Background. Spinocerebellar ataxia (SCA) is a degenerative cerebellar disease, causing progressive impairment of gait and balance in adults. To identify the ideal subjects for disease-modifying therapies it is critical to identify biomarkers for the earliest stages of SCA. Objective. We investigated whether prefrontal cortex activity is increased during walking in in early SCA or in pre-manifest SCA compared to healthy control subjects. Methods. Sixteen participants with genetically determined SCA and 15 age-matched healthy controls participated in the study. The SARA was administered by a movement disorders specialist before the gait assessment. An 8-channel, mobile, fNIRS, with two reference channels, was used to record changes in oxygenated hemoglobin (HbO2) and deoxygenated hemoglobin within the PFC. Participants walked for 2-minutes at a comfortable pace while wearing wireless, inertial sensors to derive gait characteristics. Results. Of the 16 individuals with SCA, 9 were classified as pre-manifest (SARA<3) and 7 as early SCA (SARA<10). PFC activity (HbO2) while walking was greater than controls of similar age in people with SCA. Increased PFC activity was also present even in the pre-manifest stage of SCA. Increase in PFC activity was related to worse gait (double-support time and toe-out angle). Conclusions. PFC activity is increased in pre-manifest SCA, even when clinical scores are normal in the pre-manifest stage of the disease, and may serve as a biomarker that precedes onset of clinical disease. Increased PFC activity is consistent less automatic, cortical control of gait to compensate for impaired automatic, cerebellar control, even in early stages of ataxia.

M.M, C.S-B, D.S., P.C.K., and C.M.G. report no disclosures relevant to the manuscript. V.V.S. and F.B.H. are employed by APDM Wearable Technologies, a Clario company, a company that may have a commercial interest in the results of this technology and research.

This study did not receive any funding

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Oregon Health & Science University IRB #9903

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All data produced in the present study are available upon reasonable request to the authors