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Brain Sciences
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Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives
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Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives

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

Deadline for manuscript submissions: closed (15 September 2024) | Viewed by 12101

Special Issue Editors

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
Dr. Jacopo Lisoni

E-Mail Website
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 Issue Information

Dear Colleagues,

Currently, several non-invasive brain stimulation (NIBS) techniques are available for clinical application in psychiatric disorders (including major depressive disorder, obsessive-compulsive-disorder) or are under investigation (including schizophrenia, eating, substance use and neurodevelopmental disorders). NIBS includes Transcranial Magnetic Stimulation (TMS) and transcranial Electrical Stimulation (tES). Additionally, Magnetic Seizure Therapy (MST) is a non-invasive seizure therapy that is attracting great interest due to its better tolerability and safety profiles compared to electroconvulsive therapy.

While these interventions seem to improve clinical features including cognition and behavioral manifestations, for most of psychiatric disorders the evidence is often heterogeneous, so further demonstrations of efficacy are needed to produce firm guidelines.

This Special issue invites researchers to present brand-new studies on the clinical applications of NIBS interventions in psychiatric disorders to improve clinical features, especially the cognitive dimension. Results from translational research, clinical trial, open-label studies, case reports, protocol studies, reviews or meta-analyses are welcome. Moreover, to improve acknowledges on the neurobiology of these disorders, studies combining NIBS with functional neuroimaging, Event-related-Potential (ERP) paradigms or with electroencephalography (EEG) are welcome. Additionally, studies that further elucidate NIBS mechanism of action and on modeling stimulation parameters (e.g. brand-new strategy including accelerated protocols or High-Definition tDCS) or studies that combine NIBS with psychological treatments or use NIBS as augmentative strategy to the ongoing treatments will be considered of interest.

Dr. Stefano Barlati
Dr. Jacopo Lisoni
Guest Editors

Manuscript Submission Information

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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

  • transcranial magnetic stimulation (TMS)
  • transcranial electrical stimulation (tES)
  • transcranial direct current stimulation (tDCS)
  • transcranial alternating current stimulation (tACS)
  • transcranial random noise stimulation (tRNS)
  • magnetic seizure stimulation (MST)
  • depression
  • schizophrenia
  • obsessive–compulsive disorder and anxiety disorders
  • substance use disorders
  • neurodevelopmental disorders (ADHD, autism)
  • neuroimaging
  • neurophysiology
  • cognition

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Published Papers (10 papers)

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Research

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18 pages, 1486 KiB  
Article
Repetitive Transcranial Magnetic Stimulation for the Treatment of Depression in a Real-World Setting: Findings from a Cohort Study
by Tiziano Prodi, Gabriele Pezzullo, Kevin La Monica, Alberto Priori, Matteo Vismara, Bernardo Dell’Osso and Beatrice Benatti
Brain Sci. 2024, 14(9), 949; https://doi.org/10.3390/brainsci14090949 - 22 Sep 2024
Viewed by 1456
Abstract
Background/Objectives: In the past two decades, significant advancements in neuromodulation techniques have occurred, such as transcranial magnetic stimulation (TMS) for treatment-resistant depression (TRD). According to the assumption that repeated stimulation within a condensed timeframe can yield sustained efficacy, an accelerated protocol may be [...] Read more.
Background/Objectives: In the past two decades, significant advancements in neuromodulation techniques have occurred, such as transcranial magnetic stimulation (TMS) for treatment-resistant depression (TRD). According to the assumption that repeated stimulation within a condensed timeframe can yield sustained efficacy, an accelerated protocol may be more effective in reducing time to response. With those premises, this study aimed to evaluate a sample of TRD patients treated with standard repetitive TMS (rTMS) and accelerated rTMS (arTMS). Methods: Nine subjects were treated with standard rTMS and 19 with arTMS. Psychometric assessment was made at the baseline and one week, one month, and three months after the treatment. A linear mixed-effect regression was performed along with other appropriate statistical analyses. Results: A significant improvement over time was observed for both depressive and cognitive symptoms. Moreover, considering the reduction in the Montgomery–Asberg Depression Rating Scale scores, a better treatment response was observed in subjects treated with arTMS (p < 0.05). Conclusions: Our findings showed a significant difference between the two protocols in terms of clinical response. Although further studies are needed to confirm the superiority of arTMS, the better cost-effectiveness of this technique should be considered. Full article
(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives)
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14 pages, 5953 KiB  
Article
Transcutaneous Auricular Vagus Nerve Stimulation Modulating the Brain Topological Architecture of Functional Network in Major Depressive Disorder: An fMRI Study
by Zhi-Peng Guo, Dan Liao, Lei Chen, Cong Wang, Miao Qu, Xue-Yu Lv, Ji-Liang Fang and Chun-Hong Liu
Brain Sci. 2024, 14(9), 945; https://doi.org/10.3390/brainsci14090945 - 21 Sep 2024
Viewed by 899
Abstract
Background: Transcutaneous auricular vagus nerve stimulation (taVNS) is effective in regulating mood and high-level cognition in patients with major depressive disorder (MDD). This study aimed to investigate the efficacy of taVNS treatment in patients with MDD and an altered brain topological organization of [...] Read more.
Background: Transcutaneous auricular vagus nerve stimulation (taVNS) is effective in regulating mood and high-level cognition in patients with major depressive disorder (MDD). This study aimed to investigate the efficacy of taVNS treatment in patients with MDD and an altered brain topological organization of functional networks. Methods: Nineteen patients with MDD were enrolled in this study. Patients with MDD underwent 4 weeks of taVNS treatments; resting-state functional magnetic resonance imaging (rs-fMRI) data of the patients were collected before and after taVNS treatment. The graph theory method and network-based statistics (NBS) analysis were used to detect abnormal topological organizations of functional networks in patients with MDD before and after taVNS treatment. A correlation analysis was performed to characterize the relationship between altered network properties and neuropsychological scores. Results: After 4 weeks of taVNS treatment, patients with MDD had increased global efficiency and decreased characteristic path length (Lp). Additionally, patients with MDD exhibited increased nodal efficiency (NE) and degree centrality (DC) in the left angular gyrus. NBS results showed that patients with MDD exhibited reduced connectivity between default mode network (DMN)–frontoparietal network (FPN), DMN–cingulo-opercular network (CON), and FPN–CON. Furthermore, changes in Lp and DC were correlated with changes in Hamilton depression scores. Conclusions: These findings demonstrated that taVNS may be an effective method for reducing the severity of depressive symptoms in patients with MDD, mainly through modulating the brain’s topological organization. Our study may offer insights into the underlying neural mechanism of taVNS treatment in patients with MDD. Full article
(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives)
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21 pages, 2267 KiB  
Article
Intermittent Theta Burst Stimulation Combined with Cognitive Training to Improve Negative Symptoms and Cognitive Impairment in Schizophrenia: A Pilot Study
by Alessandra Vergallito, Camilla Gesi and Sara Torriero
Brain Sci. 2024, 14(7), 683; https://doi.org/10.3390/brainsci14070683 - 8 Jul 2024
Viewed by 1075
Abstract
Schizophrenia is a chronic psychiatric disorder severely affecting patients’ functioning and quality of life. Unlike positive symptoms, cognitive impairment and negative symptoms cannot be treated pharmacologically and represent consistent predictors of the illness’s prognosis. Cognitive remediation (CR) interventions have been applied to target [...] Read more.
Schizophrenia is a chronic psychiatric disorder severely affecting patients’ functioning and quality of life. Unlike positive symptoms, cognitive impairment and negative symptoms cannot be treated pharmacologically and represent consistent predictors of the illness’s prognosis. Cognitive remediation (CR) interventions have been applied to target these symptoms. Brain stimulation also provides promising yet preliminary results in reducing negative symptoms, whereas its effect on cognitive impairment remains heterogeneous. Here, we combined intermittent theta burst stimulation (iTBS) with CR to improve negative symptoms and cognitive impairment in schizophrenia spectrum patients. One hundred eligible patients were invited, and twenty-one participated. We randomized them into four groups, manipulating the stimulation condition (real vs. sham) and CR (no training vs. training). We delivered fifteen iTBS sessions over the left dorsolateral prefrontal cortex for three weeks, followed (or not) by 50 min of training. Consensus-based clinical and cognitive assessment was administered at baseline and after the treatment, plus at three follow-ups occurring one, three, and six months after the intervention. Mixed-model analyses were run on cognitive and negative symptom scores. The preliminary findings highlighted a marginal modulation of iTBS on negative symptoms, whereas CR improved isolated cognitive functions. We herein discuss the limitations and strengths of the methodological approach. Full article
(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives)
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8 pages, 1064 KiB  
Article
Inhibition of Acute mGluR5-Dependent Depression in Hippocampal CA1 by High-Frequency Magnetic Stimulation
by Norman Holl, Marco Heerdegen, Volker Zschorlich, Rüdiger Köhling and Timo Kirschstein
Brain Sci. 2024, 14(6), 603; https://doi.org/10.3390/brainsci14060603 - 14 Jun 2024
Viewed by 817
Abstract
High-frequency magnetic stimulation (HFMS) applied directly to the hippocampal slice preparation in vitro induces activity-dependent synaptic plasticity and metaplasticity. In addition, changes in synaptic transmission following HFMS involve the activation of N-methyl-D-aspartate and metabotropic glutamate receptors (mGluR). Here, we asked whether a short [...] Read more.
High-frequency magnetic stimulation (HFMS) applied directly to the hippocampal slice preparation in vitro induces activity-dependent synaptic plasticity and metaplasticity. In addition, changes in synaptic transmission following HFMS involve the activation of N-methyl-D-aspartate and metabotropic glutamate receptors (mGluR). Here, we asked whether a short period of HFMS (5 × 10 delta-burst trains, duration of ~1 min) could alter mGluR5-mediated depression at Schaffer collateral–CA1 synapses in the acute brain slice preparation at 30 min after HFMS. To this end, we obtained field excitatory postsynaptic potential (fEPSP) slopes from Schaffer collateral–CA1 synapses after HFMS or control. First, we demonstrated that activity-dependent plasticity following HFMS depends on the slice orientation towards the magnetic coil indicating specific ion fluxes induced by magnetic fields. Second, we found that the mGluR5-specific agonist (RS)-2-chloro-5-hydroxyphenylglycine reduced the field excitatory postsynaptic potential (fEPSP) slopes in control slices but rather enhanced them in HFMS-treated slices. In contrast, the compound (S)-3,5-dihydroxyphenylglycine acting at both mGluR1 and mGluR5 reduced fEPSP slopes in both control and HFMS-treated slices. Importantly, the mGluR-dependent effects were independent from the slice-to-coil orientation indicating that asynchronous glutamate release could play a role. We conclude that a short period of HFMS inhibits subsequently evoked mGluR5-dependent depression at Schaffer collateral–CA1 synapses. This could be relevant for repetitive transcranial magnetic stimulation in psychiatric disorders such as major depression. Full article
(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives)
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12 pages, 596 KiB  
Article
No Consistent Antidepressant Effects of Deep Brain Stimulation of the Bed Nucleus of the Stria Terminalis
by Paul B. Fitzgerald, Kate Hoy, Karyn E. Richardson, Kirsten Gainsford, Rebecca Segrave, Sally E. Herring, Zafiris J. Daskalakis and Richard G. Bittar
Brain Sci. 2024, 14(5), 499; https://doi.org/10.3390/brainsci14050499 - 15 May 2024
Viewed by 1201
Abstract
Background: Applying deep brain stimulation (DBS) to several brain regions has been investigated in attempts to treat highly treatment-resistant depression, with variable results. Our initial pilot data suggested that the bed nucleus of the stria terminalis (BNST) could be a promising therapeutic target. [...] Read more.
Background: Applying deep brain stimulation (DBS) to several brain regions has been investigated in attempts to treat highly treatment-resistant depression, with variable results. Our initial pilot data suggested that the bed nucleus of the stria terminalis (BNST) could be a promising therapeutic target. Objective: The aim of this study was to gather blinded data exploring the efficacy of applying DBS to the BNST in patients with highly refractory depression. Method: Eight patients with chronic severe treatment-resistant depression underwent DBS to the BNST. A randomised, double-blind crossover study design with fixed stimulation parameters was followed and followed by a period of open-label stimulation. Results: During the double-blind crossover phase, no consistent antidepressant effects were seen with any of the four stimulation parameters applied, and no patients achieved response or remission criteria during the blinded crossover phase or during a subsequent period of three months of blinded stimulation. Stimulation-related side effects, especially agitation, were reported by a number of patients and were reversible with adjustment of the stimulation parameters. Conclusions: The results of this study do not support the application of DBS to the BNST in patients with highly resistant depression or ongoing research utilising stimulation at this brain site. The blocked randomised study design utilising fixed stimulation parameters was poorly tolerated by the participants and does not appear suitable for assessing the efficacy of DBS at this location. Full article
(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives)
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12 pages, 1099 KiB  
Article
Individualised Transcranial Magnetic Stimulation Targeting of the Left Dorsolateral Prefrontal Cortex for Enhancing Cognition: A Randomised Controlled Trial
by Donel M. Martin, Yon Su, Ho Fung Chan, Victoria Dielenberg, Esther Chow, Mei Xu, Ashley Wang, Stevan Nikolin, Adriano H. Moffa and Colleen K. Loo
Brain Sci. 2024, 14(4), 299; https://doi.org/10.3390/brainsci14040299 - 22 Mar 2024
Cited by 3 | Viewed by 1877
Abstract
Repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to produce cognitive enhancing effects across different neuropsychiatric disorders; however, so far, these effects have been limited. This trial investigated the efficacy of using a novel individualised approach to target the left dorsolateral prefrontal cortex [...] Read more.
Repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to produce cognitive enhancing effects across different neuropsychiatric disorders; however, so far, these effects have been limited. This trial investigated the efficacy of using a novel individualised approach to target the left dorsolateral prefrontal cortex (L-DLPFC) for enhancing cognitive flexibility based on performance on a cognitive task. First, forty healthy participants had their single target site at the L-DLPFC determined based on each individual’s performance on a random letter generation task. Participants then received, in a cross-over single-blinded experimental design, a single session of intermittent theta burst stimulation (iTBS) to their individualised DLPFC target site, an active control site and sham iTBS. Following each treatment condition, participants completed the Task Switching task and Colour–Word Stroop test. There was no significant main effect of treatment condition on the primary outcome measure of switch reaction times from the Task Switching task [F = 1.16 (2, 21.6), p = 0.33] or for any of the secondary cognitive outcome measures. The current results do not support the use of our novel individualised targeting methodology for enhancing cognitive flexibility in healthy participants. Research into alternative methodological targeting approaches is required to further improve rTMS’s cognitive enhancing effects. Full article
(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives)
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Review

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23 pages, 5435 KiB  
Review
Transcranial Focused Ultrasound Neuromodulation in Psychiatry: Main Characteristics, Current Evidence, and Future Directions
by Ahmadreza Keihani, Claudio Sanguineti, Omeed Chaichian, Chloe A. Huston, Caitlin Moore, Cynthia Cheng, Sabine A. Janssen, Francesco L. Donati, Ahmad Mayeli, Khaled Moussawi, Mary L. Phillips and Fabio Ferrarelli
Brain Sci. 2024, 14(11), 1095; https://doi.org/10.3390/brainsci14111095 - 30 Oct 2024
Viewed by 310
Abstract
Non-invasive brain stimulation (NIBS) techniques are designed to precisely and selectively target specific brain regions, thus enabling focused modulation of neural activity. Among NIBS technologies, low-intensity transcranial focused ultrasound (tFUS) has emerged as a promising new modality. The application of tFUS can safely [...] Read more.
Non-invasive brain stimulation (NIBS) techniques are designed to precisely and selectively target specific brain regions, thus enabling focused modulation of neural activity. Among NIBS technologies, low-intensity transcranial focused ultrasound (tFUS) has emerged as a promising new modality. The application of tFUS can safely and non-invasively stimulate deep brain structures with millimetric precision, offering distinct advantages in terms of accessibility to non-cortical regions over other NIBS methods. However, to date, several tFUS aspects still need to be characterized; furthermore, there are only a handful of studies that have utilized tFUS in psychiatric populations. This narrative review provides an up-to-date overview of key aspects of this NIBS technique, including the main components of a tFUS system, the neuronavigational tools used to precisely target deep brain regions, the simulations utilized to optimize the stimulation parameters and delivery of tFUS, and the experimental protocols employed to evaluate the efficacy of tFUS in psychiatric disorders. The main findings from studies in psychiatric populations are presented and discussed, and future directions are highlighted. Full article
(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives)
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26 pages, 394 KiB  
Review
Is It Possible to Combine Non-Invasive Brain Stimulation and Evidence-Based Psychosocial Interventions in Schizophrenia? A Critical Review
by Jacopo Lisoni, Gabriele Nibbio, Antonio Baglioni, Simona Dini, Bianca Manera, Alessandra Maccari, Luca Altieri, Irene Calzavara-Pinton, Andrea Zucchetti, Giacomo Deste, Stefano Barlati and Antonio Vita
Brain Sci. 2024, 14(11), 1067; https://doi.org/10.3390/brainsci14111067 - 26 Oct 2024
Viewed by 477
Abstract
In schizophrenia, it was suggested that an integrated and multimodal approach, combining pharmacological and non-pharmacological interventions, could improve functional outcomes and clinical features in patients living with schizophrenia (PLWS). Among these alternatives, evidence-based psychosocial interventions (EBPIs) and Non-Invasive Brain Stimulation (NIBS) represent feasible [...] Read more.
In schizophrenia, it was suggested that an integrated and multimodal approach, combining pharmacological and non-pharmacological interventions, could improve functional outcomes and clinical features in patients living with schizophrenia (PLWS). Among these alternatives, evidence-based psychosocial interventions (EBPIs) and Non-Invasive Brain Stimulation (NIBS) represent feasible treatment options targeting the clinical features that are unmet needs of PLWS (especially negative and cognitive symptoms). As no clear evidence is available on the combination of these non-pharmacological approaches, this review aimed to collect the available literature on the combination of EBPIs and NIBS in the treatment of PLWS. We demonstrated that the field of combining EBPIs and NIBS in schizophrenia is in its infancy, as only 11 studies were reviewed. In fact, only a few trials, with divergent results, combined these non-pharmacological modalities; while emerging evidence is available on the combination of cognitive remediation and rTMS/iTBS, inconclusive results were obtained. Conversely, albeit preliminary, more solid findings are available on the combination of HF-rTMS and family intervention. Moreover, despite the fact that cognitive activation could not be considered an EBPI, promising results are available in combination with tDCS to improve the working memory domain. To overcome these limitations, we considered several methodological issues to promote research in this field. Full article
(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives)

Other

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6 pages, 202 KiB  
Brief Report
A Case Series Study of Weekly or Fortnightly Transcranial Magnetic Stimulation (TMS) in Major Depressive Disorder
by Yvonne Turnier-Shea, Gregory M. Peterson, Marzena Rybak and Saxby Pridmore
Brain Sci. 2024, 14(5), 415; https://doi.org/10.3390/brainsci14050415 - 24 Apr 2024
Viewed by 1005
Abstract
Background: Major depressive disorder (MDD) is frequently chronic and relapsing. The use of maintenance or continuation transcranial magnetic stimulation (TMS) has received clinical and some research support. Objective: To conduct a case series study to report the outcomes of once-weekly (OW) or once-fortnightly [...] Read more.
Background: Major depressive disorder (MDD) is frequently chronic and relapsing. The use of maintenance or continuation transcranial magnetic stimulation (TMS) has received clinical and some research support. Objective: To conduct a case series study to report the outcomes of once-weekly (OW) or once-fortnightly (OF) continuation TMS in a real-life setting. Methods: We offered OW or OF TMS sessions to patients with MDD in remission or partial remission/relapse. Results: Ten patients received OW TMS and four received OF TMS, for 8 to 46 weeks. No patients in either group who were in remission or partial remission at baseline experienced a relapse. Improvements in HAMD6 and CGI-S scores were statistically significant or of borderline significance for the total sample and the OW group. Conclusions: This naturalistic, open-label observational study indicates that OW TMS is effective as maintenance therapy in MDD, while also offering some support for OF TMS maintenance in preventing relapse. Full article
(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives)
15 pages, 468 KiB  
Systematic Review
Efficacy of Transcranial Direct Current Stimulation on Pain Level and Disability of Patients with Fibromyalgia: A Systematic Review of Randomized Controlled Trials with Parallel-Group Design
by Anita Azarkolah, Ahmad Ali Noorbala, Sahar Ansari, Amir-Homayun Hallajian and Mohammad Ali Salehinejad
Brain Sci. 2024, 14(1), 26; https://doi.org/10.3390/brainsci14010026 - 25 Dec 2023
Cited by 4 | Viewed by 1865
Abstract
Transcranial direct current stimulation (tDCS) has been increasingly applied in fibromyalgia (FM) to reduce pain and fatigue. While results are promising, observed effects are variable, and there are questions about optimal stimulation parameters such as target region (e.g., motor vs. prefrontal cortices). This [...] Read more.
Transcranial direct current stimulation (tDCS) has been increasingly applied in fibromyalgia (FM) to reduce pain and fatigue. While results are promising, observed effects are variable, and there are questions about optimal stimulation parameters such as target region (e.g., motor vs. prefrontal cortices). This systematic review aimed to provide the latest update on published randomized controlled trials with a parallel-group design to examine the specific effects of active tDCS in reducing pain and disability in FM patients. Using the PRISMA approach, a literature search identified 14 randomized controlled trials investigating the effects of tDCS on pain and fatigue in patients with FM. Assessment of biases shows an overall low-to-moderate risk of bias. tDCS was found effective in all included studies conducted in patients with FM, except one study, in which the improving effects of tDCS were due to placebo. We recommended tDCS over the motor and prefrontal cortices as “effective” and “probably effective” respectively, and also safe for reducing pain perception and fatigue in patients with FM, according to evidence-based guidelines. Stimulation polarity was anodal in all studies, and one single-session study also examined cathodal polarity. The stimulation intensity ranged from 1-mA (7.14% of studies) to 1.5-mA (7.14% of studies) and 2-mA (85.7% of studies). In all of the included studies, a significant improvement in at least one outcome variable (pain or fatigue reduction) was observed. Moreover, 92.8% (13 of 14) applied multi-session tDCS protocols in FM treatment and reported significant improvement in their outcome variables. While tDCS is therapeutically effective for FM, titration studies that systematically evaluate different stimulation intensities, durations, and electrode placement are needed. Full article
(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives)
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