LAYER-SPECIFIC RELATIONSHIPS BETWEEN NEURONAL DENSITY AND FIRING DYNAMICS IN THE HUMAN CORTEX IN VIVO AND IN VITRO

Our knowledge about the correlation between cortical structure and neuronal firing in the human brain is still limited. Here, we combined neuronal nuclei (NeuN) immunohistochemistry with electrophysiological recordings from surgically resected human cortical tissue to examine layer-specific relationships between neuronal density and firing dynamics in vivo and in vitro.
Chronic in vivo intracortical monitoring was performed during both awake and sleep states. Following resection, acute in vitro recordings were obtained from neighbouring cortical tissue using identical 24-channel linear arrays (150 µm spacing), enabling direct comparison of neuronal and network properties across experimental conditions. Histological analyses were performed on tissue sampled both from regions surrounding the in vivo recording electrodes and from cortical tissue used for subsequent in vitro recordings, obtained from more spatially distant parts of the same resections.
NeuN-positive neuronal density was higher in supragranular than infragranular layers in both in vivo and in vitro datasets. Despite similar anatomical organization, density–physiology relationships differed markedly across layers. In vivo, supragranular layers showed higher firing rates, reduced burstiness, and more regular firing with increasing neuronal density, whereas infragranular layers exhibited the opposite pattern. In vitro, density–physiology correlations were generally weaker, although supragranular density remained predictive of firing properties.
In two patients with paired in vivo and in vitro data, supragranular physiology was similarly predicted by anatomical measures derived, whereas infragranular in vivo physiology was better reflected by anatomy sampled locally around the recording sites. Together, these findings demonstrate that structure–function relationships in the human cortex are strongly layer-dependent.