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Co-localized impaired regional cerebrovascular reactivity in chronic concussion is associated with BOLD activation differences during a working memory task

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Abstract

The purpose of this study was to quantify differences in blood oxygen level dependent (BOLD) activation on a working memory task, baseline cerebral blood flow (CBF0), and cerebrovascular reactivity (CVR) between participants with and without a history of concussion. A dual-echo pseudo-continuous arterial spin labelling (pCASL) sequence was performed on a group of 10 subjects with a previous concussion (126 ± 15 days prior) and on a control group (n = 10) during a visual working memory protocol. A separate dual-echo pCASL sequence was used to derive CVR and CBF0 measurements from a boxcar hypercapnic breathing protocol. Brain areas with significant activation differences on the working memory task between groups were identified and combined as an aggregate region of interest for CBF and CVR analyses. Areas of reduced BOLD activation during the working memory task in the concussed group included the ventral anterior cingulate cortex (ACC), the medial temporal gyrus (MTG), and the lateral occipital cortex in two loci. A single area of increased activation was located in the parietal operculum. Further analyses of CBF0 and CVR in these regions revealed reduced CVR in the concussed group in the MTG and ACC, while CBF0 did not differ. The differences in CVR between the two groups in these regions suggest that concussive injury may result in microvascular dysfunction. In turn, the decreased BOLD response during the task could be due to altered neurovascular coupling, rather than an impairment in neural activation alone. However, in other regions associated with working memory, unchanged CBF0 and CVR suggests that neural injury also persists after concussion. In the future, BOLD results should be normalized to CVR in order achieve a clearer understanding of the neural and vascular contributions to the differences in the signal.

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Acknowledgements

The authors would like to thank Cheryl Hamilton and Don Brien for their dedication and willingness to help with data collection. The authors would also like to acknowledge Dr. J. J. Wang at UCLA for sharing the pCASL sequence used in this study. The authors would also like to acknowledge Dr. Michael Germuska (Cardiff University) and Dr. Alex Bhogal (University Medical Center Utrecht) for their input regarding the pre-processing workflow used in this study to derive physiological measurements.

Funding

This work was supported by the Canadian Institutes of Health Research (CIHR) and the Natural Sciences and Engineering Research Council (NSERC) through a Collaborative Health Research Project Grant (#315705).

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Correspondence to Douglas J. Cook.

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None of the authors have conflicts of interest to disclose.

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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.

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Figure S1

Scatter plots of cerebral blood flow and cerebrovascular reactivity for the regions where activation was different during the working memory task. Open circles represent the concussed group and filled show the control group. A) Lateral occipital cortex superior (LOCs) and B) inferior (LOCi), C) medial temporal gyrus (MTG), D) parietal operculum (POp), E) region of interest (ROI), F) superior frontal gyrus (SFG), G) ventral anterior cingulate cortex (ACC). (PNG 102 kb)

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Coverdale, N.S., Fernandez-Ruiz, J., Champagne, A.A. et al. Co-localized impaired regional cerebrovascular reactivity in chronic concussion is associated with BOLD activation differences during a working memory task. Brain Imaging and Behavior 14, 2438–2449 (2020). https://doi.org/10.1007/s11682-019-00194-5

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  • DOI: https://doi.org/10.1007/s11682-019-00194-5

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