Boston Va Research Institute Inc

DEVELOPING STANDARDIZED INTRAOPERATIVE PROCESS MODELS TO ENHANCE SURGICAL SAFETY

SLOW-WAVE ACTIVITY AS A MODIFIER OF THE PROGRESSION OF NEURODEGENERATION IN ALZHEIMER'S DISEASE

PROJECT VALOR: TRAJECTORIES OF CHANGE IN PTSD IN COMBAR-EXPOSED VETERANS

MASSED COGNITIVE PROCESSING THERAPY FOR COMBAT-RELATED PTSD

LONG-TERM PSYCHOLOGICAL AND PHYSICAL HEALTH OUTCOMES FOLLOWING MILITARY DEPLOYMENT: THE VETERANS AFTER-DISCHARGE LONGITUDINAL REGISTRY (PROJECT VALOR)

SLEEP-DEPENDENT MECHANISMS OF IMPROVING CEREBRAL BLOOD FLOW AND REDUCING ALZHEIMER'S DISEASE PROGRESSION BY PHOTOBIOMODULATION WITH NEAR-INFRARED LIGHT - BRAIN PHOTOBIOMODULATION (PBM) USING NEAR-INFRARED (NIR) LIGHT IS A PROMISING NEW APPROACH FOR TREATING ALZHEIMER’S DISEASE (AD). DESPITE THE HIGH INTEREST IN USING PBM TO TREAT AD, ITS APPLICATION IS CURRENTLY HINDERED BY THE INSUFFICIENT UNDERSTANDING OF THE MECHANISMS OF NIR LIGHT ACTIONS IN THE BRAIN. ADDITIONALLY, NIR-I LIGHT (650-900 NM) HAS NOT ACHIEVED CLINICAL SIGNIFICANCE DUE TO ITS INSUFFICIENT PENETRATION INTO THE BRAIN TISSUE. WE HYPOTHESIZE THAT THE KEY MECHANISMS UNDERLYING TREATMENT PROPERTIES OF NIR LIGHT IN AD INCLUDE THE ACTIVATION OF ENDOTHELIAL NITRIC OXIDE SYNTHASE (ENOS) IN THE BRAIN, INCREASE OF NITRIC OXIDE (NO) PRODUCTION BY ENDOTHELIAL CELLS, VASOMOTION, INCREASE OF GLYMPHATIC FLOW, AND REDUCTION OF AMYLOID SS LOAD AND TAU PATHOLOGY. FURTHER, WE HYPOTHESIZE THAT THESE MECHANISMS CAN BE MARKEDLY ENHANCED BY THE PULSATION OF NIR-II LIGHT (1000-1700 NM) AT A LOW FREQUENCY DURING NON-RAPID EYE MOVEMENT (NREM) SLEEP. OUR SPECIFIC AIMS ARE DESIGNED TO TEST THE KEY ELEMENTS OF THIS HYPOTHESIS. WE PLAN TO TEST THAT NIR LIGHT TREATMENT IS MOST EFFICIENT WHEN IT IS DELIVERED IN NIR-II WINDOW AND DURING NREM SLEEP (AIM 1), THAT THE RATE OF NIR LIGHT STIMULATION RATHER THAN ITS DURATION DETERMINES THE EFFICIENCY OF THE PBM TREATMENT IN AD (AIM 2), AND THAT ENOS IS THE KEY MEDIATOR OF THERAPEUTIC EFFECTS OF NIR LIGHT IN AD, WHEREAS NEURONAL NITRIC OXIDE SYNTHASE (NNOS) IS NOT (AIM 3). THUS, WE PROPOSE A SERIES OF TRANSLATIONAL STUDIES THAT ARE AIMED TO IMPROVE OUR UNDERSTANDING OR THE ROLE OF NIR LIGHT IN REDUCING THE AD PATHOLOGY AS WELL AS TO IDENTIFY THE WAY OF NIR LIGHT DELIVERY THAT IS MOST EFFICIENT IN TREATING AD.

PRAGMATIC RANDOMIZED TRIAL OF POLYGENIC RISK SCORING FOR COMMON DISEASES IN PRIMARY CARE

PREVENTABLE FRAILTY ANCILLARY STUDY - ABSTRACT FRAILTY IS A STATE OF DEPLETED PHYSIOLOGIC RESERVE THAT IS COMMON IN OLDER ADULTS. TO DATE THERE ARE NO PROVEN THERAPIES TO PREVENT FRAILTY BEYOND RECOMMENDATIONS TO ADHERE TO A HEALTHY LIFESTYLE. FRAILTY IS ASSOCIATED WITH CHRONIC DISEASES, SUCH AS CARDIOVASCULAR DISEASE (CVD), THROUGH SHARED PATHOPHYSIOLOGY MEDIATED IN PART BY INFLAMMATION. STATINS ARE THE MAINSTAY OF CVD PREVENTION AND HAVE EFFECTS BEYOND LIPID LOWERING, INCLUDING REDUCING INFLAMMATION. YET, MANY ADULTS AGED 75 AND OLDER ARE NOT TAKING STATINS DUE TO A LACK OF EVIDENCE IN THIS AGE GROUP. THE ONGOING PREVENTABLE TRIAL WILL TEST THE EFFECT OF ATORVASTATIN 40MG VS PLACEBO IN 20,000 ADULTS AGED 75 AND OLDER FREE OF CVD FOR THE PRIMARY OUTCOMES OF SURVIVAL FREE OF DEMENTIA AND DISABILITY, AND SECONDARILY FOR INCIDENT CVD. HOWEVER, WHETHER STATINS CAN SLOW FRAILTY HAS NOT BEEN PREVIOUSLY TESTED AND IS NOT IN THE PARENT TRIAL’S PROTOCOL. THUS, THE PROPOSED STUDY IS CRITICAL TO ESTABLISH WHETHER STATINS MAY PREVENT OR SLOW THE PROGRESSION OF FRAILTY. PREVENTABLE PROVIDES A UNIQUE OPPORTUNITY TO TEST THE EFFECT OF STATINS ON FRAILTY USING THE TWO LEADING PREVALENT CONCEPTUAL FRAMEWORKS FOR QUANTIFYING FRAILTY: THE ROCKWOOD CUMULATIVE DEFICIT FRAILTY INDEX (ROCKWOOD FI) AND FRIED PHYSICAL PHENOTYPE. AS PART OF THE PARENT TRIAL, PARTICIPANTS WILL HAVE A SHORT PHYSICAL PERFORMANCE BATTERY (SPPB) PERFORMED AT BASELINE AND ASSESSMENT OF WEIGHT LOSS. A FUNDED PHYSICAL PERFORMANCE ANCILLARY STUDY WILL SUPPORT THE ADMINISTRATION OF THE SPPB AT ANNUAL FOLLOW-UP IN 2500 PARTICIPANTS AND ANNUAL QUESTIONNAIRES WILL QUANTIFY OTHER DOMAINS OF FRAILTY, INCLUDING FATIGUE AND PHYSICAL ACTIVITY. THE PROPOSED PREVENTABLE FRAILTY ANCILLARY STUDY WILL COMPLEMENT THE MAIN TRIAL BY CLEANING AND HARMONIZING EHR, CLAIMS, AND TRIAL DATA TO CALCULATE A ROCKWOOD FI FOR ALL TRIAL PARTICIPANTS (N=20,000), AND IN THE PHYSICAL PERFORMANCE SUBSET (N=2,000), ADD ANNUAL GRIP STRENGTH AND WEIGHT LOSS ASSESSMENTS TO COMPLETE THE FRIED PHENOTYPE. FINALLY, AN ANNUAL BLOOD SAMPLE WILL BE COLLECTED IN THE SAME 2,000 PARTICIPANTS TO MEASURE MARKERS OF INFLAMMATION, NEURODEGENERATION, AND OTHER MEASURES TO AUGMENT THE ROCKWOOD FI WITH SYSTEMATICALLY COLLECTED ROUTINE LABS, CALCULATE A LAB-FI, AND EXAMINE GEROSCIENCE PATHWAYS TO DETERMINE THE EFFECT OF STATINS ON MARKERS OF INFLAMMATION AND BIOLOGIC AGING. THE FRAILTY ANCILLARY STUDY WILL AUGMENT THE PARENT TRIAL AND EXISTING ANCILLARY STUDY TO DETERMINE WHETHER STATINS: 1) LOWER THE RISK OF INCIDENT FRAILTY DEFINED ACCORDING TO THE ROCKWOOD FI IN THE ENTIRE TRIAL POPULATION AND FRIED PHYSICAL PHENOTYPE IN A SUBSET, AND 2) SLOW THE PROGRESSION OF FRAILTY OVER TIME ACCORDING TO THE ROCKWOOD FI IN THE ENTIRE TRIAL POPULATION AND FRIED PHENOTYPE IN A SUBSET. FINALLY, IN THE SUBSET WITH ANNUAL BLOOD SAMPLES, WE WILL DETERMINE THE EFFECT OF STATINS ON AN FI AUGMENTED WITH LABS AND A LAB-ONLY FI. WE WILL ALSO EXPLORE THE EFFECT OF STATINS ON INFLAMMATION AND OTHER HALLMARKS OF AGING. LEVERAGING THE INFRASTRUCTURE OF THE PREVENTABLE TRIAL AND ITS PHYSICAL PERFORMANCE ANCILLARY STUDY, THIS TIMELY AND COST-EFFECTIVE PROPOSAL REPRESENTS AN EXCEPTIONAL OPPORTUNITY TO TEST THE POSSIBILITY OF STATINS AS A TREATMENT FOR FRAILTY AND BIOLOGIC AGING IN A RANDOMIZED SETTING.

BRIEF TREATMENT FOR PTSD: ENHANCING TREATMENT ENGAGEMENT AND RETENTION

REAL TIME NEUROFEEDBACK, ITS NEUROTRANSMITTER UNDERPINNINGS, AND THERAPEUTIC EFFECTS, IN CLINICAL HIGH RISK INDIVIDUALS - CLINICAL HIGH RISK (CHR) FOR PSYCHOSIS STATES ARE SYMPTOMATIC, DYNAMIC PERIODS THAT OCCUR BEFORE PSYCHOSIS ONSET AND ARE SUBJECTS OF INTENSIVE RESEARCH. THE FOCUS ON CHR IS DRIVEN BY EVIDENCE OF BEHAVIORAL AND BRAIN LEVEL IMPAIRMENTS IN MANY INDIVIDUALS EXPERIENCING THEIR ATTENUATED PSYCHOTIC SYMPTOMS WHICH ARE SIMILAR TO THOSE FOUND IN FIRST EPISODE AND CHRONIC SCHIZOPHRENIA (SZ): OUR WORK, AND THAT OF OTHERS, DEMONSTRATED THAT CHR INDIVIDUALS SHOW DEFICITS IN BOTH BRAIN FUNCTION AND COGNITION REMINISCENT OF THOSE FOUND IN SZ. FOR EXAMPLE, INCREASED DEFAULT MODE NETWORK (DMN) CONNECTIVITY FOUND IN SZ WAS ALSO IDENTIFIED IN CHR. THE CHR PERIOD OFFERS THE MOST HOPE FOR MITIGATING OR PREVENTING DISEASE DEVELOPMENT YET EFFECTIVE TREATMENT OPTIONS ARE STILL LACKING. THE OVERARCHING GOAL OF THIS R61/33 STUDY IS EARLY EFFICACY TESTING OF THE REAL-TIME FUNCTIONAL MRI-BASED NEUROFEEDBACK (RT-NFB), AIDED BY MINDFULNESS (RT-NFB+M), TO IMPACT BOTH BRAIN CONNECTIVITY AND CLINICAL AND NEUROCOGNITIVE (NP) OUTCOMES. IN THE R61 PHASE, WE WILL EXAMINE THE EFFICACY OF RT-NFB+M TARGETING THE DMN TO REDUCE MEDIAL PREFRONTAL AND POSTERIOR CINGULATE CORTEX (MPFC-PCC) HYPERCONNECTIVITY AND TO INCREASE MPFC-DORSOLATERAL PREFRONTAL CORTEX (DLPFC) ANTI-CORRELATIONS IN CHR SUBJECTS WHO WILL BE RANDOMLY ASSIGNED TO EITHER REAL-RT-NFB+M (N=24) OR SHAM/CONTROL -RT-NFB+M (N=24) CONDITION. THIRTY HEALTHY CONTROLS SCANNED ONCE WILL SERVE AS AN ADDITIONAL CONTROL GROUP. NEUROTRANSMITTERS IN MPFC AND DLPFC WILL ALSO BE ASSESSED USING MAGNETIC RESONANCE SPECTROSCOPY TO RELATE CELLULAR LEVEL MEASURES TO BRAIN NETWORK MEASURES. MPFC- PCC CONNECTIVITY REDUCTIONS AND MPFC-DLPFC INCREASED ANTICORRELATION, POST-NFB, IN THE REAL RT-NFB+M GROUP, WILL BE THE R61 GO CRITERIA. IN THE R33 PHASE, WE WILL REPLICATE R61 RESULTS IN AN INDEPENDENT SAMPLE OF 51 CHR IN THE REAL-FMRI NFB+M CONDITION, COMPARE THE EFFECTS OF RT-NFB+M (N=51 CHR) VERSUS MEDITATION ONLY (N=30 CHR), EXAMINE DOSE-RESPONSE OVER 4 SESSIONS, AND THE RELATIONSHIP BETWEEN NETWORK CONNECTIVITY AND GLUTAMATE (GLU) AND GABA CHANGES, AS WELL AS CLINICAL AND NEUROPSYCHOLOGICAL CHANGES, ESPECIALLY IN WORKING MEMORY (WM) AND ATTENTION, POST-INTERVENTION, IN BOTH RT-NFB+M AND IN THE MEDITATION ONLY GROUP. THIS PROPOSAL BUILDS ON OUR SUCCESSFUL USE OF RT-NFB IN SZ TO MODULATE THE DMN CONNECTIVITY AND MITIGATE SYMPTOMS. AS ONE OF THE FIRST IN THE FIELD, WE DEMONSTRATED THAT RT-NFB TARGETING THE DMN REDUCED ITS HYPER-CONNECTIVITY IN SZ WHICH; IN TURN, WAS ASSOCIATED WITH AUDITORY HALLUCINATIONS REDUCTION AFTER RT-NFB. INCREASED MPFC-DLPFC ANTICORRELATIONS WERE ALSO OBSERVED AND ASSOCIATED WITH INCREASES IN MPFC GABA IN A SEPARATE STUDY. FURTHERMORE, WE HAVE OBSERVED THAT INCREASES IN DMN-DLPFC ANTICORRELATIONS DUE TO PHARMACOLOGICAL OR BEHAVIORAL INTERVENTIONS ARE ASSOCIATED WITH IMPROVED WM AND ATTENTION. SINCE OUR PRELIMINARY DATA SUGGEST THAT SZ WITH THE LEAST ABNORMAL BRAIN PATTERNS BENEFITED MOST FROM OUR RT-NFB INTERVENTION, WE BELIEVE THAT ADOPTING THE RT-NFB IN CHR WILL BE HIGHLY EFFECTIVE IN ALTERING THE DISEASE TRAJECTORY.

HEMOGLOBIN A1C VARIABILITY AS A RISK FACTOR FOR DIABETES COMPLICATIONS

DEVELOPMENT AND PRELIMINARY EVALUATION OF A SELF-DIRECTED INTERNET-BASED COGNITIVE PROCESSING THERAPY INTERVENTION

A MICRO-COIL BASED CORTICAL VISUAL PROSTHESIS.

REAL-TIME FMRI NEUROFEEDBACK AS A TOOL TO MITIGATE AUDITORY HALLUCINATIONS IN PATIENTS WITH SCHIZOPHRENIA - THIS IS A RESUBMISSION APPLICATION, ORIGINALLY IN RESPONSE TO RFA-MH-16-406 AND CONSISTS OF R61 AND R33 PHASES. AUDITORY VERBAL HALLUCINATIONS (AH) HAVE LONG BEEN A HALLMARK OF SCHIZOPHRENIA (SZ) AND ARE ONE OF ITS MAJOR DIAGNOSTIC FEATURES ANDREASEN AND FLAUM 1991; DSM-IV). THEY ARE DIFFICULT TO MANAGE WITH EXISTING TREATMENT OPTIONS. HERE, WE PROPOSE THAT NEUROFEEDBACK AIMED TO REGULATE THE SUPERIOR TEMPORAL GYRUS (STG) ACTIVATION WILL NOT ONLY LEAD TO ACTIVATION CHANGES IN THE STG, BUT ALSO TO CHANGES IN THE DEFAULT MODE NETWORK (DMN) (R61), AS WELL AS TO REDUCTIONS IN AH (R33), AND THAT THE BRAIN AND CLINICAL CHANGES WILL BE CORRELATED (R33). THE THEORETICAL FRAMEWORK FOR THE CURRENT PROPOSAL IS AN AH MODEL THAT ASSUMES THAT AH RESULT FROM ABNORMALITIES IN A NETWORK OF REGIONS INCLUDING STG, AND MEDIAL PREFRONTAL CORTEX (MPFC) AND POSTERIOR CINGULATE CORTEX (PCC), THE TWO LATTER REGIONS ARE CORE MEDIAL HUBS OF DMN THAT ARE RELATED TO SELF-REFERENTIAL PROCESSING. THIS MODEL IS SUPPORTED BY THEORETICAL PAPERS NORTHOFF AND QIN 2010, ALDERSON-DAY,2016, AND EXPERIMENTAL EVIDENCE GUR 1995, LIDDLE 1992, DIERKS 1999 AS WELL AS OUR PRELIMINARY DATA (PD). IN BOTH R61 AND R33 WE WILL STUDY SZ PATIENTS WITH MEDICATION RESISTANT AH IN THE RT-FMRI INTERVENTION ARM AND IN THE SHAM-RT-FMRI ARM. IN BOTH ARMS, THE TASK AND THE RT-FMRI SESSION STRUCTURE WILL BE IDENTICAL. THE SZ-INTERVENTION GROUP WILL RECEIVE FEEDBACK FROM THE STG WHILE SZ-SHAM GROUP WILL RECEIVE FEEDBACK FROM THE MOTOR CORTEX. IN ADDITION, 2 FUNCTIONAL FMRI TASKS WILL EXAMINE THE EFFECT OF RT-FMRI NEUROFEEDBACK AND OF SHAM-RT-FMRI ON BRAIN RESPONSE. IN THE R61, WE WILL RANDOMLY ASSIGN 48 SZ PATIENTS TO EITHER SZ-INTERVENTION (N=24) OR SZ-SHAM-RTFMRI (N=24). THE STG TARGETED NEUROFEEDBACK IS PREDICTED TO BRING CHANGES IN BRAIN REGIONS INVOLVED IN AH (STG AND DMN) IN SZ-INTERVENTION GROUP ONLY. THE R61 GO CRITERION WILL BE BOLD SIGNAL REDUCTION IN THE STG, AND RESTING STATE CONNECTIVITY REDUCTION BETWEEN MPFC-PCC, POST RT-FMRI-FEEDBACK IN SZ-INTERVENTION GROUP. IN THE R33, SZ-INTERVENTION GROUP (RANDOM N=52) WILL RECEIVE 5 SESSIONS OF RT-FMRI FEEDBACK TARGETING STG, WHILE SZ-SHAM GROUP (RANDOM N=52) WILL RECEIVE 5 SHAM-RT-FMRI SESSIONS. BASED ON OUR PD, WE PREDICT THAT RT-FMRI FEEDBACK AIMED AT STG WILL REDUCE AH WHICH WILL BE, IN TURN, ASSOCIATED WITH REDUCTIONS IN THE STG ACTIVATION AND IN THE DMN CONNECTIVITY (I.E., BRAIN CHANGES ACHIEVED IN R61 AND REPLICATED IN R33) IN SZ- INTERVENTION GROUP ONLY. FIVE SESSIONS OF RT-FMRI FEEDBACK WILL ADDRESS THE QUESTION OF DOSE RESPONSE AT BRAIN AND CLINICAL LEVELS. THE IMPACT OF RT-FMRI NEUROFEEDBACK AND OF SHAM-RT-FMRI ON AH (PRIMARY OUTCOME), AND ON DELUSIONS, NEGATIVE SYMPTOMS AND WORKING MEMORY (WM) (EXPLORATORY OUTCOME) WILL BE ASSESSED WITH CLINICAL AND NEUROPSYCHOLOGICAL MEASURES. IN AN EXPLORATORY AIM, BASED ON THE EXISTING LITERATURE GARRITY 2007; WHITFIELD-GABRIELI 2009; ROTARSKA-JAGIELA 2010, WE PREDICT THE IMPROVEMENT IN DELUSIONS, NEGATIVE SYMPTOMS AND IN WM SCORE, ONLY POST-RT-FMRI NEUROFEEDBACK TARGETING THE STG AND NOT POST-SHAM-RT-FMRI.

PTSD-FOCUSED RELATIONSHIP ENHANCEMENT THERAPY FOR RETURNING VETERANS & THEIR PART

NEURAL CORRELATES OF SLEEP HOMEOSTASIS - THE BROAD OBJECTIVE OF THIS STUDY IS TO IDENTIFY THE NEURAL SUBSTRATE(S) UNDERLYING THE HOMEOSTATIC SLEEP RESPONSE (HSR), I.E. ENHANCED SLEEPINESS FOLLOWING PROLONGED SLEEP DEPRIVATION (SD). SD IS EXPERIENCED BY MANY DUE TO LIFESTYLE OR VOCATIONAL DEMANDS AND IS ACCOMPANIED BY IMPAIRED COGNITION, INCREASED IMPULSIVITY, AND AN INCREASED LIKELIHOOD OF ACCIDENTS. FURTHERMORE, DISRUPTED SLEEP IS A COMMON FEATURE OF MANY NEUROPSYCHIATRIC DISORDERS. THUS, UNDERSTANDING THE MECHANISMS UNDERLYING THE HSR IS CRITICAL TO DEVELOP MEASURES TO COMBAT THE DELETERIOUS CONSEQUENCES OF SD. SPECIFICALLY, HERE WE WILL ADDRESS THE CENTRAL QUESTION: “ARE ALL NEURAL WAKE-PROMOTING SYSTEMS EQUALLY IMPORTANT IN TRIGGERING THE HSR?” OUR OVERARCHING HYPOTHESIS IS THAT BASAL FOREBRAIN (BF) CHOLINERGIC NEURONS (CHAT+) ARE MODULATED BY GLUTAMATE AND PLAY A PRIVILEGED ROLE IN THE HSR BY CAUSING THE RELEASE OF EXTRACELLULAR ADENOSINE (ADEX), WHICH INCREASES SLEEP BY INHIBITING WAKE-PROMOTING BF NEURONS, AND THEREBY ADJUSTS THE STATE OF THE SYSTEM TOWARDS ITS' SET POINT. TOWARDS THIS GOAL, AIM 1, WILL TEST IF BF CHOLINERGIC NEURONS, BUT NOT THE BRAINSTEM PEDUNCULOPONTINE TEGMENTAL (PPT) CHOLINERGIC NEURONS, ARE REQUIRED FOR HSR. AIM 2 WILL TEST THE HYPOTHESIS THAT WITHIN BF, ONLY THOSE NON- CHOLINERGIC WAKE-PROMOTING NEURONS PROJECTING TO, AND EXCITING, BF CHAT+ NEURONS WILL INDUCE HSR. AIM 3 WILL TEST IF STIMULATION OF WAKE-PROMOTING BF-VGLUT2+ AND PPT-VGLUT2+ NEURONS WILL ONLY INDUCE HSR IF BF CHAT+ NEURONS ARE INTACT, I.E. THE INTEGRITY OF BF CHAT+ NEURONS IS NECESSARY TO TRIGGER THE HSR. FINALLY, AIM 4 WILL TEST THE DUAL ROLE OF BF CHAT+ NEURONS IN PROMOTING AROUSAL AND SLEEP HOMEOSTASIS. WE WILL USE OUR NOVEL MOUSE `OPTODIALYSIS' PROBES (ZANT ET AL., 2016) THAT COMBINE OPTICAL MANIPULATION OF SELECTIVE NEURONAL POPULATIONS WITH IN VIVO MICRODIALYSIS FOR DETECTING LOCAL NEUROCHEMICAL CHANGES AND/OR APPLICATION OF PHARMACOLOGICAL AGENTS. THE SUCCESSFUL COMPLETIONS OF THESE INVESTIGATIONS WILL FURTHER OUR UNDERSTANDING OF THE NEURAL SUBSTRATES NECESSARY FOR INDUCING THE HSR, AND THUS WILL HELP IN DEVELOPING TARGETED PHARMACOLOGICAL INTERVENTIONS AGAINST THE DELETERIOUS EFFECTS OF SLEEP LOSS.

PSTD - FOCUSED COGNITIVE BEHAVIORAL THERAPY FOR PARTNER VIOLENT OIF/OEF VETERANS

DISSECTING NEURONAL PARTICIPATION TO FOCAL EPILEPTIC EVENTS IN VIVO

REDEFINING GULF WAR ILLNESS USING LONGITUDINAL HEALTH DATA: THE FORT DEVENS COHORT

THE VA GENOMICS LEARNING HEALTH SYSTEM: IMPLEMENTING GENOMIC MEDICINE ACROSS DIVERSE VETERAN COMMUNITIES - PROJECT SUMMARY THE VETERANS HEALTH ADMINISTRATION OF THE DEPARTMENT OF VETERANS AFFAIRS (VA) IS THE LARGEST AND MOST DIVERSE LEARNING HEALTH SYSTEM (LHS) IN THE US, CARING FOR MORE THAN 9 MILLION PATIENTS ANNUALLY IN EVERY STATE AND US TERRITORY. A FULL QUARTER OF VA HEALTHCARE ENROLLEES NATIONALLY LIVE IN HRSA-DESIGNATED HEALTH PROFESSIONAL SHORTAGE AREAS (HPSAS). VA PATIENTS ALSO HAVE A GREATER BURDEN OF PHYSICAL AND MENTAL HEALTH COMORBIDITIES THAN THE GENERAL US POPULATION. NONETHELESS, A FOCUS ON PERFORMANCE MEASUREMENT AND IMPROVEMENT HAS KEPT THE QUALITY OF VA CARE AS HIGH OR HIGHER THAN IN THE PRIVATE SECTOR. THIS QUALITY HAS BEEN ACHIEVED BY VA’S INNOVATION IN IMPLEMENTATION SCIENCE AND EMBODIMENT OF LHS ATTRIBUTES, LEVERAGING ITS VAST CLINICAL ELECTRONIC HEALTH RECORD (EHR) DATA, ROBUST INFORMATICS INFRASTRUCTURE, AND PATIENT-CENTERED FOCUS TO CONTINUALLY EVALUATE AND IMPROVE PATIENT CARE BASED ON REAL-TIME MONITORING AND FEEDBACK. THE VA IS ALSO A NATIONAL LEADER IN CLINICAL GENOMIC MEDICINE, INCLUDING TELEGENETICS, PHARMACOGENOMICS, AND PRECISION ONCOLOGY. VA INNOVATIONS IN GENOMIC MEDICINE HAVE BEEN DRIVEN BY ITS LHS ECOSYSTEM OF DATA-INFORMED CONTINUOUS QUALITY IMPROVEMENT (CQI), INNOVATION, AND NATIONAL DISSEMINATION OF IMPLEMENTATION STRATEGIES FOUND TO BE EFFECTIVE AT LOCAL AND REGIONAL LEVELS. IN THIS PROJECT, VA WILL BRING ITS NATIONAL LHS INFRASTRUCTURE AND GENOMIC MEDICINE IMPLEMENTATION STRATEGIES TO A NETWORK OF OTHER GENOMICS-ENABLED LHS. THE NETWORK WILL CONDUCT IMPLEMENTATION PROJECTS CENTERED ON A MAINSTREAM MODEL FOR DELIVERY OF GENOMIC MEDICINE THAT PROMOTES THE USE OF EVIDENCE-BASED, GUIDELINE-CONCORDANT GENETIC TESTING BY FRONTLINE CLINICIANS. THE VA GENOMICS-ENABLED LHS WILL CONTRIBUTE TO THIS NETWORK EFFORT BY 1) IDENTIFYING AND SHARING WITH THE NETWORK AN IMPLEMENTATION APPROACH AND STRATEGIES WITH HIGH POTENTIAL FOR IMPLEMENTATION ACROSS DIVERSE HEALTHCARE SYSTEMS, INCLUDING UNDER-RESOURCED SETTINGS; 2) PROPOSING THREE IMPLEMENTATION TRIALS FOR NETWORK-WIDE CONDUCT (PHARMACOGENOMIC TESTING TO OPTIMIZE PHARMACOTHERAPY, GERMLINE TESTING TO INFORM CANCER TREATMENT, AND EHR IDENTIFICATION AND GERMLINE TESTING TO DIAGNOSE UNRECOGNIZED MONOGENIC DISEASE); AND 3) WORKING WITH THE NETWORK TO CONDUCT IMPLEMENTATION PROJECTS OF GENOMIC MEDICINE INTERVENTIONS ACROSS A SPECTRUM OF CLINICAL CONDITIONS AND PATIENT CHARACTERISTICS WITHIN THE VA GENOMICS-ENABLED LHS AND ITS COMMUNITY, RECRUITING UNDERSERVED POPULATIONS AND GEOGRAPHIC AREAS. THROUGH PARTICIPATION IN THIS NETWORK, THE VA WILL DISSEMINATE ITS DEEP LHS EXPERTISE TO OTHER CLINICAL SITES AND IN TURN BRING THE LEARNINGS FROM THE LARGER NETWORK TO IMPROVE THE GENOMIC HEALTH CARE AND OUTCOMES OF THE NATION’S MILITARY VETERANS, THEIR FAMILIES, AND COMMUNITIES.

DEVELOPMENTAL PROSOPAGNOSIA SUBTYPES: VALIDATION, NEURAL MECHANISMS, AND DIFFERENTIAL APPROACHES TO TREATMENT - THE GOAL OF THIS PROPOSAL IS TO BETTER CHARACTERIZE THE COGNITIVE AND NEURAL BASIS OF FACE PERCEPTION HETEROGENEITY IN DEVELOPMENTAL PROSOPAGNOSIA (DP) AND TO TEST WHETHER POTENTIAL PERCEPTUAL SUBTYPES ARE BETTER SUITED FOR ONE TYPE OF COGNITIVE TRAINING PROGRAM VS. ANOTHER. THIS IS RELEVANT TO THE NATIONAL EYE INSTITUTE'S MISSION TO BETTER TREAT VISUAL DISORDERS AND UNDERSTAND MECHANISMS OF VISUAL FUNCTION. OUR PILOT RESULTS (N=45 DPS) PROVIDE PRELIMINARY EVIDENCE THAT THERE ARE PERCEPTUALLY-IMPAIRED (PI-DPS) AND PERCEPTUALLY-UNIMPAIRED (PU-DPS) DP SUBGROUPS THAT MAY BE MECHANISTICALLY DISTINCT. WE FIND THAT PI-DPS HAVE DEFICIENT EYE PROCESSING, REDUCED HOLISTIC PROCESSING ABILITIES, REDUCED N170 RESPONSE TO EYE CONTRAST- REVERSED FACES, AND A TREND TOWARDS DECREASED WHITE MATTER INTEGRITY IN THE OCCIPITAL FACE AREA, A FACE-SELECTIVE REGION INVOLVED IN FACE PARTS PROCESSING. WE ALSO FIND THAT PI-DPS, COMPARED TO PU-DPS, SHOW A GREATER TREATMENT RESPONSE TO OUR COMPUTERIZED FACE PERCEPTION TRAINING PROGRAM. THE GOALS OF THE CURRENT PROPOSAL ARE TO BUILD ON THESE PILOT RESULTS TO FURTHER TEST AND VALIDATE THE PI-DP VS. PU-DP SUBGROUP DISTINCTION, TO BETTER UNDERSTAND THE NEURAL MECHANISMS UNDERLYING PERCEPTUAL HETEROGENEITY IN DPS, AND TO EXAMINE TREATMENT IMPLICATIONS OF POTENTIAL SUBGROUPS. IN PARTICULAR, OUR AIMS FOR THIS PROPOSAL ARE TO: 1) COLLECT A LARGE SAMPLE OF WEB-BASED AND IN-LAB DPS (N=280) AND CONTROLS (N=140) AND REPLICATE OUR PILOT FINDINGS SHOWING EYE PROCESSING AND HOLISTIC PROCESSING DEFICITS IN PI-DPS. WE WILL ALSO PERFORM LATENT PROFILE ANALYSIS TO DETERMINE IF DPS NATURALLY FORM PI-DP VS. PU-DP SUBGROUPS OR RATHER REPRESENT A CONTINUUM OF FACE PERCEPTION DEFICITS. 2) CHARACTERIZE THE NEURAL MECHANISMS OF DP FACE PERCEPTION HETEROGENEITY USING FUNCTIONAL FMRI, EEG, AND DIFFUSION TENSOR IMAGING IN 80 DPS AND 40 CONTROLS. TO TEST BETTER UNDERSTAND THE NEURAL UNDERPINNINGS OF DPS' REDUCED EYE REGION SENSITIVITY AND REDUCED HOLISTIC PROCESSING, WE SEEK EXAMINE THE N170 EVENT-RELATED POTENTIAL RESPONSE TO ISOLATED EYES VS. MOUTHS AS WELL AS FACE INVERSION AND FOR FMRI, POPULATION RECEPTIVE FIELDS OF FACE-SELECTIVE REGIONS AS WELL AS RESPONSES TO ISOLATED MOUTHS AND EYES. WE WILL ALSO EXAMINE WHETHER PI-DPS VS. PU-DPS HAVE WHITE MATTER INTEGRITY DIFFERENCES IN FACE-SELECTIVE WHITE MATTER REGIONS. 3) DETERMINE WHETHER PI-DPS VS. PU-DPS HAVE DIFFERENTIAL RESPONSES TO FACE PERCEPTION TRAINING, FACE MEMORY TRAINING, OR FACE PERCEPTION+FACE MEMORY TRAINING PROGRAMS. THIS WILL INVOLVE A LONGITUDINAL STUDY OF 120 DPS BEING ASSIGNED TO EITHER A WAITLIST CONTROL CONDITION OR 6 WEEKS OF ONE OF THE THREE COGNITIVE TRAINING PROGRAMS. BEFORE AND AFTER TRAINING/WAITING, WE WILL ASSESS DPS ON A VALIDATED BATTERY OF FACE PERCEPTION AND RECOGNITION TESTS AS WELL AS SELF-REPORTED FACE RECOGNITION. TO MEASURE THE LONGEVITY OF POTENTIAL TRAINING EFFECTS, DPS WILL ALSO REPEAT ASSESSMENTS AFTER A 6-WEEK NO-CONTACT PERIOD.

INTERACTIVE SPACED EDUCATION TO OPTIMIZE DIABETES CARE

THE STRONG STAR PTSD RESEARCH CONSORTIUM

EATING DISORDERS IN VETERANS, PREVALENCE, COMORBIDITY, RISK, AND HEALTH CARE USE

PREVENTIVING PTSB BY COPIN WITH INTRUSIVE THOUGHTS

DEVELOPMENT OF A PTSD POPULATION REGISTRY

HEMOGLOBIN A1C STABILITY AND DEMENTIA IN OLDER ADULTS WITH DIABETES

VASCULAR AND SKELETAL MUSCLE FUNCTION IN GULF WAR VETERANS ILLNESS

TARGETING THERAPEUTIC RESISTANCE IN COLORECTAL CANCER

STRENGTH AT HOME COUPLES PROGRAM TO PREVENT MILITARY PARTNER VIOLENCE

DEVELOPMENT AND VALIDATION OF A PTSD-RELATED IMPAIRMENT SCALE

IDENTIFYING GAPS IN PATIENT-PROVIDER COMMUNICATION AND IMPROVING CARE FOR VETERANS WITH GULF WAR ILLNESS.

MILITARY-RELATED TOXIC EXPOSURES AS A RISK FACTOR FOR AMYOTROPHIC LATERAL SCLEROSIS

ADAPTIVE DISCLOSURE: A COMBAT-SPECIFIC PTSD TREATMENT

EXAMINATION OF NEUROIMAGING, COGNITIVE FUNCTIONING, AND PLASMA BIOMARKERS IN A LONGITUDINAL COHORT FORT DEVENS

PRECLINICAL APPROACH TO MITOCHONDRIAL DYSFUNCTION IN GULF WAR ILLNESS...NEW GRANT, SIGNED 9/17/2019, EFFECTIVE 9/30/2019, DISTRIBUTED 9/18/2019, FAADC 9/18/2019

SUBCORTICAL INFLUENCE ON THE RESPIRATORY COORDINATION OF CORTICAL NEURODYNAMICSRELATED TO COGNITION - SLOW CORTICAL OSCILLATIONS, SUCH AS THETA BAND ACTIVITY (5-9HZ), MAY BE CRITICAL FOR COHERENCE OF ACTIVITY OVER LARGE DISTANCES, PROVIDING A MECHANISM FOR INTERREGIONAL COMMUNICATION INVOLVED IN NEURAL PROCESSING. FASTER GAMMA BAND OSCILLATIONS (GBO; 30-200 HZ) ARE THOUGHT TO PLAY A MAJOR ROLE IN HIGHER-LEVEL COGNITIVE PROCESSING INCLUDING ATTENTION. WHILE THE ROLE OF THETA/GBO COUPLING IN SELECT ASPECTS OF COGNITIVE PROCESSING HAS BEEN A TOPIC OF INTENSE INTEREST, RECENT FINDINGS SUGGEST THAT NASAL RESPIRATION CAN ALSO TEMPORALLY COORDINATE DYNAMIC NEURAL ACTIVITY IN THE BRAIN. THESE RESPIRATORY-ENTRAINED OSCILLATIONS ALSO EXHIBIT HIGH PHASE- AMPLITUDE COUPLING TO GBO (RG COUPLING) DURING SELECT BEHAVIORS. PRESENTLY IT IS UNKNOWN IF RG COUPLING HAS A ROLE IN COGNITION. OUR OVERARCHING HYPOTHESIS POSITS THAT THE STRENGTH OF RG COUPLING IN THE ATTENTION- RELATED FRONTOPARIETAL NETWORK (PRELIMBIC AND POSTERIOR PARIETAL CORTICES) WILL CORRELATE WITH VIGILANT ATTENTION- DEPENDENT PERFORMANCE. AIM 1: RG COUPLING IN THE FRONTOPARIETAL ATTENTIONAL NETWORK CORRELATES WITH PERFORMANCE IN AN ATTENTION-DEMANDING OPERANT TASK. WE WILL MEASURE RESPIRATION AND RESPIRATORY-ENTRAINED OSCILLATIONS IN LOCAL FIELD POTENTIALS IN SELECT BRAIN REGIONS TO EVALUATE RG COUPLING DURING AN OPERANT SIGNAL DETECTION TASK USED TO MEASURE VIGILANT ATTENTION, THE RODENT PSYCHOMOTOR VIGILANCE TASK (RPVT). IN THE RPVT, MICE MAINTAIN ATTENTION TO A STIMULUS LOCATION, AND RESPOND TO DETECTION OF A BRIEF AND UNPREDICTABLE CUE WITH A SHORT-LATENCY OPERANT RESPONSE TO RECEIVE FOOD REWARD. PRIOR TO CORRECT TRIALS, WE PREDICT THAT RG COUPLING WILL BE STRONG IN THE FRONTOPARIETAL ATTENTION NETWORK, AND THAT FAST REACTION TIMES WILL CORRELATE WITH ROBUST RG COUPLING. IN CONTRAST, PRIOR TO OMISSION TRIALS (ATTENTION FAILURES), WE PREDICT THAT RG COUPLING WILL BE DIMINISHED. AIM 2: ATTENUATION/PROMOTION OF RG COUPLING BY MEANS OF OPTOGENETIC MANIPULATION OF BASAL FOREBRAIN PARVALBUMIN NEURONS WILL IMPAIR/IMPROVE PERFORMANCE IN THE RPVT. OUR PRELIMINARY FINDINGS SHOW THAT CLOSED-LOOP GAMMA FREQUENCY STIMULATION OF BASAL FOREBRAIN PARVALBUMIN NEURONS IN RELATION TO RESPIRATORY INHALATION, BUT NOT EXHALATION, PROMOTES RG COUPLING. THEREFORE, WE WILL UTILIZE THIS STIMULATION PARADIGM TO DETERMINE HOW MODULATION OF RG COUPLING IMPACTS PERFORMANCE IN THE RPVT. ACROSS A RANGE OF SELECT NEUROPSYCHIATRIC ILLNESSES, THE PATHOLOGICAL PROCESSES BEHIND COGNITIVE DEFICITS INVOLVE ABNORMAL NEURAL TEMPORAL DYNAMICS. THUS, THESE BASIC RESEARCH STUDIES WILL HELP TO INFORM THE DEVELOPMENT OF TRANSLATIONAL THERAPIES TO RESTORE/ENHANCE COGNITIVE FUNCTION.

COLLABORATIVE RESEARCH: SCH: AN AI COACH FOR ENHANCING TEAMWORK IN THE CARDIAC OPERATING ROOM -CARDIAC SURGERY IS OFTEN NEEDED TO ADDRESS SOME OF THE MOST SERIOUS HEART PROBLEMS, RESULTING IN ADMINISTRATION OF MORE THAN 900,000 CARDIAC PROCEDURES EACH YEAR. THE CARDIAC OPERATING ROOM (OR) IS A COMPLEX ENVIRONMENT WHERE HEALTHCARE PROFESSIONALS FROM MULTIPLE DISCIPLINES -- INCLUDING SURGEONS, ANESTHESIOLOGISTS, PERFUSIONISTS, AND NURSES -- COLLABORATE TO ADMINISTER THIS LIFE-CRITICAL CARE. TO SUCCESSFULLY ADMINISTER CARE, ALL MEMBERS OF THE SURGICAL TEAM ARE EXPECTED TO PERFORM THEIR TASKS IN LOCKSTEP AND WITH FULL AWARENESS OF DYNAMIC SITUATIONS ENCOUNTERED DURING SURGERY. HOWEVER, ACHIEVING SUCH IDEAL TEAMWORK IS DIFFICULT IN THE COMPLEX ENVIRONMENT OF CARDIAC OR, WHERE HUMAN PERFORMANCE IS ADVERSELY AFFECTED BY FACTORS SUCH AS HIGH WORKLOAD, FATIGUE, AND INTERRUPTIONS OR DISRUPTIONS DURING SURGERY. THIS PROJECT ADDRESSES AN URGENT NEED FOR MITIGATING THESE PREVENTABLE HUMAN ERRORS AND IMPROVING PATIENT SAFETY THROUGH THE DESIGN OF AN ARTIFICIAL INTELLIGENCE (AI)-ENABLED COACHING SYSTEM (AI COACH) FOR MONITORING, ASSESSING, AND ENHANCING SURGICAL TEAMWORK IN THE CARDIAC OR. CENTRAL TO THE FUNCTIONING OF THE AI COACH WILL BE A SET OF NOVEL MACHINE LEARNING AND EXPLAINABLE ARTIFICIAL INTELLIGENCE ALGORITHMS TO COMPUTATIONALLY GENERATE INTERPRETABLE FEEDBACK AND INTERVENTIONS FOR ENHANCING SURGICAL TEAMWORK BASED ON MULTIMODAL SENSOR DATA. THE PROJECT WILL TRAIN STUDENTS IN THE MULTI-DISCIPLINARY RESEARCH AREA OF SMART HEALTH. THE PROJECT WILL INCREASE PUBLIC ENGAGEMENT WITH AI, BY INCORPORATING THE RESEARCH RESULTS INTO A PLANNED MUSEUM EXHIBIT ON HUMAN-AI COLLABORATION. THE PROJECT?S OVERARCHING GOAL IS TO DESIGN THE AI COACH SYSTEM COMPRISED OF MULTIMODAL SENSING HARDWARE, DATA-DRIVEN ALGORITHMS, AND A USER INTERFACE TO ENHANCE SURGICAL TEAMWORK IN THE CARDIAC OR. AI COACH WILL ACHIEVE ITS OBJECTIVES BY PURSUING TWO PARALLEL STRATEGIES: (I) ADDRESSING THE PROBLEM OF MODELING SURGICAL TEAMWORK; (II) COMPUTATIONALLY GENERATING FEEDBACK TO IMPROVE THIS TEAMWORK. THE PROJECT TEAM WILL FIRST DEVELOP A NOVEL TEAM MARKOV MODEL (TMKM) THAT REFLECTS THE SURGICAL TEAM?S MENTAL MODEL. THEN, THE COMPUTATIONAL CORE OF THE SYSTEM WILL BE REALIZED THROUGH THE DEVELOPMENT OF (A) MACHINE LEARNING ALGORITHMS BASED ON NOVEL MULTI-AGENT IMITATION LEARNING METHODS TO ARRIVE AT PREDICTIVE MODELS OF TEAMWORK THAT EXPLICITLY DEPEND ON LATENT PERFORMANCE-SHAPING FACTORS, SUCH AS MENTAL MODELS, AND (II) EXPLAINABLE AI TECHNIQUES TO COMPUTATIONALLY GENERATE INTERPRETABLE FEEDBACK AND INTERVENTIONS FOR ENHANCING TEAMWORK. DUE TO THE CHALLENGE OF COLLECTING LARGE DATA SETS OF SURGICAL TEAMWORK, THE ALGORITHM DEVELOPMENT WILL EMPHASIZE SAMPLE- AND LABEL-EFFICIENT TECHNIQUES. THE PROJECT TEAM WILL PROTOTYPE AND TEST USABILITY OF THE INTEGRATED SYSTEM BY EMPLOYING ITERATIVE, USER-CENTERED DESIGN APPROACHES. THE SOLUTIONS WILL BE DEVELOPED AND EVALUATED USING MULTI-MODAL EXPERT-ANNOTATED DATA OF SURGICAL TEAMWORK AND PROTOTYPED IN A STATE-OF-THE-ART OR SIMULATION FACILITY. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.

PANCREATIC CANCER RISK PREDICTED FROM ELECTRONIC HEALTH RECORDS IN U.S. VETERANS USING ARTIFICIAL INTELLIGENCE

ADAPTIVE DISCLOSURE: A COMBAT-SPECIFIC PTSD TREATMENT

FEAR CONDITIONING EFFECTS ON SENSITIVITY TO DRUG REWARD

RECONSTRUCTION OF FACIAL CARTILAGE FRAMEWORKS USING ELECTROMECHANICAL RESHAPING

SPECTRAL COMPONENTS OF ABNORMAL SPONTANEOUS GAMMA ACTIVITY IN SCHIZOPHRENIA AND TRANSLATIONAL MOUSE MODELS - SPONTANEOUS ACTIVITY IN THE GAMMA BAND (~30-100 HZ) OF THE ELECTROENCEPHALOGRAM HAS BEEN RELATED TO THE BALANCE OF EXCITATION TO INHIBITION (E/I) IN THE CORTEX (SOHAL & RUBENSTEIN, 2019). MANIPULATIONS OF E/I BALANCE BY MEANS SUCH AS OPTOGENETIC STIMULATION OF PYRAMIDAL CELLS OR INHIBITORY INTERNEURONS (E.G., YIZHAR ET AL., 2011), AND BLOCKADE OF N-METHYL-D-ASPARTATE RECEPTORS (NMDARS) ON PARVALBUMIN-EXPRESSING INHIBITORY INTERNEURONS (E.G., CARLÉN ET AL., 2012) OR PYRAMIDAL CELLS (TATARD-LEITMAN ET AL., 2015), HAVE BEEN SHOWN TO ALTER THE DEGREE OF SPONTANEOUS GAMMA ACTIVITY (SGA). AS SUCH, SGA HAS COME TO BE USED AS AN INDEX OF E/I BALANCE IN STUDIES OF NEUROPSYCHIATRIC DISORDERS (E.G., HIRANO ET AL., 2015; PICARD ET AL., 2019). HOWEVER, THE NEURAL MECHANISMS UNDERLYING SGA HAVE RECEIVED RELATIVELY LITTLE FOCUS. RECENT RESEARCH HAS SUGGESTED THAT SOME KINDS OF NEURAL ACTIVITY THAT APPEAR TO BE CONSTANT ACROSS TIME AND/OR FREQUENCY ARE ACTUALLY COMPOSED OF BRIEF BURSTS OF OSCILLATIONS THAT OCCUR AT DIFFERENT TIMES AND FREQUENCY BANDS ACROSS TRIALS (E.G., JONES, 2016). FURTHERMORE, THERE IS EVIDENCE THAT THESE OSCILLATORY BURSTS PLAY FUNCTIONAL ROLES IN INFORMATION PROCESSING (E.G., LUNDQVIST ET AL., 2016). HOWEVER, THE EXTENT TO WHICH ALTERATIONS IN SGA ARE DUE TO CHANGES IN GAMMA BURSTS OR OTHER ASPECTS OF THE POWER SPECTRUM ARE UNKNOWN. PREVIOUSLY WE REPORTED THAT SGA WAS INCREASED IN INDIVIDUALS WITH SCHIZOPHRENIA (SZ) COMPARED TO HEALTHY CONTROLS DURING AUDITORY STEADY-STATE STIMULATION (HIRANO ET AL., 2015). FURTHER ANALYSES REVEALED THAT INCREASED SGA IN SZ WAS MOST CLOSELY RELATED TO THE INCREASED POWER OF GAMMA BURSTS (SPENCER ET AL., 2023). THUS, ALTERATIONS IN SGA COULD REFLECT CHANGES IN PARTICULAR ASPECTS OF GAMMA-GENERATING CIRCUITS, WHICH MIGHT BE ATTRIBUTABLE TO SPECIFIC NEURAL CIRCUIT ABNORMALITIES AND INFORMATION PROCESSING MECHANISMS. WE WILL ANALYZE PREVIOUSLY COLLECTED DATA FROM HUMANS AND MICE IN OUR LABORATORIES TO FURTHER INVESTIGATE HOW COMPONENTS OF SGA MIGHT BE ALTERED IN SZ AND IN OPTOGENETIC AND PHARMACOLOGICAL MANIPULATION OF CORTICAL E/I BALANCE IN MICE. OUR SPECIFIC AIMS ARE: AIM 1: TO DETERMINE IF INCREASED SGA IN THE KETAMINE AND BF OPTOGENETIC MODELS IS DUE TO THE SAME CHANGES IN SGA COMPONENTS AS INCREASED SGA IN SZ. WE WILL DECOMPOSE SGA IN THE MOUSE BASELINE STATE DURING KETAMINE ADMINISTRATION AND BF PV STIMULATION INTO BURST PARAMETERS AND SPECTRAL SLOPE. WE PREDICT THAT INCREASED SGA WILL BE PRIMARILY ASSOCIATED WITH INCREASED GAMMA BURST POWER AND NOT OTHER MEASURES. AIM 2: TO DETERMINE IF COGNITIVE DEFICITS IN SZ AND IN MICE DURING BF PV NEURON STIMULATION ARE SIMILARLY ASSOCIATED WITH INCREASED SGA AND GAMMA BURST POWER. WE WILL DECOMPOSE SGA IN HUMAN VISUAL ODDBALL TASK DATA AND IN THE NOVEL OBJECT RECOGNITION TASK (NORT) IN MICE. WE PREDICT THAT REDUCED PERFORMANCE IN THE ODDBALL TASK IN SZ AND IN THE NORT IN MICE DURING BF PV NEURON STIMULATION WILL BE ASSOCIATED WITH INCREASED SGA, PRIMARILY BECAUSE OF INCREASED GAMMA BURST POWER.

SHOCK WAVE-STIMULATED PERISTEUM FOR CARTILAGE REPAIR

MTBI EFFECTS ON EMOTION SYMPTOMS, NEUROCOGNITIVE PERFORMANCE, AND FUNCTIONAL IMPAIRMENT: A LONGITUDINAL STUDY OF DEPOLOYED AND NON-DEPLOYED ARMY SOLD