Cortical oscillatory dynamics and decision deficits in suicidal behavior - Resubmission
Project Number5K23MH130664-02
Former Number1K23MH130664-01
Contact PI/Project LeaderTSYPES, ALIONA
Awardee OrganizationUNIVERSITY OF PITTSBURGH AT PITTSBURGH
Description
Abstract Text
Despite significant research efforts, the progress in understanding and prevention of suicide has been slow.
This is due at least in part to the vagueness of current suicide theories that rely on verbal specifications of all
constructs and consequent predictions and thus provide correlative rather than mechanistic accounts of
suicidal behavior (SB). In contrast, formal theoretical frameworks grounded in learning theory and decision
neuroscience, such as reinforcement learning (RL), afford a productive approach for uncovering cognitive and
decision processes involved in suicide through the use of explicit mathematical ideas to define constructs,
hypotheses, predictions, and assumptions of interest. Further, when faced with a crisis, a transition from
thinking about to attempting suicide involves the need to make a decision under increased cognitive demands
imposed by high information load (multiple decision options), uncertainty, and time pressure (current crisis).
However, although real-life decision-making is dynamic and is influenced by situational demands, existing
neural models of suicidal diathesis are relatively static and not yet integrated with the advances in decision
neuroscience. In contrast, electrophysiology augmented with computational modeling can reveal the dynamic
unfolding of within-trial neural events and is well suited for answering mechanistic questions about cortical
oscillations that underlie real-time decision-making. This project will experimentally manipulate cognitive
demands on decision-making using an RL task with a validated computational model to examine decision
processes in SB (Aim 1). It will also build on the basic electrophysiology literature that implicates alpha, beta,
and theta oscillations in working memory and cognitive control by examining neural encoding of reinforcement
history in attempted suicide (Aim 2). Exploratory Aim 3 will allow for a preliminary examination of the effects of
self-reported mood, stress, and task-related neural activity on behavior. Participants will be 120 adults (40
suicide attempters, 40 suicide ideators, and 40 healthy controls) recruited from inpatient, outpatient, and
community settings. Expert mentorship team will provide training in behavioral and computational modeling,
basic neuroscience, and electrophysiology. The work will take place at the Department of Psychiatry of the
University of Pittsburgh, which has a long track record of supporting career development of its junior faculty.
This K23 will promote the Candidate’s long-term goals of contributing to suicide research and prevention by
identifying the neurocomputational mechanisms of deficient decision-making in SB. The project is consistent
with the NIMH’s goals and funding priorities and builds on the Candidate’s prior NIMH-funded RDoC-informed
work. It also falls into several areas of emphasis for NIMH’s Computational Psychiatry Program (“translating
basic computational models into clinical research by informing the models with experimental data from clinical
population,” “understanding how individual differences in neuronal activity contribute to the transmission and
processing of pathophysiological information in the central nervous system”).
Public Health Relevance Statement
When faced with a crisis, some people but not others transition from thinking about suicide to acting on these
thoughts. This project will use a formal theoretical framework combined with electroencephalography to test
the hypothesis that individuals at risk for suicide become cognitively overwhelmed under challenging life
circumstances and make poor choices as a result. The anticipated impact of this proposal includes the
identification of more precise targets for cognitive clinical interventions.
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