Hartford Hospital

FACILITY RENOVATION AND MODERNIZATION TO SUPPORT A NATIONAL PROGRAM ON PSYCHIATRIC BIOTYPING RESEARCH - THIS IS A PROPOSAL TO RENOVATE A CURRENTLY-DISUSED BUILDING TO CREATE A MODERN, MULTI-MODAL AND INTER-DISCIPLINARY CLINICAL NEUROSCIENCE RESEARCH FACILITY AT THE INSTITUTE OF LIVING (IOL) IN HARTFORD, CT. THE IOL IS A VENERABLE PSYCHIATRIC INSTITUTION WHOSE RECENT BEHAVIORAL, CLINICAL, AND COGNITIVE NEUROSCIENCE RESEARCH HAS ATTAINED NATIONAL RECOGNITION IN ITS EFFORTS TO UNDERSTAND AND BETTER TREAT SCHIZOPHRENIA, BIPOLAR DISORDER, DEPRESSION, ADHD, AUTISM, ANXIETY DISORDERS, OCD, AND ADDICTION. MOREOVER, IOL’S PARENT ORGANIZATION HARTFORD HEALTHCARE (HHC) HAS EMBRACED A BROAD BIOMEDICAL RESEARCH MISSION ACROSS ITS SEVEN-HOSPITAL NETWORK WITHIN A STRATEGIC PLAN TO MAKE LARGE-SCALE PATIENT CARE APPROACH CHANGES THAT ACHIEVE MEANINGFUL, HIGH-IMPACT HEALTH OUTCOME GAINS. THE PROPOSED NEW IOL NEUROSCIENCE RESEARCH FACILITY REPRESENTS A KEY COMPONENT OF THAT LARGER STRATEGIC PLAN. IT WILL CENTRALIZE COMPONENTS OF BOTH ONGOING AND NEW IOL RESEARCH PROGRAMS WHOSE ACTIVITIES WILL PROMOTE THE DISCOVERY, CLINICAL TRANSLATION, AND EDUCATION/DISSEMINATION OF RESEARCH ABOUT BIOLOGICAL SUBTYPES (OR “BIOTYPES”) OF PSYCHIATRIC DISORDERS AT A NATIONALLY PROMINENT LEVEL. BIOTYPES ARE BIOLOGICALLY-DEFINED PRESUMPTIVE DISEASE ENTITIES – SETS OF PATIENT CHARACTERISTICS THAT CAN BE USED TO CLASSIFY INDIVIDUAL PATIENTS INTO SUBGROUPS WITH DIFFERENT ETIOLOGIES OR WHO RESPOND TO DIFFERENT TREATMENTS. IOL INVESTIGATORS HAVE MADE NOTEWORTHY CONCEPTUAL AND EMPIRICAL CONTRIBUTIONS TO PSYCHIATRIC NEUROSCIENCE IN THE PAST TWO DECADES BY DEMONSTRATING THE IMPORTANCE AND TRANSLATIONAL POTENTIAL OF SUCH BIOTYPES. THE PROPOSED FACILITY WILL BUILD UPON THIS FOUNDATION OF EXPERTISE BY CONSOLIDATING AND EXPANDING IOL’S BIOTYPING-RELEVANT RESEARCH RESOURCES – NEUROSCIENCE EQUIPMENT FOR HIGHLY DETAILED, MULTI-MODAL RESEARCH-BASED DEEP PHENOTYPING, THE IOL’S NEWLY-ESTABLISHED EXPERIMENTAL THERAPEUTICS RESEARCH CENTER, AND DATA ANALYSIS RESOURCES TO ENHANCE BIOTYPE DISCOVERY AND TRANSLATION EFFORTS, BOTH FOR INDIVIDUAL PSYCHIATRIC DIAGNOSES AND TRANSDIAGNOSTICALLY. STARTING WITH IOL’S PSYCHOSIS PATIENT CLINICAL SERVICES THAT ALREADY ARE BEING CONVERTED INTO RESEARCH- BASED CLINICS, A KEY PROGRAM FEATURE WILL BE TO SYSTEMATICALLY MOVE SELECT CLINICAL PROGRAMMING INTO THE NEWLY-RENOVATED RESEARCH BUILDING SO THAT CO-LOCALIZED RESEARCH AND CLINICAL RESOURCES CAN BE OPTIMALLY HARNESSED FOR THE GOAL OF GENERATING A NATIONAL BIOTYPING DATA RESOURCE, AS WELL PROVIDE AS A SUCCESSFUL MODEL FOR HOW TO BEST INTEGRATE NEUROSCIENCE BIOTYPING RESEARCH INTO CLINICAL SERVICE DELIVERY. OUR GOAL IS FOR THIS DEDICATED FACILITY-BASED RESEARCH APPROACH TO LEAD THE FIELD OVER THE NEXT DECADE IN MAKING GREAT LEAPS FORWARD IN DISCOVERING EFFECTIVE WAYS TO PERSONALIZE MEDICINE FOR MORE SUCCESSFUL 21ST CENTURY PSYCHIATRIC CARE. THE PROPOSED 18,886 SF BUILDING DESIGN VISION EPITOMIZES THE OVERARCHING GOAL OF A FACILITY THAT NOT ONLY SERVES THE PRIMARY GOAL OF NEUROSCIENTIFIC RESEARCH EXCELLENCE, BUT ALSO WILL HELP MEET OUR INSTITUTION’S STRATEGIC GOALS TO IMPROVE PATIENT ACCESS TO INNOVATIVE AND EXPERIMENTAL TREATMENTS, TO ENHANCE COMMUNITY ENGAGEMENT, AND TO DELIVER THE MOST EFFECTIVE, CUTTING-EDGE PROFESSIONAL EDUCATION IN PSYCHIATRY. DUE TO THE AMBITIOUS CONSTRUCTION SCOPE, AND REFLECTING THE INSTITUTION’S DEDICATION TO THE HIGH PROMISE OF THE PROGRAM MISSION, HHC HAS COMMITTED TO COST SHARING TO ENSURE SUCCESSFUL COMPLETION OF THE CONSTRUCTION PROJECT.

NEURAL ARCHITECTURE OF SOCIAL EMOTIONAL PROCESSING AND REGULATION IN AUTISM SPECTRUM DISORDER: A DYNAMIC CONNECTIVITY PERSPECTIVE

QUANTITATIVE NEUROIMAGING IN PSYCHOSIS

COMPUTATIONAL MODELING-INFORMED REWARD SUBGROUPS IN ADOLESCENT ADHD

NEUROIMAGING PREDICTORS OF BARIATRIC SURGICAL OUTCOMES

OLIN RESEARCH CENTER: ADDITION FOR NEW MRI SCANNER AND RESEARCH STAFF

MODULATING TEMPOROPARIETAL JUNCTION MENTALIZING-RELATED ACTIVITY IN AUTISM SPECTRUM DISORDER USING TRANSCRANIAL MAGNETIC STIMULATION - DEFICITS IN MENTALIZING, A HIGH-ORDER SOCIAL COGNITIVE PROCESS THAT ALLOWS INDIVIDUALS TO BUILD REPRESENTATIONS OF OTHERS’ STATE OF MIND (E.G. EMOTIONS AND MOTIVATION) AND ADJUST THEIR OWN BEHAVIORS ACCORDINGLY, ARE HYPOTHESIZED TO UNDERLINE THE CORE SOCIAL COMMUNICATION ABNORMALITIES THAT CHARACTERIZE AUTISM SPECTRUM DISORDER (ASD). OUR PILOT DATA OUTLINE A SPECIALIZED MENTALIZING NEURAL NETWORK THAT INCLUDES THE TEMPORO- PARIETAL JUNCTION (TPJ, INCLUDING THE POSTERIOR SUPERIOR TEMPORAL SULCUS, PSTS), THAT CAN BE MODULATED WITH REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION (RTMS). THESE DATA SHOW THAT THE ACTIVITY IN THE RIGHT TPJ/PSTS IS SPECIFICALLY MODULATED BY MENTALIZING PROCESSES, PROBED WITH A SOCIAL-COMPETITIVE FMRI DOMINO TASK, AND THAT YOUNG ADULTS DIAGNOSED WITH EITHER ASD OR SCHIZOPHRENIA SHOW DECREASED MENTALIZING RELATED ACTIVITY IN THIS REGION COMPARED TO TYPICALLY DEVELOPED (TD) CONTROLS. HOWEVER, THIS DEFICIT IS ASSOCIATED WITH SOCIAL COMMUNICATION SKILLS ONLY IN ASD. THUS, SPECIFICALLY MODULATING THE UNDERLYING NEURAL MECHANISMS OF MENTALIZING WITH RTMS COULD BE AN EFFECTIVE INTERVENTION FOR THIS CORE DEFICIT IN ASD. WITH THIS PROPOSAL, WE WILL DELINEATE THE MECHANISTIC EFFECTS OF INHIBITORY VS. EXCITATORY RTMS OF THE RIGHT TPJ, SPECIFICALLY IN MODULATING MENTALIZING TASK-RELATED (MTR) NEURAL ACTIVITY IN ADULTS DIAGNOSED WITH ASD (N=40) COMPARED TO MATCHED TD (N=40) INDIVIDUALS AGES 18-35 WITH IQ>80. ALL PARTICIPANTS WILL BE SCHEDULED FOR FOUR STUDY SESSIONS THAT INCLUDE A BASELINE AND THREE SUBSEQUENT SESSIONS THAT WILL EACH INCLUDE TWO FUNCTIONAL MAGNETIC RESONANCE IMAGING (FMRI) SCANS, ONE PRE AND ONE POST AN RTMS SESSION. DURING EACH FMRI SCAN, PARTICIPANTS WILL BE ENGAGED IN INTERSOCIAL, COMPETITIVE DOMINO TASK THAT INVOLVES MENTALIZING. OUR RTMS MANIPULATION, ADMINISTERED IN A DOUBLE-BLIND, COUNTERBALANCED FASHION, INCLUDES ONE SESSION EACH OF EXCITATORY (INTERMITTENT THETA-BURST STIMULATION, ITBS), INHIBITORY (CONTINUOUS TBS, CTBS), AND SHAM SEQUENCES. THE RTMS WILL BE GUIDED WITH INDIVIDUALIZED ELECTRIC-FIELD MODELING CALCULATED FROM A STRUCTURAL MRI SCAN COLLECTED ON THE BASELINE SESSION. THIS ROBUST DESIGN IS NECESSARY TO IDENTIFY THE OPTIMAL RTMS SEQUENCE TO ENGAGE THE RIGHT TPJ AND THE MENTALIZING NETWORK IN ASD BECAUSE FIRM CONCLUSIONS ABOUT HOW BEST TO MODULATE THIS NETWORK CANNOT BE DRAWN FROM THE FEW KNOWN PUBLISHED REPORTS. WE EXPECT TO REPLICATE OUR PREVIOUS FINDINGS OF A MENTALIZING NETWORK, WITH A RIGHT TPJ NODE, THAT WILL HIGHLIGHT DEFICITS IN ASD RELATIVE TO TD PARTICIPANTS. ALSO, WE HYPOTHESIZE THAT ITBS WILL RESULT IN INCREASED, WHILE CTBS IN DECREASED MTR NEURAL ACTIVITY IN THE MENTALIZING NETWORK, WITH THIS BEING MORE PRONOUNCED IN ASD, AND SHAM RESULTING IN NO CHANGE. UNDERSTANDING THIS MECHANISM WILL BE THE FIRST AND CRUCIAL STEP IN VALIDATING RTMS OF THE RIGHT TPJ AS A VIABLE NEURAL TARGET TO MODULATE NEURAL CIRCUIT, AND SUBSEQUENTLY TO MODULATE SOCIAL-COMMUNICATION SKILLS IN ASD IN FUTURE CLINICAL STUDIES. THE SIGNIFICANCE OF SUCH A LINE OF RESEARCH SHOULD BE CONSIDERED IN THE CONTEXT OF THE HIGH PREVALENCE OF ASD AND THE DIRE NEED OF DEVELOPING EFFECTIVE INTERVENTIONS, ESPECIALLY FOR ADULTS.

NEURAL ARCHITECTURE OF EMOTION REGULATION, ADOLESCENT DEVELOPMENT AND DEPRESSION

NEURAL MECHANISMS OF CBT RESPONSE IN HOARDING DISORDER

THE SOCIAL BRAIN IN SCHIZOPHRENIA AND AUTISM SPECTRUM DISORDERS

ADOLESCENT MATURATION OF BRAIN NETWORK INTEGRATION FOR EXECUTIVE CONTROL ABILITIE

EARLY LIFE DETERMINANTS OF CARDIOMETABOLIC HEALTH FROM BIRTH TO ADOLESCENCE AMONGST HIV-EXPOSED AND UNEXPOSED SOUTH AFRICAN CHILDREN - PROJECT ABSTRACT: DESPITE NOT LIVING WITH HIV, HIV-EXPOSED BUT UNINFECTED (HEU) CHILDREN EXPERIENCE HIGHER LEVELS OF MORBIDITY AND MORTALITY IN CHILDHOOD AND HAVE WORSE CARDIOMETABOLIC OUTCOMES, COMPARED TO HIV-UNEXPOSED (HU) CHILDREN. HEU CHILDREN HAVE SUBOPTIMAL IMMUNE DEVELOPMENT IN EARLY LIFE. THIS INCREASES THEIR RISK FOR COMORBID INFECTIONS IN CHILDHOOD, AND MAY EXACERBATE CARDIOMETABOLIC RISK BY LEADING TO INCREASED SYSTEMIC INFLAMMATION THAT ADVERSELY IMPACTS METABOLIC PATHWAYS. OUR GROUP HAS USED METABOLOMICS TO CHARACTERIZE METABOLIC DYSFUNCTION STARTING IN EARLY LIFE AND HAVE IDENTIFIED EARLY LIFE INFECTIONS AS A DRIVER OF SYSTEMIC INFLAMMATION AND THE DEVELOPMENT OF PRO-ATHEROGENIC METABOLIC PROFILES IN CHILDHOOD. THUS, THE HIGHER BURDEN OF INFECTIONS IN EARLY LIFE AMONG HEU CHILDREN MAY REPRESENT AND IMPORTANT AND UNEXPLORED PATHWAY IN THE PATHOGENESIS OF CARDIOMETABOLIC DYSFUNCTION. IN THIS PROPOSAL, WE LEVERAGE THE DRAKENSTEIN CHILD HEALTH STUDY, A WELL- CHARACTERIZED COHORT OF HEU AND HU PARTICIPANTS FOLLOWED FROM BIRTH, TO INVESTIGATE HOW HIV-EXPOSURE AND EARLY LIFE INFECTIONS AFFECT INFLAMMATORY RESPONSE CHANGES TO THE METABOLOME FROM BIRTH TO EARLY ADOLESCENCE, AND EVALUATE HOW THESE CHANGES INFLUENCE THE DEVELOPMENT OF ADVERSE CARDIOMETABOLIC OUTCOMES IN EARLY ADOLESCENCE. AIM 1 WILL CHARACTERIZE LONGITUDINAL METABOLOMIC TRAJECTORIES FROM INFANCY TO EARLY ADOLESCENCE USING 250 METABOLITES AMONG HEU (N=244) AND HU (N=735) CHILDREN OVER DIFFERENT DEVELOPMENTAL STAGES. AIM 2 WILL DEVELOP A SET OF PREDICTIVE MODELS TO IDENTIFY METABOLOMIC PROFILES IN CHILDHOOD (1 AND 5 YEARS) THAT PREDICT CARDIOMETABOLIC DYSFUNCTION, INCLUDING HIGHER BMI/ADIPOSITY, ARTERIAL STIFFNESS, BLOOD PRESSURE, DYSLIPIDEMIA, AND INSULIN RESISTANCE, IN EARLY ADOLESCENCE (10 YEARS). AIM 3 WILL EVALUATE IF RELATIONSHIPS BETWEEN EARLY LIFE INFECTION BURDEN AND METABOLOMIC PROFILES AT 10 YEARS OF AGE ARE MEDIATED BY INFLAMMATORY PATHWAYS, OVERALL AND BY HIV EXPOSURE STATUS. THE PROPOSED STUDY WILL MAKE SIGNIFICANT CONTRIBUTIONS TO THE FIELD OF HIV BY PROVIDING SOME OF THE FIRST LONGITUDINAL METABOLOMIC DATA FROM A POPULATION-BASED COHORT OF HEU AND HU PARTICIPANTS TO ELUCIDATE THE MOLECULAR PATHWAYS UNDERLYING THE DEVELOPMENT OF CARDIOMETABOLIC DYSFUNCTION STARTING IN INFANCY. IN ADDITION, FINDINGS FROM THIS PROPOSAL HAVE DIRECT CLINICAL RELEVANCE BY IDENTIFYING METABOLIC AND INFLAMMATORY BIOMARKERS IN EARLY LIFE TO SUPPORT CARDIOMETABOLIC RISK STRATIFICATION AND INFORM WHETHER FUTURE INTERVENTION EFFORTS TO ADDRESS CARDIOMETABOLIC HEALTH IN HEU SHOULD INCLUDE REDUCING INFECTION BURDEN OR SEVERITY. TAKEN TOGETHER, THIS WORK WILL PROVIDE NOVEL MECHANISTIC DATA AND BIOMARKER IDENTIFICATION THAT WILL INFORM WHETHER HEU SHOULD BE TARGETED FOR SCREENING AND INTERVENTION EFFORTS IN CHILDHOOD TO REDUCE THEIR RISK OF CARDIOMETABOLIC DISEASE.

BEHAVIORAL AND NEURAL TARGET ENGAGEMENT FOR ADHD EXECUTIVE WORKING MEMORY TRAINING - MANY INVESTIGATORS HAVE ATTEMPTED TO SHOW THAT USING INTENSIVE COGNITIVE TRAINING TO INCREASE ATTENTION- DEFICIT/HYPERACTIVITY DISORDER (ADHD) PATIENTS’ CAPACITY TO STORE INFORMATION WITHIN WM MIGHT ALSO REDUCE SYMPTOM SEVERITY OR FUNCTIONAL IMPAIRMENT. THOSE STUDIES WERE BASED ON STRONG EVIDENCE FOR WM BEHAVIORAL AND NEURAL DYSFUNCTION IN ADHD, A WIDELY-HELD BELIEF THAT WM-RELATED BRAIN DYSFUNCTION IS ETIOLOGICALLY SIGNIFICANT, AND ARGUMENTS THAT IMPAIRED WM CONTRIBUTES TO THE MAINTENANCE OF THE DISORDER. BUT DESPITE PROMISING EARLY EVIDENCE FOR WM STORAGE TRAINING POTENTIAL EFFICACY, A DECADE OF EQUIVOCAL AND NEGATIVE OUTCOMES FROM SEVERAL WELL-DESIGNED RANDOMIZED CLINICAL TRIALS HAVE LEFT INVESTIGATORS WONDERING WHY MEANINGFUL, REPLICABLE ADHD CLINICAL IMPROVEMENTS ARE NOT ALWAYS ACHIEVED WHEN WM STORAGE CAPACITY IS RELIABLY ENHANCED. BECAUSE FEW INVESTIGATORS WANT TO MISTAKENLY ABANDON SUCH A PROMISING INTERVENTION PREMISE, THERE IS A SEARCH FOR NOVEL WORKING MEMORY-RELATED TREATMENT TARGETS THAT FOCUS ON SOMETHING OTHER THAN SIMPLE WM STORAGE CAPACITY. IN THIS R61/R33 PROPOSAL, WE SYNTHESIZE PUBLISHED FINDINGS AND PROVIDE OUR OWN PILOT NEUROIMAGING EVIDENCE TO ARGUE THAT A BETTER WM TRAINING TARGET MIGHT BE BRAIN REGIONS THAT SPECIFICALLY UNDERLIE THE EXECUTIVE ASPECTS OF WM. SUCH EXECUTIVE WORKING (EWM) MEMORY OPERATIONS REPRESENT PATIENTS’ ABILITY TO EFFECTIVELY USE THE INFORMATION REPRESENTED IN WM FOR BEHAVIORAL AND COGNITIVE CONTROL. THESE ABILITIES LIKELY ARE MORE MEANINGFUL TO ADHD BEHAVIORAL IMPAIRMENT THAN MERELY HOW LARGE PATIENTS’ GENERAL WM STORAGE CAPACITY IS. AN EXTENSIVE THEORETICAL FRAMEWORK SUPPORTS THAT THE ‘WORKING’ PART OF WM INVOLVES A SMALL HANDFUL OF DISCRETE COGNITIVE OPERATIONS THAT FLEXIBLY MANIPULATE INFORMATION WITHIN WM, OR STABILIZE WM REPRESENTATIONS IN THE FACE OF DIFFERENT TYPES OF ENVIRONMENTAL DISTRACTION. DOZENS OF PRIOR FMRI STUDIES RELIABLY LINK THE FOUR PRIMARY TYPES OF THESE EWM OPERATIONS TO ACTIVITY WITHIN SPECIFIC BRAIN REGIONS – THE SUPERIOR FRONTAL SULCUS AND MID- LATERAL PREFRONTAL CORTEX. CONVERGING EVIDENCE INCLUDING OUR PILOT EVIDENCE SHOWS THESE REGIONS FUNCTION ABNORMALLY IN ADHD, PREDICT ADHD SYMPTOM SEVERITY, AND CAN BE ENHANCED BY PRACTICING EWM TASKS. NIMH’S R61/R33 EXPERIMENTAL THERAPEUTICS MECHANISM IS IDEAL TO LEARN IF A TYPICAL 5-WEEK, COURSE OF INTENSIVE TRAINING THAT USES THESE EWM EXERCISES CAN ENGAGE THE PROPOSED BRAIN TARGETS LINKED TO BOTH EWM ABILITY AND TO ADHD DYSFUNCTION. IF THIS NEUROSCIENCE-GUIDED, INITIAL 2-YEAR R61 STUDY PHASE ACHIEVES ITS MILESTONES, A SUBSEQUENT R33 STUDY PHASE WILL SEEK TO REPLICATE, AND THEN SHOW THE RELEVANCE OF TARGET ENGAGEMENT TO ADHD CLINICAL FUNCTION. IF BOTH R61/R33 AIMS ARE ACHIEVED, A SERIES OF SECONDARY ANALYSES WILL RE-EXAMINE THE TRIAL OUTCOME DATA. THESE EFFORTS WILL INFORM THE DESIGN OF ANY SUBSEQUENT PRELIMINARY EFFICACY STUDY, FACILITATING A RAPID TRANSITION INTO LARGER-SCALE EFFICACY TESTING.

THE EFFECT OF STATINS ON SKELETAL MUSCLE FUNCTION

CHARACTERIZING TWO DISTINCT ADHD NEUROBIOLOGIES WITH FMRI

USING ACCEPTANCE AND COMMITMENT THERAPY TO PROMOTE AUTONOMOUS MOTIVATION FOR INCREASED PHYSICAL ACTIVITY AND IMPROVED WEIGHT LOSS MAINTENANCE IN BARIATRIC SURGERY PATIENTS: A RANDOMIZED TRIAL - PROJECT SUMMARY/ABSTRACT NEARLY ONE IN FIVE U.S. ADULTS HAVE SEVERE OBESITY (BODY MASS INDEX ≥ 35 KG/M2), WHICH IS RELATED TO NUMEROUS COMORBIDITIES AND REDUCED LIFE EXPECTANCY. METABOLIC AND BARIATRIC SURGERY (MBS) RELIABLY PRODUCES SUBSTANTIAL, DURABLE WEIGHT LOSS AND HEALTH IMPROVEMENTS FOR THE MAJORITY OF PATIENTS WITH SEVERE OBESITY. HOWEVER, WEIGHT REGAIN OVER TIME IS COMMON AND CAN DEVELOP INTO A SERIOUS COMPLICATION MARKED BY REEMERGENCE OF COMORBIDITIES AND IMPAIRED PHYSICAL AND MENTAL QUALITY OF LIFE. THIS ISSUE IS COMPOUNDED BY A LACK OF EFFECTIVE AND ACCESSIBLE STRATEGIES TO HELP MBS PATIENTS PREVENT WEIGHT REGAIN AND ACHIEVE LIFELONG SUCCESS. INDEED, CURRENT POST-SURGICAL GUIDELINES ADVISE THAT PATIENTS INCREASE MODERATE-TO-VIGOROUS INTENSITY PHYSICAL ACTIVITY (MVPA) FOR WEIGHT LOSS MAINTENANCE AND LIFELONG HEALTH, BUT MOST DO NOT, AND AVAILABLE INTERVENTIONS DO NOT ADDRESS THEIR REPORTED LOW INTERNAL DRIVE TO ENGAGE IN REGULAR MVPA. ACCEPTANCE AND COMMITMENT THERAPY (ACT)-BASED INTERVENTIONS ARE EFFECTIVE AT PROMOTING HEALTH BEHAVIOR CHANGES VIA IMPROVED AUTONOMOUS (OR INTERNAL) MOTIVATION. ACT ACHIEVES THIS BY CLARIFYING PERSONAL VALUES, LINKING BEHAVIORAL PERFORMANCE TO THOSE VALUES, AND INCREASING ACCEPTANCE OF CONTRARY THOUGHTS AND EMOTIONS THAT ACT AS BARRIERS TO NEW BEHAVIOR ENGAGEMENT. WE PILOT-TESTED A ONE-TIME, GROUP-BASED ACT-BASED WORKSHOP INTERVENTION (+ EMAIL FEEDBACK & SUPPORT PHONE CALLS) TO INCREASE MVPA AMONG LOW-ACTIVE ADULTS WITH OBESITY. PARTICIPANTS ON AVERAGE ACHIEVED AND MAINTAINED CLINICALLY IMPORTANT INCREASES IN MVPA AND AUTONOMOUS MOTIVATION, AND LARGER IMPROVEMENTS IN MOTIVATION WERE RELATED TO LARGER MVPA INCREASES. THESE PRELIMINARY RESULTS SHOW POTENTIAL FOR OUR APPROACH TO HELP MBS PATIENTS BOOST AUTONOMOUS MOTIVATION FOR ACHIEVING SUSTAINABLE INCREASES IN MVPA. FURTHER, OUR LOW-TOUCH APPROACH MAKES IT IDEAL FOR REDUCING BARRIERS TO PARTICIPATION AND FUTURE APPLICATION IN MBS AND OTHER CLINICAL SETTINGS. WE NOW PROPOSE TO BUILD ON OUR FINDINGS BY TESTING WHETHER TARGETING MBS PATIENTS' AUTONOMOUS MOTIVATION WITH ACT-BASED INTERVENTION PRODUCES SUSTAINED INCREASES IN MVPA, AND IF SUCH INCREASES PREVENT WEIGHT REGAIN AFTER MBS. WE WILL RANDOMIZE 164 PATIENTS WHO ARE 10-20 MONTHS POST-MBS AND SHOW RELATIVE WEIGHT STABILITY TO 12 MONTHS OF: ACT TARGETING AUTONOMOUS MOTIVATION FOR MVPA; OR CONTACT-MATCHED CONTROL (CON) PROVIDING PA-FOCUSED EDUCATION AND PRESCRIBED GOALS. BOTH GROUPS WILL: (1) RECEIVE TWO 2.5-HOUR GROUP-BASED WORKSHOPS (+ 2 BOOSTER SESSIONS) VIA ZOOM VIDEO CONFERENCING, EMAIL FEEDBACK, AND TELEPHONE CALLS; AND (2) BE ASSESSED AT PRE- AND 3, 6, 12, AND 18-MONTHS POST-RANDOMIZATION. WE WILL COMPARE ACT AND CON ON CHANGES IN: 1) MVPA AND WEIGHT REGAIN (PRIMARY OUTCOMES) AND 2) AUTONOMOUS MOTIVATION AND ACCEPTANCE (SECONDARY OUTCOMES). WE WILL ALSO EXPLORE MEDIATORS OF THE TREATMENT EFFECT ON MVPA (MOTIVATION, ACCEPTANCE) AND WEIGHT REGAIN (MVPA). IF SUCCESSFUL, RESULTS COULD JUSTIFY MORE ROBUST PHYSICAL ACTIVITY GUIDELINES AND USE OF THESE STRATEGIES IN CLINICAL PRACTICE TO HELP MOTIVATE MBS PATIENTS TO ACHIEVE SUSTAINABLE INCREASES IN MVPA FOR WEIGHT REGAIN PREVENTION.

BEHAVIORAL AND NEURAL TARGET ENGAGEMENT FOR ADHD EXECUTIVE WORKING MEMORY TRAINING - MANY INVESTIGATORS HAVE ATTEMPTED TO SHOW THAT USING INTENSIVE COGNITIVE TRAINING TO INCREASE ATTENTION- DEFICIT/HYPERACTIVITY DISORDER (ADHD) PATIENTS’ CAPACITY TO STORE INFORMATION WITHIN WM MIGHT ALSO REDUCE SYMPTOM SEVERITY OR FUNCTIONAL IMPAIRMENT. THOSE STUDIES WERE BASED ON STRONG EVIDENCE FOR WM BEHAVIORAL AND NEURAL DYSFUNCTION IN ADHD, A WIDELY-HELD BELIEF THAT WM-RELATED BRAIN DYSFUNCTION IS ETIOLOGICALLY SIGNIFICANT, AND ARGUMENTS THAT IMPAIRED WM CONTRIBUTES TO THE MAINTENANCE OF THE DISORDER. BUT DESPITE PROMISING EARLY EVIDENCE FOR WM STORAGE TRAINING POTENTIAL EFFICACY, A DECADE OF EQUIVOCAL AND NEGATIVE OUTCOMES FROM SEVERAL WELL-DESIGNED RANDOMIZED CLINICAL TRIALS HAVE LEFT INVESTIGATORS WONDERING WHY MEANINGFUL, REPLICABLE ADHD CLINICAL IMPROVEMENTS ARE NOT ALWAYS ACHIEVED WHEN WM STORAGE CAPACITY IS RELIABLY ENHANCED. BECAUSE FEW INVESTIGATORS WANT TO MISTAKENLY ABANDON SUCH A PROMISING INTERVENTION PREMISE, THERE IS A SEARCH FOR NOVEL WORKING MEMORY-RELATED TREATMENT TARGETS THAT FOCUS ON SOMETHING OTHER THAN SIMPLE WM STORAGE CAPACITY. IN THIS R61/R33 PROPOSAL, WE SYNTHESIZE PUBLISHED FINDINGS AND PROVIDE OUR OWN PILOT NEUROIMAGING EVIDENCE TO ARGUE THAT A BETTER WM TRAINING TARGET MIGHT BE BRAIN REGIONS THAT SPECIFICALLY UNDERLIE THE EXECUTIVE ASPECTS OF WM. SUCH EXECUTIVE WORKING (EWM) MEMORY OPERATIONS REPRESENT PATIENTS’ ABILITY TO EFFECTIVELY USE THE INFORMATION REPRESENTED IN WM FOR BEHAVIORAL AND COGNITIVE CONTROL. THESE ABILITIES LIKELY ARE MORE MEANINGFUL TO ADHD BEHAVIORAL IMPAIRMENT THAN MERELY HOW LARGE PATIENTS’ GENERAL WM STORAGE CAPACITY IS. AN EXTENSIVE THEORETICAL FRAMEWORK SUPPORTS THAT THE ‘WORKING’ PART OF WM INVOLVES A SMALL HANDFUL OF DISCRETE COGNITIVE OPERATIONS THAT FLEXIBLY MANIPULATE INFORMATION WITHIN WM, OR STABILIZE WM REPRESENTATIONS IN THE FACE OF DIFFERENT TYPES OF ENVIRONMENTAL DISTRACTION. DOZENS OF PRIOR FMRI STUDIES RELIABLY LINK THE FOUR PRIMARY TYPES OF THESE EWM OPERATIONS TO ACTIVITY WITHIN SPECIFIC BRAIN REGIONS – THE SUPERIOR FRONTAL SULCUS AND MID- LATERAL PREFRONTAL CORTEX. CONVERGING EVIDENCE INCLUDING OUR PILOT EVIDENCE SHOWS THESE REGIONS FUNCTION ABNORMALLY IN ADHD, PREDICT ADHD SYMPTOM SEVERITY, AND CAN BE ENHANCED BY PRACTICING EWM TASKS. NIMH’S R61/R33 EXPERIMENTAL THERAPEUTICS MECHANISM IS IDEAL TO LEARN IF A TYPICAL 5-WEEK, COURSE OF INTENSIVE TRAINING THAT USES THESE EWM EXERCISES CAN ENGAGE THE PROPOSED BRAIN TARGETS LINKED TO BOTH EWM ABILITY AND TO ADHD DYSFUNCTION. IF THIS NEUROSCIENCE-GUIDED, INITIAL 2-YEAR R61 STUDY PHASE ACHIEVES ITS MILESTONES, A SUBSEQUENT R33 STUDY PHASE WILL SEEK TO REPLICATE, AND THEN SHOW THE RELEVANCE OF TARGET ENGAGEMENT TO ADHD CLINICAL FUNCTION. IF BOTH R61/R33 AIMS ARE ACHIEVED, A SERIES OF SECONDARY ANALYSES WILL RE-EXAMINE THE TRIAL OUTCOME DATA. THESE EFFORTS WILL INFORM THE DESIGN OF ANY SUBSEQUENT PRELIMINARY EFFICACY STUDY, FACILITATING A RAPID TRANSITION INTO LARGER-SCALE EFFICACY TESTING.

PHARMACOGENETIC DECISION SUPPORT IT SYSTEM FOR PSYCHIATRIC HOSPITALIZATION: RCT

THE EFFECT OF HIGH-DOSE ATORVASTATIN ON NEURONAL ACTIVITY AND COGNITIVE FUNCTION

2/3-EXPOSURE D-CYCLOSERINE ENHANCEMENT AND GENETIC MODULATORS IN PANIC DISORDER

SCHIZOPHRENIA BIOMARKERS: MEMORY GENES AND FMRI

NEUROFEEDBACK PROCESSING SPEED TRAINING TO IMPROVE SOCIAL FUNCTIONING IN TEENAGERS AND YOUNG ADULTS AT CLINICAL HIGH RISK FOR PSYCHOSIS

INTRINSIC MOTIVATION AND LEARNING IN SCHIZOPHRENIA

COENZYME Q10 IN STATIN MYOPATHY

NEURAL MECHANISMS OF COMPULSIVE HOARDING

STUDIES ON MYOCYTE APOPTOSIS IN CONGESTIVE HEART FAILURE

MECHANISMS OF HYPERVENTILATION IN ANXIETY DISORDERS

CENTRAL AND PERIPHERAL NERVOUS SYSTEM CORRELATES OF DIFFICULTY DISCARDING IN HOARDING DISORDER

HEALTH CARE AND OTHER FACILITIES

AN FMRI STUDY OF THE EFFECT OF WORKING MEMORY TRAINING ON ADHD BRAIN DYSFUNCTION

SIMULATED DRIVING UNDER THE INFLUENCE OF MARIJUANA: AN FMRI STUDY

EFFECTS OF MARIJUANA ON DRIVING: A STANDARDIZED ASSESSMENT

DENTAL REIMBURSEMENT PROGRAM - AS ONE OF THE LARGEST GENERAL DENTISTRY CLINICS IN THE HARTFORD AREA, WE RECEIVE NUMEROUS REFERRALS FROM EXTERNAL DENTISTS AND HEALTHCARE FACILITIES. MANY OF THE PATIENTS WHO SEEK CARE AT OUR CLINIC DO SO ONLY WHEN THEY ARE EXPERIENCING PAIN OR FACING DIFFICULT TREATMENT DECISIONS. OFTEN, THEY OPT FOR EXTRACTIONS AS A QUICK AND IMMEDIATE SOLUTION, RATHER THAN UNDERGOING THE MULTIPLE VISITS REQUIRED FOR RESTORATIVE TREATMENT TO SAVE THEIR TEETH. FOR CASES INVOLVING MULTIPLE EXTRACTIONS, STAGED TREATMENT IS COMMON, REQUIRING PATIENTS TO RETURN FOR MULTIPLE APPOINTMENTS. WHILE THIS APPROACH CAN IMPROVE PATIENT COMFORT AND HEALING—SUCH AS EXTRACTING TEETH IN SEPARATE VISITS TO PRESERVE FUNCTIONALITY ON ONE SIDE OF THE MOUTH, IT ALSO INCREASES THE OVERALL COST OF CARE. ONE SIGNIFICANT FACTOR CONTRIBUTING TO THESE COSTS IS ANESTHESIA. IF A PATIENT REQUIRES SEDATION FOR EACH APPOINTMENT, THE TOTAL COST PER VISIT CAN AMOUNT TO SEVERAL THOUSAND DOLLARS DUE TO THE HIGH EXPENSES ASSOCIATED WITH PROVIDING ANESTHESIA. OUR PRIMARY COMMITMENT IS TO DELIVER HIGH-QUALITY DENTAL CARE TO ALL PATIENTS, REGARDLESS OF THEIR FINANCIAL STATUS. AS A TEACHING INSTITUTION, WE PRIORITIZE PATIENT NEEDS ABOVE THEIR ABILITY TO PAY. HOWEVER, THIS APPROACH OFTEN RESULTS IN PROVIDING CARE TO INDIVIDUALS WHO CANNOT MEET THEIR FINANCIAL OBLIGATIONS, LEADING TO SIGNIFICANT AMOUNTS OF UNCOLLECTED REVENUE WHEN PATIENTS DO NOT QUALIFY FOR FINANCIAL ASSISTANCE. WHILE WE EMPHASIZE THE IMPORTANCE OF PREVENTIVE CARE—EDUCATING PATIENTS ON ORAL HEALTH, THE NECESSITY OF ROUTINE CLEANINGS, AND THE BENEFITS OF DIAGNOSTIC RADIOGRAPHS—URGENT AND ACUTE CARE REMAINS THE PRIMARY REASON FOR MOST VISITS. MANY PATIENTS DELAY PREVENTIVE CARE DUE TO FINANCIAL CONSTRAINTS, AS THEY PERCEIVE IT AS A LOWER PRIORITY COMPARED TO IMMEDIATE DENTAL EMERGENCIES. THE FINANCIAL BURDEN IS EVEN GREATER FOR THOSE WHO LACK INSURANCE OR DO NOT QUALIFY FOR ASSISTANCE, FURTHER LIMITING THEIR ACCESS TO ESSENTIAL PREVENTIVE SERVICES. TO ADDRESS THESE CHALLENGES, WE ARE REQUESTING RYAN WHITE FUNDING TO HELP COVER THE COSTS ASSOCIATED WITH PROVIDING HIGH-QUALITY DENTAL CARE TO THIS VULNERABLE PATIENT POPULATION. THIS FUNDING WILL ENABLE US TO CONTINUE OFFERING NECESSARY DENTAL TREATMENTS, IMPROVE ACCESS TO PREVENTIVE CARE, AND ENSURE THAT FINANCIAL LIMITATIONS DO NOT HINDER PATIENTS FROM RECEIVING THE CARE THEY NEED.

DENTAL REIMBURSEMENT PROGRAM

DENTAL REIMBURSEMENT PROGRAM - WE ARE ONE OF THE LARGEST ORAL SURGERY CLINICAL IN THE AREA AND THE ONLY ONE THAT TAKES RYAN WHITE-ELIGIBLE PATIENTS WITHIN GREATER HARTFORD, CT. THUS WE RECEIVE NUMEROUS REFERRALS FROM OTHER DENTAL CLINICS WHO ALSO CARE FOR THESE PATIENTS. THE MAJORITY OF OUR RYAN WHITE PATIENTS SEEK EMERGENCY DENTAL CARE WHEN THEY ARE IN PAIN OR HAVE DIFFICULTY CHEWING AND OFTEN ELECT FOR EXTRACTIONS. HOWEVER, WE ROUTINELY SEE PATIENTS WHO REQUIRE SEVERAL VISITS TO COMPLETE THE NEEDED EXTRACTIONS, WHICH, DUE TO THE NEED FOR IV SEDATION LEADS TO COSTS IN THE THOUSANDS OF DOLLARS. NEVERTHELESS, WE FEEL IT IS OUR DUE DILIGENCE TO TREAT THESE PATIENTS INDEPENDENT OF THEIR ABILITY TO PAY. RATHER AS A TEACHING INSTITUTION WE TREAT THE PATIENT’S NEEDS FIRST REGARDLESS OF THEIR FINANCIAL SITUATION. HOWEVER, MANY OF OUR PATIENTS ARE UNABLE TO PAY FOR THEIR DENTAL CARE AND THIS AMOUNT IS WRITTEN OFF AS UNCOLLECTIBLE IF THEY DO NOT QUALIFY FOR ANY OTHER ASSISTANCE. FINALLY, PREVENTATIVE CARE IS ENCOURAGED AND DISCUSSED WHEN A PATIENT SEEKS ANY TYPE OF DENTAL CARE AT OUR FACILITY. WE ATTEMPT TO EDUCATE THE PATIENT ON THE IMPORTANCE OF PREVENTION AND GOOD ORAL HYGIENE TO PREVENT FURTHER DECLINES IN THEIR ORAL HEALTH, INCLUDING THE NEED FOR PROPHYLAXIS AND RADIOGRAPHS TO PREVENT LOSS OF TEETH AND DENTAL FUNCTION. HOWEVER, THESE EFFORTS ARE NOT ALWAYS SUCCESSFUL. UNFORTUNATELY, ACUTE CARE VISITS MAKE UP A HIGHER PERCENTAGE OF OUR APPOINTMENTS AS PREVENTATIVE CARE IS INTANGIBLE AS COMPARED TO THE PAIN OF A BROKEN OR INFECTED TOOTH. MOREOVER, MOST OF OUR PATIENTS DO NOT HAVE OR QUALIFY FOR INSURANCE AND THEY DO NOT WANT TO INCUR DEBT FOR PREVENTATIVE CARE THAT IS NOT DEEMED AS ESSENTIAL HEALTH CARE. WE ARE THUS REQUESTING RYAN WHITE FUNDS TO COVER PART OF THE COSTS OF THE HIGH QUALITY DENTAL CARE WE PROVIDE TO THESE VULNERABLE PATIENTS.

DENTAL REIMBURSEMENT PROGRAM

DENTAL REIMBURSEMENT PROGRAM

DENTAL REIMBURSEMENT PROGRAM - 1) AS ONE OF THE LARGER GENERAL DENTISTRY CLINICS IN THE HARTFORD AREA WE RECEIVE NUMEROUS REFERRALS FROM OUTSIDE DENTISTS AND FACILITIES. THE PATIENTS WHO COME TO OUR CLINIC TEND TO SEEK DENTAL CARE ONLY WHEN THEY ARE IN PAIN OR ARE HAVING DIFFICULTY CHEWING. THEY COMMONLY ELECT FOR TOOTH EXTRACTIONS AS THIS CAN BE DONE QUICKLY, AND IS AN IMMEDIATE SOLUTION, WHILE GOING THROUGH THE MORE INVOLVED PROCEDURES NEEDED TO SAVE A TOOTH BY COMPLETING RESTORATIVE CARE CAN TAKE MANY VISITS. FOR CASES WHERE THERE ARE A LARGE NUMBER OF NON-RESTORABLE TEETH, IT IS NOT UNCOMMON TO SEE PATIENTS IN STAGED CARE FOR MULTIPLE APPOINTMENTS. THIS PROCESS HOWEVER, HAS THE POTENTIAL TO INCREASE THE COST OF CARE. ONE COMMON EXAMPLE IS MULTIPLE EXTRACTIONS. IF A PATIENT NEEDS FULL MOUTH EXTRACTIONS, IN ORDER TO BETTER SERVE THE PATIENT FOR COMFORT AND HEALING DURING THIS TREATMENT WE WILL PERFORM THE EXTRACTIONS AT MULTIPLE APPOINTMENTS AND EXTRACT EITHER THE TOP ARCH OR ONE SIDE OF THE MOUTH TO ALLOW THE PATIENT TO EAT ON THE OTHER SIDE OF THE MOUTH. IF THE PATIENT NEEDS IV SEDATION FOR EACH APPOINTMENT, THE TOTAL COST OF EXTRACTIONS PER APPOINTMENT CAN BE SEVERAL THOUSAND DOLLARS DUE TO THE HIGH COST OF PROVIDING ANESTHESIA. 2) OUR PRIMARY RESPONSIBILITY IS TO PROVIDE HIGH QUALITY DENTAL CARE TO ALL OUR PATIENTS. WE FEEL IT IS OUR DUE DILIGENCE TO TREAT THE PATIENT’S NEEDS INDEPENDENT OF THEIR FINANCIAL STATUS AND DO NOT REVIEW A PATIENT’S ABILITY TO PAY FOR SERVICES. RATHER, AS A TEACHING INSTITUTION WE TREAT THE PATIENT’S NEEDS FIRST REGARDLESS OF THEIR ABILITY TO PAY. THIS HOWEVER, CAN LEAD TO OUR TREATING PATIENTS WHO ARE UNABLE TO MEET THEIR FINANCIAL OBLIGATIONS AND THIS AMOUNT IS WRITTEN OFF AS UNCOLLECTIBLE BY THE CLINIC IF THE PATIENT DOES NOT QUALIFY FOR ANY OTHER ASSISTANCE. 3) PREVENTATIVE CARE IS ENCOURAGED AND DISCUSSED WHEN A PATIENT SEEKS DENTAL CARE AT OUR FACILITY. WE ATTEMPT TO EDUCATE THE PATIENT ON PREVENTION, THE NEED FOR PROPHYLAXIS AND PROV IDE RADIOGRAPHS TO IDENTIFY INCIPIENT DISEASE, ALL OF WHICH CAN PREVENT THE LOSS OF TEETH AND FUNCTION. HOWEVER, THIS IS NOT ALWAYS SUCCESSFUL. ACUTE CARE IS, UNFORTUNATELY, STILL MAKES UP THE HIGHER PERCENTAGE OF APPOINTMENTS, AS PREVENTATIVE CARE IS INTANGIBLE TO THE PATIENT WHERE AS A BROKEN TOOTH OR PAIN TRIGGERS A NEED TO SEEK DENTAL CARE. ANOTHER REASON IS THE FINANCIAL BURDEN. WHEN PATIENTS DO NOT HAVE, OR DO NOT QUALIFY FOR INSURANCE, THEY DO NOT WANT TO INCUR DEBT FOR PREVENTATIVE CARE AS IT IS NOT SEEN AS IMPORTANT COMPARED TO THEIR IMMEDIATE FINANCIAL NEEDS. WE ARE THUS REQUESTING RYAN WHITE FUNDS TO COVER PART OF THE COSTS OF THE HIGH QUALITY OF DENTAL CARE WE PROVIDE TO THESE VULNERABLE PATIENTS.

DENTAL REIMBURSEMENT PROGRAM

DENTAL REIMBURSEMENT PROGRAM

DENTAL REIMBURSEMENT PROGRAM

DENTAL REIMBURSEMENT PROGRAM

DENTAL REIMBURSEMENT PROGRAM