Frequency-dependent spike-pattern changes in motor cortex during thalamic deep brain stimulation

Abstract

The cerebellar-receiving area of the motor thalamus is the primary anatomical target for treating essential tremor with deep brain stimulation (DBS). While neuroimaging studies have shown that higher stimulation frequencies in this target correlate with increased cortical metabolic activity, less is known about the cellular-level functional changes that occur in primary motor cortex (M1) with thalamic stimulation and how these changes depend on the frequency of DBS. In this study we used a preclinical animal model of DBS to collect single-unit spike recordings in M1 before, during, and after DBS targeting the cerebellar-receiving area of motor thalamus (VPLo, nucleus ventralis posterior lateralis pars oralis). The effects of VPLo-DBS on M1 spike rates, inter-spike interval entropy, and peristimulus phase-locking were compared across stimulus pulse train frequencies ranging from 10-130 Hz. While VPLo-DBS modulated the spike rates of 20-50% of individual M1 cells in a frequency-dependent manner, the population-level average spike rate only weakly depended on stimulation frequency. In contrast, the population-level entropy measure showed a pronounced decrease with high-frequency stimulation, caused by a subpopulation of cells that exhibited strong phase-locking and general spike-pattern regularization. Contrarily, low-frequency stimulation induced an entropy increase (spike-pattern disordering) in a relatively large portion of the recorded population, which diminished with higher stimulation frequencies. These results also suggest that changes in phase-locking and spike-pattern entropy are not necessarily equivalent pattern phenomena, but rather that they should both be weighed when quantifying stimulation-induced spike-pattern changes.

Stimulation-mediated reverse engineering of silent neural networks

“…Robust changes in firing rates are prevalent during both sensory and electrical stimuli, but fine tuning of firing patterns with only modest changes in firing rates is also possible. Recent work demonstrates modulation of subtle features of cortical activity including phase locking and inter-spike intervals of subpopulations, with only modest changes in firing rates [54]. Future expansion of our method will involve non poisson spike distribution during stimulation that emphasizes changes in spiking patterns over increase in rate, in order to identify scenarios that sufficiently add to the quantity of information needed for deriving weights and predicting spikes.…”

Considerations Using Harmaline for a Primate Model of Tremor

“…Before initiating this study, S1 had no prior surgeries or equipment present. S2 and S3 had been chronically implanted with cranial chambers and unilateral (S2) or bilateral (S3) thalamic deep brain stimulation leads as part of previous studies [ 33 34 ]. Animals were acclimated to sitting in a primate chair and to wearing wrist-mounted accelerometers on one forelimb with full range of motion for the duration of recording sessions ( Figure 1A ).…”