Abstract
Deep brain stimulation (DBS) is an effective surgical therapy for Parkinson’s disease (PD). However, limitations of the DBS systems have led to great interest in adaptive neuromodulation systems that can dynamically adjust stimulation parameters to meet concurrent therapeutic demand. Constant high-frequency motor cortex stimulation has not been remarkably efficacious, which has led to greater focus on modulation of subcortical targets. Understanding of the importance of timing in both cortical and subcortical stimulation has generated an interest in developing more refined, parsimonious stimulation techniques based on critical oscillatory activities of the brain. Concurrently, much effort has been put into identifying biomarkers of both parkinsonian and physiological patterns of neuronal activities to drive next generation of adaptive brain stimulation systems. One such biomarker is beta-gamma phase amplitude coupling (PAC) that is detected in the motor cortex. PAC is strongly correlated with parkinsonian specific motor signs and symptoms and respond to therapies in a dose-dependent manner. PAC may represent the overall state of the parkinsonian motor network and have less instantaneously dynamic fluctuation during movement. These findings raise the possibility of novel neuromodulation paradigms that are potentially less invasiveness than DBS. Successful application of PAC in neuromodulation may necessitate phase-dependent stimulation technique, which aims to deliver precisely timed stimulation pulses to a specific phase to predictably modulate to selectively modulate pathological network activities and behavior in real time. Overcoming current technical challenges can lead to deeper understanding of the parkinsonian pathophysiology and development of novel neuromodulatory therapies with potentially less side-effects and higher therapeutic efficacy.
Highlights
In Parkinson’s Disease (PD), loss of dopaminergic input into the posterior striatum leads to disordered signaling throughout the basal ganglia-thalamo-cortical (BGTC) network that manifests itself as motor symptoms of bradykinesia, rigidity, and tremor (Hammond et al, 2007)
We review recent evidence regarding phase amplitude coupling (PAC) in the context of Parkinson’s disease (PD) and present our perspective on how this biomarker could be leveraged to advance neuromodulation therapies, with an emphasis on utilizing phase-dependent stimulation techniques to target new structures with a lower risk of side-effects
A recent study developed an adaptive neuromodulation system based on a real-time cortical Phase-dependent stimulation (PDS) algorithm to show that beta oscillations in the primary motor cortex can be controlled with volition and that PDS can differentially modulate the rhythmic patterns depending on the targeted phase of beta, which in turn, affects behavior (Peles et al, 2020)
Summary
In Parkinson’s Disease (PD), loss of dopaminergic input into the posterior striatum leads to disordered signaling throughout the basal ganglia-thalamo-cortical (BGTC) network that manifests itself as motor symptoms of bradykinesia, rigidity, and tremor (Hammond et al, 2007). A recent study developed an adaptive neuromodulation system based on a real-time cortical PDS algorithm to show that beta oscillations in the primary motor cortex can be controlled with volition and that PDS can differentially modulate the rhythmic patterns depending on the targeted phase of beta, which in turn, affects behavior (Peles et al, 2020). It is entirely conceivable to develop PAC-based phase-dependent neuromodulation algorithms that concurrently detect and analyze multiple time-domain and spectral features to provide additional controls, such that variables such as waveform shapes and beta amplitudes can either supplement PAC or function as backup biomarkers in failure modes Another consideration involves stimulation-related artifact, which can hinder PAC based PDS, in the context of a surface-sensing surface-stimulation paradigm. The duration of a stimulus artifact is generally very short (3–5 ms), such that online artifact removal techniques can reduce the levels of artifact and noise during stimulation and provide sustained recording
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