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Abnormal dynamic functional connectivity is linked to recovery after acute ischemic stroke

The aim of the current study was to explore the whole‐brain dynamic functional connectivity patterns in acute ischemic stroke (AIS) patients and their relation to short and long‐term stroke severity.
We investigated resting‐state functional MRI‐based dynamic functional connectivity of 41 AIS patients two to five days after symptom onset. Re‐occurring dynamic connectivity configurations were obtained using a sliding window approach and k‐means clustering. We evaluated differences in dynamic patterns between three NIHSS‐stroke severity defined groups (mildly, moderately, and severely affected patients). Furthermore, we built Bayesian hierarchical models to evaluate the predictive capacity of dynamic connectivity and examine the interrelation with clinical measures, such as white matter hyperintensity lesions. Finally, we established correlation analyses between dynamic connectivity and AIS severity as well as 90‐day neurological recovery (ΔNIHSS).
We identified three distinct dynamic connectivity configurations acutely post‐stroke. More severely affected patients spent significantly more time in a configuration that was characterized by particularly strong connectivity and isolated processing of functional brain domains (three‐level ANOVA: p < .05, post hoc t tests: p < .05, FDR‐corrected; Fig. 1).
 


Bonkhoff 2021

Figure 1. Significant dynamic connectivity differences between mildly, moderately and severely affected patient groups in State 1. The functionally segregated state 1 comprised the most significantly altered connectivity pairs. Severely affected patients comprised numerous dynamic connectivity pairs with enhanced connectivity compared with both mildly and moderately affected patients. These changes primarily involved subcortical and cortical motor networks, as well as multiple connections to the default mode network

 
 
Configuration‐specific time estimates possessed predictive capacity of stroke severity in addition to the one of clinical measures. Recovery, as indexed by the realized change of the NIHSS over time, was significantly linked to the dynamic connectivity between bilateral intraparietal lobule and left angular gyrus (Pearson's r = −.68, p = .003, FDR‐corrected).
Our findings demonstrate transiently increased isolated information processing in multiple functional domains in case of severe AIS. Dynamic connectivity involving default mode network components significantly correlated with recovery in the first 3 months poststroke (Fig. 2).
 

Bonkhoff 2021

Figure 2. Recovery in the first 3 months after stroke is linked to specific acute dynamic connectivity pairs. (a) Recovery‐correlated connectivity pairs are highlighted within dynamic connectivity State 1 (upper row) and State 3 (bottom row). These connectivity pairs were located in subcortical (SC), auditory (AUD), cognitive control (CC) and default mode network (DMN) domains. (b) Brain renderings of involved networks. In State 1, the connectivity between the bilateral intraparietal lobule and left angular gyrus was significantly correlated with recovery after correction for multiple comparison. In State 3, the connectivity between bilateral putamen and anterior insula was significantly correlated with recovery after correction for multiple comparisons, while the connectivity between bilateral putamen and superior temporal gyrus was significantly correlated with recovery before correction for multiple comparisons. (c) Correlation plots. Recovery, measured as realized change in NIHSS and adjusted for NIHSSscan, is plotted on the x‐axis, dFNC strength on the y‐axis (p‐values are FDR‐corrected). The size of the dots corresponds to an individual's stroke severity at time of scanning 1.8 (red).


 
Publication:

Bonkhoff, A. K., Schirmer, M. D., Bretzner, M., Etherton, M., Donahue, K., Tuozzo, C., Nardin, M., Giese, A.-K., Wu, O., Calhoun, V. D., Grefkes, C., & Rost, N. S. (2021). Abnormal dynamic functional connectivity is linked to recovery after acute ischemic stroke. Human Brain Mapping.