Non-Invasive Suppression of Essential Tremor Via Phase-Locked Disruption of its Temporal Coherence

Sebastian R. Schreglmann, David Wang, Robert L. Peach, Junheng Li, Xu Zhang, Anna Latorre, Edward Rhodes, Emanuele Panella, Antonino M. Cassara, Edward S. Boyden, Mauricio Barahona, Sabato Santaniello, John Rothwell, Kailash P. Bhatia, and Nir Grossman, Nature Communication 2021, Volume 12, Article number: 363, online 13 January 2021; doi: 10.1038/s41467-020-20581-7

Aberrant neural oscillations hallmark numerous brain disorders. Here, we first report a method to track the phase of neural oscillations in real-time via endpoint-corrected Hilbert transform (ecHT) that mitigates the characteristic Gibbs distortion. We then used ecHT to show that the aberrant neural oscillation that hallmarks essential tremor (ET) syndrome, the most common adult movement disorder, can be transiently suppressed via transcranial electrical stimulation of the cerebellum phase-locked to the tremor. The tremor suppression is sustained shortly after the end of the stimulation and can be phenomenologically predicted. Finally, we use feature-based statistical-learning and neurophysiological-modelling to show that the suppression of ET is mechanistically attributed to a disruption of the temporal coherence of the aberrant oscillations in the olivocerebellar loop, thus establishing its causal role. The suppression of aberrant neural oscillation via phase-locked driven disruption of temporal coherence may in the future represent a powerful neuromodulatory strategy to treat brain disorders.

The scientific and technical impact of the study can be summarized as:

  • A new technique of real-time signal processing to track the phase of neural oscillation, based on ecHT, has been applied for the first time for the identification of the phases of cerebellar activity related to ET in patients with severe adult movement disorders, such as in Parkinson’s disease
  • It was demonstrated that the severity of ET is linked to the temporal coherence of the movements, i.e., to a cascade of coherent activities generating tremor oscillations
  • Results showed that if noninvasive transcranial alternating current stimulation of the cerebellum is phase-locked to ET movement it can suppress its amplitude within a few seconds
  • The study therefore provides foundation for a potential new interventional, noninvasive, and neuromodulation strategy for the treatment of medication refractory ET patients