Reward System EEG–fMRI-Pattern Neurofeedback for Major Depressive Disorder with Anhedonia: A Multicenter Pilot Study

<b>Background/Objectives:</b> Up to 75% of patients with major depressive disorder (MDD) exhibit persistent anhedonia symptoms related to abnormalities in the positive valence system. Cumulative evidence points to brain dysfunction in the reward system (RS), including in the ventral stri...

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Main Authors: Daniela Amital, Raz Gross, Nadav Goldental, Eyal Fruchter, Haya Yaron-Wachtel, Aron Tendler, Yaki Stern, Lisa Deutsch, Jeffrey D. Voigt, Talma Hendler, Tal Harmelech, Neomi Singer, Haggai Sharon
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Language:English
Published: MDPI AG 2025-04-01
Series:Brain Sciences
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Online Access:https://www.mdpi.com/2076-3425/15/5/476
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author Daniela Amital
Raz Gross
Nadav Goldental
Eyal Fruchter
Haya Yaron-Wachtel
Aron Tendler
Yaki Stern
Lisa Deutsch
Jeffrey D. Voigt
Talma Hendler
Tal Harmelech
Neomi Singer
Haggai Sharon
author_facet Daniela Amital
Raz Gross
Nadav Goldental
Eyal Fruchter
Haya Yaron-Wachtel
Aron Tendler
Yaki Stern
Lisa Deutsch
Jeffrey D. Voigt
Talma Hendler
Tal Harmelech
Neomi Singer
Haggai Sharon
author_sort Daniela Amital
collection DOAJ
description <b>Background/Objectives:</b> Up to 75% of patients with major depressive disorder (MDD) exhibit persistent anhedonia symptoms related to abnormalities in the positive valence system. Cumulative evidence points to brain dysfunction in the reward system (RS), including in the ventral striatum, in patients with MDD with anhedonia. This study aims to evaluate the safety and efficacy of a novel neurofeedback (NF) device (termed Prism) which incorporates the EEG–FRI-Pattern biomarker of the reward system (RS-EFP) for use in self-neuromodulation training (RS-EFP-NF) for alleviating depression in patients with MDD with anhedonia. <b>Methods:</b> A total of 49 adults (age range: M = 39.9 ± 11.03) with a DSM-5 diagnosis of MDD with anhedonia (per a SHAPS-C score ≥ 25) were screened for the administration of ten sessions of RS-EFP-NF twice a week on nonconsecutive days. Depression and anhedonia severity was assessed, respectively, by HDRS-17 and SHAPS-C at baseline, midway, and treatment end. <b>Results:</b> A total of 34 patients (77%) completed the protocol and were included in the analyses. No device-related adverse events were serious or required treatment. Depression symptoms were reduced at end of treatment as indicated by the HDRS-17, with a reduction of eight points on average (95% CI: −10.5 to −5.41, <i>p</i> < 0.0001), a clinical improvement rate of 78.47%, and a remission rate of 32.25%. Anhedonia, as indicated by the SHAPS-C score, was diminished, showing an average reduction of 6.3 points (95% CI: −8.51 to −4.14, <i>p</i> < 0.0001). <b>Conclusions:</b> Self-neuromodulation using RS-EFP-NF is a promising and safe treatment for MDD with anhedonia. The intervention demonstrates substantial clinical effects on both depression and anhedonia symptoms, with high patient acceptability and retention. Prism may address a critical mechanism-driven treatment gap for anhedonia that often persists despite conventional therapies. Larger controlled implementation, efficacy, and dosing studies are warranted.
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spelling doaj-art-0ca166bdf7d44569b015c742a78a05682025-08-20T01:56:25ZengMDPI AGBrain Sciences2076-34252025-04-0115547610.3390/brainsci15050476Reward System EEG–fMRI-Pattern Neurofeedback for Major Depressive Disorder with Anhedonia: A Multicenter Pilot StudyDaniela Amital0Raz Gross1Nadav Goldental2Eyal Fruchter3Haya Yaron-Wachtel4Aron Tendler5Yaki Stern6Lisa Deutsch7Jeffrey D. Voigt8Talma Hendler9Tal Harmelech10Neomi Singer11Haggai Sharon12Barzilai Medical Center, Ashkelon 7830604, IsraelSheba Medical Center, Ramat Gan 52621, IsraelSheba Medical Center, Ramat Gan 52621, IsraelICAR Collective and Brus Rappaport Medical Facility of the Technicon, Haifa 3525433, IsraelICAR Collective and Brus Rappaport Medical Facility of the Technicon, Haifa 3525433, IsraelGrayMatters Health, Haifa 3303403, IsraelGrayMatters Health, Haifa 3303403, IsraelBiostats Statistical Consulting Ltd., Modiin 7170717, IsraelMedical Device Consultants of Ridgewood, Ridgewood, NJ 07450, USAGrayMatters Health, Haifa 3303403, IsraelGrayMatters Health, Haifa 3303403, IsraelSagol Brain Institute, Tel Aviv Sourasky Medical Center, Tel Aviv 6997801, IsraelSagol Brain Institute, Tel Aviv Sourasky Medical Center, Tel Aviv 6997801, Israel<b>Background/Objectives:</b> Up to 75% of patients with major depressive disorder (MDD) exhibit persistent anhedonia symptoms related to abnormalities in the positive valence system. Cumulative evidence points to brain dysfunction in the reward system (RS), including in the ventral striatum, in patients with MDD with anhedonia. This study aims to evaluate the safety and efficacy of a novel neurofeedback (NF) device (termed Prism) which incorporates the EEG–FRI-Pattern biomarker of the reward system (RS-EFP) for use in self-neuromodulation training (RS-EFP-NF) for alleviating depression in patients with MDD with anhedonia. <b>Methods:</b> A total of 49 adults (age range: M = 39.9 ± 11.03) with a DSM-5 diagnosis of MDD with anhedonia (per a SHAPS-C score ≥ 25) were screened for the administration of ten sessions of RS-EFP-NF twice a week on nonconsecutive days. Depression and anhedonia severity was assessed, respectively, by HDRS-17 and SHAPS-C at baseline, midway, and treatment end. <b>Results:</b> A total of 34 patients (77%) completed the protocol and were included in the analyses. No device-related adverse events were serious or required treatment. Depression symptoms were reduced at end of treatment as indicated by the HDRS-17, with a reduction of eight points on average (95% CI: −10.5 to −5.41, <i>p</i> < 0.0001), a clinical improvement rate of 78.47%, and a remission rate of 32.25%. Anhedonia, as indicated by the SHAPS-C score, was diminished, showing an average reduction of 6.3 points (95% CI: −8.51 to −4.14, <i>p</i> < 0.0001). <b>Conclusions:</b> Self-neuromodulation using RS-EFP-NF is a promising and safe treatment for MDD with anhedonia. The intervention demonstrates substantial clinical effects on both depression and anhedonia symptoms, with high patient acceptability and retention. Prism may address a critical mechanism-driven treatment gap for anhedonia that often persists despite conventional therapies. Larger controlled implementation, efficacy, and dosing studies are warranted.https://www.mdpi.com/2076-3425/15/5/476EFP biomarkerneurofeedbackself-neuromodulationdepressionanhedoniadepression treatment
spellingShingle Daniela Amital
Raz Gross
Nadav Goldental
Eyal Fruchter
Haya Yaron-Wachtel
Aron Tendler
Yaki Stern
Lisa Deutsch
Jeffrey D. Voigt
Talma Hendler
Tal Harmelech
Neomi Singer
Haggai Sharon
Reward System EEG–fMRI-Pattern Neurofeedback for Major Depressive Disorder with Anhedonia: A Multicenter Pilot Study
Brain Sciences
EFP biomarker
neurofeedback
self-neuromodulation
depression
anhedonia
depression treatment
title Reward System EEG–fMRI-Pattern Neurofeedback for Major Depressive Disorder with Anhedonia: A Multicenter Pilot Study
title_full Reward System EEG–fMRI-Pattern Neurofeedback for Major Depressive Disorder with Anhedonia: A Multicenter Pilot Study
title_fullStr Reward System EEG–fMRI-Pattern Neurofeedback for Major Depressive Disorder with Anhedonia: A Multicenter Pilot Study
title_full_unstemmed Reward System EEG–fMRI-Pattern Neurofeedback for Major Depressive Disorder with Anhedonia: A Multicenter Pilot Study
title_short Reward System EEG–fMRI-Pattern Neurofeedback for Major Depressive Disorder with Anhedonia: A Multicenter Pilot Study
title_sort reward system eeg fmri pattern neurofeedback for major depressive disorder with anhedonia a multicenter pilot study
topic EFP biomarker
neurofeedback
self-neuromodulation
depression
anhedonia
depression treatment
url https://www.mdpi.com/2076-3425/15/5/476
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