Alterations in Functional Network Topology Within Normal Hemispheres Contralateral to Anterior Circulation Steno-Occlusive Disease: A Resting-State BOLD Study

Abstract

The purpose of this study was to assess spatially remote effects of hemodynamic impairment on functional network topology contralateral to unilateral anterior circulation steno-occlusive disease (SOD) using resting-state blood oxygen level-dependent (BOLD) imaging, and to investigate the relationships between network connectivity and cerebrovascular reactivity (CVR), a measure of hemodynamic stress. Twenty patients with unilateral, chronic anterior circulation SOD and 20 age-matched healthy controls underwent resting-state BOLD imaging. Five-minute standardized baseline BOLD acquisition was followed by acetazolamide infusion to measure CVR. The BOLD baseline was used to analyze network connectivity contralateral to the diseased hemispheres of SOD patients. Compared to healthy controls, reduced network degree (z-score = −1.158 ± 1.217, P < 0.001, false discovery rate (FDR) corrected), local efficiency (z-score = −1.213 ± 1.120, P < 0.001, FDR corrected), global efficiency (z-score = −1.346 ± 1.119, P < 0.001, FDR corrected), and enhanced modularity (z-score = 1.000 ± 1.205, P = 0.002, FDR corrected) were observed in the contralateral, normal hemispheres of SOD patients. Network degree (P = 0.089, FDR corrected; P = 0.027, uncorrected) and nodal efficiency (P = 0.089, FDR corrected; P = 0.045, uncorrected) showed a trend toward a positive association with CVR. The results indicate remote abnormalities in functional connectivity contralateral to the diseased hemispheres in patients with unilateral SOD, despite the absence of macrovascular disease or demonstrable hemodynamic impairment. The clinical impact of remote functional disruptions requires dedicated investigation but may portend far reaching consequence for even putatively unilateral cerebrovascular disease.

Diaschisis Profiles in the Cerebellar Response to Hemodynamic Stimuli: Insights From Dynamic Measurement of Cerebrovascular Reactivity to Identify Occult and Transient Maxima

“…While sparse data exist on CVR in CCD in response to hypercapnic stimulation after infarction, the potential of CVR in CCD prior to infarction remains less well understood 16–18 . Importantly, given complex cerebral network alterations previously observed in patients with SOD, even without infarction, we anticipate that trans‐synaptic influences may be engendered even by noninfarcted tissues 14–19 …”

“…[16][17][18] Importantly, given complex cerebral network alterations previously observed in patients with SOD, even without infarction, we anticipate that transsynaptic influences may be engendered even by noninfarcted tissues. [14][15][16][17][18][19] The sustained, global pharmacodynamic effect of intravenous ACZ is well documented, and when coupled to BOLD imaging, hypothetically permits for sampling across broad dynamic phases of the pharmacologic response. 13 Initial approaches to BOLD-CVR have been constrained by a poor signal-to-noise ratio, limiting reactivity estimates to terminal BOLD-CVR (CVR end ) measured at arbitrarily defined exam conclusions, for example, 10-20 minutes after ACZ administration.…”