Neural Mechanisms of Impulsivity and Attention Following Traumatic Brain Injury

NIH RePORTER · VA · IK2 · · view on reporter.nih.gov ↗

Abstract

Military occupational exposure to blast overpressure from improvised explosive devices can lead to mild traumatic brain injury (blast-TBI), resulting in debilitating persistent post-concussive symptoms (PPCS) and psychological dysfunction, but diagnoses and treatment options are limited. Common PPCS complaints of Veterans with blast histories include both cognitive difficulties and physiological symptoms. Likewise, common psychological dysfunctions include impulse control disorders, substance abuse, post traumatic stress disorder, depression and anxiety, but the causal mechanisms remain unknown. Therefore, increases in preclinical research efforts using rodent models are required to provide much needed insight into the underlying mechanisms by which blast-TBI contributes to subsequent dysfunction. While rodent models of blast-TBI have largely focused on potential memory-related cognitive effects, no study to date has utilized rodent models to examine the effects of blast exposure on impulsivity or attention, which are common and recurring complaints of blast exposed Veterans and are highly implicated in psychological dysfunction among civilian populations. Likewise, the neuromodulator dopamine plays a critical role in reward processing and decision making, and in civilian populations, perturbations of phasic dopamine release have been implicated in a variety of psychological dysfunctions that are similar in nature to those seen following blast-TBI. Surprisingly, few studies to date have investigated a role for dopamine dysfunction following blast exposure. The current proposal seeks to fill these knowledge gaps and will combine a mouse model of blast-induced TBI, fast scan cyclic voltammetry (FSCV) to measure subsecond nucleus accumbens (NAc) phasic dopamine release, and behavioral measures of impulsivity and attention. Aim one will examine the near and long-term consequences of single and repetitive blast exposure on the mesolimbic dopamine system using FSCV and electrical stimulation of discrete brain regions. Aim two will examine the near and long-term consequences of single and repetitive blast exposure on measures of impulsivity and attention, and will determine a potential role for augmented phasic dopamine release following blast in these behaviors. In rodent models, maladaptive measures of impulsivity and attention have been linked to an increase in phasic NAc dopamine neurotransmission. Therefore, based on the large number of blast-TBI Veterans presenting with impulsivity and attention impairments and our preliminary data demonstrating a blast-induced increase in impulsivity related behaviors and stimulated phasic dopamine release, we hypothesize that blast exposure will result in increased NAc dopamine release that in turn drives maladaptive measures of impulsivity and attention. These experiments are intended to further our understanding of the behavioral and neurochemical mechanisms underlying blast-TBI dysfunction, and will be an imp...

Key facts

NIH application ID
9859327
Project number
5IK2BX003258-04
Recipient
VA PUGET SOUND HEALTHCARE SYSTEM
Principal Investigator
Abigail G Schindler
Activity code
IK2
Funding institute
VA
Fiscal year
2020
Award amount
Award type
5
Project period
2017-01-01 → 2021-12-31