Project Details
Description
PROJECT SUMMARY / ABSTRACT
This K23 career development project will study the neural underpinnings of impulsivity in adolescent suicidal
behavior (SB). The candidate will obtain critical skills and experience in adolescent suicidology and impulsivity
research, advanced neurophysiologic and longitudinal methods, and translation of neurophysiologic research
to interventional studies needed for a career focused on elucidating brain-behavior mechanisms of adolescent
SB. Suicide is the second leading cause of death in adolescence, and rates of adolescent SB are increasing.
However, its neurobiology remains poorly understood, and treatments specifically targeting SB are lacking. SB
in adolescents is a critical public health problem that demands urgent attention, particularly with research that
will rapidly translate knowledge to clinical applications. Negative urgency, a component of impulsivity, is the
tendency to act rashly in the context of negative emotion. It has been found to be increased among youth with
SB and attempts, and has been linked to impaired inhibition of limbic circuitry by the dorsolateral prefrontal
cortex (DLPFC), yet precise mechanisms are unclear. Transcranial magnetic stimulation (TMS) permits
noninvasive quantification of DLPFC functions such as cortical inhibition (CI), the process by which cortical
interneurons regulate the activity of other circuits. Previous research indicates that adolescents with lifetime SB
have reduced CI in the motor cortex that distinguishes them from non-suicidal youth. However, DLPFC CI has
not been measured in adolescents with SB, nor is it clear how CI relates to cognitive and emotional systems
implicated in SB, such as negative urgency. In order to study CI-related mechanisms of negative urgency in
the DLPFC, simultaneous TMS and electroencephalography (TMS-EEG) is required. The candidate proposes
a longitudinal study of inhibitory physiology and negative urgency in 40 depressed adolescents with suicidal
ideation (but no SB) and 40 depressed adolescents with SB. The study will utilize TMS-EEG and self-report
measures of negative urgency to test hypotheses that dysregulated CI is associated with negative urgency,
that DLPFC CI is deficient in adolescents with SB, and that CI deficits correlate longitudinally with changes in
negative urgency and newly emergent SB. The candidate has prior experience with more basic TMS methods;
however, to attain long-term career goals, additional training in EEG analysis, assessment of impulsivity in
suicidal adolescents, and longitudinal/neurodevelopmental research methods is necessary. A robust career
development plan, with multidisciplinary mentorship and collaboration, will involve intramural and extramural
coursework, methodology-specific seminars and training, and a well-defined plan for grant and publication
benchmarks. This will ensure the candidate’s successful transition to an independent clinical research career.
The long-term goal is to utilize data gathered in this project to design a large-scale longitudinal study assessing
neural and behavioral risk factors for developing SB, as well as trials of neuromodulatory treatments that will
reduce the transition from suicidal thoughts to behaviors by targeting alterations in CI and negative urgency.
Status | Active |
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Effective start/end date | 8/1/23 → 7/31/24 |
Funding
- National Institute of Mental Health: $198,060.00
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