Effects of combined cerebellar tACS-iTBS in individuals with ataxia (EtABeta): a crossover investigation

Abstract Background Cerebellar ataxia (CA) is a neurodegenerative disorder characterized by progressive impairments in coordination, balance, and gait disturbances. Conventional rehabilitation therapies offer only limited benefits, driving interest toward exploring alternative non-invasive interventions. Among these, non-invasive brain stimulation techniques, such as cerebellar transcranial alternating current stimulation (tACS) and intermittent theta burst stimulation (iTBS) have emerged as promising approaches. This study aims to investigate the effectiveness of a combined cerebellar tACS-iTBS protocol in alleviating symptoms of CA, specifically targeting improvements in motor coordination, balance control, and quality of life. Methods In this randomized, sham-controlled crossover study, 31 patients diagnosed with CA will participate in two experimental conditions (real and sham stimulation), each lasting 2 weeks (phase A and B) and separated by a 3-week washout period. In the real condition, patients will receive cerebellar tACS at 5 Hz (2 mA, 190 s) delivered simultaneously with iTBS (600 pulses at 50 Hz; 80% of active motor threshold). In the sham condition, TMS will be applied without active stimulation, and cerebellar tACS will be applied only briefly for participant blinding. Following each stimulation session, patients will perform sensor-based balance training using an adaptive system with a force platform for a total of 30 min. Outcome assessments will take place at baseline of each phase (A and B) (T0a, T0b) and after completion of each 2-week intervention period (T1a, T1b). Primary and secondary outcome measures will include the Scale for the Assessment and Rating of Ataxia (SARA), International Cooperative Ataxia Rating Scale (ICARS), Short Form-36 Health Survey (SF-36), postural control (center of pressure trajectory), Motor Evoked Potentials (MEPs) for assessing corticospinal excitability, and cerebellar brain inhibition (CBI) to evaluate cerebellar-motor cortex connectivity. Discussion This study will provide valuable insights into the therapeutic potential of cerebellar tACS-iTBS as a non-invasive intervention for CA. By assessing its effects on balance, coordination, and overall quality of life, the findings could help establish whether this combined stimulation method serves as a beneficial aid to sensor-based balance training. If successful, cerebellar tACS-iTBS could offer a promising new strategy to enhance clinical outcomes and improve the quality of life in individuals with CA. Trial registration ClinicalTrial.gov NCT06420271. Registered on 2024–05–20.