bioRxiv Science⌕ Search

Biology subjects

Howell, A. M.

Publications and source records attributed to Howell, A. M..

2 recordsLinked to original sources

Personalized circuit modeling captures variation in cortical functional connectivity

Functional magnetic resonance imaging (fMRI) of the human cortex reveals patterns of correlated neural dynamics that are individual-specific and associated with phenotypic variation. However, circuit mechanisms underlying individual variation in functional connectivity (FC) are not well understood. Here, we fit individual-level FC patterns with a biophysically-based circuit model of large-scale cortical dynamics. This model is fit with a small number of neurophysiologically interpretable parameters, and incorporates a hierarchical gradient in local synaptic strengths across cortex parameterized via the structural MRI-derived T1w/T2w map. We applied our modeling framework to resting-state fMRI FC from a large cohort of subjects (N=842) from the Human Connectome Project. We found that the model captures a substantial portion of individual variation in FC, especially with personalized degrees of local synaptic specialization along the hierarchical gradient. Furthermore, the model can capture to the within-subject variation in FC across scans. Empirically, we found that principal modes of individual variation in FC follow interpretable topographic patterns. We developed a framework to assess model expressivity via how these empirical modes of FC variation align with variations in simulated FC induced by parameter perturbations. This framework reveals a straightforward mapping between key parameters and the leading modes of variation across subjects and provides a principled approach to extending computational models. Collectively, our modeling results establish a foundation for personalized computational modeling of functional dynamics in large-scale brain circuits.

neuroscience↗

Spatial patterns of within-thalamus anatomical connectivity vary across the cortical hierarchy in humans and macaques

Each cortical area has a distinct pattern of anatomical connections within the thalamus, a central subcortical structure composed of functionally and structurally distinct nuclei. Previous studies have suggested that certain cortical areas may have more extensive anatomical connections that target multiple thalamic nuclei, which potentially allows them to modulate distributed information flow. However, there is a lack of quantitative investigations into anatomical connectivity patterns within the thalamus. Consequently, it remains unknown if cortical areas exhibit systematic differences in the extent of their anatomical connections within the thalamus. To address this knowledge gap, we used diffusion magnetic resonance imaging (dMRI) to perform brain-wide probabilistic tractography for 828 healthy adults from the Human Connectome Project. We then developed a framework to quantify the spatial extent of each cortical areas anatomical connections within the thalamus. Additionally, we leveraged resting-state functional MRI, cortical myelin, and human neural gene expression data to test if the extent of anatomical connections within the thalamus varied along the cortical hierarchy, from sensory and motor to multimodal associative cortical areas. Our results revealed two distinct corticothalamic tractography motifs: 1) a sensorimotor cortical motif characterized by focal thalamic connections targeting posterolateral thalamus, associated with fast, feed-forward information flow; and 2) an associative cortical motif characterized by diffuse thalamic connections targeting anteromedial thalamus, associated with slow, feed-back information flow. These findings were consistent across human subjects and were also observed in macaques, indicating cross-species generalizability. Overall, our study demonstrates that sensorimotor and association cortical areas exhibit differences in the spatial extent of their anatomical connections within the thalamus, which may support functionally-distinct cortico-thalamic information flow.

neuroscience↗