# Narrowing the mechanistic gap for anterior prefrontal cortex function

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $662,470

## Abstract

PROJECT SUMMARY
Prefrontal cortex (PFC) is a large and heterogeneous brain area comprising the front third of the human brain
that has been implicated in numerous mental health disorders. One of the least-studied subregions of PFC is
anterior lateral PFC (aLPFC). This region, whose functioning is impacted in disorders like schizophrenia, has
been implicated in reasoning, multi-tasking, planning, memory monitoring, decision-making, and more. It
behooves us to reach a mechanistic understanding of the fundamental processes subserved by this region;
however, there are numerous challenges, including the absence of a precise animal model, inconsistencies
regarding terminology and anatomical boundaries, lack of attention to individual variability in anatomy, lack of
high-resolution imaging in living participants, and limited evaluation of the generalizability of its function. In
response to these challenges, we seek to do a deep dive on its anatomy and function at the individual level in
neurotypical adults, using cutting-edge MRI technology. Leading theories presuppose that aLPFC has a
domain-general function, processing abstracted representations that are far removed from initial inputs to the
brain. However, this assumption has yet to be carefully tested. Here, we capitalize on a body of work
implicating a portion of aLPFC in relational reasoning, or the ability to reason about information by jointly
consider several sets of mental representations. First, we seek to evaluate the claim of domain-generality by
assessing aLPFC's activation and interactions with other brain regions during performance of four relational
reasoning tasks; these tasks involve both visual and—for the first time—auditory domains, as well as
visuospatial and semantic (or "where" and "what") stimuli processed by different posterior brain regions.
Second, to better localize aLPFC activation during reasoning at the single subject level, we seek to assess
whether small sulci (grooves) serve as functional landmarks, predicting the location of this functionally defined
region. Third, we seek to leverage the exquisite spatial resolution of our NexGen 7 Tesla MR scanner and a
combination of two fMRI methods to test whether aLPFC activation during reasoning is predominantly localized
to superficial cortical layers, consistent with involvement in local recurrent connectivity that supports integration
of high-level mental representations. Fourth, theories of PFC organization either presuppose that aLPFC
receives inputs exclusively from other PFC regions or that it also has long-range connections to more domain-
sensitive regions in parietal and temporal cortices. Thus, we seek to use high-resolution diffusion-weighted
imaging at 7 Tesla to shed light on the provenance of inputs to aLPFC. With strong expertise in PFC function,
neuroanatomy, high-field MR imaging technology, and MRI analytic approaches, our team is poised to yield
novel insights about PFC function. This study is both theore...

## Key facts

- **NIH application ID:** 10980947
- **Project number:** 1R01MH133637-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Silvia A. BUNGE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $662,470
- **Award type:** 1
- **Project period:** 2024-08-09 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980947

## Citation

> US National Institutes of Health, RePORTER application 10980947, Narrowing the mechanistic gap for anterior prefrontal cortex function (1R01MH133637-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10980947. Licensed CC0.

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