Laminar Circuit Motifs for Working Memory and Language Combinatorics: From Cells to Systems

Humans are uniquely capable of combining information in novel ways to give meaning and infer unobservable causes in the environment. This ability is supported by interactions between working memory and sensory processes. When applied to language, these combinatorial processes give us the ability to reason and plan. This complex behavior is thought to be grounded in information flowing both forward and backward between cortical areas, routed through the six layered organization of the mammalian neocortex. Testing this hypothesis requires gathering information of human laminar circuits at multiple scales, from the molecular (informing the composition of local circuits) to the mesoscopic (detailing information flow within an area across laminae) and network (across areas) ones. This challenging objective has so far remained out of reach, investigating laminar circuits has been mostly confined to animal models, limiting our understanding of human complex behaviors. To break through, the investigators propose a partnership that can provide these much needed multiscale observations in 100+ neurosurgery patients and: 1) record both high-density (laminar) array recordings and subdural recordings from prefrontal and temporal cortical areas while patients conduct a task that requires the manipulation of linguistic information in working memory; 2) characterize the laminar cell-specific molecular and genetic properties of tissue sampled immediately after the recordings; and 3) scale laminar circuit insights to mesoscopic levels accessible with laminar fMRI at 7 Tesla, in the same patients undergoing electrophysiological recordings. By combining this information using a (generative) computational modeling approach, the investigators will unravel how local neural dynamics and forward and backward information passing across areas supports our ability to recombine linguistic information in working memory. The unique multiscale level information of human brain function that the investigators aim to collect will benefit efforts beyond the cognitive field, such as those oriented at understanding the biophysical processes underlying non-invasive recordings such as fMRI.