Can strength training improve motor function in Friedreich ataxia?

Friedreich ataxia is a progressive neurodegenerative disease affecting coordination, balance, strength, and mobility. It is usually classed as a disorder of the sensory nervous system and cerebellum, but motor pathways and skeletal muscle are affected too. The disease degrades the corticospinal tract, disrupts cerebellar-cortical networks, involves peripheral nerves, and changes skeletal muscle intrinsically, including impaired mitochondrial function and early fatigue. These changes explain much of the progressive weakness, poor movement control, and reduced capacity for daily activity seen in Friedreich ataxia. Exercise and rehabilitation are recommended for people with Friedreich ataxia. But the neurophysiological mechanisms that determine whether, how, and for whom exercise improves function are poorly understood. This is a real gap. People with Friedreich ataxia often prioritise strengthening exercise over other rehabilitation goals, yet most rehabilitation studies measure clinical outcomes; balance, gait, and function, rather than the effects of progressive strength training on nerve and muscle function. How far corticospinal tract impairment and mitochondrial muscle dysfunction each contribute to weakness, and how this weakness limits mobility, transfers, and daily participation, remains unclear. Motor evoked potentials (MEPs) in Friedreich ataxia are delayed, prolonged, and reduced in amplitude. Muscle ultrasound shows homogeneously increased echo density, with weakness more pronounced proximally and in the lower limb than the upper limb. Muscle biopsy studies show raised oxidative stress and impaired mitochondrial function. These approaches have so far been applied in isolation. None explains the full clinical picture once concurrent sensory impairment and cerebellar dysfunction are considered. It is therefore unclear whether specific forms of strength training could deliver greater benefit by selectively targeting different motor pathways, the corticospinal tract, the reticulospinal system, and motor unit behaviour. This PhD project examines whether a structured form of strength training can improve motor control and neurophysiological function in Friedreich ataxia. The project begins with a systematic review, with meta-analysis where possible, mapping the evidence for exercise-related neurophysiological adaptation in Friedreich ataxia. It will establish what is known, which methods have been used, and where the major gaps remain. Three linked experimental studies follow. Study 1 characterises corticospinal, reticulospinal, and motor unit function in people with Friedreich ataxia against neurologically healthy controls. A multimodal approach, combining HD-EMG decomposition with measures of corticospinal tract function such as MEPs and ipsilateralMEPs, will quantify how corticospinal integrity and reticulospinal tract excitability each contribute to motor unit behaviour and muscle performance across the disease spectrum. Proprioceptive loss and cerebellar impairment will be measured as confounders. Study 2 examines the acute neurophysiological effects of self-paced and metronome-paced strength exercise, testing whether a single session shifts corticospinal excitability, reticulospinal responses, and motor unit recruitment. Metronome-paced training combines force production, timing, movement precision, and external cueing. These demands may engage motor planning, corticospinal excitability, brainstem-mediated postural pathways, and motor unit recruitment more than conventional self-paced training. Study 3, built on the findings of Study 2, tests whether a longer strength training programme produces meaningful change in neurophysiology, strength, fatigue, and functional movement. Together, these studies will show how the motor system is affected in Friedreich ataxia and whether exercise can modify it. The findings may identify neurophysiological markers of rehabilitation response and support more targeted exercise interventions for people living with Friedreich ataxia. The project suits students interested in neurorehabilitation, exercise neuroscience, motor control, transcranial magnetic stimulation, electromyography, and rare neurological disease.