WELCOME TO THE NATIONAL CENTER FOR COMPLIMENTARY AND INTEGRATIVE HEALTH FOR NCCIH HOT TOPIC WEBINAR ON PROBIN INTER O CEPTIVE PROCESSES OF BEHAVIORIAL, PSYCHOLOGICAL AND NEUROPHYSIOLOGICAL LEVELS. I'M DR. CHEN, PROGRAM DIRECTOR AT NCCIH, I WILL SERVE AS THE MODERATOR AND DISCUSS ANT AT TODAY'S WEBINAR. BEFORE WE GET STARTED I WOULD LIKE TO SHARE TODAY'S WEBINAR AGENDA, INTRODUCE OUR SPEAKERS, PANELISTS AND SHARE SOME HOUSE OR INTERNET KEEPING ISSUES. WE WILL BEGIN THE WEBINAR WITH AN OVERVIEW BY DR. ALAN LUND GREN, DUE TO AN TECHNICAL ISSUE WE WILL CHANGE THE ORDER SLIGHTLY TODAY SO THE FIRST SPEAKER WILL BE DR. FRANCOs FROM THE NCCIH INTRAMURAL PROGRAM, ASSESSING INTROCEPTIVE NEURONETWORKS VIA VAGUS. OUR SECOND SPEAKER WILL BE DR. JEANIE PARK, MICRONEUROGRAPHY TECHNIQUE, APPLICATIONS OF INTER O CEPTIVE RESEARCH AND OUR LAST SPEAKER WILL BE DR. WOLF MEHLING, VARIATIONS OF INTER O CEPTIVE EXPERIENCE AT THE INTERFACE, IF YOU HAVE QUESTIONS PLEASE E-MAIL AT THE E-MAIL AT THE BOTTOM OF THE SCREEN. OR USE THE NIH FEEDBACK FORM, WE WILL TRY TO GET TO AS MANY OF YOUR QUESTIONS DURING THE Q&A SESSION. FOLLOWING THE 3 SPEAKERS, OUR PANEL DISCUSSIONS REPRESENTING NIH INSTITUTES AND OFFS WILL SHARE WHETHER THEIR PERSPECTIVES RELATED TO TODAY'S WEBINAR TOPIC. EACH DISCUSSION WILL PRESENT A SLIDE, SPEAK FOR A MACHINEUTE OR 2, WE WILL BETO BEGIN WITH DR. JEANIE SIMONS AND THEN DR. JEAN ON NEUROLOGICAL DISORDERS AND STROKE. DR. STEVE GRANT. --AND NIMH, AS WELL AS DR. DANA FROM THE NIH OFFICE OF BEHAVIORIAL AND SOCIAL SCIENCE RESEARCH OBSSR AND WE WILL END WITH DR. EMILLEGALS SKPE BAKUGAN MYSELF FROM NICCH. AGAIN YOU'RE WELCOME TO E-MAIL YOUR QUESTIONS TO US AT THE WEBINAR CUE AND MAIL AND MAIL.NIH.GOV ANYTIME DURING THE PANEL DISCUSSION. --NOW WITHOUT FURTHER ADIEU DR., PLEASE SHARE YOUR SCREEN TO BEGIN THE WEBINAR OVERVIEW. >> THANK YOU AND IT IS A PLEASURE TO ATTEND THIS EVENT VIRTUALLY. CAN YOU SEE THE SLIDES? YEAH, GOOD. SO I WILL GIVE A BIT OF AN INTRODUCTION TO THIS WEBINAR, PLACING THE VARIOUS TALKS THAT YOU'LL BE HEARING IN THE CONTEXT OF INTER O ACCEPTION. SO WHY IS NCCIH INTERESTED IN INTROCEPTION? IT'S--IT'S A CONTEXT RIGHT THAT HAS A LOT TO DO WITH THE MIND AND BODY INTERFACE, RIGHT? AND NCCIH IS REALLY INTERESTED IN PRACTICES, TREATMENTS THAT WE CALL MIND AND BODY THAT REALLY ALSO HAVE TO DO WITH THE MIND-BODY INTERFACE. SO JUST TO GO INTO A BIT MORE DETAIL ABOUT THIS, WHAT TYPES OF PRACTICES ARE WE TALKING ABOUT OR TREATMENTS? WELL, HAVE YOU SOME WHERE WE CALL THE THERAPEUTIC INPUT OF THE INTERVENTION OR THE PRACTICE IS PRIMARILY MENTAL BUT CAN HAVE EFFECTS, PHYSIOLOGICAL EFFECTS ON THE BODY. AND THEN HAVE YOU OTHER SITES OF PRACTICES LIKE FOR EXAMPLE, MANUEL THERAPIES OR ACCUPUNCTURE WHERE THE PRIMARY THERAPEUTIC INPUT IS PHYSICAL BUT THEN THEY CAN ALSO HAVE AN EFFECT ON THE NERVOUS SYSTEM. AND THEN YOU HAVE THERAPIES THAT ARE SORT OF MIXED LIKE TAI, CHI, AND YOGA WHY YOU HAVE A MIXTURE OF MENTAL AND PHYSICAL AND THERAPEUTIC INPUT AND ALSO THERAPEUTIC EFFECTS. SO THESE TYPES OF MIND AND BODY BOTH INPUT AND OUTPUT OR EFFECTS, WE BELIEVE THAT THEIR RESEARCH ON INTROCEPTION IS REALLY RELEVANT TO THESE TYPES OF THERAPIES. SO LAST YEAR THE NIH BLUEPRINT INITIATIVE, SPONSORED A WORKSHOP THAT WAS LED BY NCCIH, ON INTER O ACCEPTION AND THIS WAS A FASCINATING WORKSHOP WHERE THERE WAS A LOT OF DISCUSSION ABOUT THE DEFINITIONS OF INTROCEPTION, WHAT DOES IT MEAN, WHAT DOES IT INCLUDE AND WHAT ARE THE GAP AREAS IN RESEARCH THAT ARE NEEDED BOTH ON THE BASIC SIDE AND ALSO IN CLINICAL SIDE TO MOVE THIS FIELD FORWARD WITH PARTICULAR INTEREST IN DEVELOPING RESEARCH THAT WILL THEN ENHANCE OUR UNDERSTANDING OF MIND AND BODY THERAPIES. SO WHOO IS THE DEFINITION OF INTROCEPTION, THAT IS NOT SOMETHING THAT IS A SIMPLE THING AND PEOPLE ARE NOT ALWAYS IN COMPLETE PERFECT AGREEMENT AND THERE WAS A LOT OF DEBATES AT THE WORKSHOP ABOUT WHAT--HOW DO YOU DEFINE INTROCEPTION AND THIS IS THE DEFINITION THAT WAS KIND OF THE CONSENSUS, THAT EMERGED FROM THIS PARTICULAR WORKSHOP, NOW THERE ARE OTHER DEFINITIONS BUT FOR THIS PARTICULAR--AT THIS PARTICULAR WORKSHOP, THIS IS WHAT WE LANDED ON, PROCESSES BY WHICH THE BODY SENSES, INTERPRETS, INGRETS AND REGULATES SIGNALS FROM WITHIN ITSELF. SO JUST TO GIVE A LITTLE MORE MEANING TO THESE WORDS SO WHAT DO WE MEAN BY WITHIN ITSELF? SO, THESE ARE SIGNALS THAT MERGE FROM THE INTERIOR OF THE BODY, THE INSIDE OF THE BODY AS OPPOSE TO SIGNALS THAT EMERGE FROM THE OUTSIDE FOR EXAMPLE, HEARING, DOES NOT INCLUDE HEARING, TASTES, SMELL, SIGHT. IT DOES INCLUDE INPUT FROM--FOR EXAMPLE, MUSK LO SKELETAL ISSUES BUT DEEP TO THE SKIN AND THIS IS WHERE THERE'S SOME DEBATE AS TO FOR EXAMPLE PROPRIMATES O ACCEPTION AND PART OF INTROCEPTION AND WE DECIDE THAD AS LONG AS SIGNALSORIGEINATE FROM TISSUES DEEP IN THE SKIN THEN WE WOULD INCLUDE THEM ON INTROCEPTION AND THE DOCTOR WILL BE TALKING ABOUT SOME OF THOSE TYPES OF INTROCEPTIVE SIGNALS THAT ARE PART OF THAT CATEGORY. IMPORTANTLY--THIS PROCESS OF SENSING, INTERPRETING, INTEGRATING INCLUDING CONSCIENCE AND UNCONSCIENCE PHENOM NATIONAL LIBRARY OF MEDICINE FACTORS AND THE OTHER THING TO POINT OUT HERE IS THAT THERE ARE DIFFERENT TYPES OF [AUDIO CUTS OUT ] THAT THEN FEEDBACKOT BRAIN VIA A CHEMICAL OR HUMERAL PATHWAY THAT ARE CAN INTROCEPTIVE. SO ON THIS WORKSHOP WE WILL FOCUS ON NEURAL CIRCUITS AND ALSO, THIS WAS THE FOCUS OF A RECENT CONCEPT CLEARANCE THAT WE PRESENTED AT OUR COUNCIL BACK IN FEBRUARY ON FUNCTIONAL NEURAL CIRCUITS OF INTROCEPTION AND THIS IS WHAT WE WILL TALK ABOUT TODAY. SO WHAT ARE SOME OF THESE NEURAL PATHWAYS, SO WE'RE GOING--WE BUILT DIAGRAMS TO SORT OF--VARIOUS SPEAKERS WILL BE REFERRING TO THESE DIAGRAMS BECAUSE THE ANATOMY OF THESE DIFFERENT NEURAL CIRCUIT SYSTEM COMPLEX, IT INVOLVES A LOT OF THE--WHAT WE CALL THE AUTONOMIC NERVOUS SYSTEM, WITH DIFFERENT PARTS OF THE AUTONOMIC NERVOUS SYSTEM, SO I WILL DESCRIBE THEM BRIEFLY TO YOU FOR NOW. SO AS FAR AS ASCENDING NEURAL PATHWAYS, I--OH, I WAS HOPING TO BE ABLE TO USE MY LITTLE--MY LITTLE DRAWING TOOL HERE BUT I DON'T SEE IT. SO I GUESS I WILL--I WILL POINT--HOPEFULLY YOU CAN SEE MY POINTER. SO, AS FAR AS THE ASCENDING NEURAL PATHWAYS, AS A PART OF THE AUTONOMIC NERVOUS SYSTEM, YOU YOU HAVE SOME PATHWAYS THAT ARE PART OF THE AUTONOMIC--PARASYMPATHETIC NERVOUS SYSTEM, WHERE THE AFERENT PATHWAYS ARISING FROM SAY THE GUT OR THE HEART GO UP THE ASCENDING PATHWAYS FOR THE JUGULAR GANGLION TO THE BRAIN VIA THE VAGUS NERVE, THEN YOU ALSO HAVE PATHWAYS THAT EMERGE FROM THE--FOR EXAMPLE, THE MUSK LO SKELETAL ISSUES THAT GO UP VIA SPINAL NERVES, RIGHT? THAT ALSO SYNAPSE AND DORSAL GANG LE AN AND THEN GO UP TO THE BRAIN THAT WAY. NOW THESE PATHWAYS WILL INVOLVE IN REGIONS OF THE BRAIN SYNAPSE INCLUDING THE BRAIN STEM AND THE NUCLEUS SOLARITRIUS, AND BACK UP AGAIN TO THE AREAS OF THE HYPOTHALAMUS AND ALSO THERE ARE SIGNALS AND WE WILL BE HERE QUITE A LOT ABOUT THIS TODAY, THAT WILL THEN SORT OF GENERATE INPUT TO STRUCTURES OF THE BRAIN EMILY CIBOL AND PARALIMBIC SYSTEM, AND THE PREFRONTAL CORTEX AREAS THAT HAVE TO DO WITH EMOTION REGULATION. NOW AS FAR AS DESCENDING NEUROPATHWAYS, AGAIN, YOU HAVE SOME PATHWAYS THAT WILL GO DOWN IN THE AUTONOMIC NERVOUS SYSTEM, VIA EITHER THE PARASYMPATHETIC EFER ENSEL, VIA THE VAGUS NERVE AND THEN ALSO SYMPATHETIC EFERENCE THAT WILL HAVE VARIOUS DIFFERENT ROUTES, ALSO SIN ESTIMATE THADING THROUGH PARAVERTEBRAL AND/OR VERTEBRAL GANGLIA AND INNERIVTE STRUCTURES SUCH AS HEART, BLOOD VESSELS, GUT, ET CETERA. SO AS YOU CAN SEE THESE PATHWAYS ARE COMPLEX BUT JUST TO HELP PEOPLE--KEEP REMINDING PEOPLE AS WE GO THROUGH THE VARIOUS TALKS, WE WILL POINT OUT WHICH PART OF THIS ANATOMY THESE TALKS ARE REFERRED TO. SO OUR 3 TALKS INTROCEPTIVE NEURAL CIRC YOUS VIA THE VAGUS NERVE, AND DR. PARKS VIA TECHNIQUES AND APPLICATIONS AND RESEARCH, AND DR. MEHLING AND THE MIND AND BODY AND WHICH PARTS OF THE INTROCEPTIVE PATHWAYS DO THESE TALKS GOING TO ADDRESS, SO FIRST--HERE WE GO, WE CANNAN OITATE. THAT'S WHAT I WAS GOING TO DO. SO I WILL JUST HIGHLIGHT THE AREA THAT DR. FRANGOS WILL ADDRESS. AND THE DOCTOR WILL TALK ABOUT AFERENT AND ALSO ABOUT EFERENT BUT MOSTLY AFERENT AND THEN SHE WILL REFER TO THE BRAIN AREAS THAT I MENTIONED PARTICULARLY THE INSURVEYS LIAISON. DR. MEHLING WILL TALK ABOUT THOSE SOMATOSENSORY AFERENTS THAT I HIGHLIGHTED EARLIER THAT ARISE FROM THE MUSK LO SKELETAL ISSUES AND GOES UP VIA THE SPINAL NERVE. SO [LAUGHTER] I'M GOING TO HAND IT OVER TO FIRST DR. FRANGOS, OKAY, GOOD. HI, EVERYONE AND THANK YOU FOR INVITING ME TO SPEAK TODAY AND SO, I HAVE ACTUALLY A VERY SHORT OUTLINE FOR US TODAY. AND SO, I WILL FOCUS ON THE BRAIN RESPONSES TO EPITHELIAL ROUGH ATOM CEPTIVE SIGNALS BY MEASURED BY FUNCTIONAL MRI AND WILL DISCUSS BRAIN RESPONSE TO INTRINSIC STIMULATION AND FINALLY HOW WE CAN MODULATE RECEPTIVE PATHWAYS VIA THE VAGUS NERVE AND ALONG THE WAY, I WILL POINT OUT GAPS IN THE FIELD THAT COULD USE ATTENTION TO HELP PUSH US FORWARD. SO SO ELEN JUST COVERED VERY NICELY THE ASCENDING PATHWAY WHICH I WAS GOING TO GO THROUGH, BUT VERY BRIEFLY AGAIN, JUST TO GIVE YOU A BIRD'S EYE VIEW BEFORE I JUMP INTO THINGS, THIS AFER ENSEL ARE CONVEYED VIA AUTONOMIC NERVES THAT TRAVEL WITH THE SPINAL NERVES AND SYNAPSE ON LAMINA 1 OF THE SPINAL CORD AND THEN AS I MENTIONED, AS HELEN MENTIONED AS WELL THEY TRAVEL OUTSIDE THE SPINAL CORD VISA THE VAGUS NERVE AND THESE ARE LOCATED WITHIN THE LOW DOSE AND THE SUPERIOR GANGLION AND THESE PROJECT DIRECTLY TO THE NTS SPECIFICALLY WITHIN THE MEDULLA SECTION OF THE BRAIN, AND THE FIBERS FROM THE FINAL CORD ALSO PROJECT ON TO REGIONS OF THE SPINAL CORD AND THEY HAVE SUBCORTICAL INPUTS THAT I'LL GET INTO NOW. SO COMMON WAY TO PROBE INTROCEPTION WITH fMRI IS TO ASK PARTICIPANTS TO PAY ATTENTION TO BODY SIGNALS AND THIS COULD BE SOMEWHAT CONFOUNDING BUT INTROCEPTION INHERENTLY REQUIRES ATTENTION TO BODILY STATES. SO STUDY SOMETIMES USE A VARIATION OF THE HEART BEAT COUNTING TASK OR, SORRY, THE BREATHING DETECTION TASK AND THESE SIGNALS ARE TYPICALLY COMPARED TO RECEPTIVE STIMULI AS CONTROLS LIKE DETECTING A DOT ON THE SCREEN FOR EXAMPLE OR LOOKING AT TEXT THAT IS BLINKING ON THE SCREEN AND OTHER INTROCEPTIVE TASKS USED TO PROBE THIS INCLUDE THINGS LIKE ESOPHAGEAL AND [INDISCERNIBLE] AS WELL AND EVEN THOUGH PAIN SENSATIONS CAN BE SOMATIC IT DOES FALL UNDER THE INTROCEPTION AND THERE IS EXTENSIVE OVERLAP BETWEEN THESE PATHWAYS, BUT FOR THIS PART OF THE TALK, I WILL FOCUS ON AWARENESS OF BODY SENSATIONS LIKE HEART BEATS AND BREATHING. AND THEY FOUND THAT FOCUSING ON HEART BEAT PRODUCING SKIN TEMPERATURE PRODUCED GREATER ACTIVATION WITHIN THE ENSUE LA AND LIMBIC REGIONS WE SEE HERE IN YELLOW AND--SORRY--FOCUSING ON THE SKIN TEMPERATURE ACTIVATED THESE REGION BUT TO A LESSER EXTENT AND GREATER WIDE SPREAD ACTIVATIONS SEEN IN BLUE HERE ARE FOUND WITHIN THE PRIMARY SENSORY CORTEX, AND EVEN THE OCCIPITAL CORTEX, USING CUES FOR EACH CONDITION. SO IN THIS CONJUNCTION ANALYSIS HERE, WE SEE SHARED REGIONS THAT RESPOND TO FOLK BEUSING ON BOTH INTROCEPTIVE CONDITIONS COMBINED AND BOTH MAPPED ON TO THE INSURVEYS LA AND SENSORY MOTOR REGIONS HERE IN RED, SO WE SLEEP APNEA AND OBESITY THAT INTROCEPTION FROM BOTH SOURCES SHARE OVERLAPPING REGIONS BUT ALSO HAVE DISTINCT REPRESENTATIONS AS WELL. AND IN THIS PARTICULAR STUDY, THE PARTICIPANTS ALSO COMPLETED THE MINA, THE MULTIDIMENSIONAL ASSESSMENT OF AWARENESS AND IT WOULD HAVE BEEN NICE FOR THIS TALK TO COME AFTER WILKES WHO WILL SPEAK MORE ABOUT THIS BUT THEY FOUND A TREND, A TREND IN NEGATIVE CORRELATION WITH SUBJECTS WITH FEWER HEART BEAT COUNTING ERRORS HAD HIGHER SCORES ON THE FIRST FACTOR OF THEIR FACTOR ANALYSIS AND THIS INCLUDED CHARACTERISTICS LIKE INCREASED TEND ENSEL TOW NOTICE BODY SENSATIONS FOR EXAMPLE. NOW THIS NEXT STUDY HAD SIMILAR FINDINGS USING A BREATHING TASK AND THEY ALSO FOUND THAT THE MORE ACCURATE PARTICIPANT WAS AT BREATHING DETECTION THAT THE GREATER ACTIVITY THEY HAD WITHIN THE INSULI AND THEY ALSO FOUND ACTIVITY IN THE SOMATOSENSORY REGIONS DURING THE INTROCEPTIVE CONDITION, COMPARED TO THE EXTROOACCEPTION POSITION. AN INTERESTING PART OF THIS STUDY WAS THEY INCLUDED A COHORT OF PATIENTS THAT HAD FOCAL REEJIONS THAT OVERLAPPED IN THE AREA IN RED, AND COMPARED TO HEALTHY CONTROLS AND ALSO COMPARED TO ANOTHER SET OF PATIENTS THAT HAD BRAIN DAMAGE TO REGIONS RPGHT THAN THE INSULA AND THE SOMATOSENSORY-RELATED REGIONS, THE INSULI PATIENTS HAD DECREASED RECEPTIVE--SORRY, THE WHOLE PANEL IS KIND OF IN MY SLIDE HERE. THERE WE GO. THE INSULAR LESION PATIENTS HAD LESS RECEPTIVE ACCURACY COMPARED TO EXTRA RECEPTIVE CAPACITY SO THIS SUGGESTED THAT THE INSULA PLAYS A SIGNIFICANT ROLE IN BREATHING DETECTION AND THIS IS INTERESTING BECAUSE A PREVIOUS CASE STUDY BY [INDISCERNIBLE] SHOWED THAT HEART BEAT COUNTING ACCURACY WAS DELAYED AND NOT EFFECTED IN A PATIENT WITH INSULARY DAMAGE AND THE 2 DASKS ARE ARE IN FOCUS SO IT'S UNCLEAR WHETHER THE DIFFERENCES ARE METHOD LOGICAL OR NEUROLOGICAL IN THIS CASE. ALL RIGHT WHILE IT SEEMS I'VE BEEN FOCUSING MAINLYOT INSULAR ACTIVITIES THAT THESE FOUND REGIONS LIKE THE SENSORY CORTEX, ANTERIOR SINGULATE, TEMPORAL AND FRONT AT REGIONS THAT VAST LITERATURE HAS SHOWN ENGAGEMENT OF THESE REGIONS DURING EMOTIONAL AND COGNITIVE TASKS AS WELL SO IN THIS PARTICULAR STUDY, THEY HAD 3 SEPARATE META-ANALYSIS PERFORMED ON STUDIES ABOUT INTROCEPTION, SOCIAL COGNITION AND EMOTION, AND THROUGH A CONJUNCTION ANALYSIS OF THESE META-ANALYSIS, THE 3 META-ANALYSIS, THEY FOUND OVERLAP BETWEEN THE INSULAR AND THE ACC AND THE AMYGDALA AND THE CAMPUS THAT MAKE UP THIS FRONTAL TEMPORAL NETWORK AND THIS LENDS SUPPORT TO THE NOTION THAT INTROCEPTIVE SIGNALS CONVERGE AND INTEGRATE WITH THESE OTHER NETWORKS. AND IN THE SAME PAPER, THE AUTHORS COMPARED HEALTHY CONTROLS TO PATIENTS WITH LESIONS WITHIN THIS PARTICULAR NETWORK AND AS WE SEE HERE, THE PATIENTS PERFORM SIGNIFICANTLY WORSE IN EACH OF THE INTROCEPTIVE AND EMOTIONAL AND COGNITIVE DOMAINS. SO TO BRIEFLY SUMMARIZE, SO FAR, THE INSULAR PLAYS A KEEL ROPE IN THE INTROCEPTION AND THE FRONTAL TEMPORAL NETWORK SEEMS TO BE A CONVERGENT SENSOR. SOPHISTICATEDY WE DISCUSSED THE RESPONSES TO PAYING ATTENTION TO BODILY SIGNALS [AUDIO CUTS OUT ] STIMULATION. NOW THE INVASIVE APPROACH TO VAGUS STIMULATION REQUIRES AN IMPLANTED ELECTRODE AND THIS ELECTRODE AND THE LEADS ARE ATTACHED TO THE VAGUS NERVE ITSELF AND THE CERVICAL VAGUS NERVE TO THE NECK AND PROVIDES STIMULATION AND THIS IS USED FOR PATIENTS WITH EPILEPSY OR REFRECTRY, OR DEPRESSION, AND IT'S BEEN DIFFICULT TO DISCERN THE EXTENT TO WHICH THE VIA, GO, ALL ACTIVATES NETD WORKS BUT TODAY THE MECHANISMS OF ACTION UNDERLYING THESE PARTICULAR CONDITIONS ARE STILL NOT ENTIRELY UNDERSTOOD. HOWEVER, WE NOW DO HAVE NONINVASIVE TOOLS THAT ALLOW US TO GAIN ACCESS TO THE VAGALL AFERENT FIBERS VIA ELECTRICAL STIMULATION OF THE NECK AND THE STIMULATION OF THE BRANCH OF THE VAGUS NERVE AS WELL. SO RECENTLY USING fMRI SHOWED WE CAN ACCESS THE PRIMARY VAGALLAR FER ENSEL FROM ELECTRICAL SIMULATION OF THE SURFACE OF THE NECK JUST ABOVE THE REGION OF THE VAGUS NERVE AND 2 MINUTES OF THE STIMULATION COMPARED TO STIMULATION OF THE CONTROL WHICH WAS A CERTAIN MASTOID MUSCLE PRODUCED ACTIVATION WITHIN THE NTS AND THE MEDU LA, AND PRIOR TO THIS, EXTENDED THE FINDINGS OF DEATRICK AND KRAUSE, BY SHOWING LOCALIZED RESPONSE TO THE ELECTRICAL STIMULATION OF THE CONCHA OF EAR, COMPARED TO THE SIMULATION OF THE EARLOBE. AND THE FIBERS OF THE BRANCH OF THE VAGUS NERVE COME FROM THE SUPERIOR JUGULAR GANGLION AAS PORKS TO THE NO DOSE GANGLION WHICH CONTAIN SENSORY FIBERS THAT CONVEY THIS REAL AFER ENSEL, BUT WE CAN SEE BOTH THESE CONVERGEOT NTS. AND MOST RECENTLY THE [INDISCERNIBLE] MAPPED THE PROJECTIONS OF THE RESPIRATORY AND THAT'S IN THE MEDULA, WHICH PRODUCED THESE HIGH RESOLUTION IMAGES AND WE CAN SEE ACTIVITY WITHIN THE NTS AND THIS WAS ALSO PART OF A LARGER DOSE RESPONSE-LIKE STUDY AND PRIOR TO THAT, [INDISCERNIBLE] AND COLLEAGUES REPORTED THAT OPTIMAL NTS ACTIVATION WAS PRODUCED BY STIMULATION OF THE KONCHA TO HERE AS OPPOSE TO STIMULATION OF THE EAR CANAL OR THE TRIGUS AND WE CAN SEE THE DIFFERENCES HERE IN THE LOWER MEDULLA. SO USING BOTH APPROACHES, I FOUND NOT ONLY CAN WE ACCESS THE NTS BUT WE CAN ALSO ACCESS VAGALL CORTICAL AND SUBCORTICAL PROJECTIONS AND THESE APPROACHES ACTIVATED THE INTROSENTIVE REGIONS JUST DISCUSSED LIKE THE INSULA AND THE PRIMARY CORTEX AND PREFRONTAL CORTEX AS WELL. SO SO WE'VE GONE OVER--SO FAR, THE AFFERENT PROJECTIONS OF INCEPTION AND INTRINSIC--I'M SORRY EXTRINSIC VAGUS STIMULATION SO NOW I'LL TALK A BIT MORE ABOUT THE EFFECTS OF MODULATING THESE PATHWAYS WITH ELECTRICAL STIMULATION OF THE VAGUS NERVE AND JEANIE WILL PRESENT NOVEL METHODS FOR REGULATING THE DESCENDING AUTONOMIC PATHWAYS SO I WILL DISCUSS MODULATION OF MORE COGNITIVE AND AFFECTIVE AND SOMATIC SENSATIONS. SO THERE IS PLENTY OF EVIDENCE THAT SUGGESTS THAT MODULATES AFFECT OR MOOD AND SO MUCH SO THAT IT'S AN FDA APPROVED TREATMENT OPTION FOR REFRACTORY DEPRESSION AND THIS IS THE INVASIVE PROCEDURE. THERE'S ALSO EVIDENCE THAT IT'S BENEFICIAL FOR OTHER TREATMENT DISORDERS LIKE OCD OR PANIC DISORDER OR PTSD. AND BECAUSE THERE'S--BECAUSE IT'S SUCH AN INVASIVE NATURE AND BECAUSE OF THE INTERLYING CONDITIONS, THERE'S ACTUALLY BEEN A LIMITED NUMBER OF STUDIES THAT SPECIFICALLY LOOKED AT THE EFFECTS OF INVASIVE SIMULATION OR COGNITIVE FUNCTION AND PAIN BUT WE DO SEE THAT IMPROVEMENT IN THINGS LIKE LOGIC REASONING AND WORKING MEMORY AND SOME DECREASE IN PAIN SENSATIONS, AS BEEN REPORTED. NOW IT IS A BIT EASIER TO STUDY THE EFFECTS OF VAGUS STIMULATIONS USING NONINVASIVE METHODS BUT KEEP IN MIND THIS IS NOT NECESSARILY THE STIMULATION AND STIMULATION PARAMETERS JUST TO NAME A COUPLE. BUT NEVERTHELESS, NEVER REPORTS NOW SHOW THAT BENEFICIAL EFFECTS USING--SORRY, SEVERAL REPORTS SHOW THE BENEFICIAL EFFECTS AGAINST DEPRESSION, ANXIETY MOOD AND WELL BEING IN HEALTHY PARTICIPANTS AND PATIENTS WITH CHRONIC PAIN OR MAJOR DEPRESSIVE DISORDERS IEWG THANKSGIVING NONINVASIVE APPROACH. AND OTHER STUDIES HAVE FOUND THAT IT IMPROVES MEMORY, IT IMPROVES LEARNING AND REACTION TIME AND IT REDUCES HEADACHES AND SOME PAIN SENSATIONS, BUT OVERALL THE RESULTS HAVE BEEN MIXED. AND WITHIN THESE PARTICULAR STUDIES AND STUDIES NOT SHOWN HERE, INVESTIGATORS HAVE ALSO FOUND EITHER NO EFFECTS OR NONRESPONDERS. SO THE LITERATURE IS STILL CONFLICTING. IT IS SUSPECTED THAT THE MODLATTORY EFFECTS OF VAGUS STIMULATION OCCURS BY ACCESSING THE NTS PROJECTIONS WITHIN THE BRAIN STEM AND THESE PROJECTIONS INCLUDE REGIONS LIKE THE [INDISCERNIBLE] THE RAFAI NUCLEI AND THE PERIAQUA DUCTAL GRAY REGIONS AND WERE ALL ACTIVATED BY NONINVASIVE AND-OF BY BOTH NONINVASIVE PROCEDURES. BUT IT'S REALLY IMPORTANT TO UNDERSTAND THAT THE--THAT OBSERVED ACTIVATION IN A PARTICULAR REGION DOESN'T NECESSARILY IMPLY RELEASE OF THE ASSOCIATED NEUROTRANSMITTERS. IT REALLY REMAINS UNCLEAR WHAT VAGALL INDUCED ACTIVATION OF THE LOCUS CIRROLEOUS, WHICH WE HAVE YET TO DO EFFECTIVELY OR OFFICIALLY AND THE SAME COULD BE SAID ABOUT THE ACTIVATIONS WITH THE CORTEX AND THE SUBCORTICAL REGIONS AS WELL. AND LUCKILY, I'M SORRY--THIS IS ACTUALLY A VERY RECENT REVIEW THAT WAS JUST PUBLISHED AND IT ESSENTIALLY CAME TO THE CONCLUSION THAT LACK OF THE CONSENSUS AMONG TBNS STUDY SYSTEM IN PART DUE TO METHOD LOGICAL DIFFERENCES AND IN SOME CASES THE STUDIES DON'T FULLY REPORT THEIR METHODS WHICH MAKES REPLICATION VERY DIFFICULT BUT LUCKILY, JULIAN KONIG REALLY RALLIED AND DRAFTED A RECOMMENDATION FOR MINIMUM REPORTING STANDARDS SPECIFICALLY FOR TBNS RESEARCH AND HOPEFULLY THIS WILL BE OUT VERY SOON, WITH THAT SAID I WILL CONTINUE AND ALSO START TO WRAP THINGS UP HERE. NOW BECAUSE I'VE BEEN CONCENTRATING ON PAIN RESEARCH, I WILL SHIFT MY FOCUS A LITTLE BIT INTO PAIN BUT THIS STILL FALLS UNDER INTROCEPTION SO FROM STUDIES OUTSIDE OF VEGAS STIMULATIO, WE KNOW THAT EMOTION AND COGNITION MODULATE PAIN DIFFERENTIALLY. SO FOR EXAMPLE, PAZZATIVE [INDISCERNIBLE] PAIN AND NEGATIVE MOOD VS BEEN SHOWN TO INCREASE PAIN. AND MANIPULATING COGNITIVE PROCESSES LIKE ATTENTION CAN ALSO MODULATE PAIN SO FOR EXAMPLE, TAKING SOMEONE'S ATTENTION AWAY FROM THEY PAINFUL STIMULUS WILL DECREASE PAIN PERCEPTION. AND THESE PSYCHOLOGICAL FACTORS INFLUENCE PAIN PERCEPTION DIFFERENTIALLY SUCH THAT MANIPULATING ENOTION WHILE MANIPULATING ATTENTION EFFECTS PAIN INTENSITY. NOW BECAUSE OF THE AFER ENSEL OR VAGUS STIMULATION IS NECESSARY THAT IT COULD MODULE PAIN PERCEPTION DIFFERENTIALLY. IN FACT AN EARLY ANECDOTE PUBLISHED BY [INDISCERNIBLE] FROM A PATIENT WITH AN IMPLANTED BASE STIMULATOR TO TREAT DEPRESSION, HIS LOW BACK PAIN QUOTE-UNQUOTE BOTHERED HIM AFTER IMPLANTATION. SO IT'S UNCLEAR IF THE INTENSITY OF THE BACK PAIN CHANGED BUT THE NEGATIVE AFFECTIVE COMPONENT OF THE PAIN WAS MODULATED BY THE VAGUS INPUT. ALTHOUGH I CERTAINLY DON'T DISMISS PLACEBO EFFECTS IN THIS CASE EITHER. NOW, IN THIS REVIEW PAPER I ALSO SHOW THAT MOST STUDIES EXAMINING THE EFFECTS OF TBNS ON PAIN PERCEPTION TYPICALLY REPORT ONLY PAIN INTENSITY RATINGS AND NOT PAIN AND PLEASANT RATINGS, SO IT'S UNCLEAR OF 1 PATHWAY OVER THE OTHER OR BOTH EQUALLY AND KNOW THANKSGIVING COULD HELP US DESIGN MORE SPECIFIC INTERVENTION SAYS GOING FORWARD. AND OF COURSE TO THIS END I HAVE AN ONGOING RANDOMIZED DOUBLE BLIND CROSS OVER STUDY HERE AT NCCIH AND WE'RE ABOUT HALFWAY THROUGH OUR DATA COLLECTION. BUT JUST TO CLOSE UP HERE WE HAVE NEW AND EXCITING NONINVASIVE TOOLS TO PROBE INTROCEPTIVE NETWORKS BUT THESE TOOLS AND THEIR METHODOLOGY ARE STILL IN PROGRESS AND WHILE WE CAN ACCESS AND MODULATE THESE INTROCEPTIVE NETWORKS WE HAVE TO REMEMBER THAT WE WILL ALSO TARGET MULTIPLE REGIONS OR MULTIPLE NETWORKS AND WE DON'T HAVE THE METHOD LOGICAL SPECIFICITY YET TO DO SO DIFFERENTIALLY. SO IT'S IMPORTANT TO CONSIDER ADDING MEASURES THAT CAPTURE CHANGES PRODUCED BY THESE DIFFERENT OVERLAPPING NETWORKS SO THAT WE CAN LEARN MORE ABOUT HOW THEY'RE MODULATING VAGALL AFRENTS AND IT'S ALSO EVIDENCE THAT MORE WORK IS NEEDED TO FULLY UNDERSTAND FULLY VAGALL AFRENTS AND UNDERSTANDING THESE MECHANISMS CAN HELP US BETTER UNDERSTAND THE THERAPEUTIC EFFECTS OF VAGUS STIMULATION AND HELP DESIGN BETTER INTERVENTIONS AND I REALLY THINK THAT TBNS PAIRED WITH MULTIMODAL APPROACHES CAN HELP AND PAIRING TOOLS LIKE TRANSCRANIAL MAGNETIC SIMULATION AND MAGNETIC RESONANCE AND SPECTROSCOPY WITH fMRI COULD PROVIDE A DEEPER FUNCTIONAL INSIGHT AS TO HOW THEY RASKT THE REGULATORY PATHWAYS OF THE INTROCEPTIVE SYSTEM WHICH ULTIMATELY COULD MAYBE 1 DAY HAVE BENEFICIAL WIDE SPREAD EFFECTS ON THE MIND AND THE BODY. ALL RIGHT. THANKS TO EVERYONE ESPECIALLY THE WEBINAR STAFF AND THE SPEAKERS FOR THEIR FEEDBACK. SO I WILL STOP SHARING NOW AND UP NEXT I BELIEVE IS JEANIE. >> THANK YOU. THAT WAS GREAT. SO I WILL NOW SWITCH GEARS AND WE HEARD A GREAT PRESENTATION ON VAGUS NERVE. AND SWITCH NOW TO TALK ABOUT MICRONEUROGRAPHY AS A TECHNIQUE TO MEASURE EFERENT SYMPATHETIC NERVE ACTIVITY AND ITS POTENTIAL APPLICATIONS AND INTROCEPTIVE RESEARCH. SO THE SYMPATHETIC NERVOUS SYSTEM IS THE ARM OF THE AUTONOMIC NERVOUS SYSTEM THAT WE COLLECTIVELY THINK OF AS RESPONSIBLE FOR THE FIGHT OR FLIGHT RESPONSE. SO THE CELL BODIES OF THE SYMPATHETIC NERVES RESIDE IN THE THROWN--EQUALLYACULAR LUMBAR REGION OF THE SPINAL CORD AND CONNECT TO SYMPATHETIC CONTROL CENTERS IN THE BRAIN STEM. AND THEN THESE PRESYNAPTIC NEURONS THEN SYNAPSE WITH POST SYNAPTIC NEURONS IN A SYMPATHETIC CHAIN GINGLIA AND THEN GO ON TO INNERIVATE TISSUES THROUGHOUT THE BODY. SO THE RESULT OF THE TRANSMISSION IS A RELEASE OF NORAEPINEPHRINE AND OTHER TRANSMITTERS AT THE NERVE TERMINALS THAT WILL INCREASE HEART RATE AND CARDIAC OUTPUT, INCREASE SODIUM AND WATER REABSORPTION FROM THE KIDNEY AND CONSTRICT BLOOD VESSELS TO INCREASE BLOOD PRESSURE. SO THE SYMPATHETIC NERVE SYSTEM IN ADDITION TO THE FIGHT OR FLIGHT RESPONSE PLAYS A CRITICAL ROLE IN BLOOD PRESSURE REGULATION. WHICH IS CONTROLLED BY AFERENT INPUT FROM THE CARDIO BARRIER REFLEX SYSTEMS, SO THE ARE--ADMINISTRATIVE TERIOLE BARRIER RECEPTORS ARE MECHANO RECEPTORS THAT RESIDE IN THE CAROTID THYMUS AND THE BIFURCATION AND AORTIC MARCH AND MODULATED ACTIVITY IN CHANGES TO BLOOD PRESSURE. SO IF THE BLOOD PRESSURE GOES UP, THEN THESE ARE--ADMINISTRATIVE TERIOLE BARRIER RECEPTORS BECOME ACTIVATED LEADING TO A REFLEX DECREASE IN SYMPATHETIC ACTIVITY. AND CONVERSELY WHEN BLOOD PRESSURE GOES DOWN, THEN THE ARTERIAL BEAR RECEPTORS BECOME UNLOADED AND LEAD TO AN INCREASE IN SYMPATHETIC ACTIVITY SO THIS IS ALL IN AN EFFORT TO KEEP BLOOD PRESSURE WITHIN A NARROW RANGE. SO THE SCROLUME SENSITIVE BARRIER RECEPTORS ON THE OTHER HAND ARE LOCATED IN THE ATRIA AND IN THE LUNGS AND THEY MODULATE SYMPATHETIC OUTPUT BASED ON CHANGES IN BLOOD VOLUME OR VENUS RETURN TO THE HEART AS MIGHT HAPPEN WITH VOLUME DEPLETION OR UPRIGHT POSTURE AGAIN TO MAINTAIN BLOOD PRESSURE HOMEOSTASIS. SO THE SYMPATHETIC NERVOUS SYSTEM PLAYS A MAJOR ROLE IN BOTH SHORT-TERM AND LONG-TERM BLOOD PRESSURE REGULATION. AND THERE ARE A NUMBER OF DISEASES IN FACT THAT ARE CHARACTERIZED BY CHRONIC OVERACTIVATION OF THE [AUDIO CUTS OUT ] SO CHRONIC OVERACTIVATION OF THE SYMPATHETIC NERVOUS SYSTEM CONTRIBUTES TO INCREASED CARDIOVASCULAR RISK BY INCREASING BLOOD PRESSURE, BUT THERE ARE ALSO A NUMBER OF DELETERIOUS AND ORGAN EFFECTS THAT ARE INDEPENDENT OF BLOOD PRESSURE BY WHICH SYMPATHETIC OVERACTIVATION CONTRIBUTES TO INCREASED RISK. SO IN ORDER FOR US TO BE ABLE TO STUDY THIS IN HUMANS WE NEED TO I HAVE RELIABLE METHOD FOR MEASURING SYMPATHETIC ACTIVITY AND THERE ARE SOME HERE THAT WE CAN CONSIDER, SO, NORAEPINEPHRINE S&P THE MAJOR NEUROTRANSMITTER THAT IS RELEASED AT SYMPATHETIC NERVE TERMINALS BUT PLASMA LEVELS OF NEUROEPINEPHRINE IS NOT JUST THE PRODUCT OF SYMPATHETIC ACTIVATION BUT ALSO INFLUENCED BY METABOLISM, REUPTAKE AND CLEARANCE AND IS NOT NECESSARILY THE MOST RELIABLE MEASURE. WHILE THERE ARE SOME HEART RATE VARIABILITY MEASURES THAT ARE VALID MARKERS OF CARDIAC PARASYMPATHETIC ACTIVITY, THE MEASURES OF HEART RATE VARIABILITY THAT ARE PURPORTED TO REFLECT SYMPATHETIC ACTIVITY ARE ACTUALLY LESS VALID AND LESS LIABLE. THERE ARE SOME STUDIES THAT HAVE SHOWN THAT THE GALVONNIC SKIN RESPONSE CORRELATES WITH SKIN SYMPATHET ICACTIVITY BUT NOT ALL STUDIES HAVE SHOWN THIS CORRELATION. THE SPILL OVER TECHNIQUE INVOLVES INFUSION OF RADIO LABELED NORAEPINEPHRINE, AND THE MAJOR ADVANTAGE OF THIS TECHNIQUE IS TO QUALIFY ORGAN OR TISSUE SPECIFIC SYMPATHETIC ACTIVITY. BUT THE USE OF THIS TECHNIQUE IS ACTUALLY QUITE LIMITED BECAUSE OF ITS INVASIVE NATURE AND IT'S ALSO PRETTY CUMBERSOME TECHNIQUE AND IT DOESN'T LEAVE FOR CHANGES IN THE ACTIVITY. SO THAT LEADS WITH US MICRONEUROGRAPHY WHICH WAS DEVELOPED 50 YEARS AGO AND IS THE GOLD STANDARD METHOD BY WHICH WE CAN MEASURE AND QUANTIFY SYMPATHETIC ACTIVITY DREECTLY IN REALTIME FROM A WAKE HUMAN. SO IN MICRONEUROGRAPHY WE PLACE A RECORDING MICROELECTRODE INSIDE 1 OF THE ACCESSIBLE PERIPHERAL NERVES IN THE BODY AND OUR LAB WE USE THE PERNEAL NERVE BUT THE OTHER NERVE SUCH AS THE MEDIA NERVE OR POST TIBIAL NERVES HAVE ALSO BEEN USED AND WE CAN MEASURE SYMPATHETIC NERVE TRAFFIC IN REALTIME FROM THIS RECORDING ELECTRODE. SO TO REMIND YOU WHERE WE ARE RECORDING FROM IN TERMS OF IMPOSSIBLE TO BUILD ROUGH ATOM CEPTIVE NEURAL PATHWAYS, SO IN MICRONEUROGRAPHY, WE ARE MEASURING DIRECTLY FROM THESE POST GANGLIONIC SYMPATHETIC MERV FIBERS AS THEY TRAVEL WITHIN THE PERIPHERAL NERVE. SO IN WE REPLACE A ELECTRODE INTO THE NERVE AND APPEARANCE ELECTRODE IS PLACE INDEED CLOSE PROXIMITY AND WHEN THERE'S ACTIVATION OF THE SYMPATHETIC NERVES, THIS CREATES A VOLTAGE DIFFERENCE BETWEEN THE RECORDING ELECTRODE AND THE REFERENCE ELECTRODE. AND THIS MULTIFIBER SIGNAL HAS BEEN AMPLIFIED AND INTEGRATED AND FILTERED. AND THEN DISPLAYED AS A NEUROGRAM SO HERE IS AN EXAMPLE OF MUSCLE SYMPATHETIC NERVE ACTIVITY, OR SYMPATHETIC ACTIVITY THAT IS DIRECTED TO THE BLD VESSELS THAT SUPPLY THE MUSCLES OF THE LOWER EXTREMITY. AND ALONG WITH THE CONCOMITANT EKG AND THE BEAT TO BEAT ARTERIAL BLOOD PRESSURE. AND WE CAN QUANTIFY MUSCLE SYMPATHETIC NERVE ACTIVITY AS BURST FREQUENCY WHICH IS SIMPLY THE NUMBER OF BURSTS PER MINUTE, OR BIFORT INCIDENCE WHICH IS THE NUMBER OF BURSTS PER NUMBER OF HEART BEATS OR TOTAL ACTIVITY WHICH TAKES INTO ACCOUNT THE AMPLITUDE OF THESE BURSTS. SO HERE'S A PICTURE FROM OUR LAB SHOWING A MICROELECTROINSIDE THE PERO NEAL NERVE AND THIS IS A REFERENCE ELECTRODE IN CLOSE PROXIMITY AND THIS DIAGRAM SHOWS THE MICROELECTRODE INSIDE THE NERVE VESICLE WITH THE TIP OF THE ELECTRODE NEXT TO THE SYMPATHETIC NERVE FIBERS. WITH SO HERE'S AN EXAMPLE OF A NEUROGRAM FROM A PATIENT WITH END STAGE KIDNEY DISEASE. AND YOU CAN SEE THAT MUSCLE SYMPATHETIC NERVE ACTIVITY IS SUBSTANTIALLY HIGHENER IN PATIENT COMPARED TO THE AGE MATCH CONTROL. AND THESE ARE THE CUMULATIVE READINGS FROM ANOTHER PATIENT POPULATION SLEEP APNEA, SHOWING ELEVATED SYMPATHETIC NERVE ACTIVITY IN SLEEP APNEA COMPARED TO OBESE INDIVIDUALS WITHOUT SLEEP APNEA AND NORNLAL WEIGHT INDIVIDUALS. SO NOT ONLY CAN WE USE MICRONEUROGRAPHY TO CHARACTERIZE BASE LINE OR ARRESTING DIFFERENCES BETWEEN PATIENT GROUPS BUT WE CAN ALSO STUDY THE REACTIVITY OF THE SYMPATHETIC NERVOUS SYSTEM TO STRESS AND IN THIS EXAMPLE WE SHOWED THAT THE CHANGE IN MUSCLE SYMPATHETIC NERVE ACTIVITY IS AUGMENTED IN PATIENTS WITH POST-TRAUMATIC STRESS DISORDER COMPARED TO VETERANS WITHOUT PTSD AND THIS IS IMPORTANT BECAUSE EXAGGERATED SYMPATHETIC REACTIVITY IS ASSOCIATE WIDE AN INCREASED RISK OF PIPER TENSION AND CARDIOVASCULAR DISEASE. SO THERE ARE MULTIPLE POTENTIAL APPLICATIONS OF MICRONEUROGRAPHY AND INTROCEPTION SCIENCE SUCH AS IN THE STUDY OF THE REAGENTSULATION OF THE SYMPATHETIC NERVOUS SYSTEM BY INTROSEPTORSORS SUCH AS RECEPTORS AND CHEMO RECEPTORS IN BOTH HEALTH AND DISEASE AND ALSO IN UNDERSTANDING THE EFFECT OF ACUTE AND LONG-TERM INTERVENTION THAT MANIPULATE OR TRARGET INTROCEPTIVE PATHWAYS ON SYMPATHETIC ACTIVITY REACTIVITY AND REGULATION. SO AS AN EXAMPLE, THE CLASSIC METHOD FOR QUANTIFYING ARTERIAL BARRIER REFLEX SENSITIVITY AND AGAIN THESE ARE THE STRESS RECEPTORS THAT MODULATE SYMPATHETIC ACTIVITY IN RESPONSE TO CHANGES IN BLOOD PRESSURE IS THROUGH THE MODIFIED OXFORD TECHNIQUE IN WHICH WE GIVE AN INTRAVENOUS BOLUS OF [INDISCERNIBLE] WHICH LEADS TO A DECREASE IN BLOOD PRESSURE AND A REFLEX INCREASE IN MUSCLE SYMPATHETIC NERVE ACTIVITY WITH THE REFLEX INCREASE IN HEART RATE AND REDUCTION IN THE RR-IRPT --RR-INTERVAL. THIS IS AN INCREASE IN BLOOD PRESSURE THAT LEADS TO A REFLEX DAMPENING OF SYMPATHETIC ACTIVITY AND A REDUCTION IN HEART RATE AND AGAIN ALL MEDIATED BY THE ARTERIAL BEARER RECEPTORS AND WE CAN QUANTIFY THE SENSITIVITY OF THE SYMPATHETIC ARM OF THE BEARER REFLEX BY EXAMINING THE RELATIONSHIP BETWEEN THESE CHANGES AND INDUCE BLOOD PRESSURE AND SYMPATHETIC NERVE ACTIVITY SUCH THAT THE STEEPER THE SLOPE OF THIS RELATIONSHIP, THE HIGHER THE SENSITIVITY AND THE FLATTER THE SLOPE AND THE LOWER THE SENSITIVITY. AND SO HERE IN THIS FIGURE, WE SHOWED THAT IN PATIENTS WITH POST-TRAUMATIC STRESS DISORDER, THE SLOPE OF THE RELATIONSHIP BETWEEN DIASTOOL DNAIC BLOOD PRESSURE CHANGES AND MUSCLE SYMPATHETIC NERVE ACTIVITY IS SIGNIFICANTLY FLATTER COMPARED TO CONTROLS WITHOUT PTSD, DEMONSTRATING AN IMPAIRMENT IN ARE--ADMINISTRATIVE TERIOLE BEARER REFLEX SENSITIVITY AND THIS IS CLINICALLY IMPORTANT BECAUSE IMPAIRED BARRIER REFLEX SENSITIVITY IS ASSOCIATED WITH AN INCREASED RISK OF HYPER TENSION AND VARDIO VASCULAR DISEASE. SO MICRONEUROGRAPHY CAN BE USED TO STUDY THE EFFECTS OF INTERVENTIONS THAT TARGET INTROCEPTIVE PATHWAYS TO MODULATE SYMPATHETIC ACTIVITY AND IN PARTICULAR WE'VE BEEN INTERESTED IN NONPHARMACOLOGIC OR MIND BODY INTERVENTIONS THAT MAY ACTIVATE BEARER RECEPTOR OR VAGALL AFERENTS VIA SLOW BREATHING, MINDFULNESS MEDICATION WITH A FOCUS ON BREATHING AWARENESS AND VAGUS NERVE STIMULATION. SO IN THESE STUDIES WE SHOWED THAT BREATHING AND PHYSIOLOGIC RATES OF FIX-6 BREATHS PER MINUTE USING THE BIOFEEDBACK DEVICE LOWERS MUSCLE SYMPATHETIC NERVE ACTIVITY WITH A CONCOMITANT REDUCTION IN BLOOD PRESSURE IN VETERANS WITH PTSD, WHEN COMPARED TO A SHAM BREATHES DEVICE THAT DIRECTED BREATHING AT NORMAL RESPIRATORY RATES. AND ALSO DEVICE GUIDE EDUCATIONAL SLOW BREATHING AS OPPOSE TO THE SHAM IMPROVED SYMPATHETIC BEARER REFLEX ACTIVITY IN PTSD. AND IN ANOTHER STUDY USING MINDFULNESS MEDITATION WITH A FOCUS ON INCREASING BREATHING AWARENESS OR BREATHING AWARENESS MEDITATION, WE FOUND THAT THERE WAS A SIGNIFICANT REDUCTION IN MUSCLE SYMPATHETIC NERVE ACTIVITY AND MEAN ARTERIAL PRESSURE AND HEART RATE COMPARED TO THE CONTROL INTERVENTION HAD INCREASED CARDIOVASCULAR DISEASE RISK. AND SO FINALLY, THERE ARE SOME ANIMAL AND HUMAN STUDIES THAT SUGGEST THAT ELECTRICAL STIMULATION OF THE VAGUS NERVE INHIBITS SYMPATHETIC ACTIVITY AND THESE ARE DATA FROM THE ONLY STUDY THAT HAS LOOKED AT CHANGES IN SYMPATHETIC ACTIVITY USING MICRONEUROGRAPHY DURING VAGUS NERVE STIMULATION AND THEY FOUND THAT SIMULATION OF THE ARICKULAR BRANCH OF THE VAGUS NERVE LEADS TO AN ACUTE REDUCTION IN SYMPATHETIC NERVE ACTIVITY. SO THE PROPORTED MECHANISMS BY WHICH THE TARGETED INTROCEPTIVE PATHWAYS ARE WITH VAGUS STIMULATION, THERE'S ACTIVATION OF THE VAGUS AFERENT NERVE THAT FEEDS INTO THE NUCLEUS TRACTUS SOLTARRUOUS THAT ACTIVATES THE KAWDAL VENTRAL LATERAL MODEL CITIZEN DUALA AND THIS THAT'S IN THE BRAIN STEM TO REDUCE SYMPATHETIC ACTIVITY. AND WITH BREATHING INTERVENTIONS INDLIEWDING SLOW BREATHING AND WITH INCREASE IN BREATHING AWARENESS THE REDUCTION IN RESPIRATORY RATE LEADS TO AN INCREASE IN TITLE VOLUME AND THIS IS THE MAINTAIN THE SAME VENTILATION AND SO WHEN THAT HAPPENS THERE'S ACTIVATION OF THE PULL MONITORARY BARORECEPTORS, AND ININCREASE IN BODYITS THE ACTIVITY. AND THERE ALSO A FEET FORWARD œCOMPONENT AS WELL AND INCREASE WITH BREATHING, AWARENESS THAT HAS AN INHIBITORY EFFECT. SO JUST IN THE LAST MINUTE, I WANT TO INTRODUCE THE METHODS PAPER THAT WAS JUST PUBLISHED LAST MONTH IN THE JOURNAL OF PHYSIOLOGY FROM DR. VON MAY FIELD FLAT IN WHICH HE REPORTS THE FIRST K-SERIES OF SUCCESSFUL VAGUS NERVE RECORDINGS USING MICRONEUROGRAPHY. SO THESE ARE THE FIRST REPORTS THAT SHOW THAT THE VAGUS NERVE CAN BE DIRECTLY ACCESSED AND RECORDED FROM IN AN AWAKE HUMAN AND IT REALLY OPENS UP A LOT OF NEW EXCITING OPPORTUNITIES TO STUDY BOTH AFER AND THEN THE EFERENT VAGUS NERVE ACTIVITY DIRECTLY SO HERE'S A PICTURE FROM THAT REPORT THAT SHOWS THE NEW MICROELECTRODE GOING INTO THE BACK OF THE NECK UNDER ULTRA SOUND AND GUIDANCE. AND HERE IS AN ULTRA SOUND IMAGE THAT SHOWS THE TUNGSTEN ELECTRODE ENTERING THE VAGUS NERVE HERE IN THE INTERJUGULAR VAIN AND THE CAROTID ARTERY. SO TO IS SUMMARIZE MICRONEUROGRAPHY ALLOWS FOR POST SYMPATHETIC NERVE TRAFFICKING IN HUMANS IN REALTIME AND IT CAN BE UTILIZED IN STUDIES EXAMINING BENEFITS OF INTROCEPTIVE MANIPULATION ON SYMPATHETIC ACTIVATION AND VAGUS NERVE MICRONEUROGRAPHY IS A VERY NEW TECHNIQUE THAT OFFERS NEW OPPORTUNITIES TO EXAMINE BOTH AFER AND THEN THE EFERENT VEGAS NERVE ACTIVITY DIRECTLY IN HUMANS. SO I WILL END THERE AND AND TURN IT OVER TO WOLF. >> OKAY, CAN YOU HEAR ME? >> OKAY, SO I HAVE TO SHOW MYSELF BRIEFLY BUT I WILL TURN MY VIDEO OFF TO MAKE SURE THAT WE HAVE A GOOD RECEPTION HERE AT THIS, AND IT WORKS GOOD ENOUGH. SO I APOLOGIZE, I'M ON VACATION AND AT THE PLACE HERE, THE INTERNET CONNECTION IS NOTER APPROXIMATE FECT SO I TAKE MY VIDEO OFF AND THEN I WILL SHARE MY SCREEN. THEN I WILL GET THIS OVER HERE. OKAY, SO I AM TALKING ABOUT MOSTLY CONSCIENCE ASPECT OF INTROCEPTION SO WE HAVE THIS FANTASTIC--AND TALK A LOT WITH PRACTITIONERS OF THESE INTERVENTIONS AND I AM TRYING TO UNDERSTAND WHAT'S HAPPENING WITHIN EPITHELIAL ROUGH ATOM CEPTIVE IN THE AREA WHAT WE CAN PERCEIVE ACTUALLY. I HAVE TO SEE THIS HERE, IS THAT BETTER? SO I'M TALKING ABOUT THE ASPECTS OF CONSCIENCE AWARENESS AND FIRST I WANT TO BRING SOME DATA THAT I GOT FROM THE NCCIH FUNDED QUALITATIVE STUDY WHERE WE HAD A GROUP OF MIND AND BODY INTERVENTIONS AND PRACTITIONERS AND PATIENTS TOGETHER OR IN SEPARATE FOCUS GROUPS HOW THEY UNDERSTAND HOW THEY RELATE--HOW THEY UNDERSTAND THEIR RELATIONSHIP OF MIEBD AND BODY. SO THEY ALL INSIGHTED IN THE STATE BUT THE MIND AND BODY ARE NOT SEPARATE ENTITIES, THERE'S INTEGRITY OF THE CELLS AND SECOND THAT THERE'S HUMAN CAPACITY THAT'S INNATE FOR ALL OF US FOR THE DEVELOPMENTAL PROCESS TO EMBODIMENT SO THAT'S A STATEMENT THAT MY MIND AND BODY PRACTITIONERS MADE THAT I WILL COME BACK TO. SO SO THE MIND BODY INTERVENTION THAT HAPPENS WITHIN THE WESTERN CULTURE IS CHARACTERIZED TO SOME DEGREE OF DISEMBODIED QUALITY THAT ALL GLOBAL CIVILIZATION HAS AN INCREASE DEPENDENCY OF THE INTERNET AND SOCIAL MEDIA AND SELF-IDENT ISKSZ, SELF-OBJECTIFICATION AND HOW WE PERCEIVE OUR BODY. AND WE SPEND INCREASING HOUR TO ASSUME CULTURE AND GO INTO CYBERSPACE AND THESE ARE ALL CHALLENGES FOR THE INTEGRITY OF MIND AND BODY. IF SOME OF YOU MAY HAVE READ [INDISCERNIBLE] HE'S A BEST-SELLING AUTHOR THESE DAYS, PHILOSOPHER AND DEDICATED MEDITATOR FROM ISRAEL WHO IN HIS LAST BOOK 21st LESSONS FOR THE 21st CENTURY 1 OF HIS MOST QUOTED SENTENCES IS IF YOU DON'T FEEL AT HOME IN YOUR BODY, YOU WILL NEVER FEEL AT HOME IN THE WORLD. AND SO THIS EMBODY, THIS DEVELOPMENTAL MODEL OF BODY AWARENESS SHOWS KIND OF 4 DIFFERENT LEVELS THAT WE ENCOUNTER WITHIN OUR STUDIES. SO THE FIRST LEVEL IS CALLED THE ABSENT BODY IS WHEN PEOPLE TAKE THE BODY FOR GRANTED, THIS IS WHEN THEY'RE YOUNG AND DON'T HAVE PAIN, YOU KNOW TEENAGERS OR HEALTHY VOLUNTEERS THEN THEY GET INTO PAIN OR SOME DYSFUNCTION IN THEIR SYSTEM AND THEN THEY GET DISRUPTINGICISM THOMAS COVINGTONS AND THEN THEY FIND THAT THESE SYMPTOMS ARE KIND OF OPPOSED TO THEM AND THEY PROCEED THE BODY AS KIND OF AN ENEMY, THEY HAVE TO FIGHT AGAINST IT BECAUSE IT CHANGES THERE, AND POSSIBILITY FOR ACTIVITIES, THEN ANOTHER LEVEL IS WHEN THEY GET INTO YOGA AND MY THOUGHT HA WAS THEY DEVELOP A NEW RELATIONSHIP TO THEIR BODY WHICH IS CHARACTERIZED BY CULTIVATING THE IMMEDIATEIACY OF PERCEPTIONS AND ACCEPTING THE BODY. SO THAT'S THE PEOPLE WHO ARE NOVICES OR GRADUATES FROM MIND-BODY INTERVENTIONS FOR INSTANCE LIKE IN YOGA AND THE FOURTH LEVEL IS WHEN THEY'RE MORE EXPERIENCED AND THE PRACTITIONERS, THEN THEY GET KIND OF THE SENSE, THE UNITY OF BODY AND MIND AND THEY LEARN THAT THE BODY CAN BE ACTUALLY A SOURCE OF LEARNING AND MEANING. AND MAYBE THEY OVERCOME THE DUALITY OF THE PERCEPTION. SO THIS IS FROM A STUDY BY CATHY CARE, SHE DIED A FEW YEARS AGO, SHE WAS AT THE OSHA CENTER AND SHE TITLED 1 OF HER BIG PAPERS, MINDFULNESS STARTS WITH THE BODY AND SHE FOUND THAT THE MBSR, MBSR, MBCT, MINDFULNESS INTERVENTIONS CHANGE OR MODULATE THE ALPHA RHYTHM IN THE BRAIN AND THIS RHYTHM IN THE GRAY IS ACTUALLY A FILTERING STATION AT THE LEVEL OF THE THALAMUS FOR HOW MUCH SENSATIONS OF THE BODY LEFT THROUGH THE SOMATOSENSORY CORTEX, SO SHE DID KIND OF 1 OF THE FIRST COMPUTATIONAL MODELS OF HOW MINDFULNESS AND MINDFULNESS BASED INTERVENTIONS [AUDIO CUTS OUT ] OF THE DEVELOPMENTAL MODEL ALSO WE DISCUSSED TOGETHER WITH A PREDICTIVE COATING MODEL WHICH IS 1 OF THE CURRENTLY LEADING THEORIES ON HOW INTERROUGH ATOM ACCEPTION PSYCHOLOGICALLY WORKS IN PREDICTIVE CODING MODEL MEANS WHEN WE HAVE THE PERCEPTION OF OUR BODY, FOR EXAMPLE, OF OURSELVES, IT'S ALWAYS A MIX OF PREDICTIONS ABOUT OUR BODY LIKE BASED ON OUR PRIOR EXPERIENCES, ALL THE STORIES WE'RE TELLING EACH OTHER, ABOUT OURSELVES ON THE 1 HAND AN AFER ENSEL OF REAL ACTUAL MOMENTARY PERCEPTIONS ON THE OTHER HAND. SO THIS ALL GETS MIXED UP AND FOR EXAMPLE, IN THE FIRST STAGE OF INTROCEPTIVE AWARENESS OF BODY AWARENESS THESE ARE ALL MIXED UP WITH EACH OTHER SO THINKING AND SENSING ARE PRETTY MUCH 1 MIX AND IN THAT MIX, WE CAN GIVE DIFFERENT WEIGHT TO WHAT WE PERCEIVE FROM THE BODY ITSELF COMPARED TO OUR REDICTIONS SO, IN SHORT-TERM, YOU CAN SAY, BETWEEN THINKING ABOUT OUR BODY AND SENSING OUR BODY, WHAT WEIGHT WE GIVE TO EACH OTHER, INFLUENCES IS THE RESULTING PERCEPTION OF OURSELVES AND MENTAL HEALTH PROBLEMS ALSO ACCORDING TO THE KHALSA LAB WHICH DOES A LOT OF RESEARCH IS THE DYSFUNCTIONAL WEIGHING OF THESE MECHANISMS, WHICH GOVERNANCE, RELATIVE INFLUENCE, PRIOR EXPECTATIONS VERSUS AFERENT BODY SIGNALS IN DETERMINING OR RESIDING INTERCEPTION, SO THAT'S A CODING MODEL WHICH IS 1 OF THE LEADING THEORIES NOW IN NEUROSCIENCE EMPLOY SO WHAT I COULD SPECULATE BUT NOBODY HAS DONE THIS SYSTEMATICALLY THERE ARE ALSO 4 LEVELS THAT MIGHT RELATE TO DIFFERENT BRAIN FUNCTION STATES LIKE THE NARRATIVE MODE, THINKING ABOUT THE BODY, AND PLAYING WITH THE BODY IN A NAIVE PERSON SIMILAR TO THE GERONTOLOGYSTS FAULT MODE NETWORK. THEN WE HAVE CHRONIC PAIN, THEN IN THIS BALANCE BETWEEN EXPECTATIONS AND REAL PERCEPTION IT'S ALL GETTING DOMINATED BY THE EMOTIONS. OT THIRD LEVEL WE CAN FINALLY FARP HAS SHOWN WITH THE MINDFULNESS STUDY WE CAN DIFFERENTIATE BETWEEN THINKING AND SENSING ABOUT THE BODY AS 2 DIFFERENT PATHS NEUROLOGICALLYY SERVE ABT FOR SELF-IDENTIFICATION AND SELF-REFERENCE, AND ON THE FOURTH LEVEL IT SHOWS THAT IF YOU HAVE MORE INTROCEPTIVE ATTENTION THAT ACTUALLY THE CORTICAL AREAS IN THE BRAIN CAN CHANGE. SO I'M TALKING MOSTLY ABOUT THE REGULATION THERE, WHICH IS ON THE RIGHT SIDE HERE OF THIS SLIDE. MORE THAN ANYTHING ELSE, AND TO HOW--HOW THIS ALL WORKS OUT IN TERMS OF REGULATING THE SYSTEM. HOW DOES IT HAPPEN. SO NOW I'M PRESENTING EXPERIENTIAL FINDINGS AND THE PHYSIOLOGICAL DETAILS, I DON'T HAVE MUCH OF THOSE SO I'M GLAD WE SAW THOSE ALREADY IN THE PREVIOUS PRESENTATIONS. SO, NCCIH SUPPORTED A TEAM THAT I LED TO DEVELOP A PROBING INSTRUMENT AND KIND OF A SELF-REPORT MEASURE CALLED THE MYA MULTIDIMENSIONAL INTROCEPTIVE DEVELOPMENT OF AWARENESS HAS BEEN TRANSLATED NOW IN MANY LANGUAGES AND THIS IS AN INSTRUMENT WITH 8 DIFFERENT SCALES AND DIFFERENT ASPECTS AND AWARENESS THAT ARE CORRELATED TO THE DIFFERENT STAGES OF THE DEVELOPMENTAL MODEL. ONE OF KEY SCALES WITHIN THIS QUESTIONNAIRE, IS THE SCALE FOR SELF-REGULATION WHICH STANDS FOR THE ABILITY TO REGULATE THE STRESS BY ATTENTION TO BODILY SENSATIONS, SO SIMILAR TO WHAT WE HAD HEARD BEFORE LIKE RELATED TO BREATH AWARENESS SO THE GOAL OF CIRCULATION IS TO CREATE HOMEOSTASIS THAT WE DON'T HAVE PAIN, THAT WE DON'T SUFFER, AND THE RESULTS IN THE PREDICTION ERROR AND THE TENSION BETWEEN REAL PERCEPTION AND PREDICTION OR MENTAL THINKING WHEN THAT GOES--THAT THIS GOES TO 0, SO WE CAN LEARN FOR EXAMPLE THE MINDFULNESS INTERVENTION THAT WHY HAVE 2 EFFECTS AND 1 IS THEY UPDATE THE EXPECTATIONS AND THE SECOND IS THAT THEY SHIFT THE WEIGHT MORE TO THE EFFORT OF PERCEPTIONS IN THE REALTIME RIGHT NOW PRESENT MOMENT RATHER THAN WHAT WE THINK ABOUT. YOU KNOW THIS GOAL FOR SELF-REGULATION MIGHT BE DIFFERENT IN OTHER CULTURES [AUDIO CUTS OUT ] AND THEY DIFFERENTIATE BETWEEN ADAPTIVE AND METAADAPTIVE ATTENTION STYLES. THEY HAVE A MINDFUL PRESENT MOMENT, CURIOUS, EVEN HANDED KIND OF NEUTRAL ACCEPTING ATTENTION STYLE TO WHAT FOR EXAMPLE PAIN OR OTHER DISCOMFORT SENSATIONS OR CAN YOU HAVE THE HYPER VIGILANT ANXIETY MELA DRAMA STYLE AND THIS HAS TO BE DIFFERENTIATED WHEN YOU TALK ABOUT INTROCEPTION BECAUSE INTROCEPTION CAN BE MALADAPTIVE IF YOU FEEL TOO MUCH FROM YOUR ANXIETY AND SENSATIONS, THAT DOESN'T HELP YOU VERY MUCH. SO, THIS DIFFERENTIATION DOES NOT HAPPENING WHEN YOU DO THE HEART BEAT POUNDING TEST OR THE HYPER TENSION TEST OR OTHER ACCURACY MEASURES AND THAT'S WHY I BELIEVE WE NEED THIS DIFFERENTIATION IN ADDITION. SO I BRING SEVERAL EXAMPLES OF SELF-REGULATION, PARTICULARLY THE SCALES OF THE MOST OF THESE STUDIES AND THEY SHOW SELF-REGULATION THIS IS AN IMPORTANT ELEMENT FOR MY BODY, IN CHANGING SELF-REGULATION IN FACTORS IN MY BODY INTERVENTIONS, THIS IS FROM 1 OF THE LARGEST STUDIES EVER ON MEDITATION IN PERLYNN [INDISCERNIBLE] WHERE THEY FOUND THAT SELF-REGULATION HERE WAS THE LARGEST EFFECT SIZE COMPARED TO CONTROLS, ATTENTION REGULATION, SECOND AND SO, ALL THESE REGULATORY ASPECTS OF INTROCEPTIVE AWARENESS WHERE THE KEY ELEMENTS IN MY BODY INTERVENTIONS AND ALSO SHOWS THAT DIFFERENT ASPECT OF INTERCEPTION CHANGE IN VERY DIFFERENT DEGREES. AND THIS IS FROM THE BRIEF INTERVENTION STUDY AND MINDFULNESS NBCT COGNITIVE THERAPY FOR DEPRESSION, WHICH SHOWS THE SEQUENTIAL MEDIATION OF THE TREATMENT ITSELF WHICH IS LIKE 4 AND HALF HOUR OF MINDFULNESS RELATED TO DEPRESSION CHANGE REGULATORY ASPECT OF SYSTEM, [INDISCERNIBLE] THAT IN TURN CHANGED THE CENTERING OR DEIDENTIFICATION FROM THE THOUS ABOUT YOUR DEPRESSION SCH THAT IN TURN MEDIATED THE CHANGES IN POST DEPRESSION, SO HAVE YOU SEQUENTIAL MEDIATION WHERE THE INTROCEPTIVE AWARENESS IS 1 ELEMENT OF THE PROCESS THAT HAPPENS IN A MINDFULNESS TREATMENT FOR DEPRESSION. THIS IS ANOTHER SEQUENTIAL MODEL OF MEDIATION WHERE HE HAD DONE IT AT UCSF, WHERE WE DID A STUDY ON MINDFULNESS BASED CHILD BIRTH AND PARENTING IN WOMEN WHO ARE PREGNANT WITH CONTROL, THERE WAS A CONTROL INTERVENTION TO BE FOUND THAT THE INTERVENTION MINDFULNESS BASED CHILD BIRTH AND PARENTING BEFORE BIRTH CHANGED POSTPARTUM DEPRESSION VIA THE SEQUENTIAL MEDIATION MECHANISM BY CHANGING ATTENTION REGULATION AND OTHER REGULATORY INTROCEPTION WHICH CHANGED [INDISCERNIBLE] WHICH IS THE KEY ELEMENTS OF PAIN CATASTROPHIZING WHICH IN TURN CHANGED THE DEPRESSION POSTPARTUM AND EVEN HAD A TREND TOWARD LOWER OPIOID USE WHILE THESE WOMEN WERE IN LABOR. ANOTHER STUDY, THIS IS [INDISCERNIBLE] WORK, MINDFULNESS BASED ON THERAPY SHE USED THE MAIA SCALE WHICH SHOWED IMPROVEMENT IN THE MINDFULNESS INTERVENTION AND SUBSTANCE USE DISORDER UNDERGOING TREATMENT, CHANGE ALL, IT MAY COME THAT THEY WANTED TO KNOW AND THIS WAS WITHOUT THE MEDIATION ON THIS, BUT IN PARALLEL, TO CHANGES AGAIN, IN SELF-REGULATION, ATTENTION REGULATION AND [INDISCERNIBLE] IN THE INTROCEPTIVE AWARENESS PROCESS. NOW THIS STUDY IS FROM PETER WANE'S GROUP AT HARVARD CENTER WHERE THEY DID [INDISCERNIBLE] STUDY, THIS IS ONLY SINGLE STUDY BUT IT'S IMPROVED SEVERAL OUTCOME MEASURES, POST SURGICAL PAIN PATIENTS FROM BREAST CANCER SURGERY AND AGAIN THAT WAS IN PARALLEL TO KEY REGULATORY OUTCOMES IN OF INTROCEPTIVE AWARENESS. NOW THIS IS THE STUDY HERE FROM ACTUALLY THE KATHRYN'S LAB AT THE INTRAMURAL NIH WHERE THEY FOUND THAT CROSS SECTIONALLY YOGA PRACTITIONERS, LONG-TERM, YOGA PRACTITIONERS HAD TO CLEARLY IMPROVE PAIN [AUDIO CUTS OUT ] FOR THE HUBS FOR INTROCEPTION AND THIS--ALSO WHAT'S CORRELATED WITH THE YEARS OF YOGA EXPERIENCE. SO THE--THE LONGER THEY DID YOGA THE NOR CHANGES THEY HAD. NOW I'M SHOWING FOR THE OTHER--FOR THIS REASON ON THE LEFT SIDE OF THE SLIDE, TO SEE THAT HOW THEY DEALT WITH THIS EXPERIMENTAL PAIN, THIS WAS A PRESSURE AND HAND AND ICE HOLDING TEST. SO THE PEOPLE WHO DID YOGA THEY ACCEPTED THE PAIN, THEY RELAXED, THEY OBSERVED WHAT THEY PERCEIVED AND THEY KEPT BREATH AWARENESS, WHEREAS THE CONTROLS, DISTRACTED THEMSELVES, IGNORED THE PAIN AND DIDN'T HAVE--HAD A MUCH LOWER PAIN THRESHOLD. SO THIS IS UNFORTUNATELY A CROSS SECTIONAL STUDY SO WE NEED TO CONTINUE IT. SO THE LAST SLIDE I WANT TO SHOW IS THE LAB WHERE WE USE NCCIH,RYALATING TO CHRONIC PAIN, THE WHOLE PURSUE WAS A CANADIAN IN CANADA THAT PUBLISHED SOME STUDY WHERE THEY FOUND THAT THE MAIA WAS ACTUALLY DOMINATING 1 OF 4 NEURAL TRAITS FOR THE TRY TO DISTINGUISH DIFFERENT TYPES OF PEOPLE THAT HAVE CHRONIC LOW BACK PAIN AND TRY TO PHENOTYPE THEM INTO DIFFERENT PATTERNS OF SUBTRAITS. SO, THE MAIA ACTUALLY REGULATION ASPECT AGAINST THE REGULATION WERE THE KEY ELEMENTS OF 1 TRAIT AND THESE KEYS SCALE AWARENESS AND HOW YOU EMOTIONAL STATES ARE RELATED TO BODY SENSATIONS THESE 3 SCALES WERE THE ONLY SCALES OUT OF 19 DIFFERENT QUESTIONNAIRES THAT THEY USE THAT WAS--THAT WERE ABLE TO PREDICT TREATMENT OUTCOME. IN THIS CASE, IT WAS A PLACEBO STUDY FOR CHRONIC LOW BACK PAIN. SO, ALL I WANTED TO SAY THERE IS WE NEED TO DO PHYSIOLOGICAL MEASURES, LIKE WHAT WAS PRESENTED ALREADY BUT WE ALSO SHOULD USE QUESTIONNAIRES BECAUSE THEY'RE DIFFERENT, THEY'RE ABLE TO DIFFERENTIATE DIFFERENT DIMENSIONS OF INTROCEPTION AND ALL THE BENEFICIAL FROM THE MALADAPTIVE TYPE OF INTROCEPTIVE AWARENESS AND THAT'S--I FINISH THIS BY MENTIONING MY MAIN CO-CONTRIBUTORS TO THIS RESEARCH IN THE PAST. SO I TAKE IT OFF HERE. SORRY IF I TAKE SO LONG. >> THANK YOU EMPLOY WE WILL NOW GO INTO THE PANEL DISCUSSIONS, WE WILL HAVE THE IC IMPLEMENTATION SO, THE FIRST 1 IS DR. GENE SIMON. >> GOOD AFTERNOON. THANKS FOR HAVING ME, SO I JUST WANTED TO TOUCH ON NATIONAL INSTITUTE ON AGING'S APPROACH TO EVERYTHING INCLUDING INTROCEPTION, SO IN GENERAL I THINK THAT ANY OF THE TECHNIQUES AND METHODOLOGIES THAT BEHAVIORIAL PSYCHOLOGICAL, NEUROPHYSIOLOGICAL LEVELS ARE GOING TO BE RELEVANT TO THE NATIONAL INSTITUTE ON AGING BECAUSE THE SCOPE OF OUR INSTITUTE'S GOALS IS VERY WIDE. WE ARE TRYING TO UNDERSTAND THE BASIC BIOLOGY, UNDERSTANDING CHANGES THAT ACCOMPANY AGING AS DISTINCT FROM THE UNDERLYING SPECIFIC DISEASES, RECOGNIZING ALSO THAT PEOPLE WITH AGING OF COURSE DEVELOP A MULTITUDE OF DISEASES THAT INCLUDES UNDERSTANDING SENSORY AND MOTOR CHANGES WHICH INCLUDES INTROCEPTION AND INCLUDING HOW NEUROBIOLOGICAL PSYCHOLOGICAL AND BEHAVIORIAL INTERACTIONS CHANGE AND EFFECT EACH OTHER THROUGH AGE. ANY OF THE APPROACHES THAT HAVE BEEN DESCRIBED TODAY COULD BE RELEVANT. THE MOST IMPORTANT THING I THINK TO EMPHASIZE HERE IS THAT ASKING INVESTIGATORS WHEN THEY'RE THINK BEING INTROCEPTION TO TAKE A LIFE SPAN PERSPECTIVE AS WELL AND CONSIDER INCLUDING LONGITUDINAL STUDIES AND WEBBINGINIZE THAT INTROCEPTIVE SENSITIVITY MEASURES OR SELF-REPORPTS OF INTROCEPTION MAY CHANGE WITH AGE OR WITH COGNITIVE CHANGE. I'LL LEAVE IT THERE. >> OKAY, THANK YOU I AM JIM FROM NINDS AND I WILL JUST QUICKLY USE THIS SLIDE TO SHOW HOW NINDS' INTEREST IN NEUROLOGY DISORDERS OF NEUROLOGY OVERLAP WITH THICISM THOMAS COVINGTONS AND THE DISORDERS WITH INTROCEPTION AND I WOULD REALLY JUST CALL YOUR ATTENTION TO APPLY APPROACHES THAT HAVE A CELL ARRA RESOLUTION THAT UNDERSTANDS THE SYSTEM THAT GIVES US A MECHANISTIC STUDY OF DYNAMIC PATHWAYS THROUGH THE BRAIN AND CELLULAR LEVELS SO THANKS TO THEM AND THE SPEAKERS TODAY. >> HI, I'M STEVEN GRANT FROM THE NATIONAL INSTITUTE ON DRUG ABUSE AND INTRO ACCEPTION IS A KEY ISSUE IN UNDERSTANDING THE ACTIONS OF DRUGS OF ABUSE. AS WAS OUTLINED IN THE TALKS TODAY THERE ARE RECEPTORS FOR ALL THE MAJOR DRUGS OF ABUSE ON VISCERAL AND ORGANS PERIPHERAL INTROSEPTIC PATHWAYS DESCRIBED, THE CENTRAL PATHWAYS THAT WERE DESCRIBED AND SELF-REPORTED INTROCEPTION IS PART OF WHAT PEOPLE REPORT WHEN THEY TAKE DRUGS OF ABUSE AND EVEN FORM THE BASIS OF ANIMAL STUDIES SUCH AS DRUGS, DISCRIMINATION. IN SUBSTANCE ABUSE DISORDER PATIENTS, DISREGULATED RESPONSES TO CORTICAL ANTERIOR RECEPTIVE BRAIN NETWORKS, PARTICULARLY THE ANTERIOR SINGULATE AND THE INSURVEYS LIE THAT WERE EMPHASIZED IN THE FITTER TALK ARE DISRUPTED IN PATIENTS WITH SUBSTANCE USE DISORDER AS IS SUBJECTIVE INTROCEPTION BOTH SENSORY AND METACOGNITION THAT IS MONITORING THE INSIGHT AND THE DENIAL WHICH IS A KEY CONTRIBUTOR IN SUBSTANCE ABUSE, BUT THE KEY CONTRIBUTION TO INTROCEPTIVE PROCESSES AND THEIR ALTERATION BY DRUGS OF ABUSE, HOW THAT CONTRIBUTES TO SUBSTANCE ABUSE DISORDER REMAINS UNCLEAR AND THEREFORE IS A BIG GAP IN OUR KNOWLEDGE. SO ADVANCES IN THIS AREA WOULD BE VERY MUCH RELATED TO THE MISSION OF NIDA. >> I'M JERRY WITH THE NATIONAL INSTITUTES OF MENTAL HEALTH. I WILL JUST POINT OUT A FEW THINGS THAT WE CONSIDER ARE IMPORTANT FOR INTROCEPTIONAL AS A ROLE AT PATHOLOGY OR EXPLORING AT A BASIC LEVEL HOW IT'S IMPACTED OR COGNITIVE AWARD ACEROUSAL OR REGULATORY SYSTEMS SO THE FIRST POINT TO CONSIDER, IS REALLY THE IMPORTANCE OF HAVING STANDARDIZED BEHAVIORIAL TASK AND MEASURING DIFFERENT FEATURES OF INTROCEPTION AND SOME OF THESE ARE REFERRED TO BY THE PREVIOUS SPEAKERS TO THE EXTENT POSSIBLE THESE TASKS SHOULD HAVE PSYCHOMETRIC PROPERTIES THAT ALLOW FOR A QUANTITATIVE ASSESSMENT AND TO BA ALSO COMPATIBLE WITH METHODS THAT MEASURE NEURAL ACTIVITY SUCH AS fMRI, EEG OR POTENTIALLY INTERCRANIAL RECORDING METHODS WHEN CLINICALLY JUDGE UTVIFYED. THE SECOND POINT IS REALLY A CONSIDERATION FOR CAUSAL EXPERIMENTAL DESIGN, TO ENHANCE MECHANISTIC UNDERSTANDING AND TO ULTIMATELY REALLY TRY TO EXPLAIN THE CAUSE AND EFFECTS OF RELATIONS BETWEEN VARIOUS ASPECTS OF INTROCEPTION AND PSYCHOPATHOLOGY. THE NEXT POINT HIGHLIGHTS THE IMPORTANCE OF COMPUTATIONAL MODELS WHICH HELPS PROVIDE A QUANTITATIVE FRAMEWORK FOR UNDERSTANDING THE COMPLEXITIES OF INTROCEPTIVE PROSELSZING AND FOR EXAMPLE, 1 OF THESE WAS MENTIONED BY DR. MEHLING, THERE ARE COMPUTATIONAL THEORIES THAT EXIST ON COMBINING AFERENT SIGNALING WITH OUR PRIOR EXPECTATIONS AND FINALLY ON A MORE TRANSLATIONAL CONSIDERATION IT WOULD BE CLEARLY VALUABLE TO IDENTIFY CLINICALLY SENSITIVE EFFECTIVE MEASURES THAT COULD POTENTIALLY SERVE AS ABOUT I O MARKER FIST ARE A DISEASE STATE. >> OKAY. DANA WOULD YOU LIKE TO SPEAK FOR FOR A MINUTE OR SO? >> SO MY NAME IS DANA [INDISCERNIBLE] AND I WORK AT THE OFFICE FOR BEHAVIORIAL AND SOCIAL SCIENCES RESEARCH AND WE ARE A COORDINATING OFFICE FOR THE NIH SO WE DON'T DIRECTLY FUND GRANTS BUT WHAT WE DO IS PROMOTE THE BEHAVIORIAL AND SOCIAL SCIENCES ACROSS THE WHOLE OF NIH CENTERS AND INSTITUTES AS FAR AS INTROCEPTION, FROM THE PRESENTATIONS CAN YOU HAVE SEEN TODAY YOU CAN CERTAINLY FIND AS I HAVE ON THE SLIDE JUST POINTING OUT A FEW OF THESE MORE BEHAVIORIAL LEANING ASPECTS OF THIS SUCH AS THE SELF-REGULATION, EMOTIONAL REGULATION, THERE'S BEEN RECENT RESEARCH OUT ABOUT THE ROLE OF INTROCEPTION AND SOCIAL CONNECTION AS WELL AS WHEN THINGS GO WRONG AND HAVE YOU ISSUES WITH INTROCEPTION, DYSFUNCTION AND MENTAL HEALTH WHERE IT'S BEEN IMPLICATED IN MENTAL HEALTH AS WELL AS OTHER DISORDERS SUCH AS OBESITY. ANOTHER POTENTIAL AREA OF INTEREST IS ALSO THE DIFFERENCES THAT YOU WOULD SEE BETWEEN DIFFERENT CULTURES AND SOCIAL ECONOMIC STATUSES BETWEEN DIFFERENT POPULATIONS AND THE DIFFERENCES IN THE INTROCEPTIVE PROCESSING IN THESE POPULATONS AND I WILL LEAVE IT AT THAT AND THANK YOU VERY MUCH FOR ALL THE SPEAKERS TODAY. >> THANK YOU DANA. SO I WILL SPEAK VERY BRIEFLY FROM NCCIH PERSPECTIVE, THIS IS WANG CHEN AGAIN, AS YOU HEARD ACTUALLY MANY OF THE TALKS TODAY, ALL OF THEM HAVE TALKED ABOUT THE INTERACTIONS BETWEEN THE COMPLIMENTARY GREAT HEALTH APPROACHES INCLUDE PREDOMINANTLY IN THE MIND AND BODY PRACTICES, AND HOW THEY MAY MODULATE THE VARIOUS STEPS OF THE INTROCEPTION PROCESSES, AS WELL AS THEY MIGHT BE ABLE TO SERVE AS A TOOL TO HELP US PROBE THOSE PROCESSES. I WANT--I ALSO WANT TO TAKE THIS OPPORTUNITY TO POINT OUT THAT THE OTHER HALF OF OUR PORTFOLIO REALLY INCLUDES NATURAL PRODUCTS WHICH INCLUDE BOTANICALS, PROBIOTICS AND MICROBIALS, YOU KNOW THE GUT MICROBES FOR INSTANCE AS WELL AS SPECIAL DIETS AND DIETARY SUPPLEMENTS AND THEN OF MEAZ MIGHT ALSO BE THE INTROCEPTIVE PROCESSING AS WELL AS THE GAIN ACCESS AND I WANT TO BRING THAT INTO THE PICTURE AS WELL AS HOW IMPORTANT THEY MAY BE IN ADDITION TO ALL THE VERY IMPORTANT ASPECTS WE TOUCH OFFICE OF DIVERSITY TODAY BY THE SPEAKERS, I WOULD BASICALLY LEAVE AT THAT AND MAYBE WE'LL OPEN, WE ARE RUNNING A BIT SHORT ON TIME. WE WILL HAVE ABOUT 6 MINUTES LEFT FOR QUESTION AND ANSWERS. WE'VE RECEIVED QUITE A FEW QUESTIONS AND I WOULD LIKE TO HAVE THE PANELISTS TURN ON THEIR VIDEO SO WE CAN ANSWER QUESTIONS. WE WILL PROBABLY NOT BE ABLE TO GO THROUGH ALL THE QUESTIONS PEOPLE SUBMITTED ONLINE AND IF YOU HAVEN'T DONE IT, YOU CAN--IF YOU WATCH THROUGH THE NIH VIDEOCAST IF YOU CAN SCROLL DOWN ON THE WEBPAGE AND YOU WILL SEE LIVE FEEDBACK AND THERE'S A LIVE FEEDBACK FORM, YOU CAN TYPE IN YOUR QUESTIONS, PLEASE SENDING THE QUESTIONS EVEN IF WE CANNOT ANSWER THEM TODAY ON THE VIEDMANIOY CAST, WE WILL TRY TO GET BACK TO YOU BY E-MAIL WITH AN ANSWERS. SO NOW FIRST OF ALL, WE WILL--THE FIRST QUESTION WE WOULD LIKE TO POSE TO THE SPEAKERS AND PANELS, I THINK IT'S PRIMARILY TO DR. [INDISCERNIBLE], REGARDING THE DEFINITION OF INTROCEPTION, WHICH WE AS THE DOCTOR MENTIONED IN THE KINDS OF UPREGULATION, SO THE QUESTION IS, DOES IT ADDRESS GENERATION OF INTERNAL SIGNAL? WOULD YOU LIKE TO TAKE THIS? p>> THE ANSWER IS CLEARLY YES, YES. THAT'S PART OF THE DEFINITION OF INTERRECEPTION AS WE TALKED ABOUT IT TODAY. AND SO, YOU KNOW THERE MIGHT BE OTHER WAYS TO DEFINE THIS, BUT THERE MAY BE OTHERS FOR THE PURPOSE OF THIS FRAMEWORK. >> YEAH, I WOULD LIKE TO ADD AS WELL THAT THE REGULATION PARTS OF INTROCEPTION IS PRIMARILY MEANT TO SAY REGULATING THE GENERATION OF INTROCEPTIVE SIGNALS. CERTAINLY THE REGULATION OF A BODILY FUNCTIONS, THAT MANY TIMES MAY OVERLAP WITH THE GENERATION SIGNALS BUT NOT ALWAYS BUT WE WANTED TO KEEP THOSE DISTINCTIONS IN MIND OKAY, ANYBODY ELSE FROM THE AUDIENCE THAT WOULD LIKE TO CHIME IN ON A PARTICULAR ISSUE? ALL RIGHT. IF NOT WE'RE GOING TO THE SECOND QUESTION, THE SECOND QUESTION IS RELATED TO--IS POSED TO DR. FRANGEL, AND IT'S ABOUT ACCUPUNCTURE. IF THERE ARE COMMENTS IN THE EVIDENCE IS ALSO WHAT ARE THE--SO THE IMPORTANT RESEARCH DIRECTION IN THE FUTURE TO ADDRESS THOSE TO SOLIDIFY THE EVIDENCE OF POTENTIAL IMPORTANCE AND RELEVANCE. WOULD YOU LIKE TO TAKE IT? >> YEAH, SURE. SO I PERSONALLY HAVE NOT DONE ANY ACCUPUNCTURE RESEARCH BUT IT'S CERTAINLY A VIABLE APPROACH. AND IF I UNDERSTAND CORRECTLY THERE ARE ACCUPUNCTURE PROCEDURES THAT DO INVOLVE SOME FORM OF ELECTRICAL STIMULATION AS WELL. AND SO IF YOU ACTUALLY LOOK AT THE ACCUPUNCTURE MAP OF THE EAR, THE REGION THAT WE TYPICALLY SIMULATE OR THAT SOME STUDIES HAVE SIMULATED WHICH IS A SIMPLE KONKA THAT I PRESENTED, IF YOU LOOK AT THE ACCUPUNCTURE MAP NEWSCAST EAR, WHAT YOU SEE IN THAT REASON YOJ IS THE VISCERA, AND IS SEEMS LIKE, YOU KNOW THIS INFORMATION HAS BEEN KNOWN FOR SEVERAL HUNDREDS OF YEARS AND IT'S ONLY NOW THAT THAT WE'RE BEGINNING TO READ DISCOVER THIS USING DIFFERENT TYPES OF TOOLS. SO IT'S SYRUPLY A VIABLE ALTERNATIVE. I AGREE THERE HAVE BEEN MIXED FINDINGS BUT I PERSONALLY HAVE NOT DONE THIS TYPE OF WORK AND I HOPE THIS ADDRESSES THE QUESTION. >> OKAY, AND ALSO I WANT TO MAKE SURE OUR PANELISTS AND SPEAKER VS A CHANCE TO ASK QUESTIONS TO EACH OTHER. [INDISCRNIBLE] YOU HAVE A QUESTION FOR-- >> SORRY. HI. >> HI THIS, IS ALEXANDRIA FROM NIMH AND JUST PRECEPTED SOY WE'RE THINKING ABOUT INTROCEPTION WHICH IS A VERY NORMAL AREA, SO I WENT TO [INDISCERNIBLE] I GUESS, HAVE THERE BEEN ANY STUDIES THAT HAVE ACTUALLY LOOKED AT THE NEUROBIOLOGICAL CHANGES AFTER NONINVASIVE VAGALL STIMULATION? SO I AM AWARE THERE ARE FMRIs FOR EXAMPLE, EXAMINING VAGALL STIMULATION IN FEAR AND CODING AND THEY HAVE LOOKED MOSTLY AS TO WHETHER THEY'RE ENGAGING THE PROJECTION TARGETS [INDISCERNIBLE] BUT I'M JUST UNAWARE OF ANY STUDIES THAT THEY ACTUALLY LOOKED SO OKAY, WITH THIS IMPROVEMENT IN RESPONSES TO FEARFUL STIMULI COINCIDES WITH KNOWN BIOLOGICAL TARGETS, THE CONNECTIVITY WITH THE PREFRONTAL BRAIN TO THE LIMBIC AND SO FORTH, SO I'M JUST WONDERING, QUESTION FOR YOU AND FOR ANYONEOT PANEL. >> YEAH, SO, THE LITERAURE ON TRANSCUTANEOUS VEGAS NERVE STIMULATION HAS REALLY GROWN EXPONENTIALLYOT PAST 10 YEARS AND INFORMATION ABOUT CONNECTIVITY ANALYSIS USING fMRI APPROACHES OR OTHER BIOLOGICAL MEASURES LIKE PUPIL DILATION MEASURES OR ACTIVITY OF THE HEART RATE VARIABILITY CHANGES. THAT HAS BEEN PUBLISHED BUT AGAIN, EVEN WITHIN THESE DIFFERENT TYPES OF EFERENT UNCLEAR AS TO WHAT ARE THE SPECIFIC PARAMETERS THAT SHOULD BE USED TO INDUCE THESE TYPE OF EFFECTS AND IT'S UNCLEAR WHAT LOCATION TO STIMULATE IN, WHAT IS THE APPROPRIATE CONTROL TO USE, SO THESE ARE STILL OUTSTANDING QUESTION ANDS THIS IS WHAT WE HOPE TO REALLY CONSOLIDATE GOING FORWARD WITH THIS CONSENSUS PAPER THAT IS UNDER REVIEW RIGHT NOW. SO HOPEFULLY WE CAN GET BETTER ANSWERS TO THESE QUESTIONS. BUT, YEAH. THIS IS A LOT OF LITERATURE IN TERMS OF DIFFERENCES IN CONNECTIVITY ANALYSIS AS WELL, PARTICULARLY IN THE MOST THAT I'VE COME ACROSS IS WITHIN THE REALM OF EFFECTS OF TBNS ON DEPRESSION OR ANXIETY. >> I KNOW WE ARE RUNNING OUT OF TIME BUT I GOT A MESSAGE SAYING WE CAN STAY ON FOR A FEW EXTRA MINUTES SO I WILL SEE IF WE CAN EXTEND ANOTHER 5 MINUTES TO ANSWER QUESTIONS ISSUES AS THE QUESTIONS ARE COMING IN. I WILL READ THE QUESTION, THIS IS A QUESTION FOR THE REPRESENTATIVE FROM NIDA, SO STEVE THIS, IS FOR YOU. THE QUESTION, THE PERSON THIS IS MARK ANDROGENNER MAN FROM HARVARD MEDICAL SCHOOL, HIS QUESTION IS: I'M WONDERING IF STUDIES EXIST DELIVERING% ANALOGUES TO DRUGS OF ABUSE--YOU NEED TO UNMUTE YOURSELF PLEASE? >> I WROTE A TEXT REPLY TO THAT RESPONSE BECAUSE I DIDN'T KNOW WHETHER WE WOULD HAVE TIME. THE SHORT ANSWER IS THERE HAVE BEEN STUDIES PARTICULARLY OF COCAINE METHYL IODIED WHICH DOES NOT CROSS THE BLOOD BRAIN BARRIER, THAT DRUG IS NOT SELF-ADMINISTERED HOWEVER, IT STILL LEAVES OPEN THE ISSUE OF OTHER DRUGS OF ABUSE, HOW MUCH PERIPHERAL ACTIONS MAY CONTRIBUTE TO SELF-ADMINISTRATION AND THE FURTHER ISSUE OF HOW MUCH PERIPHERAL ACTION INTROCEPTION PLAYS IN THE PROCESS OF ADDICTION AS OPPOSE TO DRUG ACTION. SO IT'S STILL VERY MUCH AN OPEN QUESTION AND WE DON'T HAVE A LARGE ARMADILLOSAMENTITARIUM OF PHARMACOLOGICAL TOOLS TO TEST THESE HYPOTHESIS. >> I HOPE YOU ARE HAPPY WITH THE ANSWER AND THE NEXT QUESTION IS FOR DR. FRANCO, DR. FRANCO MENTIONED THE ROLE OFF NOREPINEPHRINE RELEASES STIMULATION, DOES THERE ANYTHING WITH THIS TO AUTOIMMUNE AND INFLAMMATORY CONDITIONS AND THOSE TREATMENTS. SO THERE IS IN ANIMALS AND HUMANS THAT NOREPINEPHRINE IS RELEASED TO VAGALL STIMULATION, AS TO WHETHER THERE'S A DIRECT RELATIONSHIP BETWEEN NOREPINEPHRINE AND AUTOIMMUNE FUNCTIONS IS UNCLEAR TO ME, IT'S VERY OUTSIDE OF MY FIELD BUT IF YOU'RE INTERESTED IN THAT LINE OF WORK, THEN KEVIN TRACEY'S WORK IS REALLY WHERE YOU WANT TO LOOK AT AND I THINK YOU MAY FIND YOUR ANSWERS THERE. I WOULD VENTURE TO SAY THAT YES, THERE IS A ROLE FOR VAGALL STIMULATION AND BOOST RELEASE OF NOREPINEPHRINE ON INFLAMMATORY CONDITIONS, AND CONDITIONS BASED ON KEVIN TRACEY'S WORK. >> DEFINITELY. BUT INTROCEPTIVE IS A VERY INTERTWINED [INDISCERNIBLE] PROCESS SHOWN AS FROM THE TALK FROM JEANIE PARK, IF YOU MODULATE THE VIA, GO,A, L PROCESS COULD BE REGULATED AND SYMPATHETIC ACTIVITY AND VICE VERSA SO I THINK THERE'S A LOT OF OPPORTUNITY. RECENT OPPORTUNITIES THAT EXIST FOR PEOPLE TO EXPLORE. THE--THIS IS ANOTHER QUESTION FROM THE AUDIENCE OR LIKE ANY OF THE RESEARCHERS MAYBE THE PANELISTS AS WELL TO SPEAK ABOUT IF THEY'RE AWARE OF ANY RESEARCH CURRENT STUDIES INVOLVING DENSE MOVEMENT THERAPY AND INTROCEPTION AND THEY MENTION A SPECIFIC METHOD CALLED [INDISCERNIBLE] METHOD. I DON'T KNOW IF ANYBODY WOULD LIKE TO TAKE A RESPONSE FOR THAT. THIS IS REALLY DENSE MOVEMENT THERAPY, IN MANY WAYS IS COMPLEX THERAPY OBVIOUSLY HAS MANY COMPONENTS, SOME COMPONENTS COULD BE MODULATING THE PROCESSES, I'M NOT AWARE OF ANYBODY LOOKINGA THE ITS MODULATION OF THE INTROCEPTIVE PROCESS ALTHOUGH I WOULDN'T BE SURPRISED IF IT WOULDN'T HAVE AN EFFECT? >> SO I ACTUALLY GAVE AN INFORMAL LECTURE TO A DANCE GROUP THIS TIME LAST YEAR ON THIS TOPIC. AND THE SCIENTIFIC LITERATURE OBVIOUSLY IS VERY THIN. BUT WHEN YOU THINK ABOUT PROPROPRIOCEPTION, AND IN SPACE AND THE PARTICULARLY THE VESTIBULAR FUNCTION AND THE CIRCUITRY IN VESTIBULAR FUNCTION, IT CONVERGES ON THE SAME PATHWAY, CENTRAL PATHWAYS THAT HAVE MORE DESCRIBED IN THE TALKS TODAY. SO, I WOULDN'T BE SURPRISED THAT THERE WAS A SUBSTANTIAL EFFECT. AND IN THE CONTEXT OF SUBSTANCE ABUSE, I THOUGHT ABOUT DANCE THERAPY AND OTHER TYPES OF MOVEMENT THERAPIES INCLUDING TAI CHI AND HA MARTIAL ARTS THAT IT MIGHT BE BENEFICIAL IN TERMS OF--NOT IN TERMS OF INTROCEPTION, THAT MOVEMENT THERAPIES COULD BE A WAY OF STIMULATING THOSE CIRCUITS THAT GET BLUNTED AFTER CHRONIC DRUG ABUSE. SO IT'S A RICH FIELD, IT'S A RICH OPPORTUNITY BUT THERE IS NOT BEEN THAT MUCH WORK THAT I AM AWARE OF. >> OKAY, GREAT. THANK YOU STEVE. SO I THINK I KNOW YOU HAVE A QUESTION FOR DR. GENIE PARK AND I THINK IT'S IMPORTANT, WOULD YOU LIKE TO POSE IT DIRECTLY? >> SURE, SO I WAS WONDERING WHETHER USING THIS MICRONEUROGRAPHY APPROACH, WOULD WE BE ABLE TO DIFFERENTIATE THE NEURAL--I'M SORRY, I'M GETTING FEEDBACK FROM SOMEWHERE. --I DON'T KNOW, WELL, WOULD WE BE ABLE TO DIFFERENTIATE THE NEURAL EFERENT AND AFFERENT APPROACH IN THE CERVICAL VAGUS TRUNK WHICH IS COMPOSED OF THESE FIBERS. >> YEAH, SOPHISTICATEDY THAT WOULD BE A GREAT QUESTION FOR DR. MAYFIELD WHO IS DID THOSE FIRST INITIAL STUDIES LAST MONTH BUT YOU'RE RIGHT, THE VAGUS NERVE IS SO HETEROGENEOUS THAT IT WILL BE ESSENTIAL TO DETERMINE WHAT WE'RE ACTUALLY RECORDING WHEN WE'RE RECORDING FROM THE VAGUS NERVE AND SO THEY WERE ABLE TO TELL THAT THEY WERE RECORDING FROM CARDIAC EFFERENT NERVES BECAUSE THE NERVE SIGNALS CO VARY WIDE PHYSIOLOGIC SIGNALS IN THE HEART, AND IN THAT I WAI WERE ABLE TO DETERMINE THAT THESE ARE CARDIOACONS WE'RE RECORDING FROM. SOME OF THE AFFERENTS, THOUGH, YOU MAY NOT BE ABLE TO READILY MEASURE THE PHYSIOLOGIC SIGNALS COMING FROM THE GUT FOR EXAMPLE TO KNOW THAT YOU'RE MEASURING AFER ENSEL FROM THE GUT, SO I THINK IF THERE'S SOME WAY YOU CAN MANIPULATE THE PHYSIOLOGIC SIGNALS AND THAT CORRELATES WITH THE VAGUS NERVE, IMPULSE THAT YOU'RE RECORDING FROM THAT YOU CAN MAKE THE DETERMINATION BUT I THINK IT WILL REQUIRE BIG BREAK THROUGH IN THE FIELD BUT IT'S PROBABLY GOING TO REQUIRE MORE WORK TO WORK OUT ALL THOSE DETAILS. >> THANK YOU JEANIE, I THINK WE HAVE TIME FOR 1 MORE QUESTION AND THIS IS FOR [INDISCERNIBLE]. MIND EMPLOYNESS INTERVENTIONS BE EXPECTED TO HELP PEOPLE WHO FIND PANIC-INDUCING THROUGH TOLERATE PHYSICAL EXPERIENCE AND INCREASE CARBON DIOXIDE FOR MASK WEARING? OBVIOUSLY THAT IS VERY RELEVANT TO OUR CURRENT PANDEMIC SITUATION, WOULD YOU LIKE TO TAKE IT? >> WELL, I DON'T THINK THERE'S ANY STUDIES THAT HAVE BEEN DONE ON THAT, I DON'T KNOW. SO, PANIC DISORDER IS RELATED TO SYMPTOMS LIKE HEART BEATING FASTER, COLD FEET, ALL KINDS OF PHYSICAL SENSATIONS THAT ARE RELATED TO PANIC AND IF YOU WEAR A MASK, YOU MIGHT FEEL SOME DISPNIA WHICH IS ALSO PROVOCATION METHOD, SO THEORETICALLY, IT'S POSSIBLE, WE COULD FIND SOMETHING, I DON'T KNOW. >> OKAY. WE ARE REALLY RUNNING EXTRA TIME AND I THINK WE KIND OF HAVE TO CLOSE OUT, LET DR. EMILY EDWARDS TO CLOSE THE EEIVET TODAY. >> HI, EVERYBODY, I'M EMILY EDWARDS I'M THE DIRECTOR OF DIVISION OF EXTRA MURAL RESEARCH AT NCCIH. AND IT'S UNFORTUNATE THAT WE HAVE TO COME TO A CLOSE FOR THIS WONDERFUL SESSION, BUT BEFORE WE DO, I WANT TO THANK THE SPEAKERS AND THE PANELISTS FOR THEIR WONDERFUL PRESENTATION AND THE DISCUSSION. I ALSO WANT TO THANK THE AUDIENCE FOR THEIR PARTICIPATION. OBVIOUSLY THIS IS A VERY INTERESTING TOPIC AND AS WE HEARD THERE'S A LOT OF RESEARCH GAPS AND I LOOK FORWARD TO, YOU KNOW HAVING MORE DEVELOPMENT IN THIS AREA. BEFORE WE CLOSE, I WOULD LIKE TO EMPHASIZE THAT WE ARE GOING TO HAVE MORE FREQUENT HOT TOPIC WEBINARS AT NCCIH SO KEEP AN EYE OUT ON OUR WEBSITE, I DO BELIEVE THE NEXT 1 WILL BE SEPTEMBER ON THE CONCEPT OF IMPLEMENTATION SCIENCE. SO KEEP AN EYE OUT. SO THANK YOU VERY MUCH VERY MUCH AGAIN, IT WAS A WONDERFUL SESSION. >> OKAY, THANK YOU EVERYBODY. HAVE A GREAT REST OF THE DAY AND THANKS AUDIENCE FOR A JOINING US, TOO.