Focused ultrasound ventro-oral thalamotomy alters cortical excitability and motor control in focal hand dystonia

Abstract

Focal hand dystonia is a disabling disorder characterised by task-specific abnormal involuntary movements that disrupt motor control. Whilst the aetiology is unknown, abnormalities in sensory processing, sensorimotor organisation and maladaptive plasticity are thought to contribute to pathogenesis, with both genetic and environmental factors implicated. Current first line treatments may provide only partial or transient relief. High intensity focused ultrasound offers a means of focally ablating the target pathways implicated in dystonia. The ventro-oral complex, a relay within the motor thalamus, represents a key node in the cortico-basal ganglia-thalamo-cortical circuit involved in directing motor output. Surgical radiofrequency lesioning of the Vo-complex confers sustained benefit in focal hand dystonia however the mechanisms that underlie this improvement remain unexplored. Pallidal intervention, via deep brain stimulation, has been shown to modify abnormal cortical motor plasticity in individuals with generalised dystonia, and this modification has been correlated with symptom improvement. It has been hypothesised that, to obtain long-term symptom improvement in focal hand dystonia, similar permanent network or circuit-based modification is required.

In this prospective single arm interventional study, we analysed the clinical and neurophysiological correlates of eleven individuals who underwent high intensity focused ultrasound ventro-oral complex thalamotomy over twelve months follow up. These measurements allowed us to identify the immediate and delayed impacts of ventro-oral thalamotomy on symptom burden, motor performance, motor cortex excitability, spatial specificity and associative plasticity in individuals with focal hand dystonia. These findings were compared to ten age and sex-matched healthy control participants.

Consistent with our hypothesis, ventro-oral complex thalamotomy was associated with symptomatic improvement in focal hand dystonia as measured by standardised rating scales. There was no long-term loss of strength or motor dexterity in the treated limb, although adverse events were common and persisted in two participants. Inducible abnormalities in motor cortex excitability were attenuated following treatment and the spatial specificity of motor cortical responses shifted towards control values. Stimulus response curve analysis demonstrated modification of neuroplastic gain, echoing effects previously reported for pallidal stimulation in generalised dystonia.

We conclude that ventro-oral complex thalamotomy may be associated with symptom improvement in focal hand dystonia and is associated with identifiable changes in motor cortex excitability. This work presents an opportunity for further studies to build on the identified mechanistic insights of single target lesioning, and advance the field of personalised circuit-informed strategies for the treatment of movement disorders.