{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:34:30Z","timestamp":1787027670912,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"GrayMatters Health, Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: 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\u2013FRI-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. Methods: A total of 49 adults (age range: M = 39.9 \u00b1 11.03) with a DSM-5 diagnosis of MDD with anhedonia (per a SHAPS-C score \u2265 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. Results: 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: \u221210.5 to \u22125.41, p &lt; 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: \u22128.51 to \u22124.14, p &lt; 0.0001). Conclusions: 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.<\/jats:p>","DOI":"10.3390\/brainsci15050476","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T09:00:39Z","timestamp":1745917239000},"page":"476","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Reward System EEG\u2013fMRI-Pattern Neurofeedback for Major Depressive Disorder with Anhedonia: A Multicenter Pilot Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Daniela","family":"Amital","sequence":"first","affiliation":[{"name":"Barzilai Medical Center, Ashkelon 7830604, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8128-2430","authenticated-orcid":false,"given":"Raz","family":"Gross","sequence":"additional","affiliation":[{"name":"Sheba Medical Center, Ramat Gan 52621, Israel"},{"name":"Department of Epidemiology and Preventive Medicine & Department of Psychiatry, School of Public Health & School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadav","family":"Goldental","sequence":"additional","affiliation":[{"name":"Sheba Medical Center, Ramat Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyal","family":"Fruchter","sequence":"additional","affiliation":[{"name":"ICAR Collective and Brus Rappaport Medical Facility of the Technicon, Haifa 3525433, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5578-1331","authenticated-orcid":false,"given":"Haya","family":"Yaron-Wachtel","sequence":"additional","affiliation":[{"name":"ICAR Collective and Brus Rappaport Medical Facility of the Technicon, Haifa 3525433, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8587-7335","authenticated-orcid":false,"given":"Aron","family":"Tendler","sequence":"additional","affiliation":[{"name":"GrayMatters Health, Haifa 3303403, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaki","family":"Stern","sequence":"additional","affiliation":[{"name":"GrayMatters Health, Haifa 3303403, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2445-7561","authenticated-orcid":false,"given":"Lisa","family":"Deutsch","sequence":"additional","affiliation":[{"name":"Biostats Statistical Consulting Ltd., Modiin 7170717, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Voigt","sequence":"additional","affiliation":[{"name":"Medical Device Consultants of Ridgewood, Ridgewood, NJ 07450, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talma","family":"Hendler","sequence":"additional","affiliation":[{"name":"GrayMatters Health, Haifa 3303403, Israel"},{"name":"Department of Psychology, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Sagol Brain Institute, Tel Aviv Sourasky Medical Center, Tel Aviv 6997801, Israel"},{"name":"Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tal","family":"Harmelech","sequence":"additional","affiliation":[{"name":"GrayMatters Health, Haifa 3303403, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neomi","family":"Singer","sequence":"additional","affiliation":[{"name":"Sagol Brain Institute, Tel Aviv Sourasky Medical Center, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haggai","family":"Sharon","sequence":"additional","affiliation":[{"name":"Sagol Brain Institute, Tel Aviv Sourasky Medical Center, Tel Aviv 6997801, Israel"},{"name":"Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Institute of Pain Medicine, Department of Anesthesiology and Critical Care, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2022). 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