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Search Results (286)

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Keywords = dorso-lateral prefrontal cortex

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28 pages, 1367 KiB  
Article
A Proton Magnetic Resonance Spectroscopy (1H MRS) Pilot Study Revealing Altered Glutamatergic and Gamma-Aminobutyric Acid (GABA)ergic Neurotransmission in Social Anxiety Disorder (SAD)
by Sonja Elsaid, Ruoyu Wang, Stefan Kloiber, Kimberly L. Desmond and Bernard Le Foll
Int. J. Mol. Sci. 2025, 26(14), 6915; https://doi.org/10.3390/ijms26146915 - 18 Jul 2025
Abstract
Social anxiety disorder (SAD) is characterized by fear and avoidance of social situations. Considering the reduced availability of conventional therapies, we aimed to improve our understanding of the biological mechanisms in SAD by evaluating gamma-aminobutyric acid (GABA) and other neurometabolites (including glutamate + [...] Read more.
Social anxiety disorder (SAD) is characterized by fear and avoidance of social situations. Considering the reduced availability of conventional therapies, we aimed to improve our understanding of the biological mechanisms in SAD by evaluating gamma-aminobutyric acid (GABA) and other neurometabolites (including glutamate + glutamine/glutamix (Glx), N-acetyl aspartate (NAA), myo-inositol (mI), total choline (tCho), and total creatine (tCr) in the dorsomedial prefrontal cortex/anterior cingulate cortex (dmPFC/ACC), dorsolateral prefrontal cortex (dlPFC), and the insula). In this pilot study, we recruited 26 (age: 25.3 ± 5.0 years; 61.5% female) individuals with SAD and 26 (age: 25.1 ± 4.4 years; 61.5% female) sex-age-matched controls. Using proton magnetic resonance spectroscopy, we found that compared to the controls, GABA+ macromolecular signal (GABA+) in dlPFC (t = 2.63; p = 0.012) and Glx in the insula (Mann–Whitney U = 178.3; p = 0.024) were higher in the participants with SAD. However, no between-group differences were observed in dmPFC/ACC (t = 0.39; p = 0.699). Increased GABA+ in dlPFC could be explained by aberrant GABA transporters. In the insula, increased Glx may be associated with the dysfunction of glutamate transporters or decreased activity of glutamic acid decarboxylase in the GABAergic inhibitory neurons. However, these proposed mechanisms need to be further investigated in SAD. Full article
(This article belongs to the Section Molecular Neurobiology)
16 pages, 1435 KiB  
Case Report
Multidimensional Effects of Manual Therapy Combined with Pain Neuroscience-Based Sensorimotor Retraining in a Patient with Chronic Neck Pain: A Case Study Using fNIRS
by Song-ui Bae, Ju-hyeon Jung and Dong-chul Moon
Healthcare 2025, 13(14), 1734; https://doi.org/10.3390/healthcare13141734 - 18 Jul 2025
Abstract
Chronic neck pain is a multifactorial condition involving physical, psychological, and neurological dimensions. This case report describes the clinical course of a 25-year-old female with chronic neck pain and recurrent headaches who underwent a 6-week integrative intervention consisting of manual therapy and pain [...] Read more.
Chronic neck pain is a multifactorial condition involving physical, psychological, and neurological dimensions. This case report describes the clinical course of a 25-year-old female with chronic neck pain and recurrent headaches who underwent a 6-week integrative intervention consisting of manual therapy and pain neuroscience-based sensorimotor retraining, administered three times per week. Outcome measures included the Headache Impact Test-6 (HIT-6), Neck Pain and Disability Scale (NPDS), Pain Catastrophizing Scale (PCS), Fear-Avoidance Beliefs Questionnaire (FABQ), pressure pain threshold (PPT), cervical range of motion (CROM), and functional near-infrared spectroscopy (fNIRS) to assess brain activity. Following the intervention, the patient demonstrated marked reductions in pain and psychological distress: HIT-6 decreased from 63 to 24 (61.9%), NPDS from 31 to 4 (87.1%), FABQ from 24 to 0 (100%), and PCS from 19 to 2 (89.5%). Improvements in PPT and CROM were also observed. fNIRS revealed decreased dorsolateral prefrontal cortex (DLPFC) activation during pain stimulation and movement tasks, suggesting a possible reduction in central sensitization burden. These findings illustrate that an integrative approach targeting biopsychosocial pain mechanisms may be beneficial in managing chronic neck pain, improving function, and modulating cortical responses. This report provides preliminary evidence in support of the clinical relevance of combining manual therapy with neurocognitive retraining in similar patients. Full article
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12 pages, 251 KiB  
Article
Efficacy of Transcranial Direct Current Stimulation in the Treatment of Anorexia Nervosa—Interim Results from an Ongoing, Double-Blind, Randomized, Placebo-Controlled Clinical Trial
by Zuzanna Rząd, Joanna Rog, Natalia Kajka, Maksymilian Seweryn, Jakub Patyk and Hanna Karakuła-Juchnowicz
J. Clin. Med. 2025, 14(14), 5040; https://doi.org/10.3390/jcm14145040 - 16 Jul 2025
Viewed by 106
Abstract
Background/Objectives: Anorexia nervosa (AN) is a severe disorder with limited treatment efficacy. This interim analysis aimed to assess the preliminary efficacy and safety of transcranial direct current stimulation (tDCS) in reducing core AN symptoms, stress, depression, low self-esteem, and BMI in adolescent [...] Read more.
Background/Objectives: Anorexia nervosa (AN) is a severe disorder with limited treatment efficacy. This interim analysis aimed to assess the preliminary efficacy and safety of transcranial direct current stimulation (tDCS) in reducing core AN symptoms, stress, depression, low self-esteem, and BMI in adolescent females, to determine the rationale for continuing the study. Methods: A single-center, randomized, double-blind, placebo-controlled trial included 20 adolescent females with AN assigned to an active tDCS group (n = 10) or a sham group (n = 10). The intervention involved 30 sessions over three weeks, targeting the dorsolateral prefrontal cortex. Outcomes were assessed at baseline, post-treatment, and follow-up using the Eating Attitudes Test (EAT-26) for eating disorder symptoms, the Perceived Stress Scale (PSS-10) for stress, the Beck Depression Inventory (BDI) for depression, the Rosenberg Self-Esteem Scale (SES) for self-esteem, and body mass index (BMI) measurements. Safety and tolerability were assessed using the tDCS Side Effects Questionnaire. Results: Eating disorder symptoms significantly decreased in the active tDCS group at study end (p = 0.003) and follow-up (p = 0.02), while no significant changes were observed in the sham group. Although BMI increased more in the active group (13.78%) than in the sham group (7.31%), this difference was not statistically significant (p = 0.10). Conclusions: Adverse effects were mild and transient, with no serious safety concerns reported. Based on the results of this interim analysis, the study will proceed due to promising efficacy outcomes and good treatment tolerability. Full article
(This article belongs to the Section Mental Health)
41 pages, 699 KiB  
Review
Neurobiological Mechanisms of Action of Transcranial Direct Current Stimulation (tDCS) in the Treatment of Substance Use Disorders (SUDs)—A Review
by James Chmiel and Donata Kurpas
J. Clin. Med. 2025, 14(14), 4899; https://doi.org/10.3390/jcm14144899 - 10 Jul 2025
Viewed by 490
Abstract
Introduction: Substance use disorders (SUDs) pose a significant public health challenge, with current treatments often exhibiting limited effectiveness and high relapse rates. Transcranial direct current stimulation (tDCS), a noninvasive neuromodulation technique that delivers low-intensity direct current via scalp electrodes, has shown promise in [...] Read more.
Introduction: Substance use disorders (SUDs) pose a significant public health challenge, with current treatments often exhibiting limited effectiveness and high relapse rates. Transcranial direct current stimulation (tDCS), a noninvasive neuromodulation technique that delivers low-intensity direct current via scalp electrodes, has shown promise in various psychiatric and neurological conditions. In SUDs, tDCS may help to modulate key neurocircuits involved in craving, executive control, and reward processing, potentially mitigating compulsive drug use. However, the precise neurobiological mechanisms by which tDCS exerts its therapeutic effects in SUDs remain only partly understood. This review addresses that gap by synthesizing evidence from clinical studies that used neuroimaging (fMRI, fNIRS, EEG) and blood-based biomarkers to elucidate tDCS’s mechanisms in treating SUDs. Methods: A targeted literature search identified articles published between 2008 and 2024 investigating tDCS interventions in alcohol, nicotine, opioid, and stimulant use disorders, focusing specifically on physiological and neurobiological assessments rather than purely behavioral outcomes. Studies were included if they employed either neuroimaging (fMRI, fNIRS, EEG) or blood tests (neurotrophic and neuroinflammatory markers) to investigate changes induced by single- or multi-session tDCS. Two reviewers screened titles/abstracts, conducted full-text assessments, and extracted key data on participant characteristics, tDCS protocols, neurobiological measures, and clinical outcomes. Results: Twenty-seven studies met the inclusion criteria. Across fMRI studies, tDCS—especially targeting the dorsolateral prefrontal cortex—consistently modulated large-scale network activity and connectivity in the default mode, salience, and executive control networks. Many of these changes correlated with subjective craving, attentional bias, or extended time to relapse. EEG-based investigations found that tDCS can alter event-related potentials (e.g., P3, N2, LPP) linked to inhibitory control and salience processing, often preceding or accompanying changes in craving. One fNIRS study revealed enhanced connectivity in prefrontal regions under active tDCS. At the same time, two blood-based investigations reported the partial normalization of neurotrophic (BDNF) and proinflammatory markers (TNF-α, IL-6) in participants receiving tDCS. Multi-session protocols were more apt to drive clinically meaningful neuroplastic changes than single-session interventions. Conclusions: Although significant questions remain regarding optimal stimulation parameters, sample heterogeneity, and the translation of acute neural shifts into lasting behavioral benefits, this research confirms that tDCS can induce detectable neurobiological effects in SUD populations. By reshaping activity across prefrontal and reward-related circuits, modulating electrophysiological indices, and altering relevant biomarkers, tDCS holds promise as a viable, mechanism-based adjunctive therapy for SUDs. Rigorous, large-scale studies with longer follow-up durations and attention to individual differences will be essential to establish how best to harness these neuromodulatory effects for durable clinical outcomes. Full article
(This article belongs to the Special Issue Substance and Behavioral Addictions: Prevention and Diagnosis)
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15 pages, 1431 KiB  
Systematic Review
A Meta-Analysis of Task-Based fMRI Studies on Alcohol Use Disorder
by Maxime Roberge, Mélanie Boisvert and Stéphane Potvin
Brain Sci. 2025, 15(7), 665; https://doi.org/10.3390/brainsci15070665 - 20 Jun 2025
Viewed by 562
Abstract
Background: Previous syntheses on the neural effects of alcohol have been restricted to tasks assessing craving, cognitive control, and reward processing. Despite extensive research, a comprehensive synthesis of functional magnetic resonance imaging (fMRI) findings on alcohol use disorder (AUD) remains lacking. This [...] Read more.
Background: Previous syntheses on the neural effects of alcohol have been restricted to tasks assessing craving, cognitive control, and reward processing. Despite extensive research, a comprehensive synthesis of functional magnetic resonance imaging (fMRI) findings on alcohol use disorder (AUD) remains lacking. This study aimed to identify consistent brain activation alterations across all cognitive and emotional tasks administered to individuals with AUD while distinguishing between short-term and long-term abstinence and using activation likelihood estimation meta-analysis. Sub-analyses on task types were performed. Methods: A systematic review identified 67 fMRI studies on participants with an AUD. Results: The meta-analysis revealed significant alterations in brain activity, including both hypo- and hyperactivation in the left putamen across all AUD participants. These alterations were observed more frequently during decision-making and reward tasks. Short-term abstinent individuals exhibited hypoactivation in the right middle frontal gyrus (MFG), corresponding to the dorsolateral prefrontal cortex. In contrast, long-term abstinent individuals displayed hypoactivation in the right superior frontal gyrus (SFG) and dorsal anterior cingulate cortex (dACC). This meta-analysis highlights critical neural alterations in AUD, particularly in regions associated with reward processing (putamen), executive functions (MFG and SFG), and attentional salience (dACC). Putamen changes were predominantly observed during short-term abstinence and in decision-making, as well as reward processing tasks. dACC and SFG hypoactivation were specific to long-term abstinence, while MFG hypoactivation was specific to short-term abstinence. Conclusions: These findings support prior research indicating a motivational imbalance and persistent executive dysfunctions in AUD. Standardizing consumption metrics and expanding task diversity in future research is essential to further refine our understanding of the neural effects of AUD. Full article
(This article belongs to the Section Neuropsychiatry)
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21 pages, 1609 KiB  
Article
Resting-State Activity Changes Induced by tDCS in MS Patients and Healthy Controls: A Simultaneous tDCS rs-fMRI Study
by Marco Muccio, Giuseppina Pilloni, Lillian Walton Masters, Peidong He, Lauren Krupp, Abhishek Datta, Marom Bikson, Leigh Charvet and Yulin Ge
Bioengineering 2025, 12(6), 672; https://doi.org/10.3390/bioengineering12060672 - 19 Jun 2025
Viewed by 532
Abstract
Transcranial direct current stimulation (tDCS) is a safe, well-tolerated method of non-invasively eliciting cortical neuromodulation. It has gained recent interest, especially for its positive clinical outcomes in neurodegenerative diseases such as multiple sclerosis (MS). However, its simultaneous (during tDCS) and cumulative effects (following [...] Read more.
Transcranial direct current stimulation (tDCS) is a safe, well-tolerated method of non-invasively eliciting cortical neuromodulation. It has gained recent interest, especially for its positive clinical outcomes in neurodegenerative diseases such as multiple sclerosis (MS). However, its simultaneous (during tDCS) and cumulative effects (following repeated tDCS sessions) on the regional brain activity during rest need further investigation, especially in MS. This study aims to elucidate tDCS’ underpinnings, alongside its therapeutic impact in MS patients, using concurrent tDCS-MRI methods. In total, 20 MS patients (age = 48 ± 12 years; 8 males) and 28 healthy controls (HCs; age = 36 ± 15 years; 12 males) were recruited. They participated in a tDCS-MRI session, during which resting-state functional MRI (rs-fMRI) was used to measure the levels of the fractional amplitude of low-frequency fluctuations (fALFFs), which is an index of regional neuronal activity, before and during left anodal dorsolateral prefrontal cortex (DLPFC) tDCS (2.0 mA for 15 min). MS patients were then asked to return for an identical tDCS-MRI visit (follow-up) after 20 identical at-home tDCS sessions. Simultaneous tDCS-induced changes in fALFF are seen across cortical and subcortical areas in both HC and MS patients, with some regions showing increased and others decreased brain activity. In HCs, fALFF increased in the right pre- and post-central gyrus whilst it decreased in subcortical regions. Conversely, MS patients initially displayed increases in more posterior cortical regions but decreases in the superior and temporal cortical regions. At follow-up, MS patients showed reversed patterns, emphasizing significant cumulative effects of tDCS treatment upon brain excitation. Such long-lasting changes are further supported by greater pre-tDCS fALFFs measured at follow-up compared to baseline, especially around the cuneus. The results were significant after correcting for multiple comparisons (p-FDR < 0.05). Our study shows that tDCS has both simultaneous and cumulative effects on neuronal activity measured with rs-fMRI, especially involving major brain areas distant from the site of stimulation, and it is responsible for fatigue and cognitive and motor skills. Full article
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13 pages, 435 KiB  
Review
The Role of Transcranial Direct Current Stimulation in Chronic Shoulder Pain: A Scoping Review
by Roberto Tedeschi, Federica Giorgi and Danilo Donati
Brain Sci. 2025, 15(6), 584; https://doi.org/10.3390/brainsci15060584 - 28 May 2025
Viewed by 444
Abstract
Background: Chronic shoulder pain is a prevalent musculoskeletal disorder often associated with central sensitisation, which limits the effectiveness of conventional therapies. Transcranial direct current stimulation (tDCS) has emerged as a non-invasive neuromodulatory intervention to modulate cortical excitability and potentially improve pain and functional [...] Read more.
Background: Chronic shoulder pain is a prevalent musculoskeletal disorder often associated with central sensitisation, which limits the effectiveness of conventional therapies. Transcranial direct current stimulation (tDCS) has emerged as a non-invasive neuromodulatory intervention to modulate cortical excitability and potentially improve pain and functional outcomes. Methods: This scoping review followed the Joanna Briggs Institute (JBI) framework and PRISMA-ScR guidelines. A systematic search was conducted across MEDLINE, CENTRAL, Scopus, PEDro, and Web of Science to identify studies evaluating the effects of tDCS on pain and function in adults with rotator cuff disorders, myofascial pain syndrome (MPS), or subacromial pain syndrome (SAPS). Data were extracted and synthesised qualitatively. Results: Four studies met the inclusion criteria. tDCS demonstrated variable efficacy: some trials reported no additional benefit when used alongside corticosteroid injections or sensorimotor training (e.g., SAPS and rotator cuff tendinopathy), while others showed enhanced pain reduction and functional gains, particularly in MPS. Targeting the dorsolateral prefrontal cortex (DLPFC) appeared more effective than stimulating the primary motor cortex (M1) in modulating pain. Functional improvements were generally observed, though not consistently superior to sham interventions. Conclusions: Preliminary evidence suggests that tDCS may represent a promising adjunctive treatment for chronic shoulder pain, particularly in MPS. However, due to the limited number of studies and heterogeneity in methods, conclusions should be interpreted with caution. However, heterogeneity in study protocols, stimulation targets, and patient populations limits conclusive recommendations. Standardised protocols and larger trials are needed to determine the optimal application of tDCS in clinical shoulder pain management. Full article
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22 pages, 2339 KiB  
Article
Safety, Feasibility, and Tolerability of Ten Days of At-Home, Remotely Supervised tDCS During Gamified Attention Training in Children with Acquired Brain Injury: An Open-Label, Dose-Controlled Pilot Trial
by Athena Stein, Justin Riddle, Kevin A. Caulfield, Paul E. Dux, Maximilian A. Friehs, Philipp A. Schroeder, Michael P. Craven, Madeleine J. Groom, Kartik K. Iyer and Karen M. Barlow
Brain Sci. 2025, 15(6), 561; https://doi.org/10.3390/brainsci15060561 - 24 May 2025
Viewed by 659
Abstract
Background/Objectives: Chronic attention problems occur in approximately 25% of children after acquired brain injury (ABI). When delivered daily, transcranial direct current stimulation (tDCS) may improve attention; however, access to daily in-clinic tDCS treatment can be limited by other commitments, including concurrent therapy, school [...] Read more.
Background/Objectives: Chronic attention problems occur in approximately 25% of children after acquired brain injury (ABI). When delivered daily, transcranial direct current stimulation (tDCS) may improve attention; however, access to daily in-clinic tDCS treatment can be limited by other commitments, including concurrent therapy, school commitments, and caregiver schedules. Treatment access can be improved through home-based interventions, though these require several practical and safety considerations in a pediatric ABI population. This study evaluated the safety, feasibility, and tolerability of remotely monitored at-home tDCS during online gamified attention training in pediatric ABI. Methods: We conducted a randomized, single-blind, dose-controlled clinical trial of at home tDCS in Brisbane, Australia (10 tDCS sessions; 20 min; 1 mA or 2 mA; bilateral dorsolateral prefrontal cortex). Participants attended our clinic at baseline for clinical assessments, fitting of the personalized tDCS headband, and training in how to use tDCS at home. All sessions were remotely supervised using live videoconferencing. We assessed the feasibility and tolerability of at-home tDCS and our customized, personalized at-home tDCS headband as primary outcomes. As secondary outcomes, we evaluated changes in functional connectivity (fc) and reaction time (RT). Results: Seventy-three participants were contacted over six months (January-June 2023) and ten were enrolled (5 males; mean age: 12.10 y [SD: 2.9]), satisfying a priori recruitment timelines (CONSORT reporting). All families successfully set up tDCS and completed attention training with excellent protocol adherence. There were no serious adverse events over the 100 total sessions. Nine participants completed all stimulation sessions (1 mA: n = 5, 2 mA: n = 4). Participants in the 2 mA group reported greater tingling, itching, and discomfort (all p < 0.05). One participant in the 1 mA group was unable to complete all sessions due to tolerability challenges; however, these challenges were resolved in the second half of the intervention by gradually increasing the stimulation duration across the 10 days alongside additional coaching and support. Conclusions: Overall, daily remotely supervised at-home tDCS in patients with pediatric ABI is safe, feasible, and tolerable. Our results support larger, sham-controlled efficacy trials and provide a foundation for the development of safe and effective at-home stimulation therapeutics that may offer targeted improvement of neurocognitive symptoms in children. Full article
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13 pages, 501 KiB  
Article
Aberrant Effective Connectivity Within and Between the Default Mode, Executive Control, and Salience Networks in Chronic Insomnia Disorder—Toward Identifying the Hyperarousal State
by Todor Georgiev, Rositsa Paunova, Anna Todeva-Radneva, Krasimir Avramov, Aneliya Draganova, Sevdalina Kandilarova and Kiril Terziyski
Biomedicines 2025, 13(6), 1293; https://doi.org/10.3390/biomedicines13061293 - 24 May 2025
Viewed by 702
Abstract
Background: Chronic insomnia (CID) is a highly prevalent sleep disorder, yet the precise mechanisms underlying it remain incompletely understood. The aim of this study is to analyze effective connectivity between key regions of the default mode network (DMN), executive control network (ECN), [...] Read more.
Background: Chronic insomnia (CID) is a highly prevalent sleep disorder, yet the precise mechanisms underlying it remain incompletely understood. The aim of this study is to analyze effective connectivity between key regions of the default mode network (DMN), executive control network (ECN), and salience network (SN) in patients with CID as potential neurologic correlates of the hyperarousal state. Methods: Thirty-one CID patients and 24 healthy controls (HC) were recruited. All the subjects filled out the Insomnia severity index scale (ISI), Beck depression inventory (BDI), and Epworth sleepiness scale (ESS), underwent polysomnography, and were scanned on functional magnetic resonance imaging. Statistical Parametric Mapping 12 was used to analyze the results. Spectral dynamic causal modeling was applied to the chosen regions of interest. Results: There were three significant connections present in the CID group—inhibitory from the dorsolateral prefrontal cortex (DLPFC) to the right hippocampus (Hippocamp R); excitatory from the dorsomedial prefrontal cortex to the ventromedial prefrontal cortex; and excitatory from the common medial prefrontal cortex to the right anterior insula (AIR). Two statistically significant excitatory connections were lacking in the patients’ group—from the posterior cingulate cortex (PCC) to AIR, and from precuneus to PCC. CID patients scored higher on the ISI and BDI. Significant negative correlations between DLPFC-Hippocamp R connectivity and both ISI and BDI scores were identified. Conclusions: Disruptions within the DMN and between the DMN, SN, and ECN reflect an impaired ability to appropriately shift between internally and externally directed cognitive states—an imbalance that potentially underlies the hyperarousal state of CID. Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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12 pages, 232 KiB  
Review
The Impact of Chronic Pain on Cognitive Function
by Milan Patel, Jamal Hasoon, Rodrigo Diez Tafur, Giuliano Lo Bianco and Alaa Abd-Elsayed
Brain Sci. 2025, 15(6), 559; https://doi.org/10.3390/brainsci15060559 - 24 May 2025
Viewed by 1003
Abstract
Background: Chronic pain affects a significant proportion of the population in the United States and poses a significant public health concern. Beyond physical discomfort, chronic pain has been increasingly linked to cognitive dysfunction, including impairments in memory, attention, executive function, and decision-making. [...] Read more.
Background: Chronic pain affects a significant proportion of the population in the United States and poses a significant public health concern. Beyond physical discomfort, chronic pain has been increasingly linked to cognitive dysfunction, including impairments in memory, attention, executive function, and decision-making. The relationship is particularly pronounced in older adults and may contribute to the onset or progression of neurodegenerative diseases. Objective: This comprehensive review explores the relationship between chronic pain and cognitive function, emphasizing the underlying neurobiological mechanisms, structural brain changes, and associated comorbidities. Methods: A review was conducted using peer-reviewed studies that began with the earliest pain and cognition mechanisms, followed by further investigation of cognitive effects of chronic pain, neuroimaging findings, and comorbid neuropsychiatric and neurodegenerative conditions. Sources included large-scale cohort studies, functional MRI analyses, and neurobiological investigations focusing on prefrontal cortex activity, default mode network alterations, and gray matter atrophy. Results: Chronic pain is associated with cognitive deficits through multiple converging pathways. It contributes to measurable impairments in cognitive function and is linked to structural and functional brain alterations. Regions of interest include the dorsolateral prefrontal cortex, medial prefrontal cortex, and default mode network, which can be connected to the neural resource hypothesis because of their cognitive domain impairments. A better understanding of these mechanisms highlights the importance of early recognition and multidisciplinary management strategies, including neuromodulation and cognitive rehabilitation. Future research should prioritize longitudinal studies and integrated interventions targeting both pain and cognitive health. Full article
(This article belongs to the Special Issue Aging-Related Changes in Memory and Cognition)
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 707
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
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16 pages, 1423 KiB  
Article
Frontal Transcranial Direct Current Stimulation in Moderate to Severe Depression: Clinical and Neurophysiological Findings from a Pilot Study
by Florin Zamfirache, Gabriela Prundaru, Cristina Dumitru and Beatrice Mihaela Radu
Brain Sci. 2025, 15(6), 540; https://doi.org/10.3390/brainsci15060540 - 22 May 2025
Viewed by 729
Abstract
Background/Objectives: Transcranial Direct Current Stimulation (tDCS) has proven to be a promising intervention for major depressive disorder (MDD). Even so, the specific neurophysiological mechanisms underlying its therapeutic effects, particularly regarding frontal EEG markers, remain insufficiently understood. This pilot study investigated both the [...] Read more.
Background/Objectives: Transcranial Direct Current Stimulation (tDCS) has proven to be a promising intervention for major depressive disorder (MDD). Even so, the specific neurophysiological mechanisms underlying its therapeutic effects, particularly regarding frontal EEG markers, remain insufficiently understood. This pilot study investigated both the clinical efficacy and neurophysiological impact of frontal tDCS in individuals with mild to severe depression, with particular focus on mood changes and alterations in Frontal Alpha Asymmetry (FAA), Beta Symmetry, and Theta/Alpha Ratios at the F3 and F4 electrode sites. Methods: A total of thirty–one participants were enrolled and completed a standardized Flow Neuroscience tDCS protocol targeting the dorsolateral prefrontal cortex using a bilateral F3/F4 montage. The intervention included an active phase of five stimulations per week for three weeks, followed by a Strengthening Phase with two stimulations per week. Clinical outcomes were assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS), while neurophysiological changes were evaluated via standardized quantitative EEG (QEEG) recordings obtained before and after the treatment course. Among the participants, fourteen individuals had a baseline MADRS score of ≥20, indicating moderate to severe depressive symptoms. Results: Following tDCS treatment, significant reductions in MADRS scores were observed across the cohort, with clinical response rates notably higher in the moderate/severe group (71.4%) compared to the mild depression group (20.0%). Neurophysiological effects were modest: no significant changes were detected in FAA or Beta Symmetry measures. However, a substantial reduction in the Theta/Alpha Ratio at F4 was found in participants with moderate to severe depression (p = 0.018, Cohen’s d = −0.72), suggesting enhanced frontal cortical activation associated with clinical improvement. Conclusions: These findings indicate that frontal tDCS is effective in reducing depressive symptoms, particularly in cases of moderate to severe depression. While improvements in FAA and Beta Symmetry were not significant, changes in the Theta/Alpha Ratio at F4 point toward dynamic neurophysiological reorganization potentially linked to therapeutic outcomes. The Theta/Alpha Ratio may serve as a promising biomarker for tracking tDCS response, whereas other EEG metrics might represent more stable trait characteristics. Future research should prioritize individualized stimulation protocols and incorporate more sensitive neurophysiological assessments, including functional connectivity analyses and task-evoked EEG paradigms, to understand the mechanisms underlying clinical improvements. Full article
(This article belongs to the Special Issue Advances in Non-Invasive Brain Stimulation)
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20 pages, 642 KiB  
Review
Efficacy and Safety of Transcranial Magnetic Stimulation for Treating Late-Life Depression: A Scoping Review
by Ciprian-Ionuț Băcilă, Monica Cornea, Andrei Lomnasan, Claudia Elena Anghel, Andreea Maria Grama, Cristina Elena Dobre, Silvia Rusu and Bogdan Ioan Vintilă
J. Clin. Med. 2025, 14(10), 3609; https://doi.org/10.3390/jcm14103609 - 21 May 2025
Viewed by 1127
Abstract
Background/Objectives: Transcranial magnetic stimulation (TMS) is a non-invasive and well-tolerated treatment, offering an effective alternative for elderly patients with depression, especially when side effects or comorbidities limit medication. Methods: This scoping review analyzes 16 studies published over the past seven years, [...] Read more.
Background/Objectives: Transcranial magnetic stimulation (TMS) is a non-invasive and well-tolerated treatment, offering an effective alternative for elderly patients with depression, especially when side effects or comorbidities limit medication. Methods: This scoping review analyzes 16 studies published over the past seven years, to evaluate the efficacy, safety, and clinical applications of TMS in older adults with depression. Results: The review examines various TMS modalities, including repetitive TMS (rTMS), deep TMS, and theta burst stimulation (TBS), with most protocols targeting the dorsolateral prefrontal cortex (DLPFC). Adverse effects were rare, mild, and transient, supporting the treatment’s safety profile. Pharmacological co-treatment was common but not essential for clinical improvement, highlighting TMS’s potential as a standalone therapy. A subset of studies used neuroplasticity (SICI, ICF, CSP) or neuroimaging measures (MRI and MRI-based neuronavigation), revealing that age-related cortical inhibition may limit plasticity rather than depression itself. Conclusions: Overall, TMS demonstrates promising effectiveness and tolerability in managing late-life depression. Across studies, remission rates varied from 20% to 63%, with higher efficacy generally observed in bilateral stimulation or high-frequency protocols. Standardization of protocols and further research into individualized targeting and long-term outcomes are warranted to support broader clinical adoption. Full article
(This article belongs to the Special Issue Innovations in the Treatment for Depression and Anxiety)
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15 pages, 2346 KiB  
Article
Neurometabolite Changes After Transcranial Photobiomodulation in Major Depressive Disorder: A Randomized Controlled Trial Investigating Dose-Dependent Effects
by David R. A. Coelho, Ümit Tural, Aura Maria Hurtado Puerto, Katherine Anne Collins, Maia Beth Gersten, Zamfira Parincu, Kari Siu, Dan Vlad Iosifescu, Eva-Maria Ratai, Paolo Cassano and Akila Weerasekera
J. Clin. Med. 2025, 14(10), 3402; https://doi.org/10.3390/jcm14103402 - 13 May 2025
Viewed by 719
Abstract
Background: Transcranial photobiomodulation (t-PBM) is a promising non-invasive therapy for Major Depressive Disorder (MDD). MDD is associated with altered brain metabolism, including changes in N-acetylaspartate (NAA), choline (Cho), and creatine (Cr). This study assessed the effects of varying t-PBM doses on neurometabolite levels [...] Read more.
Background: Transcranial photobiomodulation (t-PBM) is a promising non-invasive therapy for Major Depressive Disorder (MDD). MDD is associated with altered brain metabolism, including changes in N-acetylaspartate (NAA), choline (Cho), and creatine (Cr). This study assessed the effects of varying t-PBM doses on neurometabolite levels in the dorsolateral prefrontal cortex (dlPFC) and their correlations with clinical outcomes. Methods: In this randomized, sham-controlled, cross-over study, 33 adults with MDD received one session of t-PBM at low, medium, and high doses and a sham treatment. Proton magnetic resonance spectroscopy (1H-MRS) measured NAA, Cho, and Cr pre- and post-treatment. Clinical outcomes were assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Symptoms of Depression Questionnaire (SDQ). Statistical analyses included paired t-tests or Wilcoxon signed-rank tests for neurometabolite changes, and linear mixed-effects regression models for t-PBM dose, neurometabolites, and time effects. Results: NAA levels increased significantly (7.52 ± 0.777 to 8.12 ± 1.05 mmol/L for one session; 7.36 ± 0.85 to 7.85 ± 0.68 mmol/L across all sessions); however, these changes were not associated with specific t-PBM doses or sham. No significant changes were observed for Cho and Cr levels. Positive correlations were found between Cho levels and MADRS scores (r = 0.59, p = 0.017), and negative correlations between Cr levels and SDQ scores at the medium dose (r = −0.91, p = 0.011). Conclusions: While NAA levels increased, and correlations between neurometabolites and clinical outcomes were observed, these findings do not suggest a specific effect of t-PBM. Larger randomized controlled trials with optimized dosing protocols, extended follow-up, and advanced spectroscopy are needed to clarify the neurometabolic therapeutic potential of t-PBM in MDD. Full article
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20 pages, 2857 KiB  
Article
NeuroSafeDrive: An Intelligent System Using fNIRS for Driver Distraction Recognition
by Ghazal Bargshady, Hakki Gokalp Ustun, Yasaman Baradaran, Houshyar Asadi, Ravinesh C Deo, Jeroen Van Boxtel and Raul Fernandez Rojas
Sensors 2025, 25(10), 2965; https://doi.org/10.3390/s25102965 - 8 May 2025
Cited by 1 | Viewed by 909
Abstract
Driver distraction remains a critical factor in road accidents, necessitating intelligent systems for real-time detection. This study introduces a novel fNIRS-based method to to classify varying levels of driver distraction across diverse simulated scenarios, including cognitive, visual–manual, and auditory sources of inattention. Unlike [...] Read more.
Driver distraction remains a critical factor in road accidents, necessitating intelligent systems for real-time detection. This study introduces a novel fNIRS-based method to to classify varying levels of driver distraction across diverse simulated scenarios, including cognitive, visual–manual, and auditory sources of inattention. Unlike previous work, we evaluated multiple neurophysiological metrics—including oxygenated, deoxygenated, and combined haemoglobin—to identify the most reliable biomarker for distraction detection. Neurophysiological data were collected, and three multi-class classifiers (SVM, KNN, decision tree) were applied across different fNIRS metrics. Our results show that oxygenated haemoglobin outperforms other signals in distinguishing distracted from non-distracted states, while the combined signal performs best in differentiating distraction from baseline. The proposed SVM model achieved ≈ 77.9% accuracy in detecting distracted and relaxed driving states based on brain oxygen levels. Our findings also show that increased distraction correlates with elevated activity in the dorsolateral prefrontal cortex and premotor cortex, whereas driving without distraction exhibits lower neurovascular engagement. This study contributes to affective computing and intelligent transportation systems and could support the development of future driver distraction monitoring systems for safer and more adaptive vehicle control. Full article
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