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. 2025 Feb;15(1):40-54.
doi: 10.1089/brain.2023.0087. Epub 2024 Nov 12.

Cerebello-Cerebral Resting-State Functional Connectivity in Poststroke Aphasia

Joan Stilling  1   2 , Ji Hyun Kim  1 , Sarah Cust  1 , Zafer Keser  3   4 , Jamie L Murter  1 , Donna C Tippet  1   3   5 , Argye E Hillis  1   3   6 , Rajani Sebastian  1
Affiliations

Cerebello-Cerebral Resting-State Functional Connectivity in Poststroke Aphasia

Joan Stilling et al. Brain Connect. 2025 Feb.

Abstract

Introduction: The influence of the cerebellum in poststroke aphasia recovery is poorly understood. Despite the right cerebellum being identified as a critical region involved in both language and cognitive functions, little is known about functional connections between the cerebellum and bilateral cortical hemispheres following stroke. This study investigated the relationship between chronic poststroke naming deficits and cerebello-cerebral resting-state functional connectivity (FC). Methods: Twenty-five cognitively normal participants and 42 participants with chronic poststroke aphasia underwent resting-state functional magnetic resonance imaging. Participants with aphasia also underwent language assessment. We conducted regions of interest (ROI)-to-ROI analyses to investigate the FC between the right cerebellar Crus I/II (seed ROI; Cereb1r/Cereb2r) and bilateral cortical language regions and compared these results to cognitively normal controls. Single-subject connectivity parameters were extracted and used as independent variables in a stepwise multiple linear regression model associating Boston Naming Test (BNT) score with FC measures. Results: FC analyses demonstrated correlations between the right cerebellar Crus I/II and both left and right cortical regions for both cognitively normal controls and stroke participants. Additionally, aphasia severity and lesion load had an effect on the cerebello-cerebral network connectivity in participants with aphasia. In a stepwise multiple linear regression, controlling for aphasia severity, time poststroke and lesion load, FC between the right Cereb2-left Cereb1 (standardized beta [std B]= -0.255, p < 0.004), right Cereb2-right anterior MTG (std B = 0.259, p < 0.004), and the right Cereb2-left anterior STG (std B = -0.208, p < 0.018) were significant predictors of BNT score. The overall model fit was R2 = 0.786 (p = 0.001). Conclusion: Functional connections between the right cerebellum and residual bilateral cerebral hemisphere regions may play a role in predicting naming ability in poststroke aphasia.

Keywords: aphasia; cerebellum; functional magnetic resonance imaging (fMRI); stroke.

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Conflict of interest statement

J.S.—full-time salaried faculty member, Weill Cornell Medicine. Site PI for industry-sponsored clinical trials: (1) Merz Pharmaceuticals. Prospective, randomized, double-blind, placebo-controlled, multicenter study to investigate the efficacy and safety of NT 201 in the treatment of lower limb spasticity caused by stroke or traumatic brain injury in adult subjects, followed by an open label extension with or without combined upper limb treatment. (2) Ipsen Pharmaceuticals. A multicenter, interventional, post-marketing, randomized, double-blind, crossover study to evaluate the clinical safety and efficacy of AbobotulinumtoxinA (Dysport®) in comparison with OnabotulinumtoxinA (Botox®) when treating adults with upper limb spasticity. J.H.K.—no disclosures. S.C.—no disclosures. Z.K.—full-time salaried faculty member, Mayo Clinic. Editorial member for Elsevier’s Practice Update. D.C.T.—full-time salaried faculty member, Johns Hopkins University; grant support NIH National Institute on Aging (NIA) R01AG075111, NIH National Institute on Deafness and Other Communication Disorders (NIDCD)/NIA R01 DC011317; Review Editor, Frontiers in Neurology, Applied Neuroimaging; Associate Editor, Frontiers in Neurology, Stroke; member of the Collaboration of Aphasia Trialists, International Stroke Rehabilitation and Recovery Alliance, and Primary Progressive Aphasia Task Force of the National Aphasia Association. A.E.H.—full-time salaried faculty member, Johns Hopkins University; grant support R01 DC 05375, P50 NIDCD P50 DC014664, R01 DC015466, R25NS065729; Editor-in-Chief of Stroke; Associate Editor, Practice Update Neurology. R.S.—full-time salaried faculty member, Johns Hopkins University; grant support NIH NIDCD R01 DC019639. Review Editor for Frontiers in Neurology.

Figures

FIG. 1.
FIG. 1.
Lesion overlay map of the individual lesions of all 42 patients. Maps were overlaid on a MNI152 T1-template using MRIcroGL. Color scale indicates the number of patients with a lesion in a particular voxel.
FIG. 2.
FIG. 2.
Resting-state FC between the right Cerebellar Crus I/II, seed ROI with the other cerebellar and cortical ROIs in healthy controls. Warmer colors indicate increased degree of connectivity (positive correlations) and cooler colors indicate decreased connectivity (negative correlations). FC, functional connectivity; ROI, regions of interest.
FIG. 3.
FIG. 3.
Resting-state FC between the right Cerebellar Crus I/II, seed ROI with the other cerebellar and cortical ROIs in stroke participants. Warmer colors indicate increased degree of connectivity (positive correlations) and cooler colors indicate decreased connectivity (negative correlations).
FIG. 4.
FIG. 4.
Resting-state FC between the right Cerebellar Crus I/II, seed ROI with the other cerebellar and cortical ROIs in stroke participants after controlling for lesion load. Warmer colors indicate increased degree of connectivity (positive correlations) and cooler colors indicate decreased connectivity (negative correlations).
FIG. 5.
FIG. 5.
Resting-state FC between right Cerebellar Crus I/II, seed ROI with the other cerebellar and cortical ROIs in stroke participants after controlling aphasia severity. Warmer colors indicate increased degree of connectivity (positive correlations) and cooler colors indicate decreased connectivity (negative correlations).
See this image and copyright information in PMC

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