Effect of blast-related mTBI on the working memory system: a resting state fMRI study
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Reduced working memory is frequently reported by Veterans with a history of blast-related mild traumatic brain injury (mTBI), but can be difficult to quantify on neuropsychological measures. This study aimed to improve our understanding of the impact of blast-related mTBI on the working memory system by using resting state functional magnetic resonance imaging (fMRI) to explore differences in functional connectivity between OEF/OIF/OND Veterans with and without a history of mTBI. Participants were twenty-four Veterans with a history of blast-related mTBI and 17 Veterans who were deployed but had no lifetime history of TBI. Working memory ability was evaluated with the Auditory Consonants Trigrams (ACT) task. Resting state fMRI was used to evaluate intrinsic functional connectivity from frontal seed regions that are known components of the working memory network. No significant group differences were found on the ACT, but the imaging analyses revealed widespread hyper-connectivity from the frontal seed regions in the Veterans with a history of mTBI relative to the deployed control group. Further, within the mTBI group, but not the control group, better performance on the ACT was associated with increased functional connectivity to multiple brain regions, including cerebellar components of the working memory network. These results were present after controlling for age, PTSD symptoms, and estimated premorbid IQ, and suggest that long-term alterations in the functional connectivity of the working memory network following blast-related mTBI may reflect a compensatory change that contributes to intact performance on an objective measure of working memory.
KeywordsTraumatic brain injury Resting state fMRI Working memory Auditory consonant trigrams test Veterans Blast injury Neuropsychology
This work was supported by Career Development Award #IK2CX000516 from the United States (U.S.) Department of Veterans Affairs Clinical Science Research and Development Service, Merit Review #I01 RX000521 from the U.S. Department of Veterans Affairs Rehabilitation Research and Development Service, the U.S. Department of Veterans Affairs Medical Research Service, as well as VA Northwest Network MIRECC and University of Washington Royalty Research Fund.
The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.
Compliance with ethical standards
Conflict of interest
Author Raskind has received consultant fees from Takeda Pharmaceuticals and Merck Pharmaceuticals. Author Peskind has received consultant fees from Takeda, Merck, Aramis, and Eli Lilly. Author Meabon is Chief Operations Officer for Neurogenix Pharmaceuticals, Inc. Authors Cook, Hendrickson, Kleinhans, Mayer, Pagulayan, Petrie, Rau, and Reilly declare that they have no conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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