# Prefrontal Anatomic Pathways in Executive Control

> **NIH NIH R01** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2020 · $755,692

## Abstract

Goal-directed behavior requires selection of signals from the external and internal emotional environments
based on memory and prior experience for action. Processes that rely on emotions and memory engage the
network of medial frontal area 25 and medial temporal lobe (MTL) cortices, which are affected in psychiatric
diseases. The goal of the proposed studies is to investigate specific circuits of the medial frontal (subgenual
area 25) and MTL regions in rhesus monkeys. Pathways will be studied in the context of the excitatory and
inhibitory neuronal composition in both monkeys and humans, which critically affects function and disruption in
brain diseases. Our overarching hypothesis is that the Structural Model, which predicts the patterns and
strength of cortical connections studied in non-human primates, apply for study of pathology in brain diseases
in humans. Subgenual area 25 and MTL areas are affected in depression, which often manifests early in
chronic traumatic encephalopathy (CTE). Medial frontal and temporal areas show distinct types of pathology in
CTE by unknown circuit mechanisms. The goal of the proposed studies is to use high resolution connections in
monkeys to investigate the circuit mechanisms of the distinct pathology in medial frontal and MTL areas in CTE
through study of: (1) The synaptic targets of frontal area 25 to MTL area 28 in monkeys, and the excitatory-
inhibitory neuronal composition of the respective areas in both monkeys and humans; (2) Laminar connections
within MTL in monkeys, to compare with laminar-specific tau pathology in CTE; (3) The normal excitatory and
inhibitory neuronal and glial make-up of frontal area 25 in monkeys and humans to compare with CTE, based
on evidence that hyperactivity in area 25 perturbs normal function in depression; and (4) The density and
integrity of axons below area 25 in human control and CTE brains, which give rise to bidirectional pathways
that link with nearby prefrontal and distant cortices. Hypotheses about pathway relationships are based on the
theoretical and data based Structural Model, in the context of principles of excitatory and inhibitory control in
primates. Pathways in rhesus monkeys will be labeled with distinct neural tracers, combined with multiple
labeling for inhibitory neurons and receptors. High-resolution data from monkeys will be compared with CTE
cortex to identify distinct pathology in MTL and medial frontal regions. Quantitative data will be obtained using
correlated light, confocal and electron microscopy, analyzed using advanced statistical methods and
synthesized through modeling. Findings will establish the still unknown circuit basis for distinct pathology in
MTL and medial frontal areas in CTE, which perturbs the excitation-inhibition balance in depression and the
processes of interoception, emotion and memory.

## Key facts

- **NIH application ID:** 9969964
- **Project number:** 2R01MH117785-31
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Helen Barbas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $755,692
- **Award type:** 2
- **Project period:** 1987-07-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969964

## Citation

> US National Institutes of Health, RePORTER application 9969964, Prefrontal Anatomic Pathways in Executive Control (2R01MH117785-31). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9969964. Licensed CC0.

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