# Organization and Circuit Interactions of Thalamocortical Attentional Networks in Health and Disease

> **NIH NIH R01** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2024 · $824,998

## Abstract

Thalamocortical networks consist of two parallel circuits that involve distinct thalamic and cortical neurons and
have distinct nuclear, areal, and laminar distribution. A more specialized ‘core’ system consists of excitatory
thalamic neurons that focally target the middle cortical layers, as classically described for sensory systems. A
more diffuse ‘matrix’ system consists of excitatory thalamic neurons that broadly target the upper layers of
multiple areas, integrating information across cortices. Growing evidence suggests differential involvement of
core and matrix systems in the vital processes of sleep, attentional modulation and states of vigilance, multimodal
integration, cognition, emotion, and action, and in the disruption of these processes in schizophrenia. However,
little is known about the organization of these networks in the human brain and the distinct mechanisms of
disruption of core vs matrix systems in schizophrenia and associated sleep disorders. Our overarching
hypothesis is that core and matrix thalamocortical circuits vary in parallel with the systematic variation of cortical
laminar structure and exhibit graded connection patterns, function, and dysfunction, such that the most plastic
thalamocortical circuits allow functional flexibility but are also more vulnerable to disruption in psychiatric
diseases, and prominently in schizophrenia. Based on this, we will test the hypotheses that core and matrix
pathways differ in density, structure, termination pattern, and interactions with cortical inhibitory interneurons in
prefrontal cortices and exhibit distinct pathophysiology in schizophrenia, with matrix circuits primarily affected
along with their preferential innervation of limbic medial and orbital prefrontal areas, whereas core circuits will
mostly affect lateral prefrontal cortices. The goal of the proposed studies is to investigate the unknown circuit
interactions between core and matrix thalamocortical systems in humans, then compare and cross-validate these
findings in rhesus macaques, using archival postmortem tissue and identical approaches, so we can then reliably
study their pathophysiology in schizophrenia. We will use high-resolution microscopy to label and image
pathways at multiple scales, from system to synapse in the brains of both species and will additionally use tract-
tracing in monkeys and neurochemical labeling to cross-validate circuit interactions. We will study the density,
caliber, and myelination of axons in core vs matrix pathways and estimate the g-ratio, which is directly associated
with the speed of conduction, and thus reflects axonal function and integrity. Then we will use the novel
quantitative circuit data to computationally model core and matrix thalamocortical network dynamics and
disruptions in schizophrenia and associated sleep disorders. Our proposed studies are predicated on primate
specializations that likely underlie normal and pathologic function through thalamus and cortex in pr...

## Key facts

- **NIH application ID:** 10979293
- **Project number:** 2R01MH118500-06A1
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Arash Yazdanbakhsh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $824,998
- **Award type:** 2
- **Project period:** 2019-02-15 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10979293

## Citation

> US National Institutes of Health, RePORTER application 10979293, Organization and Circuit Interactions of Thalamocortical Attentional Networks in Health and Disease (2R01MH118500-06A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10979293. Licensed CC0.

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