Distinct perceptive pathways selected with tonic and bursting patterns of thalamic stimulation

Abstract

Background: Novel patterns of electrical stimulation of the brain and spinal cord hold tremendous promise to improve neuromodulation therapies for diverse disorders, including tremor and pain. To date, there are limited numbers of experimental studies in human subjects to help explain how stimulation patterns impact the clinical response, especially with deep brain stimulation. We propose using novel stimulation patterns during electrical stimulation of somatosensory thalamus in awake deep brain stimulation surgeries and hypothesize that stimulation patterns will influence the sensory percept without moving the electrode. Methods: In this study of 15 fully awake patients, the threshold of perception as well as perceptual characteristics were compared for tonic (trains of regularly-repeated pulses) and bursting stimulation patterns. Results: In a majority of subjects, tonic and burst percepts were located in separate, non-overlapping body regions (i.e., face vs. hand) without moving the stimulating electrode (p < 0.001; binomial test). The qualitative features of burst percepts also differed from those of tonic-evoked percepts as burst patterns were less likely to evoke percepts described as tingling (p ¼ 0.013; Fisher's exact test). Conclusions: Because somatosensory thalamus is somatotopically organized, percept location can be related to anatomic thalamocortical pathways. Thus, stimulation pattern may provide a mechanism to select for different thalamocortical pathways. This added control could lead to improvements in neuromodulation -such as improved efficacy and side effect attenuation -and may also improve localization for sensory prostheses.

Perception of microstimulation frequency in human somatosensory cortex

“…Similar to ICMS, increasing the stimulation amplitude increased percept intensity (Swan et al, 2018). However, changing stimulation frequency and temporal patterns have had different effects on perception, with high frequency stimulation (333 Hz) evoking the most natural percepts (Heming et al, 2010), burst stimulation evoking more natural percepts than tonic stimulation (Willsey et al, 2020), and two-pulse bursts evoking less natural sensations (Swan et al, 2018). Ultimately, temporal factors have clear effects on the sensations evoked through thalamic stimulation, but it remains unclear how to optimally control these parameters to manipulate percept quality.…”

“…More is known about the perceptual effects of stimulating the human thalamus (Davis, Kiss, Tasker, & Dostrovsky, 1996;Heming, Sanden, & Kiss, 2010;Ohara, Weiss, & Lenz, 2004;Swan, Gasperson, Krucoff, Grill, & Turner, 2018;Willsey et al, 2020). Similar to ICMS, increasing the stimulation amplitude increased percept intensity (Swan et al, 2018).…”

Proceedings of the Ninth Annual Deep Brain Stimulation Think Tank: Advances in Cutting Edge Technologies, Artificial Intelligence, Neuromodulation, Neuroethics, Pain, Interventional Psychiatry, Epilepsy, and Traumatic Brain Injury

“…Recent studies have highlighted that patterned stimulation may engage the nervous system in fundamentally different ways than can be achieved with conventional single-frequency stimulation (Tass and Majtanik, 2006;Mastro et al, 2017;Seier et al, 2018;Lo et al, 2020;Spix et al, 2020;Willsey et al, 2020;Ho et al, 2021;Pfeifer et al, 2021). Coordinated reset stimulation may affect synaptic plasticity and result in long-lasting (after stimulation is turned off) effects (Tass and Majtanik, 2006;Ho et al, 2021;Pfeifer et al, 2021).…”

“…Spatio-temporal paired pulse stimulation can be used to induce spike timing dependent strengthening or weakening of synaptic connections between brain regions and might be used for therapeutic purposes (Lo et al, 2020). Burst stimulation may enable cell-type specific targeting, as recently shown in rodent models of PD and in thalamic stimulation studies in humans (Mastro et al, 2017;Spix et al, 2020;Willsey et al, 2020). Further, adaptive processes of the nervous system would be expected to respond differently to patterned stimulation than to single-frequency stimulation; for example, potentially avoiding the habituation sometimes seen in DBS for ET (Paschen et al, 2019).…”

Spinal Cord Stimulation for Painful Diabetic Neuropathy

“…28 HF 10-kHz SCS, but not burst SCS, stimulates dorsal horn inhibitory neurons, resulting in decreased spinal pain processing. 29 The exact mechanism of burst SCS is not known, but as burst and traditional stimulation in the same location of the thalamus can activate distinct, nonoverlapping perceptive pathways, 30 a unique mechanism for this form of SCS will likely be eventually discovered. Traditional SCS (50 Hz) was originally approved by the FDA as a treatment for intractable back and leg pain in 1989, 31 and in 2015, the FDA also approved HF SCS for these indications.…”