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Principal Investigator: Steve W. C. Chang
Organization: UNIVERSITY OF ARIZONA
Fiscal Year: 2024
Award: $651,458
Funding agency: National Institute of Mental Health
ABSTRACT
Adolescence is a time of substantial development attributed to the maturation of brain circuits that underlie the
acquisition of new cognitive, emotional, and social skills. It is also a time of maximum vulnerability for mental
disorders. In the past decade, the incidence of anxiety, depression, and suicide increased by ~60% in
adolescents, remarkably more in females than in males. The social isolation during the COVID-19 pandemic
added to the severity of the national and international statistics. To fully address the current youth mental
health crisis, we need to understand how and why the dramatic reorganization of the adolescent brain
contributes to the increased vulnerability to mental disorders. The studies proposed here rest on the
assumption that the remodeling of the reward circuits of the brain creates the shared foundation of cognitive,
affective, and social maturation during adolescence. Our multifaceted project addresses foundational gaps in
our knowledge on how reward-driven motivational states inform adolescent behaviors such as risk-taking,
pleasure-seeking, impulsivity, and a range of emotional responses to challenges of the social environment. We
designed a within-subject, longitudinal study that spans the 2.5 - 3-year duration of adolescence in non-human
primates. During this period, we will obtain repeated samplings of neurophysiological data recorded from the
amygdala and orbitofrontal cortex in the context of the same behavioral tasks. In parallel, we will longitudinally
monitor morphometric and microstructural changes in the gray and white matter of the brain through serial MRI
scans, complemented by physical and hormonal measures of pubertal maturation. The three specific aims
address the neural basis of three different aspects of reward processing in the subcircuit of the amygdala and
orbitofrontal cortex. First, we will use a delay discounting task to determine the cellular and circuit level
changes that underlie the increasing tolerance (or lack thereof) for delayed rewards. Second, we use a social
reward-allocation task to test the neural underpinning of social reward processing in a self-oriented and an
other-oriented social frame of reference. Finally, we will determine where and how social status is processed in
the adolescent brain. Understanding social status relies on the ability to form abstract representations and is
also a prerequisite for the successful integration of the individual into a hierarchical adult social group. The
team, with combined expertise in human and non-human primate social behavior, neurophysiology,
neuroimaging, and endocrinology, will apply conceptually and technically innovative approaches to generate
unique and translational data, at both cellular and circuit levels, that account for the emerging cognitive,
affective, and social skills acquired during adolescence.
Terms: <12-20 years old><21+ years old><Address><Adolescence><Adolescent><Adolescent Behavior><Adolescent Youth><Adult><Adult Human><Affective><Amygdala><Amygdaloid Body><Amygdaloid Nucleus><Amygdaloid structure><Anxiety><Area><Behavior><Behavior monitoring><Behavioral><Benefits and Risks><Brain><Brain Nervous System><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 years><Cell Body><Cells><Cognitive><Data><Decision Making><Development><Disparities><Disparity><Economics><Education><Educational aspects><Emotional><Emotional Bonds><Encephalon><Endocrine><Endocrinology><Female><Foundations><Frequencies><Glean><Goals><Hormonal><Human><Impulsivity><Incidence><Individual><International><Joints><Knowledge><Longitudinal Studies><MRI Scans><Macaca><Macaque><Magnetic Resonance Imaging Scan><Measures><Mental Depression><Mental Health><Mental Hygiene><Mental disorders><Mental health disorders><Metabolism and Endocrinology><Modeling><Modern Man><Monitor><Monkeys><Motivation><NIH><National Institutes of Health><Nerve Cells><Nerve Unit><Neural Cell><Neurocyte><Neurons><Outcome><Partner in relationship><Peer Group><Performance><Population><Prefrontal Cortex><Process><Property><Psychiatric Disease><Psychiatric Disorder><Psychological Health><Psychological reinforcement><Puberty><Race><Races><Reinforcement><Rest><Rewards><Risk><Risk Estimate><Risk Taking><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Saccades><Saccadic Eye Movements><Saccadic Pursuit><Sampling><Serial Magnetic Resonance Imaging><Series><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severities><Social Behavior><Social Environment><Social Interaction><Social isolation><Social status><Stress><Suicide><Testing><Time><United States National Institutes of Health><Youth><Youth 10-21><adolescence (12-20)><adulthood><amygdaloid nuclear complex><behavioral monitoring><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><depression><design><designing><developmental><discounting><economic><emotion regulation><emotional attachment><emotional regulation><fatal attempt><fatal suicide><gaze><gray matter><innovate><innovation><innovative><insight><intent to die><interpersonal competence><interpersonal competency><joint attention><juvenile><juvenile human><long-term study><longitudinal outcome studies><longterm study><male><mate><mental illness><multidisciplinary><myelination><neural><neural circuit><neural circuitry><neural imaging><neuro-imaging><neurocircuitry><neuroimaging><neurological imaging><neuronal><neurophysiological><neurophysiology><non-human primate><nonhuman primate><nutrition><peer><pleasure><psychiatric illness><psychological disorder><racial><racial background><racial origin><response><reward processing><serial MRI><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><sex><skill acquisition><skill development><social><social climate><social competence><social competency><social context><social group><social position><social skills><social standing><sociobehavior><sociobehavioral><socioenvironment><socioenvironmental><statistics><substantia alba><substantia grisea><suicides><synaptic circuit><synaptic circuitry><white matter>