Effects of Intracortical Microstimulation on Neural Activity in Distant Cortical Regions

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Electrical stimulation has been shown to be a useful technique for delivering information to the brain from brain-machine interfacing technology. The brain is remarkably capable of learning to interpret such information, most notably demonstrated by the success of cochlear implants. Learning to translate stimulation into useful information can be attributed to neural plasticity, yet little is known about the relationship between localized electrical stimulation and subsequent effects on brain regions distant from the simulation site. In the specific context of stimulating cortical gray matter, or intracortical microstimulation (ICMS), a common assumption is that post-stimulation effects remain localized to a small volume of neurons near the stimulating electrode. However, there is evidence that suggests the effects can spread substantial distances. Prior work in my lab has shown that subjects can learn to interpret ICMS delivered to four different electrodes in the primary somatosensory cortex (S1) as instructions to perform four different arbitrarily- assigned movements. My preliminary studies using that dataset suggest that ICMS delivered in S1 can have two types of effects on neurons in distant cortical areas: 1) ICMS pulses can directly elicit spikes in neurons from both ventral premotor cortex (PMv) and primary motor cortex (M1) – either antidromically, monosynaptically, or oligosynaptically – which I term “direct driving”. 2) Other neurons not directly driven by the ICMS pulses may nevertheless fire differently between trials instructing the same movements with only trains of ICMS pulses versus with only visual cues, which I term “instruction-modality dependent modulation”. Thus, the effects of ICMS may extend to parts of the cortical network more distant than previously appreciated. I propose to investigate the effects of ICMS instructions for arbitrarily-associated movements delivered in S1 on several distant cortical areas involved in motor control. Specifically, I will study effects in seven frontal and parietal regions: pre-supplementary motor area, dorsal premotor cortex, ventral premotor cortex, rostral primary motor cortex, caudal primary motor cortex, anterior intraparietal area, and dorsal posterior parietal cortex. Aim I will examine which of those cortical areas contain neurons that are directly driven by ICMS pulses delivered in S1. Aim II will examine which of those cortical areas contain neurons that show instruction- modality dependent modulation. The proposed studies will show the extent to which ICMS in S1 modulates distant parts of the cortical network, and how such modulation develops over time as subjects learn to use the ICMS as instructions to perform arbitrarily-associated movements. That information can be used to design inputs to cortex from brain-machine interfacing technology that is clearer to the subject and encourages healthy plasticity to reduce cognitive demand during the training process. Those improvements serve to benefit patients with diseases of the nervous system that can be treated with brain-machine interfacing technology including stroke, sensory neuropathies, or head trauma.