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Altered cerebello-cerebral resting-state connectivity as a neural correlate of verbal fluency deficits in cerebellar degeneration
Poster Session E, Friday, October 2, 11:00 am - 1:00 pm, Wangari Maathai
Alisha Reinhardt1,2, Laura Semsroth1,3, Vikshana Raveendrarajah1,3, Ezequiel Farrher4, Nadim Joni Shah4,5,6, Dagmar Timmann7, Katrin Amunts1,8, Christian Bellebaum2, Ian H Harding9, Stefan Heim1,10, Martina Minnerop1,11,12; 1Institute of Neuroscience and Medicine 1, INM-1, Research Centre Juelich, Germany., 2Faculty of Mathematics and Natural Sciences, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., 3Faculty of Medicine, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., 4Institute of Neuroscience and Medicine 4, INM-4, Research Centre Juelich , Germany., 5Department of Neurology, RWTH Aachen University, Aachen, Deutschland, 6Institute of Neuroscience and Medicine – 11, JARA – BRAIN – Translational Medicine, Forschungszentrum Juelich, Germany, 7Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Essen University Hospital, University of Duisburg-Essen, Essen, Germany., 8Cécile and Oskar Vogt Institute for Brain Research, University Hospital Düsseldorf, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., 9QIMR Berghofer Medical Research Institute, Brisbane, Australia, 10Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University, Aachen, Germany., 11Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty & University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Germany., 12Department of Neurology, Center for Movement Disorders and Neuromodulation, Medical Faculty & University Hospital Düsseldorf, Heinrich-Heine University, Düsseldorf, Germany.
The cerebellum is increasingly recognized as an active hub in language processes, particularly in verbal fluency, extending its role beyond motor functions. Cerebellar degeneration provides a valuable model to investigate how an impairment of this hub alters language networks involved in different verbal fluency (VF) tasks (e.g., semantic, phonemic, category-switching), which may differentially reflect the cerebellum’s role and possible impairments. This study aimed to investigate the impact of cerebellar degeneration on resting-state functional connectivity between the cerebellar and cerebral language networks in relation to VF performance, and to explore potential dissociations across fluency subtypes. A total of 22 ataxia patients with predominantly cerebellar degeneration (13 male, mean age = 55.8±13.3 years) and matched controls underwent 3T resting-state fMRI and completed VF tasks outside the scanner, covering phonemic, semantic, and semantic category-switching VF. Dysarthria severity was assessed via diadochokinesis rate as a control measure. fMRI data from all participants were analyzed using SPM25 (Version 25.01.02) and the CONN toolbox (Version 25.b). Seed-to-voxel analysis was conducted using the right hemispheric cerebellar functional network S1 from the Nettekoven cerebellar atlas (2024) as a seed. Significant clusters were labeled using the Jülich Brain Atlas (Version 3.0). Extracted cluster-level FDR-corrected Fisher-z connectivity values were entered into linear regression models, with VF T-scores as outcomes. Multiple comparisons were corrected using the Benjamini-Hochberg false discovery rate procedure (p<.05). Robustness was tested using a confound model including depression severity (PHQ-9), premorbid intelligence (MWT-B), and ataxia severity (SARA). Group comparison showed anticorrelated functional connectivity between the right cerebellar S1 seed and three cerebral clusters. The clusters were distributed across the right fronto-temporal opercular cortex, including Area 44 (Cluster_1), the right premotor cortex (Cluster_2), and the left superior-temporal cortex and insula (Cluster_3). Patients showed increased anticorrelated connectivity across all clusters and worse verbal fluency performance compared to controls. Verbal fluency performance was not significantly associated with dysarthria severity (all p>.05). In a combined sample of patients and controls, semantic VF was significantly associated with all clusters in the FDR-corrected primary model (B=44.36-59.59, p-FDR=.001-.012), and covariate analyses showed that the effect sizes for the semantic VF associations with Cluster_1 and Cluster_2 remained nominally significant after controlling for all covariates simultaneously (p < .05). Our findings suggest that increased anticorrelated connectivity between the cerebellar language network and right premotor cortex, as well as right temporo-frontal opercular areas, may underlie verbal fluency deficits in cerebellar degeneration. The absence of associations with dysarthria severity and category-switching performance suggests that the observed connectivity alterations reflect language-specific rather than motor or domain-general executive processes. We hypothesize that impaired cerebellar function drives compensatory reorganization toward right-hemispheric homolog regions to maintain language function, as observed in similar patient cohorts, e.g., Friedreich's ataxia or post-stroke aphasia. Whether this reflects true compensation or interhemispheric dysfunction remains to be determined. Future studies combining functional and effective connectivity analyses or task-based paradigms could help clarify whether right-hemispheric recruitment is adaptive or maladaptive in cerebellar language impairment.
Topic Areas: Disorders: Acquired, Language Production