Deep brain stimulation induces sparse distributions of locally modulated neuronal activity

Abstract

Deep brain stimulation (DBS) therapy is a potent tool for treating a range of brain disorders. High frequency stimulation (HFS) patterns used in DBS therapy are known to modulate neuronal spike rates and patterns in the stimulated nucleus; however, the spatial distribution of these modulated responses are not well understood. Computational models suggest that HFS modulates a volume of tissue spatially concentrated around the active electrode. Here, we tested this theory by investigating modulation of spike rates and patterns in non-human primate motor thalamus while stimulating the cerebellar-receiving area of motor thalamus, the primary DBS target for treating Essential Tremor. HFS inhibited spike activity in the majority of recorded cells, but increasing stimulation amplitude also shifted the response to a greater degree of spike pattern modulation. Modulated responses in both categories exhibited a sparse and long-range spatial distribution within motor thalamus, suggesting that stimulation preferentially affects afferent and efferent axonal processes traversing near the active electrode and that the resulting modulated volume strongly depends on the local connectome of these axonal processes. Such findings have important implications for current clinical efforts building predictive computational models of DBS therapy, developing directional DBS lead technology, and formulating closed-loop DBS strategies.

Frequency-dependent antidromic activation in thalamocortical relay neurons: effects of synaptic inputs

“…Even though excitatory inputs are mainly distributed further from the soma, they are more dense than inhibitory inputs [25] and played a stronger role in determining antidromic activation than inhibitory inputs. Earlier recordings made in thalamic neurons exhibited both excitation and inhibition within the stimulated nucleus [52], which may stem in part from the prevalence or strength of excitatory relative to inhibitory inputs within the thalamus [53]. Similar responses were recorded in STN neurons during STN DBS [18] and globus pallidus externus (GPe) neurons during GPe DBS [9].…”

7T MRI and Computational Modeling Supports a Critical Role of Lead Location in Determining Outcomes for Deep Brain Stimulation: A Case Report

“…While one could interpret the data based on a volume of tissue activated (VTA) approach, there is a growing number of studies showing that the VTAs are significantly less accurate than the pathway-specific approach adopted in this study ( Gunalan et al, 2017 ; Howell et al, 2019 ). Additionally, the use of volumes is a misnomer when considering neuronal responses to stimulation, which have shown that electrical stimulation results in a sparse density map of neuronal activation ( Histed et al, 2009 ; Xiao et al, 2018 ; Michelson et al, 2019 ).…”

Altered Primary Motor Cortex Neuronal Activity in a Rat Model of Harmaline-Induced Tremor During Thalamic Deep Brain Stimulation

“…Previous studies have shown that DBS in the subthalamic nucleus (Welter et al, 2004) and internal globus pallidus (Dostrovsky et al, 2000) of humans showed decreased neuronal firing rates at the site of DBS during stimulation. In a more recent study, DBS at the motor thalamus has been shown to inhibit spike activity and modulate spike patterns locally using a single-unit electrophysiology measurement (Xiao et al, 2018). In this study, we also used a sophisticated single-unit electrophysiology and characterized the neural activity pattern at the M1 to determine DBS function distally.…”