Phase-dependent suppression of beta oscillations in Parkinson’s disease patients

Abstract

Synchronized oscillations within and between brain areas facilitate normal processing, but are often amplified in disease. A prominent example is the abnormally sustained beta-frequency (~20Hz) oscillations recorded from the cortex and subthalamic nucleus of Parkinson's Disease patients. Computational modelling suggests that the amplitude of such oscillations could be modulated by applying stimulation at a specific phase. Such a strategy would allow selective targeting of the oscillation, with relatively little effect on other activity parameters. Here we demonstrate in awake, parkinsonian patients undergoing functional neurosurgery, that electrical stimulation arriving on consecutive cycles of a specific phase of the subthalamic oscillation can suppress its amplitude and coupling to cortex. Stimulus-evoked changes in spiking did not have a consistent time course, suggesting that the oscillation was modulated independently of net output. Phase-dependent stimulation could thus be a valuable strategy for treating brain diseases and probing the function of oscillations in the healthy brain.

Differential dopaminergic modulation of spontaneous cortico-subthalamic activity in Parkinson’s disease

“…This activity became significant only ON medication (IntraMed analysis). Since synchrony limits information transfer, 48–50 local oscillations are a potential mechanism to prevent excessive communication with the cortex. Another possibility is that a loss of cortical afferents causes, local basal ganglia oscillations to become more pronounced.…”

The phase of tACS-entrained pre-SMA beta oscillations modulates motor inhibition

“…Excessive synchronization of beta oscillations attributed to dopamine deficiency in PD has for example been observed across cortical areas and the BG (Williams et al, 2002;Litvak et al, 2010;Hirschmann et al, 2011;Koren et al, 2022), and disrupting beta synchronization in cortical (Doyle Gaynor et al, 2008) and BG nodes, including striatum (Costa et al, 2006;McCarthy et al, 2011), pallidum , subthalamic nucleus (de Solages et al, 2010;Darcy et al, 2022) and thalamus (Van Der Werf et al, 2006), results in improvements of bradykinesia, rigidity, and freezing. Precisely timing transcranial magnetic stimulation (TMS) to the opposing phase of the optimal window of ongoing beta oscillations in cortical regions may likewise present an effective non-invasive intervention for personalized modulation (Cassidy et al, 2002;Sharott et al, 2018), similar as has been demonstrated for phase-specific STN stimulation (Holt et al, 2019).…”