Evidence map›Paper›PMID 41353354›Full record

ArticleBMC psychiatry2025

Real-time neurofeedback, its neurotransmitter underpinnings, and therapeutic effects: study protocol for a randomized controlled trial in individuals at clinical high risk.

Marlee M Vandewouw, Clemens C C Bauer, Jiahe Zhang, Jude Hammoud, Keara D Greene, Oliver Hinds, Paul Wighton, Jordan W Smoller, William S Stone, A Eden Evins and 3 more

Registry-linked trialAbstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06492343 (Real Time Neurofeedback, Its Neurotransmitter Underpinnings, and Therapeutic Effects, in Clinical High Risk Individuals), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06492343 nanot yet recruitingnot on this map

Real Time Neurofeedback, Its Neurotransmitter Underpinnings, and Therapeutic Effects, in Clinical High Risk Individuals

TypeinterventionalSponsorBoston VA Research Institute, Inc.Ran2024 to 2028Enrolled40ConditionsReal Neurofeedback From DMN, Sham Neurofeedback From Motor CortexArmsfMRI based neurofeedback
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Marlee M VandewouwCenter for Precision Psychiatry, Department of Psychiatry, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA, 02114, USA. mvandewouw@mgh.harvard.edu.
Clemens C C BauerDepartment of Psychology, Northeastern University, Boston, MA, USA.
Jiahe ZhangCenter for Precision Psychiatry, Department of Psychiatry, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA, 02114, USA.
Jude HammoudCenter for Precision Psychiatry, Department of Psychiatry, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA, 02114, USA.
Keara D GreeneCenter for Precision Psychiatry, Department of Psychiatry, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA, 02114, USA.
Oliver HindsOrchard Scientific, Yucca Valley, CA, USA.
Paul WightonAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA.
Jordan W SmollerCenter for Precision Psychiatry, Department of Psychiatry, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA, 02114, USA.
William S StoneDepartment of Psychiatry, Harvard Medical School, Boston, MA, USA.
A Eden EvinsDepartment of Psychiatry, Harvard Medical School, Boston, MA, USA.
Alexander P LinCenter for Clinical Spectroscopy, Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA.
Margaret A NiznikiewiczDepartment of Psychiatry, Harvard Medical School, Boston, MA, USA.
Susan Whitfield-GabrieliCenter for Precision Psychiatry, Department of Psychiatry, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA, 02114, USA.

Funding

Real time neurofeedback, its neurotransmitter underpinnings, and therapeutic effects, in clinical high risk individualsR61MH129479 · NIMH · BOSTON VA RESEARCH INSTITUTE, INC. · PI LIN, ALEXANDER PETER, NIZNIKIEWICZ, MARGARET A · 2023 to 2024
$2.4M
NIH HHS 5R61MH129479-02NIMH NIH HHS R61 MH129479
6 · The paper itself

Abstract

backgroundThe clinical high risk (CHR) phase of psychosis, characterized by attenuated psychotic symptoms and cognitive impairments, represents a critical window for intervention. Neurobiological alterations observed in schizophrenia (e.g., default mode network (DMN) hyperconnectivity and weakened DMN anticorrelations with the central executive network (CEN)), have been shown to extend to CHR. While neurochemical alterations, specifically glutamate (Glu) and gamma-aminobutyric acid (GABA) activity, are implicated in schizophrenia, their involvement in CHR remains less clear, as does their influence on the large-scale network alterations (e.g., DMN). Previous studies suggest that real-time neurofeedback (rtNFB) using functional magnetic resonance imaging (fMRI) modulates DMN connectivity, offering a potential therapeutic intervention for CHR. However, the efficacy of this approach in modulating neurobiological mechanisms in CHR remains unexplored.

methodsThis protocol describes a randomized controlled trial evaluating the efficacy of modulating atypical DMN connectivity in CHR individuals. Forty CHR participants (aged 18–30) will be randomized to either a real-rtNFB (N = 20) or sham-rtNFB (N = 20) condition. In the real-rtNFB group, neurofeedback will be derived from DMN-CEN activity, while the sham group will receive feedback from the somatomotor (SMOT) network. We will measure network connectivity pre- and post-intervention, testing two hypotheses: (1) real-rtNFB will reduce DMN hyperconnectivity and strengthen DMN-CEN anticorrelations in CHR, with no such changes occurring in the sham condition, and (2) post-intervention connectivity in the real-rtNFB group will more closely resemble that of neurotypical (NT; N = 20) individuals. A secondary aim will explore the relationship between network connectivity and neurotransmitter concentrations (GABA and Glu) across all participants, and whether they are altered pre- and post-rtNFB. DISCUSSION: This study will contribute to our understanding of the neurobiological mechanisms of CHR and assess whether rtNFB can alter atypical connectivity in CHR. Ultimately, we aim to inform intervention strategies that could improve both clinical and cognitive outcomes in CHR individuals.

trial registrationThe study has been registered with ClinicalTrials.gov (ID: NCT06492343, https://clinicaltrials.gov/study/NCT06492343 , Last Update Posted: July 9th, 2024).

Indexed as

Default Mode NetworkNeurofeedbackPsychotic DisordersAdolescentAdultFemalegamma-Aminobutyric AcidGlutamic AcidHumansMagnetic Resonance ImagingMaleRandomized Controlled Trials as TopicRiskSchizophreniaYoung Adultgamma-Aminobutyric AcidGlutamic AcidClinical high riskFunctional magnetic resonance imagingMagnetic resonance spectroscopyNeurotransmittersPsychosisReal-time neurofeedbackSchizophrenia

Identifiers

PMID41353354
PMCPMC12797838

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.