Audreyana Jagger-Rickels1,2,3, Anna Stumps2,3, David Rothlein1,2, Hannah Park2, Francesca Fortenbaugh3,4, Agnieszka Zuberer2,5,6,7, Jennifer R Fonda3,4,5, Catherine B Fortier3,4,8, Joseph DeGutis2,3,4, William Milberg3,4,9, Regina McGlinchey3,4,9, Michael Esterman1,2,3,5,8. 1. National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA. 2. Boston Attention and Learning Lab (BALAB), VA Boston Healthcare System, Boston, MA, USA. 3. Translational Research Center for TBI and Stress Disorders (TRACTS), VA Boston Healthcare System, Boston, MA, USA. 4. Department of Psychiatry, Harvard Medical School, Boston, MA, USA. 5. Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA. 6. Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany. 7. Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany. 8. Neuroimaging Research for Veterans (NeRVe) Center, VA Boston Healthcare System, Boston, MA, USA. 9. Geriatric Research, Education and Clinical Center (GRECC), VABoston Healthcare System, Boston, Massachusetts, USA.
Abstract
BACKGROUND: A major obstacle in understanding and treating posttraumatic stress disorder (PTSD) is its clinical and neurobiological heterogeneity. To address this barrier, the field has become increasingly interested in identifying subtypes of PTSD based on dysfunction in neural networks alongside cognitive impairments that may underlie the development and maintenance of symptoms. The current study aimed to determine if subtypes of PTSD, based on normative-based cognitive dysfunction across multiple domains, have unique neural network signatures. METHODS: In a sample of 271 veterans (90% male) that completed both neuropsychological testing and resting-state fMRI, two complementary, whole-brain functional connectivity analyses explored the link between brain functioning, PTSD symptoms, and cognition. RESULTS: At the network level, PTSD symptom severity was associated with reduced negative coupling between the limbic network (LN) and frontal-parietal control network (FPCN), driven specifically by the dorsolateral prefrontal cortex and amygdala Hubs of Dysfunction. Further, this relationship was uniquely moderated by executive function (EF). Specifically, those with PTSD and impaired EF had the strongest marker of LN-FPCN dysregulation, while those with above-average EF did not exhibit PTSD-related dysregulation of these networks. CONCLUSION: These results suggest that poor executive functioning, alongside LN-FPCN dysregulation, may represent a neurocognitive subtype of PTSD.
BACKGROUND: A major obstacle in understanding and treating posttraumatic stress disorder (PTSD) is its clinical and neurobiological heterogeneity. To address this barrier, the field has become increasingly interested in identifying subtypes of PTSD based on dysfunction in neural networks alongside cognitive impairments that may underlie the development and maintenance of symptoms. The current study aimed to determine if subtypes of PTSD, based on normative-based cognitive dysfunction across multiple domains, have unique neural network signatures. METHODS: In a sample of 271 veterans (90% male) that completed both neuropsychological testing and resting-state fMRI, two complementary, whole-brain functional connectivity analyses explored the link between brain functioning, PTSD symptoms, and cognition. RESULTS: At the network level, PTSD symptom severity was associated with reduced negative coupling between the limbic network (LN) and frontal-parietal control network (FPCN), driven specifically by the dorsolateral prefrontal cortex and amygdala Hubs of Dysfunction. Further, this relationship was uniquely moderated by executive function (EF). Specifically, those with PTSD and impaired EF had the strongest marker of LN-FPCN dysregulation, while those with above-average EF did not exhibit PTSD-related dysregulation of these networks. CONCLUSION: These results suggest that poor executive functioning, alongside LN-FPCN dysregulation, may represent a neurocognitive subtype of PTSD.
Authors: Audreyana Jagger-Rickels; David Rothlein; Anna Stumps; Travis Clark Evans; John Bernstein; William Milberg; Regina McGlinchey; Joseph DeGutis; Michael Esterman Journal: Transl Psychiatry Date: 2022-06-27 Impact factor: 7.989