Search Prime Grants

R01MH128720

Project Grant

Overview

Grant Description
Disrupted Neural Synchrony During Naturalistic Perception in Schizophrenia: Toward a New Biomarker of Social Dysfunction - Project Summary/Abstract

Social dysfunction is a core feature of schizophrenia. Many individuals with schizophrenia experience social disconnection, a lack of social contact with friends and family. Social disconnection is associated with reduced quality of life and many negative health effects, but most current treatments do little to address it.

The development of new interventions is currently hindered by a lack of scientific understanding about how differences in the way individuals' brains process information contribute to social disconnection, and a lack of biomarkers associated with social functioning.

Recent research in non-clinical social neuroscience points to a compelling model that may help to explain social disconnection in schizophrenia and would provide the basis for a new biomarker of social dysfunction. Specifically, research using functional magnetic resonance imaging (fMRI) and inter-subject correlation (ISC) analysis methods shows that people whose brains tend to respond more normatively to dynamic, naturalistic stimuli (e.g., video clips) tend to have more social connections, perhaps because more other people experience the world in a similar way, whereas people with less normative responses tend to have fewer social connections.

Converging evidence suggests that many individuals with schizophrenia are likely to have less normative responses to such naturalistic stimuli, which could help to explain why social disconnection is common in the disorder. However, the ISC method has not yet been used to study social dysfunction in schizophrenia.

This project will fill this research gap by translating ISC research methods from non-clinical research in order to investigate how ISCs relate to social disconnection in schizophrenia. Individuals with schizophrenia (N=200) and matched healthy controls (N=100) will each complete one fMRI scan during which they will view naturalistic video stimuli and complete two established paradigms that assess important domains of social processing: social cue perception and mentalizing.

We will characterize ISCs based on responses to the naturalistic video stimuli and characterize brain activity related to social cue perception and mentalizing using standard analyses. The study will test whether ISCs differ between the two participant groups and evaluate to what extent group ISC differences relate to individual differences in social connection.

We will also characterize ISC normativity for each member of the schizophrenia group, using the control group as a reference, to assess whether brain response normativity is associated with social disconnection, and whether individuals' degree of social disconnection can be predicted from it.

The project will also test whether an ISC-based measure is more sensitive to individual differences in social disconnection than established fMRI measures. Results from this project will improve understanding of how brain activity relates to social dysfunction in schizophrenia.

ISC measures are also expected to constitute a biomarker of social dysfunction that may be useful for identifying individuals at high risk of social disconnection, targeting treatments toward individuals most likely to benefit from them, or assessing outcomes in future clinical trials.
Funding Goals
THE MISSION OF THE NATIONAL INSTITUTE OF MENTAL HEALTH (NIMH) IS TO TRANSFORM THE UNDERSTANDING AND TREATMENT OF MENTAL ILLNESSES THROUGH BASIC AND CLINICAL RESEARCH, PAVING THE WAY FOR PREVENTION, RECOVERY, AND CURE. IN MAY 2020, NIMH RELEASED ITS NEW STRATEGIC PLAN FOR RESEARCH. THE NEW STRATEGIC PLAN BUILDS ON THE SUCCESSES OF PREVIOUS NIMH STRATEGIC PLANS BY PROVIDING A FRAMEWORK FOR SCIENTIFIC RESEARCH AND EXPLORATION, AND ADDRESSING NEW CHALLENGES IN MENTAL HEALTH. THE NEW STRATEGIC PLAN OUTLINES FOUR HIGH-LEVEL GOALS: GOAL 1: DEFINE THE BRAIN MECHANISMS UNDERLYING COMPLEX BEHAVIORS GOAL 2: EXAMINE MENTAL ILLNESS TRAJECTORIES ACROSS THE LIFESPAN GOAL 3: STRIVE FOR PREVENTION AND CURES GOAL 4: STRENGTHEN THE PUBLIC HEALTH IMPACT OF NIMH-SUPPORTED RESEARCH THESE FOUR GOALS FORM A BROAD ROADMAP FOR THE INSTITUTE'S RESEARCH PRIORITIES OVER THE NEXT FIVE YEARS, BEGINNING WITH THE FUNDAMENTAL SCIENCE OF THE BRAIN AND BEHAVIOR, AND EXTENDING THROUGH EVIDENCE-BASED SERVICES THAT IMPROVE PUBLIC HEALTH OUTCOMES. THE INSTITUTE'S OVERALL FUNDING STRATEGY IS TO SUPPORT A BROAD SPECTRUM OF INVESTIGATOR-INITIATED RESEARCH IN FUNDAMENTAL SCIENCE, WITH INCREASING USE OF INSTITUTE-SOLICITED INITIATIVES FOR APPLIED RESEARCH WHERE PUBLIC HEALTH IMPACT IS A SHORT-TERM MEASURE OF SUCCESS. THE NEW STRATEGIC PLAN ALSO ADDRESSES A NUMBER OF CROSS-CUTTING THEMES THAT ARE RELEVANT TO ALL RESEARCH SUPPORTED BY NIMH, THESE THEMES HIGHLIGHT AREAS WHERE NIMH-FUNDED SCIENCE MAY HAVE THE GREATEST IMPACT, BRIDGE GAPS, AND OFFER NOVEL APPROACHES TO ACCELERATE ADVANCES IN MENTAL HEALTH RESEARCH. FOR EXAMPLE, NIMH VALUES A COMPREHENSIVE RESEARCH AGENDA THAT TAKES AN INCLUSIVE APPROACH THAT ENSURES RESEARCH INTERESTS ARE VARIED, MAINTAIN DIVERSE PARTICIPATION AND PARTNERSHIPS, AND ACHIEVE RESEARCH GOALS ACROSS MULTIPLE TIMEFRAMES. THIS INCLUDES DIVERSE METHODOLOGIES, TOOLS, AND MODELS, RESEARCH ADDRESSING COMPLEX BASIC, TRANSLATIONAL, AND APPLIED QUESTIONS, RESEARCH INCLUDING BOTH SEXES AND, AS APPROPRIATE, GENETIC BACKGROUND, AND, PARTICIPANTS FROM DIVERSE RACIAL AND ETHNIC BACKGROUNDS, AND ACROSS GENDER IDENTITIES, GEOGRAPHICAL CONTEXT, SOCIOECONOMIC STATUS, NEUROTYPE, AND AGE OFFERING THE BEST POSSIBLE REPRESENTATION, FOR THE BROADEST NUMBER OF INDIVIDUALS WHO MAY ULTIMATELY BENEFIT FROM THESE SCIENTIFIC ADVANCES. TO ACCOMPLISH THE GOALS OUTLINED IN THE NEW STRATEGIC PLAN, NIMH WILL SUPPORT RESEARCH THAT AIMS: TO CHARACTERIZE THE GENOMIC, MOLECULAR, CELLULAR, AND CIRCUIT COMPONENTS CONTRIBUTING TO BRAIN ORGANIZATION AND FUNCTION, TO IDENTIFY THE DEVELOPMENTAL, FUNCTIONAL, AND REGULATORY MECHANISMS RELEVANT TO COGNITIVE, AFFECTIVE, AND SOCIAL DOMAINS, ACROSS UNITS OF ANALYSIS, AND, TO GENERATE AND VALIDATE NOVEL TOOLS, TECHNIQUES, AND MEASURES TO QUANTIFY CHANGES IN THE ACTIVITY OF MOLECULES, CELLS, CIRCUITS, AND CONNECTOMES. TO DISCOVER GENE VARIANTS AND OTHER GENOMIC ELEMENTS THAT CONTRIBUTE TO THE DEVELOPMENT OF MENTAL ILLNESSES IN DIVERSE POPULATIONS, TO ADVANCE OUR UNDERSTANDING OF THE COMPLEX ETIOLOGY OF MENTAL ILLNESSES USING MOLECULAR EPIDEMIOLOGIC APPROACHES THAT INCORPORATE INDIVIDUAL GENETIC INFORMATION IN LARGE COHORTS, TO ELUCIDATE HOW HUMAN GENETIC VARIATION AFFECTS THE COORDINATION OF MOLECULAR, CELLULAR, AND PHYSIOLOGICAL NETWORKS SUPPORTING HIGHER-ORDER FUNCTIONS AND EMERGENT PROPERTIES OF NEUROBIOLOGICAL SYSTEMS, AND, TO DEVELOP NOVEL TOOLS AND TECHNIQUES FOR THE ANALYSIS OF LARGE-SCALE GENETIC, MULTI-OMIC DATA AS IT APPLIES TO MENTAL HEALTH. TO UTILIZE CONNECTOMIC APPROACHES TO IDENTIFY BRAIN NETWORKS AND CIRCUIT COMPONENTS THAT CONTRIBUTE TO VARIOUS ASPECTS OF MENTAL FUNCTION AND DYSFUNCTION, TO DETERMINE THROUGH BRAIN-WIDE ANALYSIS HOW CHANGES IN THE PHYSIOLOGICAL PROPERTIES OF MOLECULES, CELLS, AND CIRCUITS CONTRIBUTE TO MENTAL ILLNESSES, TO DEVELOP MOLECULAR, CELLULAR, AND CIRCUIT-LEVEL BIOMARKERS OF IMPAIRED NEURAL FUNCTION IN HUMANS, AND, TO DEVELOP INNOVATIVE TECHNOLOGIES, INCLUDING NEW IMAGING, COMPUTATIONAL, PHARMACOLOGICAL, AND GENETIC TOOLS TO INTERROGATE AND MODULATE CIRCUIT ACTIVITY AND STRUCTURE ALTERED IN MENTAL ILLNESSES. TO ELUCIDATE THE MECHANISMS CONTRIBUTING TO THE TRAJECTORIES OF BRAIN DEVELOPMENT AND BEHAVIOR, AND, TO CHARACTERIZE THE EMERGENCE AND PROGRESSION OF MENTAL ILLNESSES, AND IDENTIFYING SENSITIVE PERIODS FOR OPTIMAL INTERVENTION. TO DETERMINE EARLY RISK AND PROTECTIVE FACTORS, AND RELATED MECHANISMS, TO SERVE AS NOVEL INTERVENTION GROUPS, AND, TO DEVELOP RELIABLE AND ROBUST BIOMARKERS AND ASSESSMENT TOOLS TO PREDICT ILLNESS ONSET, COURSE, AND ACROSS DIVERSE POPULATIONS. TO DEVELOP NOVEL INTERVENTIONS USING A MECHANISM-INFORMED, EXPERIMENTAL THERAPEUTICS APPROACH, AND, TO DEVELOP AND IMPLEMENT MEASUREMENT STRATEGIES TO FACILITATE MECHANISM-BASED INTERVENTION DEVELOPMENT AND TESTING. TO INVESTIGATE PERSONALIZED INTERVENTION STRATEGIES ACROSS DISEASE PROGRESSION AND DEVELOPMENT, AND, TO DEVELOP AND REFINE COMPUTATIONAL APPROACHES AND RESEARCH DESIGNS THAT CAN BE USED TO INFORM AND TEST PERSONALIZED INTERVENTIONS. TO DEVELOP AND TEST APPROACHES FOR ADAPTING, COMBINING, AND SEQUENCING INTERVENTIONS TO ACHIEVE THE GREATEST IMPACT ON THE LIVES AND FUNCTIONING OF PERSONS SEEKING CARE, TO CONDUCT EFFICIENT PRAGMATIC TRIALS THAT EMPLOY NEW TOOLS TO RAPIDLY IDENTIFY, ENGAGE, ASSESS, AND FOLLOW PARTICIPANTS IN THE CONTEXT OF ROUTINE CARE, AND, TO ENHANCE THE PRACTICAL RELEVANCE OF EFFECTIVENESS RESEARCH VIA DEPLOYMENT-FOCUSED, HYBRID, EFFECTIVENESS-IMPLEMENTATION STUDIES. TO EMPLOY ASSESSMENT PLATFORMS WITHIN HEALTHCARE SYSTEMS TO ACCURATELY ASSESS THE DISTRIBUTION AND DETERMINANTS OF MENTAL ILLNESSES AND TO INFORM STRATEGIES FOR IMPROVED SERVICES, TO OPTIMIZE REAL-WORLD DATA COLLECTION SYSTEMS TO IDENTIFY STRATEGIES FOR IMPROVING ACCESS, QUALITY, EFFECTIVENESS, AND CONTINUITY OF MENTAL HEALTH SERVICES, AND, TO COMPARE ALTERNATIVE FINANCING MODELS TO PROMOTE EFFECTIVE AND EFFICIENT CARE FOR INDIVIDUALS WITH SERIOUS EMOTIONAL DISTURBANCES AND SERIOUS MENTAL ILLNESSES. TO STRENGTHEN PARTNERSHIPS WITH KEY STAKEHOLDERS TO DEVELOP AND VALIDATE STRATEGIES FOR IMPLEMENTING, SUSTAINING, AND CONTINUOUSLY IMPROVE EVIDENCE-BASED PRACTICES, TO BUILD MODELS TO SCALE-UP EVIDENCE-BASED PRACTICES FOR USE IN PUBLIC AND PRIVATE PRIMARY CARE, SPECIALTY CARE AND OTHER SETTINGS, AND, TO DEVELOP DECISION-SUPPORT TOOLS AND TECHNOLOGIES THAT INCREASE THE EFFECTIVENESS AND CONTINUOUS IMPROVEMENT OF MENTAL HEALTH INTERVENTIONS IN PUBLIC AND PRIVATE PRIMARY CARE, SPECIALTY CARE, AND OTHER SETTINGS. TO ADAPT, VALIDATE, AND SCALE-UP PROGRAMS CURRENTLY IN USE THAT IMPROVE MENTAL HEALTH SERVICES FOR UNDERSERVED POPULATIONS, TO DEVELOP AND VALIDATE SERVICE DELIVERY MODELS THAT PROVIDE EVIDENCE-BASED CARE FOR INDIVIDUALS THROUGHOUT THE COURSE OF MENTAL ILLNESS, TO DEVELOP AND VALIDATE SYSTEMS-LEVEL STRATEGIES USING TECHNOLOGY AND OTHER APPROACHES, TO IDENTIFY, SUPPORT, AND MONITOR THE EFFECTIVENESS OF EVIDENCE-BASED CARE THROUGHOUT THE COURSE OF ILLNESS, AND, TO DEVELOP AND VALIDATE DECISION-MAKING MODELS THAT BRIDGE MENTAL HEALTH, MEDICAL, AND OTHER CARE SETTINGS TO INTEGRATE THE APPROPRIATE CARE FOR PEOPLE WITH SERIOUS MENTAL ILLNESSES AND COMORBID MEDICAL CONDITIONS.
Place of Performance
Los Angeles, California 900958353 United States
Geographic Scope
Single Zip Code
Analysis Notes
Amendment Since initial award the total obligations have increased 383% from $752,235 to $3,630,321.
Los Angeles University Of California was awarded Schizophrenia Biomarker: Neural Synchrony & Social Dysfunction Project Grant R01MH128720 worth $3,630,321 from the National Institute of Mental Health in September 2021 with work to be completed primarily in Los Angeles California United States. The grant has a duration of 5 years and was awarded through assistance program 93.242 Mental Health Research Grants. The Project Grant was awarded through grant opportunity NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed).

Status
(Ongoing)

Last Modified 8/20/25

Period of Performance
9/8/21
Start Date
8/31/26
End Date
79.0% Complete

Funding Split
$3.6M
Federal Obligation
$0.0
Non-Federal Obligation
$3.6M
Total Obligated
100.0% Federal Funding
0.0% Non-Federal Funding

Activity Timeline

Interactive chart of timeline of amendments to R01MH128720

Transaction History

Modifications to R01MH128720

Additional Detail

Award ID FAIN
R01MH128720
SAI Number
R01MH128720-3068345645
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Public/State Controlled Institution Of Higher Education
Awarding Office
75N700 NIH National Institute of Mental Health
Funding Office
75N700 NIH National Institute of Mental Health
Awardee UEI
RN64EPNH8JC6
Awardee CAGE
4B557
Performance District
CA-36
Senators
Dianne Feinstein
Alejandro Padilla

Budget Funding

Federal Account Budget Subfunction Object Class Total Percentage
National Institute of Mental Health, National Institutes of Health, Health and Human Services (075-0892) Health research and training Grants, subsidies, and contributions (41.0) $1,382,976 100%
Modified: 8/20/25