Proof-of-concept study indicates utility of evoked-interference DBS in Parkinson’s disease

David Escobar

Closed-loop evoked-interference deep brain stimulation (DBS) has been shown to be potentially utilisable in characterising the role of oscillatory dynamics in Parkinson’s disease and other brain conditions—indicating that this DBS modality could play a role in developing personalised neuromodulation systems.

This is the key message delivered by David Escobar (Cleveland Clinic, Cleveland, USA), and colleagues from the University of Minnesota in Minneapolis, USA, in a recent proof-of-concept, in-human study published in Brain Stimulation.

Escobar and colleagues offer some initial context to their study, stating that—while much research has been dedicated to understanding the pathophysiology of Parkinson’s disease—the neural circuit dynamics underlying the manifestation of specific motor signs are yet to be demonstrated. They go on to note that, while current theories propose that the amplitude and incidence of 13–35Hz ‘beta’ band oscillations play a role here, approaches to control basal ganglia neural activity in real time are needed to clarify whether a causal relationship between these oscillations and motor signs exists.

As such, they tested evoked-interference DBS in a 55-year-old male patient diagnosed with idiopathic Parkinson’s disease roughly six years before being implanted with a directional DBS lead in the unilateral globus pallidus internus (GPi). The researchers subsequently evaluated the suppression and amplification capabilities of this neuromodulation approach.

“We used a feedback (closed-loop) control strategy in which stimulation pulses were delivered in the GPi with precise amplitude and timing relative to the targeted GPi oscillations to evoke neural responses that suppress or amplify these oscillations,” the authors write. “The rationale behind this approach, referred to as closed-loop evoked-interference DBS, is that synaptic-related neural responses evoked by electrical pulses can modulate spontaneous, synaptic-related oscillations via synaptic integration when the pulses are delivered with precise amplitude and timing relative to the phase of spontaneous oscillatory activity.”

Five days after this procedure, the patient was admitted at the University of Minnesota Clinical Research Unit (Minneapolis, USA), where experiments took place over the course of two days to ascertain identification and characterisation of neural evoked responses. These experiments generated three key findings, according to Escobar and colleagues:

  • Evoked-interference DBS was capable of suppressing or amplifying frequency-specific GPi activity, in real time, in the targeted frequency band (16–22Hz)
  • Stimulation-evoked responses that mediated this modulation resonated in the beta band, within the same frequency range where the peak power of the spontaneous local field potentials (LFPs) was located
  • Because the evoked responses resided in the beta band, evoked-interference DBS required less stimulation amplitude to modulate beta oscillations than the stimulation needed to modulate neural activity in other frequency bands

“This study provides the rationale for future studies to assess the causal role (direct or indirect) of oscillatory dynamics in Parkinson’s disease using evoked-interference DBS,” Escobar and colleagues note. “It also highlights the prospect of developing personalised neuromodulation systems based on interference between stimulation-evoked and spontaneous neural activity.

“[Our results] are also a step towards developing closed-loop DBS systems that control circuit-wide neurophysiological dynamics associated with brain dysfunction in real time.”

Discussing limitations of their work, the researchers note that the current implementation of evoked-interference DBS employs a constant stimulation level to suppress the mean amplitude of the spontaneous oscillations—an approach that is suboptimal for suppression of neural activity because it does not account for dynamic changes in the amplitude of spontaneous neural oscillations. They also highlight the fact that the evoked-interference DBS algorithm implemented in their study creates another limitation, as suppression of oscillations in the targeted frequency band resulted in amplification of neural activity in an adjacent band (12–16Hz). “This side-band amplification can be a confounding factor when analysing the effect of suppressing targeted neural activity via evoked-interference DBS on brain function,” they add.

Escobar and colleagues conclude their report by noting that, to potentially overcome these limitations, future evoked-interference DBS algorithms will require instantaneous changes in stimulation amplitude to precisely suppress spontaneous oscillations in real time. In addition, future iterations of these systems will need to track the oscillations’ frequency and reduce filtering-related phase distortions to minimise side-band amplification during the suppression of neural activity.


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