Lateralization-specific motor network reorganization in pontine infarction revealed by resting-state functional connectivity magnetic resonance imaging

Background: Pontine infarction (PI) accounts for 7% of ischemic strokes, yet motor recovery varies significantly despite comparable lesion topography. The neural mechanisms underlying this heterogeneity remain unclear. This study aimed to investigate lesion laterality–dependent functional reorganization within the motor execution network following PI through the use of region of interest (ROI)-based resting-state functional magnetic resonance imaging (rs-fMRI).

Methods: A total of 31 patients with acute unilateral PI [19 with left PI (LPI) and 12 with right PI (RPI)] and 31 matched controls underwent rs-fMRI. Seed-based functional connectivity (FC) analysis of the motor execution network was performed with spherical ROIs (6-mm radius). Group differences in FC were tested with one-way analysis of variance (ANOVA) and post hoc Bonferroni correction [cluster-level family-wise error (FWE)-corrected P<0.05]. Correlations between FC, infarct volume, and National Institute of Health Stroke Scale (NIHSS) scores were assessed.

Results: No significant intergroup differences were observed in age, education years, head motion parameters, or gender distribution (P>0.05). Lesion volumes during the acute phase and NIHSS scores did not differ significantly between the LPI and RPI groups (P>0.05). In patients with LPI, FC was enhanced between the right dorsolateral prefrontal cortex (DLPFC) and the thalamus/basal ganglia, between the right supplementary motor area (SMA)/precentral gyrus and ipsilateral basal ganglia, and between the thalamus and bilateral cerebellum (all cluster-level FWE-corrected P values <0.05). In contrast, FC was reduced within the ipsilateral motor cortex and between the ventral premotor cortex and sensory cortex (all cluster-level FWE-corrected P values <0.05). In patients with RPI, FC was enhanced between the posterior cingulate cortex (PCC)/precuneus and thalamus and between the left SMA and contralateral basal ganglia (all cluster-level FWE-corrected P values <0.05). Within the LPI group, the FC between the right DLPFC and thalamus correlated positively with infarct volume (r=0.575; P=0.012). However, no significant correlations were observed between FC alterations and NIHSS scores or the NIHSS motor subscores (upper and lower extremity items), respectively, in either the LPI or RPI groups (all P values >0.05).

Conclusions: Motor recovery post-PI may be influenced by dynamic imbalances in multinetwork early alterations and potentially shaped by lesion laterality: left-sided lesions primarily show recruitment of contralateral prefrontal cognitive resources, whereas right-sided lesions appear to engage default mode network (DMN)-mediated spatial remapping. The thalamo-basal ganglia hub may orchestrate transhemispheric integration, and its FC alterations, such as those within the DLPFC-thalamic pathway, might reflect compensatory potential, potentially offering insights into rehabilitation strategies. However, longitudinal studies are needed to validate these preliminary findings.