# Neuroimaging studies of mechanism, modulation, and plasticity of cognitive impairment in first-episode schizophrenia

> **NIH NIH K01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $185,209

## Abstract

ABSTRACT
 Cognitive impairment is a core, treatment-resistant symptom of schizophrenia that has strong
influence on functional outcome. In particular, deficits in working memory, an important component of
higher order cognition, have been well documented in schizophrenia. Nevertheless, mechanisms
underlying these deficits are poorly understood. Recent advances in functional MRI connectivity methods
provide an opportunity to better understand working memory dysfunction at the network level.
Understanding cognitive impairment especially in its early phase could accelerate the development of new
personalized treatments. Indeed, functional connectivity MRI is increasingly utilized to precisely select
targets for Transcranial Magnetic Stimulation (TMS). In the proposed series of neuroimaging studies and
analyses, our goals are to (1) identify circuit-level mechanisms that underlie working memory impairment
in first-episode patients with schizophrenia, (2) modulate and measure activity in target networks that are
disrupted in these patients, and (3) determine if TMS responsiveness predicts longitudinal outcomes.
These goals are directly in line with NIMH’s strategic research objectives in that (1) they define the
mechanism of a complex behavior and (2) they include a follow-up assessment over a 1-year period, and
thus chart progression of an illness in its early phase. To achieve these goals, we designed imaging and
brain stimulation experiments that will allow us to study rest-task dynamics between working memory-
related brain networks. Aim 1 will combine functional connectivity and graph theory to characterize the
segregation-integration dynamics of task-related networks such as frontoparietal control network and
default mode network; and determine the degree to which first-episode patients differ from healthy
controls in these network measures. It will also link these differences to behavioral performance. Aim 2
will utilize TMS to modulate activity in networks that underlie disrupted cognition in first-episode patients
with schizophrenia. Importantly, we will individualize the target region for each patient using a combination
of resting and task-based connectivity. We will then compare pre- and post-TMS behavioral and
connectivity measures and determine how the degree of TMS-induced change in connectivity predicts
improvement in behavior. Finally, Aim 3 will determine the degree to which TMS-induced plasticity is
associated with functional outcome measured longitudinally over one year in patients. The PI’s main
training goals are (1) to acquire expertise on theoretical and practical aspects of TMS, (2) to develop
expertise on clinical and cognitive aspects of schizophrenia, and (3) extend his skills in connectivity
methods via graph theoretical approaches and apply these techniques on fMRI data.

## Key facts

- **NIH application ID:** 9998735
- **Project number:** 5K01MH116369-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** H Hamdi Eryilmaz
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $185,209
- **Award type:** 5
- **Project period:** 2018-09-10 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998735

## Citation

> US National Institutes of Health, RePORTER application 9998735, Neuroimaging studies of mechanism, modulation, and plasticity of cognitive impairment in first-episode schizophrenia (5K01MH116369-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9998735. Licensed CC0.

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