Phase- targeted stimulation modulates phase-amplitude coupling in the motor cortex of the human brain

Abstract

Background: Phase-amplitude coupling (PAC) in which the amplitude of a faster field potential oscillation is coupled to the phase of a slower rhythm, is one of the most well-studied interactions between oscillations at different frequency bands. In a healthy brain, PAC accompanies cognitive functions such as learning and memory, and changes in PAC have been associated with neurological diseases including Parkinson's disease (PD), schizophrenia, obsessive-compulsive disorder, Alzheimer's disease, and epilepsy. Objective: /Hypothesis: In PD, normalization of PAC in the motor cortex has been reported in the context of effective treatments such as dopamine replacement therapy and deep brain stimulation (DBS), but the possibility of normalizing PAC through intervention at the cortex has not been shown in humans. Phasetargeted stimulation (PDS) has a strong potential to modulate PAC levels and potentially normalize it. Methods: We applied stimulation pulses triggered by specific phases of the beta oscillations, the low frequency oscillations that define phase of gamma amplitude in beta-gamma PAC, to the motor cortex of seven PD patients at rest during DBS lead placement surgery We measured the effect on PAC modulation in the motor cortex relative to stimulation-free periods. Results: We describe a system for phase-targeted stimulation locked to specific phases of a continuously updated slow local field potential oscillation (in this case, beta band oscillations) prediction. Stimulation locked to the phase of the peak of beta oscillations increased beta-gamma coupling both during and after stimulation in the motor cortex, and the opposite phase (trough) stimulation reduced the magnitude of coupling after stimulation. Conclusion: These results demonstrate the capacity of cortical phase-targeted stimulation to modulate PAC without evoking motor activation, which could allow applications in the treatment of neurological disorders associated with abnormal PAC, such as PD.

Cortical phase-amplitude coupling is key to the occurrence and treatment of freezing of gait

“…Moreover, our results provide evidence supporting the clinical utility of M1 PAC as a reliable feedback biomarker in the development of symptom-specific adaptive DBS. In previous reports, cortical PAC in humans was almost exclusively recorded though ECoG in intraoperative settings 17 , 56 , 57 or through high-density scalp EEG. 58 , 59 While in both scenarios, a considerable extent of fixation/stationary is needed.…”

The phase of sensorimotor mu and beta oscillations has the opposite effect on corticospinal excitability

“…2). Salimpour et al [44] applied real-time electrical motor cortex stimulation in Parkinson's disease patients during surgery. Although direct comparison of results from electrical stimulation and ECoG data to ours may be challenging, it is interesting to point out that phase-dependency was similar, with beta peak and falling phase leading to the largest motor output.…”

The phase of sensorimotor mu and beta oscillations has the opposite effect on corticospinal excitability

“…Our data showed largest MEP amplitudes during beta peak and falling phase (Figure 2). Salimpour et al (2022) applied real-time electrical motor cortex stimulation in Parkinson’s disease patients during surgery. Although direct comparison of results from electrical stimulation and ECoG data to ours may be challenging, it is interesting to point out that phase-dependency was similar, with beta peak and falling phase leading to the largest motor output.…”

“…Keeffe et al, 2020). Furthermore, beta phase-dependent stimulation in these patients has been shown to ameliorate motor deficits (Cagnan et al, 2017;Holt et al, 2019;Salimpour et al, 2022).…”

“…Electrocorticography (ECoG) has shown phase-dependency of motor network betarhythm activity in Parkinson's disease patients (de Hemptine et al, 2013;Miller et al, 2012;O'Keeffe et al, 2020). Furthermore, beta phase-dependent stimulation in these patients has been shown to ameliorate motor deficits (Cagnan et al, 2017;Holt et al, 2019;Salimpour et al, 2022).…”