Cerebello‐Prefrontal Connectivity Underlying Cognitive Dysfunction in Spinocerebellar Ataxia Type 2
ABSTRACT Objective Spinocerebellar ataxia type 2 (SCA2) is a hereditary cerebellar degenerative disorder, with motor and cognitive symptoms. The constellation of cognitive symptoms due to cerebellar degeneration is named cerebellar cognitive affective syndrome (CCAS), which has increasingly been rec...
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Wiley
2025-06-01
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| Series: | Annals of Clinical and Translational Neurology |
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| Online Access: | https://doi.org/10.1002/acn3.70028 |
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| author | Ami Kumar Ruo‐Yah Lai Zena Fadel Yicheng Lin Pia Parekh Rachel Griep Ming‐Kai Pan Sheng‐Han Kuo |
| author_facet | Ami Kumar Ruo‐Yah Lai Zena Fadel Yicheng Lin Pia Parekh Rachel Griep Ming‐Kai Pan Sheng‐Han Kuo |
| author_sort | Ami Kumar |
| collection | DOAJ |
| description | ABSTRACT Objective Spinocerebellar ataxia type 2 (SCA2) is a hereditary cerebellar degenerative disorder, with motor and cognitive symptoms. The constellation of cognitive symptoms due to cerebellar degeneration is named cerebellar cognitive affective syndrome (CCAS), which has increasingly been recognized to profoundly impact patients' quality of life; however, the brain circuits underlying these cognitive dysfunctions remain elusive. Methods We utilized a novel technique, cerebello‐cortical electroencephalogram (EEG), to investigate the resting‐state functional connectivity in different frequency domains in 12 SCA2 patients and 24 age‐matched controls. Given that the prefrontal cortex is strongly connected to the cerebellum, we studied the EEG connectivity between the cerebellum and the prefrontal cortex. We also conducted correlation analyses to explore the association between this connectivity and the severity of cognitive dysfunction, determined by CCAS scores. Results Source‐space spectral analysis differences between SCA2 patients and controls were observed in the cerebellum at the delta, theta, and beta frequencies. Functional connectivity between the posterior cerebellum and the prefrontal cortex revealed decreased theta and increased beta connectivity in SCA2 patients, with no differences in delta connectivity. Increased beta connectivity was unique to the prefrontal regions, not seen in the connectivity to the primary motor cortex or mid‐temporal lobe. Interestingly, this beta connectivity correlated with CCAS scores in SCA2 patients. Conclusion Our findings demonstrated that SCA2 patients have an increase in beta cerebello‐prefrontal connectivity that correlates with cognitive performance. These findings suggest cerebello‐cortical EEG could track circuit dysfunction underlying cognitive symptoms in SCA2, paving the way for developing targeted neuromodulation therapeutics. |
| format | Article |
| id | doaj-art-3d2e418b5d444684ab6a18054d5b997f |
| institution | Kabale University |
| issn | 2328-9503 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Annals of Clinical and Translational Neurology |
| spelling | doaj-art-3d2e418b5d444684ab6a18054d5b997f2025-08-20T03:45:40ZengWileyAnnals of Clinical and Translational Neurology2328-95032025-06-011261109111710.1002/acn3.70028Cerebello‐Prefrontal Connectivity Underlying Cognitive Dysfunction in Spinocerebellar Ataxia Type 2Ami Kumar0Ruo‐Yah Lai1Zena Fadel2Yicheng Lin3Pia Parekh4Rachel Griep5Ming‐Kai Pan6Sheng‐Han Kuo7Department of Neurology, College of Physicians and Surgeons Columbia University New York New York USADepartment of Neurology, College of Physicians and Surgeons Columbia University New York New York USAInitiative for Columbia Ataxia and Tremor Columbia University New York New York USADepartment of Neurology, College of Physicians and Surgeons Columbia University New York New York USADepartment of Neurology, College of Physicians and Surgeons Columbia University New York New York USADepartment of Neurology, College of Physicians and Surgeons Columbia University New York New York USACerebellar Research Center National Taiwan University Hospital, Yun‐Lin Branch Yun‐Lin TaiwanDepartment of Neurology, College of Physicians and Surgeons Columbia University New York New York USAABSTRACT Objective Spinocerebellar ataxia type 2 (SCA2) is a hereditary cerebellar degenerative disorder, with motor and cognitive symptoms. The constellation of cognitive symptoms due to cerebellar degeneration is named cerebellar cognitive affective syndrome (CCAS), which has increasingly been recognized to profoundly impact patients' quality of life; however, the brain circuits underlying these cognitive dysfunctions remain elusive. Methods We utilized a novel technique, cerebello‐cortical electroencephalogram (EEG), to investigate the resting‐state functional connectivity in different frequency domains in 12 SCA2 patients and 24 age‐matched controls. Given that the prefrontal cortex is strongly connected to the cerebellum, we studied the EEG connectivity between the cerebellum and the prefrontal cortex. We also conducted correlation analyses to explore the association between this connectivity and the severity of cognitive dysfunction, determined by CCAS scores. Results Source‐space spectral analysis differences between SCA2 patients and controls were observed in the cerebellum at the delta, theta, and beta frequencies. Functional connectivity between the posterior cerebellum and the prefrontal cortex revealed decreased theta and increased beta connectivity in SCA2 patients, with no differences in delta connectivity. Increased beta connectivity was unique to the prefrontal regions, not seen in the connectivity to the primary motor cortex or mid‐temporal lobe. Interestingly, this beta connectivity correlated with CCAS scores in SCA2 patients. Conclusion Our findings demonstrated that SCA2 patients have an increase in beta cerebello‐prefrontal connectivity that correlates with cognitive performance. These findings suggest cerebello‐cortical EEG could track circuit dysfunction underlying cognitive symptoms in SCA2, paving the way for developing targeted neuromodulation therapeutics.https://doi.org/10.1002/acn3.70028cerebellumcognitionelectroencephalogram (EEG)functional connectivityspinocerebellar ataxia type 2 (SCA2) |
| spellingShingle | Ami Kumar Ruo‐Yah Lai Zena Fadel Yicheng Lin Pia Parekh Rachel Griep Ming‐Kai Pan Sheng‐Han Kuo Cerebello‐Prefrontal Connectivity Underlying Cognitive Dysfunction in Spinocerebellar Ataxia Type 2 Annals of Clinical and Translational Neurology cerebellum cognition electroencephalogram (EEG) functional connectivity spinocerebellar ataxia type 2 (SCA2) |
| title | Cerebello‐Prefrontal Connectivity Underlying Cognitive Dysfunction in Spinocerebellar Ataxia Type 2 |
| title_full | Cerebello‐Prefrontal Connectivity Underlying Cognitive Dysfunction in Spinocerebellar Ataxia Type 2 |
| title_fullStr | Cerebello‐Prefrontal Connectivity Underlying Cognitive Dysfunction in Spinocerebellar Ataxia Type 2 |
| title_full_unstemmed | Cerebello‐Prefrontal Connectivity Underlying Cognitive Dysfunction in Spinocerebellar Ataxia Type 2 |
| title_short | Cerebello‐Prefrontal Connectivity Underlying Cognitive Dysfunction in Spinocerebellar Ataxia Type 2 |
| title_sort | cerebello prefrontal connectivity underlying cognitive dysfunction in spinocerebellar ataxia type 2 |
| topic | cerebellum cognition electroencephalogram (EEG) functional connectivity spinocerebellar ataxia type 2 (SCA2) |
| url | https://doi.org/10.1002/acn3.70028 |
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