Stimulation-Evoked Effective Connectivity (SEEC): An in-vivo approach for defining mesoscale corticocortical connectivity

Abstract

BackgroundCortical stimulation has been a versatile technique for examining the structure and function of cortical regions as well as for implementing novel therapies. While stimulation has been used to examine the local spread of neural activity, it may also enable longitudinal examination of mesoscale interregional connectivity. Recent studies have used focal intracortical microstimulation with optical imaging to show cross-region spread of neural activity, but the exact neural mechanisms elucidated by these modalities is uncertain.ObjectiveHere, we sought to use intracortical microstimulation (ICMS) in conjunction with recordings of multi-unit action potentials to assess the mesoscale effective connectivity within sensorimotor cortex.MethodsNeural recordings were made from multielectrode arrays placed into sensory, motor, and premotor regions during surgical experiments in three squirrel monkeys. During each recording, single-pulse ICMS was repeatably delivered to a single region. Mesoscale effective connectivity was calculated from ICMS-evoked changes in multi-unit firing.ResultsMulti-unit action potentials were able to be detected on the order of 1 ms after each ICMS pulse. Across sensorimotor regions, short-latency (<2.5 ms) ICMS-evoked neural activity strongly correlated with known anatomic connections. Additionally, ICMS-evoked responses remained stable across the experimental period, in spite of small changes in electrode locations and anesthetic state.ConclusionsThese results show that monitoring ICMS-evoked neural activity is a viable way to longitudinally assess effective connectivity, enabling studies comparing the time course of connectivity changes with the time course of changes in behavioral function.HighlightsShort-latency neural responses to single-pulse intra-cortical microstimulation (ICMS) was evaluated as a surrogate for anatomical connectivity.Across three new-world monkeys, the strength of neural responses strongly correlated with known anatomical connections.Neural responses to stimulation were repeatable across the duration of the experiments and were invariant to minor deviations in electrode positions and anesthetic state.

Microstimulation of human somatosensory cortex evokes task-dependent, spatially patterned responses in motor cortex

“…However, neither the time course of these signals nor their spatial specificity could be gleaned from these measurements of aggregate neuronal activity in M1. While short latency ICMS-evoked responses have been found across sensorimotor cortex in other organisms 13–17 , the present report is the first to document systematic signaling between somatosensory and motor cortices of humans at the cellular level. Some of the short-latency, low-jitter M1 responses to ICMS in S1 may reflect antidromic activation, but the latency, jitter, and spiking probabilities of the pulse-locked responses were smoothly distributed over a range, offering no hint of a separation between two classes of activation (antidromic vs. orthodromic)(Supplementary Figure 6).…”