Brain changes underlying emotional and executive alterations in TBI

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

Abstract

The primary goal of this proposal is to elucidate the possible mechanistic basis of emotional disorders, particularly posttraumatic stress disorder, after mild traumatic brain injury. Problem: Posttraumatic stress disorder (PTSD) is common in military Veterans and often causes chronic suffering including damaging social relationships, employment prospects, health, and overall happiness of those who experience it. Mild traumatic brain injury (mTBI) is a frequent preceding injury and the relationship between injury characteristics associated with mTBI and emotional dysregulation disorders such as PTSD remains unclear, with mixed findings reported in the literature. mTBI can damage important connections between brain regions, especially brain regions critical for emotional experience. Veterans who have suffered one or more mTBIs also are more likely to have other psychiatric conditions, and they also have worse health and social outcomes. Many of these poor outcomes are due to emotional dysregulation. Individuals who have suffered a mTBI or who have PTSD often show changes in brain function in emotional and executive brain regions. Even when their performance on executive tasks is still normal, the underlying brain regions show altered functional relationships including increased activity. Interpretation of these functional changes presents challenges, however. In other populations, these sorts of findings are often associated with pathology or are leading indicators of functional decline. Further, such activity may reflect differences in the capacity to adaptively manage cognitive and emotional resources. When performing emotional tasks, individuals with PTSD show increased activity in emotional brain regions. This may be due in part to reduced executive capacity or to increased demands placed on executive capacity by an overactive emotional system, possibly mediated by dysfunctional neurotransmitter systems. Notably, PTSD is associated with a reduction in the receptors of and the levels of the brain's primary inhibitory neurotransmitter, GABA. Similarly, GABA is reduced after a TBI and this change is associated with a reduced ability to forget fearful memories and to regulate emotions. This overlap in brain changes may suggest a linkage between injury characteristics associated with mTBI and the development of PTSD. Preliminary Work: Consistent with our theoretical model, our pilot data demonstrate damage in limbic and prefrontal connectivity is related to symptoms of PTSD in patients with mTBI. Further, we showed that injury characteristics of mTBI affect performance on emotional tasks. Finally, we demonstrated feasibility for each of the magnetic resonance measures and tasks that we will use in the proposed research. Plan: The proposed investigation will examine the relationship between two key brain networks, limbic (emotional) and prefrontal, which are dysfunctional in individuals with emotional dysregulation and the function of which may ...

Key facts

NIH application ID
9937526
Project number
5IK2RX002490-03
Recipient
VETERANS HEALTH ADMINISTRATION
Principal Investigator
Damon G Lamb
Activity code
IK2
Funding institute
VA
Fiscal year
2020
Award amount
Award type
5
Project period
2018-03-01 → 2023-02-28