Closed-Loop Deep Brain Stimulation for Refractory Chronic Pain

Abstract

Pain is a subjective experience that alerts an individual to actual or potential tissue damage. Through mechanisms that are still unclear, normal physiological pain can lose its adaptive value and evolve into pathological chronic neuropathic pain. Chronic pain is a multifaceted experience that can be understood in terms of somatosensory, affective, and cognitive dimensions, each with associated symptoms and neural signals. While there have been many attempts to treat chronic pain, in this article we will argue that feedback-controlled ‘closed-loop’ deep brain stimulation (DBS) offers an urgent and promising route for treatment. Contemporary DBS trials for chronic pain use “open-loop” approaches in which tonic stimulation is delivered with fixed parameters to a single brain region. The impact of key variables such as the target brain region and the stimulation waveform is unclear, and long-term efficacy has mixed results. We hypothesize that chronic pain is due to abnormal synchronization between brain networks encoding the somatosensory, affective and cognitive dimensions of pain, and that multisite, closed-loop DBS provides an intuitive mechanism for disrupting that synchrony. By (1) identifying biomarkers of the subjective pain experience and (2) integrating these signals into a state-space representation of pain, we can create a predictive model of each patient's pain experience. Then, by establishing how stimulation in different brain regions influences individual neural signals, we can design real-time, closed-loop therapies tailored to each patient. While chronic pain is a complex disorder that has eluded modern therapies, rich historical data and state-of-the-art technology can now be used to develop a promising treatment.

A Deep Brain Stimulation Trial Period for Treating Chronic Pain

“…At present, while there are numerous individual anecdotes of patients obtaining pain relief from the stimulation of various targets, there is a lack of clear evidence pointing to reliable targets for long-term pain relief. Advances in longitudinally stable pain biomarker detection will ideally inform next-generation closed-loop DBS therapy for chronic pain that may avert long-term tolerance [ 19 , 20 , 24 ]. The hope is that through individual “N-of-1” DBS trial periods, we may find brain targets that produce acute pain relief that further extends to longer time periods.…”

CLoSES: A platform for closed-loop intracranial stimulation in humans

“…However, intracranial local field potentials (LFP) measured with iEEG clinical macro-electrodes provide stable recordings for longer periods than single/multi-unit recordings (Flint et al, 2012). Therapeutically, LFP events detection reduces seizure occurrence (Morrell, 2006) and LFPs have been considered as control signals for closedloop control in movement disorders (Tan et al, 2019;Tinkhauser et al, 2017) and pain (Shirvalkar et al, 2018).…”

Endogenous controllability of closed-loop brain-machine interfaces for pain

“…The eventual goal of closed-looped brain-machine interfaces for pain is to use brain activity patterns to dynamically control a therapeutic intervention, such that the level of intervention is automatically tuned to the level of pain (Shirvalkar et al, 2018;Zhang and Seymour, 2014). Recent studies have showed that multivariate pattern analysis (MVPA 'decoding') methods can be used to discriminate pain intensity related brain (BOLD) responses in humans with reasonable accuracy (Brodersen et al, 2012;Marquand et al, 2010;Schulz et al, 2012;Wager et al, 2013), and so in principle pain-related brain activity can be used to guide interventions in closed-loop settings.…”