FV 12. Non-invasive Suppression of Essential Tremor via Phase-Locked Disruption of its Temporal Coherence

Aberrant neural oscillations hallmark the pathophysiology of numerous neurological and psychiatric disorders. Here, we first report a method to accurately track the phase of neural oscillations in real-time by a Hilbert transform that avoids the characteristic Gibbs distortion at the end of the signal, aka endpoint-corrected Hilbert transform (ecHT). The ecHT method maintains the same computational complexity class of the original Hilbert transform allowing implementation in simple digital hardware. We then used the ecHT method to show that the aberrant neural oscillation that hallmarks treatment-resistant essential tremor (ET), the most common adult movement disorder, can be noninvasively supressed via transcranial electrical stimulation at a fixed phase lag over the cerebellar hemisphere ipsilateral to the tremor movement. This was tested in a quadruple-replication randomized way including stimulation at 6 fixed phases, sham and without phase-locking. In a total of 11 subjects, the suppression of ET activity was sustained after the end of the stimulation and was phenomenologically predicted, post-hoc, from the features of the tremor movement before the start of the stimulation. To test for reproducibility, 6 of the original participants werer stimulated exactly the same way three years after the original experiments: the observed, significant stimulation response remained, i.e. responders continued to respond and non-responders did not. Finally, we used a highly-comparative feature extraction (> 8000 features) with statistical learning and neurophysiological computational modelling to show that the suppression of ET activity can be mechanistically attributed to a disruption of the temporal coherence in the tremor movement that can be originated in a higher bursting entropy at the cortico-olivo-cerebello-thalamic circuitry. The suppression of aberrant neural oscillation via phase-locked driven disruption of temporal coherence may represent a powerful neuromodulatory strategy to treat neurological and psychiatric disorders.