Ruge, Diane; (2015) Deep brain stimulation-mediated and non-invasive modulation of neuronal circuits. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Deep brain stimulation (DBS) has emerged as an effective treatment for therapy resistant psychiatric and neurological disorders, such as dystonia. For subforms, so called task specific dystonia, interventions utilizing the effects of shift of locus of attention have been used. The mechanism of the latter nor of DBS are well understood. My work in the context of this thesis involved various methods including the use of combined DBS and functional Magnetic Resonance Imaging and cohorts with neuropsychiatric patients. However, this write-up summarizes four conceptually linked projects that explore the mechanistic relevance of cortical circuits for the aforementioned interventions. First, using electrophysiological methods, I explored the mechanisms of DBS during the early treatment phase in dystonia. Typically the time course is gradual, despite the fact that DBS instantly interacts with abnormal oscillations. The results led to the hypothesis that pre-existing high levels of plasticity had formed motor memories of dystonic movement patterns, and that even though synaptic plasticity was reduced quickly by DBS, it took time for the motor system to acquire more normal movement. Second, in long term DBS treated patients intriguingly it has been found that, in some cases (but not all), DBS can be stopped for many days without any return of symptoms. My research suggested that DBS leads to persisting functional changes in the brain and that different electrophysiological signatures are associated with the retention or the loss of achieved clinical benefit when DBS is stopped and that via the programming of DBS these can be shaped. In a subsequent study results suggested that the achieved clinical benefit might be at risk when DBS is interrupted for too long. Finally, non-invasive interventions using attention modulation unexpectedly shift cortical circuit excitation towards increased excitability irrespective of the locus of attention. This finding has several clinical implications.

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