| Abstract |
Background While dysfunctional neurovascular unit may play a major role in the pathophysiology of mTBI, most previous neuroimaging studies examined functional connectivity and cerebral perfusion separately. However, these two processes are interrelated, and poor coupling between them has been noted in other disorders such as Alzheimer’s disease. Purpose To examine alterations in hemodynamics, functional connectivity and neurovascular coupling and their association to neurocognitive and mental health indices in patients with chronic mTBI. Methods Resting state functional MRI (rs-fMRI) and neuropsychological assessment of 37 patients with chronic mTBI were performed. Intrinsic connectivity contrast (ICC) and time-shift analysis (TSA) of the rs-fMRI data allowed the assessment of the degree of regional hemodynamic alterations, functional connectivity disturbances and neurovascular coupling (or uncoupling) without the use of contrast agents and without an a priori selection of regions of interest. Scans from 39 healthy age- and gender-matched participants were used as imaging controls. Results The two groups did not differ on regional perfusion metrics, although mTBI patients displayed hypoconnectivity in bilateral hippocampi and parahippocampal gyri, and increased connectivity in parietal areas, bilaterally (right primary somatosensory cortex (SI), right angular gyrus and left superior parietal lobule (SPL)). Bivariate correlational analyses indicated that faster perfusion in left anterior hippocampus was associated with lower self-reported symptoms of depression (r=-0.53, p=.0006) and anxiety (r=-0.484, p=.002). Furthermore, faster perfusion in the right SI was associated with lower primary and secondary verbal memory scores, while faster perfusion in the left SPL was associated with lower with semantic fluency (r=-0.474, p=.002). Finally, functional coupling (relatively high connectivity and hemodynamic lead) in right anterior cingulate cortex (ACC; an anterior Default Mode Network [DMN] region), was associated with lower performance on tests of attention and visuomotor coordination (r=-0.50, p=.001), while dysfunctional coupling (low connectivity and hemodynamic lag) of left ventral posterior cingulate cortex (PCC) and right SPL; regions of the posterior DMN, was associated with lower scores on immediate passage memory (r=-0.52, p=.001; r=-0.53, p=.0006, respectively). Uncoupling in the right ventral PCC was negatively associated with cognitive flexibility scores (r=-0.50, p=.001), and in the left ventral PCC was negatively associated with semantic fluency (r=-0.50, p=.001). Conclusions
To our knowledge this the first study to examine hemodynamic and functional connectivity differences in conjunction with neurovascular (un)coupling in chronic mTBI via rs-fMRI and identified links with mental health and neurocognitive indices.
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