title: Neurobiological indicators of disinhibition in posttraumatic stress disorder.
abstract: Deficits in impulse control are increasingly recognized in association with posttraumatic stress disorder (PTSD). To our further understanding of the neurobiology of PTSD-related disinhibition, we examined alterations in brain morphology and network connectivity associated with response inhibition failures and PTSD severity. The sample consisted of 189 trauma-exposed Operation Enduring Freedom/Operation Iraqi Freedom veterans (89% male, ages 19-62) presenting with a range of current PTSD severity. Disinhibition was measured using commission errors on a Go/No-Go (GNG) task with emotional stimuli, and PTSD was assessed using a measure of current symptom severity. Whole-brain vertex-wise analyses of cortical thickness revealed two clusters associated with PTSD-related disinhibition (Monte Carlo cluster corrected P < 0.05). The first cluster included portions of right inferior and middle frontal gyri and frontal pole. The second cluster spanned portions of left medial orbital frontal, rostral anterior cingulate, and superior frontal gyrus. In both clusters, commission errors were associated with reduced cortical thickness at higher (but not lower) levels of PTSD symptoms. Resting-state functional magnetic resonance imaging analyses revealed alterations in the functional connectivity of the right frontal cluster. Together, study findings suggest that reductions in cortical thickness in regions involved in flexible decision-making, emotion regulation, and response inhibition contribute to impulse control deficits in PTSD. Furthermore, aberrant coupling between frontal regions and networks involved in selective attention, memory/learning, and response preparation suggest disruptions in functional connectivity may also play a role.
authors.affiliation: National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, MA, USA.|Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Naomi
authors.initials: N
authors.lastname: Sadeh
authors.affiliation: Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, MA, USA.|Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Spielberg
authors.affiliation: National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, MA, USA.|Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Miller
authors.affiliation: Translational Research Center for TBI and Stress Disorders and Geriatric Research, Educational and Clinical Center, VA Boston Healthcare System, Boston, MA, USA.|Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: William P
authors.initials: WP
authors.lastname: Milberg
authors.affiliation: Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, MA, USA.|Department of Radiology, Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USA.|Department of Radiology, Harvard Medical School, Boston, MA, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Salat
authors.affiliation: Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.|Translational Research Center for TBI and Stress Disorders and Geriatric Research, Educational and Clinical Center, VA Boston Healthcare System, Boston, MA, USA.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Amick
authors.affiliation: Translational Research Center for TBI and Stress Disorders and Geriatric Research, Educational and Clinical Center, VA Boston Healthcare System, Boston, MA, USA.|Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Fortier
authors.affiliation: Translational Research Center for TBI and Stress Disorders and Geriatric Research, Educational and Clinical Center, VA Boston Healthcare System, Boston, MA, USA.|Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: Regina E
authors.initials: RE
authors.lastname: McGlinchey
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping; D004644:Emotions / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009929:Organ Size; D012146:Rest; D012720:Severity of Illness Index; D013313:Stress Disorders, Post-Traumatic / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology*; D014728:Veterans / Q000523:psychology; D055815:Young Adult
keywords: cortical thickness; go/no-go; impulsivity; resting-state connectivity; trauma; veterans