# Enhancing prefrontal oscillatory activity and working memory performance with noninvasive brain stimulation in early-course schizophrenia

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $730,416

## Abstract

Project Summary. Schizophrenia is a severe mental illness with an estimated economic burden of more than
$160 billion per year in the US alone. To mitigate this burden, a promising approach involves the discovery of
novel treatment interventions targeting specific neuronal circuit dysfunction, especially early in the illness, thus
ameliorating the course of the disorder. In recent work, we found that the oscillatory activity of the dorsolateral
prefrontal cortex (DLPFC), assessed with Transcranial Magnetic Stimulation (TMS) and EEG, was markedly
reduced in chronic schizophrenia (Ch-SCZ) patients. DLPFC oscillatory deficits are also present in early course
(EC-SCZ) patients and are associated to their reduced working memory (WM) performance. But findings to date
are limited by a correlational/cross-sectional design, leaving the potential causal role of DLPFC oscillatory deficits
in SCZ cognitive dysfunction unclear. The overarching goal of this proposal is to establish whether, by acutely
enhancing DLPFC oscillatory activity, we see a corresponding improvement in WM function in EC-SCZ patients.
In addition to being used to assess cortical function, as in combination with EEG, TMS can be delivered in
repetitive, high-frequency patterns (rTMS), to modulate brain activity, including prefrontal cortical oscillations.
Theta Burst Stimulation (TBS) is a type of rTMS that induces more rapid effects on neural activity than
conventional rTMS; continuous TBS (cTBS) and intermittent TBS (iTBS) can decrease and enhance cortical
excitability, respectively. Recent studies have shown that iTBS of DLPFC can acutely enhance prefrontal
excitability in healthy individuals. Yet, the immediate impact of TBS on DLPFC oscillatory activity in patients with
SCZ remains unknown. The first broad Aim of this proposal is to use iTBS to acutely ameliorate deficits in DLPFC
oscillatory activity in EC-SCZ patients.
WM relies on a neural network in which DLPFC serves as a central hub. EEG studies have reported that SCZ
patients have DLPFC oscillatory abnormalities during WM tasks, and we recently found that reduced DLPFC
oscillatory activity predicts poorer WM performance in EC-SCZ patients. It therefore stands to reason that
enhancing DLPFC oscillatory activity with TBS may benefit cognitive functioning. The second broad Aim of this
proposal is to use iTBS to acutely ameliorate WM impairments in EC-SCZ patients.
To achieve these goals, we will perform TMS/EEG assessments of DLPFC oscillatory parameters and evaluate
WM ability before and after two TBS sessions (iTBS and sham TBS of DLPFC) in seventy-five EC-SCZ patients.
The proposed study aims to provide initial evidence that TBS can acutely enhance DLPFC oscillatory activity,
which in turn predicts better WM performance, in EC-SCZ patients. Building on these findings, future
neuromodulation-based treatment interventions applying chronic doses of TBS may more persistently
ameliorate/restore DLPFC oscillatory parameters and relat...

## Key facts

- **NIH application ID:** 10364064
- **Project number:** 1R01MH125816-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Fabio Ferrarelli
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $730,416
- **Award type:** 1
- **Project period:** 2021-09-07 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364064

## Citation

> US National Institutes of Health, RePORTER application 10364064, Enhancing prefrontal oscillatory activity and working memory performance with noninvasive brain stimulation in early-course schizophrenia (1R01MH125816-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10364064. Licensed CC0.

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