10. Central physiology of dystonia – Insights from deep brain recordings

Abstract

The pathophysiology of dystonia is not fully understood, and pathological findings are evident at the cortical, brainstem and basal ganglia levels of the motor and sensory network. Deep brain stimulation (DBS) of the globus pallidus internus is a highly effective treatment in patients with dystonia. However, the mechanism is still not entirely understood. One hypothesis is that DBS suppresses abnormally enhanced synchronized oscillatory activity within the motor cortico – basal ganglia network. Several electrophysiological studies in patients undergoing DBS for movement disorders have revealed evidence for disease-specific oscillatory patterns of neuronal basal ganglia activity that may act as a noisy disruptive signal disturbing both local and distant neuronal network functioning causing characteristic movement disorders. In patients with dystonia, increasing evidence suggests that neuronal activity in the basal ganglia is characterized by enhanced synchronized oscillations in the low frequency band (4–12 Hz). Such synchronization correlates and is coherent with EMG activity during involuntary (mainly phasic) dystonic muscle contractions, suggesting that it may contribute to the pathophysiology of dystonia. Pallidal low frequency activity significantly drives EMG of the affected muscles, increases during involuntary movements and correlates with the strength of the muscle spasms. In my presentation, I will discuss the role of neuronal oscillations in the basal ganglia for the pathophysiology of dystonia. I will show most recent findings from our group in dystonia patients undergoing DBS using a specially designed amplifier allowing simultaneous high frequency stimulation (HFS) at therapeutic parameter settings and neuronal recordings. Here, HFS led to a significant reduction of mean power in the 4–12 Hz band by 24.8 ± 7.0% in patients with predominantly phasic dystonia. Our findings suggest that HFS may suppress pathologically enhanced low frequency activity in patients with phasic dystonia. These dystonic features are the quickest to respond to HFS and may thus directly relate to modulation of pathological basal ganglia activity, whereas improvement in tonic features may depend on long-term plastic changes within the motor network.