WELCOME TO THE SECOND DAY OF THE OPEN SESSION OF THE NDCD ADVISORY COUNCIL MEETING. IT'S GREAT TO SEE YOU ALL AND TO BE STARTING ON TIME TODAY, AND THANK YOU, CRAIG AND GINGER, FOR ALL YOUR EFFORTS YESTERDAY TO GET US GOING DESPITE SOME REALLY SIGNIFICANT CHALLENGES. SO WE HAVE A REALLY EXCITING PROGRAM FOR YOU THIS MORNING. IT'S RATHER BRIEF BUT I THINK VERY IMPACTFUL AND WE'LL CONVEY A LOT OF INFORMATION ABOUT ACTIVITIES OF THE INSTITUTE. AND TODAY WE WILL START WITH A REPORT OF THE DIVISION OF SCIENTIFIC PROGRAMS BY DR. COOPER. JUDITH, PLEASE GO AHEAD WITH YOUR REPORT. >> OKAY, THANK YOU, DEB. GOOD MORNING, EVERYONE. I'M SO PLEASED TO BE ABLE TO INTRODUCE YOU TO OUR NEWEST MEMBER OF THE DIVISION OF SCIENTIFIC PROGRAMS, DR. MARY PARUKART. LET'S SEE IF I CAN SEE HER. I CAN'T SEE HER ON MY SCREEN. BUT I'LL GO ON WITH HER INTRODUCTION AND THEN HOPEFULLY YOU CAN SEE HER WAVING HER HAND SO YOU'LL GET TO KNOW HER. SHE'S PART OF OUR NIDCD CLINICAL TRIALS TEAM IN MY DIVISION. MARY HAS BOTH AN M.D. WITH BOARD CERTIFICATION IN INTERNAL MEDICINE, CRITICAL CARE MEDICINE AND PULMONARY DISEASE, AS WELL AS A PH.D. AND AN MS IN MOLECULAR BIOLOGY. SHE'S BEEN A PART OF THE COMMISSION CORPS OF THE UNITED STATES PUBLIC HEALTH SERVICE AND SHE RECENTLY RETIRED AT THE RANK OF A CAPTAIN. HER EXPERIENCE ALSO EXTENDS INTO PEDIATRICS, WHICH IS SO EXTENSIVE THAT SHE RECEIVED AN INVITATION TO MEMBERSHIP IN THE VERY PRESTIGIOUS PROFESSIONAL GROUP, THE SOCIETY FOR PEDIATRIC RESEARCH. SHE'S WORKED AT THE FDA, AND WHEN SHE CAME TO THE NIH, SHE COORDINATED THE CTSAs, THOSE ARE THE CLINICAL AND TRANSLATIONAL SCIENCE AWARDS. MOST RECENTLY, SHE WAS A PART OF NCATS. THAT'S ONE OF THE NIH INSTITUTES, THE CLINICAL -- I'M SORRY, THE NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES, NCATS. SHE WAS THE DIRECTOR OF THEIR PROGRAM HUBS. SHE HAS A LONG LIST OF AWARDS AND PUBLICATIONS, AND SHE BRINGS A GREAT BREADTH OF EXPERIENCE AND CLINICAL KNOWLEDGE, AND WE'RE VERY FORTUNATE TO HAVE HER BE A PART OF NIS NIDCD. ALL RIGHT. WELL, HOPEFULLY THERE WILL COME A TIME WHEN WE'LL BE MEETING FACE-TO-FACE AGAIN, AND YOU'LL HAVE A BETTER CHANCE TO MAYBE EVEN INTERACT WITH MARY. I WANT TO GIVE YOU JUST A BRIEF OVERVIEW OF A COUPLE OF THINGS THAT HAVE HAPPENED WITH REGARD TO COVID OVER THE LAST YEAR. BACK IN MARCH AND APRIL, WHEN THE PANDEMIC WAS BECOMING MORE AND MORE AN ISSUE FOR US TO LOOK AT AND DEAL WITH, THE NIDCD ISSUED -- YOU'LL RECALL THAT REVISIONS ARE THE NIH TERM FOR SUPPLEMENTS, WE ISSUED A REQUEST FOR SUPPLEMENTS TO ACTIVE NIDCD GRANTS. WE ISSUED IT IN APRIL. OBVIOUSLY THEY NEEDED TO BE FOCUSED WITHIN OUR MISSION AREA BECAUSE THEY WERE TO ACTIVE GRANTS. WE REVIEWED THEM IN JUNE, AND WE MADE AWARDS IN JULY. SO YOU CAN SEE IN THE CHART THAT WE MADE 18 SUPPLEMENT AWARDS, ACTUALLY ONE OF THEM WAS AWARDED BY THE OFFICE OF THE DIRECTOR, AND THEY WERE ACROSS ALL OF OUR PROGRAM AREAS. AND WE SPENT A LITTLE OVER $3 MILLION FOR THOSE SUPPLEMENTS. AND AROUND THE SAME TIME, THERE WERE MANY OTHER ACTIVITIES GOING ON ACROSS THE NIH, AND ONE OF THEM THAT BENEFITED SOME OF OUR INVESTIGATORS WAS AN ACTIVITY RELATED TO SOCIAL, BEHAVIORAL AND ECONOMIC IMPACT OF COVID. AND THERE WAS A TRANS-NIH COMMITTEE THAT NIDCD STAFF WERE INVOLVED IN, AND THE OFFICE OF THE DIRECTOR WITH THEIR DOLLARS DECIDED TO SUPPORT TWO SUPPLEMENTS TO OUR ACTIVE GRANTS, AND WITH THOSE DOLLARS, THEY WERE FOCUSED IN THE AREAS OF CHILD LANGUAGE AND APHASIA. NOW I WANT TO SAY A WORD ABOUT RADX RAD PROGRAM. THERE ARE SEVERAL RADX PROGRAMS HERE AT NIH THAT STANDS FOR RAPID ACCELERATION OF DIAGNOSTICS, BUT PROBABLY BACK IN MAY OR SO, THE PROGRAM BEGAN TO BE DEVELOPED. THE GOAL WAS TO SUPPORT NON-TRADITIONAL APPROACHES, NEW APPLICATIONS OF EXISTING TOOLS THAT ADDRESS THE GAPS IN COVID-19 TESTING. SO FROM THE POINT WHERE THAT IDEA WAS DEVELOPED TO DECEMBER, WHEN THE OFFICE OF THE DIRECTOR AWARDED OVER $107 MILLION TO SUPPORT 49 RESEARCH PROJECTS AND GRANT SUPPLEMENTS AT 43 INSTITUTIONS ACROSS THE UNITED STATES. SO LET ME SHOW YOU THE NEXT SLIDE, JUST TO SHOW YOU HOW FAST ALL THAT HAPPENED, THERE WAS AN IDEA OF TELL US WHAT YOU WOULD LIKE TO DO WITH REGARD TO RADICAL DIAGNOSTICS. THAT CAME OUT IN MAY AND JUNE. SOME OF THE IDEAS WERE SELECTED IN JULY AND AUGUST, ACTUAL FOAs, RFAs WERE ISSUED. THEN IN AUGUST AND SEPTEMBER AND OCTOBER, THE APPLICATIONS CAME IN AND WERE REVIEWED, AND IN NOVEMBER AND DECEMBER, DECISIONS HAD TO BE MADE AND GRANTS WERE AWARDED AS I INDICATED IN DECEMBER. SO WHY AM I TELLING YOU ABOUT RADX-RAD? WHAT DOES THAT HAVE TO DO WITH NIDCD? WELL, IT HAS A LOT TO DO WITH NIDCD. NEXT SLIDE. WHEN THE NIH DIRECTOR SAID, SEND US YOUR IDEAS, WELL, ONE OF THE THINGS THAT WAS REALLY CIRCULATING IN THE PRESS A LOT WAS THAT PEOPLE SEEMED TO BE LOSING THEIR SENSE OF SMELL AND MAYBE EVEN TASTE RIGHT BEFORE THEY BEGAN TO SHOW OTHER SYMPTOMS OF COVID. SO SUSAN SULLIVAN OF NIDCD AND HER COLLEAGUE IN DENTAL AND CRANIOFACIAL, AMANDA, DECIDED THEY WOULD SUBMIT AN IDEA TO THE OFFICE OF THE DIRECTOR ABOUT LOOKING AT AND DEVELOPING A SUBJECTIVE SMELL TEST THAT COULD BE USED TO SCREEN FOR COVID. TESTS THAT COULD BE SELF-ADMINISTERED THAT WOULD BE QUICK, AFFORDABLE, AND ALSO WE NEEDED TO LOOK AT A SMELL TEST, SMELL LOSS, CAN IT BE AN EARLY INDICATOR OF COVID, AND PREDICTIVE MAYBE EVEN OF DISEASE SEVERITY AND PERSISTENCE OR MAYBE EVEN OTHER NEUROLOGICAL PROBLEMS. SO THAT IDEA WAS SUBMITTED. YOU SAW THE TIMELINE. SO THE OFFICE OF THE DIRECTOR AND OTHERS DECIDED, HEY, WE LIKE THAT IDEA, SO LET'S DEVELOP AN RFA. AND THAT'S EXACTLY WHAT SUSAN AND HER COLLEAGUES AND A TEAM DID. CHEMO SENSORY TESTING AS A COVID-19 SCREENING TOOL. SO THAT WAS ISSUED IN THE SUMMER. THE PURPOSE, YOU CAN SEE THERE ON THE SLIDE, TO ENHANCE THE UTILITY OF CHEMOSENSORY TESTING AS A SCREENING TOOL, USING OBJECTIVE TESTS TO EXAMINE THE ONSET AND PROGNOSTIC VALUE, AND ALSO DEVELOP THESE TESTS THAT CAN BE USED AS HOME-BASED, ON-SITE TESTS. SO AS A RESULT OF THAT RFA, THE RESPONSE WAS 9 APPLICATIONS. 3 WERE ACTUALLY APPROVED AT THE OFFICE OF THE DIRECTOR, AND AS A RESULT, THIS AREA OF OUR SCIENCE RECEIVED $3.4 MILLION FROM THE DIRECTOR TO SUPPORT THESE APPLICATIONS. SO WHO GOT THE AWARDS? HERE WE HAVE THE 3PIs WHO WERE SUCCESSFUL, MUNGER, RAPID OLFACTORY TOOLS FOR TELEMEDICINE-FRIENDLY COVID-19 SCREENING AND SURVEILLANCE. TATAR: LONGITUDINAL AT HOME SMELL TESTING TO DETECT INFECTION BY SARS COV-2, AND DR. DALTON, A RAPID SMELL TEST FOR COVID-19 SURVEILLANCE, SCENTINEL. SO SUSAN AND HER COLLEAGUES DECIDED MAYBE THERE MIGHT BE A REASON TO DO SOME SUPPLEMENTS ALONG THE SAME LINES. THEY HAD THE SAME PURPOSE AS THE RFA THAT I JUST SHOWED YOU, AND SURE ENOUGH, DR. TRAVERS SUBMITTED AN APPLICATION THAT WAS JUDGED QUITE MERITORIOUS BY THE OFFICE OF THE DIRECTOR. DR. TRAVERS' SUPPLEMENT TO HER ACTIVE GRANT IS A CONFECTIONARY BASED SCREENING TOOL. AGAIN, THE MONEYS FOR THAT SUPPLEMENT WERE PROVIDED BY THE OFFICE OF THE DIRECTOR. ONE FINAL THING I WANT TO SAY IS THAT AFTER WE DID THE SUPPLEMENT WAY BACK IN THE SPRING, WE REALIZED, WELL, WE MAY NEED TO CONTINUE TO DO SOMETHING. I MEAN, THAT SUPPLEMENT WAS A ONE-TIME OPPORTUNITY, SO THEY PUT TOGETHER THIS NOTICE ENTITLED NIDCD IS INTERESTED IN SUPPORTING RESEARCH ON THE IMPACT OF COVID-19 ON MISSION-SPECIFIC SENSORY AND COMMUNICATION DISORDERS. BRACIE REMAINS THE CONTACT ON THIS INITIATIVE, CLEARLY THE APPLICATIONS HAVE TO BE RELEVANT TO OUR MISSION AREAS, AND IN THE ANNOUNCEMENT, WE ENCOURAGE MULTIDISCIPLINARY APPROACHES. WE WANTED TO HOPEFULLY MOVE THE RESEARCH BEYOND ANY IN VITRO AND ANIMAL MODELS. THE FIRST SUBMISSION DATE WAS JUST A FEW MONTHS AGO AND I'M VERY HAPPY TO REPORT, WE RECEIVED ALREADY 14 APPLICATIONS THAT CROSS ALL OF OUR MISSION AREAS SO THE NEXT TIME WE'RE TOGETHER, WE'LL BE LOOKING AT SOME COVID-RELATED THAT FOCUS ON ALL OF OUR AREAS. I DID JUST WANT TO SHARE SINCE THE LAST TIME WE MET, THOSE DECISIONS ABOUT THE RFAs, NO DECISIONS HAVE BEEN MADE, SO I WANTED TO BRING YOU UP TO DATE ON THAT. AND IF YOU HAVE ANY QUESTION, I KNOW SUSAN IS ON THE LINE AND SHE CAN ANSWER THEM. BUT I'M HAPPY TO TAKE ANY QUESTIONS. >> ARE THERE ANY QUESTIONS FOR JUDITH? OKAY. THANK YOU. VERY GOOD. THANK YOU, JUDITH. >> OH, I'M SORRY, I JUST HAD A -- I WAS JUST TRYING TO FIND MY MUTE BUTTON. HELLO. SO WHAT DO YOU SEE IS THE LONGEVITY FOR THESE VARIOUS PROGRAMS? BECAUSE YOU HAVE TALKED ABOUT THE RFA AND SUPPLEMENTS PROGRAM, SO IT'S OBVIOUSLY A ROLLING KIND OF A THING, BUT SO RECOGNIZING THAT YOU DON'T HAVE A LONG-TERM PLAN, CAN YOU SAY IF THE ONES THAT EXIST NOW WILL CONTINUE TO REMAIN OPEN FOR SOME TIME OR THEY'LL BE REPLACED BY NEWER THINGS AS THE FIELD CHANGES AND AS WE START TO UNDERSTAND? >> THANK YOU, NIRUPA. THE CURRENT ANNOUNCEMENT, WHICH WAS THE LAST SLIDE I SHOWED THAT SOLICITS R21s, SBIRs, ET CETERA, ET CETERA, THAT ONE IS ACTIVE UNTIL 2022. SO WE HAVE THAT ONE. THE FATE OF THE RADX-RAD APPLICATIONS THAT SUSAN COORDINATED, THOSE HAVE FUNDING BUT WHAT HAPPENS WHEN THEY END, THAT DEPENDS ON WHETHER THE OFFICE OF THE DIRECTOR WANTS TO DO NEW INITIATIVES. THERE'S TALK RIGHT NOW ABOUT COVID DOLLARS THAT THE NIH HAS RECEIVED, AND THERE'S TALK ABOUT HOW THOSE DOLLARS MIGHT BE AVAILABLE TO THE INSTITUTES, BUT THAT'S TO BE DETERMINED. FOR NOW WE HAVE THE DOORS OPEN FOR INVESTIGATIONS IF NEW INFORMATION LIKELY WILL HAPPEN COMES THAT'S RELEVANT TO OUR MISSION AREA AND WE NEED TO DO SOMETHING, WE WILL BE READY TO ACT. >> OKAY, GREAT. THANK YOU. >> I HAD A QUICK QUESTION. I WONDERED IF THIS IS GOING TO TRANSLATE INTO SORT OF LONGER-TERM REGULAR SORT OF R01 GRANTS WHERE WE'RE LOOKING IN GENERAL AT VIRAL ENTRY INTO THE BRAIN OR THE BODY THROUGH THE OLFACTORY SYSTEM. IT SEEMS LIKE ONCE WE GET PAST THE INITIAL CRISIS MODE, THERE'S A LOT OF SCIENCE WE CAN BUILD ON THAT WOULD BE APPLICABLE TO MANY KINDS OF DISEASES BESIDES JUST COVID. BUT BUILD ON THE STRENGTH WE'VE LEARNED IN THE PAST YEAR. SEEMS LIKE A GREAT OPPORTUNITY FOR SORT OF A LONGER-TERM RFA. >> THANK YOU FOR THAT SUGGESTION, AND WE'LL CERTAINLY PUT THAT INTO THE HOPPER OF THINGS TO CONSIDER AS WE MOVE AHEAD. >> BEN, THAT SPECIFIC ISSUE OF VIRAL ENTRY INTO THE BRAIN THROUGH THE NASAL MUCOSA REALLY HAS COME UP A LOT WITH NINDS, SO THERE'S BEEN A LOT OF CONVERSATION NIH-WIDE ABOUT THAT BECAUSE IT APPLIES TO OTHER CONDITIONS SUCH AS POTENTIALLY PARKINSON'S DISEASE OR ALZHEIMER'S. SO I THINK THAT IS AN ISSUE WHICH HAS BEEN BROUGHT TO THE FOREFRONT BY THIS EPIDEMIC. >> THE SPECIFIC REASON I WAS RAISING IT IS THAT EVEN MY UNDERSTANDING OF THE LITERATURE IS EVEN AFTER QUITE A BIT OF WORK, IT'S STILL AMBIGUOUS IN TERMS OF THE ROLE OF THE ACTUAL RECEPTOR CELLS, THE BRAIN CELLS, VERSUS THE SUPPORTING CELLS. SO WHETHER THIS CONTEXT IS SORT OF A NEUROSCIENCE CONTEXT OR SORT OF A MORE GENERAL BIOLOGICAL CONTEXT MEDIATES THE PATHOLOGY SEEMS JUST LIKE A FUNDAMENTAL QUESTION. IT MUST BE A DEEP QUESTION BECAUSE THIS IS STILL OPEN, AND QUITE A LOT OF WORK. SO THAT'S WHY I SAY TAKE ADVANTAGE OF THE COVID, BUT THEN MAKE IT A LONG-TERM THING TO TRY AND GET A RESOLUTION OF THIS LONG-TERM QUESTION. >> SUSAN, DID YOU WANT TO SAY SOMETHING? >> I JUST WANT TO MENTION THAT WE HAD SOME SUPPLEMENTS THAT WE GAVE THAT JUDITH MENTIONED VERY EARLY ON, AND WE DO HAVE SOME OF OUR NIDCD PIs LOOKING AT POSTMORTEM HUMAN TISSUE FROM INDIVIDUALS WHO PASSED AWAY DUE TO COVID. SO THAT'S SOMETHING THAT WE ARE ACTIVELY WORKING ON, AND HOPEFULLY WE'LL HAVE SOME MORE INFORMATION SOON. >> THAT'S GREAT. THANK YOU, SUSAN. >> I HAD ANOTHER QUESTION FOR JUDITH OR SUSAN, AND THAT IS, IF A PI IS FUNDED THROUGH A DIFFERENT INSTITUTE BUT THEY ARE STUDYING A POPULATION THAT HAS HEARING LOSS OR OTHER COMMUNICATION DISORDERS, COULD THAT WORK BE CONSIDERED FOR ONE OF THE KIND OF SUPPLEMENT THAT YOU JUST MENTIONED THAT PREVIOUS >> THAT COULD COME UNDER THE LAST NOTICE JUDITH MENTIONED, NOT NECESSARILY A SUPPLEMENT FROM US, BUT THEY COULD APPLY FOR R01 OR R21 TO PURSUE THAT WORK. >> OKAY. THANK YOU. >> ANY OTHER COMMENTS? RUTH ANNE? >> JUST A QUICK ONE, AND I'M SORRY IF I MISSED THIS ALREADY. APART FROM THE QUESTION OF WHETHER THE NEURONS ARE ACTIVELY AFFECTED BY COVID, THERE'S BEEN A LOT OF TALK, AT LEAST AT THE "NEW YORK TIMES" LEVEL, ABOUT COGNITIVE PROBLEMS FOR PEOPLE WHO'VE LOST THEIR SENSE OF SMELL, AND I'M WONDERING IF THERE'S ANY ACTION IN NIDCD TO PARTNER WITH NIMH OR OTHER INSTITUTES ON THAT QUESTION, KIND OF QUESTION. >> CERTAINLY FOR THE COVID TESTING, PEOPLE THAT WE HAVE ALREADY FUNDED THROUGH RADX-RAD, PEOPLE ARE VERY INTERESTED IN UNDERSTANDING WHETHER THE LOSS OF SMELL PREDICTS OTHER NEUROLOGICAL LOSSES OR DAMAGE. SO THAT IS ONGOING, AND CERTAINLY AS THINGS DEVELOP, WE'LL BE HAPPY TO COLLABORATE WITH OTHER INSTITUTES. AND IN FACT, ON OUR RFA FOR RADX-RAD, NEUROLOGY, I THINK MENTAL HEALTH, SEVERAL INSTITUTES PARTICIPATED ON THAT. DEFINITELY NEUROLOGY DID, THE DENTAL INSTITUTE DID, AGING WAS VERY MUCH INVOLVED, AS WELL AS THE NURSING INSTITUTE. >> A LOT OF THESE COVID INITIATIVES ARE TRANS-NIH, WHICH IS A NICE THING ABOUT THEM. THEY REALLY DO TRY TO INTEGRATE PERSPECTIVES FROM ALL OF THE RELEVANT INSTITUTES. THE OTHER ISSUE, WHICH IS COMING UP A LOT, IS THE LONG HAULERS SYNDROME, YOU KNOW, THE FACT THAT PEOPLE WHO HAVE HAD COVID, EVEN SOME PEOPLE WHO WERE NEVER DIAGNOSED WITH COVID, HAVE THESE LONG-TERM SYMPTOMS THAT ARE QUITE DEBILITATING, AND SMELL LOSS AND CHANGES IN THE SENSE OF SMELL ARE ALSO PART OF THAT. SO SUSAN REPRESENTS US ON THAT TRANS-NIH GROUP. ALL RIGHT. THANK YOU, JUDITH. THANKS FOR THE GOOD DISCUSSION. SO NOW WE WILL MOVE ON AND TALK ABOUT THE BRAIN INITIATIVE. SO THE NIDCD IS ONE OF 10 NIH INSTITUTES AND CENTERS THAT PARTICIPATES IN THE BRAIN INITIATIVE, AND THIS IS A VERY EXCITING PROGRAM. THIS IS -- OR THE NIDCD IS REPRESENTED WITHIN THE BRAIN PROGRAM BY DR. AMY POREMBA AS WELL AS BY DR. ROGER MILLER AND DR. ALBERTO RIVERA RENTES. SO AMY IS GOING TO GIVE A PRESENTATION NOW ON TRANS-NIH BRAIN INITIATIVES. AND TELL US ABOUT THAT. THANK YOU, AMY. >> GOOD MORNING. I'M NOT GOING TO TURN ON MY MICROPHONE -- OR ON MY PICTURE BECAUSE THERE'S A LOT OF PROCESSING GOING ON FOR THE SLIDES. >> OKAY. >> SO AS DR. TUCCI MENTIONED, I'M AMY POREMBA, THE NIDCD PROGRAM DIRECTOR FOR CENTRAL AUDITORY AND BALANCE PROCESSING IN MY REGULAR JOB HERE AT NIDCD BUT I'M ALSO THE REPRESENTATIVE WHO WORKS WITH THE BRAIN INITIATIVE, A REALLY LARGE TRANS-NIH PROGRAM THAT WILL END UP PROVIDING OVER $5 BILLION IN NEUROSCIENCE FUNDING BY 2026. SO THE BRAIN INITIATIVE WAS ACTUALLY ESTABLISHED IN 2013 BY PRESIDENT BARACK OBAMA WITH A PROPOSAL FROM HIS OFFICE OF SCIENCE AND TECHNOLOGY, ESSENTIALLY GIVING NIH A GRAND CHALLENGE TO FIGURE OUT HOW TO EMPLOY THIS. SO THE IMPETUS FOR THIS BRAIN RESEARCH EFFORT WAS A SIMPLE STAGGERING STATISTIC, THAT 1 IN 4 FAMILIES WORLDWIDE INCLUDE SOMEONE WHO SUFFERS FROM A BRAIN INJURY, DISEASE OR DISORDER, AND THIS INITIATIVE HOPES TO ACCELERATE DEVELOPMENT OF INNOVATIVE TECHNOLOGY TO DISCOVER NEW THINGS AND MAKE DISCOVERIES UTILIZING INTERDISCIPLINARY RESEARCH WHILE PROMOTING TEAM SCIENCE AMONG A NUMBER OF DIFFERENT DISCIPLINES. BASICALLY THE PLAY BOOK ON HOW RESEARCH IS USUALLY DONE, WHICH IS CONSERVATIVE AND NARROW, HAS BEEN DE-EMPHASIZED. TO DO THIS SPECIAL ATTENTION BY PROGRAM OFFICERS, SCIENTIFIC REVIEW OFFICERS, PEER REVIEWERS AND COUNCIL, HAS TO BE PAID TO KIND OF MAINTAIN THIS MAVERICK APPROACH. I'M GOING TO UPDATE YOU BRIEFLY ON THE BRAIN INITIATIVE AND HOW IT INTERACTS WITH OUR MISSION HERE AT NID BUILDING ON MY INITIAL PRESENTATION I GAVE IN 2019. SO THE NAME OF THE INITIATIVE BRAIN IS ACTUALLY A AN ACRONYM FOR BRAIN RESEARCH THROUGHED A VANING INNOVATIVE NEUROTECH NEUROTECHNOLOGIES. IN WHICH MANY INSTITUTES ALREADY PARTICIPATE, BUT RATHER IT'S FOCUSED ON FINDING AND ADVANCING TOOLS AND TECHNOLOGIES TO STUDY THE BRAIN. OVER THE PAST FIVE YEARS, THE INITIATIVE HAS FUNDED HUNDREDS OF RESEARCH PROJECTS NATIONWIDE THAT HAVE LED TO SEVERAL BREAKTHROUGHS, INCLUDING THE CREATION OF SYSTEMS FOR STUDYING NEURAL CIRCUITS IN BEHAVIOR AND ANIMAL MODELS, DEVELOPMENT OF COMPUTER PROGRAM FOR NATURAL SPEECH FROM PERSONS' BRAIN SIGNALS AND THE DON'T STRUX OF CONSTRUCTIO N OF BASICALLY A BRAIN CELLS PARTS LIST. THERE ARE 10 INSTITUTES AND FOUR OFFICES INVOLVED MAINLY DIRECTED BY THE NEUROLOGY AND MENTAL HEALTH INSTITUTES. SO OVER 100 PEOPLE AT NIH SERVE IN SEVERAL CAPACITIES TO SUPPORT THE BRAIN INITIATIVE, MANY OF THEM VOLUNTEERING FROM THEIR INSTITUTES ARE ON LOAN FROM THEM, AND LAST YEAR ONE OF NIDCD'S LONG TIME PIs IN DR. SUSAN SULLIVAN'S PORTFOLIO, DR. JOHN NGAI WAS RECRUITED TO HEAD THE BRAIN INITIATIVE. SO DR. NGAI NORMALLY STUDIES THE OLFACTORY SYSTEM AND HE REALLY USED HIS EARLY TRAINING IN MOLECULAR BIOLOGY WITH THE GENES INVOLVED IN RECEIVING AND PROCESSING ODOR INFORMATION, AND HE RECEIVED ONE OF THE VERY FIRST NIH BRAIN INITIATIVE GRANTS TO HELP CLASSIFY CELLS IN THE BRAIN USING SINGLE CELL SEQUENCING. HIS LATEST INTERESTS ARE REALLY LOOKING AT HOW THE OLFACTORY SYSTEM CAN REPAIR ITSELF. SO DR. NGAI BEGAN HIS POSITION LAST MARCH AND HE'S OVERSEEING THE LONG TERM STRATEGY AND DAY TO DAY OPERATIONINGS OF THE INITIATIVE VIRTUALLY AS WE ALL HAVE BEEN, AND HE WILL EVENTUALLY MOVE HIS LAB HERE TO NIH AFTER THE PANDEMIC. SO WE'RE REALLY ENJOYING HAVING A DEDICATED LEADER FOR THE BRAIN INITIATIVE AND WE'RE EXCITED THAT HE'S SO FAMILIAR WITH OUR INSTITUTE. THE BRAIN INITIATIVE ACTUALLY HAS ITS OWN FUNDING COUNCIL, THE MULTI-COUNCIL WORKING GROUP, AND OUR OWN DR. DAN SANES IS SERVING ON THAT. THERE'S A REPRESENTATIVE FROM EACH OF THE INSTITUTES THAT RECEIVE BRAIN INITIATIVE FUNDING. SO THANKS TO DAN FOR SERVING AS A DOUBLE COUNCILMEMBER. I KNOW HE WAS IN A COUPLE DAYS OF MEETINGS EARLIER THIS WEEK. SO A WHOLE WEEK OF COUNCIL MEETINGS. THERE ARE SEVEN HIGH PRIORITY RESEARCH AREAS DEFINED WITHIN THE BRAIN INITIATIVE AS YOU SEE HERE. THERE WERE TWO WORKING GROUPS OF EXPERTS TO HELP TO CONTINUE DEFINE THESE DIRECTIONS AS WE MOVE FORWARD. THE BRAIN 2025 ACTUALLY GOT AN EARLY CHECK BY ANOTHER EXPERT'S GROUP, THE BRAIN INITIATIVE 2.0, BECAUSE IT WAS MOVING ALONG SO WELL, AND BRAIN INITIATIVE 2.0 MET WITH PIs AND USING EXPERTS FROM ALL ACROSS THE COUNTRY TO COME UP WITH FORWARD LOOKING DIRECTIONS. SOME OF THOSE ARE SHOWN ON THE SLIDE FOR THE TRANSFORMATIVE PROJECTS FROM BRAIN 2.0. THE FIRST THREE LISTED ARE ALREADY IN PROCESS NOW, AND ACTUALLY HAVE RECEIVED SOME SPECIAL FUNDING FROM CONGRESS JUST RECENTLY AND I'LL SHOW YOU IN THE NEXT COUPLE SLIDES. THE LAST TWO, NUMBER FOUR IS BEING WORKED ON IN MULTIPLE WAYS WITHIN THE BRAIN INITIATIVE, AND NUMBER FIVE IS GOING TO HAVE TO WAIT A LITTLE BIT INTO THE FUTURE. THERE'S ALSO A NEW AGREEMENT IN PLACE TO CONTINUE THE BRAIN INITIATIVE AS IT IS NOW THROUGH 2030. SO THAT'S GOOD THAT'S ANOTHER FOUR OR FIVE YEARS BEYOND WHAT WE WERE EXPECTING. SO FROM 2014 TO 2020, BRAIN HAS SUPPORTED OVER 700 AWARDS WITH OVER $1.4 BILLION INVESTED, AND IT STARTED OUT WITH ABOUT, I THINK, $58 MILLION WORTH OF FUNDING HERE IN 2014, AND THIS YEAR, THE BUDGET JUST CAME DOWN FROM CONGRESS WHICH WAS EXPECTED TO BE AROUND $500 MILLION AND THEY ADDED ANOTHER $60 MILLION ON TOP OF THAT, 40 MILLION EARMARKED FOR THE HUMAN BRAIN CELL ATLAS AND $20 MILLION FOR THE SINGLE CELL -- FOR THE CELL-TYPE SPECIFIC ARMAMENTARIUM. OVER THE LIFETIME, AT LEAST -- 2026, SOME COMES FROM FUNDING THROUGH THE INSTITUTES THAT GOES OVER TO NIMH AND NEUROLOGY TO GIVE OUT THE GRANTS AND THEN SOME OF IT COMES FROM THE 21ST CENTURY CURES ACT. SO THE BRAIN INITIATIVE IS ORGANIZED INTO TEAMS INTERNALLY HERE AT NIH THAT ARE COMPOSED OF PROGRAM OFFICERS AND SCIENTIFIC REVIEW OFFICERS WORKING CLOSELY WITH THEM AS WELL AS OTHER INTERESTED PARTIES. THE TEAMS HELPED TO WRITE FOAs RELATED TO THE MISSIONS FOR EACH TEAM, THE 10 GRANT REVIEWS, ADJUST FUNDING PLANS, AND BASICALLY CREATE THOSE FUNDING PLANS TO BE APPROVED ALONG THE WAY BY THE COORDINATING TEAM, THE DIRECTORS OF THE INSTITUTES, THE MULTI-COUNCIL WORKING GROUP, WHICH I MENTIONED, AND THEN EVENTUALLY BACK OUT TO SPECIFIC ICs. WE'VE ADDED A NEW TEAM THIS YEAR, TEAM TIE, TRAINING, INCLUSION AND EQUITY. THIS WAS BROKEN OFF TEAM D WHICH WAS FOR DISSEMINATION AND USED TO ALSO BE FOR TRAINING. DR. LAURA COLE CONTINUES TO SERVE FOR DISSEMINATION, AND DR. ALBERTO R IVERA-RENTAS MOVED OVER TO INCLUSION AND EQUITY AND I KNOW THEY'VE BEEN TALKING A LOT ABOUT DIVERSITY IN THOSE PLANS THAT WILL PROBABLY BE PUT FORWARD IN THE NEAR FUTURE. DR. ROGER MILLER USES HIS EXPERTISE ON TEAM B FOR ENGINEERING, NEURORECORDING AND MODULATION TECHNOLOGY, AND I DO NEURAL CIRCUITS IN TEAM E AS WELL AS SERVE ON THE COORDINATING TEAM. SO THE OUTPUT FROM THE BRAIN INITIATIVE HAS BEEN SUBSTANTIAL. THERE'S OVER A THOUSAND PUBLICATIONS AND I THINK AT LAST COUNT, I SAW SOMETHING OVER 1300 ON THE BRAIN INITIATIVE SITE, YOU CAN SEARCH THROUGH THOSE IF YOU HAVE SOME TIME TO READ THEM ALL, BUT THEY COVER SUCH A WIDE RANGE OF TOPICS. THERE HAVE BEEN HUNDREDS OF FUNDING ANNOUNCEMENTS BUT THERE ARE CURRENTLY 19 UP AND THEY COME OUT THROUGHOUT THE YEAR. YOU CAN ALSO -- THEY HAVE A SEARCHABLE DATABASE ON THE BRAIN INITIATIVE.NIH.GOV WEBSITE. COVERS A VARIETY OF FUNDING MECHANISMS. YOU'LL NOTICE WE HAVE A NUMBER OF NEW GRANT MECHANISMS, THOSE ARE COOPERATIVE GRANTS. THEY REQUIRE A SCIENTIFIC PROGRAM OFFICER TO BE ASSIGNED FROM NIH, AND IN MANY CASES, THESE ARE LARGE AMOUNTS OF MONEY SO IT'S NICE TO HAVE THAT INPUT FROM BOTH SIDES. AND ALSO THERE'S SOME BUSINESS MONEY THAT SBIR, STTR, SMALL BUSINESS GRANTS ARE ALSO SUPPORTED, JUST LIKE WE DO IN OUR LOCAL ICs. SO WHAT DO WE HOPE TO GAIN FROM THE BRAIN INITIATIVE? WELL, I PERSONALLY MIGHT WANT A MAP OF MY BRAIN TO FIND MY CAR KEYS OR REMEMBER MY COMPUTER PASSWORDS THESE DAYS, BUT WHAT DOES NIDCD WANT? ARE WE BENEFITING FROM THE MONEY BEING SPENT TO THE BRAIN INITIATIVE? IT IS CLEAR NOW AFTER SIX YEARS THAT WE ARE GAINING SOME POWERFUL GLOBAL TECHNIQUES AND TOOLS TO HELP ANSWER OUR MISSION-RELATED QUESTIONS. BUT OUR MISSION AREAS ARE ALSO DIRECTLY BENEFITING. THE NEXT FEW SLIDES WILL HIGHLIGHT THE PORTION OF BRAIN INITIATIVE FUNDING GRANTS THAT ARE RELATED TO OUR NIDCD MISSION AREAS. EITHER BY COUNTING GRANTS THAT ARE DEVELOPED TOOLS THAT HAPPEN TO BE TESTED IN BRAIN AREAS IMPORTANT TO OUR MISSION AREAS, THEY MIGHT BE USING A RELATED MODEL SYSTEM SUCH AS OLFACTION, OR THEY MIGHT BE STUDYING QUESTIONS THAT ARE CRITICAL TO OUR MISSION AREAS, NEURAL CIRCUITS AND BEHAVIORS WITH A VARIETY OF NEW TOOLS. THE MONEY FOR BRAIN ACTUALLY PASSES TO OUR INSTITUTE THROUGH CONGRESS AND THE GRANTS RELATED TO OUR MISSION AREAS ARE NOT USUALLY CODED AS AN NIDCD GRANT. SO IT TAKES SOME DETECTIVE WORK TO REALLY DISCOVER WHICH GRANTS ARE RELATED TO OUR NIDCD MISSION AREAS, EITHER BY SEARCHING THROUGH THE DATABASES AND/OR READING THE INDIVIDUAL GRANTS. SO THIS IS THE NUMBER OF NIDCD-RELATED BRAIN INITIATIVE GRANTS OVER THE PAST SIX YEARS, FROM 2014 TO 2020, WHICH WE HAVE COMPLETE DATA FOR. THERE WERE FOUR GIVEN IN 2014, THE FIRST YEAR, OUT OF 58 GRANTS. THAT'S ABOUT 7% OF THE BRAIN GRANTS WERE RELATED TO OUR MISSION AREAS. IN 2020, THERE WERE 23 OUT OF ALMOST 200 BRAIN INITIATIVE GRANTS, SO WE'RE UP TO ABOUT 17%. THAT'S PRETTY GOOD CONSIDERING THE FACT THAT OUR PASSTHROUGH FROM CONGRESS ARE PART OF THE BUDGET FOR BRAIN IS A LITTLE OVER 1% OF THE BRAIN BUDGET AT 6 TO $7 MIL LION. YOU'LL SEE THAT THERE'S A BUMP HERE IN 2018. THIS IS BECAUSE SOME OF THE DOLLARS FROM -- SOME OF THE GRANTS FROM 2019 WERE PAID WITH LEFTOVER DOLLARS FROM 2018, CAUSING A BIG INCREASE HERE IN 2018. THIS IS THE FIRST YEAR TOTAL COSTS COMPETING NIDCD-RELATED BRAIN INITIATIVE GRANTS, SO THIS IS JUST THE FIRST YEAR TOTAL COST FOR ANYTHING THAT WAS AWARDED THAT YEAR, AND IN 2020 HERE, WE STARTED LESS THAN $5 MILLION IN 2014. IN 2020, WE ARE AT $35.5 MILLION, AND FOR COMPARISON SAKE, WE SPEND ABOUT -- NIDCD ITSELF, ABOUT $100 MILLION EACH YEAR IN COMPETING GRANTS, SO THIS IS ABOUT 35% OF THAT VALUE. SO WHAT ABOUT THE INDIVIDUAL MISSION AREAS? NIDCD IS A BIG -- IT'S A SMALL INSTITUTE BUT WE COVER A LARGE NUMBER OF AREAS. SO WE HAVE TASTE AND SMELL, THE CHEMICAL SENSES, WE HAVE VOICE, SPEECH AND LANGUAGE, AND WE HAVE HEARING/BALANCE. SO I'VE DONE THE NUMBERS BY THESE INDIVIDUAL AREAS. SO THIS IS NUMBER OF GRANTS ACROSS ALL SIX YEARS THAT WERE AWARDED IN EACH OF THESE AREAS RELATED TO OUR MISSION AREAS. THERE WERE 41 IN CHEMICAL SENSES. MOST OF THESE ARE FOR OLFACTION, A FEW ARE FOR TASTE. THERE WERE 45 IN HEARING AND BALANCE. AGAIN MOST FOR HEARING AND A FEW FOR BALANCE, AND THERE WERE 24 IN VOICE, SPEECH AND LANGUAGE. MOST OF THESE ARE FOR SPEECH AND LANGUAGE AND JUST A COUPLE FOR VOICE. THIS IS A TOTAL OF 110 GRANTS OVER THE SIX-YEAR PERIOD THAT WERE MISSION-RELATED. SO IN THE LAST COUPLE YEARS, USUALLY OLFACTION WINS OUT AND HAS THE MOST NUMBER OF GRANTS RELATED TO BRAIN, BUT HEARING AND BALANCE ACTUALLY CAME OUT NUMBER-WISE ABOVE HEARING AND BALANCE, IN TOTAL DOLLARS, YOU'LL SEE THAT CHEMICAL SENSES BY FAR WENT UP WITH $189 MILLION IN TOTAL COSTS, THIS IS DIRECT PLUS INDIRECT, FOR THOSE SIX YEARS, 135 TO HEARING AND BALANCE, AND 84 TO VOICE, SPEECH AND LANGUAGE, WHICH IS NOT TOO SHABBY, AND THIS TOTALS A LITTLE OVER $407 MILLION TO MISSION-RELATED AREAS, EITHER THROUGH TECHNOLOGY TO UTILIZE ANSWERING QUESTIONS IN OUR MISSION AREA OR TO DIRECT ANSWERS TO OUR QUESTIONS THAT WE'RE INTERESTED IN OVER THE SIX-YEAR PERIOD. SO NOW I'D JUST LIKE TO TAKE A COUPLE OF MINUTES TO HIGHLIGHT SOME OF THE FINDINGS THAT HAVE BEEN COMING OUT THAT EITHER AFFECT NIDCD PROJECTS OR THAT WE'RE DOING OURSELVES WITHIN THE BRAIN INITIATIVE. SO THIS IS DR. ELIZABETH HILLMAN WHO DEVELOPED HIGH-SPEED CAMERA TECHNOLOGY WITH MICROSCOPY TO ACHIEVE REALLY HIGH RESOLUTION, LARGE-SCALE VOLUMETRIC IMAGING. THIS IS JUST AMAZING. THIS IS SHOWING YOU THE NEURONS OVER A HUGE DISTANCE HERE IN INCREDIBLY HEID HIGH DETAIL. THIS WAS A GRANT GIVEN OUT THE FIRST YEAR OF BRAIN, SO OVER FIVE YEARS, SHE HAS DEVELOPED THIS AND IT HAS COME QUITE SOME WAY. I'M GOING TO GO AHEAD AND SHOW YOU THAT THIS CAN ALSO BE USED IN LIVING SPECIMENS. ON THIS SIDE WILL BE THE BLOOD CELLS PUMPING THROUGH A HEART OF A ZEBRAFISH, AND ON THIS SIDE WILL BE A C. ELEGANS MOVING, AND THIS IS PRACTICALLY IN REALTIME, AND WHAT YOU SEE IS THAT THESE ARE LABELED FOR DIFFERENT CELLS AND FOR DIFFERENT NEURONS AND CELLS OF ACTIVITY. SO I'M GOING TO GO AHEAD AND PRESS PLAY HERE. AND YOU CAN SEE JUST THE BLOOD CELLS BEING PUMPED THROUGH. THIS IS VERY THREE-DIMENSIONAL, THIS IS VERY FAST TIMING HERE WITH THIS TECHNOLOGY CALLED SCAPE 2.0 NOW. SO HOW IS THAT BEING APPLIED TO NIDCD? WELL, THEORY SECHERS ARE THESE RESEARCHERS ARE FUNDED NOW BY US, BY NIDCD, AND THIS IS LOOKING ACROSS THE OLFACTORY EPITHELIUM, AND IT'S IN A LIVING ANIMAL. THERE'S A LITTLE BIT OF SKULL REMOVED SO YOU CAN ACTUALLY GET A BETTER VAUGH VIEW, BUT IT'S LOOKING ACROSS THE ENTIRE OLFACTORY EPITHELIUM. IT'S GOING TO SHOW YOU ACTIVITY WITH CALCIUM INDICATORS AND WHEN THE ODOR IS PRESENTED YOU'RE GOING TO SEE, YEP, THAT BRIGHT FLASH OF GREEN, AND YOU CAN SEE ALL THE INDIVIDUAL CELLS THAT ARE BEING ACTIVATED BY THAT ODOR. AND AS WE COME AROUND HERE, WE'RE GOING TO SEE ONE FROM THE SIDE, YOU CAN SEE JUST A HUGE DISTANCE COVERED BY THIS TECHNIQUE, BEING ABLE TO SEE THIS ALLOWS THEM TO SEE THE PATTERNS AND THEY'VE ALREADY DISCOVERED THAT THE PATTERNS BEING ACTIVATED ARE VERY DIFFERENT FOR INDIVIDUAL CELLS VERSUS COMPOSITE CELLS, AND THAT THIS IS HAPPENING MUCH EARLIER THAN THE OLFACTORY CORTEX, WHERE IT WAS EXPECTED. ABOUT A YEAR AND A HALF AGO, DR. DI RINBE RG, CRACKING THE OLFACTORY CODE, ALL OF THESE PEOPLE LISTED HERE ARE INDEED PEOPLE WHO RECEIVED MONEY FROM OUR INSTITUTE, AND ALSO FROM THE BRAIN INITIATIVE. THIS IS A VERY LARGE GRANT. IT'S OVERSEEN BY A SCIENTIFIC OFFICER AS WELL AS AN EXTERNAL ADVISORY BOARD CHAIRED BY OUR OWN DR. SUSAN SULLIVAN, WHOSE RESEARCH, THIS FALLS WITHIN HER PORTFOLIO. AND THIS TOTALS OVER FIVE YEARS, $19 MILLION IN DIRECT AND INDIRECT COSTS THAT IS VERY MUCH IN OUR MISSION AREA. THEY'VE ALREADY BEEN SHOWING GREAT RESULTS FROM THIS U19 GRANT. I WON'T GO INTO THE DETAILS HERE, BUT IN GREAT SPATIAL AND TEMPORAL RESOLUTION, THEY'RE FINDING OUT NEW THINGS ABOUT THE OLFACTORY CORTEX. DR. EDDIE CHANG, I TOLD YOU ABOUT A COUPLE YEARS AGO, AND HE'S BEEN CONTINUING TO DEVELOP DECODING BRAIN ACTIVITY THAT UNDERLIES SPEECH. SO THEY RECORD FROM HUMANS OVERLAID ON THE CORTEX HERE, AND THEY HAVE THE HUMANS THINK ABOUT SILENT WILLING MININSILENTLY MINING SENTEN CES. THEY CAN TAKE THIS, USING MACHINE ALGORITHMS, DECODER AND A SYNTHESIZER AND OUTPUT WHAT THIS ACTIVITY WOULD HAVE SOUNDED LIKE IF THE PERSON HAD ACTUALLY SPOKE OUT LOUD. SO I'M GOING TO PLAY THIS, THIS TAKES JUST A MINUTE TO COME UP SO FIRST YOU'LL HEAR IT SYNTHESIZE IN JUST A MOMENT. >THE PROOF THAT YOU ARE SEEKING IS NOT AVAILABLE IN BOOKS. >> NOW ONE MORE TIME, THE SYNTHESIZED. >> [INAUDIBLE] >> SO IT'S NOT PERFECT BUT IT'S AMAZING PROGRESS ALL THE SAME. AND THIS WAS A VERY EXPENSIVE UNDERTAKING PAID FOR BY BRAIN, RIGHT, AND NOW THAT WORK IS GOING TO BE CONTINUED FUNDED BY US AT NIDCD FOR A CLINICAL TRIAL FOR SPEECH NEURAL PROSTHESIS. THIS IS IN DR. LANA SHEKHAM'S PORTFOLIO. DR. CHANG IS ACTUALLY RECEIVING FURTHER FUNDING TO STUDY MULTIPLE LANGUAGES TO HELP TO INCREASE THE OUTPUT OF THIS POSSIBLE NEUROPROSTHESIS. DR. SUSAN SHORE WAS ONE MORE PERSON THAT I TALKED ABOUT A COUPLE YEARS AGO. SHE'S WORKING ON AUDITORY SOMATOSENSORY STIMULATION TO TREAT TINNITUS. SHE'S MOVED ON FROM HER BRAIN INITIATIVE FUNDING. SHE'S NORMALLY FUNDED IN DR. JANET SEARS' PORTFOLIO, AND SHE HAS NOW A PATENT AND IS LOOKING FOR FDA APPROVAL FOR HER DEVICE TO TREAT TINNITUS TUS. DR. HUBERT LIMM IS STILL RECEIVING FUNDING FROM THE BRAIN INITIATIVE, ALSO RECEIVES FUNDING FROM US, FROM DR. ROGER MILLER'S PORTFOLIO, AND HE'S WORKING ON A AUDITORY NERVE INTRACRANIAL NEVER IMPLANT THAT NERVE IMPL ANT. HE'S WORKED WITH LOWER ANIMALS AND NOW JUST RECENTLY FOR THE LAST TWO YEARS OF THIS GRANT WILL HAVE APPROVAL TO WORK IN HUMANS AND TO START TO IMPLANT THIS. HE'S RECEIVED $11 MILLION FROM DIRECT AND INDIRECT COST FROM THE BRAIN INITIATIVES. HE'S ALSO BUILDING ON A RIPPLE EFFECT FROM DR. SHORE'S WORK WHICH I JUST SHOWED YOU IN TINNITUS AND HE'S BUILDING ON THOSE FINDINGS IN USING SOMATOSENSORY STIMULATION OF THE TONGUE, AWD DRI STIMULATION IN AUDITORY ST IMULATION TO CHANGE THE PATTERNS AND HELP REDUCE TINNITUS. THIS IS BEING PAID FOR BY A COMPANY FOR A DEVICE FOR FDA APPROVAL. SO THIS IS JUST A LIST, SCROLLING THROUGH JUST FROM THE LAST TWO YEARS, OF GRANT TITLES AND THEIR MAIN PIs OF FUNDING THAT WE'VE RECEIVED THAT'S NID MISSION-RELATENIDCDMISSION-RELAT ED NOW BEI NG FUNDED BY BRAIN, AND WE HOPE THERE'S A LOT MORE OF THIS TO COME IN THE FUTURE. EVERYTHING FROM SPEECH PERCEPTION TO OLFACTION TO FINDING YOUR WAY IN SPACE. THERE'S A HUGE RANGE OF RESEARCH HERE. SO TECHNICAL -- SO IN SUMMARY, NIDCD BENEFITS IN A NUMBER OF DIRECT AND INDIRECT WAYS FROM BRAIN INITIATIVE FUNDING. CERTAINLY IN TECHNICAL ADVANCES AND MISSION-RELATED RESEARCH QUESTIONS. WE WERE WORRIED THAT THIS MIGHT STEAL SOME OF OUR PIs AWAY, WITH YOU WHAT IT REALL IT'S REALLY DONE IS GIVEN THEM MORE MONEY TO DO THEIR WORK AND WE'RE STILL SEEING THEM IN OUR OWN INSTITUTE, SOMETIMES THEY MIGHT GO AWAY FOR A LITTLE BIT AND COME BACK AND THERE'S ACTUALLY AN EXPANSION OF PEOPLE INTERESTED IN USING OUR MODELS FOR SOME OF THESE TOOL TECHNIQUES AND DEVELOPMENT. A LOT OF DATA SHARING THAT'S GOING ON AS WELL. SO TO PROMOTE INCREASED SYNERGY BETWEEN THE BRAIN INITIATIVE AND NIDCD, I CAN TELL YOU THAT DR. TUCCI HAS APPROVED IN THEORY A NEW 50/50 SHARED PROGRAM OFFICER WHERE THEY WOULD DO 50% IN OUR INSTITUTE AND THEN 50% DEVOTED TO THE BRAIN INITIATIVE. AND THAT WOULD ALLOW THEM TO PLAY A MORE DIRECT ROLE AND TIME INVESTED IN MANAGING BRAIN GRANTS, BEING A SCIENTIFIC OFFICER ON THESE U COOPERATIVE GRANTS, AND WE HOPE THAT THAT WILL HELP TO ENCOURAGE OUR PIs TO UNDERSTAND THE BRAIN RFAs BY DEVOTING MORE TIME. SO I JUST REMIND YOU QUICKLY THAT YOU CAN ATTEND THE ANNUAL BRAIN MEETING. ATTENDANCE AND REGISTRATION IS ABSOLUTELY FREE. IT'S VUR ACTUAL AGAIIT'S VIRTUAL THIS YEAR , IT WAS VIRTUAL LAST YEAR, OVER 4,000 PEOPLE ATTEND ACROSS THE WORLD. REALLY WELL DONE, PLENARY SPEAKERS, DR. ERIC JARVIS, NEUROBIOLOGY OF LOCAL LEARNING, DR. MURPHY, NORMALLY PAID FOR BY MENTAL HEALTH BECAUSE IT'S SOCIAL COMMUNICATION, AND BY BRAIN INSTITUTE, BUT STILL RELATED. AND GENERAL IF HE EVER DUADENA WHO WON A NOBEL PRIZE FOR CRISPR IS ALSO COMING TO SPEAK. SO I WANTED TO SAY THANK YOU TO MY COLLEAGUES AT NIDCD WHO HELPED WITH THE DATA ANALYSIS AND HELPED IN THE DETECTIVE WORK AND ALSO TO ALL THE PEOPLE WHO WORK ON THE BRAIN INITIATIVE. I CAN ALWAYS SAY THAT MY COLLEAGUES AT THE NIDCD ALWAYS COME THROUGH WITH WHATEVER WE MIGHT NEED. SO NOW I HOPE TO TAKE ANY QUESTIONS. I KNOW WE'RE RUNNING A LITTLE BIT LATE ON TIME BUT I'M GOING TO STOP SHARING. >> THANK YOU, AMY. THAT WAS A WONDERFUL DISCUSSION. BEN? >> THIS WAS WONDERFUL INFORMATION THAT I THINK WE ALL WANTED, AND IT'S JUST A PITY IT TOOK SO MUCH DETECTIVE WORK TO SEE THE CONNECTIONS BETWEEN OUR INSTITUTE HERE AND THE BIGGER BRAIN INITIATIVE. SO I THINK IT'S JUST WONDERFUL TO SEE HOW SUCCESSFUL THIS HAS BEEN. I'VE JUST -- TWO QUESTIONS. ONE IS, CAN YOU SAY ANYTHING ABOUT THE SUCCESS RATES? THESE USED TO DO BETTER THAN THE REGULAR R01s. IS THAT STILL TRUE? >> THEY'RE STILL AROUND 25%. >> YEAH, SO THAT'S GREAT. AND THE OTHER QUESTION IS, LIKE, IN THE SORT OF THE BEGINNINGS OF THE BRAIN INITIATIVE RFAs, THERE WERE VERY CONSTRAINED, SO THEY WERE -- YOU HAD TO BE DOING AWAKE ANIMAL, AWAKE MAMMALS OR SOME MODEL ORGANISMS, BUT IT WAS A PUSH TO UNDERSTAND HOW CELLS WORK IN THE CONTEXT OF A BEHAVING ANIMAL. AND THAT'S A WONDERFUL THING AND THAT'S FUNDED A LOT OF WORK THAT WAS MAYBE VERY DIFFICULT TO GET THROUGH THE R01s LIKE COMPUTATIONAL MODELS AND STUFF, BUT THERE'S ANOTHER SIDE TO THIS WHERE IT'S MORE MECHANISTIC, IT'S USING MORE REDUCED PREPARATIONS, SMALLER TEAMS, QUESTIONS THAT CAN BE BETTER ADDRESSED BY SMALLER, NIMBLE TEAMS. IS THAT A PUSH TO SORT OF HAVE SOME OF THE STREAM OF MONEY NOW GO INTO SORT OF THESE SORT OF REDUCED PREPARATION QUESTIONS, OR IS THAT STILL REGARDED AS THE REGULAR R01 POOL DOES VERY WELL IN COVERING THAT AREA AND SO THE BRAIN POOL SHOULD BE SORT OF THESE BIGGER TEAMS, BIGGER QUESTIONS? >> I THINK IT'S YOUR SECOND. IT'S REALLY ABOUT PUSHING THE ENVELOPE, TRYING TO PUT ALL THOSE TECHNIQUES TOGETHER IN ONE SPACE, RIGHT, GETTING THE RESOLUTION, THE TEMPORAL AND SPATIAL RESOLUTION ALL AT ONCE. AND IT'S NOT TO SAY THAT SOME OF THE TECHNIQUES BEING DEVELOPED DON'T NEED A SMALLER PREP SYSTEM. BUT I WILL SAY THAT BRAIN HAS ADDED SOME OF THESE SMALLER GRANTS, MORE EXPLORATORY, SOMETIMES IF IT'S A SMALLER CONCEPT THAT NEEDS TO BE DONE BEFORE A BIGGER GRANT, THEY'VE ADDED SOME OF THOSE. BUT I AGREE THAT SOME OF THESE OTHER QUESTIONS CERTAINLY CAN BE ANSWERED WITHIN OUR OWN INSTITUTE, RIGHT, SO THEY NEED TO BE DONE THAT WAY. >> I WOULD JUST FOLLOW UP AND SAY IF IT'S STILL MOSTLY EMPHASIZING THESE LARGE GROUPS, OR COLLABORATIONS, THEN IT SEEMS LIKE ONE THING OUR INSTITUTE COULD DO WITH ALL THIS DETECTIVE WORK IS TO PUT TOGETHER EXAMPLES OF HOW TEAMS HAVE COME TOGETHER AND USE THE PROGRAM OFFICERS, THE STRENGTH OF ALL OUR PROGRAM OFFICERS TO MAYBE PROMPT SOME PEOPLE THAT MAYBE DON'T KNOW ABOUT OTHER PEOPLE THAT HAVE SYNERGISTIC TOOLS OR SYNERGISTIC MOLECULAR APPROACHES THAT MAYBE THE DC COULD SYNERGIZE SOME NEW TEAMS. >> IT'S A GOOD TIME TO START THINKING ABOUT THAT, AND MAYBE WE CAN USE THEIR EXPERTISE IN HAVING THOUGHT ABOUT THE WAYS IN WHICH TO FORMULATE THEIR BRAIN PROPOSAL. SO NOW THE EXPERTISE PROBABLY DOES EXIST WITHIN OUR INSTITUTE TO BE ABLE TO HELP START TO DO THAT. AND THERE ARE SOME INDIVIDUAL GRANTS, I DON'T WANT TO SAY IT'S ALL TEAM SCIENCE, BUT CERTAINLY FOR THE NEURAL CIRCUITRY STUFF THAT OUR PIs ARE LISTED IN, A LOT OF THAT IS TEAM SCIENCE. >> JUST ONE COMMENT ON THE SIDE BECAUSE I'VE TALKED TO SOME PEOPLE WHO HAVE THEM -- IS MY COLLEAGUE, HE ACTUALLY SHARED WITH ME THAT HUGE OLFACTORY GRANT. ONE OF THE THINGS THAT CAME ACROSS TO ME IS THAT THERE'S A HUGE AMOUNT OF IMPORTANT INFORMATION ABOUT HOW TO DO THESE THINGS AND HOW TO PREPARE FOR THEM, KIND OF LIKE WHAT'S UNDER THE HOOD. SO SORT OF UNDERSTANDING WHAT THE PROCESS IS AT THE NIH ADMINISTRATIVE LEVEL, AND THEN THERE'S UNDERSTANDING WHAT THE PROCESS IS AS A UNIVERSITY INVESTIGATOR WHO'S NOW GOING TO HAVE TO PUT THIS TOGETHER. AND SO WHAT I'M THINKING IS, ET CETERA KIND OF LIKE BEN'S SUGGESTION BUT CARRY IT FORWARD. DO YOU THINK WE COULD GET AN INFORMAL GROUP OF SUCCESSFUL INVESTIGATORS TOGETHER WHO WOULD PERHAPS BE ABLE TO OFFER US THIS BEHIND THE SCENES LOOK AT WHAT IT TOOK, PERHAPS ESPECIALLY DURING A REAPPLICATION PROCESS TO GET THESE THINGS TO WORK? >> YEAH, I THINK WE'LL DEFINITELY EXPLORE WHAT WE CAN DO ON THAT FRONT, AND I AGREE WITH YOU ABOUT THE REAPPLICATION PROCESS. THERE ARE A LOT OF WAYS TO ANSWER QUESTIONS FROM YOUR REVIEW WITHIN THE BRAIN INITIATIVE. IT'S TALKED ABOUT AT SO MANY DIFFERENT LEVELS THAT PEOPLE REALLY DO DIG INTO THE DETAILS AND TRY TO HELP PEOPLE ON REAPPLICATION. SO WE'LL TALK ABOUT HOW WE CAN INSTITUTE SOMETHING LIKE THAT. >> I THINK IT WOULD BE GOOD TO HAVE SOMETHING OF A ROAD SHOW TO TAKE TO VARIOUS MEETINGS LIKE ARO AND TELL PEOPLE ABOUT THIS PROGRAM BECAUSE ALTHOUGH WE DO UTILIZE THIS RESOURCE AS INDICATED VERY SIGNIFICANTLY, I THINK THERE'S MORE THAT COULD BE DONE, AND I THINK PEOPLE ARE INTIMIDATED BY THINKING ABOUT APPLYING FOR ONE OF THESE GRANTS, BECAUSE IT DOES REQUIRE SOME OUT OF THE BOX THINKING AND PEOPLE AREN'T USED TO IT, BUT AMY AND DAN, I THINK WE CAN PUT TOGETHER A GROUP TO TALK ABOUT WAYS THAT WE CAN MAKE PEOPLE MORE INFORMED ABOUT THE PROCESS THAT THEY NEED TO GO THROUGH TO APPLY FOR THESE GRANTS TO PUT TOGETHER A CONSORTIUM. >> I KNOW THAT THE TEAM LEADS FROM BRAIN AND EVEN JOHN NGUI ARE AVAILABLE TO COME AND SPEAK AND THAT WOULD BE HELPFUL TOO. >> GREAT. WELL, ARE THERE ANY OTHER COMMENTS? BECAUSE I THINK WE ARE A LITTLE BIT BEHIND AND WE CAN MOVE ON TO CRAIG NOW IF THAT'S OKAY. ALL RIGHT. THANK YOU, AMY. THAT WAS WONDERFUL. ALL RIGHT. SO NOW WE WILL MOVE ON TO THE REPORT OF THE DIVISION OF EXTRAMURAL ACTIVITIES AND DR. JORDAN WILL PROVIDE THIS REPORT. IN HIS COMMENTS, CRAIG WILL ALSO LEAD US THROUGH THE ANNUAL REVIEW OF OUR COUNCIL OPERATING PROCEDURES. >> THANK YOU. SO I'LL ACTUALLY START OFF WITH THAT PIECE OF REVIEW FOR THE ANNUAL -- ANNUAL REVIEW OF THE COUNCIL OPERATING PROCEDURES. THIS IS A DOCUMENT IN NEGOTIATION WITH THE COUNCIL THAT TELLS US HOW WE INTERACT WITH THE COUNCIL DURING THE YEAR, AND WE HAVE TO RENEW THIS EACH YEAR. THERE ARE NO RECOMMENDED CHANGES TO THIS DOCUMENT THIS YEAR. SO I'M JUST GOING TO QUICKLY REVIEW THE THREE DIFFERENT PIECES OF THE DOCUMENT. IT WAS AVAILABLE IN ADVANCE ON THE WEBSITE AND IN THE COUNCIL WORKBOOK. THIS FIRST PAGE HIGHLIGHTS QUICKLY THE SPECIFIC SITUATIONS THAT ARE RAISED AT EACH COUNCIL MEETING, LIKE THE HIGH PROGRAM PRIORITY DISCUSSIONS, APPLICATIONS EXCEEDING $500,000, APPLICATIONS FROM FOREIGN INSTITUTIONS, A NUMBER OF THINGS INCLUDING APPEAL LETTERS AND LETTERS FROM INVESTIGATORS. ON THE NEXT SLIDE, I TALK A LITTLE BIT ABOUT A SECOND PIECE IN THIS DOCUMENT, AND THAT IS ACTIONS THAT STAFF TAKE BETWEEN COUNCIL MEETINGS, AND THEN WE JUST BRING THEM BACK IN A SUMMARY DOCUMENT TO COUNCIL CALLED THE ADMINISTRATIVE ACTIONS REPORT. THOSE ARE THINGS LIKE CHANGING THE PRINCIPAL INVESTIGATOR, TRANSFER OF THE AWARD TO A NEW INSTITUTION, ORDERLY TERMINATION, AND SOME OF THE SUPPLEMENTS THAT GET ADDED TO GRANTS IN BETWEEN COUNCIL ROUNDS. YOU HEARD ABOUT SOME OF THOSE SUPPLEMENTS EARLIER. AND THEN THE FINAL PIECE OF THIS DOCUMENT IS APPLICATION PIECES THAT ARE JUST TAKEN CARE OF AS A MATTER OF COURSE, LIKE TERMINATION AND THINGS LIKE THAT, OR EXTENSION OF PROJECT PERIODS. SO IF THERE'S ANY DISCUSSION, NOW IS THE TIME ON THIS DOCUMENT. AND IF NOT, I THINK WE WOULD ENTERTAIN A MOTION TO APPROVE THE COUNCIL OPERATING PROCEDURES FOR THE NEXT YEAR. ANYONE WANT TO MAKE THAT NOMINATION? >> SO MOVED. >> I HEARD A MOVE AND A SECOND. ALL THOSE IN FAVOR, SAY AYE OR PUT A COMMENT IN THE CHAT BOX. >> AYE. >> THANK YOU. AND AYES IN THE CHAT BOX AS WELL. ANY OPPOSED? ALL RIGHT, THANK YOU. THE NEXT PIECE OF MY PRESENTATION, I'M GOING TO TELL YOU A LITTLE BIT ABOUT WHAT GOES ON DURING THE LAST YEAR OF 2020 IN THE DIVISION OF EXTRAMURAL ACTIVITIES, AND I'M GOING TO START OFF WITH, AS INDICATED ON THIS SLIDE, TELLING YOU A LITTLE BIT ABOUT THE GRANTS MANAGEMENT BRANCH. IT'S STAFFED WITH A BUNCH OF PEOPLE THAT ARE MOSTLY CALLED GRANTS MANAGEMENT SPECIALISTS. AND THEY DO ALL THE PROCESSING OF THE AWARDS BUT THEY DON'T DO IT IN ISOLATION. THEY NEED HELP AND THEY WORK ALSO AS A COLLABORATIVE TEAM. SO THE GRAPH IN FRONT OF YOU SHOWS THE NUMBER OF PROCESSING OF AWARDS THAT HAPPEN IN 2018, '19 AND '20. I'M JUST GOING TO FOCUS ON THE FAR RIGHT SIDE, WHERE 2020 IS LISTED. THAT BLUE LINE AT THE TOP, 1,157 ACTIONS, IS THE TOTAL. THE LINE BELOW THAT, THE GOLD COLORED LINE, IS 777 AND THAT'S THE NONCOMPETING AWARDS. THOSE ARE AWARDS THAT WERE AWARDED IN PRIOR YEARS, BUT THEY'RE COMING BACK FOR THE YEAR TWO, YEAR THREE, YEAR FOUR PIECES OF THE AWARDS. THEY HAVE PROGRESS REPORTS AND A LOT OF OTHER PIECES THAT HAVE TO BE MANAGED BY THE GRANTS MANAGEMENT BRANCH. MOVING DOWN TO THE NEXT LINE, THE BLUE LINE WITH 255, THOSE ARE THE NEW AWARDS. THOSE ARE THE AWARDS THAT COME THROUGH THE COUNCIL EACH YEAR AND THEN ARE ABLE TO BE MADE. THE LOWEST LINE ON THE SORT OF ORANGE COLORED LINE ALSO COMES THROUGH THE COUNCIL. THESE ARE THE COMPETING RENEWALS, INVESTIGATORS THAT ALREADY HAD SUPPORT AND ARE COMING BACK FOR A NEXT BOLUS OF SUPPORT, 47 AWARDS THERE, AND THEN THE GREY LINES ARE SUPPLEMENTS THAT ARE ADDED ON TO EXISTING AWARDS. NEXT SLIDE WILL SHOW YOU A LITTLE BY DIFFERENT LOOK AT SOME OF THESE THINGS. ACTUALLY LET ME STEP BACK A MOMENT. THERE ARE LOTS OF THINGS THAT GO ON IN MAKING THESE AWARDS. NOW YOU CAN MOVE THE SLIDE FORWARD, GINGER. LOTS OF THINGS GOING ON IN THESE AWARDS. MANY OF THEM, I CAN'T REALLY PUT INTO NUMBERS AND PUT ON A SCREEN, BUT THERE ARE SOME THAT I CAN. JUST KNOW THAT THE GRANTS MANAGEMENT SPECIALISTS ARE DEALING WITH THE PROGRAM OFFICERS, THE PIs, THE INSTITUTIONS, AND OTHER NIH OFFICES TO MANAGE ALL OF THESE AWARDS AND GET THEM TO COME TO FRUITION. ONE THING THAT I CAN SORT OF DOCUMENT IN NUMBERS IS HUMAN SUBJECTS. SO THIS GRAPH SHOWS YOU IN THE GREEN BARS ONLY I'LL CONCENTRATE ON THE 2020 NUMBERS, ON THE FAR LEFT, A LOT OF GRANTS DON'T HAVE HUMAN SUBJECTS. BUT IN THE MIDDLE GREEN BAR, 134 DID HAVE HUMAN SUNT SUBJECTS AND DID NOT HAVE ANY CONCERNS IDENTIFIED BY THE INITIAL REVIEW GROUP, BUT THE GRANTS MANAGEMENT STAFF STILL HAVE TO TAKE CARE OF A LOT OF ISSUES RELATED TO HUMAN SUBJECTS BEFORE THE GRANT CAN BE ISSUED, INCLUDING DOCUMENTING IRG APPROVALS BACK AT THE INSTITUTION. BUT THE MORE COMPLICATED GROUP IS IN THE FAR RIGHT. FORTUNATELY THERE'S ONLY THREE LAST YEAR IN 2020, AND THOSE ARE APPLICATIONS THAT HAVE HUMAN SUBJECTS CONCERNS AND BEFORE THOSE CAN BE AWARDED, THOSE CONCERNS HAVE TO BE RECTIFIED. AND AGAIN, THAT INVOLVES LOTS OF ENTITIES, AND THE GRANTS MAN MANAGEMENT STAFF TOUCHED BASES WITH PROGRAM OFFICERS, PRINCIPAL INVESTIGATORS, INSTITUTIONS, TO RECTIFY THOSE ISSUES, AND THEN THEY HAVE TO NEGOTIATE THAT FINAL CLEARANCE WITH AN NIH OFFICE. ON THE NEXT SLIDE, THERE'S A SIMILAR STORY FOR THOSE APPLICATIONS THAT INVOLVE ANIMALS. AGAIN, IN THE MIDDLE BAR, THE GREEN BAR, 126 GRANTS HAD ANIMALS INVOLVED, EVEN THOUGH THERE WERE NO CONCERNS, THERE WERE STILL SOME PROCESSING ISSUES THAT HAD TO BE TAKEN CARE. AND AGAIN, THE TRICKIER PART IS IN THE FAR RIGHT, THERE WERE ONLY SIX FORTUNATELY, BUT THEY HAD HUMAN SUBJECTS CONCERNS. THOSE HAD TO BE RESOLVED BEFORE AWARDS COULD BE FUNDED OR BEFORE AWARDS COULD BE PROVIDED FOR THOSE GRANTS. THIS IS A DIFFERENT ISSUE. THE GRANTS MANAGEMENT GROUP TRIES TO MOVE ALONG WIC QUICKLY WITH THEIR AWARDS. THEY TRY TO GET SOME DONE IN DECEMBER, JANUARY, FEBRUARY TO SPREAD THEIR WORKLOADS OUT, AND THE INVESTIGATORS DEPEND ON THOSE AWARDS TO COME THROUGH, TO MAINTAIN THEIR LABS, TO MAINTAIN THE RESEARCH INFRASTRUCTURE AND THEIR STAFFING. SOME YEARS, MOST YEARS, WE DON'T HAVE AN APPROPRIATION BY THE TIME OF DECEMBER AND SOMETIMES JANUARY OR EVEN LATER. BUT THE GRANTS MANAGEMENT BRANCH, THE STAFF CONTINUE TO MAKE AWARDS AND BASED ON NIH GUIDANCE, THOSE AWARDS ARE USUALLY MADE AT ONLY 90% LEVEL. WE RESERVE ABOUT 10% UNTIL WE REALLY KNOW IF WE HAVE AN APPROPRIATION THAT WILL ALLOW US TO MAKE THOSE. THEN THEY HAVE TO GO BACK AND REVISE THOSE AWARDS, GIVE THEM BACK AT 10%. BACK IN FISCAL YEAR '18, THE BAR ON THE LEFT, THAT APPROPRIATION DOLLARS, THE ABILITY TO GO BACK AND REVISE THOSE AWARDS, DIDN'T HAPPEN UNTIL APRIL. IN FISCAL YEAR '19, AN AMAZING THING HAPPENED. WE GOT AN APPROPRIATION ON TIME. IT'S THE FIRST TIME IN OVER TWO DECADES THAT HAS HAPPENED. IT SURE MADE THE GRANTS MANAGEMENT BRANCH EFFORTS EASIER. THEY DIDN'T HAVE TO REVISE ANY AWARDS. IN FISCAL YEAR '20, A FAIR NUMBER HAD TO BE REVISED STARTING IN THE MIDDLE OF JANUARY, AND THIS YEAR, WE WERE ABLE TO START THOSE REVISIONS IN EARLY JANUARY. THERE WEREN'T QUITE AS MANY. THE LAST ONE IN THE GRANTS MANAGEMENT BRANCH I'M GOING TO MENTION IS THOSE GRANTS THAT INVOLVE FOREIGN INSTITUTIONS, FOREIGN SITES. THOSE REQUIRE SPECIAL PROCESSING, AND THAT INVOLVES ANOTHER COMPONENT OF THE NIH, THE FOGARTY INTERNATIONAL CENTER. SO THE GRANTS MANAGEMENT SPECIALISTS INTERACT WITH FOGARTY TO MAKE SURE WE GET THE PROPER CLEARANCES TO MAKE THOSE AWARDS THAT WILL HAVE IMPACT ON FOREIGN SITES. USUALLY IN THE MID 20s OF THOSE EACH YEAR THAT ARE ACTUALLY AWARDED. SO NOW I'M GOING TO SWITCH ON THE NEXT SLIDE AND TALK A LITTLE BIT ABOUT THE SCIENTIFIC REVIEW BRANCH COMPOSED OF SCIENTIFIC REVIEW OFFICERS AND SOME ASSISTANTS, AND AGAIN, A LOT OF WORK GOES ON BEHIND AND I CAN'T REALLY TELL YOU ALL THE WORK BUT I DO HAVE A FEW NUMBERS TO ACTUALLY SORT OF DEMONSTRATE JUST WHAT KIND OF EFFORT GOES INTO THIS. ON THIS ONE, YOU'LL NOTICE IN THE UPPER BOX ON THE RIGHT SIDE, DISTINCT REVIEWERS. SO THERE ARE 248 INDIVIDUALS THAT WERE RECRUITED. THEY OBVIOUSLY START ASKING A LARGER NUMBER, BUT THEY GOT DOWN TO 248 INDIVIDUALS TO SERVE ON THE REVIEW PANELS DURING 2020. NOW SOME OF THOSE PEOPLE ARE SO COMMITTED THAT THEY'LL SERVE ON MULTIPLE REVIEW PANELS, EITHER THE SAME PANEL THAT RECURS DURING THE YEAR, OR ON DIFFERENT SPECIAL EMPHASIS PANELS. SO IF YOU LOOK ANY MEDDLE OF THAT UPPER BOX, THERE WERE 392 REVIEWER SLOTS THAT HAD TO BE SCHEDULED, ASSIGNMENTS MADE, AND A LITTLE BIT OF THE MAGNITUDE OF THE EFFORT. THE LOWER TABLE ON THIS PAGE DOWN INTO TWO DIFFERENT TYPE OF PEER REVIEW MEETINGS, THE STANDING IRG REVIEW GROUPS, AND THAT'S WHERE THE MEMBERSHIP IS DESIGNATED. WE HAVE ONE STANDING REVIEW GROUP THAT'S COMMUNICATION DISORDERS OF REVIEW COMMITTEE WITH 21 STANDING MEMBERS. BUT YOU'LL SEE THAT THEY STILL SUPPLEMENT THAT WITH EXTRA PEOPLE DURING THE YEAR TO MAKE SURE THE EXPERTISE IS APPROPRIATE FOR THE REVIEW MEETINGS. AND IN THE RIGHT BOTTOM CORNER, THE SEP, THE SPECIAL EMPHASIS PANEL, AGAIN, LOTS OF REVIEWERS USED, AND IN THAT CASE, THEY HAVE TO BE RECRUITED DE NOVO EACH TIME BASED ON THE SCIENCE THAT'S BEING REVIEWED IN THAT PANEL. SO THE UPPER BOX REALLY IS ANOTHER WAY TO SLICE AND DICE WHAT THE REVIEWERS USED BUT I WANTED TO FOCUS ON NUMBER OF IRG MEETINGS. SO THE STAFF AT THE REVIEW BRANCH LAST YEAR ASSEMBLED 33 DIFFERENT MEETINGS, 3 WERE FROM THE STANDING IRGs, BUT 30, ROUGHLY 10 EACH COUNCIL ROUND, WERE SPECIAL EMPHASIS PANELS THAT HAD TO BE BASICALLY BUILT UP FROM SCRATCH WITH FULL RECRUITMENTS, READING ALL THE GRANT APPLICATIONS AND MAKING SURE THE RIGHT SCIENCE WAS REPRESENTED ON THE REVIEW PANEL. THIS IS THE TYPES OF APPLICATIONS THAT ARE REVIEWED IN HOUSE, IN THE SCIENTIFIC REVIEW BRANCH. YOU'LL NOTICE A REAL SPECTRUM OF ACTIVITY CODES HERE. STARTING AT THE TOP WITH THE R13 OR THE CONFERENCE GRANTS, FOLLOWED BY A LARGE NUMBER OF Ks OR OUR CAREER DEVELOPMENT AWARDS, AND THEN A CADRE OF Ls. YOU DON'T EVEN SEE THESE AT COUNCIL BECAUSE THESE ARE RESEARCH CONTRACTS, THEY'RE ACTUALLY LOAN REPAYMENT GRANTS FOR PEOPLE THAT ARE DOING PAYBACK TO GET PAYMENT FOR THEIR EDUCATIONAL LOANS. WE'VE GOT THE CLINICAL CENTERS, THE R GRANTS, THEN AT THE BOTTOM, THE SERIES OF Fs, Ts, FOR FELLOWSHIP TRAINING. THE LOWER RIGHT CORNER, THAT REPRESENTS 416 GRANT APPLICATIONS THAT WERE REVIEWED LAST YEAR IN A LARGE NUMBER OF MEETINGS COVERING A LARGE SPECTRUM OF RESEARCH ACTIVITIES AND WE ALREADY SAW REQUIRING A LARGE NUMBER OF RESEARCHERS TO VOLUNTEER AS PEER REVIEWERS. THAT ALSO REQUIRES SUMMARY STATEMENTS FOR EACH ONE AND RESEARCH CODES AND THINGS LIKE THAT. SO LAST SLIDE ON THIS IS THE OTHER COMPONENT OF THE DIVISION, OFFICE OF THE DIRECTOR. AND WE HAVE A BUNCH OF ACTIVITIES GOING ON HERE. I'M GOING TO CHARACTERIZE THESE AS MOST OF THESE ACTIVITIES CUT ACROSS THOSE OF THE INSTITUTE OR EVEN CUT ACROSS INTO OTHER PIECES OF THE NIH. THE FIRST ONE IS LIAISON TO THE NIH GUIDE. NOW THAT'S HOW THE INSTITUTE PUBLISHES THE RFAs, THE PROGRAM ANNOUNCEMENTS, NOTICES OF INFORMATION, AS WELL AS HOW WE SIGN ON TO ALL THESE TRANS-NIH INITIATIVES LIKE THE FELLOWSHIP SOLICITATIONS AND THE CAREER DEVELOPMENT SOLICITATIONS, AND EVEN OUR STANDARD R01 SOLICITATIONS FOR GRANTS. ANOTHER ASPECT DONE IN THE OFFICE IS THE ADVISORY COUNCIL. AS YOU WELL KNOW, BOTH OF THESE ACTIVITIES, GINGER TAKES THE LEAD ON. IN THIS LAST YEAR, 2020 WAS A PARTICULAR CHALLENGE BECAUSE WE CONDUCTED VIRTUAL MEETINGS AS YOU ALL KNOW, WE HAD TO INCORPORATE VIDEOCASTING, CLOSED CAPTIONING AND CONVERT IT OVER TO THE TWO-DAY MEETING FORMAT. THE THIRD MAJOR BULLET HERE IS NIDCD'S POINT OF CONTACT FOR FREEDOM OF INFORMATION ACT. AS YOU KNOW, AS A FEDERAL AGENCY, ANYBODY IN THE PUBLIC CAN ASK TO SEE OUR DOCUMENTS. AND THEY DO THAT THROUGH A FEDERAL INFORMATION ACT REQUEST. GINGER MANAGED THIS FOR US AS WELL, AND THIS CUTS ACROSS ANY DOCUMENTS IN THE INSTITUTE. 15 CASES WERE CLOSED THIS YEAR. SOME OF THOSE WERE REFERRED TO OTHER ENTITIES, SOME WERE DENIED BECAUSE THEY COULDN'T GET THE CONFIDENTIAL DOCUMENTS THEY WANTED. SOMETIMES THEY DON'T EVEN HAVE THE RECORDS THEY THINK WE HAVE. BUT OVER 700 PAGES WAS RELEASED. AND OF COURSE ALL THAT RELEASING REQUIRES REDACTION FIRST, AND NEGOTIATION WITH THE OWNER OF THOSE DOC DOCUMENTS SOMETIMES. COMMITTEE MANAGEMENT EXPERTISE IS FOCUSED IN OUR OFFICE HERE. THE NET, YOU'VE ALL WORKED WITH THE NET AS PART OF COMING ON BOARD AS SPECIAL GOVERNMENT EMPLOYEES. AND SHE ALSO PUTS FEDERAL REGISTER NOTICES OUT FOR ALL OF THE MEETINGS, BOTH IN THE REVIEW SHOP, IN COUNCIL, AS WELL AS MEETINGS A THAT THE INTRAMURAL OFFICE HOLDS FOR BOARD OF SCIENTIFIC COUNSELORS. MANAGEMENT OF THE SCIENTIFIC REVIEW EVALUATION ACCOUNT, THE DOLLARS THAT REALLY PAY FOR THE RESEARCH ENTERPRISE, REVIEWERS, TRANSPORTATION, HOTELS, AND ALSO TRAVEL PLANNING FOR THE STAFF OF BOTH DIVISION OF EXTRAMURAL ACTIVITIES AS WELL AS THE DIVISION OF SCIENTIFIC PROGRAMS. SO I THINK MY FINAL SLIDE IS NEXT, AND I JUST WANT TO TAKE A MOMENT TO LET YOU SEE ALL THE PEOPLE THAT DO THE WORK, IMPRESSIVE WORK I JUST TOLD YOU ABOUT. WE HAVE IN THE OFFICE OF THE DIRECTOR NICHELLE, NANETTE, GINGER, JACQUE. THE SCIENTIFIC REVIEW BRANCH LED BY DR. MELISSA STICK, ELIANE, NAKIA, KAUSIK, SINGH, KATHRYN AND SHIGUANG, SORRY FOR THE MISSPELLING THERE. THE GRANTS MANAGEMENT GROUP LED BY CHRIS MYERS AND INCLUDES HOAI, MARIA, CASTILLA, EDDIE AND ERIC. I WANT TO PAY PARTICULAR THANKS TO CHRIS AND EDDIE, THEY PUT TOGETHER A BUNCH OF THE SLIDES FOR THE GRANTS MANAGEMENT INFORMATION THAT I SHARED TODAY. AND SORRY, I WAS TRYING TO HURRY UP A LITTLE BIT, BUT I'LL STILL BE HAPPY TO TRY AND TAKE SOME QUESTIONS. >> THANKS, CRAIG. ARE THERE ANY QUESTIONS FOR CRAIG? >> I JUST HAVE A SMALL POINT. I WAS AWARE THAT WHEN THE APPROPRIATIONS COME SORT OF LATE IN A FISCAL YEAR, THAT WHEN YOU GET THAT FINAL AMOUNT THAT YOU WERE WAITING FOR, DO YOU USE THE OPPORTUNITY TO MAKE SOME SPECIAL PROJECT TYPE GRANTS THAT THINKS THAT PERHAPS HBPs -- THEY WERE PRIORITY BUT YOU JUST DIDN'T HAVE THE MONEY FOR THEM AT THAT TIME OR THINGS LIKE THAT, OR ARE THEY -- THE FUNDS TYPICALLY DISBURSED BACK INTO THE R01s BECAUSE THEY COULDN'T RECEIVE THE LEVEL OF FUNDING, OR R01s IN OTHER GRANTS? >> I'LL SAY THAT FUNDS ARE ALREADY PLANNED FOR, BEFORE WE COME, ALL RIGHT? SO WE'RE ACTUALLY MAKING SOME OF THOSE AWARDS IN ADVANCE OF HAVING THE ACTUAL MONEY, SO WE THEN COME BACK AND GIVE THEM THE EXTRA DOLLARS. NOW, THAT SAID, THERE ALWAYS ARE PLANS FOR ADDITIONAL POCKETS OF MONEY. THE PROGRAM STAFF HAVE ALREADY MADE ANNOUNCEMENTS FOR RFAs POTENTIALLY OR SPECIFIC PROGRAM ANNOUNCEMENTS, MAYBE PLANS FOR OUR STRATEGIC PLANNING PROCESS. SO THEN WE FIND OUT IF WE GOT THE SAME WE THOUGHT WE WERE GOING TO GET, A LITTLE BIT MORE THAN WE THOUGHT WE WERE GOING TO GET, AND THEN WE START TO FIND OUT WHAT THE COST OF OR THE GRANTS COMING IN THE DOOR, DID THE COST OF THE GRANTS GO UP. SO, AS YOU CAN IMAGINE, IT THEN BECOMES A SHELL GAME. IF WE CAN CARVE OUT SOME MONEY FOR EXTRA ACTIVITIES, THAT'S GOING TO HAPPEN, BUT IT REALLY DEPENDS ON A WIDE VARIETY OF FACTORS COMING IN. >> CYNTHIA, YOU'RE MUTED. >> I JUST WANTED TO SAY THANK YOU TO ALL THE STAFF, AND I JUST -- ALL THE THINGS THAT YOU HANDLE. THANK YOU VERY MUCH. >> WELL, YOUR APPRECIATION IS MUCH RECEIVED AND APPRECIATED, AND HOPEFULLY MANY OF THE STAFF ARE ON THE LINE TO ACTUALLY HEAR THAT. SO THAT'S MUCH APPRECIATED. THANK YOU. >> JOHN? >> I ECHO THAT APPRECIATION, CRAIG AND ALL OF YOU, WE REALLY APPRECIATE WHAT YOU DO. I DO HAVE A BRIEF QUESTION. YOU KNOW, WE'RE ALL AFFECTED BY THE DIRECTIVE FROM THE LAST WHITE HOUSE OFFICE OF SCIENCE AND TECHNOLOGY POLICIES DIRECTIVES ABOUT FORWARD INVOLVEMENT. PRINCIPAL INVESTIGATORS NOW HAVE TO ANSWER A SLEW OF CONCERNS ABOUT POSSIBLE WAYS OF OUR GRANTS BEING ENTRAPPED WITH WHAT THE FEDERAL GOVERNMENT CONSIDERS FOREIGN INVOLVEMENT. DO WE EXPECT ANY REVISIONS OF THAT? >> I'M A LITTLE OUT OF MY LANE BUT I'M GOING TO SAY I DON'T THINK SO. I THINK THAT THERE'S BEEN ENOUGH EVIDENCE THAT IT IS IMPACTFUL. CONGRESS HAS COME AND ASKED FOR FEEDBACK ON THAT. DR. COLLINS HAS GONE DOWNTOWN TO ACTUALLY RESPOND TO QUESTIONS. OBVIOUSLY IN SOME CASES, THE FBI HAS BEEN BROUGHT IN TO PLAY. I THINK THERE HAS BEEN ENOUGH BAD ACTORS FOUND THAT IT'S GOING TO BE REALLY DIFFICULT TO BACK THAT OFF. >> YEAH, I AGREE WITH THAT. IT'S REALLY A POINT OF FOCUS OF THE OFFICE OF EXTRAMURAL ACTIVITIES RUN BY MIKE LAUER, AND I DON'T SEE THAT GOING AWAY AT ALL. >> IT MIGHT BE GOOD IN FUTURE REPORTS. I THINK THE SCIENTIFIC COMMUNITY WOULD APPRECIATE SEEING WHAT POSITIVE IMPACTS THAT'S HAD. >> OKAY. GOOD POINT. >> THAT MAKES ME THINK OF SOMETHING. DO YOU THINK THERE MIGHT BE ANY REVISION WITH THE USE OF FETAL TISSUES? >> I'M SORRY, CYNTHIA, YOUR SOUND IS GOING BAD AGAIN. >> I THINK SHE'S ASKING ABOUT FETAL TISSUE. >> OH. >> WE HAVEN'T SEEN ANY CHANGES IN POLICY YET, BUT I WOULD ANTICIPATE THEM, DON'T YOU THINK, CRAIG? >> THE PANEL THAT MADE THOSE DECISION LAST SUMMER WAS HAND PICKED BY LAST YEAR'S ADMINISTRATION, AND IT WAS RATHER STACKED. WE'LL HAVE TO SEE HOW THAT GOES IN THE FUTURE. THEY TEND TO GO THROUGH A PANEL AND WE'LL HAVE TO SEE THE MEMBERSHIP OF THE PANEL. >> RUTH ANNE? >> WELL, FIRST I REALLY FOUND THE PRESENTATIONS THIS MORNING REALLY CONTENTFUL, INTERESTING, AND THANK YOU ALL FOR THOSE. AND I JUST WAS THINKING SOME OF WHAT CRAIG SHOWED AN ALSO WHAT WE SAW YESTERDAY ON THE BUDGET BROUGHT TO MIND THAT IT MAY BE GETTING EVEN MORE DIFFICULT FOR NEW INVESTIGATORS TO GET MONEY BECAUSE I SEE THAT THAT SLOPE FOR NEW GRANTS GOING DOWN. AND AT A FUTURE COUNCIL MEETING, IF WE COULD MAYBE BRING UP THAT ISSUE. BECAUSE IT ALL TIES IN WITH SOME OF OUR OTHER PRIORITY ISSUES INCLUDING DIVERSITY. >> YEAH. WE CAN GET SOME DATA ON THAT. >> YEAH. >> I SEE A HAND BY SANDY. >> YES, I, TOO, WOULD LIKE TO ADD MY APPRECIATION FOR THE GREAT PRESENTATION AND HE HAVE BEEN'S INPUT INTO IT. HAVING BEEN ON THE OTHER SIDE ON SERVING ON CDRC AND MANY OTHER SPECIAL EMPHASIS PANELS OVER THE YEARS, IT'S GREAT TO SEE HOW IT ALL COMES TOGETHER. BUT MY QUESTION CONCERNS THE FUTURE OF THESE REVIEW PANELS. NOW THAT WE ARE USED TO DOING VIRTUAL MEETINGS SO MUCH, AND I'M SURE ALL OF THESE PANELS HAVE BEEN MEETING VIRTUALLY OVER THE LAST YEAR, AND I'M SURE IT REPRESENTS A BIG COST SAVING. IS THERE ANY DISCUSSION ABOUT USING THIS FORMAT INTO THE FUTURE FOR REVIEWS MANAGED BY YOUR OFFICE, CRAIG? >> BOTH OUR OFFICE AS WELL AS THE CENTRAL OFFICE AT NIH HAVE BEEN USING A VARIETY OF PLATFORMS, TELECONFERENCES AND ONLANONLINE MEETINGS. WE HAVE NOT AT THIS POINT STARTED TO PLOT THE FUTURE. WE HAVE BEEN DICTATED BY NIH TO CONTINUE OUR INITIAL PEER REVIEW MEETINGS IN VIRTUAL FORMAT THROUGH THE SUMMER. I CAN'T IMAGINE WE WON'T BENEFIT FROM THE CLOSURE TO ALL THESE VIRTUAL MEETINGS THE LAST YEAR AND WE'LL TRY TO LEVERAGE THOSE. THE TRICKY PART IS TRYING TO DECIDE WHEN IS THE VIRTUAL A PREFERRED OVER THE FACE-TO-FACE. BECAUSE THERE ARE A LOT OF BENEFITS OF A FACE-TO-FACE, BUT WE'LL BE PURSUING THAT IN THE FUTURE. AS WE CLOSE, I JUST WANT TO THANK EVERYBODY FOR YOUR KIND WORDS, AND I WANT TO REFLECT THAT BACK TO THE STAFF. THE STAFF THAT DON'T HAVE AN OPPORTUNITY TO SIT HERE BEFORE YOU DO ALL THAT WORK, AND I REALLY THANK THEM FOR ALL THEIR SUPPORT AND EFFORTS. THANK YOU. >> APPLAUSE. GOOD. THANK YOU. ALL RIGHT. SO WE ARE GOING TO TAKE A VERY SHORT BREAK NOW. WE WERE SCHEDULED FOR 15 MINUTES BUT I THINK WE WILL TRY TO SHORTEN TO 5. HOW DOES THAT SOUND, CRAIG? AND ROGER? >> YOU'RE DRIVING THE BUS. I NOTICED THAT OUR OTHER SPEAKERS ARE ALREADY ONLINE, SO THEY'RE AVAILABLE. >> OKAY. VERY GOOD. SO YEAH. ALL RIGHT. LET'S COME BACK AT 11:20. INCLUDES BIOMEDICAL ENGINEERING, NEUROPROPROSTHESES AND TINNITUS. ROGER IS GOING TO PRESENT A REVIEW OF OPEN APPROACHES FOR NEURAL ENGINEERING FROM CONCEPT TO CLINIC AND THEN SET THE STATE YOUR NAME FOR TWO PRESENTATIONS BY DRS. RAZI HAQUE AND DR. CHARLES DELLA SANTINA. >> I BELIEVE MOST OF US ARE FAMILIAR WITH THE COCHLEAR IMPLANT AND ITS ABILITY TO RESTORE HEARING TO MANY INDIVIDUALS WITH HEARING LOSS SO SEVERE THAT HEARING AIDS DON'T PROVIDE USEFUL HEARING. THERE ARE A NUMBER OF COMMERCIAL ENTITIES THAT MANUFACTURE COCHLEAR IMPLANTS OF THEIR OWN DESIGN SO THE QUESTION FOR NIDCD FUNDED RESEARCHERS IS HOW TO PURSUE A REAL RESEARCH SETTING THAT GOES BEYOND JUST EXERCISING THE CAPABILITIES ALREADY BAKED IN TO THE COMMERCIAL DEVICE. IF A RESEARCHER FORMS A TIGHT COLLABORATION WITH A COMMERCIAL COMPANY TO GAIN ACCESS TO HIDDEN PROCESSING FEATURES, THAT PI WILL THEN HAVE TO CONVINCE THE PEER REVIEW PROCESS THAT THEY'RE ABLE TO PUBLISH THE RESULT INDEPENDENTLY, INDEPENDENT FROM THE APPROVAL OF THE MANUFACTURER. THE RESEARCH PROGRAM WOULD BE LIMITED AGAIN TO EXERCISING FEATURES ALREADY BAKED IN BY THE MANUFACTURER. THIS IS A FAR CRY FROM THE RESEARCH AND DEVELOPMENT THAT WAS POSSIBLE WITH THE IMPLANTED PORTION OF A COCHLEAR IMPLANT WHEN IT WAS BROUGHT -- THE ELECTRICAL CONTACTS ARE BROUGHT TO THE SURFACE OF THE SKIN, ANY RESEARCH THAT SOMEONE COULD IMAGINE COULD BE DONE BUT THE QUESTION WAS HOW TO DO IT SAFELY. TO ADDRESS THIS BOTTLENECK AND TO FOSTER CONTINUED INNOVATION FOR THE FIELD, NIDCD HAS WORKED TO CREATE RESEARCH TOOLS TAILORED TO THE NEEDS OF ACADEMIC PIs. FOR EXAMPLE, ILLUSTRATED IN THE LEFT-HAND SIDE OF THIS PICTURE, IS AN OPEN HARDWARE OPEN SOFTWARE SYSTEM, THE CCI MOBILE DEVELOPED AT THE UNIVERSITY OF TEXAS DALLAS. THAT REPLACES THE EXTERNAL PORTION OF THE COCHLEAR IMPLANT AND ALLOWS SCIENTISTS TO RUN STUDIES WITH ARBITRARY RESEARCH SOFTWARE WHILE ASSURING SAFE OPERATION OF THE COCHLEAR IMPLANT JUST AS A COMMERCIAL IMPLANT HAS SYSTEMS IN PLACE TO ENSURE SAFE OPERATION OF THE DEVICE IN ARBITRARY SOUND FEELTDZ. IT'S NOW AVAILABLE TO THE RESEARCH COMMUNITY. YOU CAN READ MORE ABOUT IT AT THE LINKS THERE. AND TODAY, I WANTED TO TAKE THIS OPPORTUNITY TO HAVE TALKS FROM TWO OTHER RESEARCHERS WHO ARE DOING SIMILAR EFFORTS TO MAKE THEIR RESEARCH AND DEVELOPMENT CAPABILITIES AVAILABLE TO THE RESEARCH COMMUNITY. THIS EFFORT, THE NEXT TWO TALKS ABOUT HERE, WILL BE A LITTLE LESS OPEN SO THERE'S INTELLECTUAL PROPERTY THAT CAN BE CREATED TO FOSTER COMMERCIALIZATION. DR. RAZI HAQUE WILL SHARE HIS SCREEN NOW. GOOD MORNING. >> GOOD MORNING. AND DR. DELA SANTINA'S TALK, BASIC PRINCIPLES OF THE COCHLEAR IMPLANT INTO AN ENTIRELY NEW DEVICE TAILORED TO THE VESTIBULAR SYSTEM. RAZI, GO AHEAD. >> THANK YOU, ROGER. HELLO, EVERYONE. I'M GOING TO HAVE MY VIDEO ON FOR JUST A MOMENT, JUST TO SAY HI TO EVERYONE, THEN I'LL TURN IT OFF JUST TO SAVE SOME BANDWIDTH. THANK YOU FOR THE INTRODUCTION, ROGER. MY NAME IS RAZI HAQUE, LAWRENCE LIVERMORE NATIONAL LABORATORY IN LIVERMORE, CALIFORNIA. LIVERMORE IS IN THE BAY AREA AND JUST ABOUT 45 MILES FROM SAN FRANCISCO. WE'RE A LARGE NATIONAL LABORATORY WITH A FOCUS ON A WIDE VARIETY OF TECHNOLOGIES FROM LASERS, ADVANCED COMPUTATION AND OF COURSE BIOMEDICAL EC ENGINEERING. TODAY I'M GOING TO TALK TO YOU ABOUT THE WORK WE DO AT LIVERMORE AND IN PARTICULAR I HOPE TO CONVEY THE APPROACH WE TAKE AND UNIQUE POSITION WE HAVE IN ECOSYSTEM OF RESEARCH AND DEVELOPMENT AND IN PARTICULAR, I'LL BE FOCUSING ON OUR UNIQUE TECHNOLOGIES AND CAPABILITIES FOR BUILDING IMPLANTABLE DEVICES AND TALK TO YOU ABOUT SOME OF OUR LATEST WORK WITH SOME REALLY OUTSTANDING COLLABORATORS WITH POTENTIAL TO MAKE A HUGE IMPACT IN IMPROVING LIVES, OUR MAIN DRIVING FORCE. SO OUR WORK PRIMARILY FOCUS ON INTERFACING WITH THE NERVOUS SYSTEM. THIS FIELD HAS A LONG PAST WITH COCHLEAR IMPLANTS, NEUROPROSTHETIC CAN IMMEASURABLE IMPACT OVER THE LAST FEW DECADES. THE ARRAYS USED IN THESE DEVICES ARE HANDMADE BY SPECIALISTS. IN THE TOP RIGHT YOU CAN SEE A PHOTOGRAPH FROM MED L, A COCHLEAR IMPLANT MANUFACTURER SHOWING A NUMBER OF THE INDIVIDUAL WIRES AND ELECTRODES THAT ARE HAND ASSEMBLED INTO FINISHED COCHLEAR IMPLANT. WHILE THESE AND OTHER COMPANIES HAVE DEVELOPED AN ADVANCED MANUFACTURING TECHNIQUE THEY STILL RELY ON MACRO SCALE SOLUTIONS, MAN NI MANIPULATED BY HAND. THIS MAY LIMIT TECHNOLOGICAL ADVANCEMENTS THAT MIGHT ALLOW NEW FEATURES, FOR EXAMPLE, INTRODUCING ADDITIONAL CHANNELS. DUE TO ITS HAND-BUILT NATURE, CLEAN ROOM TECHNICIANS MUST BE HIGHLY SKILLED IN THE ART OF THE MAKING THESE ARRAYS. THE ADVANTAGE IS IT HAS BEEN HONED OVER MANY YEARS, IMPROVED, RESULTING IN A VERY HIGH RELIABILITY THAT WE EXPECT AND KNOW TODAY. WE UTILIZE A FUNDAMENTALLY DIFFERENT BASE TECHNOLOGY TO BUILD A VARIETY OF IMPLANTABLE ELECTRODE ARRAYS. AS YOU SEE IN THE BOTTOM TWO PHOTOGRAPHS HERE OF OUR LIVERMORE ENGINEERS IN BUNNY SUITS, WE ALSO USE CLEAN ROOMS BUT OUR DEVICES ARE BUILT AT THE MICRO SCALE AND THE DETAILS CAN REALLY ONLY BE SEEN UNDER THE MICROSCOPE. WHAT THAT MEANS IS WE TYPICALLY MAKE DEVICES THAT ARE MEASURED IN MICRONS RATHER THAN MILLIMETERS AND THEREFORE REQUIRE A WHOLE NEW SPECIALIZED SET OF TOOLS, INFRASTRUCTURE AND EQUIPMENT. LUCKY FOR US, WE ARE ABLE TO LEVERAGE THE KNOW-HOW AND EXPERTISE ACQUIRED OVER MANY YEARS FROM THE SEMICONDUCTOR INDUSTRY, STEADILY BUILDING SMALLER AND FASTER MICROCHIPS OVER THE LAST SEVERAL DECADES. HERE WE HAVE REPURPOSED THEM FOR MEDICAL DEVICE MANUFACTURING, AND THIS ALLOWS US TO MICRO FABRICATE ELECTRODE ARRAYS WITH MUCH FINER PRECISION IN DIMENSION CONTROL ALLOWING US TO MAKE, FOR EXAMPLE, MUCH HIGHER -- THE SIM CONDUCT TER INDUSTRY IS BUILT UPON QUALITY, REPEATABILITY AND RELIABILITY WHICH IS ALSO ANOTHER IMPORTANT FACTOR FOR IMPLANTABLE MEDICAL DEVICES. ANOTHER ADVANTAGE IS THAT WE CAN SCALE OUR DEVICES MUCH LIKE THE SEMICONDUCTOR INDUSTRY HAS, RESULTING IN REDUCED MANUFACTURING COSTS, BECAUSE WE CAN MAKE HUNDREDS OF DEVICES AT IT TIME. ANOTHER KEY DESIGN FACTOR THAT FUNDAMENTALLY DEFINES THE ARRAYS WE BUILD IS THEIR FLEXIBILITY. MUCH MORE COMMONLY YOU WILL FIND THAT ELECTRODE ARRAYS BUILT USING TECHNIQUES AT THE MICRO SCALE LIKE OURS TEND TO BE BUILT OUT OF RIGID MATERIALS LIKE SILICON. THE SEMICONDUCTOR INDUSTRY WAS BUILT ON SILICON SO MANY MICRO FABRICATED ELECTRODE ARRAYS ARE MADE OF THAT MATERIAL. ON THE OTHER HAND, RIGID MATERIALS AREN'T EXACTLY COMPATIBLE WITH SOFT TISSUE LIKE THE BRAIN. YOU CAN IMAGINE SOMETHING LIKE A THORN IN YOUR SCAN THAT GETS SLOWLY PUSHED OUT OVER TIME. SO INSTEAD, WE USE BIOCOMPATIBLE POLYMERS THAT WE CAN CONTROL TO VERY FINE THICKNESSES. OUR ARRAYS ARE OFTEN 10 TO 20 MICRONS THICK AND CAN THEORETICALLY MOVE WITH THE TISSUE. ON THE RIGHT HALF OF THIS SLIDE, YOU SEE A VARIETY OF DESIGNS WE'VE BUILT IN THE PAST. ARRAYS THAT ARE SUPER FLEXIBLE AND A SURFACE RECORDING ARRAY FUNDED BY NIDCD FOR A FELINE MODEL THAT IS FLEXIBLE AND HAS FINGER-LIKE EXTENSIONS THAT ALLOW TO CONFORM TO THE COMPLEX SHAPES OF THE BRAIN. MORE RECENTLY WE'VE DEVELOPED A FOUR-SHANK PENETRATING MICRO ARRAY THAT PROVIDES 128 CHANNELS OF RECORDING SHOWN HERE IN THE MIDDLE BOTTOM OF THE SLIDE. WE BELIEVE THE ADVANTAGE OF BUILDING THIN FLEXIBLE ARRAYS IS THAT IT IMPROVES LONGEVITY IN THE BRAINS OF FREELY MOVING ANIMALS. WE HAVE DEMONSTRATED WITH OUR COLLABORATORS AT UCSF LONG LIFETIMES IN A RAT MODEL WITH EXCELLENT STABILITY OVER LONG PERIODS OF TIME AS SHOWN IN THE PLOT. THIS ALLOWS RESEARCHERS TO CONDUCT STUDIES THAT WEREN'T PREVIOUSLY POSSIBLE DUAL TO A VARIETY OF FAILURE MECHANISMS. WE CONTINUE TO DEVELOP DIFFERENT KINDS OF ELECTRODE ARRAYS TO FURTHER ENHANCE OUR FUNCTIONALITY AND PROVIDE THE MOST ROBUST SET OF TOOLS TO OUR NEUROSCIENTIST PARTNERS. ONE KEY QUESTION THAT ARISES WHEN MAKING SOMETHING VERY FLEXIBLE IS, HOW DO YOU IMPLANT SUCH A DEVICE? AFTER ALL, IT'S LIKE TRYING TO PUSH A WET NOODLE INTO GE JELL-O. SO LIVERMORE HAS DEVELOPED UNIQUE SOLUTIONS TO SUCH PROBLEMS. WHAT YOU SEE IN THIS VIDEO IS A FLEXIBLE ARRAY WHICH IS TRANSPARENT BEING ALIGNED WITH A RIGID SILICON STIFFENER OR SHUTTLE. IT'S ADHERED TO THE POLYMER WITH A WATER-SOLUBLE BIOCOMPATIBLE ADHESIVE WHICH MAKES IT EASY TO DETACH ONCE INSERTED INTO THE BRAIN. AFTER A SET AMOUNT OF TIME AND WITH ADDITIONAL FLUSHING OF SALINE, THE STIFFENER IS COMPLETELY DETACHED FROM OUR THIN FLEXIBLE POLYMER ARRAY AND IS REMOVED, LEAVING BEHIND THE FLEXIBLE ARRAY. THIS TECHNIQUE HAS BEEN USED OVER MANY YEARS NOW AND PROVEN QUITE SIMPLE AND SUCCESSFUL FOR IMPLANTING OUR FLEXIBLE ARRAYS AND IS BEING CURRENTLY REPLICATED IN ANIMAL MODELS RANGING FROM NHP TO SONGBIRD AND OTHER NIH BRAIN FUNDED PROGRAM, AND WORKED WITH OUR COLLABORATORS AT UCSF AND LAUREN FRANK'S RESEARCH GROUP. I WANTED TO HIGHLIGHT ONE OF OUR IMPORTANT PROJECTS FUNDED BY NIDCD AND A VERY IMPORTANT SUCCESSFUL COLLABORATION OVER THE LAST FEW YEARS. DR. CHARLIE DELA SANTEE NA AT JOHNS HOPKINS UNIVERSITY HAS BEEN STUDYING THE NEUROSCIENCE BEHIND BALANCE AND COMPLEX NEUROCIRCUITRY NEEDED TO IMPLEMENT. FLEXIBLE ELECTRODE ARRAYS IN THE SHAPE OF PADDLES ARE PLACED STRATEGICALLY SUCH THAT STIMULATING CURRENT CAN BE APPLIED TO REGIONS OF INTEREST. THE DESIGN WAS PRIMARILY DEVELOPED BY HIS RESEARCH GROUP WITH INPUT FROM US AND THEN HIS GROUP DEVELOPED THE IMPLANTATION PROCESS AND COLLECTED DATA IN THIS ANIMAL MODEL. THIS WORK HAS LED TO SEVERAL PUBLICATIONS AND FINDINGS THAT WILL HOPEFULLY PROVIDE INSIGHT FOR THE DEVELOPMENT OF A POTENTIAL VESTIBULAR PROSTHESIS. I ALSO WANTED TO SHARE A FEW SLIDES TALKING ABOUT HOW WE INTERACT WITH THE RESEARCH COMMUNITY. WE UNDERSTAND THAT WHILE WE BUILD THESE ARRAY, ULTIMATELY IT IS THE USERS OF THE TECHNOLOGY THAT NEED TO HAVE SOME TANGIBLE BENEFIT AND KNOWLEDGE OF HOW TO USE THEM. WITH SUPPORT PROVIDED INTERNALLY BILL LLNL, WE HOSTED A DAY-LONG SYMPOSIUM TWICE NOW. THE THIRD WOULD HAVE BEEN THIS PAST FALL BUT WAS CANCELED DUE TO COVID UNFORTUNATELY. THE WORKSHOP IS A FORUM TO SHARE IDEAS AND TECHNIQUES SUCH AS SURGICAL APPROACHES AND TO SHARE TIPS AND TIME SAVING TRICKS. AT THE LA LAST MEETING, THEY PRESENTED A VIDEO AND DETAILED DESCRIPTION OF HOW HE IMPLANTS ONE OF OUR MOST ADVANCED ARRAYS INTO THE RODENT MODEL. OUR KEYNOTE SPEAKER WAS DR. CHARLIE DELLA SANTINA, WHO ALONG WITH ONE OF HIS GRADUATE STUDENTS CAME ALL THE WAY FROM JOHNS HOPKINS AND SHARED A MOTIVATING TALK ABOUT HIS WORK ALONG WITH DETAILS ABOUT HIS RESEARCH GROUP'S APPROACH TO USING LIVERMORE-PRODUCED ELECTRODE ARRAYS. IMPORTANTLY, THE SYMPOSIUM PROVIDES AN OPPORTUNE TIME FOR US AT LIVERMORE TO -- AND WHAT KINDS OF ENHANCEMENTS OR IMPROVEMENTS WOULD BE HELPFUL AND BENEFICIAL. THIS HELPS TARGET OUR NEXT GENERATION WORK, THE PROPOSALS THAT WE WRITE AND THE NEAR TERM ENGINEERING SOLUTIONS THAT WE COME UP WITH. IT IS OPEN TO EVERYONE THAT WANTS TO WORK WITH US AND WE HOPE TO HOST AGAIN SOME DAY SEUN IN SUNNY SAN FRANCISCO. ADDITIONALLY WITH STRONG SUPPORT FROM THE NIDCD WE HAVE DEVELOPED WHAT WE CALL A STANDARD FABRICATION PROCESS SO THAT WE MAKE THE DEVICES THAT WE DO. WHAT WE'VE DONE IS BUILT A DESIGN MANUAL THAT IS DISTRIBUTABLE TO OTHER RESEARCH GREUCHES THAT WANGROUPS THAT WANT TO WORK WITH US AND LEVERAGE OUR EXPERTISE. THESE DESIGN ROLES ALSO ALLOWS UALLOW USTO ENSURE -- HIGH CHANCE OF THINGS TURNING OUT THE WAY THEY WERE INTENDED. PERIODIC UPDATES TO THE DESIGN RULES ADD ENHANCEMENTS AND IMPROVED TOLERANCES IN ORDER TO REDUCE THE BURDEN ON OUR SIDE, WE HAVE DEVELOPED AUTOMATIC SOFTWARE-BASED RULE CHECKING THAT CAN HELP FLAG A DESIGNER TO LOOK MORE CAREFULLY AT THEIR DESIGN AND ENSURE THE DESIGN RULES ARE FOLLOWED. WE'VE ALSO FOCUSED ON SOFTWARE TOOLS THAT ARE OPEN SOURCE AND, THEREFORE, EASILY ACCESSIBLE. THE GOAL IS TO GO FROM DESIGN TO FINISH DEVICE AS SIMPLE AND STRAIGHTFORWARD AS POSSIBLE. WE'VE PREVIOUSLY PRODUCED ARRAYS UNDER A MULTIUSER STANDARD FABRICATION RUN AND ALSO FUNDED BY OUR WORK WITH NIDCD. THIS ALLOWED US TO WORK WITH MULTIPLE COLLABORATORS AT A TIME AND PLACE THEIR UNIQUE DESIGNS ALL TOGETHER IN A SINGLE MICRO FABRICATION RUN WHICH CAN TAKE SEVERAL WEEKS AT A TIME. GENERALLY EACH FABRICATION RUN RESULTS IN AT LEAST TENS OF DEVICES PER DESIGN DEPENDING ON HOW MANY DIFFERENT USERS WE HAVE. HERE'S AN IMAGE THAT YOU CAN SEE IN THE LOWER LEFT-HAND CORNER OF SUCH A MULTIUSER WAFER AND SHOWS MULTIPLE DIFFERENT TYPES OF DESIGNS HERE. MOVING ON TO OTHER AREAS THAT ARE IMPORTANT TO THE SUCCESS OF OUR WORK BUT TYPICALLYLESS RESEARCH-Y AND THEREFORE LESS PUBLISHABLE SOMETIMES IS LIFETIME TESTING. WHILE ACCELERATED TESTING IS ALSO CONSIDERED THE GOLD STANDARD IT IS CLEARLY NOT A GOOD MODEL FOR WHAT TRULY HAPPENS TO DEVICES IN THE BODY. IN THE IMAGES ON THE TOP LEFT, A COLORIZED IMAGE OF A RIGID TYPE SILICON E ELECTRODE ARRAY SHOWS SIGNIFICANT DEGRADATION, NOT REALLY SEEN IN ACCELERATED -- TESTS. SEVERAL RESEARCHERS PUBLISHED A PAPER SHOWING THAT A NEW TECHNIQUE THAT INTRODUCES REACTIVE SPEESES INTO THE ACCELERATED -- TEST COULD BE A BETTER EMULATION OF WHAT ACTUALLY HAPPENS INSIDE AN ORGANISM, WHICH THIS IS CALLED REACTIVE ACCELERATED AGING. LLNL HAS BUILT A VERSION OF THIS DESIGN WHICH YOU SEE IN THE RIGHT SIDE PHOTOGRAPH AND OF THIS OPEN SOURCE DESIGN, INSTALLED IT IN OUR TESTING LAB TO CONDUCT LONG TERM STUDIES AND COMPARE IT WITH REAL ANIMAL DATA ON OUR ARRAYS. ASIDE FROM HELPING US CLOSE THE LOOP FASTER ON POTENTIAL DESIGN IMPROVEMENTS OR ENHANCING LIFE TIMES IS THE REAL POSSIBILITY OF AVOIDING ANIMAL STUDIES TO ANALYZE THE DEVICE ITSELF AND FAILURE MODES. AS WE DEVELOP RECIPES AND OPTIMIZATION FOR THE PROPER CHEMICAL BATH, WE WILL SHARE OUR FINDINGS IN PUBLICATIONS AS WELL SO THIS CAN BE EASILY REPLICATED ACROSS RESEARCH LABS. WE HAVE ALSO DEVELOPED ADVANCED AUTOMATED SOFTWARE AND HARDWARE APPROACHES. PUSH OUR ELECTRODE ARRAYS TO HIGHER AND HIGHER CHANNEL COUNTS. OUR COLLABORATOR SEE A REAL NEED FOR DISCOVERING THE DATA BURIED WITHIN HUNDREDS OR EVEN THOUSANDS OF NEURAL SIGNALS SIMULTANEOUSLY RECORDED. THIS MAKES TESTING AND VERIFICATION OF OUR ELECTRODES VERY CHALLENGING. AS A MANUAL PROCESS, IT COULD TAKE DAYS. NOW WITH OUR NEWLY DEVELOPED AND OPERATIONAL SETUP, WE CAN EASILY DO 128-CHANNEL ARRAYS FULLY AUTOMATED WITH THE CAPABILITY TO DO A SINGLE 512 CHANNEL ARRAY AT ONCE. THIS TESTING SETUP PERFORMS BASIC ELECTROSCOPIC IMPEDANCE MEASUREMENTS AS WELL AS CHARGE STORAGE MEASUREMENTS, AND THESE ARE IMPORTANT FACTORS FOR UNDERSTANDING AND MEASURING PERFORMANCE FOR RECORDING OR STIMULATING THE NERVOUS SYSTEM. EVENTUALLY WE HOPE TO ENCAPSULATE IT IN THE OPEN SOURCE DATA MODEL THAT CAPTURES METADATA LIKE PROBE TYPE ELECTRODE SIZE, MATERIALS AND SO ON. BY FOCUSING ON SUCH A STANDARD, DATA COLLECTED BY DIFFERENT ELECTRODE ARRAYS MANUFACTURED BY DIFFERENT GROUPS CAN BE MORE DIRECTLY COMPARED. WE HOPE THIS TESTING AND DATA FORMAT WILL HELP RESEARCHERS CONFIDENTLY CHOOSE THE RIGHT TYPE OF ELECTRODE ARRAY FOR THE STUDY THAT THEY ARE PLANNING ON PERFORMING, EVEN IF IT'S NOT ONE OF OURS. MOVING ON TO ADVANCED TECHNOLOGY DEVELOPMENT, I'LL SHOW YOU A FEW NEW TECHNOLOGIES THAT WE ARE WORKING ON. HERE WE ARE WORKING ON DEVELOPING ADVANCED MANUFACTURING TECHNIQUES THAT INCORPORATE 3D PRINTING OR ADDITIVE METHODS ALONGSIDE OUR MICRO FABRICATION TECHNIQUES. LLNL HAS A LARGER RESEARCH EFFORT IN THIS SPACE SO IT IS NATURAL TO FIND RESEARCHERS INTERNAL TO LIVERMORE TO HELP US LAUNCH THIS EFFORT. IN THIS SLIDE, WE'VE WORKED WITH ADVANCED POLYMERS CALLED ORMOCERES. THEY ARE EXTREMELY FLEXIBLE AND ALSO HAVE AN EXTREMELY HIGH OPTICAL -- WHICH IS ATYPICAL. ON THE LEFT, YOU CAN SEE WE 3D PRINTED THIS MATERIAL TO CONNECT TWO STANDARD OPTICAL FIBERS AND ON THE RIGHT, WE'VE PRINTED THIS MATERIAL DIRECTLY ON TOP OF A TINY LASER CHIP. THAT'S JUST A COUPLE HUNDRED MICRONS ON THE SIDE. ALL OF THIS WORK IS RELATED TO DEVELOPING LASER BASED LASER ARRAY WITH BUILT-IN WAVE GUIDES, AND YOU CAN SEE SOME PHOTOS THERE IN THE CENTER OF THE SLIDE. THIS HAS THE POTENTIAL TO PUSH THE FEEL OF OPT GENETICS FURTHER BY PROVIDING OUR LONG LIFETIME FLEXIBLE ELECTRODE ARRAYS TO RESEARCH GROUPS STUDYING GENETICALLY MODIFIED ANIMALS. ONE EXCITING AREA THAT NIDCD IS SUPPORTING US ON IN THIS APPLICATION SPACE IN PARTICULAR IS WORKING WITH ANOTHER NIDCD-FUNDED RESEARCHER, DR. CLAUSE PETER RICT TER AT NORTHWESTERN. STUDIES HE AND OTHERS HAVE PERFORMED SUGGEST THAT BY IRRADIATING LIGHT INSIDE THE COCHLEA COULD REDUCE THE REQUIRED STIMULATION CURRENT FOR COCHLEAR IMPLANTS. ADDITIONALLY, IT MAY LEAD TO AN IMPROVED LOCALIZATION OF THE STIMULATING CURRENT, MEANING MORE CHANNELS MIGHT BE HELPFUL TO PATIENT WHO RECEIVE SUCH COCHLEAR IMPLANTS. THAT MIGHT MEAN MICRO FABRICATED WAVE GUIDES WHICH IS WHERE WE WOULD FIT IN. ON OUR END, WE'VE DEVELOPED PROTOTYPE OP TROADS WHICH YOU SEE ON THE LEFT SIDE HERE, WITH A LASER CHIP MOUNTED ON THE FLEXIBLE SUBSTRATE, FAR AWAY FROM THE TARGET BY WAY OF GUIDING THE LIGHT. LEVERAGING THIS TECHNOLOGY, WE HAVE BUILT A FEW TEST SAMPLES RECENTLY THAT WE SHARED WITH CLAUS THAT HE IS EVALUATING. IT WILL OF COURSE REQUIRE SEVERAL ITERATIONS BUT WE'RE QUITE EXCITED ABOUT THE APPROACH AND THE POTENTIAL. OUR ANIMAL WORK IS FUNDAMENTAL TO ENABLING US TO FOCUS ON WHAT I CONSIDER ONE OF THE ULTIMATE CHALLENGES: TRANSLATING ENGINEERING INTO PRACTICE IN THE CLINIC. WE LOVE TO BUILD COOL TOLS AND SOLVE CHALLENGING PROBLEMS, BUT THE ULTIMATE TEST FOR US IS IF WE CAN GET THESE DEVICES INTO A HUMAN. THE PATH IS LONG AND RIGHTLY SO, BUT BY KEEPING AN EYE ON THE CLINICAL TARGET, WE HAVE WELL-DEFINED MILESTONES ALONG THE WAY. AS YOU'LL SEE ON THIS ILLUSTRATION, WE USE ANIMAL MODELS TO DEMONSTRATE WORKABLE PROTOTYPES OF EXPERIMENTAL TECHNOLOGIES. AN EXAMPLE OF THIS IS DEVELOPING EMBEDDED WAVE GUIDES FOR OPT JI NE TICS STUDIES. IN THE ANIMAL DOMAIN, WE CAN CONDUCT BASIC RESEARCH THAT CANNOT BE DONE IN HUMANS DUE TO RISK THAT NEEDS TO BE THOROUGHLY ADDRESSED. AS WE GO FURTHER TO THE RIGHT, WE START INTRODUCING CONTROLS AND NARROW DOWN THE FEATURE SET AND CAPABILITIES TO THOSE THAT SPECIFICALLY LEAD US TO THE ULTIMATE GOAL. THIS MEANS REPEATABILITY, QUALITY CONTROL, LIFETIME TESTING AND PROCESS VALIDATION ARE ALL CRITICAL FACTORS. FINALLY, AFTER SUBMITTING THE PROCESS -- THE PROPER DOCUMENTATION AND TESTING DATA TO THE FDA, A SUCCESSFUL IDE SUBMISSION WILL ALLOW PROTOTYPE IMPLANTATION IN HUMANS FOR FIRST IN MAN STUDIES. WE ARE UNIQUELY POSITIONED TO PROVIDE THIS BRIDGE AS A NATIONAL LAB. ACADEMIA OFTEN FACES CHALLENGES IN INFRASTRUCTURE WHILE INDUSTRY, ESPECIALLY IN THE MEDICAL FIELD, IS RISK-AVERSE. BY DEMONSTRATING A FEW PATIENTS IMPLANTED WITH ADVANCED IMPLANTS, WE CAN HELP DE-RISK INVESTMENTS ON THE INDUSTRY SIDE AND PROVIDE A MORE DIRECT PATH TO THE CLINIC FOR ACADEMIC PARTNERS. OVER THE YEARS, WE'VE BUILT A VARIETY OF HUMAN-GRADE ELECTRODE ARRAYS IN OUR DEDICATED CLEAN ROOM FACILITY. WE MAINTAIN QUALITY CONTROLLED ENVIRONMENT, MEANING THAT DEVICES BUILT IN THIS FACILITY ARE ISOLATED FROM OTHER PROJECTS IN THE SHARED FACILITY. IT MEANS THAT WE HAVE EQUIPMENT THAT IS ONLY USED FOR MEDICAL DEVICES AND IS ONLY EXPOSED TO SPECIFIC MATERIALS THAT ARE KNOWN SAFE FOR IMPLANTABLE DEVICES. WE PROVIDE ACCESS CONTROL TO THIS EQUIPMENT WITH SPECIAL TRAINING REQUIRED TO FAMILIARIZE US WITH QUALITY CONTROL SYSTEMS AND DOCUMENTATION. BY HAVING OUR FACILITY AS PART OF A BROADER CLEAN ROOM, WE DO ENJOY THE BENEFIT OF THE SPECIALIZED TOOL ENGINEERS AND THEIR SKILLSET TO MAINTAIN OUR EQUIPMENT AS WELL. AND ALL OF THIS IS SUPPORTED BY LLNL AT THE INSTITUTIONAL LEVEL WHICH WE ARE GRATEFUL FOR. RUNNING A CLEAN ROOM IS A VERY EXPENSIVE PROPOSITION. WHAT THAT HAS ALLOWED US TO DO IS TO BUILD DEVICES LIKE THE ONES YOU SEE HERE. THE TOP ROW SHOWS OUR MICRO FABRICATED DEVICES THAT HAVE BEEN CLEARED BY THE FDA THAT'S CONSIDERED TO BE NON-SIGNIFICANT RISK OR NSR. OFTENTIMES THIS IS A PREFERRED APPROACH FOR GETTING APPROVALS RATHER THAN THROUGH THE LOCAL IRBs AT AN INSTITUTION. TO BE CLEAR, THESE DEVICES ARE NSR BECAUSE THEY ARE ONLY USED INTRAOPERATIVELY. STILL, THEY CAN PROVIDE A WEALTH OF DATA THAT CAN BE ANALYZED AT A LATER TIME. IN CONTRAST TO THE BOTTOM ROW, WHICH OUR STANDARD COMMERCIAL-GRADE HANDMADE ELECTRODE ARRAYS, WE HAVE THE ABILITY TO BUILD SMALLER ELECTRODES, MANY MORE ELECTRODES IN A SMALLER VOLUME AND A VERY THIN GRID ELECTRODE ARRAY THAT CONFORMS TO THE SURFACE OF THE BRAIN THAT YOU SEE IN THE TOP LEFT. THE COMMERCIAL DEPTH ARRAY, FOR EXAMPLE, HAS FOUR CHANNELS AND IS 1.27 MINNEAPOLIS I 1.27 MILLIMETERS IN DIAMETER. -- BY SEGMENTING THE ELECTRODES WHICH YOU CAN KIND OF SEE IN THE INSET OVER HERE. THESE INTRAOPERATIVE STUDIES AS MENTIONED CAN BE QUITE USEFUL. HEROUR COLLABORATORS AT UCSF, A NEUROSURGEON AND WAS MENTIONED JUST EARLIER TODAY FOR ONE OF HIS FUNDED STUDIES, HAS IMPLANTED SEVERAL DEVICES WE BUILT WITH DARPA FUNDING. A CORTICAL GRID ARRAY IS PLACED NEXT TO A COMMERCIAL STRIP ARRAY FOR DATA COMPARISON AND WAS FOUND TO BE SUBSTANTIALLY SIMILAR IN PERFORMANCE, BUT WITH THE ABILITY TO CAPTURE MORE LOCALIZED NEURAL DATA. IN ADDITION, IN THE LOWER RIGHT PHOTO, YOU CAN SEE WE'VE BEEN ABLE TO IMPLANT A DEPTH ARRAY AS WELL. THE FIRST KNOWN SUCH ADVANCED DEPTH ARRAY AND DEMONSTRATING CAPTURING DATA. UNIQUELY, THESE PARTICULAR ARRAYS WERE ALSO ABLE TO PROVIDE BOTH RECORDING AND STIMULATION, ALLOWING A LARGE NEW SUBSET OF STUDY WHICH WAS DEMONSTRATED IN THIS INTRAOPERATIVE STUDY. ONE VERY INTERESTING FINDING WE HAD RECENTLY IS THE ABILITY TO RECORD FROM THE SURFACE OF THE HIPPOCAMPUS. THIS DEEP STRUCTURE HAD BEEN HYPOTHESIZED TO HAVE SURFACE WAVES AND HAVE BEEN INDIRECTLY MEASURED BUT WE BELIEVE THIS IS THE FIRST TIME IT WAS DIRECTLY MEASURED WITH A SURFACE TYPE GRID ARRAY. THE REASON THIS WAS POSSIBLE IS BECAUSE OF THE SMALL SIZE AND FLEXIBILITY OF OUR ELECTRODE ARRAY AND THE UNIQUE PATIENT CASE. A PUBLICATION ON THIS WORK IS FO RFORTHCOMING. TO BE EVEN MORE USEFUL, A FULL IDE SUBMISSION WOULD BE REQUIRED SO PATIENTS CAN BE IMPLANTED WITH THESE DEVICES OVER LONGER PERIODS OF TIME. INTRAONTIVE STUDIES ALLOW REALLY ONLY ABOUT FIVE TO 15 MINUTES OF DATA COLLECTION IN ORDER TO KEEP THE RISK LOW. SO OUR GOAL IN THE NEAR TERM IS TO PROPOSE AND SUBMIT AN IDE WHICH IS LIMITED BY PROPOSED SPECIFIC STUDIES SO THE FDA CAN PROPERLY EVALUATE THE RISK TO THE PATIENT. WE ALSO DO PUSH NEW TECHNOLOGIES EVEN IN THE HUMAN DOMAIN AND WHILE WE TYPICALLY DON'T PROPOSE AND DEVELOP TECHNOLOGY THAT COULD POTENTIALLY INTRODUCE SUBSTANTIAL NEW CHALLENGES BUT OCCASIONALLY WE DO NEED TO INNOVATE IN THAT SPACE AS WELL. SO HERE'S A PHOTO OF A NEW SIMPLE ADAPTER THAT WAS BUILT TO INTERFACE OUTSIDE THE BODY WITH ONE OF OUR THIN FILM HIGH CHANNEL COUNT ELECTRODE ARRAYS WHILE IN THE O.R. IN AN INTRAOPERATIVE SETTING. THIS SOLUTION SIMPLIFIES MAKING CONNECTIONS IN THE O.R. WHERE SIMPLICITY AND TIME ARE OF UTMOST PRIORITY. AND THIS ADAPTER SPECIFICALLY WAS BUILT TO INTERFACE ONE OF OUR 512-CHANNEL SURFACE ARRAYS AND CONNECT TO A STANDARD BACK END ELECTRONICS DEVICE TO CAPTURE DATA WHILE IN THE O.R. WHILE THIS IS A CLEVER SOLUTION, WE REALLY ONLY SEE THIS AS A STEP TO 512, 1,000 OR MAYBE EVEN 2,000 CHANNELS. IT'S A HUGE STEP ABOVE INDIVIDUALLY CONNECTING ONE WIRE AT A TIME, WHICH IS WHAT HAPPENED IN THE PAST. BUT THIS SOLUTION WILL ALSO BECOME CUMBERSOME EVENTUALLY, JUST BASED ON THE SIZE. AND SO FOR THAT INTENT, WE ARE DEVELOPING MICRO SCALE CONNECTORS TO ADDRESS THIS CHALLENGE AND HAVE SOME PROTOTYPES IN THE WORKS. AND AS I MENTIONED OUR 512-CHANNEL SURFACE ARRAY, I'LL JUST REALLY BRIEFLY SHOW ONE OF OUR LATEST ITERATIONS OF THIS DESIGN. IT'S CURRENTLY BEING FABRICATED IN OUR CLEAN ROOM AT LAWRENCE LIVERMORE. TRAVIS WHO YOU SEE IN THE TOP RIGHT IS LEADING THIS EFFORT, AND WE ARE HAPPY TO SAY THAT WE'VE SHARED SOME EARLY PROTOTYPES TO OUR COLLABORATORS AT UCSF, DR. EDDIE CHANG, AND HOPE TO HAVE APPROVALS IN HAND READY TO GO. WORK ON THIS EVIDENT IS SUPPORTED DIRECTLY BY NIDCD. FINALLY I WANTED TO SHOW SOME OF OUR SYSTEM LEVEL SOLUTIONS THAT WE'VE BEEN WORKING ON OVER THE YEARS. SOME OF YOU MAY KNOW THAT LAWRENCE LIVERMORE WAS INVOLVED WITH ARTIFICIAL RETINA PROGRAM MANY YEARS AGO. LLNL DEVELOPED THE POLYMER ELECTRODE ARRAYS WHICH SERVEDS A THE FOUNDATION FOR ALL THE WORK I PRESENTED TODAY. THIS IS A STRONG FOUNDATION AND IT WAS A COLLABORATIVE EFFORT ACROSS SEVERAL INSTITUTIONS THAT RESULTED IN THE COMMERCIALIZATION OF THE FIRST RETINAL PROSTHESIS. SUBSTANTIALLY SM LAR T SIMILAR TO THE DESIGN DEVELOPED BY LLNL WHICH YOU SEE HERE. FDA CLEARED AS OF SEVERAL YEARS AGO. AS PART OF THE WORK WE DID, WE ALSO FOCUSED ON THE INTERCONNECTED PACKING ON ELECTRONICS IN ORDER TO PROTECT IT FROM THE BODY. THIS EXPERTISE IN OUR ELECTRODE ARRAYS COMBINE TOGETHER FOR SOME PROPOSALS FOR EARLY BRAIN INITIATIVE FUNDING PROGRAM, AND IN PARTICULAR, THE DARPA -- PROGRAM SUPPORTED LIVERMORE'S EFFORTS, OUR EFFORTS, WITH UCSF AS THE LEAD INSTITUTION TO DESIGN A FULLY INTEGRATED IMPLANTABLE SYSTEM THAT TARGETED MOOD DISORDERS. IN THIS SYSTEM, WE DESIGNED THE PACKAGING INTERCONNECT AND CABLING FOR THE MAJORITY OF THE SYSTEM AND ENABLED -- ACROSS 256 CHANNELS USING EITHER A GRID OR DEPTH ELECTRODE ARRAYS, AND YOU CAN SEE THAT THIS SYSTEM HAS SEVERAL DIFFERENT COMPONENTS TO IT. SO WHAT'S NEXT? WELL, WE ARE VERY EXCITED ABOUT THE CAPABILITIES WE'VE DEVELOPED AT LIVERMORE. THE ABILITY TO BUILD ELECTRODE ARRAYS UNDER A GMP OR GOOD MANUFACTURING PRACTICE AS NEEDED BY THE FDA AND THE DESIGN OF REQUIRED PACKAGING. IT'S NOT JUST THE ELECTRODES, IT'S THE ENTIRE SYSTEM. WE'VE RECENTLY BROUGHT ON SOME ELECTRONICS EXPERTISE, WHICH WILL HOPEFULLY ALLOW US TO BE A SINGLE KIND OF ONE-STOP SHOP FOR VIRTUALLY ANY NEAR PROSTHETIC SUCH AS A COCHLEAR IMPLANT OR VESTIBULAR PROSTHESIS TO ALLOW OUR COLLABORATORS TRANSLATE TO A COMMERCIAL ENTITY, JUST LIKE WE'VE BEEN ABLE TO DEMONSTRATE IN THE PAST WITH OUR SUCCESSES WITH SECOND SIGHT. AND ON THIS SLIDE, I JUST WANTED TO BRIEFLY MENTION OUR SPECIFIC ADVANCED TECHNOLOGY RESEARCH THRUST. AS YOU SAW EARLIER, WE'VE DEVELOPED RECENTLY EXPERTISE IN OPTICAL WAVE GUIDING TECHNOLOGIES AND CAN NOW INCORPORATE SUCH TECHNOLOGIES IN A NUMBER OF WAYS. WE ALSO HAVE IN THE PAST DEMONSTRATED CHEMICAL SENSING AS A TECHNOLOGY, AS WELL AS AND CONTINUE TO WORK IN THAT DOMAIN IMPROVING OUR SENSING CAPABILITY. SO WE CALL THIS DEVELOPING MULTI-MODALITY ELECTRODE ARRAYS, BUILDING UPON OUR BASE FOUNDATION OF WHAT I STARTED THIS TALK WITH: FLEXIBLE ELECTRODE ARRAYS THAT ARE MICRO FABRICATED. I'M VERY EXCITED TO BE ABLE TO INCORPORATE SOME OF THE TECHNOLOGY, SOME OF THESE TECHNOLOGIES AS THEY SEE FIT IN FUTURE DEVELOPMENTS. FOR EXAMPLE, NEXT GENERATION COCHLEAR IMPLANTS WHICH COULD INDEED INCORPORATE -- AS I MENTIONED PREVIOUSLY. AND SO FINALLY JUST AS A STEP BACK FROM ALL THE TECHNOLOGY, I JUST WANTED TO SPEND A MOMENT TALKING ABOUT OUR APPROACH WORKING WITH COLLABORATORS. FIRST, WE LIKE TO DEFINE TECHNOLOGY PULLS RATHER THAN WORKING WHERE WE END UP DEVELOPING A TECHNOLOGY PUSH. A PULL IS WHERE COLLABORATORS AND RESEARCHERS THAT I'VE MENTIONED THROUGHOUT THIS TALK COME TO US WITH SPECIFIC CHALLENGES AND WE SOLVE THEM, CAN USE THEM RIGHT AWAY AND ADDRESSES AN IMPORTANT NEED. A PUSH, ON THE OTHER HAND, IS MORE DIFFICULT BECAUSE WE NEED TO FIND USERS OF THIS POTENTIALLY LESS USEFUL TECHNOLOGY SOLUTION. WHILE IT MAY BE A COOL NIFTY IDEA, IT'S REALLY DIFFICULT SOMETIMES TO FIND SOMEONE TO USE YOUR NIFTY IDEA. IN ACTUAL PRACTICE. SO WE PRIMARILY WORK AND FOCUS ON THE PULL SIDE AND WE DO THAT BY SEVERAL METHODS. ONE I MENTIONED A WORKSHOP EARLIER IN THIS TALK, BUT GENERALLY WE HAVE THIS REALLY TIGHT-KNIT RELATIONSHIP WITH OUR PARTNERS IN THE MEDICAL FIELD. AND THIS IS WHY THROUGHOUT THIS TALK YOU'VE HEARD A LOT OF SPECIFICALLY NAMES AND I'M VERY HAPPY TO BE HERE TODAY PRESENTING TO YOU WITH DR. CHARLIE DELLA SANTINA, WHO WILL TALK ABOUT HIS SIDE OF THINGS AND HOPEFULLY YOU CAN SEE THAT SYNERGY THAT WE BRING TOGETHER. WE DO WORK WITH ALL SORTS OF PARTNERS, ACADEMIC, GOVERNMENT, AS WELL AS INDUSTRY THROUGH COOPERATIVE RESEARCH AGREEMENTS, AND WE CAN ALSO WORK INTERNALLY WITH THE DEPARTMENT OF ENERGY AS WELL. I OFTEN FIND THAT THIS CAN BE DIFFICULT TO UNDERSTAND, SO THIS GRAPHIC HERE IN THE LOWER RIGHT-HAND CORNER HERE KIND OF SHOWS HOW WE AT NATIONAL LABS FIT IN ON THE SPECTRUM OF RESEARCH AND DEVELOPMENT ALL THE WAY TO MANUFACTURING. ACADEMIA IS OFTEN MORE ON THE DISCOVERY SIDE, WHILE INDUSTRY IS MORE ON THE DEVELOPMENT SIDE. MANUFACTURING SIDE. SO WE'RE SORT OF A BRIDGE BETWEEN THE TWO. ANOTHER AREA THAT WE DO FOCUS ON IS TRAINING AS WELL. MANY POSTDOCS COME THROUGH THE LAB AND WORK WITH US AND MOVE ON TO BECOME PRINCIPAL INVESTIGATORS OR MOVE ON TO DIFFERENT CAREERS. WE SEE THAT THIS TRAINING IS ALSO AN IMPORTANT PART OF WHAT WE DO AS A NATIONAL LAB. AND FINALLY, IT IS IMPORTANT TO KNOW THAT ONE OF OUR IMPORTANT MISSIONS IS TO DISTRIBUTE TECHNOLOGY. WE DO THIS IN A FEW WAY, BY DEVELOPING AND PATENTING NEW IP WHICH WE THEN LICENSE TO OTHER RESEARCH GROUPS. WE DEVELOP UNIQUE TECHNOLOGIES WITH INDUSTRY AND OF COURSE WE PUBLISH THE DATA IN OUR FINDINGS WHERE POSSIBLE AND ANOTHER MAJOR PUSH CONTINUING TO FIND WAYS BETTER RELEASING DATA AND OTHER DATA OPENLY TO THE COMMUNITY. MY LAST SLIDE, I JUST REALLY WOULD LIKE TO THANK EVERYONE FOR LISTENING TO MY TALK. I'D LIKE TO THANK ALL OF OUR TEAM MEMBERS AT LLNL, INCLUDING STAFF THAT MAINTAINS OUR CLEAN ROOM. OUR WORK WOULD NOT BE POSSIBLE WITHOUT OUR GENEROUS SPONSORS AT NIH AND IN PARTICULAR THE NIDCE AS WELL AS DARPA AND DEPARTMENT OF ENERGY FOR INFRASTRUCTURE SUPPORT. WITHOUT OUR COLLABORATORS, WE'D JUST BE A BUNCH OF NG NEAR ENGINEERS BUILDING COOL TOYS. >> THANK YOU, RAZI. THAT WAS A TERRIFIC PRESENTATION AND I LOVE THE GRAPHICS. I THINK WE HAVE TIME FOR ONE QUICK QUESTION, BUT WHILE WE'RE DOING THAT, GINGER, WOULD YOU PLEASE SHARE THE SCREEN FOR DR. DELLA SANTINA SO WE'RE READY FOR THAT PRESENTATION? DOES ANYBODY WANT TO ASK A QUESTION? NIRUPA? >> SO RAZI, THAT WAS JUST TERRIFIC, I GOT SO MUCH OUT OF IT AND I DON'T EVEN WORK IN VESTIBULAR PROSTHESES. BUT SO I THINK THAT NIDCD -- WHAT ARE THE PLANS SO PERHAPS THE QUESTION ISN'T REALLY ADDRESSED TO YOU, BUT I THINK THAT THERE ARE SO MANY PEOPLE WHO COULD USE THIS, YOU KNOW, I MEAN PIs OUT IN THE FIELD, WE'RE BIOLOGISTS, WE'RE NEAR OWE SCIENTISTS, SOMETIMES WE'RE EVEN ELECTRICAL ENGINEERS, BUT YOU KNOW, GETTING THE MECHANICS OF THINGS FIGURED OUT AND THE MICRO FABRICATION, NANOFABRICATION AND THINGS LIKE THAT. SO THIS AS A FACILITY AND RESOURCE JUST REALLY SHOULD BE SHOWCASED. BETTER THAN IT IS. >> I AGREE. I THINK IT'S A UNIQUE FACILITY AND I HAVE TO SAY, I THINK -- AND I CAME FROM INDUSTRY SHORTLY BEFORE I JOINED THE LAB, AND ONE OF THE MAJOR NEEDS THAT I NOTICED WAS A FACILITY LIKE THE ONE WE HAVE AT LAWRENCE LIVERMORE WAS MISSING. AND CERTAINLY WE'D LOVE TO WORK WITH COLLABORATORS, THAT'S KIND OF OUR ROLE, I SEES AS A NATIONAL LAB AND HELP BRIDGE THAT GAP FOR ALL KINDS OF PIs. SO WE'RE VERY HAPPY WITH WHAT WE'VE BEEN ABLE TO ACHIEVE RECENTLY. AND A LOT OF IT IS WITH SUPPORT FROM NIDCD. >> RAZI, JUST BEFORE WE LEAVE, PERHAPS YOU CAN PUT SOME CONTACT INFORMATION IN THE CHAT BECAUSE I THINK THERE ARE MANY -- >> OH, SURE. >> I DON'T QUITE KNOW HOW TO MOVE FORWARD WITH ANYTHING YOU PRESENTED UNLESS I KIND OF KNOW WHO THE CONTACT IS AND WHERE AND SO FORTH. SO THAT WOULD BE GREAT. I CERTAINLY AM INTERESTED IN IT AND I HAVE COLLEAGUES WHO ARE AS WELL, SO WONDERFUL TALK. >> I'LL BE HERE SO IF YOU WANT TO CHAT WITH ME, FEEL FREE TO SEND A CHAT VIA THE CHAT BUT I'LL SHARE MY EMAIL ADDRESS. THANK YOU. >> THANK YOU. NOW I'D LIKE TO INVITE DR. DELLA SANTINA TO BEGIN HIS PRESENTATION. CHARLEY? >> I'LL TURN ON MY VIDEO BRIEFLY TO SAY HELLO FACE-TO-FACE BEFORE TURNING IT OFF FOR BANDWIDTH PURPOSES. THANKS FOR THE OPPORTUNITY TO TALK TO YOU ABOUT WHAT IS I THINK A CASE STUDY IN HOW NIDCD AND LAWRENCE LIVERMORE INTERAGENCY AGREEMENT AND COLLABORATION CAN HELP TO ADVANCE DEVELOPMENT OF NOVEL IMPLANTS, IN THIS CASE, A VESTIBULAR IMPLANT. I'D LIKE TO DISCLOSE THE AFFILIATION I HAVE WITH -- DEVICES, A SPINOFF FROM MY LAB, AND CREATES THE VESTIBULAR IMPLANT THAT WE USE IN A CLINICAL TRIAL THAT I'LL MENTION AS WELL AS OTHER EQUIPMENT. AND RIGHT UP FRONT, I'D LIKE TO MAKE THE POINT THAT ALTHOUGH OUR CURRENT LAB IS SMALL, WE JUST HAVE FOUR GRADUATE STUDENTS, POSTDOC AND TWO STAFF MEMBERS AND ME, THE WORK THAT WE'RE DOING, OF COURSE, DEPENDS ON WORK OVER THE PAST 18 YEARS NOW, MANY FORMER STUDENTS AND CURRENT COLLABORATORS THAT YOU SEE ON THE SCREEN HERE, AND ALSO I'D LIKE TO SPECIFICALLY EMPHASIZE THAT ALL THE DATA I'LL SHOW YOU FROM OUR CLINICAL TRIAL WERE ACQUIRE BY THE LAB MEMBERS YOU SEE ON THE SCREEN HERE, WITH SUPPORT OF ENGINEERS FROM -- AND WITH SUPPORT FROM NIDCD OVER THE YEARS, AND I'D LIKE TO AFTER GIVE YOU GO AN UPDATE ON OUR CLINICAL TRIAL, TALK ABOUT WORK [INAUDIBLE] WITH OUR [INAUDIBLE] LAWRENCE LIVERMORE [INAUDIBLE]. FOR THOSE OF YOU WHO MAY NOT ALREADY KNOW, WE'VE BEEN WORKING ON A VESTIBULAR IMMAN IMPLANT NOW FOR SOME YEARS TARGETING THE SEMI-CIRCULAR CANALS AND AVOIDING FOR NOW CLINICAL IMPLANT FOR THE [INAUDIBLE] FOR REASONS I'LL EXPLAIN LATER. I'D LIKE TO QIF YO GIVE YOU A SENSE OF WHERE WE'VE BEEN AND WHERE WE ARE ON DEVELOPING A CANAL IMPLANT SO THAT YOU CAN BETTER UNDERSTAND WHERE WE ARE NOW AND WHERE WE HOPE TO GO IN THE FUTURE OF DEVELOPING A -- STIMULATING IMPLANT. YOU'RE ALL FAMILIAR WITH COCHLEAR IMPLANTS, AND OUR LABYRINTH DEVICES, MED EL, IS REALLY JUST A MODIFIED COCHLEAR IMPLANT WHERE THE ELECTRODE ARRAY THAT USUALLY GOES INTO THE COCHLEA HAS BEEN REPLACED WITH A SERIES OF ELECTRODE ARRAYS INTENDED TO GO INTO THE ANTERIOR HORIZONTAL AND POSTERIOR CANAL AM PEW LAY OF THE SEMI-CIRCULAR CANALS. THIS ON THE SLIDE HERE IS NOT A COCHLEAR ARRAY BUT RATHER A REFERENCE -- THAT CAN BE PUT ELSEWHERE IN THE LABYRINTH OR OUTSIDE. THEN UNLIKE THE COCHLEAR IMPLANT ON WHICH ITS BASED, THE VESTIBULAR IMPLANT HAS A COUPLE EXTRA MAGNETS TO MATE WITH THE EXTERNALLY HEAD-WORN UNIT WHICH PROVIDES POWER AND SIGNALS, BUT ALSO CONTAINS A MOTION SENSOR THAT IS SENSING HEAD ROTATION AND THEN SENDING THAT INFORMATION TO THE POWER AND CONTROL UNIT AND ULTIMATELY DRIVING THE STIMULATION. WE TEST OUR PATIENTS' RESPONSES WITH -- WE HEAD MOTION SYSTEMS DESIGNED TO BE COMPACT SO THEY COULD BE ROLLED OUT TO OTHER INSTITUTIONS AND ULTIMATELY TO PRIVATE CLINICS. THE WAY THIS WORKS IS SOMETHING LIKE IS SHOWN HERE. WHERE AN ABSTRACTED -- AN ELECTRODE ARRAY, THREE ELECTRODES EACH INTO THE ANTERIOR SEMI-CIRCULAR CANAL AMPULLA, HORIZONTAL AMPULLA, THAT MEANS THEY'RE BOUND TOGETHER TO MAKE ONE UNIT -- AND THEN A REFERENCE ELECTRODE OFTEN PROVIDES COMMON CLUES FOR OUTSIDE OF THE EAR. WHEN THE SENSOR DETECTS HEAD MOTION, IT BREAK IT IS INTO THREE DIMENSIONS. HERE YOU SEE IN RED HORIZONTAL MOVEMENT SIDE TO SIDE. THAT'S THEN PASSED THROUGH A MAP THAT DETERMINES THE PULSE RATE AND PULSE AMPLITUDE, AND THEN THAT'S COMBINED BY THE POWER CONTROL UNIT BY THE IMPLANT TO WHICHEVER CANALS ARE EXCITED OR INHIBITED NORMALLY. TO GET A SENSE OF WHERE WE HOPE TO GO WITH OUR WORK AT LAWRENCE LIVERMORE AND -- LET ME TELL YOU ABOUT THE PATH FOR OUR CANAL IMPLANT FOR BASIC SCIENCE TO FIRST IN HUMAN TRIAL. WE STARTED THIS WORK IN 2002 SUPPORTED BY THE AOS, AND THEN EARLY ON BY AN NIDCD KO8 GRANT. THAT WORK WAS INITIALLY IN RODENTS AND THEN OVER A SERIES OF NIDCD SUPPORTED R01s, WE TRANSCENDED THAT WORK INTO NON-HUMAN PRIMATES AND THEN ULTIMATELY TO HUMANS USING AN UNUSUAL MECHANISM THAT SUPPORTED BOTH ANIMAL RESEARCH AND PREPARATION FOR FIRST IN HUMAN TRIAL AND THEN THE FLICIAL -- OF THAT FIRST IN HUMAN TRIAL. FIRST IRB APPLICATION WAS IN 2012, THE IRB APPROVAL AND FDA APPROVAL PROCESS TOOK UNTIL 2016, SO FOUR YEARS, AND WE WERE INITIALLY APPROVED TO DO FIVE PATIENTS. WE'VE SINCE GONE TO EXPANSION UP TO 30 PATIENTS IN THIS TRIAL. SO FAR I'VE IMPLANTED NINE INDIVIDUALS. MOST OF THEM HAVE ANTIBIOTIC TOXICITY, EITHER THEY WERE GIVEN INTRAVENOUS GENTAMICIN TO TREAT INFECTION ELSEWHERE IN THEIR BODY OR SOME WERE ACTUALLY DELIBERATELY INJECTED WITH STREPMYCIN OR GENTAMICIN INTO THEIR EARS IN AN ATTEMPT TO TREAT MENIERE'S DISEASE WHICH UNFORTUNATELY LED TO BILATERAL VESTIBULAR LOSS. THE FIRST PATIENT IMPLANTED WAS NOW FOUR YEARS AGO, AND OUR MOST RECENT IMPLANTATION OF THAT PATIENT WAS A FEW MONTHS AGO. TO GIVE US YOU A SENSE OF WHAT THE SURGERY LOOKS LIKE, YOU CAN SEE HERE LEFT MASTOID CAVITY, THIS BONE WALL IS THE BACK WALL OF THE LEFT EAR CANAL, THE LEFT EAR CANAL WOULD BE IN FRONT OF US HERE. THIS WALL UP ON THE RIGHT SIDE OF YOUR SCREEN IS THE FLOOR OF THE BRAIN CAVITY, AND YOU CAN SEE THIS IS JUST A STANDARD OPENING FOR OUR MASTOIDECTOMY. THE IMPLANT STIMULATORS CAN BE UNDER THE SKIN WAY BACK HERE, AND ONCE WE'RE IN, OPEN UP A PATHWAY TO THE MIDDLE EAR, IDENTIFY THE FACIAL NERVE, AND THEN IDENTIFY THE AREA OF THE HORIZONTAL SEMI-CIRCULAR CANAL, THE AREA OF THE ANTERIOR SEMI-CIRCULAR CANAL AND THE POSTERIOR SEMI-CIRCULAR CANAL. ULTIMATELY OPEN HOLES INTO THE AMPULLA OF EACH, AND INTO THE POSTERIOR CANAL, ULTIMATELY BRINGING IN THIS ELECTRODE ARRAY AND FIDDLING AROUND FOR A WHILE TO GET IT INTO PLACE, AND THEN PUTTING THE -- AND PACKING WITH BONE CHIPS AND CLOSING. WE'VE HAD TO DEVELOP SOME NOVEL TECHNIQUES OF 3D RECONSTRUCTIVE CT SCANS IN ORDER TO IDENTIFY WHERE THE ELECTRODES WERE PLACED. ON THE LEFT OF THE SCREEN, YOU SEE OUR ORIGINAL VERSION OF CT IMAGING, BUT NOW YOU CAN SEE IN THE CENTER SET OF PANELS THE THREE ELECTRODES THAT ARE IN THE ANTERIOR CANAL, THE THREE IN THE HORIZONTAL, THREE IN THE POSTERIOR AND A REFERENCE -- MUCH HIGHER RESOLUTION IMAGE DEVELOPED BY OUR COLLEAGUES. YOU CAN SEE WHERE THEY ARE IN RELATION TO THE 3D RENDERING OF THE LABYRINTH. JUST TO GIVE YOU A BRIEF SENSE OF WHERE WE ARE ON THE CANAL PROSTHESIS, WHICH IS TRADITIONAL TECHNOLOGIES, WE NOW HAVE IMPLANTED 9 SUBJECTS AS I MENTIONED. ALL OF THEM HAVE ELECTRICALLY EVOKED THREE DIMENSIONAL VESTIBULOOCULAR REFLEX, THOSE RESPONSES ALIGN WITH THE ANATOMIC ACCESS OF THE CANAL. WE CAN STIMULATE THEM IN PAIRS OR ALL THREE, 3D AK AXI AXIS OF HEAD MOTION. THEY'RE STILL SMALL COMPARED TO NON-HUMAN PRIMATES, WHICH GIVES ME SOME HOPE THAT WE CAN DO EVEN BETTER. VESTIBULOOCULAR REFLEX DURING WHOLE BODY AND HEAD ON BODY ROTATION WITH MOTION MODULATED STIMULATION EXCEEDS PLACEBO-CONTROL IN ALL SUBJECTS. JUST BRIEFLY SCHOLL THAT A SHOW THAT AS WE INCREASE STIMULATION SAY TO THE HORIZONTAL CANAL, WE CAN GET MUCH BIGGER EYE MOVEMENTS AS THEY GROW IN CURRENT OR PULSE RATE AND THEY TEND TO BE ALIGNED WITH THE AXIS OF THE CANAL THAT WE'RE STIMULATING SO HERE FOR THE HORIZONTAL CANAL AND THEN -- HERE IN BLUE FOR THE LEFT POSTERIOR CANAL, HERE IN GREEN FOR THE [INAUDIBLE]. I THINK IT'S EASIER TO SEE WHAT I MEAN IF WE JUST SHOW YOU A VIDEO, SO IN THIS CASE, I'M GOING TO WIGGLE THE HEAD-WORN MOTION SENSOR FOR -- AND YOU CAN SEE THAT THAT WILL DIRECTLY DRIVE REFLEX EYE MOVEMENT IN THE PLANE OF HEAD MOTION THAT SHE'S PERCEIVING. THAT'S EVEN IN BRIGHT, WELL-LIT ROOMS SO IN DARKNESS, IT'S QUITE A BIT LARGER RESPONSE. AS THESE RESPONSES GROW WITH CURRENT, THEY'RE NOT HUGE IN ALL SUBJECTS, SO WE HAVE ROOM TO IMPROVE. THEY ALIGN PRETTY WELL WITH THE ANATOMIC AXE EASE O AXES BUT DUE FROM CURRENT SPREAD OF OUR TARGETED CANAL OVER TO NEARBY CANNAS SOMETIMES WE SEE A RESPONSE OVER TO A NON-TARGET CANAL INSTEAD OF GETTING A HORIZONTAL AXIS ROTATION, STIMULATING LEFT ANTERIOR CANAL, SO WE HAVE WORK TO DO TO GET BETTER ALIGNMENT OF OUR RESPONSES. BUT WE CAN STILL GIVE IMI NAIGINGCOMBINATION OF STIMULI BETWEEN DIFFERENT CANALS AND CONTROL AXIS OF HEAD MOTION THAT PATIENTS PERCEIVE. FOR QUICK HEAD MOVEMENTS, WE DO THIS HEAD IMPULSE TEST, TYPICALLY DONE WITH HAND MOTION BY THE CLINICIAN. WE USE A MOTORIZED TOOL LIKE THIS. IDEALLY WHAT YOU WOULD SEE IS THAT THE EYE MOVEMENT RESPONSE HERE IN BLACK WOULD FOLLOW THE HEAD MOTION HERE IN BLUE IN THIS PATIENT'S LEFT SIDE OR RIGHT SIDE. YOU CAN SEE IN SUBJECT NUMBER TWO, AFTER IMPLANTATION, HIS RESPONSES ACTUALLY WENT DOWN FROM PRE-OP BECAUSE AS A COCHLEAR IMPLANT, THE IMAGE IS NATURAL HEARING -- DAMAGE VESTIBULAR NATURAL FUNCTION IN THE -- CANAL BUT THEN WITH ACTIVATION WE WERE ABLE TO BOOST THEM UP AND A BIT FURTHER UP SINCE THAT EIGHT-WEEK RESULT. ONE THING WE JUST RECENTLY REALIZED IS THAT THE DELAY IN THE RESPONSES THAT WE SEE HAS TO DO WITH THE FACT THAT WE'RE USING A -- MAP AND WE REALLY OUGHT TO BE PAYING ATTENTION TO THE ACCELERATION WITH WHICH THE HEAD MOVES BECAUSE THE ACCELERATION STARTS WELL BEFORE THE HEAD REACHES A VERY BIG VELOCITY TO DRIVE A HIGH PULSE RATE. SO JUST A MONTH AGO, WE STARTED TESTING NOW OUR FIRST SUBJECT USING AN ACCELERATION-BASED STIMULATION PARADIGM AND YOU CAN SEE HERE THERE'S VERY LITTLE RESPONSE TO HEAD MOTION PRE-OP. HERE WITH OUR STANDARD RESPONSE WE HAD SOMETHING LIKE -- RESPONSES ON SUBJECT TWO BUT NOW WITH THIS NEW ACCELERATION BOOST WE'RE ESSENTIALLY BOOSTING ALL THE WAY UP TO NORMAL RESPONSES ON IMPACTED SIDE. THIS IS VERY EXCITED AND WE'RE LOOKING FORWARD TO DOING THIS WITH ALL OF OUR OTHER SUBJECTS WHEN THEY RETURN IN THE NEXT COUPLE OF MONTHS. SO THE STATUS ON THAT IS THAT WE HAVE EYE MOVEMENTS THAT WE CAN DRIVE FOR ALL OF OUR PATIENTS, THESE HEAD IMPULSE RESPONSES WITH QUICK IRRITATIONS ARE OKAY WITH OUR STANDARD MAPPING AND IT LOOKS LIKE THEY'RE GOING TO BE QUITE A BIT BETTER WITH THIS ACCELERATION BOOST PARADIGM. NOW WHAT ABOUT POSTURE AND GAIT? ALL OF OUR SUBJECTS REPORT BERT WALKING AND GREATER INDEPENDENCE. ALL WHO USED TO DEPEND ON A FAMILY MEMBER TO TRAVEL FOR THEIR VISITS NOW COME INDEPENDENTLY. WE USE MULTIPLE DIFFERENT METHODS OF POSTURE AND GAIT, AND FOUR OUT OF FIVE OF THEM ARE BETTER, ALL EXCEPT FOR GAIT SPEED. THEY'RE ALWAYS BETTER THAN CONSTANT RATE PLACEBO CONTROL STIMULUS CONDITION BUT SOME OF THE PATIENTS STILL HAVE A PROBLEM STANDING WITH EYES CLOSED ON FOAM AND THEY HAVE OTHER MEDICAL CONDITIONS LIKE ARTHRITIS THAT SEEM TO MAKE THESE DATA A LITTLE BIT DIRTIER THAN THEY WOULD BE OA OTHERWISE. WE HAVE TWO DIFFERENT POSTURE TESTS THAT WE USE. HERE YOU CAN SEE RESULTS SIX MONTHS OUT FROM IMPLANTATION. THESE GREEN MARKERS SHOW THE CHANGE FROM PREOPERATIVE BASELINE FOR EACH OF THE INDIVIDUALS -- MEDIAN RANGE AND THIS IS SIGNIFICANTLY BETTER THAN A MINIMALLY IMPORTANT DIFFERENCE ON THE -- TEST OF MOSS TOUR. HERE YOU CAN SEE THOSE RESULTS HOLD UP AT A YEAR, AND THE RESULTS WITH TREATMENT MODE STIMULATION ARE ALWAYS BETTER FOR THE GROUP THAN WITH PLACEBO CONTROLLED STIMULATION WHERE WE'RE NOT GETTING ANY MOTION INFORMATION -- AND YOU CAN SEE SIMILAR FINDINGS ACROSS OTHER POSTURE AND GATE AXIS. I THINK IT'S EASIER TO SEE THAT WITH A VIDEO OF AVID, SO YOU CAN SEE HERE OUR FIRST PATIENT STANDING WITH EYES CLOSED ON FOAM, THIS MAN, IN FACT, HE USED TO RUN MARATHONS BEFORE HE LOST VESTIBULAR FUNCTION TO A GENTAMICIN TOXICITY EVENT FOUR YEARS BEFORE WE MET HIM. NOW, YOU CAN SEE HERE AT A YEAR OUT, HE HE' HE'S ABLE TO DO THIS TEST CONTINUOUSLY WITHOUT FALLING, WHICH IS A BIG IMPROVEMENT FOR HIM. YOU WATCH HIS WALKING IN A WELL LIT ROOM, IT DOESN'T LOOK THAT BAD, ALTHOUGH HE'S SLOW TO MAKE THE TURN THERE. AND WHAT YOU CAN SEE IS THAT WHEN YOU ASK HIM TO LOOK SIDE TO SIDE, HE BECOMES UNSTABLE. AGAIN, EVEN IN A WELL LIT ROOM PREOPERATIVELY. NOW, HE SENT US A SERIES OF VIDEOS. FOUR MONTHS OUT HE STARTED RUNNING ON A TREADMILL. 16 MONTHS OUT HE STARTED A BOXING CLASS AND JUMPING ROPE, AND 20 MONTHS AFTER, HE CAME TO VISIT WITH SOME OF US AND WENT FOR A RUN AROUND THE BALLPARK AT HARVARD. SO WE'VE HAD A REAL IMPACT ON POSTURE AND GAIT, MAYBE EVEN MORE SO THAN EYE MOVEMENTS THAN WE ORIGINALLY THOUGHT WERE GOING TO BE THE MAIN TARGET OF THIS WORK. QUALITY OF LIFE OUTCOMES HAVE SHOWN THAT DIZZINESS HANDICAPPED INVENTORY, WHICH IS A MEASURE OF PATIENTS' PERCEIVED DIZZINESS HAS IMPROVED IN ALL OF OUR SUBJECTS TO A SIGNIFICANT DEGREE FOR THE GROUP, AS HAS THE VESTIBULAR ACTIVITIES OF DAILY LIVING ASSESSMENT, WHICH MEASURES THEIR SELF-PERCEIVED VESTIBULAR-RELATED DISABILITY. GENERAL MEASURE OF HEALTH-RELATED QUALITY OF LIFE HAS ALSO IMPROVED, THE SF36 UTILITY, WHEREAS THE HEALTH UTILITY INDEX, ANOTHER ONE, HAS NOT SIGNIFICANTLY CHANGED UP OR DOWN, PARTLY REFLECTS HEARING LOSS IN FOUR OF OUR PATIENTS SO FAR, THREE OF WHOM HAVE BEEN SEVERE. THE OVERALL STATUS OF A CANAL IMPLANT MADE WITH TRADITIONAL ELECTRODE TECHNIQUES IS THAT ALL OF OUR PATIENTS ARE USING THE SYSTEM EITHER 24 HOURS A DAY OR THEY WEAR IT DURING ALL WAKING HOURS AND TAKE IT OFF AT NIGHT. THEY ALL REQUESTED FDA-APPROVED LONG-TERM USE OF THE SYSTEMS, AND THEY ALL HAVE ELECTRICALLY EVOKED VESTIBULOOCULAR FOR EACH OF THREE CANALS, BEING ABLE TO STIMULATE DIFFERENT FREQUENCY REGIONS OF THE COCHLEA. AND THIS ACCELERATION BOOST SEEMS LIKE IT GREATLY IMPROVES PERFORMANCE. DUE TO TIME CONSTRAINTS I WON'T TALK ABOUT THE HEARING RESULTS BUT SO FAR WE HAVE USEFUL HEARINHEARING IN FIVE OF NINE, THREE HAVE PROFOUND WITH NORMAL HEARING IN THE OPPOSITE YEAR AND ONE WAS IMPLANTED RECENTLY AND SEEMS TO BE TRENDING UPWARD FROM AN INITIAL HEARING LOSS. THEY ALL REPORT GREATER INDEPENDENCE, THEY HAVE BETTER POSTURE, GAIT, QUALITY OF LIFE, AND WE HAVE APPROVAL NOW BASED ON THESE INTERIM RESULTS TO 30 SUBJECTS. FREQUENT QUESTIONS COME EP, HOE, IUP,THOUGH, IS THIS GOING TO WORK FOR PEOPLE WHO MAY BE OLDER AND HAD INITIAL ONSET OF LOSS MANY YEARS AGO. I THINK OUR FINDINGS SO FAR ARE YES, THIS MAN WAS IMPLANTED 24 YEARS AFTER THE ONSET OF HIS LOSS DUE TO GENTAMICIN. AND SO CLEARLY THIS CAN WORK EVEN AFTER A QUARTER CENTURY OF DEFICIT WHICH I THINK BODES WELL FOR THIS WORKING WELL IN OUR OLDER SUBJECTS WHO HAVE HAD A LONG TERM LOSS. AND CAN IT WORK IN PEOPLE WHO HAVE IDIOPATHIC LOSS THAT'S NOT DUE TO A KNOWN GENTAMICIN OR OTHER TOXIC INJURY TO HERT CELLS AND SO FAR -- SUBJECT NUMBER NINE, AGAIN, HAS A VERY PROMINENT RESPONSES WHICH I THINK BODES WELL FOR PEOPLE WITH NON-OAT TOXIC LOSS. BUNON-OTOTOXIC LOSS. -- ARE IMPORTANT -- COCHLEA AND BY US -- CANALS. CLEARLY THEY DO A LOT FOR YOU EVEN THOUGH YOU MAY NOT THINK ABOUT IT MOMENT BY MOMENT. DRIVES SENSATION OF HEAD TILT AND TRANSLATION AND ALTHOUGH YOU DON'T NORMALLY THINK ABOUT IT CONSCIOUSLY, THAT'S IMPORTANT TO OTOLITH OCULAR TILT REFLEXES AND TRANSLATION REFLEXES THAT KEEP YOUR EYES AND YOUR HEAD AND YOUR BODY STEADY WHEN YOU TILT TO ONE SIDE. IF YOU DAMAGE A LABYRINTH, IN ADDITION TO KNOCKING OUT SOME OF THE -- CANALS, IF YOU KNOCK OUT THE UTRICLE AND SACULE YOU'LL SEE THIS HEAD TILT SENSATION, WHERE THE PERSON'S HEAD WILL TILT OFF TO THE SIDE, THE EYES WILL ROTATE AROUND THE ORIGINAL AXIS AND THEN YOU'LL GET A SKEWED DEVIATION AND DOUBLE VISION ALL BECAUSE OF THE IMBALANCE FROM THE LEFT AND RIGHT EARS. SO CLEARLY THAT INPUT HAS REAL IMPACT EVEN THOUGH ITS PRESENCE IS USUALLY BENEATH THE LEVEL OF CONSCIOUS PERCEPTION. IN ADDITION TO CONTROLLING HEAD AND BODY WRITIN RIGHTING REFLEXES AND POSTURE, IT CONTROLS AUTONOMIC REFLEXES AS WELL. OUR CANAL IMPLANT DOESN'T DO ANYTHING ABOUT THE UTRICLE AND SK YOU'LL DRIB RATTILY BUT WE HAVE SPREAD CURRENT BY MISTAKE AND PATIENTS GET PERCEPTION THAT THEY'RE SLIDING TO THE LEFT AND RIGHT. SO WE TURNED TO WORKING WITH OUR COLLEAGUES AT LAWRENCE LIVERMORE TO TRY TO ADDRESS THE ORIGINAL CHALLENGE THAT MADE US STEER AWAY FROM THE UTRICLE AND SACULE AND INSTEAD FOCUS ON THE CANALS, AND WE'RE GOING TO TRY TO FOLLOW THE SAME PATHWAY THAT WE TOOK SUCCESSFULLY SO FAR TO A TRADITIONAL CANAL, TRADITIONAL TECHNOLOGY CANAL IMPLANT RUNNING FROM RODENTS TO NON-HUMAN PRIMATE WORK ULTIMATELY TO HUMANS, EXCEPT UNLIKE THE CANALS, WE HAD MORE CHALLENGING ANATOMY TO WORK WITH, BEING IN THE HAIR BEARING SURFACE, ALL OF THE HAIR CELLS -- HEAD MOTION NOT ONLY THE SAME AXIS BUT ALSO IN THE SAME DIRECTION. SO NO MATTER WHERE WE END UP PUTTING AN ELECTRODE AS A SURGEON, NO MATTER WHERE CURRENT SPREADS ON THAT CANAL CHRISTA, WE'RE GOING TO GIVE THE ANIMAL THE SAME SENSATION OF HEAD ROTATION, MAYBE AT DIFFERENT SPEEDS, BUT NOT IN DIFFERENT DIRECTIONS. IT'S MORE COMPLEX, EACH OF THESE IS SORT OF A TWOL-DIMENSIONAL SURFACE WITH A COMPLEX POLARIZATION OF HAIR CELLS, SO IN NORMAL FUNCTION, IF YOU HAPPEN TO HAVE A HAIR CELL THAT'S EXCITED AT THIS POINT IN THE SACCULE, THEN THE ANIMAL OR THE PERSON IS PERCEIVING ACCELERATION ALONG THIS DIRECTION, BUT IF YOU HAPPEN TO MOVE A COUPLE HUNDRED MICRONS AWAY, THEN YOU'D BE PERCEIVING SOMETHING IN A DIFFERENT DIRECTION. SO IF WE PUT OUR ELECTRODES IN THE UTRICLE AND SACULE REGION WITH THE SAME SORT OF SURGICAL PRECISION I CAN DO WITH CANALS, WE COULD GET RESPONSES IN WHATEVER DIRECTION AND REALLY NOT HAVE MUCH CONTROL. THIS IS A TEXTBOOK SITUATION WHERE YOU NEED SMALLER, DENSER ELECTRODE ARRAYS, SO WORKING WITH LAWRENCE LIVERMORE AND WORKING UNDER THE DESIGN RULE SET THAT HE DESCRIBED EARLIER, WE DESIGNED A SERIES OF ELECTRODE ARRAYS THAT HAVE SOME 13 ELECTRODES EACH ON PADDLES FOR THE UTRICLE AND SACULE AND ALSO HAVE AN 8 BY 1 ELECTRODE AWAY MEANT TO SIT ON HORIZONTAL CANAL, SUPERIOR CANAL AND POSTERIOR CANAL AMPULLA TO ALLOW US TO DO EXPERIMENTS ON HOW IMPORTANT THE DISTANCE FROM THE ELECTRODE TO THE TARGETED AMPULLA IS. THE REASON THESE ARE JOINING CANAL SHANK WITH A PADDLE IS IN THE CHIN CHICAGTHECHIN CHICAGOTHE -- PASS THE ELECTRODE ALL THE WAY DOWN PASS THAT AMPULLA AND INTO THE SACULE OR PASS THIS ONE DOWN INTO THE UTRICLE, THERE'S A LARNG PIECE OF BRAIN IN THE MIDDLE OF THE LABYRINTH THAT GETS IN THE WAY OF DOING SURGICAL APPROACHES. SO HERE YOU CAN SEE IN THE MIDST OF A SURGERY, ONE OF THE ELECTRODE ARRAYS HAS BEEN INSERTED DOWN THE HORDES CANAL AMPULLA, THIS ONE IS GOING TO BE TARGETING THE UTRICLE. WE'VE BEEN USING MICRO CT TO SEE WHERE THOSE ELECTRODES ACTUALLY END UP, AN BECAUSE THEY'RE FLEXIBLE, IT'S BEEN HARD FOR US TO -- WE'RE HOPING USING THE RIGID SYSTEM SHOWED EARLIER WE'LL BE ABLE TO DO BETTER IN THAT REGARD. WE HAVE TO DEVELOP SOME NEW STIMULATOR TECHNOLOGY FOR THIS, SO WE'VE ADAPTED FROM OUR FIRST GENERATION JOHNS HOPKINS VESTIBULAR ENGINEERING LAB PROSTHESIS CIRCLE STRI THAT WAS ABOUT AN INCH SQUARE, THEN TO OUR SECOND GENERATION WHICH WAS A LITTLE BIT SMALLER BUT WE WANT TO BE ABLE TO FIT THIS INTO A COMMERCIAL COCHLEAR IMPLANT CANISTER AND TO GET THAT SMALL, WE NEEDED TO GO WITH A DIFFERENT TECHNOLOGY. AT THE SAME TIME, WE NEEDED TO ADD TO THE CANAL STIMULATING FUNCTION ALL OF THE FUNCTIONS NEEDED TO STIMULATE THE UTRICLE AND SACULE INCLUDING ACCELEROMETERS AND HAVE AN INCREASED NUMBER OF STIMULATION CHANNELS AND BE ABLE TO MULTIPLEX TO NOT 50 ELECTRODES, WHICH IS A LOT. WE COLLABORATED WITH JOHNS HOPKINS ELECTRICAL ENGINEERING TO MAKE CUSTOM SILICON CHIPS THAT ARE CUSTOM-DESIGNED TO TAKE UP MOST OF THE CIRCUITRY OF OUR IMPLANT, THEN AT THE SAME TIME ADD THAT FUNCTIONALITY THAT WE NEED TO DO THESE EXPERIMENTS. OF THE CANAL ELECTRODES WORK JUST LIKE OUR MORE TRADITIONAL ELECTRODES, AND WITH H WE CAN STIMULATE A GIVEN CANAL OVER OFTEN MANY ELECTRODES. WE'RE SEEING NOW UNIQUE RESPONSES THAT AS FAR AS I KNOW, NO ONE HAS BEEN ABLE TO GET BEFORE IN DECADES OF TRYING TO SELECTIVELY STIMULATE THE UTRICLE AND SACULE, IT'S JUST A HARD THING TO DO. BUT BY USING BIPOLAR STIMULATION BETWEEN PAIRS OF ELECTRODES ON THAT UTRICLE OR SACULE ARRAY, WE CAN GET STATIC RESPONSES OF THE EYES THAT ARE SIMILAR TO WHAT YOU SEE OF THE EYES RESPOND TO A HEAD TILT, WHERE THEY JUMP UP TO A NEW POSITION AND HOLD THAT POSITION FOR A LONG TIME, WHICH IS NOT WHAT WE SEE WHEN WE STIMULATE CANALS. PULSE RATE, PULSE AMPLITUDE, THEN AGAIN, WE CAN METHODICALLY CONTROL EYE STATIC POSITION, AND THAT SHOWS THAT WE'RE PROBABLY DELIVERING A -- TO THE ANIMAL SIMILAR TO A NORMAL UTRICLE AND SACULE DURING A HEAD TILT. WHEN WE TRY TO STIMULATE THE CANNAS, WE GET THE NYSTAGMUS TYPICAL OF NATURAL RESPONSES TO HEAD ROTATIONAL VELOCITY, SO IF YOU SPIN AROUND ON A CHAIR, YOUR EYES ARE GOING TO DRIFT TO THE OTHER SIDE AND THEN BEAT THAT AND THAT WILL HAPPEN VERY QUICKLY, AND IT WILL ALSO FADE RATHER QUICKLY. SO IN THESE THREE EXEMPLARS, YOU CAN SEE THERE'S A VERY RAPID RESPONSE, THEN IT FADES IN 10 TO 30 SECONDS OR SO. WHEN WE TARGET EITHER THE SACULE OR THE EU TR UTRICLE, WE MONITOR THE ELECTRODE, SPREADING CURRENT NOT ONLY TO THAT TARGETED UTRICLE OR SACULE BUT ALSO TO NEARBY CANALS. THEN WE GET THIS MIXED RESPONSE WHERE WE RAPIDLY GET UP TO A NEW ROTATION BUT WE HAVE SOME NYSTAGMUS PROBABLY DRIVEN BY THE KA WILL NAS. THE INTERESTING THING HERE IS WHEN YOU USE A NEAR -- TARGETING -- WE SEE RESPONSES WE'VE NEVER SEEN OAR WISE IN ALL OOTHERWISE INALL OF OUR YEARS OF STIMULATI NG CANALS, EITHER A SLOW DRIFT OF THE EYES UP TO A NEW CONDITION OR JUST A DELAY UNTIL THERE'S A SUDDEN CHANGE TO POSITION. -- REPRESENTS THE BRAINSTEM'S RESPONSE TO FOCAL STIMULATION OF THE UTRICLE OR SACULE, SOMETHING THAT'S HARD FOR US TO ACHIEVE IN OUR NATURAL EXPERIMENTS BECAUSE WE CAN'T REALLY TILT AN ANIMAL WITHOUT ROTATING. SO WHERE ARE WE ON THAT PATH SO FAR? WE'VE CREATED A MODEL, AN ANIMAL MODEL THAT WE CAN USE TO STUDY THIS, WE'VE CREATED A COMPUTATIONAL MODEL THAT MAPS THE EYE MOVEMENTS BACK ON TO THE NATURAL HEAD TILT, WE'VE CREATED NEW ELECTRODE ARRAYS AND STIMULATION CIRCUITS, WE'VE GOT A REASONABLY SUCCESSFUL IMPLANTATION APPROACH, AND WE'VE SHOWN THAT WE CAN SELECTIVELY STIMULATE THE UTRICLE AND SACULE AND GET THESE STATIC OCULAR COUNTER-ROLL RESPONSES BUT ONLY IF WE HAVE SMALL BIPOLAR ELECTRODE ARRAYS. WHERE WE'RE GOING TO HEAD NEXT IS TO FOLLOW THE SAME PATHWAY WE DID FOR OUR CANAL-DRIVEN IMPLANT USING TRADITIONAL ELECTRODES, CONTINUING TO BUILD THE SCIENTIFIC FOUNDATION BY EXTENDING THIS TO NON-HUMAN PRIMATES AND THEN TOWARD HUMANS. TO MINIMIZE OUR USE -- AND THEN ADAPTING THE TECHNOLOGIES THAT I'VE SHOWN YOU TODAY WHILE AT THE SAME TIME TRYING TO ASSESS AND MINIMIZE EFFECT ON HEARING. SO WHAT LESSONS CAN WE LEARN FROM THIS EXAMPLE OF JUST ONE OF I'M SURE THE MANY COLLABORATIONS. ONE THING I FOUND IS THAT THE PATH FROM A BASIC LABORATORY RESEARCH, YOU CAN JUST -- WHAT LOOKS LIKE FEASIBILITY IN AN ANIMAL SO ACTUAL CLINICAL APPLICATION TAKES A LONG TIME FOR FDA CLASS 3 MEDICAL ADVICE -- SO SHORTER DURATION FUNDING MECHANISMS ESPECIALLY FOR DEVELOPMENT OF DEVICES LIKE THIS, TO LOOK AT LONG TERM COLLABORATIONS BETWEEN ACADEMIA, GOVERNMENT, OTHER AGENCIES, LAWRENCE LIVERMORE AND INDUSTRY. BUT IT'S NOT A ONE-WAY ROAD. COMMONLY WE'VE -- MOTIVATED OR FORCED US TO CREATE TECHNOLOGIES THAT BECOME THINGS THAT ENABLE -- PARADIGMS SO IT'S REALLY A BI-DIRECTIONAL THING THAT REALLY FEEDS SCIENCE WHILE WORKING ON DEVELOPMENT. JUST TO REALIZE, I WAS SHOCKED A COUPLE YEARS AGO THAT I USING THE TERM R & D, RESEARCH & DEVELOP THINKING IT WAS ONE WORD MORE OR LESS. I REALLY NEVER SEPARATED IT IN MY MIND THE WAY I SHOULD V THEN I REALIZED LABS LIKE MINE, THEY'RE REALLY -- TO THE GREAT HYPOTHESIS DRIVEN ENGINEERING TECHNOLOGY RESEARCH BUT MOST OF US ARE NOT WELL SUITED TO DEVELOPING A CLASS - 3 MEDICAL DEVICE. IT OFTEN REQUIRES FORMAL ADHERENCE TO A STANDARD THAT -- QUALITY SYSTEMS OF COMPLIANCE -- ECECK STEN SIEVE DOCUMENTATION, IT'S A DIFFERENT BEAST. AND I THINK THIS IS WHERE THE NIDCD AND LAWRENCE LIVERMORE INTERAGENCY COMMUNITY REALLY HELP US WITH NOT ONLY GIVE US ACCESS TO THESE NEW TECHNOLOGIES BUT HELPING TO BRIDGE THE GAPS BETWEEN WHAT WE AS NIDCD EXTRAMURAL PROSTHESIS RESEARCHERS DO AND WHAT HAS TO HAPPEN TO GET THINGS INTO A DEVELOPMENT PATH THAT'S GOING TO PROPERLY BENEFIT OUR PATIENTS. I FOUND OUR LAB COMMUNICATING WITH LAWRENCE LIVERMORE CLEARLY SPECIFIED DESIGN RULES THAT HAVE HELPED US, WE DESIGN THINGS ON POWERPOINT AS LONG AS WE ADHERE TO A SET OF WELL SPECIFIED DESIGN RULES AND END UP WITH DEVICES THAT ARE JUST LIKELY DESIGNED, IDEALLY THESE NIDCD SUPPORTED LABS WILL ULTIMATELY -- 3D PRINTER MAKER VERSE WHERE IF YOU GO ONLINE AND SHARE DESIGNS AND TIPS AND TOOLS FOR 3D PRINTED PROJECTS, A MILLION PEOPLE NOW ON ONE FORUM FOR DOING THAT, AND HOPEFULLY WE AS A COMMUNITY OF RESEARCHERS USING THESE TECHNOLOGIES CAN BUILD SOMETHING SIMILAR. AND ALTHOUGH IT WASN'T A FOCUS OF TODAY, I THINK A SIMILAR APPROACH COULD BE APPLIED TO THE CIRCUITRY THAT CONNECTS TO THESE EELECTRODE ARRAY, LIKE FOR INSTANCE 16-CHANNEL STIMULATOR THAT WE DESIGNED IN OUR LAB IS NOW IN USE FOR STUDYING AUDITORY CORTEX ACTIVITY IN COCHLEAR IMPLANT AND CEREBELLAR NORMAL LEARNING MECHANISMS. I'LL STOP THERE, AND I THANK YOU ALL FOR YOUR ATTENTION. >> THANK YOU, CHARLEY, THAT WAS JUST A FABULOUS TALK COVERING SO MANY AREAS THAT REQUIRED DEEP TECHNICAL EXPERTISE. I REMEMBER AS A PROGRAM OFFICER READING ONE OF YOUR PROGRESS REPORTS WHERE YOU SAID YOU WERE GOING TO START PROGRAMMING A MICRO CONTROLLER TO DO THIS, AND THAT'S JUST A DROP THE IN BUCKET COMPARED TO WHAT YOU'VE ACCOMPLISHED SINCE THEN. SO THIS IS OPEN FOR DISCUSSION. WOULD ANYBODY LIKE TO RAISE QUESTIONS FOR EITHER ONE OF OUR SPEAKERS? >> CAN WE TAKE DOWN THE SLIDES SO WE CAN SEE EVERYBODY? >> I THINK RUTH ANNE HAD HER HAND UP. >> CHARLEY AND RAZI, THESE WERE REALLY WONDERFUL PRESENTATION. THANK YOU SO MUCH. I WANT TO ASK CHARLIE A COUPLE OF QUESTIONS. FIRST ACKNOWLEDGING HOW EXCITED WE ALL ARE TO SEE THE IMPLANT COMING ON, IT'S GREAT THAT YOU DIDN'T REST ON YOUR SEMI-CIRCULAR CANAL LAURELS, TAKING ON THE NEW CHALLENGE. I WONDER, YOU KNOW, MANY PEOPLE WORKING ON THE BASIC SCIENCE OF VESTIBULAR INNER EAR ARE INTERESTED IN DIFFERENTIAL ENCODING OF HEAD MOTION STIMULI BY DIFFERENT AFFERENT POPULATIONS, AND I WONDER IF YOUR WORK WITH THE IMPLANTS FIRST GIVE YOU ANY INSIGHT INTO WHICH POPULATIONS ARE MORE ENGAGED, THE IRREGULAR OR THE REGULARLY DISCHARGING AFTER RANS, AND ALSO YOU ACTUALLY NOW HAVE HUMAN EXPERIMENTS ON WHAT HAPPENS WHEN YOU STIMULATE THE BRAIN IN THIS WAY, WHETHER YOU'RE GAINING ANY BASIC SCIENCE INSIGHTS THAT YOU WEREN'T EXPECTING? >> THANK YOU, RUTH ANNE. AS YOU KNOW, THE IRREGULARLY FIRING VESTIBULAR AFFERENTS TEND TO BE MORE SENSITIVE TO -- TRADITIONALLY APPLIED CURRENTS, THEY TEND TO BE LARGER IN CURRENT AS WELL. SO GIVEN THAT WE ONLY USE ONE ELECTRODE PER SEMI-CIRCULAR CANAL, WE'RE EFFECTIVELY TREATING ALL NEURONS IN THAT BRANCH OF THE VESTIBULAR NERVE AS ONE NEURON, BUT IT'S PRETTY CLEAR TO ME THAT WE'RE PREFERENTIALLY STIMULATING IRREGULAR AFFERENTS WHEN WE'RE AT LOWER CURRENTS, AND THEN AS WE INCREASE OUR CURRENT, WE'RE SURELY SHOCKING THE ENTIRE NERVE. I DIDN'T HAVE TIME TO GO OVER IT TODAY, BUT -- AND NOW BRIAN MORRIS AT OUR LAB HAVE BEEN DOING SIMILAR RECORDING FROM THE VESTIBULAR NERVE FOR SOME TIME NOW, BOTH IN CHINCHILLAS AND RHESUS MONKEYS. IT'S CHALLENGING BECAUSE THE -- ARTIFACT IS HUGE BUT WE'RE ABLE TO SEE THAT -- ARE MORE SENSITIVE TO THE STIMULI WE DELIVER AND I THINK THAT HELPS EXPLAIN WHY WE WERE GETTING KIND OF MIXED RESULTS WHEN WE WERE GIVING VELOCITY ENCODED STIMULUS TO WHAT REALLY ARE NEURONS THAT WANT TO SEE AN ACCELERATION TYPE OF SIGNAL. SO I'M REALLY HOPEFUL THAT THIS FINDING WE FOUND IN ONE OF OUR HUMAN SUBJECTS IS GOING TO PLAY OUT IN OUR OTHER EIGHT. I THINK IN TERMS OF OTHER THINGS THAT WE'VE FOUND, ONE NICE THING ABOUT THIS IS THAT AS FAR AS I KNOW, IT'S THE ONLY WAY FOR AN EXPERIMENTALIST TO TURN ON AND TURN OFF A LABYRINTH REPEATEDLY. WE CAN DO SORT OF A ONE-WAY EXPERIMENT AND DESTROY THE INNER EAR BY DO BE A LABYRINTHECTOMY AND WATCH HOW THE BRAIN COMPENSATES FOR THAT UNILATERAL LOSS, BUT THIS IS A CHANCE NOWP WHERE WE CAN TURN ON, TURN OFF OR EVEN REORIENT THE LABYRINTH IN THE ANIMAL'S HEAD. AND WE CAN, USING SOFTWARE, REVERSIBLY REORIENT THE SENSOR IN OUR PATIENTS TANGENTIALLY AS WELL, SO THIS ALLOWS US TO GET SOME REAL INSIGHTS INTO THE TEMPORAL DYNAMICS NOT ONLY TO HOW THE BRAIN COMPENSATES AND RECOVERS AFTER INJURY, BUT ALSO HOW IT COMPENSATES DURING -- FUNCTION AS WELL. >> THANKS. >> JUST TREMENDOUS TALK, CHARLEY. SO INSPIRING. I GUESS FROM A BASIC RESEARCH POINT VIEW, I'M WONDERING NOW THAT YOU CAN STIMULATE ANY ONE OR ANY COMBINATION OF SENSORY SURFACES, DO YOU GET SOME SENSE FOR HOW THE NERVOUS SYSTEM IS INTEGRATING IT? IN OTHER WORDS, DOES THE FRAMEWORK THAT YOU CAME TO THE SYSTEM WITH ACTUALLY APPLY OR ARE THERE SURPRISES NOW THAT YOU CAN DO ONE OR A FEW AT A TIME? >> THANKS, DAN. FOR CANALS, PRETTY MUCH EVERYTHING IS WORKING OUT THE WAY YOU'D EXPECTED BASED ON THINGS THAT SUZUKI AND TELLEN PUBLISHED THE YEAR I WAS BORN, SO WE KNEW IN THE EARLY 60s THAT YOU COULD SELECTIVELY STIMULATE DIFFERENT BRANCHES OF THE VESTIBULAR NERVE GOING TO DIFFERENT CANALS, AND THE RESPONSES YOU'D ELICIT AND PROBABLY THE PERCEPTION THAT IT ELICIT WOS KINS WOULD KIND OF ADD UP IN A VECTOR SENSE. SO WHAT WE'VE SEEN IN OUR ANIMALS AND IN OUR PATIENTS HAS BORNE THAT OUT. FOR -- AND SACULE IT'S REALLY CONFUSING BECAUSE WITH THE CANALS, I CAN LOOK AT AN EYE MOVEMENT THAT A PERSON IS MAKING AND TELL YOU WHICH COULDALS WERE EXCITED OR INHIBITED. WITH THE UTRICLE AND SACULE, IT'S NOT A ONE TO ONE MAPPING THAT'S REVERSIBLE. INSTEAD, THERE ARE ALL KINDS OF STIMULI, YOU CAN TILT IN THE GRAVITATIONAL FIELD, YOU CAN TRANSLATE, THAT ARE IMPACTING THE UTRICLE AND SACULE IN WAYS THAT ARE COMPLICATED FOR US TO WORK OUT, AND THEN THE EYE MOVEMENTS THAT WE GET PARTICULARLY IN OUR -- ANIMALS HAVE SIX DIMENSIONS TO THEM AND THEY DON'T MAP OBVIOUSLY BACKWARD TO THE NATURAL STIMULI. SO WE'VE HAD TO DO A LOT OF STATISTICAL MODELING JUST TO MAKE UP SOME KIND OF A REVERSE MODEL TO EXPLAIN TO OURSELVES WHEN WE SEE EYE MOVEMENTS IN AN ANIMAL THAT GO IN A CERTAIN DIRECTION, WHAT WITH WE ACTUALLY GIVING THE ANIMAL A --. I'M HOPING THIS WILL BE A CASE WHERE A SCIENTIST CAN REALLY BENEFIT LEARNING FROM -- NON-HUMAN PRIMATES AND ULTRAMATELY PEOPLE BECAUSE THERE WE HAVE A BETTER SENSE OF HOW A -- ON A MAP -- AS OPPOSED TO -- ANIMALS WHERE FRANKLY SO FAR IT'S AN OPEN QUESTION IN OUR LAB, EXACTLY WHY WE GET THE EYE MOVEMENTS THAT WE DO. >> LISA, DID I SEE YOUR HAND UP EARLIER? I'M SORRY. OKAY. LAURA. >> THAT WAS A FANTASTIC TALK. BOTH PRESENTATIONS WERE GREAT. A QUICK QUESTION. IN YOUR EARLY SUMMARY OF THE INITIAL NINE PATIENTS, YOU MENTIONED THAT THE PROGRESS IN GAIT WAS LESS THAN YOU HOPED FOR. I'M CURIOUS WHETHER THE ACCELERATION BASED STIMULATION IN THAT ONE SUBJECT HAD AN AFFECT ON GAIT AND WHETHER YOU ANTICIPATE THAT THAT COULD REALLY HAVE AN IMPACT THERE. >> THANKS, LAUREL. ACTUALLY TO BE COMPLETELY HONEST, WHEN WE STARTED THIS WORK, I WAS ALL ABOUT EYE MOVEMENTS AND THE VESTIBULOOCULAR REFLEX AND THOUGHT THAT WAS THE ONLY THING THAT WAS GOING TO MATTER. AND I HAD THIS MISCONCEPTION THAT IF WE RETURNED SOME CANAL FUNCTION, WE WEREN'T GOING TO DO ANYTHING FOR POSTURE AND GAIT BECAUSE I THOUGHT THAT POSTURE AND GAIT REALLY DEPENDED MAINLY ON THE -- AND SACULE, SO I WAS SURPRISED TO SEE JUST HOW GREAT AN EFFECT WE'RE GETTING IN POSTURE AND GAIT AN IMPLANT THAT MAKES NO EFFORT AT ALL TO RESTORE UTRICLE AND SACULE FUNCTION. WHERE THE RESULTS ARE A LITTLE BIT -- IS FOR REALLY QUICK HEAD ROTATIONS, WE WEREN'T SEEING THE HUGE EYE MOVEMENT THAT I WOULD HAVE EXPECTED BASED ON OUR ANIMAL WORK, AND THIS IS WHERE ADDING THAT ACCELERATION -- PARADIGM HAS REALLY MADE A BIG DIFFERENCE IN ONE SUBJECT, AND I'M HOPING WE'LL SEE FOR THESE QUICK HEAD MOVEMENT EYE MOVEMENT REFLEXES THAT WE'LL BETTER -- >> I SEE DR. TUCCI'S CAMERA IS ON. >> I JUST WANTED TO ASK CHARLEY A QUICK QUESTION AS WELL. SO I IMAGINE IN THINKING DOWN THE ROAD HOW THIS WOULD BE APPLIED IN CLINICAL POPULATIONS THAT MANY OF THESE PATIENTS WILL HAVE BILATERAL LOSS OF HEARING AS WELL AS VESTIBULAR FUNCTION, AND I KNOW YOU THOUGHT ABOUT COMBINED COCHLEAR IMPLANTS AND VESTIBULAR IMPLANTS. CAN YOU TALK ABOUT THAT A LITTLE BIT? >> YEAH, THIS IS A GREAT EXAMPLE OF THE DIFFERENCE BETWEEN RESEARCH IN AN ACADEMIC LAB AND DEVELOPMENT OF A MEDICAL DEVICE. OBVIOUSLY WE'VE KNOWN FOR A LONG TIME THAT HEARING IS GOING TO BE EITHER ALREADY DOWN IN OUR CANDIDATES SO IT WOULD BE NICE TO HAVE A COCHLEAR IMPLANT, OR IT'S GOING TO BE DAMAGED. IN FACT, I TOLD ALL OF OUR PATIENTS TO EXPECT A DEAF EAR AFTER IMPLANTATION AND WE WERE SURPRISED THAT THEY MAINTAINED GOOD HEARING IN THE FIRST FOUR OUT OF FOUR PATIENTS. SO -- AT A COCHLEAR ARRAY. IT'S NOT A HARD CONCEPT HOW YOU DO IT. BUT THE -- HAS 12 CHANNELS OF STIMULATION AVAILABLE. WE DECIDED TO ANGLE FORWARD HAVING MULTIPLE ELECTRODES PER CANAL TRYING TO MAKE SURE WE COULD GET THE RESULT WE'RE AFTER, RATHER THAN RESERVING NINE OF THOSE EE LEK TROATS FOR A COCHLEAR IMPLANT AND THEN ONLY HAVING ONE ELECTRODE PER CANAL TO GET IT WHERE IT NEEDS TO GO. ONCE WE FOUND THAT WE DO OKAY AND REALLY WE ALWAYS HAVE AT LEAST TWO ELECTRODES THAT THAT WORK OKAY FOR AMPULLA, WE COULD HAVE MADE A QUICK SWITCH TO A COMBINED COCHLEAR VESTIBULAR IMPLANT BUT THE DESIGN SIG CYCLES, THE FDA -- ARE VERY LONG, SO THIS IS WHERE THE DESIGN TIME AND CYCLES FOR DEVELOPMENT ARE DIFFERENT FOR RESEARCH AND THIS IS WHY I THINK ACADEMIC RESEARCHERS AND INDUSTRY DEVELOPERS WORK AT DIFFERENT TIME SCALES BUT LEAD TO OVERLAP. THERE ARE OTHER DEVICES, A SYSTEM BEING USED IN SEATTLE, ANOTHER BEING USED IN EUROPE THAT INCLUDE COCHLEAR -- ARRAY AND -- ARRAY. ALL OF THOSE HAVE BEEN PUT INTO PATIENTS WHO NEEDED A COCHLEAR IMPLANT AT THE TIME, AND SO IN OUR CASE, WE'VE BEEN WORKING IN PATIENTS WHO DIDN'T NEED A COCHLEAR IMPLANT BEFORE IMPLANTATION. MY HOPE IS THAT OUR FUTURE WILL SHOW THAT THIS WORKS, WE'LL HONE DOWN TO ONE ELECTRODE PER CANAL AND THEN WE'LL BE ABLE TO ADD A COCHLEAR ARRAY THAT WE'D EITHER PUT IN AT THE TIME SURGERY OR BANK ELSEWHERE IN THE TEMPORALIS MUSCLE SO THAT IF A PERSON DOES HAVE HEARING LOSS, WE'D BE ABLE TO PUT IT BACK IN. >> GREAT. >> I DID HAVE A SIMILAR QUESTION TO WHAT DEB JUST ASKED, BUT ALONG THOSE LINES RELATED CLINICAL QUESTION IS, DO YOU THINK THE VESTIBULAR IMPLANTS COULD BE USED FOR PATIENTS WITH MENINGITIS? THEY WOULD START OUT, OF COURSE, WITH SIGNIFICANT HEARING LOSS AND I'M THINKING ABOUT THAT BONY GROWTH INSIDE THE LABYRINTH. SO I WOULD BE DER I WONDER IF IT FEASIBLE AT ALL. >> THAT'S AN INTERESTING QUESTION. WE'VE HAD A NUMBER OF APPLICANTS TO THE TRIAL, I THINK WE ARE WELL OVER 300 UNIQUE APPLICATIONS RIGHT NOW. SOME OF THOSE ARE FOLKS WHO HAVE MENINGITIS WHO INTERESTINGLY HAVE -- BUT DON'T NEED COCHLEAR IMPLANT. THEN THERE ARE OTHERS WHO HAVE LOST THEIR HEARING. IN THOSE CASES, I THINK THAT HEARING WINS OVER VESTIBULAR IMPLANT RESEARCH AND ADVICES THOSE PATIENTS TO GET A COCHLEAR IMPLANT EARLY BEFORE THEY HAVE OSSIFICATION THAT MAKES GETTING A COCHLEAR IMPLANT IN THERE IN THE FUTURE HARD. BUT I THINK WE'LL FIND THAT WITH VESTIBULAR IMPLANTS, ALTHOUGH WE'RE NOT IMPLANTING ANYONE WITH MENINGITIS, IT WOULD BE A CONFRONTATION IN OUR INVESTIGATION -- NOW, RIGHT NOW. I THINK WE'LL FIND THAT IT WILL WORK ABOUT AS WELL AS COCHLEAR IMPLANTS DO. IF YOU GET IT IN EARLY, WHILE THE ANATOMY STILL ALLOWS YOU TO DO IT, BEFORE THE LABYRINTH IS FULL BONE, YO OF BOARNTION YOU CAN GET A B ONE, YOU CAN GET A GOOD RESULT. >> I THINK WITH THAT, WE'RE GETTING CLOSE TO THE END OF THE MEETING. DEB? >> ALL RIGHT. GOOD, YES, THANK YOU ALL VERY MUCH. THOSE WERE FANTASTIC TALKS AND A GREAT DISCUSSION. SO ILL THINK GIVEN THE HOUR, I WILL JUST WRAP IT UP, UNLESS THERE ARE ANY FINAL COMMENTS. I THINK CRAIG HAD SOMETHING ELSE. YEP. >> ACTUALLY TWO QUICK COMMENTS. FIRST A REMINDER TO MEMBERS TO SIGN AND RETURN YOUR CONFLICT OF INTEREST DOCUMENTS, OKAY? AND THEN, ONE OF YOUR FELLOW COUNCILMEMBERS, CYNTHIA MORGAN, ASKED ME TO RAISE AN ISSUE WITH THE COUNCIL. SHE WANTED TO KNOW IF MEMBERS WOULD BE INTERESTED IN SIGNING OFF ON A LETTER TO DR. FRANCIS COLLINS IN RECOGNITION OF HIS CONTINUED SERVICE GOING FORWARD AND THANKING HIM FOR HIS LONG-TERM SERVICE. HE'S ONE OF THE FEW NIH DIRECTORS WHO HAVE SPANNED THREE PRESIDENTS, AND IT TAKES A LITTLE HOOTSBA TO DO THAT AS WELL AS THE FANTASTIC CLI CLINICAL AND SCIENTIFIC SHOW THAT HE PUTS ON FOR NIH IN REPRESENTING US. I'M SEEING SOME THUMBS UP. I'M SEEING SOME NODS. SO I WILL CHALLENGE CYNTHIA TO GO AHEAD AND WRITE SOMETHING, SEND TO ME AND I'D BE HAPPY TO SEND THAT AROUND AND GET SOME SIGNATURES. ONE NOTE. I ONLY KNOW OF ONE TIME IN HISTORY WHEN THE COUNCIL HAS COMMUNICATED TO THE INSTITUTE DIRECTOR, OR THE NIH DIRECTOR. IT WAS A NEGATIVE COMMENT AT THAT POINT IN TIME. SO HE'LL BE APPRECIATIVE TO GET A VERY POSITIVE ONE THIS TIME. THAT'S ALL I HAD, DEB. >> THANK YOU. ALL RIGHT. WE'LL LET EVERYBODY GO. THANKS SO MUCH FOR YOUR TIME AND ALL OF YOUR EXPERTISE. TAKE CARE, AND WE'LL SEE YOU IN MAY.