Objective: This study examined response inhibition deficits using the Stop-Signal Reaction Time (SSRT) paradigm in different Spinocerebellar Ataxia (SCA) subtypes and explored cortical involvement through Transcranial Magnetic Stimulation (TMS) paradigms, comparing findings with age-matched healthy controls.

Background: SCAs are autosomal dominant ataxia primarily characterized by cerebellar atrophy. But, emerging evidence suggests cortical involvement, which is poorly explored. Impaired response inhibition, commonly linked to fronto-striatal and cerebellar dysfunction, can be assessed using SSRT. While SSRT deficits are well-documented in neurodegenerative disorders, studies in SCAs are limited. Additionally, TMS-based cortical excitability paradigms provide insights into cortical dysfunction in movement disorders but remain underutilized in SCAs. Investigating SSRT and TMS parameters may help identify subtype-specific cortical-cerebellar dysfunction and its role in disease progression.

Method: This cross-sectional study included genetically confirmed SCA1 (n=7), SCA2 (n=9), SCA3 (n=6), and SCA12 (n=7) patients, along with 15 age-matched healthy controls. Disease severity was assessed using the Scale for the Assessment and Rating of Ataxia (SARA), and cognition with the Cerebellar Cognitive Affective Syndrome (CCAS) scale. SSRT was measured using a custom Android application, and standard TMS parameters MEP, CMCT, SICI, LICI, ICF were analyzed.

Results: SSRT was significantly prolonged in SCA1 and SCA2 compared to controls (p<0.05), with a similar but non-significant trend in SCA3 and SCA12. CMCT was prolonged in SCA1 and SCA12 (p<0.05), indicating corticospinal tract involvement. SCA2 patients showed a marked loss of SICI (116%) compared to controls (44%), suggesting impaired GABA-A mediated cortical inhibition. Despite severe ataxic features, SCA3 patients exhibited no cortical involvement in TMS measures. ICF remained unchanged across all groups.

Conclusion: Our findings reveal distinct cortical involvement across SCA subtypes, with significant corticospinal tract dysfunction in SCA1 and SCA12, and impaired GABA-A mediated inhibition in SCA2. Additionally, SSRT deficits were most pronounced in SCA1 and SCA2, likely reflecting greater cortical-striatal-cerebellar dysfunction. These results highlight the need for targeted interventions to modulate cortical circuits in specific SCA subtypes.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/response-inhibition-and-cortical-excitability-in-selected-sca-subtypes-in-an-indian-cohort/