Sulcal pits and their clinical symptoms associations reveal sex-specific neurodevelopmental mechanisms in schizophrenia

cortical layer events and computations in the human brain have remained sparse and difficult to validate. Being unable to record in vivo or image activity from single cells intracellularly using optogenetics in the human brain due to clear concerns for safety remains one reason cortical layer-specific activity has not been widely characterized in humans. The Neuropixels probe, however, allows us to get considerably closer to cortical layer-specific single-cell activity using their high-resolution spatial sampling. These short, but very rich intraoperative neuropixels recordings allow us to reveal cortical layer-specific LFP oscillations and dynamics which may have consistent characteristics across individuals or frontal and temporal lobe brain regions. We established three lines of investigation to identify cortical layers: 1) anatomical reconstruction using either CT and MR modalities or surgical parameters (implantation coordinates, highquality video recordings); 2) local field potential (LFP); 3) single neuron activity. We use these approaches to confirm the angle and tracts of these recordings and cross-validate the layer specificity identified through extracellular electrophysiology. We then use this spatial electrophysiological and anatomical map and compare single and multi-neuron dynamics per cortical layer calculating several different single-channel and multi-channel waveform features of the clustered SUAs. By using algorithms and criteria from published rodent literature, we have also found in vivo evidence for neural action potential backpropagation (bAP). Interestingly, the appearance of bAP events did not depend on the spike amplitude, firing frequency, or spike count of the clustered SUA, but was more correlated with the putative cell type. Our data set, and the subsequent analyses, highlight the importance of high-density sampling in translational human in vivo recordings for disentangling cell types and laminar contributions to the local neocortical microcircuit. These results may also help inform our understanding of fundamental neural circuit features in the human brain, both in cognition and in pathological conditions (such as tumors or epilepsy), which have clinical relevance in the future. References: