKE FOUR TO EIGHT WEEKS TO WORK, FOR EXAMPLE SEROTONIN REUPTAKE AND OTHERS. YOU HAVE TO WAIT. THAT LEAVES THE QUESTION HOW SHOULD I DOSE THIS INDIVIDUAL WHO I'M WORKING WITH TODAY WHEN I WON'T KNOW IF THAT IS GOING TO MANIFEST AND BENEFIT FOR QUITE A WHILE? AND THE ASSUMPTION SOME CHANGE HAPPENS IN THE BRAIN OVER TIME, SYNAPTONEOGENESIS, NEUROGENESIS, DEEP BRAIN STIMULATION TRIGGERS THAT MEDIATES THE ANTI-DEPRESSANT EFFECT THAT'S DISTINCT FROM WHAT HELPS WHEN YOU ORIGINALLY STIMULATE, AND WHETHER THERE'S ANY INDICATOR OF THAT IN THE INITIAL STIMULUS RESPONSE AND WHETHER OR NOT IT'S NECESSARY FOR THIS 4 TO 8 WEEK PERIOD TO HAPPEN TO GET A ROBUST ANTI-DEPRESSANT EFFECT IS LARGELY BASED ON THEORY AND HISTORY BUT WE KNOW FROM RECENT EXPERIENCE WITH DRUGS LIKE KETAMINE AND SOME OTHER EXPERIENCES ONE OF WHICH I'LL TALK ABOUT IN A LITTLE BIT THAT YOU CAN SEE IMMEDIATE BENEFIT. SO IF YOU CAN SEE IMMEDIATE BENEFIT, IT CALLS INTO QUESTION THAT THIS IS REALLY NECESSARY OR ACTUALLY REALLY FUNDAMENTAL TO THE WAY ANTIDEPRESSANTS WORK. GIVEN THESE CHALLENGES, IT'S NOT SURPRISING SOME OF THE PIVOTAL STUDIES CARRIED OUT TO DATE WITH DEEP BRAIN STIMULATION FOR DEPRESSION HAVE NOT SHOWN THERAPEUTIC EFFECTS, THIS IS ONE STUDY WITH VENTRAL CAPSULE STIMULATION, NO EFFECT VERSUS SHAM. AND ANOTHER WHERE TREATMENT WAS STOPPED IN THE MIDWAY ANALYSIS DUE TO LACK OF CLEAR EVIDENCE THAT THERE'S LIKELY TO BE BENEFIT, SUBCOLOSSAL STIMULATION, IN BOTH STUDIES I PARTICIPATED AND IT WAS COMPLICATED BECAUSE WE WERE TOLD TO TITHE RATE BASED ON IMMEDIATE EFFECT BUT WE SHOULD USE THAT AS WAY TO DOSE, CONFUSING BECAUSE IT'S NOT SO CLEAR THOSE ARE INTIMATELY RELATED TO EACH OTHER.. ONE THAT IS PROMISING IS TO ACTUALLY DO EXPLORATORY STIMULUS RESPONSE MAPPING TO TRY TO DETERMINE THE BEST LOCATION AND STIMULUS PARADIGM SETTINGS. FOR EXAMPLE, AMPLITUDE PULSE WITH FREQUENCY AND SO ON. THAT FOR EACH PERSON. AND THIS IS CONSISTENT WITH MODEL OF HETEROGENEITY, WE MIGHT NEED TO STIMULATE DIFFERENT PEOPLE IN DIFFERENT WAYS, BUT IT RAISES AN IMPORTANT QUESTION WITH RESPECT TO PREVAILING MODEL THAT YOU CAN'T DO THIS IF YOU CAN'T PREDICT THE THERAPEUTIC EFFECT RIGHT AWAY. YOU HAVE TO -- IDEALLY YOU WOULD SEE A THERAPEUTIC EFFECT RIGHT AWAY AND COULD TRY OUT A BUNCH OF LOCATIONS AND PARADIGMS AND SO ON BUT IMAGINE IF YOU WERE TRYING TO DO THIS IN THE CURRENT MODEL YOU'D HAVE TO TRY SOMETHING, WAIT 4 TO 8 WEEKS, TRY SOMETHING AGAIN AND SEE DOES IT WORK. IT'S JUST UNTENABLE. IT'S HUGELY LIMITING AND IF THAT'S WHAT'S NEEDED, THAT'S WHAT NEEDED AND PROGRESS WILL BE SLOW. BUT IF THERE'S AN ALTERNATIVE YOU CAN DO SOMETHING LIKE THIS IT WOULD BE A GAME CHANGER FOR BEING ABLE TO OPTIMIZE AND PERSONALIZE. SO, ANOTHER ELEMENT IS BASED ON THE IDEA THAT THE SYMPTOMS AREN'T PRESENT ALL THE TIME AND WHAT ARE WE DOING WHEN SYMPTOMS ARE ABSENT AND DURING SLEEP AND SO ON. AND THE STRATEGY IS TO USE CLOSED LOOP. CLOSED LOOP IS BASED ON ONLY STIMULATING WHEN NEEDED BASED ON BIOMARKER OF THE STATE YOU'RE HOPING TO TREAT SO YOU CONTINUOUSLY SENSE BRAIN -- IN THIS CASE BRAIN ELECTRICAL ACTIVITY RECORDED WITH INTRACRANIAL EEG AS BIOMARKER, SENSE THE SIGNALS CONTINUOUSLY, AND YOU HAVE A MODEL FOR WHAT CONSTITUTES THE BRAIN ELECTRICAL ACTIVITY DURING THE STATE OF INTEREST, IN OUR CASE SEVERE DEPRESSION, AND YOU DO SOME COMPUTATION CONTINUOUSLY TO ASSESS DOES THE BRAIN ELECTRICAL ACTIVITY CONFORM TO THE PATTERN THAT IS PREDICTIVE OF BEING IN A MORE SEVERE DEPRESSED STATE AND THEN ONLY TRIGGER STIMULATION WHEN THAT BRAIN ELECTRICAL ACTIVITY PATTERN IS PRESENT. SO USE THE BIOMARKER TO DRIVE TREATMENT, CLOSED LOOP COULD BE DONE WITH THINGS OTHER THAN BIOMARKER, COULD BE DONE WITH BEHAVIOR, WIDE VARIETY OF THINGS, BUT YOU'RE USING SOME METRIC OF THE STATE YOU'RE TRYING TO TREAT TO FEED IT BACK JUST LIKE YOU USE THE THERMOSTAT IN YOUR HOME, A DEVICE SIMILAR TO CLOSED LOOP FOR TREATMENT OF DEPRESSION TRIGGERS THE HEAT OR AIR CONDITIONING TO COME ON ONLY WHEN A MEASURE OF THE ENVIRONMENTAL TEMPERATURE SAYS THAT IT'S NEEDED. AND KICKS IN AND TURNS OFF SO YOU GET VERY LIMITED TIME PERIOD OF EFFECT BUT ONLY WHEN IT'S NEEDED. THE OPEN-LOOP APPROACH WOULD BE TURN ON HEAT AND LEAVE IT ON ALL THE TIME, AND IF THE HOUSE GETS TOO HOT YOU MANUALLY TURN IT OFF. BUT IN THEORY IT ONLY CAN MOVE IN ONE DIRECTION. SO, THIS REQUIRES AN IMMEDIACY MODEL BECAUSE YOU'RE HOPING YOU'LL GET BENEFIT WHEN YOU STIMULATE AND YOU'RE GOING TO STOP AND IF YOU CAN'T GET BENEFIT FROM THAT IT HAS TO BE THE CASE THAT YOU NEED CONTINUOUS TREATMENT FOR A LONG PERIOD OF TIME THIS SHOULDN'T WORK IN THE 4 TO 8 WEEK MODEL. IT MEANS THERE'S A STABLE BIOMARKER, A BIOMARKER CAN BE FOUND AND THAT IT'S STABLE. WE TOOK THIS APPROACH TO JUMP TO THE CHASE, AND WE DID IT WITH THE STRONG BELIEF THAT WE COULD ACHIEVE IMMEDIATE THERAPEUTIC EFFECTS WITH DEEP BRAIN STIMULATION ON THE WORK OF OUR TEAM DIE EDDIE CHANG, LEAD INVESTIGATOR FOR THE DARPA SUBNETS STUDY IN EPILEPSY, ABILITY TO MODULATE MOOD SYMPTOMS RIGHT AWAY, LED TO SOME SENSE THIS COULD BE POSSIBLE. HYPOTHESIS THAT WE COULD DO STIMULUS RESPONSE MAPPING AND OPTIMIZATION AND PERSONALIZATION FOR DEPRESSION WITH DEEP BRAIN STIMULATION AND THAT WE COULD THEN USE THAT CLOSED-LOOP MODEL AND THAT THIS WOULD BE POSSIBLE AND FEASIBLE. WE CARRIED OUT A STUDY, PRESIDIO TRIAL, MEANT TO BE PROOF-OF-CONCEPT APPROACH TO THESE FEATURES, TO SEE IF WE COULDN'T DO DEEP BRAIN STIMULATION IN A CLOSED-LOOP MODEL THAT'S PERSONALIZED WITH A MODEST NUMBER OF PEOPLE WHO HAD SEVERE TREATMENT RESISTANT DEPRESSION, TARGETING TREATING APPROXIMATELY 13 PEOPLE, AND THESE PEOPLE HAD TO BE VERY RESISTANT, FAIL EVERYTHING BASICALLY OUT THERE, USING THE NEUROPACE RNS DEVICE TO DELIVER CLOSED LOOP TREATMENT, FDA APPROVED FOR TREATING EPILEPSY, SO IT'S AVAILABLE. STUDY COMPRISED OF THREE STAGES. FIRST WHERE PEOPLE ARE ADMITTED TO EPILEPSY MONITORING UNIT, AND WITH IMPLANTATION OF 10 DEPTH ELECTRODES, EACH WITH 16 CONTACTS, AND WE DO A STIMULUS RESPONSE MAPPING AND CONTINUOUS EEG, RECORDING, WITH GOAL OF DEVELOPING PERSONALIZED STIMULATION STRATEGY FOR EACH PERSON AND BIOMARKER, AND THEY GET EXPLANTED AFTER 10 DAYS AND THEY GET IMPLANTED WITH NEUROPACE SYSTEM, RNS SYSTEM, PROGRAMMED TO IMPLEMENT CLOSED-LOOP OVER THE CAPACITY FOR THAT, AND TO IMPLEMENT CLOSED LOOP WITH STIMULATING IN THE PERSONALIZED APPROACH IDENTIFIED IN STAGE 1 AND USING THE BIOMARKER TO TRIGGER TREATMENT IN STAGE 2. BIOMARKER THAT WAS ALSO IDENTIFIED IN STAGE 1. STAGE 2 INVOLVES ADDITIONAL PERIOD OF REESTABLISHING THE BIOMARKER AND THERAPEUTICS EFFECTS BECAUSE ELECTRODES ARE NOW NEW AND WHILE WE HOPE THEY ARE IN EXACTLY THE SAME SPOT WE KNOW IT'S NOT HUMANLY POSSIBLE EVEN THOUGH EDDIE SEEMS TO BE SUPER HUMAN, HE'S NOT AND THERE ARE SLIGHT DIFFERENCES IN LOCATION. THEN WE HAVE A THIRD PHASE WHERE WE DO A RANDOMIZED DOUBLE BIND CROSSOVER STUDY OF EFFICACY VERSUS SHAM AND SAFETY. THIS IS A PICTORIAL REPRESENTATION OF STAGE 1 WHERE WE DO THIS 10-DAY STIMULUS-RESPONSE MAPPING AND RECORDING PERIOD, IF WE'RE SUCCESSFUL IN IDENTIFYING THERAPEUTIC EFFECT IN SOME AREA WITH SOME SET OF STIMULUS PARAMETERS WE MOVE TO STAGE 2, DO THE VERIFICATION AND THEN OPTIMIZATION IMPLEMENTS CLOSED LOOP AND ONCE WE HAVE IMPLEMENTED THAT AND SHOWN 50% REDUCTION WE MOVE TO CROSSOVER STUDY IN THE FOLLOWING STAGE. SHOWING HERE WE IMPLANTED 10 DEPTH ELECTRODES IN FIVE LOCATIONS BILATERALLY. THIS IS BASED ON EXHAUSTIVE REVIEW OF THE PUBLISHED LITERATURE AND EXPERIENCE IN THE FIELD WITH DEEP BRAIN STIMULATION OF THE SITES MOST EFFECTIVE AND WHERE BIOMARKERS HAVE BEEN IDENTIFIED AND SO ON. JUST TRYING TO PULL TOGETHER A COMPLEX LITERATURE TO LOOK AT THE MOST PROMISES SITES. JUMP TO THE CHASE, WE'VE ACTUALLY GOTTEN THREE PATIENTS THROUGH STAGE 1, ONE PATIENT ALL THE WAY THROUGH, ONE FINISHED STAGE 2. WE PUBLISHED A CASE REPORT, TWO CASE REPORTS ACTUALLY OF THE FIRST PATIENT, AND WE HAD DONE THROUGHOUT OUR INITIAL ASSESSMENT IN THE EPILEPSY MONITORING UNIT INITIAL PERIOD AND THROUGH ALL THE STAGES WE USE A SERIES OF MEASURES TO ASSESS DEPRESSION, A WHOLE OTHER DISCUSSION HOW BEST TO DO THIS BECAUSE WE HAVE TO GET REPEATED ASSESSMENTS, EITHER OUT SELF-RATED SHORT VERSION OF HAMILTON THAT PICKS UP THINGS THAT CHANGE QUICKLY OVER TIME, VISUAL SCALE RATING. IN ALL THREE EFFECTS OF STIMULATION IN SOME PLACES ARE IMMEDIATE AND REPRODUCIBLE, THAT IS STIMULATE THE SAME AREA MULTIPLE TIMES YOU ALMOST ALWAYS SEE THE SAME EFFECT. IT'S AN EFFECT LIKE AN RDoC LIKE DIMENSION, INCREASING ACTIVITIES, PLEASURE, NOT NECESSARILY ANTI-DEPRESSANT AND FOR SOME PEOPLE THAT GOES WITH ANXIETY OR DOESN'T FIX THE PROBLEM. IF THEY DON'T HAVE A PROBLEM WITH LOSS OF PLEASURE, DOING SOMETHING THAT INCREASES PLEASURE IN INTEREST DOESN'T FIX THEIR PROBLEM. WE SAW THIS LITERALLY THERE WAS VARIATION WHETHER PEOPLE FOUND THOSE INCREASES IN CAPACITY AND SPECIFIC DIMENSIONS THERAPEUTIC, SOME HELPFUL IN SOME CASES, SOME HELPFUL IN OTHER PLACES. IF WE STIMULATE FIVE MINUTES TO KEY EFFECTS UP TO 30 MINUTES, SOMETIMES AN HOUR. WE COULDN'T HAVE LUXURY OF WAITING TO SEE HOW LONG THEY LASTED, ALMOST ALL CASES, BECAUSE THE 10-DAY PERIOD OF EXPLORATION WAS JAM-PACKED. THE LONGEST WE WOULD SEE WAS WHEN WE WOULD DO INTERMITTENT STIM TESTING TO IDENTIFY OPTIMAL SETTINGS AND SOMETIMES SEE FOR UP TO 3 HOURS OF EFFECT. WE ALSO SAW STATE DEPENDENCE WHICH SHOULD HAVE BEEN ANTICIPATED BUT I THINK I HADN'T THOUGHT OF THIS THAT SOMETIMES YOU DON'T SEE EFFECTS BUT THAT'S BECAUSE THE STATE OF THE PERSON, STATE OF THEIR BRAIN, VARIES. SOMETIMES WHEN PEOPLE ARE SLEEPY THE CIRCUITS ARE IN DIFFERENT STATES THAN ALERT, DIFFERENT NUMBER OF DEPENDENCIES, THIS WAS A CLEAR ONE FROM OUR INITIAL EFFORTS TO DO THIS, TURNED OUT TO BE USEFUL IN STRIKE TO UNDERSTAND. QUICKLY SHOWING FIGURES ON THE LEFT, DOSE-RESPONSE, EVIDENCE WE SAW BENEFIT IN IMPROVEMENT IN ANTI-DEPRESSANT EFFECTS, WE ONLY HAD A 20-MINUTE PERIOD HERE BETWEEN FIRST STIM AND NEXT STIM, SO WE COULDN'T SAY IT LASTED MORE THAN 30 MINUTES FROM ONSET OF THE STIMULATION, BECAUSE WE HAD TO GO ON TO THE NEXT THING WE DID BUT SAW THIS REPEATEDLY. THE OTHER, ON THE RIGHT SIDE IS THREE FIGURES, FIGURES THAT DEPICT STATE DEPENDENCE. ON THE LEFT YOU SEE THE LEVEL OF AROUSAL, WHETHER POSITIVE ALERT, IF YOU'RE NEGATIVE IT MEANS YOU'RE MORE SEDATED. AND THE ARROW GOING UP ANTI-DEPRESSANT, GOING DOWN SAYS YOU GOT WORK IN YOUR ANTI-DEPRESSANT EFFECT AND THIS SAYS WE FOUND IN THE CORTEX THE PATIENT SLEEPY THAT IT MAKES THEM WORSE, IF THEY ARE MORE ALERT THEN IT IMPROVES THEIR DEPRESSION. WHEREAS THE SAME SORT OF PATTERN WAS SEEN IN THE CINGULATE, THE STRIATUM WAS NOT DEPENDENT ON THIS AND THIS KIND OF THING SEEMS TO VARY FROM SITE TO SITE. LIMITING TIME I JUST NEED TO SUMMARIZE A FEW THINGS AND THEN I'LL STOP. WE MOVE THEN TO THE NEXT PHASE. FIRST WE WERE ABLE TO FIND A BIOMARKER, 77% ACCURATE, LED TO BENEFIT, A FEW TIMES IT DIDN'T. THE SITE FUNCTIONED AS AN INTERCONNECTED CIRCUIT AND WE VERIFIED THIS BY DOING EVOKED POTENTIAL MAPPING STIMULATING STRIATUM, YOU CAN SEE THE DOTS HOW MUCH RESPONSE DID YOU GET IN DIFFERENT PARTS OF THE BRAIN. ONE OF THE RELATIVELY HIGHER RESPONDING PARTS WAS THE BASOLATERAL AMYGDALA, THE ORANGISH -- NOT THE BRIGHT ORANGE, THAT WAS IN HIPPOCAMPUS, BUT AMYGDALA LOTS OF SITES ARE INTERCONNECTED BUT THE BIOMARKER WAS PRESENT IN AMYGDALA, THE FIGURE ON THE RIGHT SHOWS THAT WHEN YOU STIMULATE IT AND THERE'S IMPROVEMENT THEN YOU NORMALIZE THE BIOMARKER WHICH IS CRITICAL FOR IMPLEMENTING CLOSED LOOP, YOUR STIMULATION DOESN'T NORMALIZE THEN YOU DON'T STOP SIMULATING SO THESE WERE THE INGREDIENTS THAT LED US TO DO THAT CHOICE, WE WENT TO STAGE 2, VERIFIED THERAPEUTIC EFFECTS AT TWO CONFIGURATIONS, IN THE VENTRAL CAPSULE, TITRATED BELOW DETECTED BY THE PATIENT, WE WANTED THIS EFFECT TO BE AS SUBTLE AS POSSIBLE, TURNED OUT IT WAS POSSIBLE FOR LEADING TO THERAPEUTIC EFFECT, VERIFIED BIOMARKER WITH AMYGDALA GAMMA BEING ASSOCIATED WITH THE DEPRESSION OUTCOME. AND WE FOUND CHRONICALLY THAT THIS WAS QUITE THERAPEUTIC FOR THIS PATIENT. INTERESTINGLY, JUST TO GIVE A DIFFERENCE BETWEEN CLOSED LOOP AND OPEN LOOP, THIS PERSON IS BEING STIMULATED IN 6-SECOND BURSTS, AND GETS AROUND 470 OF THESE A DAY, WHICH IS A TOTAL OF AROUND -- BETWEEN 15 AND 30 MINUTES OF STIMULATION A DAY VERSUS OPEN LOOP WHICH WOULD BE 24 HOURS. SO A LOT LESS INTENSIVE IN INTERVENTION, ALSO CONSERVES BATTERY LIFE, ET CETERA. THIS PERSON SAW DRAMATIC REDUCTION IN SYMPTOMS IMMEDIATELY FIRST TIME WE STIMULATED VENTRAL CAPSULE, EVERY TIME AFTERWARDS, LOWERED TO WHERE YOU CAN DETECT IT, AND DID CLOSED LOOP SHE HAD SIGNIFICANT AND SUSTAINED REDUCTION AS YOU CAN SEE ON THE RIGHT, HAMILTON DEPRESSION, AND SCALES DROPPED AND STATE DOWN DRAMATICALLY AND HAVE DONE SO FOR A YEAR. THERE'S DETAILS TO THAT, I DON'T HAVE TIME TO GO INTO, BUT ALSO THE IMPROVEMENT IN SYMPTOMS WAS LINKED TO THE BIOMARKER AND STIMULATIONS RECEIVED. THIS IS SOMETHING THAT WAS VERY EVIDENT TO THIS INDIVIDUAL WHO FEELS LIKE HER LIFE HAS BEEN CHANGED BY THIS AND HAS BEEN HUGELY VALUABLE IN HER ABILITY TO FUNCTION AND GET ON WITH HER LIFE WHICH WAS STYMIED BY SEVERE TREATMENT RESISTANT DEPRESSION. I WANT TO MAKE THE LAST POINT THAT WE'VE TREATED A SECOND PERSON WHO MADE IT THROUGH STAGE 2 AND WE'VE SEEN THE STADIUM KIND OF RESULTS. MORE COMPLICATED IN TERMS OF THIS IS A PERSON WITH WAY MORE VARIATION IN SYMPTOMS, AND AT ONE POINT WE THOUGHT THAT SHAM WAS BEING AFFECTED BECAUSE WHEN WE STARTED TO DELIVER TREATMENTS, THERE WERE PRESUMABLY ADAPTATIONS WHETHER THIS IS SEVERITY LEVEL DROPPED ON AVERAGE SIGNIFICANTLY BELOW BUT AT 10 HERTZ WAS MORE EFFECTIVE THAN A SHAM AND HE'S NOW GOING INTO OUR THIRD PHASE FOR THE CROSSOVER STUDY IN THE NEAR FUTURE. SO TO CONCLUDE, WE HAVE SEEN SOME PROOF OF CONCEPT HERE THAT YOU CAN DO PERSONALIZED TARGETING USING STIMULUS-RESPONSE MAPPING AND WE SEE CONSISTENT EFFECTS ACROSS PEOPLE IN DIMENSIONS OF BEHAVIOR BUT DIFFERENT TYPES ARE EFFECTIVE. WE TREATED THREE THROUGH STAGE 1, ALL WERE DIFFERENT. VENTRAL CAPSULE, VENTRAL STRIATUM IN ONE. WE WERE ABLE TO FIND BIOMARKERS IN ALL THREE, SOME PEOPLE THEY WERE STRONGER RELATIONSHIP WITH SYMPTOMS BUT BIOMARKERS IN DIFFERENT LOCATIONS AND DIFFERENT BANDS AND SO ON. WE'VE SEEN THIS IS SAFE AND CAN BE EFFECTIVE IN TWO PEOPLE ESTABLISHING PROOF OF CONCEPT FOR THE APPROACH, I THINK, AND WE'VE SEEN OVER AND OVER IMMEDIATE THERAPEUTIC EFFECTS WHICH CHALLENGES THE MODEL TO STIMULATE CONTINUOUSLY OR WAIT 4 TO 8 WEEKS AND WE'RE IN THE MIDDLE OF THIS STUDY WHICH I FEEL PRIVILEGED TO BE ABLE TO CARRY OUT. I'LL STOP AND SEE IF WE HAVE TIME FOR QUESTIONS. >>THANK YOU, DR. KRYSTAL. DOES ANYONE HAVE AN IMMEDIATE FACTUAL QUESTION FOR DR. KRYSTAL? IF SO NOW WOULD BE THE TIME, BEFORE WE INTRODUCE THE SECOND SPEAKER, AND THEN WE'LL HAVE A DISCUSSION OF OVERARCHING ETHICAL QUESTIONS THAT WERE PUT UP. NITA. GO AHEAD. >>THANK YOU FOR THE WONDERFUL PRESENTATION, RICH AND DEEPLY INFORMATIVE. SINCE THE STIMULATION SITE IS DIFFERENT PER PATIENT AND BIOMARKERS ARE DIFFERENT CAN YOU UNPACK A LITTLE BIT BOTH HOW YOUR TRAINING ON PARTICULAR SITES OF INDIVIDUALS -- HOW YOU'RE TRAINING ON PARTICULAR SITES OF THE INDIVIDUALS TO FIGURE THAT OUT AND SINCE STIMULATION IS CLOSED LOOP VERSUS OPEN LOOP OVER TIME HOW DO YOU ENSURE THE SITE IS STABLE OVER TIME ONCE THE STIMULATION ACTUALLY OCCURS? >>GREAT QUESTIONS. IF I HAD THREE HOURS I COULD START TO DO JUSTICE TO THE ANSWERS. THE SHORT ANSWERS ARE WE GO IN WITH THE ASSUMPTION WE DON'T HAVE ANY IDEA WHERE THIS STIMULATION WILL BE BEST, MOST EFFECTIVE FOR PEOPLE, WHAT THE BIOMARKER WILL BE. WE DO STIMULUS/RESPONSE MAPPING STARTING WITH A WIDE SET AND BASED ON ASSUMPTION WE SHY SEE IMMEDIATE THERAPEUTIC EFFECTS HONE DOWN TO A SMALLER NUMBER AND EACH PERSON WE GET A SET OF FINALISTS BY THE END OF THAT WEEK THAT WE TEST IN MORE DEPTH SO WE START OUT WITH BASICALLY A SAFETY SCREEN TO FIGURE OUT MAKING SURE WE CAN BE IN A RANGE WITHOUT EPILEPTIC ACTIVITY, AT LEAST TWO STIMES IN EACH LOCATION UNLESS THERE'S NEGATIVE EFFECT ELICITED. THE BIOMARKER IS WE TAKE ALL THAT DATA THAT WE COLLECT FROM THE INTRACRANIAL EEGs AND DO EXPLORATORY ANALYSIS WITH HIGH STANDARD REQUIRING HUGE EFFECTS NOT SEEN BY CHANCE AND COME OUT WITH AN EFFECT -- A PERSONALIZED STRATEGY AND PERSONALIZED BIOMARKER THAT THEN GET VERIFIED IN STAGE 2. SO THAT'S SORT OF HOW WE GET TO DIFFERENT STRATEGIES OF DIFFERENT PEOPLE. THERE WAS A SECOND QUESTION I FORGOT. >>JUST THE STABILITY OF STIMULATION OVER TIME. >>RIGHT. SO WE OF COURSE DON'T KNOW THAT IN ANY GREAT WAY. I WOULD SAY SO FAR WE'VE SEEN SUSTAINED BENEFIT HAPPENING FOR PERIODS UP TO A YEAR. WE HAD ONE COMPLICATED THING, ONE OF OUR -- OUR FIRST PATIENT GOT COVID, AND ALSO WHAT LOOKS LIKE LONG -- IS A LONG HAUL, WHICH IS A COMPLICATION, YOU KNOW, YOU HOPE IS NOT GOING TO HAPPEN. BUT SHE CAN TELL DIFFERENCE BETWEEN HER DEPRESSION AND THERAPEUTIC STIMULATION AND BY AND LARGE THE STIMULUS HAS REMAINED THERAPEUTIC OVER TIME BUT IT'S VERY CLEAR THAT WE HAVE IMMEDIATE EFFECTS THAT WE CAN SEE, REFLECTED IN POWER AND COHERENCE AND THINGS LIKE THAT PROBABLY ACTIVITY RELATED BUT OVER THE LONG TERM IT'S CLEAR WE GET CHANGES IN CIRCUIT CONNECTIVITY, CAN SEE WITH EVOKED POTENTIAL, THE CIRCUIT IS CHANGES, MAY NEED TO BE UPDATED BUT WE'RE JUST LEARNING THIS. I THINK INSTABILITY IS THE NATURE OF THE BRAIN. IT'S AN ADAPTIVE ORGAN. THE FACT THAT WE SEE EFFECTS THAT ARE THERAPEUTIC THAT SUSTAIN IS SURPRISING TO ME. I WOULD HAVE EXPECTED WE WOULD HAVE TO ADAPT MORE THAN WE HAVE BUT WITH BIOMARKER IT LOOKS LIKE WE'RE GOING TO HAVE TO ADAPT MORE. >>GREAT. MAY EVEN BE A GOOD THING. JIM, NICE TO SEE YOU AGAIN. >>YOU TOO, CHRISTINE. THANKS, DR. KRYSTAL. REALLY QUITE INTERESTING. YOU PARTIALLY ADDRESSED THIS IN YOUR COMMENTS TO NITA, WONDERING THERAPEUTIC EFFECT IS IT GRADED? IT'S NOT THE SAME EACH TIME I PRESUME. HOW DO YOU MEASURE AND MAKE SENSE OF ALL OF THAT? >>SO ANOTHER COMPLICATED QUESTION. IN THE INITIAL PHASE WE HIT THE CIRCUITRY I THINK PRETTY HARD AND WE SEE PEOPLE SAYING LIKE WOW, I FEEL THIS LIKE BETTER FEELING, I FEEL MORE ENERGY, MORE ALERT, OR I FEEL BAD, I FEEL ANXIOUS BUT THEY FEEL BIG EFFECT WAS EVERY STIMULUS. WHEN WE GET TO WHERE WE IMPLEMENT WE DON'T WANT PEOPLE TO HAVE AN UP EVERY TIME THEY GET STIMULATE AND IT DISRUPTS THEIR LIFE NOT CONDUCIVE WITH GOOD FUNCTION, WE'RE NOT TRYING TO MAKE PEOPLE HAPPY, WE'RE TRYING TO TAKE AWAY DEPRESSION WHICH IS DIFFERENT. HIGH INTENSITY STIMULATION LIKE IN THE VENTRAL CAPSULE LIKE THE FIRST PATIENT WE COULD MAKE HER HAPPY BUT I COULDN'T LIVE THIS WAY, I'M LIKE TOO -- IT'S LIKE I'M HIGH, THERE'S A DISCUSSION TO BE HAD AROUND THAT. WHEN WE LOWERED TO BELOW, I JUST FEEL GOOD, THE PROBLEM IS GONE. WHEN GOOD THINGS HAPPEN SHE FEELS BETTER, WHEN BAD THINGS HAPPEN SHE FEELS WORSE. WE DON'T WANT TO TAKE THAT WE. CRITICAL ADAPTIVE FUNCTIONS THAT HUMANS HAVE THAT ARE HUGELY IMPORTANT FOR THEIR EFFECTIVE LIFE. SO IT'S MORE BASICALLY WHAT THE PATIENTS SAY IS I JUST DON'T FEEL THE DEPRESSION NOW. IT'S NOT THAT OH, I KNOW I'M BEING STIMULATED. THEY THINK THEY KNOW AND ARE USUALLY WRONG ONCE WE GET TO THE SUBDETECTION LEVEL. I HOPE THAT ANSWERS THE QUESTION. >>THANK YOU, IT DOES. I WONDER THOUGH IN THE CLOSED-LOOP SYSTEM THEN SHOULD YOU GEAR IT TOWARDS HOW THE PATIENT IS FEELING OR TO THE BIOMARKER? >>THIS IS A GREAT QUESTION. WHAT HAPPENED IS WE DEVELOP A BIOMARKER THAT'S AT THE LEVEL OF -- THIS IS A GUESS -- AT THE LEVEL OF WHAT CORRELATES WITH THEIR SYMPTOM REPORT. BUT THEN WHEN IT OPERATES, IT SEEMS TO BE PICKING UP SOMETHING AT A LEVEL THAT'S BEFORE THAT. THEY DON'T HAVE TO HAVE A -- YOU KNOW, LET'S SAY WE HAVE A VISUAL ANALOG SCALE 0 TO 100, 0 IS GREAT, 100 IS TERRIBLE, THEY DON'T HAVE TO -- WHILE THE BIOMARKER IS DEVELOPED WITH RANGE OF SYMPTOMS THAT GO FROM 0 TO 100, IT SEEMS MORE THAT WHEN IN OPERATION THEY STAY IN A RANGE OF LIKE 0 TO 40, AND THEY DON'T -- IT'S DOING SOMETHING OVER TIME THAT'S NOT COMPLETELY CLEAR TO ME THAT IS PICKING THIS UP BEFORE THEIR SYMPTOMS, BEFORE THEY GET AN EXPERIENCE THAT LEADS TO INCREASED SCORES BUT SOMEHOW MORE SENSITIVE TO THE PROCESS, IT SEEMS LIKE, THAN I WOULD HAVE ANTICIPATED. THE OTHER POSSIBILITY IS THAT THE BIOMARKER IS DOING NOTHING AND THAT IT'S JUST DRIVING INTERMITTENT STIMULATION AND BECAUSE OF THAT POSSIBILITY WE'RE ACTUALLY ADDING A THIRD ARM TO STAGE 3 OF INTERMITTENT STIMULATION VERSUS CLOSED LOOP STIMULATION VERSUS SHAM. BECAUSE IT IS POSSIBLE THAT IT'S NOT RELATED TO THE PATHOLOGICAL PROCESS AND THE BIOMARKER IS MEASURING SOMETHING ELSE IT'S CREATING INTERMITTENT STIM THAT WORKS, THAT'S ANOTHER POSSIBILITY. >>VERY INTERESTING. DR. LANGEVIN AND WE'LL MOVE ON. OH, I SEE ANOTHER HAND. WE'LL DO TWO SHORT QUESTIONS AND MOVE TO THE NEXT SPEAKER. >>WHICH ONE FIRST? >>DR. LANGEVIN. >>I THINK YOU WERE AHEAD OF ME. >>I DIDN'T SEE THE HAND. SORRY. >>DON'T WORRY ABOUT IT. GO AHEAD. >>OKAY. THANK YOU. SO, MY QUESTION IS QUICK. YOU DESCRIBED A PRETTY ROBUST PLACEBO EFFECT WHICH IS NOT SURPRISING, IN FACT IT WOULD BE SURPRISING IF THERE WASN'T ONE BUT I'M CURIOUS ABOUT WHEN YOU'RE DOING YOUR STIMULUS/RESPONSE MAPPING YOU JUST DESCRIBED HOW DO YOU KNOW YOU'RE NOT MAPPING TO A PLACEBO RESPONSE? >>SO, THIS IS A GREAT QUESTION. IN THE FIRST PATIENT AND THIRD PATIENT WE DIDN'T HAVE MUCH OF A PLACEBO EFFECT AT ALL BUT IN THE SECOND ONE WE DID. THAT CAUSED COMPLICATIONS. WHAT WE HAD TO DO WAS DOING MANY MORE TRIALS TO CONVINCE OURSELVES WE HAD SOMETHING THERAPEUTIC. IT WAS PRETTY CLEAR IN THE 10-DAY STIMULUS/RESPONSE PERIOD THIS WAS HAPPENING BECAUSE WE DO BLINDED SHAM STIMULATION AND STARTED TO SEE THINGS NOT REPLICATES AS WELL AS WITH THE FIRST PERSON AND STARTED TO DISCOVER THAT IT WAS HAPPENING BECAUSE OF A GREATER SHAM RESPONSE. BASICALLY WE UPPED OUR N OF TRIALS. BUT THAT DID LEAD TO SIGNIFICANT COMPLICATIONS IN THE NEXT STAGE. THE OTHER THING THAT HAPPENS, I THINK AS WE START TO DO STIMULATION, YOU GET ADAPTATION OF CIRCUITRY AND WE'RE TRYING DIFFERENT THINGS, THAT YOU MAY END UP WITH A PERSON HAVING SOME SUSTAINED BENEFIT FROM THE THINGS THAT WERE DONE BEFORE. AND SO THAT LED US TO -- WE WERE AT THE VERGE FOR THE SECOND PATIENT WE GOT TO A STATE HAVING DONE A NUMBER OF TRIALS WITH CLOSED LOOP WHEN WE DID TRIALS OF SHAM HE DID WAY BETTER THAN HAD HE WHEN WE DID SHAM LIKE BEFORE WE STARTED DOING CLOSED LOOP. AND SO THAT WAS CORRELATED WITH CHANGES IN HIS EVOKED POTENTIAL RESPONSES, EVEN HARDER TO TELL WE DID FIND CONFIGURATION THAT WAS BETTER THAN THE SHAM RELIABLY, BY FAR, BUT WE HAD TO KEEP PUSHING ON. IT DOES CREATE SIGNIFICANT CHALLENGES. >>WHAT'S GOING ON IN ACUPUNCTURE LITERATURE, 25 YEARS OF EXPERIENCE ON STUFF LIKE THAT, SO, YEAH, GOOD LUCK. THIS IS CHALLENGING FOR SURE. >>SAMEER, THANK YOU FOR WAITING. >>I HAVE A COUPLE QUESTIONS, I'LL KEEP IT TO ONE FOR THE SAKE OF TIME, MAYBE GET BACK TO THE OTHER ONE IN THE DISCUSSION. THANKS A LOT FOR THE GREAT TALK, ENJOYED IT. KIND OF FOLLOWING FROM THE VERY END OF YOUR RESPONSE TO JIM'S QUESTION, RESPONSE VERSUS INTERMITTENT, PHILOSOPHICALLY HOW YOU KIND OF THINK ABOUT VARIOUS VARIATIONS FOR NEUROMODULATION. CLOSED LOOP, WE TALKED ABOUT TREMOR, EPISODIC, SOMETIMES NOT THERE, YOU DON'T NEED IT WHEN YOU'RE NOT SHAKING, LIKE DEPRESSION SLIPPING IN AND OUT BUT PERIODS OF DEPRESSION CAN LAST LONG PERIODS OF TIME. THE DIAGNOSE IT ITSELF IS DEFINED IN TEMPORAL WINDOWS SO DO YOU THINK OF EPISODIC ILLNESS THAT REQUIRES PUNCTUATED TREATMENT LIKE TREMOR, AN ENGINE BACKFIRING AND TRIGGER PTSD VERSUS SOMETHING THERE ALL THE TIME WHERE YOU NEED SOMETHING THAT IS MAYBE CONTINUOUS, MAYBE INTERMITTENT, REALLY INTERESTED IN THAT INTERMITTENT EXPERIMENT. MAYBE YOU DON'T NEED CONTINUOUS, MAYBE YOU NEED TO PING THE CIRCUIT PERIODICALLY, IS IT THAT YOU'RE SLIPPING IN AND OUT OF PERIODS, STATES OF DEPRESSIVE SYMPTOMS WHERE YOU NEED TO BE KICKED BACK OUT WITH STIMULATION WHICH IS SOMETHING THAT REQUIRES RESPONSIVE ADAPTIVE CLOSED LOOP ET CETERA VERSUS OTHER ALTERNATIVES. >>GREAT QUESTION. YOU RAISED A BUNCH OF QUESTIONS. I'VE WORKED WITH DEPRESSION PATIENTS FOR A LONG TIME, NEVER UNTIL I STARTED TO DO THIS STUDY AND STUDIES LIKE IT DID I GET AN OPPORTUNITY TO BE WITH A DEPRESSED PATIENT MOMENT TO MOMENT, ACTUALLY TRYING TO ASSESS SEVERITY OF THEIR DEPRESSION. WHAT WE FOUND IS THAT WE HAVE SOME PEOPLE WHO WHILE BEING IN AN EPISODE OF SEVERE TREATMENT RESISTANT DEPRESSION HAVE SUBSTANTIAL VARIATION OVER THE SYMPTOMS, ONE OF OUR PATIENTS VERY LITTLE VARIATION IS EXTREMELY SEVERE AND SORT OF FIXED BUT WHEN WE STARTED TO DO STIMULATIONS AND EXPLORE EFFECTS WE FOUND VARIATION IN THAT INDIVIDUAL AS WELL, MAYBE TRIGGERED BY THIS STIM PROCESS. AND THE OTHER IS PEOPLE ARE AFFECTED DIFFERENTLY BY HAVING OTHERS IN THE ROOM. YOU KNOW, YOU START TO GET THESE RELATIONSHIPS AND EXPECTATION EFFECTS, WE TRY TO NOT DRIVE THAT SO WE SEE VARIATION. AND IN DEPRESSION THERE'S A HISTORY OF PROBLEMS THAT IF YOU STIMULATE A PERSON WHO HAS DEPRESSION WITH A TREATMENT WHEN THEY ARE NOT DEPRESSED YOU HAVE THE RISK OF TRIGGERING MANIA. THAT CAN ALSO HAPPEN WHEN THEY ARE DEPRESSED, FOR EXAMPLE, ANTI-DEPRESSANT MEDS HAVE A REASONABLE CHANCE OF TRIGGERING MANIA SO WE DON'T USE THEM IN BIPOLAR PATIENTS WITH DEPRESSION BUT IN UNIPOLAR, DBS STUDIES TRIGGERED MANIA SO STIMULATING WHEN PEOPLE DON'T HAVE DEPRESSION DOES RUN SOME DEGREE OF RISK. AND BUT I CAN'T SAY FOR SURE THAT THAT'S NOT SOME SUBGROUP OF PEOPLE, THAT IT WOULD BE OKAY TO STIMULATE SOME PEOPLE ALL THE TIME. I THINK THE QUESTION OF THE INTERMITTENT STIMULATION VERSUS OPEN, I DO THINK THAT THERE IS SOME DEGREE TO WHICH INTERMITTENT STIMULATION WAS THE RIGHT STRATEGY, HAS THERAPEUTIC EFFECTS THAT PROBABLY ARE NOT SPECIFICALLY CRITICAL TO BEING BIOMARKER DRIVEN. WHEN WE'RE -- BEFORE WE HAVE A BIOMARKER WHEN WE'RE TRYING TO TEST PARADIGMS WE DO SOME INTERMITTENT STIMULATION AND SEE LIKE IF YOU TIME IT RIGHT, THIS IS AN OPEN AREA OF RESEARCH THAT NEEDS TO BE DONE, YOU CAN GET LONGER LASTING EFFECTS. WE HAD EFFECTS FOR 3 HOURS IN STIMULATING IN LIKE 5-SECOND CHUNKS INTERMITTENTLY FOR SOME PERIOD IN STAGE 1, ONE OF THE PATIENTS I WAS TALKING ABOUT. IT'S CLEAR THERE IS INTERMITTENTCY EFFECT, ALSO WITH CLOSED LOOP WE'RE SEEING CHANGES IN CIRCUITRY WHICH LEAD TO SUSTAINED BENEFIT OVER TIME SO I THINK I MENTIONED BEFORE IF YOU START STIMULATING THIS MAY NOT BE TRUE IN OTHERS BUT FOR DEPRESSION IF YOU START STIMULATING AND SO FAR IN PEOPLE WE'VE SEEN YOU GET AN EFFECT THAT LASTS 30 MINUTES, 40 MINUTES, BUT AFTER WE'VE BEEN DOING CLOSED LOOP FOR A BIT YOU STOP STIMULATING AND GET BENEFIT THAT LASTS 3 TO 5 DAYS, MAYBE A WEEK IN ONE PERSON. SO IT'S HARD TO CONCEPTUALLY THINK ABOUT IT. DOES IT NEED TO BE LINKED TO BIOMARKER ONCE YOU HAVE BENEFIT SUSTAINING FOR A WEEK? I SUSPECT PROBABLY NOT BUT I THINK IT NEEDS TO BE RIGOROUSLY TESTED. INTERMITTENTSY IS THERAPEUTIC, OPEN QUESTIONS, LOTS OF WORK TO BE DONE. >>THANK YOU. I HOPE YOU CAN STICK AROUND FOR MORE DISCUSSION AFTER THE NEXT SPEAKER. THE SECOND SPEAKER WILL TALK ABOUT INCORRECT OR MORE INDIRECT METHOD OF AFFECTING THE BRAIN. DR. VIVEK PANDRANGI, FOURTH YEAR OTOLARYNGOLOGY RESIDENT AT OREGON HEALTH AND SCIENCE UNIVERSITY, COMPLETED UNDERGRADUATE DEGREE IN BIOLOGY AND ANTHROPOLOGY AT WASHINGTON UNIVERSITY IN ST. LOUIS, OBTAINED MEDICAL DEGREE AT VIRGINIA COMMONWEALTH UNIVERSITY OF SCHOOL OF MEDICINE, INVOLVED IN RESEARCH EXPLORING USE OF VIRTUAL REALITY IN THE MEDICAL FIELD ALONG WITH HIS MENTOR DR. RYAN LEE, ASSOCIATE PROFESSOR OF OTOLARYNGOLOGY AND OHSU AND TODAY WILL SPEAK TO US ON THE EFFECT OF VIRTUAL REALITY ON PAIN MANAGEMENT AND OPIOID USE. THANK YOU, DR. PANDRANGI, FOR BEING WITH US TODAY. >>THANK YOU. IT'S AN HONOR TO BE HERE. LET ME SEE IF MY SLIDES ARE SHARED. THAT LOOKS OKAY. >>LOOKS GOOD. >>THANKS SO MUCH. AGAIN, GOOD AFTERNOON AND THANK YOU FOR THE OPPORTUNITY FOR US TO PRESENT RESEARCH, AND I LOOK FORWARD TO DISCUSSION AFTERWARDS. AGAIN, I'M VIVEK, I'LL BE PRESENTING RESEARCH, EFFECT OF VIRTUAL REALITY ON PAIN MANAGEMENT AND OPIOID USE AMONG HOSPITALIZED PATIENTS AFTER HEAD AND NECK SURGERY, A RANDOMIZED CLINICAL TRIAL. AND I HAVE NO DISCLOSURES. POSTOPERATIVE PAIN AFTER SURGERY RECEIVED GROWING ATTENTION TO IMPROVED FUNCTIONAL RECOVERY, REDUCE HOSPITAL STAYS, IMPROVE QUALITY OF LIFE. BUT POOR POSTOPERATIVE PAIN CONTROL CAN LEAD TO POOR FUNCTIONAL RECOVERY, DISCHARGE AND CHRONIC PAIN, BALANCED WITH RISKS OF PAIN MEDICATION PARTICULARLY NARCOTICS, A MAJOR PART OF THE POSTOPERATIVE PAIN MANAGEMENT PATHWAY WITH KNOWN RISKS, NAUSEA, SEDATION, DEPENDENCE, CONSTIPATION AND MORE, AND THIS REPRESENTS STAYS 65 AND OLDER. AS YOU CAN SEE FROM 2015 DATA, OREGON WAS AN UNFORTUNATE LEADER IN THIS. MULTI-MODAL ANALGESIA IS AN AREA OF EXPLORATION FOR OPTIMAL PAIN CONTROL AND THESE APPROACHES MINIMIZE USE OF NARCOTICS AND PROVIDE STABLE RELIABLE PAIN CONTROL, BUT A MAJOR CHALLENGE OF IMPLEMENTING THIS ARE PATIENTS' MEDICAL COMORBIDITIES. A PATIENT WITH KIDNEY DISEASE OR HIGH BLEEDING RISK MAY NOT BE A GOOD CANDIDATE FOR NSAIDs LIKE IBUPROFEN OR WITH LIVER DYSFUNCTION AND ACETAMINOPHEN. NOVEL AND COST EFFECTIVE STRATEGIES COULD CONFRONT THIS COMPLEX ISSUE. VIRTUAL REALITY, VR, PROVIDES A THREE DIMENSIONAL IMERSIVE EXPERIENCE USED IN A VARIETY OF HEALTH CARE SETTINGS INCLUDING TREATMENT OF ANXIETY, PHYSICAL REHABILITATION, INTERMITTENT PROCEDURE DISTRACTION, EVEN PAIN CONTROL. YOU CAN SEE USERS WEAR A HEAD-MOUNTED DISPLAY, HELMET WITH MOTION TRACKER SO USERS CAN MOVE THROUGH SIMULATED ENVIRONMENT, HEADPHONES OR SPEAKERS FOR SOUND TO FACILITATE IMMERSION, AND SOME SORT OF INPUT DEVICE, HAND-HELD CONTROLLERS OR GLOVES EVEN TO ENABLE INTERACTION WITH VIRTUAL OPTIONS. THE THOUGHT IS VR CAN OFFER DISTRACTION THROUGH THE MULTI-SENSORY OF AUDITORY, VISUAL, PROPRIOCEPTIVE STIMULI. THERE'S SIGNIFICANT CONTENT FOR PATIENTS TO USE FROM DIFFERENT MEDITATION TO EXPLORATION EXPERIENCES, EVEN SOME ACTIVE GAMING EXPERIENCES. USE OF VR IS GAINING SIGNIFICANT TRACTION IN MANY ACADEMIC CENTERS, NUMEROUS PUBLICATIONS OUT NOW ON VR AROUND 400 PUBLISHED IN 2010 COMPARED TO 3,000 ARTICLES PUBLISHED IN 2022. I SHOULD ADD THAT ONE OF THE MAIN LIMITATIONS IN CURRENT VR LITERATURE IS LACK OF COMPARATIVE CONTROL GROUPS BECAUSE OF THE DIFFERENT EXPERIENCES OFFERED IN VR COMPARED TO TRADITIONAL MEDIA PLATFORMS. SOME STUDIES WOULD BE COMPARING VR INTERVENTIONS TO EITHER PASSIVELY VIEWING SOME SORT OF MEDIA ON A 2D SCREEN, BUT THESE CAN BE DIFFERENT AND CONFOUND POTENTIAL BENEFITS FROM USE OF VR. AND THEN ON TOP OF THAT LITERATURE SPECIFIC ON USE OF VR IN POSTOPERATIVE MANAGEMENT IS SPARSE. BUT VR MAY SERVE AS BOTH MEANS FOR NON-PHARMACOLOGIC PAIN MANAGEMENT AND MEANS TO IMPROVE PATIENT QUALITY OF LIFE IN THE HOSPITAL, BOTH OF WHICH MAY FACILITATE POSTOPERATIVE RECOVERY. SO THE PURPOSE OF THIS STUDY WAS TO EVALUATE THE IMPACT OF AN ACTIVE VR GAME COMPARED TO A SIMILAR 2D GAME ON POSTOPERATIVE PAIN AMONG PATIENTS HOSPITALIZED AND HEAD AND NECK SURGEONRY TO EVALUATE CHANGES IN SUBJECTIVE PAIN SCORES AND SECONDARY AIMS TO EVALUATE CHANGES IN OPIOID UTILIZATION AND SUBJECTIVE PATIENT EXPERIENCES WITH THEIR INTERVENTION. WE HYPOTHESIZE PATIENTS USING IT WOULD HAVE LOWER SCORES COMPARED TO CONTROL GROUP. THIS IS FROM JULY OF 2020 TO OCTOBER 2021. APPROVED BY OHSU IRB, REGISTERED ON clinicaltrials.gov, NUMEROUS INCLUSION CRITERIA LISTED HERE, PATIENTS WHO WERE HOSPITALIZED AFTER HEAD AND NECK SURGERY WERE ASKED TO PARTICIPATE IF THEY HAD MODERATE TO SEVERE PAIN DEFINED BY AVERAGE OF PAIN SCORE FROM THEIR MEDICAL RECORD OF 3 OR HIGHER IN THE 24 HOURS PRIOR TO SCREENING FOR STUDY ELIGIBILITY AND ENGLISH SPEAKING, AS THAT IS WHERE MOST CONTENT AVAILABLE ON CURRENT PLATFORMS, LANGUAGE IS AN OPTION FOR PATIENTS TO USE. AND THEN WE ALSO HAD EXCLUSION CRITERIA INCLUDING INTENSIVE CARE UNIT STAY, ACTIVE INFECTIONS, NAUSEA, VERTIGO, SEIZURE DISORDERS, ALSO NOTABLY POSTOPERATIVE LIMITATIONS SUCH AS RECONSTRUCTIONS OR WOUND CARE CONDITIONS THAT WOULD PREVENT THE SAFE OR COMFORTABLE USE OF A VR HEADSET. NUMEROUS DEMOGRAPHICS INCLUDING AGE, SELF-REPORTED SEX, COMORBIDITIES, PREOPERATIVE OPIOID USE, SURGICAL CHARACTERISTICS, OPIOID USE WAS MEASUREDS MILLIGRAM EQUIVALENT. PATIENTS WERE RANDOMLY ASSIGNED USING SOFTWARE-GENERATED RANDOMIZATION TO VR INTERVENTION OR CONTROL GROUP. VR HEAD SET USED WAS OCULUS QUEST, A SILICON HEADSET, DISPOSABLE SANITARY COVERS, EYE MASKS, FACE MASKS BEFORE USE TO MINIMIZE DIRECT DEVICE CONTACT. PATIENTS IN THIS GROUP VR GROUP PARTICIPATED IN THE 15-MINUTE INTERACTIVE GAMING EXPERIENCE, ANGRY BIRDS, AS YOU CAN SEE IN THE PICTURE HERE PATIENTS UTILIZING THIS GAME, USING CONTROLLERS, SITTING IN BED, CONTENT IS INTERRUPTION FREE, INCLUDES MUSIC, SOUND, ANIMATION, AND MEANWHILE PATIENTS IN THE CONTROL GROUP PLAYED SIMILAR GAME, ANGRY BIRDS 2, SIMILARLY FOR 15 MINUTES ON HAND-HELD SMARTPHONE DEVICES WHILE SITTING IN BED WITH THE AUDIO PLAYED THROUGH THE SPEAKER. ALTHOUGH THE TWO GAMES HAD DIFFERENCES BASED ON THE PLATFORM USE, THERE THEY WERE SIMILAR IN THEMES, AUTOMATION, AUDIO, GENERAL GAME PLAYED STYLE. PRIMARY OUTCOME WAS CHANGE IN PAIN SCORE AFTER INTERVENTION USE, SO PRIOR TO INTERVENTION PATIENTS SELF-REPORTED PAIN ON AN 11-POINT SCALE FROM 0-10, EASY TO ADMINISTER, PATIENTS REPEATED IMMEDIATELY AFTER AND HOURLY 4 HOURS AFTER USE. SECONDARY OUTCOMES INCLUDED CHANGES IN OPIOID USE AND PATIENT SATISFACTION WITH INTERVENTION, ANALGESIC USE INCLUDING OPIOID AND NON-OPIOID DOCUMENTED FROM THE MEDICAL REPORT 8 HOURS PRE-INTERVENTION AND 8 HOURS POST INTERVENTION. AND AFTER THE INTERVENTION PARTICIPANTS WERE ASKED TO COMPLETE RESPONSES TO TWO QUESTIONS REGARDING THEIR EXPERIENCE AND DESIRE TO USE AUDIO/VISUAL INTERVENTION IN THE FUTURE, THESE WERE RATED ON FIVE POINT LIKERT SCALES WITH THE FOLLOWING ANSWER CHOICES. THIS WAS A PILOT STUDY, THERE'S INEFFICIENT COMPARATIVE PUBLISHED DATA AVAILABLE BEFORE THE STUDY. MEAN VALUES WITH STANDARD DEVIATION, WITH INTERQUARTILE RANGES, CONFIDENCE INTERVALS REPORTED, P-VALUES RESULT OF TWO-SIDED TESTS. THE FIRST FIGURE, 30 PATIENTS RANDOMIZED FOR INCLUSION, ONE ABLE TO COMPLETE UTILIZATION OF THE VR INTERVENTION DUE TO DISCOMFORT IN USING THE PERSONAL PROTECTIVE EQUIPMENT, SO THE FINAL POPULATION INCLUDED 14 PATIENTS IN OUR VIRTUAL REALITY COHORT, 15 IN THE CONTROL COHORT. THIS TABLE HERE DEMONSTRATES CHARACTERISTICS, NO DIFFERENCES BETWEEN THE TWO GROUPS, MAJORITY OF PATIENTS WERE MALE, MEAN AGE AROUND 58 YEARS, PRIMARY SURGICAL SITES WERE ORAL CAVITY AND ORAL PHARYNX, MAJORITY OF SECONDARY SURGICAL SIDES INCLUDED NECK. FOR THOSE UNFAMILIAR WITH THE FIELD, THESE PROCEDURES PRIMARILY INVOLVED CANCER RESECTIONS FROM DIFFERENT SITES INCLUDING RESECTION OF REGIONAL METASTATIC DISEASE THAT SPREAD TO NECK AND SOME RESECTIONS ARE RECONSTRUCTED USING TISSUE FROM THE OTHER PARTS OF THE BODY SUCH AS RADIAL FOREARM, FIBULA AND OTHER SITES. ALL PATIENTS HAD OPIOIDS AVAILABLE TO THEM TO USE FOR POSTOPERATIVE ANALGESIA. WE FOUND NO DIFFERENCE IN PRE-INTERVENTION BETWEEN THE TWO GROUPS AND DIDN'T FIND DIFFERENCE IN TIME TO INTERVENTION AFTER MOST RECENT OPIOID USE, PRE-INTERVENTION PAIN SCORES, 4-HOUR OPIOID USE OR 8-HOUR USE BETWEEN THE GROUPS. WE LOOK AT CHANGES IN PAIN SCORES. GRAPHICAL ANALYSIS IDENTIFIED ONE EXTREME OUTLIER IN THE CONTROL GROUP WITH PRE-INTERVENTION PAIN SCORE OF 7 TO POST PAIN SCORE OF ZERO, AFTER WE REMOVED THE OUTLIER AMONG 28 FOUND A MEANINGFUL REDUCTION IN PAIN REDUCTION IN THE VIRTUAL REALITY GROUP IMMEDIATELY AFTER THE INTERVENTION USE COMPARED TO THE CONTROL GROUP, 1.4 POINTS, ALSO SOME RELATIVE DIFFERENCES IN ONE HOUR, TWO HOURS, THREE HOURS POST INTERVENTION PAIN SCORE IMPROVEMENTS IN THE VIRTUAL REALITY GROUP COMPARED TO CONTROL GROUP, THIS DIDN'T APPEAR TO PERSIST UNTIL 4-HOUR MARK. WE ALSO LOOKED AT CHANGES IN OPIOID USE AFTER THE INTERVENTION, AND WHAT WE FOUND WAS A MEANINGFUL DECREASE IN 4-HOUR POST INTERVENTION OPIOID USE COMPARED TO 4-HOUR PRE-INTERVENTION OPIOID USE, PATIENTS UTILIZING VR HEADSET, MEAN DIFFERENCE AROUND 9 MME, AROUND 1 TO 2.5 MILLIGRAMS TABLETS OF OXYCODONE, A DIFFERENCE AMONG VR PATIENTS WITH MEAN DIFFERENCE AROUND 14 MME, ALMOST ONE 10-MILLIGRAM TABLET OF OXYCODONE. WE DIDN'T FIND DIFFERENCES IN RESPONSE TO QUESTION OF I ENJOYED MY AUDIO/VISUAL EXPERIENCE OR WOULD LIKE TO SEE MY AUDIO/VISUAL EXPERIENCE USED MORE OFTEN IN HEALTH CARE, BOTH COHORTS HAD HIGH RATINGS OF ENJOYMENT OF THEIR INTERVENTIONS. NO ADVERSE EVENTS RELATED TO INTERVENTION USE IN EITHER COHORT IDENTIFIED. IN THIS STUDY USE OF VR INTERVENTION WAS ASSOCIATED WITH MEANINGFUL REDUCTION IN PAIN AND OPIOID USE COMPARED TO SIMILAR 2D INTERVENTION. IMMERSIVE ENVIRONMENT MAY EXPLAIN THE PAIN ATTENUATION COMPARED TO TRADITIONAL DISTRACTION SUCH AS 2D VIDEO OR MEDIA. THERE'S A RISE OF STUDIES, ONLY A FEW HAVE AIMED TO EVALUATE USE OF VR AFTER SURGERY, NONE HAVE EVALUATED OUTCOMES ON OPIOID UTILIZATION. WE THINK THIS IS A SIGNIFICANT FINDING THAT MAY ENCOURAGE LARGER ADOPTION AND APPLICATION OF VR EXPERIENCES FOR MANAGEMENT OF POST-OPERATIVE PAIN. NOW,IVE NOTE THERE DID NOT APAIR TO BE A PAIN SCORE DIFFERENT PERSISTING UP TO 4 4-HOUR MARK, POST OPIOID UP TO 8 HOURS, THERE MAY BE OTHER FACTORS ASIDE FROM SUBJECTIVE PAIN INTENSITY INFLUENCING USE AMONG PATIENTS, IT'S SHOWN IN THE PAST VR HAS BEEN BENEFITING TREATMENT OF ANXIETY AND DEPRESSION SO IT'S POSSIBLE THAT THERE MAY HAVE BEEN A THERAPEUTIC EFFECT ON ETIOLOGY ASIDE FROM SUBJECTIVE PAIN, ASSOCIATED WITH THE REDUCTION IN OPIOID UTILIZATION. PATIENTS WHO UNDERGO HEAD AND NECK SURGERY POSE UNIQUE CHALLENGE TO THE USE OF VR DUE TO INCISIONS OR RECONSTRUCTS THAT MAY PRECLUDE USE OF WEARING THE HEADSET OR PREVENT COMFORTABLE OR SAFE USE OF VR IN THE POSTOPERATIVE PERIOD. SO FUTURE STUDIES ARE NECESSARY TO BETTER UNDERSTAND THE RISKS OF UTILIZING VR HEADSET IN POSTOPERATIVE PERIOD AND DEFINE INCLUSION CRITERIA FOR SURGICAL PATIENTS. THERE'S A PILOT STUDY WITH A SMALL SAMPLE SIZE, 23% OF PATIENTS WHO WERE APPROACHED FOR RECRUITMENT DECLINED PARTICIPATION, THERE MAY BE BIAS IN ENROLLMENT FOR SELECTING PATIENTS MORE LIKELY TO BENEFIT FROM OR ENJOY GAMING EXPERIENCE. THIS WAS A ONE-TIME VR USE, SO NOVELTY OF THE USE AMONG PATIENTS WITHOUT EXPOSURE TO THE TECHNOLOGY MAY ALSO PLAY A ROLE. SO QUICKLY A COUPLE FUTURE DIRECTIONS TO CONSIDER HOW TO FURTHER EVALUATE THIS TECHNOLOGY FOR PATIENT CARE AROUND ESPECIALLY IN OUR SURGICAL CONTEXT, OF COURSE LARGER SCALE STUDIES ARE NEEDED TO FURTHER EVALUATE UTILIZATION AND EFFICACY. ADDITIONAL OUTCOMES ASIDE FROM SUBJECTIVE PAIN SHOULD BE CONSIDERED SUCH AS ANXIETY AND DEPRESSION, WHICH CAN BE COMMON IN THE PERIOPERATIVE PERIOD. THERE SHOULD BE A COMPARISON OF DIFFERENT TYPES OF EXPERIENCE AND OUTCOMES. OUR GROUP COMPARED MINDFULNESS EXPERIENCE TO VR GAMING EXPERIENCE ON PREOPERATIVE ANXIETY AND POSTOPERATIVE PAIN, MANUSCRIPT UNDER REVIEW. OUR GROUP FINISHED A LARGER TRIAL PROVIDING SIMILAR TO SCHEDULED MEDICATION HOSPITALIZED AFTER HEAD AND NECK SURGERY, JUST ENDING AND WE'RE BEGINNING THE DATA EVALUATION PROCESS. IN CONCLUSION VIRTUAL REALITY WAS ASSOCIATED WITH REDUCED PAIN SCORES HOURS AFTER INTERVENTION, 8 HOURS OPIOID, MAY BE A USEFUL ADJUNCT FOR PAIN CONTROL AFTER SURGERY. >>I CAN'T WAIT TO HEAR THE RESULTS OF THE REPEATED USE AND ALSO GAMING VERSUS MEDITATION USE, WHETHER THEY WERE DIFFERENT. DO PEOPLE HAVE QUESTIONS FOR DR. PANDRANGI ABOUT THIS STUDY OR USE OF VR IN PAIN CONTROL? CAROLINE? SO NICE TO HAVE YOU HERE. ARE YOU THERE? >>YEAH. THANK YOU. CAN YOU HEAR ME? MAYBE NOT. CAN YOU HEAR ME? >>WE CAN HEAR YOU, YEP. NOW WE CAN'T. >>CAN YOU HEAR ME NOW? >>I THINK YOUR SOUND IS COMING IN AND OUT A LITTLE BIT. >>OKAY, LET ME SEE. IS THAT BETTER, CHRISTINE? >>THAT IS BETTER. YEP, THAT'S BETTER. >>THANK YOU. YEAH, THANK YOU, DR. PANDRANGI, FOR THE INTERESTING TALK. IN YOUR STUDY WHETHER YOU WERE ABLE TO ASK SUBJECTS ABOUT THEIR PRIOR EXPERIENCE OR EXPOSURE TO VR PLATFORMS, I THINK YOU HAD ALLUDED TO THAT A LITTLE BIT EARLIER, ONE OF THE AREAS OF INTEREST. AND I WAS ALSO INTERESTED IN THE QUESTION ALSO THAT CHRISTINE JUST POSED ABOUT SOME OF PERHAPS SOME EARLY RESULTS IN LOOKING AT THE DIFFERENT CONDITIONS UNDER WHICH YOU'RE TESTING SUBJECTS, IN THE BEGINNING YOU MENTIONED NOT ONLY GAMING BUT MEDITATION AND NATURE BEING ANOTHER CONDITION. CURIOUS ABOUT THOSE >>YEAH, IN RESPONSE TO THE FIRST QUESTION, WE DIDN'T FORMALLY LOOK AT THIS BUT JUST FROM MY OWN AN ANECDOTAL EXPERIENCE, USE OF VR IS GAINING TRACTION, CONSUMER HEAD SETS ARE OUT THERE, IT'S STILL NOT NEARLY MAINSTREAM AT ALL. FROM THIS ONE STUDY I'M PRETTY SURE EVEN THOUGH WE DIDN'T FORMALLY LOOK AT THIS, NO MORE THAN ONE OR TWO PATIENTS HAVE USED VIRTUAL REALITY BEFORE, SO THAT WAS PART OF THE LEARNING CURVE, I HADN'T USED IT BEFORE, TEACHING THEM HOW TO USE IS, PART OF THE IMPLEMENTATION ASPECT, CHALLENGING, THOSE WHO MAY NOT BE FAMILIAR, NOT COMFORTABLE WITH TECHNOLOGY, FOR EXAMPLE, BARRIER IS HIGHER. SO I WOULD SURPRISED THAT A LOT OF PEOPLE HAD NOT EVEN HEARD ABOUT VIRTUAL REALITY BEFORE EVEN THOUGH WE THINK IT'S SO COMMON IN THE MEDIA AT THIS TIME. STILL A LOT OF OUR PATIENTS HAVE NOT BUT THAT BEING SAID INTERESTING THAT THEY WERE ABLE TO PICK IT UP QUICKLY AND HAVE THE BENEFITS THEY DID. SIMILARLY IN SOME REPEATED STUDIES A FEW OF MY PATIENTS HAVE USED BEFORE BUT MOSTLY THEY BOUGHT AS GIFTS FOR GRANDCHILDREN OR KIDS OR SOMETHING LIKE THAT AND THEY THEMSELVES HADN'T REALLY TRIED THEM BEFORE. SO FROM AT LEAST MY OWN EXPERIENCE USING THE VIRTUAL REALITY IN HEALTH CARE WAS THE FIRST TIME MAJORITY OF PATIENTS HAD USED IT AND THAT BUILDS TO THE STUDY WE JUST FINISHED, PATIENTS GOT THE OPPORTUNITY TO USE IT REPEATED IN THE HOSPITALIZATION, COMBING THROUGH DATA I FELT LIKE ONE OF THE THINGS STARTING TO APPEAR IS WHATEVER SUBJECTIVE PAIN BENEFIT THEY MAY HAVE PERCEIVED MAY NOT JUST BE JUST FROM THE NOVELTY BUT MAY BE PERSISTENCE WITH THAT DISTRACTION. I'M STILL INTERESTED TO SEE HOW LONG THAT DISTRACTION PERIOD LASTS FOR. IS IT REALLY JUST AN HOUR OR SO, CAN IT BE LONGER, WE'LL HAVE TO SEE HOW IT PARSES OUT. THE OTHER DATA, WE LOOKED AT THE IDEA OF MINDFULNESS EXPERIENCE FROM BIOFEEDBACK WHICH I THINK WILL BE REALLY IMPORTANT WITH THE USE OF EMERGING VIRTUAL REALITY TECHNOLOGY ESPECIALLY IN FIELD OF ANXIETY, FOR PREOPERATIVE ANXIETY AND FROM EARLY DATA IT DOESN'T LOOK LIKE TO BE HONEST THERE'S ANY DIFFERENCE BETWEEN THE INTERVENTION USED IN VIRTUAL REALITY AND OUTCOMES WE'RE FINDING. AND THAT WAS SURPRISING TO ME AT FIRST BECAUSE I -- PART OF ME WAS THINKING IF SOMEONE'S PARTICIPATING IN A GAME IT GRABS YOUR ATTENTION MORE, THOUGHT THEY WOULD HAVE REDUCED PAIN OR ANXIETY, BASICALLY THE DATA IS NOT SHOWING REAL DIFFERENCE BUT THERE'S STILL BENEFIT FROM PRE-INTERVENTION SCORES SUGGESTING MAYBE BEING IN VIRTUAL REALITY RATHER THAN TARGETED INTERVENTION, AN INTERESTING AREA TO LOOK MORE AND MORE NOT JUST COMPARING EXISTING TECHNOLOGIES AND EXPERIENCES BUT AS WE HAVE TO MOVE TOWARDS CREATING TECHNOLOGIES THAT WILL BE GEARED TOWARDS CERTAIN SPECIFIC PATIENT POPULATIONS AND HEALTHCARE SCENARIOS. >>GREAT. THANK YOU. SEVERAL PEOPLE HAVE HANDS UP AND A QUESTION IN THE CHAT. WHY DON'T YOU GO WITH THE PEOPLE ON THE SCREEN AND ASK WALTER'S QUESTION, UNLESS WALTER WANTS TO ASK HIMSELF. SYD? >>THANKS. REALLY INTERESTING. SO YOUR COMMENT YOU JUST MADE ABOUT BIOFEEDBACK AND SO I'M CURIOUS IF YOU WERE DOING ANY MEASUREMENTS LIKE THAT FOR THE PATIENTS OTHER THAN THE SORT OF SUBJECTIVE MEASURES YOU WERE USING ABOUT THEIR OWN PAIN RATING, BUT I'M CURIOUS ABOUT WHAT'S YOUR HYPOTHESIS ABOUT WHY VR IS MORE EFFECTIVE THAN A 2D DISTRACTION WOULD BE IN TERMS OF RELIEVING SUBJECTIVE EXPERIENCE OF PAIN. >>GREAT QUESTION. TO THE FIRST POINT, I HAVEN'T LOOKED AT ANYTHING SPECIFICALLY, WE WEREN'T LOOKING AT BIOFEEDBACK BUT MEDITATION APPLICATION WE USED, IT ENCOURAGES BIOFEEDBACK AS PART OF THE PLATFORM SO ONE THING THAT I WANT TO CONSIDER FOR FUTURE STUDIES IS ACTUALLY RATHER THAN LOOKING AT JUST ASSESSMENTS OF ANXIETY OR PAIN BEFORE THEY PUT ON THE HEADSET, AFTER IT COMES OFF FINDING A WAY TO GET SCORES DURING USE AND DURING DIFFERENT TIME POINTS OF THEIR INTERVENTION TO GAUGE BASED ON WHAT THEY ARE ACTUALLY DOING IN VR HOW THAT'S IMPACTING WHATEVER SCORES THEY MIGHT HAVE. SO I THINK THAT'S AN IMPORTANT POINT, SOMETHING TO THINK ABOUT BECAUSE ANOTHER AREA TO LOOK AT IS HOW LONG CAN PATIENTS BE IN VR FOR, SO SO FAR MOST STUDIES SUGGEST UP TO 30 MINUTES IS FINE, SOME RISK OF CYBER SICKNESS IS THERE, EYE STRAIN, BUT SHORTER INTERVALS ARE REALISTIC, 15 OR 20 MINUTES, AND IF WE SEE EVERY 5 MINUTES THERE'S OBJECTIVE EVALUATION WE CAN GET ON SOME SORT OF NUMBERS AND WE KNOW IN THAT EXPERIENCE AT THE 7-MINUTE MARK IS WHERE THEY ARE DOING BIOFEEDBACK THAT LASTS FOR 2 MINUTES, COLLECTING SCORES BEFORE THE ACTUAL SPECIFIC MEASURES ARE BEING DONE VERSUS SIMPLY BEING IN THE VIRTUAL REALITY WORLD, THOSE MORE NUANCED POINTS WILL COME FROM FUTURE WORK. REGARDING -- REPEAT YOUR SECOND QUESTION. >>YOUR HYPOTHESIS WHY VR IS BETTER THAN 2D? I THINK IMMERSION. MY PATIENTS RECOVERING FROM SURGERY, THERE'S SO MUCH GOING ON AROUND THEM IN THE HOSPITAL ROOM, THAT'S TAKING THEIR ATTENTION, TALKING TO THEM, TRYING TO FOCUS ON RECOVERY, SO MUCH EXTRA NOISE FROM MACHINES, HOSPITAL LIFE. BUT WHEN YOU'RE IN THE HEADSET AND IMMERSIVE ENVIRONMENT YOU'RE NOT PATION -- PAYING ATTENTION. YOU'RE FULLY IN THE VIRTUAL REALITY WORLD, I THINK IT'S JUST THE ATTENTION THAT YOU'RE FULLY THERE IN THIS SPACE, PUTTING YOUR ATTENTION THERE IS, TO ME, THAT DISTRACTING ELEMENT COMPARED TO HAVING AN iPHONE OR 2D SCREEN YOU'RE STILL SOAKING IN THE REST OF THE ROOM, EVERYTHING ELSE AROUND YOU EVEN THOUGH YOU'RE TRYING TO PAY ATTENTION TO SOMETHING I DON'T THINK IT'S THE SAME. I THINK THAT'S REALLY WHERE VR'S IMPACT IS. >>THANK YOU. DR. TED ABEL? >>THANKS FOR AN INTERESTING TALK. I HAVE A QUESTION, ANDREW HAS LEFT BUT A QUESTION FOR BOTH OF YOU. I'LL ASK FOR YOU. IT HAS TO DO WITH PERSPECTIVE FROM CIRCADIAN MEDICINE. THIS IDEA FROM JOHN HOEINGENESH AND OTHERS THAT TIMING OF TAKING PILLS CAN IMPACT EFFICACY AND IN THE CONTEXT OF PAIN THERE'S A CIRCADIAN RHYTHM IN OUR -- I DON'T KNOW IF IT'S SENSITIVITY OR RESPONSIVENESS, NOTICING OF PAIN. I WONDERED IF YOU THOUGHT ABOUT THAT, WOULD SEEM LIKE ONE DIFFERENCE BETWEEN A PILL AND VR IS YOU HAVE TO DO VR AT SOME TIME, A PILL AT SOME TIME TOO BUT IT CAN HAVE A LONGER DURATION ACTION, THERE'S SOME EVIDENCE PAIN -- YOU EXPERIENCE MORE PAIN AT NIGHT, YOU DON'T WANT TO WAKE SOMEBODY UP TO GIVE THEM VR BUT GIVE THEM A PILL BEFORE SLEEP. >>THAT TIES INTO THE STUDY WE JUST FINISHED TRYING TO USE VIRTUAL REALITY SIMILAR TO SCHEDULED MEDICATION, BRING IT TO PATIENTS TO USE EVERY 4 TO 6 HOURS IN THE DAYTIME TO GET THEM TO USE THAT. I THINK THAT'S REALLY ONE OF THE CHALLENGES OF VR COMPARED TO THE PILL, AS THINGS ARE RIGHT NOW REALLY TO SAFELY GIVE SOMEONE VR WE NEED TO HAVE SOMEONE WATCHING THEM, BEING AROUND THEM, WE HAVE TO -- IF WE HAVE NOT A MEMBER OF THE RESEARCH TEAM BUT NURSING STAFF OR SOMEONE ELSE THERE, THEY HAVE TO BE TRAINED IN VR, UNDERSTAND THE RISKS, EVEN THOUGH THEY ARE MINIMAL, AND I THINK THAT INFRASTRUCTURE IS LACKING RIGHT NOW TO BE ABLE TO LOOK AT THOSE POINTS BECAUSE IN AN IDEAL SETTING PATIENTS WOULD HAVE THE HEAD SET IN THE ROOM, WE ASK THEM TO USE IT A FEW TIMES AND WE ENCOURAGE IT BUT WE HAVE TO HAVE SOMEONE TO BRING IT TO THEM, MONITOR THEM, HAVE THEM USE IT, A CHALLENGING PERSPECTIVE FROM A REGULATION AND INFRASTRUCTURE STANDPOINT THAT I THINK THAT'S HARDER TO ASSESS BUT I THINK THAT HAS TO HAPPEN BECAUSE SIMILARLY I WANT THE PATIENTS TO USE IT ESPECIALLY AT NIGHT BEFORE THEY BOW TO SLEEP EVEN THOSE MEDITATION ONES BECAUSE MY THOUGHT IS THOSE WERE HELPFUL WITH SLEEP AND PAIN, MAYBE CONFOUNDING MIGHT HELP IN OUTCOMES BUT I DON'T THINK WE'RE THERE FROM IMPLEMENTATION STANDPOINT THAT LET US DO THAT. THAT'S ONE OF THE PROBLEMS THAT I HOPE GETS SOLVED IN THE NEXT FOUR TO FIVE YEARS, DEVELOPING HOSPITAL-BASED PROTOCOLS USING VIRTUAL REALITY TO MAKE THIS PART OF THE SYSTEM. >>THERE'S A WILDER OLDER STUDY WHERE THEY HAVE DONE THIS THING TRYING TO REACTIVATE MEMORY DURING SLEEP WHICH IS WILD, WITH ODORS PRESENT AT THE TIME OF LEARNING. YOU CAN MAJOR PAIRING SOMETHING WITH THE VR EXPERIENCE AND USE THAT TO QUOTE/UNQUOTE TO REPLAY. YOU'LL THINK I'VE LOST MY MIND. I PROMISE YOU I HAVE NOT. >>GREAT STORY. >>THERE'S A BUNCH OF NEUROMARKETING COMPANIES CIRCLING AROUND INCUBATING DREAMS. IT'S A TECHNIQUE PEOPLE ARE TRYING TO PAIR TOGETHER. >>EXACTLY. I DON'T KNOW IF WALTER WANTS TO ASK HIM QUESTION OR MAYBE I CAN INSERT IT. HE WANTS TO KNOW ABOUT POTENTIAL MISUSE OF VR, ARE THERE CONCERNS, HOW WOULD YOU CLASSIFY THEM? >>INTERESTING QUESTION. SOMEBODY IS PUTTING ON A HEADSET, TRYING IT, BUT THAT'S THEIR INTRODUCTION TO THE EXPERIENCE. MAYBE ON THE MISUSE SIDE THEY DON'T KNOW WHAT THEY ARE GETTING INTO UNTIL THEY ARE DOING IT BASICALLY. SO I THINK THAT COMES DOWN TO EQUAL INFORMED CONSENT APPROACH WHERE DO YOU YOUR BEST TO TELL THE PATIENT WHAT TO EXPECT FROM THE EXPERIENCE AND THEY CAN STOP AT ANY TIME BUT THAT COMES INTO THEN BEING AS DESCRIPTIVE AS YOU CAN WITH WHAT THEY ARE GOING TO BE GOING THROUGH AND, AGAIN, MOST OF THESE -- IT'S HARD TO CLASSIFY HOW PATIENTS WILL INTERACT WITH WHAT THEY ARE GOING THROUGH, YOU MAY THINK SOMETHING IS PRETTY STANDARD, ANGRY BIRDS GAME, THIS IS GOING TO BE FINE FOR MOST PEOPLE, BUT YOU NEVER KNOW, THERE CAN BE SOMEONE WHO THAT TRIGGERS SOMETHING AND THAT BECOMES AN UNFORTUNATE OCCURRENCE AND SO AS OF RIGHT NOW THE BEST I THOUGHT ABOUT OF IT HOW TO BE AS DETAILED AS POSSIBLE, SHOW PICTURES TO ACCLIMATE THEM BUT THAT'S A CHALLENGE, THEY WON'T KNOW WHAT IT'S LIKE UNTIL THEY ARE IN THERE. YOU CAN ONLY DESCRIBE IT SO WELL. >>THANK YOU. KAREN? >>THANKS FOR THAT GREAT PRESENTATION. GREAT TO SEE EVERYBODY. EVEN IF WE COULDN'T MEET IN PERSON. DR. PANDRANGI, I'M CURIOUS WHAT YOUR CONSIDERATIONS WERE IN PICKING THAT PARTICULAR DEVICE, PICKING THOSE GAMES, AND I'M SORRY IF YOU MENTIONED IT BUT THE REASON I BRING IT UP IS IT SEEMS THOSE WHO WORK IN LOOKING AT THERAPEUTIC APPLICATIONS FOR GAMING ARE REALLY FINDING IT DIFFICULT TO DRAW COMPARISONS IN THE FIELD BECAUSE THE GAMES ARE SO DIFFERENT. ALSO RELATED TO TECHNOLOGY ITSELF, OFTEN CONSIDERATIONS ARE LESS SCIENTIFIC AND MORE AROUND CONVENIENCE, THAT DOESN'T MEAN IT'S UNETHICAL, SOMETIMES IT LEADS TO GREATER ACCESSIBILITY, CURIOUS IF YOU COULD SHARE MORE ABOUT THE DECISION-MAKING PROCESS. >>YEAH, AT THE TIME OF DOING THE STUDY THE MAINSTREAM HEADSET, CONSUMER HEADSET WAS OCULUS QUEST. OUR GOAL WAS TO USE SOMETHING CONSUMER FACING, EASIER TO USE THEORETICALLY THAN WHAT IS BEING BROUGHT ABOUT FROM THE HEALTH CARE SPACES, ALSO SOMETHING THAT COULD BE COST EFFECTIVE IF WE'RE THINKING HOW TO IMPLEMENT THIS LIKE A MEDICATION, HEAD SETS IS AROUND $400, IF YOU HAVE SANITARY PROCESS, YOU BUY A GAME TO REUSE FOR EVERY PATIENT, UNLESS IT'S STANDARD OF PRACTICE IN THE HOSPITAL, YOU DON'T NEED A NEW HEADSET FOR EVERY TIME YOU USE VR, YOU HAVE ONE, $500, THE COST GOES AWAY PRETTY QUICKLY. WE WANTED TO USE SOMETHING CONSUMER FACING LIKE THAT AND KNOWING THAT WOULD MAKE IT EASIER TO TRAIN PATIENTS TO USE VR BECAUSE IT'S EASIER FROM THAT STANDPOINT. IN TERMS OF THE ACTUAL INTERVENTIONS, IT TOOK A LOT OF RESEARCH AND ESSENTIALLY CAME DOWN TO ME REALIZING THERE'S SO LITTLE COMPARATIVE EXPERIENCES IN WHAT'S OFFERED IN VR SPACES VERSUS 2D SPACES. WE WANTED TO USE A GAME BECAUSE I WANTED SOMETHING MORE DISTRACTING, SOME OTHER STUDIES SAID IF YOU'RE DOING GAMING IT'S GOING TO GETTINGS MORE BUT HOW DO YOU FIND SOMETHING THAT'S COMPARABLE AND FROM MY EARLIER RESEARCH I COULDN'T FIND ANYTHING IN THE LITERATURE THAT HAD TRIED -- BEEN ABLE TO DO BECAUSE THERE ISN'T THAT COMPARISON. I JUST THINK IT'S MORE LUCK AND CHANCE THAT REALLY ONE OF THE GAMES SO POPULAR IS ANGRY BIRDS AND BECAUSE OF THAT THEY HAD CREATED A VIRTUAL REALITY GAME. SO AT LEAST BEING ABLE TO DO THAT BOTH THE GAMES ON THE PHONE AND IN VIRTUAL REALITY IT'S REALLY THE SAME ANIMATION, SOUNDS, CRITICAL THINKING HOW YOU PROGRESS THROUGH A GAME. BASICALLY HELPS MINIMIZE FACTORS BETWEEN VR AND THE PHONE, SOME MORE DIFFERENCES COME TO NOW YOU'RE IN A 3D WORLD VERSUS ON YOUR SCREEN, USING CONTROLLERS TO FLING THINGS IN THE VIRTUAL SPACE SO IT BRINGS PROPRIOCEPTION DIFFERENCES AND THAT SPATIAL DIFFERENCES THAT COME WITH VR AND HOPEFULLY MAKE IT MORE SO IT'S LOOKING AT THE IMPACT OF VR SPECIFICALLY THAN JUST WHAT WE'RE DOING IN VR. SO THAT'S CHALLENGING, STILL A BIG CHALLENGE FOR LITERATURE, AND CURRENT RESEARCH PRACTICES, BUT MY THOUGHT IS NOW BASED ON THIS STUDY AND SOME OF OUR OTHER STUDIES THAT I'M MORE AND MORE OF THE LEARNING THAT I DON'T NECESSARILY THINK THAT IT MATTERS WHAT PATIENTS DO IN VR. I DON'T NECESSARILY THINK THE EXACT EXPERIENCE CARRIES THAT MUCH WEIGHT RATHER THAN JUST BEING IN THAT SPACE AND DOING SOMETHING THEY WANT TO DO IN VR. SO OUR LAST STUDY WE UTILIZED APPLIED VR, A COMPANY THAT HAS A CATALOG OF EXPERIENCES PATIENTS CAN DO FROM GAMES TO MEDITATION TO SEEING DIFFERENT THINGS, AND WE LET PATIENTS CHOOSE WHATEVER THEY WANT AND I THINK THAT'S WHERE THINGS ARE MOVING TOWARDS BECAUSE I THINK IF THEY CHOOSE IT THEY ARE GOING TO GET MORE BENEFIT, IT WILL BE MORE ENGAGING FOR THEM AND MAY NOT BE THAT I NEED THEM TO DO A GAME TO GET MORE PAIN CONTROL OR NEED THEM TO DO MEDITATION BUT PERHAPS THEIR OWN WISHES WILL HELP WITH THAT PROCESS. >>INTERESTING. JIM? THANK YOU. I HAVE A LONGER QUESTION, THAT HAS TO DO WITH PATIENT CONSENT, SINCE THE 3D VIRTUAL REALITY IS DIFFERENT FROM 2D, THE PATIENT MUST HAVE BEEN TOLD DIFFERENCE THINGS, I WONTEDDER IF THEY WERE TOLD ABOUT EXPECTATION, VIRTUAL REALITY IS NOVEL, PROBABLY 2D GAMING EXPERIENCE MANY HAD PROBABLY ALREADY EXPERIENCED, SO THINKING ABOUT THE THERAPEUTIC BENEFIT IS IT RELATED TO ASPECTS OF NOVELTY WHERE PATIENTS EXPECT, AND IN PARTICULAR I'M INTERESTED IN THIS FROM THE LONGER TERM OPIATE EFFECT, WHAT PATHWAY MIGHT BE IMPACTED BY THIS DISTINCTION THAT WOULD ALLOW FOR LONG-TERM EFFECT ON OPIATE USE? >>GOOD POINT, RAISES SEVERAL IMPORTANT CONSIDERATIONS, ONE IS THE FACT THIS IS HARD TO BLIND PATIENTS TOWARDS WHAT THE INTERVENTION IS BECAUSE THEY ARE GOING TO KNOW IF THEY ARE DOING VIRTUAL REALITY OR NOT. YOU CAN'T DO A SHAM. BUT MOST PATIENTS SURPRISINGLY GIVEN OUR POPULATION, MOSTLY CANCER PATIENTS, A LOT ARE OLDER, A LOT OF THEM DON'T HAVE THAT MUCH GAMING EXPERIENCE. I DIDN'T FIND A BIG DIFFERENCE, STILL EXPLAINING THE SAME MECHANICS TO BOTH, BUT ESSENTIALLY I HAD TO LEAVE IT, WE'RE DOING DIFFERENT AUDIO/VISUAL EXPERIENCES, RANDOMIZED TO THIS GROUP, I TRIED TO EXPLAIN VR SHOWING PICTURES OF THE HEADSET BUT IT'S CHALLENGING BECAUSE IT'S DIFFERENT IF SOMEONE HAS NOT USED VR BEFORE. THE NOVELTY WAS AN IMPORTANT CONSIDERATION BECAUSE, AGAIN, MOST HADN'T USED IT BEFORE BUT IN SOME FOLLOW-UP STUDIES REPEATING USE OF VIRTUAL REALITY I THINK WE'VE DONE WELL TO ADDRESS THAT AND I DON'T THINK THE NOVELTY CARRIES AS MUCH WEIGHT AS I THOUGHT BECAUSE I STILL THINK FOR A LOT OF THESE PATIENTS EVEN THOUGH IT MAY BE NOVEL IT'S NOT AN EASY INTERVENTION BY ANY MEANS. IT'S CUMBERSOME TO PUT ON THE HEAD SET, USE CONTROLLERS, EVEN THOUGH IT'S A NOVEL EXPERIENCE I THINK IT'S HARDER TO USE AND USE WELL THAN A SIMPLE HANDHELD GAME AND I THINK WHEN I STARTED WATCHING PATIENTS DO THAT SOME OF THAT STRUGGLE AND LEARNING CURVE I WOULD HAVE THOUGHT MAY HAVE DONE SOME OF THE OPPOSITE, YOU HAVE TO LEARN HOW TO USE A NEW THING THEY ARE NOT USED TO RATHER THAN JUST BEING ABLE TO SAY, WOW, I'M IN THIS 3D WORLD. SO I THINK IT SOMETIMES CAN WORK AGAINST VR WITH THAT LEARNING CURVE AND HOW CUMBERSOME IT IS. IN TERMS OF WHERE I THINK THE OPIOID PATH COMES FROM, I THINK IT'S INTERESTING BECAUSE I THINK THAT MORE AND MORE WE'RE LEARNING HOW TO SEPARATE SUBJECTIVE PAIN AND FEELING OF PAIN FROM ACTUAL USING OPIATE MEDICATIONS, WHETHER THAT SUBJECTIVE FEELING OF PAIN IS TRULY PAIN DERIVED THAT YOU NEED MEDICATION TO TREAT OR IS IT ACCUMULATION OF BOREDOM, ANXIETY, AS YOU'RE RECOVERING FROM A SIGNIFICANT SURGERY, AND SO MOVING -- I'M STARTING TO GET THE SENSE OF MOVING AWAY FROM THESE SUBJECTIVE PAIN SCALES THAT MAY NOT REALLY BE OBJECTIVE MEASURES OF PAIN WHEREAS OPIOID USE MAY BE OBJECTIVE BECAUSE SOMEONE'S TREATING PAIN WITH MEDICATION RATHER THAN SOMEONE SAYING 7 OUT OF 10 ON A PAIN SCALE, WHAT ELSE ARE THEY FEELING IN TERMS OF ANXIETY AND STRESS AND I'M STARTING TO SEE MORE OF THAT PSYCHOSOCIAL STUFF PLAY A ROLE, THAT'S WHERE I'M ALSO INTERESTED SEEING HOW WE CAN WORK TOWARDS SEPARATING THAT WITH ACTUAL PHYSICAL PAIN AND NEED FOR PAIN MEDICATION TO TREAT THAT PAIN AFTER SURGERY. >>WE ARE GOING TO TAKE BREAK BUT I'D LIKE TO ASK YOU ONE LAST QUESTION BEFORE WE DO, DR. PANDRANGI. IN YOUR EXPERIENCE WHAT ARE THE ETHICAL QUESTIONS OR CHALLENGES THAT HAVE BEEN SORT OF FACING YOU IN THESE EXPERIMENTS? ANYTHING THAT STANDS OUT? >>YEAH, THERE ARE A FEW. I THINK ONE IS CHALLENGING, AGAIN FROM MY PERSPECTIVE IN HEAD AND NECK SURGERY, PATIENT INCLUSION AND EXCLUSION. IT'S TOUGH BECAUSE IF WE'RE STARTING TO SEE ALL THIS BENEFIT FROM THIS TECHNOLOGY, START SAYING, WOW, THIS CAN HELP PATIENTS IN SOME WAY, HOW MANY PATIENTS HAVE I HAD TO EXCLUDE SIMPLY BECAUSE WE DIDN'T FEEL SAFE USING THIS TECHNOLOGY IN POSTOPERATIVE CARE. A LOT OF PATIENTS HAVE WOUND INCISIONS ON THE HEADS, THEORETICAL RISK THAT WE DON'T WANT THE PRESSURE OF THE HEADSET ON THOSE INCISIONS IN THE OFF CHANCE IT CAUSES WOUND BREAKDOWN, THAT WOULD BE ITS OWN THING BUT THERE'S NO DATA THAT I CAN FIND THAT HELPS US GAUGE HOW MUCH PRESSURE, HOW LIGHT THE HEADSET IF WE'RE RAMPING UP USE, NEEDS TO BE ADDRESSED, AND OTHER TYPE OF HEAD SETS, HOW MUCH PRESSURE IS APPLIED ON FACE, NASAL BRIDGE, ALL THE PLACES WE'RE OPERATING ON BECAUSE WE'RE EXCLUDING A FAIR AMOUNT OF OUR PATIENTS SIMPLY BECAUSE OF WHERE THE SURGERY WAS, ONE FRUSTRATING CHALLENGE. THE OTHER PART OF IT, WE'VE BEEN USING CONSUMER TECHNOLOGY, EVEN WITH HEALTH CARE RELATED TECHNOLOGY, IT'S GEARED TO PEOPLE ENGLISH SPEAKING, SO THE PATIENTS WE HAVE EXCLUDE A SIGNIFICANT SPANISH-SPEAKING POPULATIONS, CAN'T USE THE TECHNOLOGIES EITHER, THOSE ARE BEEN TWO OF THE MAIN THINGS THAT COME TO MIND WITH STUDIES. THEORETICAL RISK OF SEIZURES, BUT THE RISK IS LOW, YOU KNOW AS PEOPLE ARE TRYING TO CREATE VIRTUAL REALITY HEAD SETS OR EXPERIENCES GEARED TO HEALTH CARE, I THINK IT'S IMPORTANT TO START LOOKING AT HOW YOU MINIMIZE RISKS TO PATIENTS BASED ON WHAT YOU'RE CREATING COULD YOU COULD HAVE SOMETHING STANDARDIZED A WIDER GROUP CAN UTILIZE. >>THANK YOU VERY MUCH. WE'RE GOING TO TAKE A BREAK UNTIL 2:00, RIGHT, NITA? AND EVERYBODY PLEASE COME BACK, RIGHT AT 2:00 SO WE CAN DIVE INTO THE DISCUSSION. THANK YOU SO MUCH FOR JOINING US, DR. PANDRANGI. >>MAYBE WE CAN START BY ADDRESSING SOME OF THE QUESTIONS THAT NITA THOUGHTFULLY SENT OUT AHEAD OF TIME. YOU KNOW, TALKING AMONGST OURSELVES ABOUT WHAT ARE THE ETHICAL QUESTIONS RAISED BY SOME OF THESE TECHNOLOGIES, HEALTH-RELATED TECHNOLOGIES THAT AFFECT THE BRAIN? THE TWO WE HEARD ABOUT ARE USED FOR CLINICAL PURPOSES BUT WE CAN IMAGINE CERTAINLY THE LATTER ONE, MAYBE THE FORMER ONE MAYBE SOME DAY, MAYBE FOR ANYONE CLINICAL PURPOSE, WHAT ARE THE ETHICAL CHALLENGES WE SHOULD BE TALKING ABOUT, THINKING ABOUT, WORRYING ABOUT? DOES IT MATTER WHETHER THE TECHNOLOGIES ARE DIRECT OR INDIRECT? AS WERE EXEMPLIFIED AND ARE THERE ADDITIONAL CONSIDERATIONS IF WE USE THESE TECHNOLOGIES IN PEOPLE CONSIDERED VULNERABLE. LET'S START WITH THAT AND THEN WE'RE GOING TO SEGUE INTO DISCUSSING WHAT IN PARTICULAR NEWG SHOULD DO ON THESE QUESTIONS. AND, AGAIN, THANKS TO NITA FOR THESE QUESTIONS. WHAT'S THE APPROPRIATE CONTRIBUTION OF NEWG, SCOPE, LET'S START WITH FRAMING ETHICAL QUESTIONS. BOTH PRESENTATIONS WE HAD WERE VERY INTERESTING AND VERY -- RAISED REALLY INTERESTING QUESTIONS ABOUT THE KINDS OF EFFECTS THAT WE CAN HAVE ON THE BRAIN RIGHT NOW. SO, WHAT ARE THE ETHICAL QUESTIONS THAT YOU ALL SEE IN TERMS OF THESE, THE USE OF THESE KINDS OF TECHNOLOGIES THAT WE SHOULD BE TALKING ABOUT? WINSTON? CAN'T HEAR YOU, WINSTON. NO. WE HEAR A SQUIGGLE BUT IT'S NOT YOUR VOICE. >>TRY SELECTING YOUR AUDIO ON ZOOM AND RECONNECTING. IF THAT DOESN'T WORK YOU MIGHT HAVE TO REJOIN. LIKE CLOSE AND REJOIN THE MEETING. >>SOUNDS LIKE HELIUM IS IN THE ROOM. >>EXACTLY. >>WHILE YOU'RE WORKING ON THAT I'LL GO TO JIM AND COME BACK TO YOU WHEN YOU'RE READY. GO AHEAD, JIM. >>THANKS. BOTH WERE INTERESTING PRESENTATIONS, HIGHLIGHTING ONE DISTINCTION THAT'S I THINK IMPORTANT FOR ME ANYWAYS. AND IT'S NOT SO MUCH THE DIRECT VERSUS INDIRECT BUT IT'S MORE HOW EASILY REVERSIBLE SOMETHING IS. SO, WITH IMPLANTATION, OBVIOUSLY THAT'S A DIRECT INTERVENTION THAT REALLY CAN'T BE REVERSED. YOU CAN TAKE AN ELECTRODE OUT, TAKE STIMULATING ELECTRODE OUT, BUT FOR THE VR BY VIRTUE OF HOW IT WORKS, WE REALLY DON'T KNOW HOW IT REALLY WORKS BUT IF OPIATE EFFECT IS REMODULATING NEURAL CONNECTIVITY, LONG-TERM VR EFFECTS, ACUTE EFFECTS, BUT BY VIRTUE OF CAUSING A CHANGE IN ADULT NEURONAL RESPONSIVENESS, THAT TELLS YOU IT HAS TO BE REVERSIBLE, EVEN IF WE DON'T KNOW HOW TO REVERSIBLE. FOR ME A DISTINGUISHING FEATURE IS HOW EASILY REVERSIBLE SOMETHING IS, VERSUS NOT REVERSIBLE. >>THAT'S A REALLY IMPORTANT POINT. THERE'S ANOTHER QUESTION ABOUT -- FOR BOTH MODALITIES, THE MEASURED EFFECT WAS RELATIVELY SHORT TERM BUT WE DON'T KNOW THAT'S THE ONLY EFFECT THAT THOSE ARE HAVING. JOHN AND THEN WINSTON. >>IF I COULD AMPLIFY IT UNDERSCORES IMPORTANCE OF UNDERSTANDING MECHANISM BECAUSE WE DON'T -- WE'RE NOT GOING TO HAVE A WAY OF UNDERSTANDING WHAT THE LONG TERM CONSEQUENCES WILL BE WHEN YOU'RE USING THERAPY, WHAT HAPPENS WHEN YOU WITHDRAW, IF WE DON'T UNDERSTAND THE UNDERLYING MECHANISM AT ANY LEVEL, MOLECULAR, CELLULAR, SYSTEM CIRCUITS, WHAT HAVE YOU, SOMETHING WE SHOULD KEEP TOP OF MINE. >>I AGREE. IS DR. PANDRANGI STILL ON WITH US? I DON'T THINK SO. >>NO, HE HAD TO LEAVE FOR THE OPERATING ROOM. >>OKAY. I WAS GOING TO ASK IF THEY ARE MEASURING ANYTHING BEYOND SUBJECTIVE EFFECTS BUT DOESN'T SOUND LIKE IT. WINSTON, ARE YOU WITH US? >>I DON'T KNOW, CAN YOU HEAR ME NOW? DO I SOUND LIKE MYSELF AGAIN? >>YOU SOUND LIKE YOURSELF. >>I WAS STRUGGLING WITH THE SCOPE OF TECHNOLOGIES THAT AFFECT THE BRAIN. NITA SAID AT THE BEGINNING EVERYTHING THAT AFFECTS BRAIN, MAYBE NOT EVERYTHING, BUT MOST OF THE THINGS THAT IMPACT THE BRAIN BY DIFFERENT MECHANISMS, THE TWO THINGS WE HEARD ABOUT WERE QUITE DIFFERENT IN TERMS OF HOW EFFECTS WERE DELIVERED AND SO I GUESS I WAS STRUGGLING TO GET MY ARMS AROUND WHAT IS THE SCOPE OF THE QUESTION THAT'S BEING ASKED HERE. I THINK WE CAN TAKE THESE AS TWO EXAMPLES BUT OUR ABILITY TO GENERATE EXAMPLES DEPENDING ON WHAT WE CONSIDER UNDER THE HEADING OF TECHNOLOGY, WHAT EFFECTS ON THE BRAIN WE THINK WE'RE INTERESTED IN, JUST BECAUSE, YOU KNOW, ANYWAY THE BOUNDARIES OF BOTH OF THOSE SEEM VERY BLURRY TO ME. MAYBE ONE GOAL, I MIGHT HAVE FOR MYSELF TO GET A BEAD ON BETTER SET OF TECHNOLOGIES OR BRAIN EFFECTS THAT WE'RE TRYING TO FOCUS ON AND WHETHER THERE'S SOME KIND OF INTERESTING COMMONALITY TO THE ETHICAL QUESTIONS THAT MAKES IT WORTHWHILE FOR US TO CONSIDER THEM TOGETHER. >>WINSTON, I WANT TO RESPOND. INTENTIONALLY THESE ARE EXTREMES THAT WE WANTED TO BRING TO THE CONVERSATION. WHICH IS TO LOOK AT WHAT IS, YOU KNOW, THROUGH A CONSUMER HEADSET, A VERY DIFFERENT KIND OF EFFECT ON THE BRAIN, IMMERSIVE EFFECT, HAS A HEALTH-BASED APPLICATION VERSUS INTERVENTIONAL EFFECT, WHETHER OR NOT ETHICAL ISSUES ARE DIFFERENT, THE SAME, WITHIN A SPECTRUM, BUT REALLY TO TRY TO MAKE THAT SCOPE MODULATING THE BRAIN AND HOW WE MIGHT THINK ABOUT IT FROM NEWG, WE MIGHT WANT TO NARROW THE SCOPE IF WE THINK ETHICAL ISSUES ARE QUITE DIFFERENT ACROSS THE SPECTRUM OR MIGHT THINK IT'S REALLY, YOU KNOW, TECHNOLOGIES THAT IMPACT THE BRAIN FROM A HEALTH-RELATED PERSPECTIVE AND THINKING ABOUT THAT IN THAT WAY. BUT IT WAS INTENTIONAL TO MAKE THE SCOPE LARGE IN THE NATURE OF THE INTERVENTION TO STIMULATE OUR THINKING ON THIS TOPIC. >>I GUESS I'M STIM STRUGGLING A LITTLE BIT WITH LIKE HOW TO DRAW BOUNDARIES AROUND -- A LOT OF THINGS INVOLVE TECHNOLOGY, AFFECT THE BRAIN, I'M NOT SURE SO LIKE TELEPSYCHOTHERAPY AFFECTS THE BRAIN, OR ONLINE EDUCATION IS A TECHNOLOGY THAT AFFECTS THE BRAIN, SO I GUESS HOW TO, YOU KNOW, GET MY ARMS AROUND WHAT WE THINK IS IN SCOPE AND WHAT'S NOT IN SCOPE. >>I THINK IT DEPENDS ON WHAT IT IS WE WANT TO DO WITH IT, RIGHT? SO IF WHAT WE WANT TO DO IS A WORKSHOP TO EXPLORE ISSUES MORE BROADLY AND THEN TO DECIDE WHAT A PRODUCT MAY BE, A BROADER CONVERSATION MAY MAKE SENSE TO NARROW IN SCOPE. IF WE THINK IT'S SPECIFIC WE'RE READY TO DIVE INTO THINKING ABOUT WORKING ON A WHITE PAPER OR GUIDANCE, THINKING ABOUT THESE ISSUES WITHIN THE CONTEXT OF GIVEN THE BREADTH, THE EFFECT, WHAT IS THE NEXT STEP FOR NEWG WITH RESPECT TO TARGETED GUIDANCE OR TARGETED -- NOT GUIDANCE BUT TARGETED CONTRIBUTIONS AND HOW MIGHT WE DO THAT. IT MAY BE WE NEED TO NARROW THROUGH A WORK SHORTSTOP OR ADDITIONAL CONVERSATIONS. >>MAYBE I CAN ADD ONE THING BEFORE I HAVE A WHOLE ARRAY OF HANDS UP. WE TALKED AT SOME POINT IN THE PLANNING OF THIS DAY, WE TALKED ABOUT THE QUESTION OF SHOULD THERE BE I DON'T KNOW, LIMITS I GUESS IS THE WORD I WOULD USE, THAT'S PROBABLY NOT THE RIGHT WORD, LIMITS ON INTERVENTIONS THAT AFFECT THE BRAIN. AND AS NITA POINTED OUT TO US THEN, AND YOU SAID, WINSTON, THE NUMBER OF THINGS THAT AFFECT THE BRAIN IS HUGE. SO THE QUESTION IS, IF THERE ARE LIMITS ARE THERE LIMITS FOR CERTAIN KINDS OF INTERVENTIONS ONLY AND IF SO WHY? AND/OR ARE THERE NO LIMITS? HOW TO THINK ABOUT QUOTES -- THOSE KINDS OF QUESTIONS DROVE US TO THINK ABOUT TODAY AS PLANNED. SO, JIM? >>THANKS. ONE ORB COMMENT. SORRY, KAREN, MAYBE I JUMPED AHEAD OF YOU. SORRY ABOUT THAT. ONE OF THE THINGS STRIKING, THERE'S REALLY NOTHING THESE GUYS CAN DO ABOUT IT, BUT I WORRY ABOUT GOING TOO FAR DOWN THE ROAD OF ETHICAL CONSIDERATIONS WHEN THE POWER OF A STUDY IS SO LOW. SO I WONDER ABOUT WHETHER OR NOT IN THINKING ABOUT THESE TYPES OF NEURAL INTERVENTIONS WHETHER OR NOT THERE'S SOME GUIDANCE WE CAN GIVE ABOUT POWER OF THE STUDIES, OR GETTING DATA. IN MY FIELD IT CAN TAKE TWO YEARS TO GET A PAPER PUBLISHED. I DON'T KNOW ABOUT THIS FIELD BUT I WONDER IF THERE'S GUIDANCE GETTING DATA OUT MORE RAPIDLY SO MORE DECISIONS OR INSIGHT CAN BE PROVIDED WITH RESPECT TO THESE TYPES OF CONSIDERATIONS. >>INTERESTING POINT. I'M GOING FROM LEFT TO RIGHT, MAYBE THAT'S NOT THE RIGHT WAY. IF I'M DOING IT RIGHT, TED ABEL IS NEXT. YOU'RE ON MUTE, TED. >>LET KAREN GO. SHE WAS -- I WAS GOING TO ASK BASICALLY THE SAME QUESTION THAT JIM ASKED, SEEMS LIKE WITH THE NEUROSURGICAL STUDIES YOU COULD ALMOST NEVER HAVE THE N, AND I'M ON A WORKING GROUP OF THE NATIONAL ADVISORY MENTAL HEALTH COUNCIL THAT'S THINKING ABOUT HIGH DIMENSIONAL DATASETS, AND HOW TO HANDLE THEM. YOU KNOW, WE'RE REMINISCING ON Ns OF SIX SCIENCE PAPERS OF GENETIC IMAGING STUDIES, YOU KNOW, WHATEVER. IT'S REALLY A CONCERN. SO I REALLY WANT TO UNDERSCORE THAT, WHAT JIM JUST SAID. I THINK THE MECHANISM MIGHT HELP YOU IF YOU HAVE A SENSE OF IT BUT ONE OF THE THINGS YOU OBVIOUSLY REALLY HAVE TO BE CONCERNED ABOUT IS SELECTION BIAS, IN TERMS OF THE PATIENTS, NOT JUST WILLING TO DO THIS BUT AT THAT LEVEL OF BEING -- NEEDING THE NEUROSURGERY AND BEING DEPRESSED, SEEMS LIKE IT'S HARD TO GENERALIZE SO I THINK IT'S VERY CHALLENGING. THE OTHER POINT I WANT TO MAKE, QUESTION I WANT TO ASK, THERE WAS THIS -- THERE IS THE THINKING ABOUT THE BLACK BOX WARNING ON ANTIDEPRESSANTS, AND YOU WONDER, OBVIOUSLY THERE'S A LOT OF CONTROVERSY ABOUT THAT, WE JUST DID AN INTERESTING STUDY GROUP HERE ON SO CALLED TWICE EXCEPTIONAL INDIVIDUALS DIAGNOSED WITH AUTISM WITH A GIFTED I.Q., THEY HAVE INCREASED SUICIDAL IDEATION AND THAT GOT A LOT OF RESPONSES ON SOCIAL MEDIA. IT'S AN IMPORTANT ISSUE. I WONDER HOW MUCH WE'RE THINKING ABOUT THAT. I WAS STRUCK BY THE DESCRIPTION OF THE PATIENT. I'M NOT A HUMAN PSYCHIATRIST, I'M A MOUSE PSYCHIATRIST, BUT STRUCK BY THE DESCRIPTION OF THE PATIENT ANDREW GAVE BECAUSE IT SEEMED LIKE SOMEBODY WHO WOULD BE SUFFICIENTLY NOT DEPRESSED TO BE ACTIVATED TO MAYBE BE ABLE TO COMMIT SUICIDE. OBVIOUSLY CAN'T DO THAT BUT I WONDER HOW WE HANDLE SIDE EFFECTS OF THIS AND THERE'S AN OBVIOUS ONE HERE WHICH IS THAT. AND I DIDN'T REALLY HEAR THAT. I HEARD EVERYONE FOLKING FOLKI- FOCUSING ON IMPACT, HOW WOULD WE THINK ABOUT THE SIDE EFFECT -- NOT SIDE EFFECTS BECAUSE I DON'T KNOW THAT SUICIDE IDEATION IS NECESSARILY A SIDE EFFECT. >>IMPORTANT PART OF THE PROBLEM. DID WE LOSE KAREN? THERE SHE IS. KAREN, GO AHEAD. >>SORRY, I HAVE A FUSSY PUPPY. SO, I REALLY LIKED THE BREADTH AND INVITATION FOR US TO THINK ABOUT EVEN MORE FOUNDATIONAL NEUROETHICS ISSUES WE DON'T DIVE INTO BECAUSE I THINK THERE IS A BIG PROBLEM ON THE HORIZON, OR CHALLENGE AND INTENTION AROUND MAKING KIND OF THE INVISIBLE -- SOMETHING THAT'S INVISIBLE TO THE PATIENT OR PARTICIPANT VISIBLE TO THEM. AND WHETHER THAT REALLY RESEMBLES THEIR TRUTH. AND WHETHER THAT REALLY EMPOWERS THEM. SO, YOU KNOW, I THINK FOR THE DBS EXAMPLE, DR. KRYSTAL SAID I THINK WE'RE ADDRESSING A POINT IN THE PROCESS BEFORE MAYBE A PATIENT IS EVEN AWARE OF WHAT'S HAPPENING TO THEM. SO THAT'S A POSITIVE INTERVENTION, RIGHT? MAYBE YOU DON'T WANT A PATIENT TO BECOME AWARE IF YOU'RE DEPRESSED. AND DR. PANDRANGI SAID -- HE WAS TALKING ABOUT SOMETHING INVISIBLE, SOMETHING ABOUT THE SUBJECTIVE NATURE OF PAIN, WHICH HAS ALWAYS BEEN A PROBLEM. IT'S EVEN MORE PROBLEMATIC FOR THE PATIENT. SO, I THINK THAT AS WE -- AND THE BRAIN BEHAVIOR QUANTIFICATION AND SYNCHRONIZATION EFFORT TRYING TO QUANTIFY BEHAVIORAL COMPONENTS FITS TOGETHER IN STILL ADDRESSING THAT TENSION AND WHAT HAPPENS IF WHAT WE RECORD OR WHAT WE QUANTITATIVELY THINK WE'RE ASSESS DIFFERS FROM THE SUBJECTIVE EXPERIENCE IN THE PARTICIPANT AND HOW DO WE MAKE THAT RIGHT AND THE PARTICIPANT IS EMPOWERED OR PATIENT IS EMPOWERED, IT'S A HARD QUESTION BUT SOMETHING THAT'S GOING TO BE RELEVANT TO A LOT OF BIOMETRIC TECHNOLOGY, EVEN MORE TRICKY WITH BRAIN TECHNOLOGY. AND I THINK AS FAR AS SCOPE, I MEAN, WE'VE BEEN -- MAYBE FOR GOOD REASONS, WE'VE BEEN PRETTY TRADITIONAL HOW WE'VE SCOPED OUR NEUROETHICS ISSUES, TRYING TO PUSH BEYOND THAT AS WE THINK DEEPLY ABOUT JUSTICE ISSUES, D.E.I., AND HOW IT INTERSECTS. I WAS PLEASED TO SEE HELENE LANGEVIN ON THEIR TALKING ABOUT PLACEBO, WHAT A BIG DEAL TO HAVE NOT TALKED ABOUT YET BUT MAYBE THIS OFFERS AN OPPORTUNITY TO TALK ABOUT BRAIN MECHANISMS. AND MAYBE WE COULD SCOPE IT AT FIRST ON TECHNOLOGY THAT BRAIN FUNDS, SO WE'RE NOT LOOKING AT EVERYTHING BECAUSE PART OF OUR APPROACH SHOULD BE USING THE BRAIN INITIATIVE KIND OF AS A PILOT AREA WHERE WE DISSEMINATE TOOLS AND BEST PRACTICES THAT OTHERS CAN USE. >>GREAT POINTS. THANK YOU, KAREN. CAROLINE? >>YEAH, THANK YOU, CHRISTINE. I ALSO WANT TO THANK NITA AS WELL FOR INVITING US TO OPEN THIS CONVERSATION AND CONSIDER WHAT NEWG COULD DO AND ENVISION THAT FOR THE FUTURE. I THINK THIS PROMPT WAS INTERESTING TO ME BECAUSE IT MADE ME THINK ABOUT THE EVOLUTION OF THE BRAIN INITIATIVE. AND ITS START IN THE DEVELOPMENT OF NEW TOOLS AND TECHNOLOGY TO BETTER MAP AND STUDY THE BRAIN AND THEN WITH THE SECOND PHASE THE BRAIN INITIATIVE BUILDING ON THE PROGRESS OF THAT FIRST PHASE. AND APPLYING THAT TOWARD DISCOVERY-DRIVEN SCIENCE, IN SOME CASES WE'RE ALREADY SEEING NEAR-TERM HEALTH POTENTIAL APPLICATIONS AS WE SAW TODAY FROM THESE TWO TALKS. AND WHILE I'M STILL NEW TO THE NEWG, I HAD MY FIRST MEETING LAST TIME, I THINK WHAT THIS PROMPT HELPED ME THINK ABOUT IS HOW THE NEWG COULD EVEN STAND WHAT IT'S DONE IN THE PAST TO THINKING ABOUT HEALTH APPLICATIONS, IN TERMS OF SCOPE PERHAPS THINKING ABOUT IT IN TERMS OF SOME OF THE BREAD AND BUTTER OF WHAT NIH AND "BRAIN" HAVE CONTINUED TO FOCUS ON. ONE DIMENSION TO THIS I THINK THAT CAME TO MY MIND WAS THINKING ABOUT THE SBIR PATH, AND THINKING ABOUT AN SBIR PATH, HAVING THE NEWG ENGAGE MORE CLOSELY WITH APPLICATIONS AND PROJECTS THAT ARE GOING THROUGH THAT PIPELINE COULD BE A UNIQUE -- I THINK THAT'S HOW YOU PUT IT, NITA, A UNIQUE APPLICATION TO LEVERAGE SKILL SETS OF NEWG MEMBERS INCLUDING YOURSELF, NITA, KAREN, MANY OTHERS WHO HAVE BEEN INVOLVED IN TRANSLATION OF NEUROTECHNOLOGIES AS WELL AS ETHICAL COMPONENTS OF IT. ONE THE OTHER REASONS I THOUGHT ABOUT THIS TOO IN THE CONTEXT OF THOSE TWO TALKS IS BECAUSE IT'S STILL SOMEWHAT AGNOSTIC TO PARTICULAR TYPE OF BRAIN INTERVENTION. INSTEAD, THE DIE MENTION IS HOW FAR ALONG ARE THESE TECHNOLOGIES IN LET'S SAY POTENTIAL COMMERCIALIZATION. IT'S ALSO SOMEWHAT AGNOSTIC TO THE LEVEL OF EXPLANATION OF MECHANISM, AS JOHN HAD PUT, SO FOR BETTER OR WORSE THAT PATHWAY COULD BE BETTER OR NOT SO EXPLAINED IN TERMS OF MECHANISM. SO THAT WAS ONE MODEL I THINK THAT I THOUGHT ABOUT THAT COULD BE UNIQUE FOR THIS GROUP. IT COULD, AS KAREN HAD TALKED ABOUT EARLIER, BE A CHUNK THAT COULD BE BITTEN OFF OF IN A MORE MANAGEABLE STYLE, BUT I THINK WE ALSO HAVE A LOT OF MODELS THAT KIND OF ADVISING FROM VARIOUS DOMAINS, WHETHER IT BE IEEE BRAIN NEUROETHICS, THE SEE KAREN'S LOGO BEHIND HER, PERHAPS THAT COULD BE ONE AVENUE FOR A NEW TYPE OF ENGAGEMENT. THAT WAS ONE THOUGHT. THE SECOND THOUGHT I HAD, AS I WATCHED THESE TALKS, ALSO REFLECTED ON NEWG MEETING, POST TRIAL RESPONSIBILITIES WORKSHOP BACK IN MAY, IS THAT IT SEEMS LIKE THE INVITATION TO INCLUDE PATIENT OR END USER PERSPECTIVE IN THESE CONVERSATIONS WAS REALLY STRONG. I THINK THAT IT COULD BE A STARTING POINT FOR EVEN DEEPER ENGAGEMENT THROUGH LET'S SAY FOLLOW-ON RESEARCH GRANTS OR GRANTS THAT CAN FUND ENGAGEMENT OPPORTUNITIES BETWEEN RESEARCHERS AND PATIENTS. SO THAT'S ANOTHER AVENUE JUST BASED ON WHAT I'VE OBSERVED SO FAR. >>GREAT. >>LET ME JUMP IN FOR JUST A MOMENT TO SAY THANK YOU, CAROLINE, FOR THOSE. AND I THINK THINKING ABOUT EACH OF THOSE ENGAGEMENTS IS PART OF WHAT I'M HOPING WE'RE GOING TO BE THINKING ABOUT, WHERE ARE WE GOING, WHAT'S THE IMPACT WE WANT TO HAVE. I WANT TO CONNECT UP THE TWO TALKS FOR A MOMENT AS FOLKS ARE THINKING ABOUT IT. A LOT OF THE EMERGING VR HEADSETS ALSO HAVE INTEGRATED SENSORS FOR EEG TO PICK UP BRAIN WAVE ACTIVITY, AT LEAST TO A LIMITED EXTENT. AS WE THINK ABOUT CLOSED LOOP VERSUS OPEN LOOP, JUST TO PUT AN ETHICAL PIECE ON THE TABLE FOR US TO THINK ABOUT, SOME OF IT IS ABOUT CLOSED LOOP EVEN WITHIN VR, RIGHT? THAT ISN'T LIMITED JUST AT ONE END OF THE SPECTRUM OR THE OTHER. AS WE THINK ABOUT WHAT WE MIGHT DO AND DIMENSIONS AND ETHICAL PIECES AND ENGAGING WITH OTHERS, IT'S NOT REALLY THAT THESE ARE TWO ENDS OF THE SPECTRUM. THEY ARE INTEGRATED IN A LOT OF ETHICAL ISSUES WE MIGHT CONFRONT AND THINK ABOUT AND HOW WE MIGHT THINK ABOUT ENGAGING OTHER EFFORTS THAT ARE UNDERWAY FOR TRANSLATIONAL IMPACT AS CAROLINE POINTS TO. >>GREAT. BE . >>ANDREA DID WE LOSE YOU'RE HAND? >>YOU'RE NICELY BROUGHT IT BACK TO BRAIN AND IN TERMS OF RESEARCH SO WE DO GET AWAY FROM SOME OF THE THINGS THAT ARE STILL VERY INTERESTING BUT WINSTON RAISED THE SCOPE ISSUE. BUT I FEEL LIKE YOU'VE ALREADY GOTTEN THERE WITHOUT MY HELP. >>OKAY. WITH YOUR HELP THOUGH. JIM? >>THANKS. I PROMISE THIS WILL BE MY LAST COMMENT. I WANTED TO FOLLOW UP ON WHAT SOME OTHER HAD SAID, IN PARTICULAR, CAROLINE. JUST AS REMINDER, THE NEUROETHICS ROAD MAP HAD SUGGESTIONS AND COMMENTS WITH RESPECT TO THESE VARIOUS ISSUES, AND SO DRAWING ATTENTION TO IT AND HOW NEWG OR OTHER ENTITIES MIGHT BE INVOLVED IN HELPING TO ADDRESS SOME OF THESE, RECOGNIZING THESE ISSUES AND HELPING ADDRESS THEM BUT I ACTUALLY THOUGHT CAROLYN'S SUGGESTION ABOUT THE SBIR MECHANISM IS REALLY INTRIGUING. I DON'T KNOW THAT BRAIN DOES SBIRs, BUT TO ENGAGE COMPANIES EARLY ON WHEN THEY ARE JUST STARTING OUT WITH ETHICAL GUIDANCE, IF YOU WILL, OR AT LEAST AN OPPORTUNITY TO INTERACT ON ETHICAL ISSUES, IT'S A REALLY GOOD IDEA, IT'S SOMETHING THAT NEWG COULD BE INVOLVED WITH. AND MIGHT HAVE AN IMPACT VERY ON IN DEVELOPMENT OF THESE TECHNOLOGIES. >>GO AHEAD, JOHN. >>WE DO INDEED FUND SBIRs. WE'RE MANDATED BUT WE ACTUALLY DO SELECT OUT ONES THAT FIT OUR SPACE. I THINK WE SHOULD LOOK INTO. THERE'S CERTAINLY ONES THAT WOULD BENEFIT AS TO MANY OF OUR OTHER FUNDED STUDIES, FOR THEIR CONSIDERATION, WE MIGHT EXPAND OUR THINKING WHAT MIGHT BE APPROPRIATE AND RELEVANT. THAT'S A GREAT POINT. THANK YOU. >>WE DO HAVE MEMBERS OF THAT TEAM ON THIS CALL SO I'M SURE THEY HEARD THE COMMENT AS WELL. >>RIGHT. >>JIM, I WOULD ENCOURAGE YOU TO HIGHLIGHT SOME OF -- KAREN PUT THE REPORT BACK UP BUT SOME WAYS NEWG COULD ENGAGE ON THESE ISSUES PULLING THEM OUT OF THE REPORT INTO THE CHAT FOR US TO BRING BACK AS A THREAD THROUGH THE CONVERSATION WOULD BE TERRIFIC. INCLUDING OBVIOUSLY THE SBIRs THAT YOU HIGHLIGHTED. >>THANKS. >>SYD? >>YEAH, THIS IS A FOLLOW-UP ON JOHN'S COMMENT ABOUT MECHANISM BUT ONE OF THE KIND OF STRIKING DIFFERENCES FOR ME BETWEEN THESE TWO STUDIES THAT WE HEARD ABOUT IS THE FIRST ONE, DBS FOR DEPRESSION, IS VERY HYPOTHESIS DRIVEN. THEY HAVE, YOU KNOW, TARGET AREAS OF THE BRAIN WHICH HAVE BEEN STUDIED, WHICH THEY ARE GOING TO TRY TO INTERVENE ON, WHEREAS THE VR STUDY STRUCK ME AS BEING A LITTLE UNDERBAKED. THEY DIDN'T SEEM TO HAVE AN IDEA OF HOW THIS MIGHT WORK OTHER THAN, YOU KNOW, IT'S MORE DISTRACTING OR SOMETHING, THAN A 2D ENVIRONMENT MIGHT BE. AND SO, YOU KNOW, REALLY NOT HIGH HYPOTHESIS DRIVEN, I TRIED TO PUSH ON WHAT QUESTION, WHAT IS YOUR HIGH -- HYPOTHESIS, COOL, THEY WORK, BUT NOT UNDERSTANDING HOW OR WHY THEY WORK, YOU KNOW, OBVIOUSLY THE BRAIN IS INVOLVED WHEN WE'RE TALKING ABOUT PAIN BOTH IN TERMS OF THE SUBJECTIVE EXPERIENCE BUT THERE ARE ALSO, YOU KNOW, OBJECTIVE MEASURES OF PAIN, RIGHT? SOMEONE'S HEART RATE AND HOW FAST THEY ARE BREATHING AND ALSO OBVIOUSLY THINGS GOING ON IN THE BRAIN SO THERE'S ALL KINDS OF BIOMARKERS OR BIOFEEDBACK THEY MIGHT BE STUDYING TO HAVE A HYPOTHESIS ABOUT WHAT'S GOING ON WHEN THEY ARE USING THAT. SO, I DON'T KNOW TO WHAT EXTENT WE WANT TO GET INTO THAT ISSUE OF SHOULD OUR RESEARCH BE HYPOTHESIS DRIVEN THIS WAY OR, YOU KNOW, IS THIS JUST KIND OF AN INTERESTING THING AND MAYBE WE WANT TO SEE WHAT HAPPENS. I WOULD LIKE TO SEE RESEARCHERS WHO ARE THINKING MORE CAREFULLY AND DEEPLY ABOUT WHY SOMETHING MIGHT WORK AND WHY IT IS WORKING. WITH THE VR ONE REASON IS BECAUSE I THINK THERE IS POTENTIAL FOR ABUSE WITH A COMMERCIALLY AVAILABLE PRODUCT THAT PEOPLE MIGHT JUST SAY, HEY, I FEEL BETTER WITH THIS, I'M GOING TO KEEP DOING IT. >>GOOD POINT. SAMEER? >>YEAH, I WANT TO PICK UP A COUPLE THREADS, NITA, CAROLINE, A COUPLE OTHERS, AND MAYBE KIND OF PUT UNDER CATEGORY OF THIS CONFLICT BETWEEN INDIVIDUALIZATION VERSUS GENERALIZABILITY. SO, WE TALKED ABOUT THE WORKSHOP BACK IN MAY, IT WAS AMAZING. UNANIMOUSLY EVERYONE ENJOYED HEARING FROM THE RESEARCH SUBJECT PATIENT INDIVIDUAL AND HEARING THEIR THOUGHTS ABOUT WHY THEY PARTICIPATED, WHAT THEY GOT OUT OF IT, ET CETERA, SOMEONE COMMENTED HERE ABOUT ANDREW'S PRESENTATION. YOU KNOW, UNDERSTANDING THE HUMAN -- YOU TALKED ABOUT THIS IN THE MOUSE PSYCHIATRY THING ABOUT, YOU KNOW, KNOWING WHAT IT IS FROM THEIR PERSPECTIVE, WHAT THEY FELT LIKE, WHAT THEY WENT THROUGH. SO, THIS IS OVER A HUMAN NATURAL IDENTIFIABLE POIGNANT, I THINK THE CONFLICT THERE IS PERHAPS WITH HOW FAR DOWN THIS INDIVIDUALIZATION RABBIT HOLE DO WE GO VERSUS IDENTIFYING THERAPIES THAT ARE GENERALIZABLE, BECAUSE IF YOU GO DOWN REALLY FAR THEN YOU'RE IN THE SITUATION WHERE YOU HAVE TO DO THIS VERY -- TO TAKE ANDREA'S EXAMPLE, THIS COMPLEX IMPLANT, A LOT OF TIME, MONEY, EFFORTS, ET CETERA, PERHAPS EVERY SINGLE PATIENT WHICH IS JUST NOT FEASIBLE. I WANTED TO ASK THE QUESTION. WE HAVE A STUDY IN SOME WAYS SIMILAR BUT IN THAT WAY VERY DIFFERENT. IT WOULD BE FUN TO TALK ABOUT THAT. I THINK THIS GETS INTO THE NEUROETHICS SPACE BECAUSE IT'S A MATTER OF ACCESS AND USE OF RESOURCES. SO HOW MANY -- HOW MUCH CAN WE INVEST IN BEING SO HYPERINDIVIDUAL THAT EVERYONE IS SUPER DIFFERENT AND WE HAVE TO DO SOMETHING THAT'S EXPENSIVE OR TIME CONSUMING OR EFFORT CONSUMING, YOU KNOW, FOR EVERY PERSON BECAUSE WE KNOW THERE'S GOING TO BE SLIGHT DIFFERENCES VERSUS HOW MUCH DO WE SAY, LOOK, WE HAVE TO FIND THINGS THAT ARE GENERALIZABLE AND IT'S OKAY THAT MAYBE NOT EVERY SINGLE ONE IS AN ABSOLUTE, LIKE BOTTOM OF THE 9th GRAND SLAM BUT THERE'S MANY THAT ARE SOLID TWO-BASE HITS THAT STILL WIN THE GAME. THIS I THINK CUTS THROUGH A COUPLE DIFFERENT -- MANY OF THE ISSUES WE TALKED ABOUT. IT'S NOT SPECIFIC TO INVASIVE OR NON-INVASIVE OR HUMAN OR ANIMAL, WHATEVER. THIS MAY SOMETHING THAT WE COULD IDENTIFY AS MAYBE A CROSS-CUTTING THEME THAT IS WORTH THINKING ABOUT AT VARIOUS DIFFERENT LEVELS. >>DO YOU SEE WALTER'S QUESTION FOR YOU IN THE CHAT, SAMEER? >>THANKS, WALTER. HOW IS THIS DIFFERENT THAN WHAT OCCURS IN EPILEPSY? IT'S NOT. IT'S JUST HARDER TO FIND DEPRESSION BECAUSE WE DON'T KNOW WHAT WE'RE LOOKING FOR. IT'S NOT. THIS IS WHERE IT'S BORROWED FROM. WE DO THIS IN EPILEPSY, BUT DO WE REALLY? HOW MANY PEOPLE CAN ACTUALLY HAVE THAT DEGREE OF ACCESS AND SO WE DO IT THEORETICALLY AND A LOT OF CENTERS OF COURSE DO IT PRACTICALLY. BUT NOW ARE ARE GOING TO DO THAT FOR EVERY BRAIN-BASED DISORDER, EVERY NERVOUS SYSTEM-BASED DISORBED? DISORDER? WHAT CAN WE DO THAT IT'S GOING TO BENEFIT MANY MORE PEOPLE, MAYBE NOT TO THE Nth DEGREE BUT ENOUGH TO GET THEM BETTER, FUNCTIONAL. >>GREAT POINTS. WE TALKED ABOUT THIS AS WELL. ON THE ONE HAND VARIABILITY SEEMS TO BE VEXING, OBSTACLE. ON THE OTHER HAND VARIABILITY ONCE YOU FOLKS HAVE ENOUGH PATIENTS THAT YOU'VE WORKED WITH, YOU MIGHT UNDERSTAND BETTER THE SOURCES AND VARIABILITY, AT LEAST WHAT THEY MEAN IN TERMS OF PATIENT'S CONDITION AND RESPONSE TO DIFFERENT THERAPIES. I MEAN, NOT TO BE TOTAL POLLYANNA BUT I THINK THESE ARE STILL EARLY DAYS. WE HAVE A LOT YET TO LEARN. I SEE IN ALL AREAS OF BIOLOGY THERE'S THE INITIAL KIND OF REACTION TO RUN, BUT IF YOU EMBRACE IT, IT CAN TEACH US SOMETHING, SOMETHING TO KEEP OUR MINDS ON. THE OTHER THING, IF WE ARE TRULY AS A FIELD TO DEMOCRATIZE THESE KINDS OF TECHNOLOGIES FOR THESE DISORDERS, YOU WON'T BE ABLE TO IMPLANT THEM AND STUDY THEM FOR TEN DAYS, IT'S JUST NOT GOING TO BE I DON'T THINK FEASIBLE. BUT TO THE EXTENT THAT YOU CAN GENERATE GOOD DATA, UNDERSTAND THE VARIABILITY, MAYBE ONE DAY USING NON-INVASIVE RECORDING METHODS MIGHT GET YOU CLOSE ENOUGH TO HELP PEOPLE OUT. THESE ARE ISSUES WE WANT TO KEEP OUR EYES ON BUT THE EXPECTATION IS THE TECHNOLOGY AND OUR UNDERSTANDING IS NOT GOING TO BE STATIC, RIGHT? IF WE ASSUME THAT, WE WOULDN'T BE DOING THIS. IT'S IMPORTANT TO KEEP OUR EYES KIND OF ON THAT LONGER TERM GOAL, AND WITH THE -- REALLY WITH THE EXPECTATION IT'S GOING TO GET BETTER ENOUGH TO DO THIS IN A DIFFERENT WAY MORE SCALABLE BECAUSE ULTIMATELY WE DO NEED TO SCALE THIS. >>RIGHT. THAT'S ONE ANSWER, MAYBE ONE OF THE BETTER OR BEST ANSWERS. YOU KNOW, LIKE, RIGHT, WE HAVE TO DO DISCOVERY, UNDERSTAND WHAT OF THE VARIABILITY, WHAT ARE THE FIRST COUPLE PRINCIPLE COMPONENTS OF IT, AND WE HAVE TO HAVE SOME SENSE OF BREADTH BEFORE WE CAN IDENTIFY WHAT THOSE ARE SO MAYBE ONE POTENTIAL ANSWER TO THE QUESTION IS WE NEED TO THINK OF, VISUALIZE SOME PATHWAY TOWARDS HOW THIS IS GOING TO HELP WITH EVENTUAL GENERALIZATION BECAUSE OF UNPROVEN TECHNOLOGY THAT MAKES IT COSTLY, WHATEVER, BUT THAT KEEPS US ON TRACK SO WE DON'T GET SO OFF THE TRAIL THAT WE'RE LIKE REALLY FOCUSING ON ONE INDIVIDUAL IN THE WORLD AT THE EXPENSE OF MANY, MANY OTHERS. >>GREAT POINT. NITA? >>YES, SO THIS IS A RICH AND REALLY GREAT STARTING POINT I THINK TO THE CONVERSATION. FOCUSING ON WHAT IF ANYTHING NEWG MIGHT DO IN THIS SPACE THAT COULD BE SPECIFIC, CONCRETE, IMPACTFUL. I THINK THE QUESTION IS WHERE AND HOW WE MIGHT WANT TO ENGAGE, AND JIM MENTIONED THAT THE REPORT TALKED THROUGH SOME OF THE OPPORTUNITIES FOR ENGAGEMENT, AND I WONDER IF I MIGHT PUT HIM ON THE SPOT AND INVITE HIM TO PUT SOME OF THOSE ON THE TABLE FOR US TO DISCUSS AS A STARTING PLACE RATHER THAN REINVENTING THE WHEEL. BUT THE QUESTION I THINK AT HAND IS, YOU KNOW, FIRST SHOULD WE, AND I THINK THE ANSWER TO SHOULD WE, IF WE CAN DO SOMETHING CONCRETE, SPECIFIC, IMPACTFUL, COULD BE WE NEED FURTHER CONVERSATIONS, WE'RE READY TO DIVE INTO A PAPER OR SPECIFIC KINDS OF RECOMMENDATIONS ACROSS A PARTICULAR SPACE, BUT SOMETHING THAT COULD BE USEFUL IS MY HOPE WE'LL FOCUS OUR EFFORTS ON. JIM, COULD I ASK YOU TO PUT YOU ON THE SPOT TO SAY PUT SOME OF THOSE ON THE TABLE SO WE DON'T REINVENT THE WHEEL OF THE IMPORTANT WORK YOU'VE ALREADY DONE ON THIS? >>YOU CAN CERTAINLY ASK BUT UNFORTUNATELY I HAVEN'T LOOKED AT THE REPORT IN A WHILE. WHAT I HAVE TO DO IS LOOK THROUGH AND SEND PEOPLE AN E-MAIL WITH, TO WHAT RECOMMENDATIONS WERE UNLESS KAREN OR CHRISTINE, ALSO ON THE COMMITTEE, MIGHT REMEMBER MORE SELECTIVELY. WE DID HIGHLIGHT VARIOUS ISSUES THAT MAY COME UP AND MIGHT BE ADDRESSABLE, AND THERE WERE SOME RECOMMENDATIONS ALONG THE WAY BUT UNFORTUNATELY WHAT I HAVE TO DO IS SEND AN E-MAIL FOLLOW-UP WITH RESPECT TO IT. SORRY, NITA. >>THAT'S OKAY. LET ME OPEN THE CONVERSATION THEN -- >>I CAN ADD A FEW RELATED TO THAT IF YOU'D LIKE. >>PLEASE, KAREN. >>I THINK ACTUALLY FOR FUTURE REFERENCE, CHAPTERS 5 AND 6 ARE PARTICULARLY HELPFUL, AND AT THE END OF ALL OF THEM WE HAD A GREAT STRUCTURE, THERE'S BULLETED POINTS IN THE END, ACTION ITEMS. A LOT OF THEM I THINK HAVE SPECIFIC THINGS BUT FIT AROUND GENERAL THEMES THAT WITHIN WHAT MOST OF US THINK NEWG SHOULD BE DOING, AND A LOT OF THAT PROCESS AND METHODOLOGY IS RAISING AWARENESS, AND SOME OF THAT WILL BE A DEVELOPMENT OF CERTAIN RESOURCES, TOOLS, WE TALKED ABOUT THAT FOR A LONG TIME BUT NEUROETHICS ROADMAP DEMOCRATIZES THAT. THE OTHER IS ABOUT CONVENING, SOMETHING WE'VE DONE WELL, AND I THINK ALSO CAROLINE MENTIONED SOMETHING IMPORTANT THAT I HOPE COMES BACK TOO, WHICH IS INVITATION TO INCLUDE ADVOCATES, AND CHAPTER 5 ESPECIALLY TALKS ABOUT REAL WORLD TRANSLATION SO I THINK THERE'S PIECES IN THERE THAT TALK ABOUT BUILDING COMMUNITY THAT RAISE AWARENESS, BUILDING TOOLS, THAT WE COULD SPEAK TOWARDS. TOOLS COULD BE CERTAINLY BREAD AND BUTTER OF THIS ECOSYSTEM, HIGH IMPACT ACADEMIC PAPER, BUT THERE MIGHT BE SOME OTHER THINGS THAT WE CO-CREATE TOO. GENERALLY THOSE ARE THINGS I WOULD ENCOURAGE US TO LOOK AT THOSE SPECIFIC BULLETED POINTS AND CALL OUT BOXES AROUND THOSE THEMATIC AREAS. I'LL LEAVE IT AT THAT. >>YOU MAY REMEMBER WE HAD A LIST OF THINGS THAT CAME OUT OF THE ROADMAP THAT WERE POSSIBLE TOPICS FOR THE NEWG TO WORK ON. AND I HAVE THAT LIST, I THINK. I DON'T KNOW IF IT'S THE MOST UP-TO-DATE ONE BUT I COULD PULL IT UP. IT'S GOT A LOT OF STUFF ON IT. AS KAREN SAID, SOME OF IT IS SPECIFIC CHAPTERS BUT THERE'S IDEAS THROUGHOUT THE ROADMAP FOR DIFFERENT THINGS THAT MIGHT BE RELEVANT TO WHAT WE'RE TALKING ABOUT TODAY. >>IT WOULD BE GREAT TO FOLLOW THAT UP, CHRISTINE. WHILE YOU DO THAT, I MIGHT INVITE US TO THINK ABOUT WHATEVER WE LAND ON IN THIS SPACE THAT WINSTON SAID HE WAS TRYING TO WRAP HIS HEAD AROUND WHAT THE SCOPE OF THE CONVERSATION REALLY IS ABOUT. AND I WANT TO INVITE REFLECTIONS ON THAT, THE CONVERSATION ON PERSUADING, MODULATING, MANIPULATING, CHANGING THE BRAIN WHICH, AGAIN, COULD BE AN ENORMOUS SCOPE. ANDREA'S POINT IT'S FOCUSED ON HEALTH AND BRAIN IS A LIMITING FACTOR BUT NOT PRECISELY LIMITING FACTOR SO I WANT TO INVITE ANY COMMENTS ON INTEREST IN SCOPING THE PROBLEM FOR CONSIDERATION BY NEWG. >>JOHN, YOU HAD A HAND THAT WENT UP FOR A MILLISECOND? NO? IT WAS MY EYES PLAYING TRICKS ON ME. JIM? >>YEAH, THANKS, NITA. YEAH, WITH RESPECT TO THE SCOPE, AGAIN MAYBE GOING BACK TO WHAT I MENTIONED AT THE VERY BEGINNING OF THIS DISCUSSION, FOR ME REALLY ONE OF THE MOST IMPORTANT ASPECTS IS REVERSIBLE VERSUS NON-REVERSIBLE. REVERSIBLE COULD BE PROBLEMATIC BUT SOMETHING THAT'S NOT REVERSIBLE MAYBE THERAPEUTIC FOR A WHILE BUT THE TRIAL STOPS AND THERE'S NO RECOURSE FOR THE PATIENT AFTER THAT, I THINK THEY DO REQUIRE DIFFERENT ETHICAL CONSIDERATIONS AND WE MAY WANT TO LIMIT OURSELVES TO ONE VERSUS THE OTHER, MAYBE DISCUSS DISTINCTIONS MORE BUT I THINK THAT'S ONE OF THE KEY ASPECTS FOR ME. >>THAT'S HELPFUL. I WILL SAY ONE IS A CATEGORY IS IMPACT, RIGHT? AS JIM HAS PUT WITHIN THAT IMPACT WHETHER IT'S REVERSIBLE OR IRREVERSIBLE. TO ME PART OF THE QUESTION IS HOW IT'S DONE AS WELL SO THAT'S WHY I RAISE THE OPEN LOOP VERSUS CLOSED LOOP, BECAUSE I THINK THAT HAS INTERESTING DIFFERENCES AND IMPLICATIONS PARTICULARLY AS YOU BRING MORE A.I. INTO THE PICTURE OF CLOSED LOOP FOR WHAT MEANS AND HOW WE MONITOR AND EFFECTS AND POSSIBLE RISKS AS WELL. WINSTON? >>IF I COULD JUMP IN TO FOLLOW UP ON JIM'S COMMENT. THAT'S AN IMPORTANT POINT BUT JUST TO MAKE IT A LITTLE BIT MORE INTERESTING I MEAN HOW WILL WE NECESSARILY KNOW AHEAD OF TIME WHAT WILL BE REVERSIBLE OR NOT REVERSIBLE? >>AND WHAT DOES THAT EVEN MEAN, RIGHT? >>I WAS GOING TO PIVOT OFF OF THAT ALSO. I THINK THAT, YOU KNOW, IT'S MAYBE IMPORTANT TO THINK ABOUT BUT THERE'S A CONTEXT OF OTHER THINGS THAT PEOPLE ARE DOING TO AFFECT BRAIN FUNCTION, AS WE SAID BEFORE, PROBABLY WOULDN'T FULL UNDER THE SCOPE OF THIS TECHNOLOGY BUT HAVE WIDE RANGING IMPACTS WE DON'T UNDERSTAND. YOU KNOW, THE NOVEL TECHNOLOGIES ARE IN A SPACE WHERE THOSE OTHER THINGS THAT ARE GOING ON WHERE WE REALLY DON'T KNOW, I THINK THAT, YOU KNOW, FOR ALL WE SAID ABOUT MECHANISM OF ACTION LIKE A LOT OF MEDICATIONS WIDELY USED IN THE BRAIN WE DON'T REALLY UNDERSTAND MECHANISM OF ACTION AND STATISTICS IS 1 IN 8 AMERICANS IS TAKING AN SSRI, WE DON'T REALLY KNOW HOW THEY WORK, THERE'S A LOT OF CONTROVERSY ABOUT WHAT THE LONG-TERM EFFECTS OF THESE MEDICATIONS ARE AND SO FORTH. OF COURSE, THE CLINICAL TRIALS ON WHICH THEY WERE APPROVED FOLLOWED PEOPLE FOR MUCH SHORTER PERIODS OF TIME AND WITH A DIFFERENT MODEL FOR PSYCHOPHARMACOLOGIC TREATMENT THAN IS CURRENTLY BEING USED. THERE'S SIMILAR QUESTIONS THAT MIGHT -- THAT WE MIGHT HAVE ABOUT OTHER WIDESPREAD INTERVENTIONS, THINGS LIKE UNIVERSAL CHILDHOOD EDUCATION IS ONE THING WITH THE MOST INFLUENCE ON BRAIN FUNCTION, WE SEE IT IN MY FIELD OF DEMENTIA, WHY AGE ADJUST THE RATES ARE FOLLOWING IN MANY PLACES, PROBABLY HAS TO DO WITH THINGS LIKE THAT AS WELL AS OTHER SORT OF HEALTH BEHAVIORS. SO, I THINK THIS ISSUE OF DISENTANGLING LONG-TERM EFFECT IT'S OF BRAIN INTERVENTIONS FROM ALL KINDS OF OTHER DOWNSTREAM EFFECTS OF LIFESTYLE CHANGES OR CHANGES IN THE KINDS OF LINES OPENED UP TO PEOPLE, I THINK GETS US INTO SOME OF THE REAL MESSINESS ABOUT TRYING TO STUDY THE BRAIN IN THE FIRST PLACE. >>I THINK THAT'S RIGHT. JOHN? >>YEAH, THANKS, WINSTON. IN TERMS OF WHAT WOULD HELP "BRAIN," FROM OUR POINT OF VIEW, REALLY THIS IS I THINK NEWG'S ROLE AND THE VALUE TO "BRAIN" IS LET ME TRY TO SYNTHESIZE A COUPLE POINTS RAISED. THERE'S AN ISSUE THAT CAME UP ABOUT HAVING MECHANISM OR EVEN ABSENT MECHANISM AT LEAST HAVING A HYPOTHESIS FOR WHAT MIGHT BE GOING ON, WHETHER YOU'RE GIVING A PATIENT, YOU KNOW, A PILL OR IMMERSIVE EXPERIENCE OR DIRECTLY STIMULATING THE BRAIN WITH AN IMPLANT OR INDIRECTLY SAY THROUGH FOCUSED ULTRASOUND, WHATEVER THE CASE, TO THE EXTENT THAT WE UNDERSTAND MECHANISM WOULD HELP US TRY TO NAVIGATE THESE ISSUES, I THINK IT'S SAFE TO SAY THAT THE BRAIN INITIATIVE IS A NEUROSCIENCE INITIATIVE, NEUROTECHNOLOGY INITIATIVE, NOT A BRAIN SCIENCE. WHEN WE'RE ULTIMATELY WORKING WITH THE BRAIN IT'S BIOLOGICAL ORGAN, BIOLOGICAL SYSTEM. SO TO THE EXTENT WE MIGHT CONSIDER HOW TO NOT SO MUCH LIMIT BUT CONSTRAIN AT LEAST THE INITIAL SET OF ARGUMENTS OR QUESTIONS IN ORDER TO GET SOME TRACTION I THINK IF WE STAY WITHIN THE SPACE OF LOOKING AT STUDIES OR FIELDS WHERE WE MAY NOT UNDERSTAND -- WE STILL DON'T UNDERSTAND FULLY THE MECHANISM OF HOW THE BRAIN WORKS AND THAT'S WHY WE'RE HERE, FOR MANY GENERATIONS TO COME, BUT IF WE CAN KEEP THE CONVERSATION IN THE REALM OF WHAT'S BIOLOGICALLY POSSIBLE AND WHAT'S EXPERIMENTALLY TESTABLE, I THINK THAT MIGHT KIND OF KEEP THE CONVERSATION A LITTLE BIT MORE REAL AND FROM, YOU KNOW, GETTING TOO DIFFUSE BECAUSE ULTIMATELY FROM -- I HATE TO BE TRANSACTIONAL FROM THE BRAIN STANDPOINT WE NEED TO UNDERSTAND THE IMPACT OF WHAT WE'RE SUPPORTING IN THESE DIFFERENT AREAS THAT AFFECT HUMANS. AND IT'S HARD FOR ME TO KIND OF UNDERSTAND HOW WE'RE GOING DO THAT IF WE'RE NOT THINKING ABOUT A TESTABLE HYPOTHESES OR REALITY OF MECHANISMS SO THAT'S MY THOUGHTS FROM HEARING A LOT OF YOUR INPUT HERE TODAY BASED ON THE PRESENTATIONS AND CONVERSATION HERE. >>THANKS, JOHN. TED? >>YEAH, JOHN, TO EXTEND THAT MORE, I'M THINKING BACK TO SOME DISCUSSIONS WE HAD THINKING ABOUT BRAIN-COMPUTER INTERFACE, AND THE NEUROETHICS AROUND THAT, THAT THAT SEEMS LIKE A MORE CONCRETE DISCUSSION IN SOME WAYS BECAUSE WHAT I WAS GOING TO SAY IS WE'RE ACTUALLY ASSUMING -- I MEAN ALL THESE THINGS AFFECT THE BRAIN, DEPRESSION AND ET CETERA, BUT WHAT THEY ARE AND THE NATURE AS A DISORDER AND WHETHER THEY ARE MICROBIOME OR OUR MOTHER'S PLACENTA OR OUR ADRENAL OR OTHER THINGS THAT ARE NOT NECESSARILY MAPPED TO THE PREFRONTAL CORTEX OR SOMETHING IS SOMETHING THAT YOU KIND OF GET INTO WHEN YOU THINK ABOUT THESE AS DISEASE ENTITIES. WHICH IS NOT WHAT WE'RE DOING, RIGHT? SO THAT'S I THINK WHAT YOU SAID, JOHN, IS AN IMPORTANT AND ANDREA CHIMED IN TO KEEP US THINKING ABOUT THE BRAIN INITIATIVE. THAT MAY MEAN THERE ARE PARTICULAR ASPECTS IN THIS SPACE WE MIGHT WANT TO FOCUS ON, AND THE NEUROETHICS ISSUES OF THAT, FOR EXAMPLE, THE BRAIN-COMPUTER INTERFACE WORK. >>PERFECT. KAREN? >>AGAIN, I REALLY LIKED THESE THREE QUESTIONS. I REALLY APPRECIATE THIS APPROACH. I THINK I WANT TO RESONATE WITH OTHERS THE APPROPRIATE SCOPE SEEMS TO BE WHATEVER "BRAIN" IS DOING AND FUNDING, AND WHAT I APPRECIATED CHRISTINE DID AT ONE POINT, HANK ALSO DID AT EACH MEETING, ASK THE RESEARCHERS WHO WE INVITED TO ATTEND WHAT THEY NEED AND WHAT WE CAN DO TO HELP THEM. AND I THINK KIND OF MY VISION, MY PERSONAL VISION STATEMENT FOR THIS GROUP HAS ALWAYS BEEN THAT WE'RE EMPOWERING THE RESEARCHERS SO THEY CAN EMPOWER THE PUBLIC TO RECEIVE THE BENEFITS OF THEIR SCIENCE. THAT'S AN ORIENTATION, HOW CAN WE HELP THE BRAIN RESEARCHERS? AN OPEN QUESTION WHICH DOESN'T FOCUS HERE LIKE FOR SCOPE BUT STILL WHETHER WE WANT TO SERVE IN A FORESIGHT FUNCTION OR EVEN A FOUNDATIONAL ISSUE, KIND OF ADDRESSING ISSUES LIKE WHAT IT MEANS TO QUANTIFY THE HUMAN EXPERIENCE. MAYBE THIS IS DISTINCTION THAT "BRAIN" HAS ON PURPOSE FROM THE HUMAN BRAIN PROJECT BUT THE HUMAN BRAIN PROJECT PUT OUT A LOT OF MATERIALS ON THOSE TYPES OF ISSUES THAT REALLY INTERESTED THE SCIENTISTS IN THAT GROUP. YOU'D BE SURPRISED. THAT FURTHER CALLED FOR THEM TO DEVELOP MODULES FOR THE SCIENTISTS ON THESE SPECIFIC TARGETED ISSUES, AND NOW WE SEE IN THE SECOND GENERATION TOWARDS E BRAINS, A COMMUNITY OF RESEARCHERS READY TO BE ENGAGED. IT'S NOT FREE OF PROBLEMS. THEY HAVE HAD A LOT OF CHALLENGES TOO BUT IT'S INTERESTING MODEL. I GUESS AS FAR AS SCOPE I THINK I'M CLEAR ABOUT THINKING ABOUT WHAT BRAIN RESEARCHERS WANT AND NEED, BUT ALSO A QUESTION WHETHER WE WANT TO THINK ABOUT FORESIGHT AND FOUNDATIONAL ISSUES BECAUSE IF WE'RE GOING TO DO THOSE THINGS WE MIGHT HAVE BROADER REACH, PARTICULARLY WALTER KEPT PUSHING US TO ASK ABOUT MISUSE, AND CHRISTINE ALSO ASKED ABOUT THAT TOO. YOU COULD SEE IT WAS QUITE DIFFICULT FOR THEM TO GO BEYOND HARM, LIKE THE TYPICAL RCR COMPLIANCE TRAINING THAT WE REQUIRE PEOPLE TO TAKE. SO I THINK THAT'S A NON-TRIVIAL ISSUE FOR US TO DISCUSS. >>THANKS, KAREN. THAT'S HELPFUL. I AGREE, WE ALL AGREE ON SCOPE STARTING WITH AT LEAST BRAIN, RIGHT? THAT'S PART OF WHY WE ROOTED THIS CONVERSATION IN BRAIN, GOING FORWARD OBVIOUSLY THAT'S WHERE IT COULD BE MOST IMPACTFUL AND HELPFUL. AGREED ALSO WE NEED TO FIGURE OUT FROM THE RESEARCHER'S PERSPECTIVE, PROGRAM OFFICERS' PERSPECTIVE, WHAT ARE THE BIG QUESTIONS. BUT PART OF IT IS FORESIGHT, KAREN, FORESIGHT WITH RESPECT TO THE EMERGING ETHICAL ISSUES THAT ARE BEYOND RCR, AND HELPING TO HAVE FORESIGHT WITH RESPECT TO WHAT THOSE ISSUES ARE. CHRISTINE WILL SHARE WITH US HERE JUST THE SLIDES FROM BRAIN 2.0, BUT LET ME SUGGEST BASED ON THIS CONVERSATION GIVEN WE'RE IN THE EARLY STAGES OF IT MAYBE A WORKSHOP IS A GOOD NEXT STEP FOR US TO FLESH OUT THESE ISSUES, DOESN'T SOUND LIKE WE'RE READY TO COALESCE AROUND CO-CREATED PAPER OR SOMETHING TO THAT EFFECT. SO I'M PUTTING THAT OUT THERE FOR A TEMPERATURE CHECK TO SEE HOW PEOPLE FEEL ABOUT THAT AS A POSSIBILITY FOR MOVING AHEAD. CHRISTINE, WILL YOU SHARE THAT IN THIS IS A DEEP DIVE, COMPREHENSIVE WITH JUST 8 MINUTES REMAINING WE'RE NOT GOING TO GO THROUGH ALL OF IT BUT JUST REFRESH OUR RECOLLECTION AS TO THE ISSUES ON THIS. >>SURE. I THINK IT MIGHT TAKE US IN A DIFFERENT DIRECTION BUT I'LL PUT THEM UP BECAUSE IT IS WORTH SEEING. THIS IS FROM JANUARY OF 2021. SO TWO YEARS AGO. >>I WONDER IF YOU COULD DO IT AS A SLIDE SHOW BECAUSE IT'S SMALL. >>I CAN. IT TAKES ME A MINUTE TO FIGURE IT OUT. CAN YOU SEE THAT? >>YES, GREAT. >>SO, THIS WAS TWO YEARS AGO. AND WE ASKED OURSELVES SOME OF THE SAME QUESTIONS. >>CAN YOU FLIP THE SCREEN? >>WHAT THE SCREEN? MAYBE. >>YOU'RE IN PRESENTER MODE. >>THAT WAY? >>YEP, YEP. >>OKAY. WE WERE ASKING OURSELVES WHAT WE SHOULD DO THEN. THIS WAS THE SORT OF SUMMARY OF THE ENTIRE SET OF CHAPTERS WITHIN THE ROADMAP. NO, SORRY. THIS IS THE CHARGE TO THE NEUROETHICS WORKING GROUP, REMIND THE PEOPLE WHAT OUR CHARGE WAS. PRETTY FAMILIAR, I WON'T READ THEM. YOU CAN SEE IT IS A VERY USEFUL SET OF REMINDERS. THESE WHY THE CATEGORIES FROM THE ROADMAP. JIM, JUMP IN IF THERE'S ANYTHING YOU SEE TO HIGHLIGHT. THESE WERE THE CHAPTERS. AND THEN WE LISTED, AGAIN THIS IS -- WE LISTED SOME THINGS THAT WERE INCLUDED IN THE CONCEPTUAL AND EMPIRICAL SPACE, BACK FROM THE ROADMAP INCLUDING EQUITY, PRIVACY, VULNERABILITY, LONG-TERM OBLIGATIONS, ANIMAL MODELS. AND OF COURSE HAD SOME VERY SPECIFIC EXAMPLES OF THINGS UNDER THOSE CATEGORIES. I'LL GIVE YOU A MINUTE TO LOOK AT THEM WITHOUT READING THEM. AND THEN WE ASKED THIS QUESTION WE HAD SOME IDEAS FOR GUIDANCE NOT CALLED GUIDANCE, THINGS WE COULD THINK ABOUT SPECIFICALLY FOR RESEARCHERS RELATED TO THE DESIGN OF RESEARCH AND CONDUCT OF RESEARCH. IF I'M GOING TOO FAST, TELL ME. WE HAD IDEAS OF IMPROVEMENT AND GUIDANCE FOR REGULATORS, POLICYMAKERS, IRBs, FUNDERS. >>INTERESTING WE DON'T HAVE ANYTHING ON MODULATING CHANGING ON THE BRAIN. >>WE DON'T. I MEAN, OTHER THAN THE SORT OF -- THERE WAS GENERAL STUFF N RISK BUT IT WASN'T SPECIFIC. ETHICAL FRAMEWORKS. RESOURCES. INTEGRATING NEURAL SCIENCE AND NEUROETHICS. AND TRAINING IDEAS. AND PUBLIC ENGAGEMENT. WE ALSO HAD I THINK THE LAST SLIDE -- OH, HERE WE GO. POSSIBLE NEWG ACTIVITIES. RECOMMENDING RESEARCH TOPICS, HOLDING WORKSHOPS, SUPPORTING CHANGES TO NEUROSCIENCE RESEARCH OR REVIEW, AND ENDORSING TRAINING AND INTEGRATION OF PUBLIC ENGAGEMENT. I THINK THERE'S A SLIDE -- I THOUGHT THERE WAS ONE ON THE TRANSFORMATIVE IDEAS THAT JIM WILL REMEMBER. >>YEAH, MAYBE I COULD JUMP IN FOR A MOMENT, CHRISTINE. THIS IS A GOOD HELICOPTER VIEW OF THE REPORT BUT THERE WAS VERY LITTLE ON CHAPTER 6, WHICH IS WHAT ACTUALLY PRIMARILY DEALT WITH WHAT WE DISCUSSED TODAY. THERE ARE THINGS WITH RESPECT TO BRAIN STIMULATION, EARLIER CHAPTER, I THINK CHAPTER 2. I ENCOURAGE PEOPLE TO LOOK AT CHAPTER 6 IN PARTICULAR, AND CHAPTER 5 AS KAREN MENTIONED, DEALING MORE WITH THE ISSUE OF DIFFERENT RANGE OF TECHNOLOGIES IN PARTICULAR CONSUMER POTENTIAL TECHNOLOGIES, SUCH AS VR AND TRYING TO, YOU KNOW, ASSESS SOME OF THE ISSUES THAT MIGHT COME UP AND SOME PARTICULAR RECOMMENDATIONS SO THOSE WEREN'T SPECIFICALLY IN THIS PRESENTATION SINCE CHAPTER 6 SEEMED TO BE A LITTLE BIT BEYOND WHAT NEWG MIGHT BE ADDRESSING AT THE MOMENT WHEN THIS WAS PUT TOGETHER. >>I THINK IT ALSO GOES BACK TO SOMETHING WE JUST DISCUSSED TODAY. I DO HAVE NOTES ON THESE THINGS THAT SAID, YOU KNOW, SOME OF THE TOPICS RAISED IN CHAPTER 6 WERE SPECIFICALLY ABOUT USING NEURAL TECHNOLOGIES OUTSIDE OF THE CLINICAL SPACE, YOU KNOW, IN EDUCATION, LEGAL AREAS, ET CETERA, EMPLOYMENT, NATIONAL SECURITY. AND THE DISCUSSION AT THE TIME WE DISCUSSED THIS A COUPLE YEARS AGO WAS THAT WAS OUTSIDE THE SCOPE OF BRAIN. >>WELL, THAT'S A LOT FOR US TO DIGEST. WE PUT A PARTICULAR TOPIC THAT ISN'T ON THE CLEAR LIST THERE BUT THIS GIVES US A LOT OF SCOPE TO THINK ABOUT THAT. I MIGHT SUGGEST THAT FOLKS -- WE WON'T MAKE ANY DECISIONS I DON'T THINK HERE IN A MINUTE AND 15 SECONDS, BUT I WOULD SUGGEST THAT WE, YOU KNOW, RECIRCULATE THAT POWERPOINT AND IT WOULD BE TERRIFIC TO HAVE PEOPLE WEIGH IN BY QUICK E-MAIL,ER WHO NEXT ST, MODULATING, CHOOSING SOMETHING, THINKING ABOUT SPECIFIC CONCRETE IMPACTFUL CONTRIBUTIONS THAT WE COULD MAKE IN NEWG FOR THE BRAIN INITIATIVE. KAREN, YOU GET THE LAST WORD ON THIS TOPIC. >>I WAS JUST GOING TO SUGGEST ACTUALLY WORKSHOP FOR NEWG IN ITS NEW COMPOSITION AND NEW LEADERSHIP TO INTERNALLY THINK ABOUT HOW TO ALIGN OUR DESIRED IMPACT WITH THE EXPECTED IMPACT THAT OUR STAKEHOLDERS MIGHT HAVE FOR US, AND I THINK USING YOUR RUBRIC OF THE THREE QUESTIONS WOULD BE WONDERFUL AND ALSO GOING BACK TO WHAT A LOT OF GREAT STUFF THAT WAS IN THE NEUROETHICS ROAD MAP. THANKS AGAIN TO JIM, HEROIC LEADER OF THAT EFFORT. >>THANKS, KAREN. THAT'S A GREAT SUGGESTION. WE'LL SUGGEST EVERYBODY TAKE THAT INTO CONSIDERATION AND ALSO TAKE INTO CONSIDERATION THE CONVERSATION TODAY AS WELL AS WHAT RECIRCULATES, WEIGH IN ON YOUR NEXT STEPS, MINI VIRTUAL RETREAT AS WE DO EXACTLY THAT WHICH IS TO FIGURE OUT OUR NEXT STEPS TOGETHER. SHOULD I CLOSE US OUT, CHRISTINE? OKAY. WELL, THANK YOU, EVERYBODY, FOR JOINING US TODAY. THIS HAS BEEN A RICH AND VALUABLE CONVERSATION, STIMULATED A LOT OF THINKING AND CHANGED MY BRAIN. HA, HA. I HOPE IT CHANGED ALL OF YOURS IN WAYS THAT ARE BENEFICIAL. AS ALWAYS, GRATEFUL FOR YOUR TIME AND CONTRIBUTIONS, AND SERVICE, IN THIS EFFORT. THANKS, EVERYBODY. LOOKING FORWARD TO THE CONTINUED CONVERSATIONS ON THIS TOPIC. >>COME BACK FOR THE CLOSED SESSION. >>WAIT, CHRISTINE, WE HAVE ONE MORE ITEM ON THE AGENDA. >>OH, YES, SORRY, SORRY. NITA WILL RETURN THAT. >>YOUR CHARTER IS WAITING FOR YOU. >>I'VE GOT TO GO, GREAT TO SEE YOU ALL. >>TAKE PICTURES, SEND PICTURES. >>I WILL. >>SO JUST BEFORE THE BREAK WE'RE GOING TO DO OUR ROUNDTABLE UPDATE TO SEE WHAT ALL THE NEWG MEMBERS HAVE BEEN UP TO IN THE SPACE. SO I'LL CALL ON FOLKS ONE BY ONE, FEEL FREE TO SHARE AND LET US KNOW WHAT'S BEEN HAPPENING SINCE THE LAST TIME WE MET. NITA, WE'LL START WITH YOU. >>THANKS, EVERYBODY. I'VE ENJOYED A LOT OF RICH CONVERSATIONS IN THE SPACE AROUND NEUROTECHNOLOGIES, MOST RECENTLY, AND THE LAST WEEK WAS AT THE WORLD ECONOMIC FORUM IN DAVOS WHERE I HAD AN OPPORTUNITY TO PRESENT ON BRAIN TRANSPARENCY AS A TOPIC, THERE WAS A LOT OF INTEREST I THINK FROM DIFFERENT STAKEHOLDERS ACROSS THE WORLD ENGAGING ON THAT TOPIC, ALSO HAD AN OPPORTUNITY TO ENGAGE IN A PANEL ABOUT REIMAGINING HEALTH CARE AND TRANSFORMATIVE ISSUES IN THAT SPACE. I THINK TOP OF MIND FOR A LOT OF PEOPLE ARE ISSUES AROUND PRIVACY, AND THINKING ABOUT DATA SHARING AND HOW WE MIGHT MOVE TO A PLACE IN WHICH DATA SHARING COULD BE SOMETHING THAT IS DONE CONFIDENTLY BY INDIVIDUALS WHILE SAFEGUARDING AGAINST RISK OF MISUSE. THAT'S WHAT I'VE BEEN UP TO, AND MY BOOK, THE BATTLE FOR YOUR BRAIN, COMES OUT IN MARCH, I'LL BE ON THE ROAD TALKING ABOUT THAT OVER THE NEXT COUPLE OF MONTHS. >>WINSTON? >>MAJOR UPDATES FOR ME IS I'VE BEEN NAMED EXECUTIVE DIRECTOR OF BIOETHICS AT UCSF, THINKING ABOUT THE RELATIONSHIP BETWEEN SOME QUESTIONS WE'RE ASKING IN NEUROETHICS AND A LONG HISTORY OF SCHOLARSHIP AND BIOETHICS THAT IS OVERLAPPING. SO, HOW TO INCORPORATE PARTICULARLY AS WE'RE TALKING ABOUT THINGS LIKE CLINICAL OR HEALTH-RELATED APPLICATIONS OF NEUROTECHNOLOGY, THERE'S A LOT TO DRAW ON, AND THERE'S A LOT OF OVERLAP ALSO WITH OUR COLLEAGUES IN GERIATRICS AND PEDIATRICS, YOU THINK ABOUT BRAIN DEVELOPMENT THROUGHOUT THE LIFESPAN. >>THANKS, WINSTON. JIM? >>THIS WILL BE SHORT. I HAVE NO NEUROETHICS UPDATE FOR EVERYONE. >>THANKS, JIM. SYD? >>I'VE HAD A COUPLE OF PAPERS ON -- A PAPER AND A BOOK CHAPTER ON BRAIN DEATH RECENTLY, AND MONDAY I'LL BE IN D.C. FOR A CONGRESSIONAL BRIEFING WHICH I'VE NEVER DONE BEFORE, AND SO KIND OF EXCITED AND ANXIOUS ABOUT THAT. THAT'S GOING TO BE ON ANIMAL RESEARCH. >>THANKS, SYD. COME SAY HI TO NIH IF YOU'RE IN THE AREA. CAROLINE? >>YEAH, THANK YOU, NINA. A LOT OF UPDATES ACTUALLY COMING FROM OUR SIDE. IT'S BEEN A BUSY SET OF MONTHS SINCE WE LAST MET. MANY PEOPLE ON THE CALL ARE AWARE THE DANA FOUNDATION REFINED ITS MISSION TO ADVANCING NEUROSCIENCE THAT BENEFITS SOCIETY AND REFLECTS ASPIRATIONS OF ALL PEOPLE, AND SO UNDER THAT MISSION AREA WE'VE DEVELOPED OUR THREE PROGRAMMATIC PILLARS, PROGRAMMATIC STRATEGIES LED BY KAREN RAMOS FORMERLY AT NIH, VERY GLAD TO HAVE HER, ALSO THE PROGRAMMATIC PILLARS ARE DINA EDUCATION, NEXT GEN AND DINA FRONTIERS, AND SO A FEW RELEVANT I THINK NEWG UPDATES, JUST UPDATES FROM THE NEUROETHICS COMMUNITY, ONE OF THEM COMING FROM THE DINA EDUCATION PILLAR IS BRAIN AWARENESS WEEK WHICH THE FOUNDATION SPONSORS, COMING UP MARCH 13-19. YOU MIGHT HAVE DIFFERENT ACTIVITIES AT THAT TIME, SO WE TRY TO HELP PROMOTE ALL OF THOSE ACTIVITIES. ANOTHER RELATED UPDATE IS COMING FROM THE DINA NEXT GEN PROGRAM, THE SIGNATURE OF THAT PROGRAM IS THE CENTERS IN NEUROSCIENCE AND SOCIETY WHICH I SHARED ABOUT WITH EVERYBODY HERE DURING OUR LAST MEETING, WE WERE VERY HAPPY LAST FALL TO AWARD 11 PLANNING GRANTS FOR THE DINA CENTERS, IN THE PROCESS OF COMPLETING DEMONSTRATION PROJECTS, TO ILLUSTRATE THE SPIRIT OF THE KIND OF WORK THE DINA CENTERS SHOULD THEY BE ESTABLISHED THERE WOULD BE UNDERGOING, AND SO THE TIMELINE, PLAN TO SELECT TWO CENTERS BY THIS COMING FALL. AND WE -- A SHOUT OUT TO THE SUMMIT HELD TODAY FUNDING GRANTS APPLICANTS FROM HARVARD, HOSTED A REALLY INTERESTING SET OF TALKS THAT ARE RELATED TO SOME OF THE WORK THEY WOULD BE PROPOSING FOR A DANA CENTER, AND FROM THE DANA FRONTIERS PROGRAM FOCUSING ON GROWING CAPACITY FOR INFORMED PUBLIC REFLECTION ON NEUROSCIENCE AND NEUROSCIENCE IN SOCIETY, SOMETHING THAT MIGHT BE OF INTEREST TO FOLKS HERE IS A PUBLIC POLLING -- PUBLIC SURVEY WE DID IN COLLABORATION WITH RESEARCH AMERICA, TO TEST OUR ASSUMPTION, QUESTION OUR OWN ASSUMPTION OF PUBLIC PERCEPTION AND UNDERSTANDING AROUND NEUROSCIENCE, INTERESTING FOR US TO GO THROUGH THE PROCESS SO IT COULD HELP INFORM OUR STRATEGY AROUND WHAT THE NEEDS ARE IN PUBLIC ENGAGEMENT. WE FOUND THAT THERE'S A DESIRE FOR AN INCREASE IN PATIENT VOICES IN SETTING RESEARCH PRIORITIES WHICH IS VERY RELEVANT TO THE CONVERSATIONS WE'VE BEEN HAVING TODAY. AND SO I THINK THAT'S IT IN A NUTSHELL SOME THINGS HAPPENING HERE. YOU'LL FIND OUT MORE ABOUT THIS FROM A NEW WEBSITE THAT WE'RE LAUNCHING THIS SUMMER ENCAPSULATING VISION MISSION, PILLARS AND ACTIVITIES THAT WE'RE HAVING BUT IT'S ALL VERY RELATED TO THIS GROUP AND WE'RE SO EXCITED TO THINK ABOUT HOW WE CAN COMPLEMENT AND PARTNER WITH ALL OF YOU IN HELPING TO PUSH FORTH THE ELEVATED VISIBILITY OF THE NEEDS IN NEUROSCIENCE AND SOCIETY. I'LL END WITH THAT. >>THANKS, CAROLINE. KAREN? >>GREAT. I THINK WHAT I'D LIKE TO SHARE ARE SOME UPDATES ON THE INTERNATIONAL STAGE, AND THEN ONE MORE NATIONALLY ORIENTED UPDATE. ON THE INTERNATIONAL FRONT THERE'S BEEN A LOT OF DISCUSSION IN REGULATION AND POLICY AND GUIDANCE AROUND NEUROTECHNOLOGY IN SPECIFIC, SEEMS TO BE PROLIFERATING RAPIDLY MORE THAN I'VE SEEN IN THE PAST. WHAT YOU MAY HAVE HEARD ABOUT IS AN INFAMOUS NEURAL RIGHTS CONVERSATION, THAT PROPOSES NOVEL HUMAN RIGHTS RELATED TO NEUROTECHNOLOGY AND NEUROSCIENCE. AND IN I THINK IT WAS NOVEMBER OR DECEMBER THE UNESCO INTERNATIONAL BIOETHICS COMMUNITY CREATED A NEUROTECHNOLOGY REPORT THAT TALKED ABOUT A NUMBER OF RECOMMENDATIONS FOR NEUROTECHNOLOGY, SOME RESONATE WITH SOME OF THE ACTIVITIES WE'VE PROPOSED IN WHAT CHRISTINE SHOWED, BUT ALSO CONCLUDES THERE'S NO NEED FOR NEW RIGHTS BUT A NEED TO TAILOR EXISTING REGULATION. NITA SPOKE AT OECD EVENT, DO WE NEED NEURAL RIGHTS, THAT WAS FINALIZED IN EARLIER -- ACTUALLY IN DECEMBER, EARLIER THIS YEAR, COMING OUT SOON WITH A SERIES OF VIDEOS AND, AGAIN, THE FINDING IS THE SAME. AROUND DATA, MAYBE OUR CONVERSATION HERE TODAY IS MORE RELEVANT THAN WE MIGHT ANTICIPATE. AND SO WE DO KNOW THAT ACTUALLY YOU MAY BE AWARE MANY OF YOU WERE INVOLVED IN OECD RECOMMENDATION ON RESPONSIBLE INNOVATION AND NEUROTECHNOLOGY ADOPTED AS A LEGAL INSTRUMENT IN DECEMBER 2019, BY 2024 ALL MEMBER COUNTRIES ARE -- ALL 38 MEMBER COUNTRIES ARE EXPECTED TO DEMONSTRATE HOW THEY HAVE IMPLEMENTED THIS DOCUMENT. OECD CONSIDERS THIS FIRST INTERNATIONAL STANDARD IN RESPONSIBLE INNOVATION IN NEUROTECHNOLOGY BUT REALLY IT'S A BUNCH OF PRINCIPLES THAT NEED TRANSLATION AND IMPLEMENTATION. SO WE'VE JUST WORKED THROUGH THE FIRST IMPLEMENTATION GUIDE WHICH SHOULD BE -- IS BEING FINALIZED TO BE FORTH COMING SOON. I WON'T MENTION OTHER ENTITIES AND WILL GO STRAIGHT TO NATIONAL. FEBRUARY 16 AND 17 THE DEPARTMENT OF COMMERCE, SOME OF YOU WILL BE INVOLVED IN THAT EVENT, HOSTING A WORKSHOP, PUBLICLY WEBCAST EVENT ON BCI EXPERT CONTROL REGULATION, WHAT'S THE STATE OF THE ART AND WHAT MIGHT BE NEEDED FOR EXPERT CONTROL REGULATION, AND THERE WILL NEED TO BE MORE RELATED TO THAT. I DON'T THINK YOU CAN FIND ANYTHING ONLINE ABOUT IT YET BUT THEY DO HAVE THEIR CALL FOR COMMENT IN THE FEDERAL REGISTER FOR BCI EXPERT CONTROL CLOSED NOVEMBER 21, COMPILED RESPONSES, DIDN'T GET A LOT LIKE WE DON'T GET A LOT WHEN WE ASK FOR RESPONSES AT NIH, AND THEN ARE TRYING TO FIGURE OUT HOW TO ENGAGE MORE OF A BROAD AUDIENCE FOR THIS EVENT. THAT'S IT. >>THANKS, KAREN. ELBA? >>SORRY I'M LATE. THIS IS A BIG TEACHING DAY FOR ME. GOOD TO SEE EVERYBODY. WHAT I HAVE TO SHARE IS TANGENTALLY RELATED, THE SOCIETY FOR NEUROSCIENCE OFFERS RESPONSE CONDUCT IN RESEARCH WORKSHOPS, THE ONE IN THE FALL WAS OUTSTANDING. IT WAS ON DATA SCIENCE, DATA MANAGEMENT, DATA CURATION, RIGOR AND REPRODUCIBILITY, PROTECTION, ALL THE ISSUES THAT ARE JUST GOING TO ESCALATE REGARDING THE AVAILABILITY OF DATA, ORGANIZATION OF DATA, META DATA TAGGING AND OF COURSE PROTECTION OF HUMAN SUBJECTS DATA. I'LL POST THAT IN THE CHAT AND I DON'T KNOW IF THERE WOULD BE AN OPPORTUNITY FOR THIS COMMUNITY OR THIS GROUP TO PERHAPS SPONSOR, ASSEMBLE ON A PAGE SCIENTISTS DEALING WITH DATA. I CANNOT PUBLISH ANYTHING WITHOUT MAKING ALL THE DATA AVAILABLE ON A WEBSITE LIKE DRYAD, SO THIS IS A NEW REQUIREMENT AND IT'S A REALLY IMPORTANT ONE. SO THAT'S IT. >>THANKS, ELBA. AND SAMEER? >>YEAH, TWO QUICK THINGS. THERE'S APPARENTLY A FLASH FLOOD OUTSIDE MY WINDOW, TWO INCHES OF WATER, THIS WILL BE FUN. THE OTHER ONE MORE RELEVANT IS IN PARALLEL, I HAD THE PLEASURE, REALLY LEARNED A LOT FROM WORKING WITH A PARALLEL GROUP, NEUROETHICS WORKING GROUP IN A BRANCH WITHIN "BRAIN," WE PUT OUT A PAPER A YEAR AGO, NOW WE'RE OFF TO THE NEXT PROJECT, A FUN PROJECT, LOOKING AT ISSUES AROUND DATA SHARING, DATA REUSE, WHAT ARE THE ADVANTAGES, DISADVANTAGES FROM ALL THE DIFFERENT PERSPECTIVES. DOING THIS WITH AMY MAGUIRE HERE, DIRECTOR OF CENTER FOR MEDICAL ETHICS AT BAYLOR WHO I WORK WITH A LOT THROUGH THE SHARED R01, BRAIN SHARE THROUGH BRAIN, THIS IS NEAT BECAUSE IT ADDRESSES A LOT OF ISSUES WE TALKED ABOUT TODAY, A COUPLE THINGS IN THE CHAT, AND SPANS A BUNCH OF AREAS, WE'RE FOCUSING LARGELY ON THE ROH ITSELF, INVASIVE OPPORTUNITIES IN HUMANS TO LEARN HOW THE BRAIN WORKS, AND THINGS WE'VE TALKED ABOUT EVEN RELATED TO THIS DEPRESSION PROJECT, DATA THAT COMES FROM THIS, HOW IS IT USED, HOW SHOULD IT BE USED, WHO HAS ACCESS, WHO OWNS IT, AND HOW CAN WE INCENTIVIZE REUSE OF DATA, FROM THE PERSPECTIVE OF INVESTIGATORS AND JOURNALS, THE PUBLIC, PATIENT, PARTICIPANTS, ET CETERA. THIS IS ONGOING. WE HAVE A WORKING GROUP ASSIGNED TO THIS, IN THE PROCESS OF SKETCHING OUT A DRAFT WITH CERTAIN CASE USES, PERHAPS THREE SPECIFIC CASE USES THAT SPAN DIFFERENT ASPECTS OF THIS TOPIC. STAY TUNED. NEXT TIME WE MEET IT WILL BE PUBLISHED HOPEFULLY. PROBABLY NOT. BUT FURTHER THAN IT IS NOW. >>I'M GOING TO TOSS TO SASKIA BRIEFLY. >>IT MIGHT BE A GOOD TIME TO MENTION WE'RE WORKING A WORKSHOP FOR THE NEUROETHICS WORKING GROUP RELATED TO DATA AND PRIVACY AND DATA SHARING. WE'RE HOPING TO HAVE IT THIS SUMMER, I THINK THE SAVE THE DATES WILL GO OUT SOON-ISH. YEAH, WE HOPE TO PULL TOGETHER ALL OF THE THREADS THAT WE'VE HEARD IN THE LAST COUPLE OF MINUTES ABOUT DATA AND PRIVACY. >>THANKS. YEAH, STAY TUNED. I'LL TURN IT NOW OVER TO JOHN AND ANDREA TO CLOSE US OUT. >>GO AHEAD, JOHN. I'LL DO THE HOUSEKEEPING WHEN YOU'RE DONE. >>YOU'LL HAVE THE TIME WORD, THE IMPORTANT PART. THANKS. IT'S BEEN A GREAT SET OF DISCUSSIONS, AND REALLY ENJOYED THE PRESENTATIONS AND DISCUSSIONS THAT FOLLOWED. I THINK WE SURFACED A LOT OF IMPORTANT ISSUES, AND I ASK YOU AS YOU LEAVE HERE AND THINK ABOUT WHAT WE TALKED ABOUT IN TERMS OF WHAT CAN NEWG DO AND HOW CAN NEWG HELP TO CONSIDER THE THINGS THAT CAME UP ABOUT ONE BEING KIND OF LET'S -- WE CAN START WITH BRAIN AS OUR FOCUS, NOT TO SAY THAT WE WOULDN'T WANT THE IMPACT TO BE MUCH LARGER BUT ONE COOL THING ABOUT THE BRAIN INITIATIVE, SOME THINGS WE START HERE ARE APPLICABLE MORE PRODUCTLY IN NOT JUST NEUROSCIENCE BUT ACROSS BIOMEDICINE, FOR EXAMPLE MANY ISSUES COMING UP ACUTELY IN THE POST-TRIAL SPACE ARE DISCUSSED ACROSS NIH AND BIOMEDICINE. AND AGAIN TO THINK ABOUT THIS AS A NEUROSCIENCE INITIATIVE WHERE WE'RE LOOKING AT BUILDING TOOLS ETHICALLY TO UNDERSTAND MECHANISM AND IF YOU UNDERSTAND MECHANISM YOU GET A LOT FURTHER IN ALL WE DO. AND FINALLY I THINK BRAIN INITIATIVE FROM THE OUTSET HAS MADE THE ETHICAL CONSIDERATIONS TO BE INTEGRAL TO WHAT WE DO AND HENCE WHY WE'RE ALL HERE TODAY AND REALLY THE VALUE OF THE NEWG AND HOW CAN WE MORE FULLY INTEGRATE THESE VIEWS INTO THE RESEARCH NOT AS AN ADD-ON AT THE END BECAUSE BY THEN WE ALL KNOW IT'S TOO LITTLE TOO LATE. WE CAN WORK TOWARDS AN INTERESTING AND PRODUCTIVE CONVERSATION IN THE FUTURE, WHETHER HERE AT NEWG MEETINGS OR IN WRITING UP SOME SCHOLARLY PAPERS, TRYING TO FIGURE OUT OR TO SOLICIT INTERESTING APPLICATIONS TO FUND IN THE NEUROETHICS SPACE AND ALSO OF COURSE HOLDING WORKSHOPS THAT DIG IN DEEPER. WE LOOK FORWARD TO YOUR INPUT AS WE CHART FORWARD IN THE NEXT YEAR PLUS. I'LL HAND IT OVER TO ANDREA WITH MY THANKS FOR YOUR PARTICIPATION AND ATTENTION TODAY. >>JOHN GETS THE MORE FUN CLOSING REMARKS. MY JOB IS TO LET YOU KNOW THAT WE ARE CONCLUDING THE OPEN SESSION OF THE NEUROETHICS WORK GROUP, TRANSITIONING TO CLOSED SESSION AT 45 MINUTES PAST THE HOUR, THE ZOOM ROOM WILL BE OPEN EARLY TO GET STARTED ON TIME. FOR NEWG MEMBERS, INVITED GUESTS, YOU HAVE A SEPARATE LINK IN YOUR MEETING INVITATION OR E-MAIL OR PROBABLY BOTH. ALSO A QUICK PLUG, MULTI-COUNCIL WORK GROUP TOMORROW, OPEN SESSION AT NOON EASTERN TIME. SO FOR NOW WE ADJOURN OUR OPEN SESSION, AND WE WILL SEE NEWG MEMBERS FOR CLOSED SESSION AGAIN AT 45 MINUTES PAST THE HOUR. THANK YOU ALL.