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Principal Investigator: Sarah Ann Thomas
Organization: EMMA PENDLETON BRADLEY HOSPITAL
Fiscal Year: 2024
Award: $196,776
Funding agency: National Institute on Drug Abuse
7. PROJECT SUMMARY:
Cannabis use (CU) initiated in adolescence is associated with substantial consequences, from cognitive
decline to addiction. While CU may disrupt normal processes of adolescent brain development, relatively little
is known about how adolescent CU disrupts circuits mediating cognitive flexibility (adaptation to changing
rewards and punishments) and intrinsic resting state functional connectivity (RSFC), and impacts reward
motivation (the amount of goal-directed behavior to earn reinforcement). These domains are all understudied
areas relative to adult CU yet advancing knowledge of these processes may explain why adolescent-onset CU
is linked to functional impairments and higher rates of problematic substance use. Dr. Thomas’s long-term
career goal is to become an independent researcher identifying bio-behavioral mechanisms of risks and effects
of adolescent drug use in order to improve identification methods for targeted prevention and treatment. The
central hypothesis to be tested in this 4-year patient-oriented mentored career award is that CU in the context
of adolescent brain development is linked to frontostriatal alterations and impaired cognitive flexibility, reward
motivation, and intrinsic RSFC that will vary as a function of CU exposure. The central methodology is to use
symptom, circuit, and behavioral data in 14-17 year old adolescents who are engaged in CU and also typically-
developing control adolescents (n=40 of each). The career development objectives of this NIDA K23
application are to gain hands-on mentorship in (a) phenomenology and assessment of adolescent CU, (b) the
use of fMRI to measure brain/behavior alterations underlying adolescent CU, and (c) advanced statistical
methods for greater level of inference from these data, by learning a computational psychiatry model. The
research objectives of this K23 are to: (1) to identify the brain/behavior mechanisms of cognitive flexibility and
RSFC associated with CU using fMRI; (2) to define behavioral alterations in reward motivation; (3) to use
advanced statistical methods, including a specific computational model, to integrate the neural and behavioral
contributions to decision-making during a cognitive flexibility task and determine how decision-making
components vary for CU adolescents and control adolescents. Brown University is a rich scientific environment
to conduct this research due to the expertise of mentors in adolescent substance use, neuroscience, and
advanced statistical methods with ample resources to carry out Dr. Thomas’s training plan consisting of hands-
on mentorship, workshops, coursework (e.g., neuroanatomy), and professional development (conference
presentations, publications). This project is significant because addressing the dearth of knowledge about
cognitive flexibility, reward motivation, and RSFC is the first step towards facilitating mechanism-based (a)
predictors of progression from regular CU to addiction, and (b) treatments for CU among adolescents. This
project is innovative in its use of fMRI to probe the relatively understudied domains of cognitive flexibility and
reward motivation among adolescents with and without CU using computational psychiatry analyses.
Terms: <12-20 years old><17 year old><17 years of age><21+ years old><Acceleration><Address><Adolescence><Adolescent><Adolescent Youth><Adolescent marijuana use><Adult><Adult Human><Affect><Age><Area><Award><Behavior><Behavioral><Behavioral Mechanisms><Behavioral Model><Biological><Brain><Brain Nervous System><Brain region><Cannabinoids><Cannabis><Causality><Chronic><Cognitive><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive function abnormal><Computer Models><Computerized Models><Corpus Striatum><Corpus striatum structure><Data><Data Analyses><Data Analysis><Decision Making><Development><Development and Research><Diffusion><Disturbance in cognition><Drug Therapy><Drug usage><Education><Educational aspects><Educational workshop><Encephalon><Environment><Etiology><Exhibits><Failure><Functional MRI><Functional Magnetic Resonance Imaging><Functional impairment><Goals><Impaired cognition><Impairment><Individual><Intervention><Intervention Strategies><Investigation><Investigators><Knowledge><Learning><Link><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Measures><Mechanisms of Behavior and Behavior Change><Mediating><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Mentors><Mentorship><Methodology><Methods><Modeling><Motivation><NIDA><NMR Imaging><NMR Tomography><National Institute of Drug Abuse><National Institute on Drug Abuse><Neuranatomies><Neuranatomy><Neuroanatomies><Neuroanatomy><Neurosciences><Nuclear Magnetic Resonance Imaging><Occupational><Outcome><Pathway interactions><Pharmacotherapy><Prefrontal Cortex><Prevention><Probabilistic Models><Probability Models><Process><Psychiatry><Psychological reinforcement><Public Health><Publications><Punishment><R & D><R&D><R-Series Research Projects><R01 Mechanism><R01 Program><Receptor Protein><Reinforcement><Research><Research Grants><Research Personnel><Research Project Grants><Research Projects><Research Resources><Researchers><Resources><Rest><Reversal Learning><Rewards><Risk><Scientific Publication><Scientist><Statistical Methods><Statistical Models><Stimulus><Strategic Planning><Striate Body><Striatum><Symptoms><THC co-use><THC use><Testing><Tetrahydrocannabinol co-use><Tetrahydrocannabinol use><Training><Universities><Visit><Work><Workshop><Zeugmatography><addiction><addictive disorder><adolescence (12-20)><adolescent brain development><adolescent drug use><adolescent substance use><adulthood><adverse consequence><adverse outcome><age 17 years><ages><behavior mechanism><biobehavior><biobehavioral><biologic><brain based><cannabis use><cannabis use among adolescents><cannabis user><career><career development><causation><cognitive control><cognitive dysfunction><cognitive loss><computational modeling><computational models><computer based models><computerized modeling><conference><convention><data interpretation><design><designing><developmental><diffused><diffuses><diffusing><diffusions><disease causation><drug treatment><drug use><fMRI><flexibility><flexible><high school><improved><innovate><innovation><innovative><interventional strategy><juvenile><juvenile human><longitudinal design><maladaptive behavior><marijuana use><marijuana use among adolescents><marijuana use in adolescence><marijuana user><neglect><neural><neural circuit><neural circuitry><neural imaging><neural recruitment><neuro-imaging><neurobehavioral><neurocircuitry><neuroimaging><neurological imaging><non-drug><nondrug><novel><pathway><patient centered><patient oriented><phenomenological models><phenomenology><receptor><research and development><response><response to therapy><response to treatment><seventeen year old><seventeen years of age><skills><statistic methods><statistical linear mixed models><statistical linear models><striatal><substance use><substance use among adolescents><substance use among youth><substance using><success><summit><symposia><symposium><synaptic circuit><synaptic circuitry><therapeutic response><therapy response><treatment response><treatment responsiveness><youth drug use><youth substance use>