Microscale Physiological Events on the Human Cortical Surface

Abstract

Despite ongoing advances in our understanding of local single-cellular and network-level activity of neuronal populations in the human brain, extraordinarily little is known about their “intermediate” microscale local circuit dynamics. Here, we utilized ultra-high-density microelectrode arrays and a rare opportunity to perform intracranial recordings across multiple cortical areas in human participants to discover three distinct classes of cortical activity that are not locked to ongoing natural brain rhythmic activity. The first included fast waveforms similar to extracellular single-unit activity. The other two types were discrete events with slower waveform dynamics and were found preferentially in upper cortical layers. These second and third types were also observed in rodents, nonhuman primates, and semi-chronic recordings from humans via laminar and Utah array microelectrodes. The rates of all three events were selectively modulated by auditory and electrical stimuli, pharmacological manipulation, and cold saline application and had small causal co-occurrences. These results suggest that the proper combination of high-resolution microelectrodes and analytic techniques can capture neuronal dynamics that lay between somatic action potentials and aggregate population activity. Understanding intermediate microscale dynamics in relation to single-cell and network dynamics may reveal important details about activity in the full cortical circuit.

Large-scale neural recordings with single-cell resolution in human cortex using high-density Neuropixels probes

“…Participants were informed that participation in the experiment would not alter their clinical treatment in any way, and that they could withdraw at any time without jeopardizing their clinical care. Recordings in the operating room were acquired with 9 participants (mean= 59 years old, ranging from 34 to 75; 7 female; Supplemental Table 1 ) who were already scheduled for a craniotomy for concurrent clinical intraoperative neurophysiological monitoring or testing for mapping motor, language, and sensory regions and removal of tissue as a result of tumor or epilepsy or undergo intra-operative neurophysiology as part of their planned deep brain stimulator (DBS) placement 1–4 . Prior to inserting the Neuropixels probe, a small superficial incision in the pia was done using an arachnoid surgical knife.…”

“…Images obtained during surgery and locations as indicated using Brainlab (Brainlab, Inc.) captured during the surgery were aligned to the 3D reconstructions using Blender software (https://www.blender.org/) and MMVT 7–9 . The method involved projecting the surgical image onto the patient’s reconstructed brain using Blender and then placing a 3D model of the Neuropixels probe on that location similar to other coregistration approaches 4,7,8,10 . Angles were calculated from photographs taken during the surgery as well as trajectories limited by the location and angle of the burr hole for DBS surgery.…”

“…These include microwire bundles 10,11 , an array of microelectrodes arranged in laminar fashion 12,13 , microelectrode contacts arranged on a grid for use above the pia or on the shaft of a depth electrode 14–16 , and the 'Utah' planar array of penetrating microelectrodes 17–19 . Recent technological developments to move beyond more rigid structures include thin-film based systems with organic polymer electrodes (often referred to as micro-electrocorticography, ‘μECoG’), which provide access to surface recordings in the cortex 20–25 and even from the surface of the hippocampus intraoperatively 26 .…”

Impact of stimulation location relative to grey and white matter on single pulse electrical stimulation responses in the human brain

“…It is possible that repeated pulses act to engage larger reverberating or oscillating networks with increasing amplitude while the mechanisms underlying responses to SPES can reach a limit by not engaging these widespread networks. Further tests, including the use of microelectrode recordings to parse individual neuronal activity during these different stimulation approaches [92].…”

“…We posit there could be an effect of being closer to the axon hillocks of large pyramidal cells in cortical layers 4-6 and that the grey-white boundary is a convergence point for multiple output neurons or is a site with a higher concentration of excitatory versus inhibitory contributions which could explain the peak local responses [83]. To test these ideas, modelling in combination with cytoarchitectonic maps are likely necessary [84,85] in addition to sampling of neural data on microscale levels [14,92,95].…”