Neurophysiological mechanisms of deep brain stimulation across spatiotemporal resolutions

Abstract

Deep brain stimulation is a neuromodulatory treatment for managing the symptoms of Parkinson’s disease and other neurological and psychiatric disorders. Electrodes are chronically implanted in disease-relevant brain regions and pulsatile electrical stimulation delivery is intended to restore neurocircuit function. However, the widespread interest in the application and expansion of this clinical therapy has preceded an overarching understanding of the neurocircuit alterations invoked by deep brain stimulation. Over the years, various forms of neurophysiological evidence have emerged which demonstrate changes to brain activity across spatiotemporal resolutions; from single-neuron, to local field potential, to brain-wide cortical network effects. Though fruitful, such studies have often led to debate about a singular putative mechanism. In this Update we aim to produce an integrative account of complementary instead of mutually exclusive neurophysiological effects to derive a generalizable concept of the mechanisms of deep brain stimulation. In particular, we offer a critical review of the most common historical competing theories, an updated discussion on recent literature from animal and human neurophysiological studies, and a synthesis of synaptic and network effects of DBS across scales of observation, including micro-, meso-, and macroscale circuit alterations.

Dopamine and DBS accelerate the neural dynamics of volitional action in Parkinson’s disease

“…In the future, decoding of movement intention could inform adaptive stimulation algorithms to support movement initiation. Given that DBS suppresses STN activity and thus the indirect pathway, 57 DBS may have similar effects to a phasic dopamine release. We might speculate that this could not only improve movement intention but reenact the connection of volition and neural reinforcement that is lost in the parkinsonian OFF state.…”

Dopaminergic reinforcement in the motor system: Implications for Parkinson's disease and deep brain stimulation

“…Most commonly, DBS electrodes are implanted in the subthalamic nucleus (STN), which has been identified as a target based on non‐human primate studies reporting the alleviation of motor symptoms after STN lesion (Bergman et al, 1990). While the mechanisms of STN‐DBS are not completely understood (Neumann, Horn, & Kühn, 2023; Neumann, Steiner, & Milosevic, 2023), it is assumed that high‐frequency stimulation (130 Hz) inhibits neural firing in the STN and consequently suppresses indirect pathway output (Milosevic et al, 2018). A key advantage of DBS over drug treatment such as levodopa is the fact that it can be adapted within milliseconds, constituting an unprecedented temporal precision (Neumann, Gilron, et al, 2023).…”

“…In the last decade, important advances have been made that pave the way for the application of adaptive STN‐DBS. Activity in the beta band has been identified as a biomarker of symptom severity (Lofredi et al, 2023), which can be disrupted by DBS (Neumann, Steiner, & Milosevic, 2023) and enables the adaptation of STN‐DBS to the concurrent symptom severity (Neumann, Gilron, et al, 2023).…”

Push-pull effects of basal ganglia network in Parkinson’s disease inferred by functional MRI

“…For each subject, we performed 20 optimization iteration procedures using BADS (Fig. 2a), there the loss value is then calculated by equation ( 9) and (10), and the ultimate goal of BADS fitting is to converge the loss value to the minimum.…”

“…Especially, it is challenging to seprate the specific neural expression that corresponds to different motor symptoms. Over the years, various forms of neurophysiological evidence demonstrates changes in brain activity across different spatiotemporal resolutions 10,11 , ranging from single neurons to local field potentials and brain-wide cortical network effects, are closely associated with the fluctuations of Parkinson's disease motor symptoms. Although these investigations have yielded significant findings, they have not yet been instrumental in the implementation of symptom-specific diagnostic and therapeutic strategies for Parkinson's disease.…”