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Brain Sciences
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Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives—2nd...
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Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives—2nd Edition

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neuropsychiatry".

Deadline for manuscript submissions: 30 December 2025 | Viewed by 4443

Special Issue Editors

Dr. Jacopo Lisoni

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Guest Editor
Department of Mental Health and Addiction Services, ASST Spedali Civili of Brescia, 25123 Brescia, Italy
Interests: psychiatry; non-invasive neruostimulation; tDCS; depression; schizophrenia
Special Issues, Collections and Topics in MDPI journals
Dr. Stefano Barlati

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Guest Editor
1. Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy
2. Department of Mental Health and Addiction Services, ASST Spedali Civili of Brescia, 25123 Brescia, Italy
Interests: clinical psychiatry; schizophrenia; mood disorders; cognitive functions in severe mental illness; cognitive remediation in severe mental illness psychiatric rehabilitation in severe mental illness
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

With the introduction of neuromodulation treatments targeting specific neural circuits, we are rapidly approaching a new era in the treatment of psychiatric disorders. These interventions can be used for treatment purposes to not only enhance neuroplasticity and improve clinical manifestations but also translationally investigate the neurobiology behind mental health disorders and, combined with EEG or neuroimaging, they can be used to trace the effects of stimulation through brain networks.

Over recent decades, a host of non-invasive brain stimulation (NIBS) techniques have been employed in the treatment of mental health disorders (including depression, schizophrenia, OCD, PTSD, ADHD, autism, and substance use disorders), representing attractive alternatives, especially in the case of treatment-resistant conditions. NIBS techniques that use electromagnetic stimulation include repetitive transcranial magnetic stimulation (rTMS) and Theta burst stimulation (TBS), whereas electrical NIBS techniques that utilize small and wearables devices include transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS). Additional innovative neuromodulation interventions include magnetic seizure therapy (MST), which has a safer profile compared to classical electroconvulsive therapy (ECT).

For this Special Issue, we encourage researchers in this field to submit recent findings to add to the currently available data on NIBS applications in psychiatric disorders. Contributions should include results from translational research, clinical trial, open-label studies, case reports, protocol studies, reviews or meta-analyses. We especially welcome studies combining NIBS techniques with psychotherapy or cognitive training, functional neuroimaging, and EEG. Moreover, studies providing new data on parameters optimization, modeling, bioengineering, mechanisms of action, and invasive brain stimulation interventions are also welcome.

Dr. Jacopo Lisoni
Dr. Stefano Barlati
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • repetitive transcranial magnetic stimulation (rTMS) and Theta burst stimulation (TBS)
  • transcranial electrical stimulation (tES) (transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), transcranial random noise stimulation (tRNS))
  • magnetic seizure therapy (MST)
  • depression, bipolar disorder, and other mood disorders
  • schizophrenia and psychosis
  • obsessive–compulsive disorder and anxiety disorders
  • substance use disorders
  • neurodevelopmental disorders (ADHD, autism)
  • neuroimaging
  • neurophysiology
  • cognition

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Published Papers (7 papers)

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Research

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16 pages, 3834 KiB  
Article
Reward System EEG–fMRI-Pattern Neurofeedback for Major Depressive Disorder with Anhedonia: A Multicenter Pilot Study
by 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 and Haggai Sharon
Brain Sci. 2025, 15(5), 476; https://doi.org/10.3390/brainsci15050476 - 29 Apr 2025
Viewed by 748
Abstract
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 [...] Read more.
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–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. Methods: 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. 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: −10.5 to −5.41, p < 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, p < 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. Full article
(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives—2nd Edition)
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15 pages, 1374 KiB  
Article
A Methodological Evaluation of Four Different Paired Associative Stimulation Paradigms in Healthy Controls
by Kenan Hodzic, Magnus Thordstein, Joakim Strandberg, Elisabet Jerlhag and Caroline E. Wass
Brain Sci. 2025, 15(5), 461; https://doi.org/10.3390/brainsci15050461 - 27 Apr 2025
Viewed by 242
Abstract
Background/Objectives: Plasticity deficits play a key role in the pathophysiology of various psychiatric and neurological disorders. Paired associative stimulation (PAS) leverages Hebbian principles to induce synaptic plasticity in the human brain. By repeatedly pairing (1) the peripheral nerve stimulation of the median [...] Read more.
Background/Objectives: Plasticity deficits play a key role in the pathophysiology of various psychiatric and neurological disorders. Paired associative stimulation (PAS) leverages Hebbian principles to induce synaptic plasticity in the human brain. By repeatedly pairing (1) the peripheral nerve stimulation of the median nerve with (2) transcranial magnetic stimulation over the primary motor cortex (M1) at different inter-stimulus intervals (25 ms; PAS-25, or 10 ms; PAS-10), corticospinal excitability can be increased (PAS-25, mimicking long-term potentiation (LTP)) or decreased (PAS-10, mimicking long-term depression (LTD)). However, variations in the number of pairings and inter-pair intervals lack consensus. The aim of the study was to evaluate four different PAS paradigms, i.e., PAS-10 and PAS-25 with both 180 versus 225 pairings each, to establish the most reliable PAS protocols for LTP- and LTD-like cortical changes. Methods: In a randomized, double-blind, crossover study, 14 healthy participants underwent PAS-10 and PAS-25 with 180 and 225 pairings. Excitability was assessed by quantifying the EMG response amplitude of a hand muscle to a single stimulus. Results: PAS-25 with 225 pairings produced a robust enhancement of corticospinal excitability, while PAS-25 with 180 pairings was less effective. Surprisingly, PAS-10 with both 180 and 225 pairings also increased excitability. Conclusions: While all four PAS paradigms enhanced M1 excitability, PAS-25 with 225 pairings induced the strongest group-level effects and was most time-efficient. Significant individual variability of PAS responses suggests that optimizing PAS parameters, including pairing number and interstimulus intervals, may be necessary for personalized approaches. Full article
(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives—2nd Edition)
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12 pages, 952 KiB  
Article
Theta Burst TMS over the Pre-SMA Improves Inhibitory Control in Gambling Disorder Subjects as Assessed with Stop Signal Task
by Gioele Gavazzi, Carlo Cavaliere, Marco Salvatore, Nikolaos Makris and Stefano Pallanti
Brain Sci. 2025, 15(5), 448; https://doi.org/10.3390/brainsci15050448 - 25 Apr 2025
Viewed by 364
Abstract
Background. Inhibitory control failure represents a central trait in substance and behavioral addictions, which includes patients affected with gambling disorder (GD). In GD patients, research on this trait of the addiction cycle has primarily focused on the use of pharmacological treatments for its [...] Read more.
Background. Inhibitory control failure represents a central trait in substance and behavioral addictions, which includes patients affected with gambling disorder (GD). In GD patients, research on this trait of the addiction cycle has primarily focused on the use of pharmacological treatments for its assessment. More recently, modification of neural activity using transcranial magnetic stimulation (TMS) has been used to explore the dimensions of GD using patient questionnaires. Methods. Herein, we evaluated the use of continuous Theta burst stimulation (cTBS) over the pre-supplementary motor area (pre-SMA) to determine if it modified inhibitory control in the stop signal task of patients affected by GD when compared with a group of healthy controls without cTBS treatment. Results. To the best of our knowledge, our study is the first to report that TMS treatment of GD patients is associated with a behavioral improvement of stop signal reaction time. Conclusion. Our results suggest that this TMS-mediated improvement in the efficiency of inhibitory control in GD patients warrants further mechanistic studies in a larger cohort to determine if can be used as a treatment modality. Full article
(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives—2nd Edition)
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17 pages, 2368 KiB  
Article
Can Amygdala-Derived-EEG-fMRI-Pattern (EFP) Neurofeedback Treat Sleep Disturbances in PTSD?
by Aron Tendler, Yaki Stern and Tal Harmelech
Brain Sci. 2025, 15(3), 297; https://doi.org/10.3390/brainsci15030297 - 12 Mar 2025
Viewed by 2282
Abstract
Background: Sleep disturbances are a core feature of post-traumatic stress disorder (PTSD), affecting up to 90% of patients and often persisting after standard PTSD treatment. As all the current interventions have limitations, amygdala-targeted neuromodulation may offer a novel treatment pathway. Methods: Secondary analysis [...] Read more.
Background: Sleep disturbances are a core feature of post-traumatic stress disorder (PTSD), affecting up to 90% of patients and often persisting after standard PTSD treatment. As all the current interventions have limitations, amygdala-targeted neuromodulation may offer a novel treatment pathway. Methods: Secondary analysis of a prospective, single-arm trial (n = 58) was carried out evaluating Prism™ amygdala-derived-EEG-fMRI-Pattern neurofeedback (Amyg-EFP-NF). Sleep outcomes were assessed using the Clinician-Administered PTSD Scale (CAPS-5) sleep item, PTSD Checklist (PCL-5) sleep item, and Patient Health Questionnaire (PHQ-9) sleep items at baseline, post-treatment, and 3-month follow-up. Treatment consisted of 15 sessions over 8 weeks. Results: At 3-months’ follow-up, 63.79% of participants demonstrated clinically meaningful reduction in sleep disturbances (≥1 point reduction in CAPS-5 Item 20). Sleep improvement showed a moderate correlation with overall PTSD symptom reduction (r = 0.484, p < 0.001) and a balanced improvement pattern (−15.1% early, −9.1% late). Sleep responders sustained improvement across multiple measures and showed significant increases in cognitive reappraisal (mean change: +2.57 ± 1.0, p = 0.006), while non-responders showed initial but un-sustained improvement in trauma-related dreams. Conclusions: Amyg-EFP-NF shows preliminary promise for treating PTSD-related sleep disturbances. Our exploratory analyses suggest distinct temporal patterns of sleep improvement and potential associations with enhanced cognitive reappraisal capacity that warrant rigorous investigation in future randomized controlled trials. Full article
(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives—2nd Edition)
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Review

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14 pages, 532 KiB  
Review
Transcranial Direct Current Stimulation (tDCS) for Borderline Personality Disorder (BPD): Why and How?
by Lionel Cailhol, Kamilia Soltani, Cécilia Neige, Marine Mondino, Jérôme Brunelin and Martin Blay
Brain Sci. 2025, 15(6), 547; https://doi.org/10.3390/brainsci15060547 - 23 May 2025
Viewed by 196
Abstract
Background: Borderline Personality Disorder (BPD) is a severe psychiatric condition characterized by pervasive emotional dysregulation, impulsivity, and unstable interpersonal relationships. Affecting over 1% of the general population, BPD carries significant morbidity, frequent hospitalizations, and an increased risk of suicide. Although specialized psychotherapeutic approaches [...] Read more.
Background: Borderline Personality Disorder (BPD) is a severe psychiatric condition characterized by pervasive emotional dysregulation, impulsivity, and unstable interpersonal relationships. Affecting over 1% of the general population, BPD carries significant morbidity, frequent hospitalizations, and an increased risk of suicide. Although specialized psychotherapeutic approaches have shown efficacy, their impact is often constrained by availability, lengthy treatment durations, moderate effect sizes, and high dropout rates. Pharmacological treatments for BPD remain inadequate and are usually accompanied by adverse side effects. Objective: This narrative review seeks to explore the potential of transcranial direct current stimulation (tDCS) as a safe, cost-effective, and accessible neuromodulation intervention aimed at alleviating core BPD symptoms—namely, emotional dysregulation and impulsivity—while also addressing common comorbidities and opportunities for integration with existing therapeutic modalities. Methods: We conducted a narrative literature synthesis in accordance with the SANRA (Scale for the Assessment of Narrative Review Articles) guidelines. A PubMed/MEDLINE search was performed using keywords related to transcranial direct current stimulation (tDCS) and BPD, identifying five published randomized controlled trials on the topic. To provide a broader perspective, we also included studies from related fields examining mechanisms of action, safety and tolerability, cost-effectiveness, stimulation parameters, and clinical outcomes relevant to BPD. Results: Conventional tDCS protocols—typically involving 1–2 mA currents for 20–30 min—have demonstrated an excellent safety profile, resulting in only minimal and transient side effects without any risk of overdose or misuse, which is a key advantage for populations at high risk of suicidality. With moderately priced devices and the feasibility of home-based administration, tDCS provides a substantially more affordable alternative to both long-term pharmacotherapy and intensive psychotherapy. Neurobiologically, tDCS modulates the excitability of the dorsolateral and ventrolateral prefrontal cortex and enhances fronto-limbic connectivity, thereby strengthening top-down regulatory control over emotion and behavior. Pilot randomized controlled trials report moderate effect sizes for improvements in emotional regulation, inhibitory control, and rejection sensitivity, along with ancillary gains in executive functioning and reductions in depressive and substance-use symptoms when stimulating the left dorsolateral prefrontal cortex. Conclusions: tDCS stimulation emerges as a safe and scalable adjunctive treatment for BPD, leveraging targeted neuromodulation to address core features and common comorbidities like depression. However, variability in current protocols and the scarcity of well-powered randomized trials underscore the pressing need for standardized methodologies, longer-term follow-up, and individualized stimulation strategies to establish enduring clinical benefits. Full article
(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives—2nd Edition)
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Other

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16 pages, 300 KiB  
Systematic Review
Psychiatric Outcomes of Subthalamic Nucleus Deep Brain Stimulation: A Systematic Review of Short- and Long-Term Effects
by Mattia Vittorio Pomes, Giordano D’Urso, Ilaria Bove, Luigi Maria Cavallo, Lorenzo Della Ragione, Carmela Palmiero, Francesco Perrotta, Felice Esposito and Teresa Somma
Brain Sci. 2025, 15(6), 566; https://doi.org/10.3390/brainsci15060566 - 25 May 2025
Viewed by 67
Abstract
Background/Objectives: Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) is a widely used intervention for Parkinson’s disease (PD) and obsessive-compulsive disorder (OCD). While motor and OCD symptom benefits are established, increasing evidence highlights psychiatric side effects. The underlying mechanisms involve stimulation parameters, [...] Read more.
Background/Objectives: Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) is a widely used intervention for Parkinson’s disease (PD) and obsessive-compulsive disorder (OCD). While motor and OCD symptom benefits are established, increasing evidence highlights psychiatric side effects. The underlying mechanisms involve stimulation parameters, electrode positioning, and medication adjustments. This systematic review aims to evaluate the short-term and long-term psychiatric effects of STN-DBS and identify influencing factors. Methods: A systematic literature search (PubMed, Scopus, Web of Science, Embase; 2015–2024) was conducted following PRISMA guidelines. Studies examining psychiatric effects of STN-DBS in PD or OCD, reporting quantitative/qualitative psychiatric measures, and specifying stimulation parameters were included. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) for observational studies and the Cochrane Risk of Bias Tool for randomized controlled trials (RCTs). Results: A total of 16 studies met the inclusion criteria, with sample sizes from 10 to 149 patients and short- to long-term follow-ups (up to 17 years). Short-term effects included transient hypomania, euphoria, increased impulsivity (especially with medial STN stimulation), and sometimes anxiety reduction. Long-term effects showed a tendency towards apathy and depression (apathy increased significantly in one large cohort), particularly linked to ventromedial STN stimulation or dopaminergic medication reduction. Impulse control disorders (ICDs) improved long-term in one study following medication reduction, while impulsivity slightly worsened in another. Verbal fluency decline was commonly reported, though global cognition often remained stable. Psychiatric outcomes (mood/apathy, attention/memory) depended on stimulation location within STN subregions. Higher total electrical energy delivered (TEED) correlated with depressive trait shifts in one study. Conclusions: STN-DBS has complex psychiatric consequences. Electrode positioning, stimulation parameters (including location within STN subregions and possibly TEED), and medication adjustments significantly influence outcomes. Careful patient selection, preoperative psychiatric screening, optimized programming targeting specific STN subregions, and cautious medication management are essential to minimize psychiatric risks while maximizing therapeutic benefits for motor and OCD symptoms. Full article
(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives—2nd Edition)
15 pages, 1060 KiB  
Protocol
Longitudinal Effects of Transcranial Direct Current Stimulation on Daily Rejection-Related Emotions in Borderline Personality Disorder: An Ecological Momentary Assessment Study Protocol
by Chiara De Panfilis, Alessandro Lisco, Kevin B. Meehan, Maria Lidia Gerra, Emanuele Preti, Paolo Riva and Leonor Josefina Romero Lauro
Brain Sci. 2025, 15(5), 530; https://doi.org/10.3390/brainsci15050530 - 20 May 2025
Viewed by 124
Abstract
Background: Borderline Personality Disorder (BPD) is a debilitating mental health condition characterized by emotional dysregulation and interpersonal dysfunction, with perceived social rejection exacerbating these issues. Emerging evidence suggests that a single session of transcranial direct current stimulation (tDCS) over the right ventrolateral prefrontal [...] Read more.
Background: Borderline Personality Disorder (BPD) is a debilitating mental health condition characterized by emotional dysregulation and interpersonal dysfunction, with perceived social rejection exacerbating these issues. Emerging evidence suggests that a single session of transcranial direct current stimulation (tDCS) over the right ventrolateral prefrontal cortex (rVLPFC) may decrease the unique tendency of BPD patients to feel rejected even when socially included during a laboratory task. Objectives: This protocol outlines a double-blind, sham-controlled study evaluating the longitudinal effects of repeated anodal tDCS over the right ventrolateral prefrontal cortex (rVLPFC) on rejection-related emotions (RRE) during real-life social interactions in individuals with BPD. Methods: Sixty BPD patients will be randomized to receive real or sham tDCS across 10 daily sessions, coupled with an ecological momentary assessment (EMA) protocol capturing emotional and behavioral responses to real-life social interactions over four timepoints: baseline, during treatment, ten days post-treatment, and three months post-treatment. Primary outcomes include changes in RRE, with exploratory analyses examining feelings of social connection, aggressive tendencies, trust toward others, and interpersonal and affective dynamics. Multilevel modeling will assess temporal and group-level effects. Expected Results and Impact: This study aims to establish the efficacy of tDCS in reducing BPD patients’ negative emotional response in real-life social situations and to determine whether such effects are maintained in time. The findings could advance the clinical application of tDCS as an adjunctive intervention to alleviate social–emotional impairments in BPD, addressing gaps in current treatment approaches and guiding future research into the neural mechanisms of social emotion regulation. Full article
(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives—2nd Edition)
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