Cargando…
Altered basal forebrain BOLD signal variability at rest in posttraumatic stress disorder: A potential candidate vulnerability mechanism for neurodegeneration in PTSD
Individuals with posttraumatic stress disorder (PTSD) are at increased risk for the development of various forms of dementia. Nevertheless, the neuropathological link between PTSD and neurodegeneration remains unclear. Degeneration of the human basal forebrain constitutes a pathological hallmark of...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249881/ https://www.ncbi.nlm.nih.gov/pubmed/33960558 http://dx.doi.org/10.1002/hbm.25454 |
_version_ | 1783716993644363776 |
---|---|
author | Olivé, Isadora Makris, Nikos Densmore, Maria McKinnon, Margaret C. Lanius, Ruth A. |
author_facet | Olivé, Isadora Makris, Nikos Densmore, Maria McKinnon, Margaret C. Lanius, Ruth A. |
author_sort | Olivé, Isadora |
collection | PubMed |
description | Individuals with posttraumatic stress disorder (PTSD) are at increased risk for the development of various forms of dementia. Nevertheless, the neuropathological link between PTSD and neurodegeneration remains unclear. Degeneration of the human basal forebrain constitutes a pathological hallmark of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. In this seed‐based resting‐state (rs‐)fMRI study identifying as outcome measure the temporal BOLD signal fluctuation magnitude, a seed‐to‐voxel analyses assessed temporal correlations between the average BOLD signal within a bilateral whole basal forebrain region‐of‐interest and each whole‐brain voxel among individuals with PTSD (n = 65), its dissociative subtype (PTSD+DS) (n = 38) and healthy controls (n = 46). We found that compared both with the PTSD and healthy controls groups, the PTSD+DS group exhibited increased BOLD signal variability within two nuclei of the seed region, specifically in its extended amygdaloid region: the nucleus accumbens and the sublenticular extended amygdala. This finding is provocative, because it mimics staging models of neurodegenerative diseases reporting allocation of neuropathology in early disease stages circumscribed to the basal forebrain. Here, underlying candidate etiopathogenetic mechanisms are neurovascular uncoupling, decreased connectivity in local‐ and large‐scale neural networks, or disrupted mesolimbic dopaminergic circuitry, acting indirectly upon the basal forebrain cholinergic pathways. These abnormalities may underpin reward‐related deficits representing a putative link between persistent traumatic memory in PTSD and anterograde memory deficits in neurodegeneration. Observed alterations of the basal forebrain in the dissociative subtype of PTSD point towards the urgent need for further exploration of this region as a potential candidate vulnerability mechanism for neurodegeneration in PTSD. |
format | Online Article Text |
id | pubmed-8249881 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82498812021-07-09 Altered basal forebrain BOLD signal variability at rest in posttraumatic stress disorder: A potential candidate vulnerability mechanism for neurodegeneration in PTSD Olivé, Isadora Makris, Nikos Densmore, Maria McKinnon, Margaret C. Lanius, Ruth A. Hum Brain Mapp Research Articles Individuals with posttraumatic stress disorder (PTSD) are at increased risk for the development of various forms of dementia. Nevertheless, the neuropathological link between PTSD and neurodegeneration remains unclear. Degeneration of the human basal forebrain constitutes a pathological hallmark of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. In this seed‐based resting‐state (rs‐)fMRI study identifying as outcome measure the temporal BOLD signal fluctuation magnitude, a seed‐to‐voxel analyses assessed temporal correlations between the average BOLD signal within a bilateral whole basal forebrain region‐of‐interest and each whole‐brain voxel among individuals with PTSD (n = 65), its dissociative subtype (PTSD+DS) (n = 38) and healthy controls (n = 46). We found that compared both with the PTSD and healthy controls groups, the PTSD+DS group exhibited increased BOLD signal variability within two nuclei of the seed region, specifically in its extended amygdaloid region: the nucleus accumbens and the sublenticular extended amygdala. This finding is provocative, because it mimics staging models of neurodegenerative diseases reporting allocation of neuropathology in early disease stages circumscribed to the basal forebrain. Here, underlying candidate etiopathogenetic mechanisms are neurovascular uncoupling, decreased connectivity in local‐ and large‐scale neural networks, or disrupted mesolimbic dopaminergic circuitry, acting indirectly upon the basal forebrain cholinergic pathways. These abnormalities may underpin reward‐related deficits representing a putative link between persistent traumatic memory in PTSD and anterograde memory deficits in neurodegeneration. Observed alterations of the basal forebrain in the dissociative subtype of PTSD point towards the urgent need for further exploration of this region as a potential candidate vulnerability mechanism for neurodegeneration in PTSD. John Wiley & Sons, Inc. 2021-05-07 /pmc/articles/PMC8249881/ /pubmed/33960558 http://dx.doi.org/10.1002/hbm.25454 Text en © 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Articles Olivé, Isadora Makris, Nikos Densmore, Maria McKinnon, Margaret C. Lanius, Ruth A. Altered basal forebrain BOLD signal variability at rest in posttraumatic stress disorder: A potential candidate vulnerability mechanism for neurodegeneration in PTSD |
title | Altered basal forebrain BOLD signal variability at rest in posttraumatic stress disorder: A potential candidate vulnerability mechanism for neurodegeneration in PTSD |
title_full | Altered basal forebrain BOLD signal variability at rest in posttraumatic stress disorder: A potential candidate vulnerability mechanism for neurodegeneration in PTSD |
title_fullStr | Altered basal forebrain BOLD signal variability at rest in posttraumatic stress disorder: A potential candidate vulnerability mechanism for neurodegeneration in PTSD |
title_full_unstemmed | Altered basal forebrain BOLD signal variability at rest in posttraumatic stress disorder: A potential candidate vulnerability mechanism for neurodegeneration in PTSD |
title_short | Altered basal forebrain BOLD signal variability at rest in posttraumatic stress disorder: A potential candidate vulnerability mechanism for neurodegeneration in PTSD |
title_sort | altered basal forebrain bold signal variability at rest in posttraumatic stress disorder: a potential candidate vulnerability mechanism for neurodegeneration in ptsd |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249881/ https://www.ncbi.nlm.nih.gov/pubmed/33960558 http://dx.doi.org/10.1002/hbm.25454 |
work_keys_str_mv | AT oliveisadora alteredbasalforebrainboldsignalvariabilityatrestinposttraumaticstressdisorderapotentialcandidatevulnerabilitymechanismforneurodegenerationinptsd AT makrisnikos alteredbasalforebrainboldsignalvariabilityatrestinposttraumaticstressdisorderapotentialcandidatevulnerabilitymechanismforneurodegenerationinptsd AT densmoremaria alteredbasalforebrainboldsignalvariabilityatrestinposttraumaticstressdisorderapotentialcandidatevulnerabilitymechanismforneurodegenerationinptsd AT mckinnonmargaretc alteredbasalforebrainboldsignalvariabilityatrestinposttraumaticstressdisorderapotentialcandidatevulnerabilitymechanismforneurodegenerationinptsd AT laniusrutha alteredbasalforebrainboldsignalvariabilityatrestinposttraumaticstressdisorderapotentialcandidatevulnerabilitymechanismforneurodegenerationinptsd |