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INTRODUCTION: Craving is a multifactorial behavior caused by central circuit imbalance. The proposed treatments involve exercise and reduced food intake. However, the treatments frequently fail. This study aimed to investigate the effect of 10 consecutive sessions of anodal transcranial direct current stimulation over the right dorsolateral prefrontal cortex on food craving and eating consumption of women affected by overweight and obesity. METHODS: A randomized double-blind controlled trial with 50 volunteers was divided into two groups (active-tDCS: n = 25 and sham-tDCS: n = 25). There were a total of 10 consecutive tDCS sessions (2 mA, for 20 min) with an F4 anodal-F3 cathodal montage. We evaluated the effects on eating behavior (food craving, uncontrolled eating, emotional eating, and cognitive restriction), food consumption (calories and macronutrients), and anthropometric and body composition variables (weight, body mass index, waist circumference, and body fat percentage). RESULTS: There were no statistically significant results between groups at the baseline regarding sociodemographic and clinical characteristics. Also, there was no significant interaction between time versus group for any of the variables studied. Treatment with tDCS was well tolerated and there were no serious adverse effects. CONCLUSIONS: In women affected by overweight and obesity with food cravings, 10 sessions of F4 (anodal) and F3 (cathodal) tDCS did not produce changes in eating behavior, food consumption, and anthropometric and body composition.

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Primary progressive aphasia comprises a group of neurodegenerative diseases characterized by progressive speech and language dysfunction. Neuroimaging (structural and functional), biomarkers, and neuropsychological assessments allow for early diagnosis. However, there is no pharmacological treatment for the disease. Speech and language therapy is the main rehabilitation strategy. In this case report, we describe a female patient diagnosed with nonfluent primary progressive aphasia who underwent sessions of high-frequency transcranial magnetic stimulation in the left dorsolateral prefrontal cortex and showed improvement in depression scores, naming tasks in oral and written speech, and comprehension tasks in oral and written discourse.

As afasias progressivas primárias (APP) representam um grupo de doenças neurodegenerativas caracterizadas por disfunção progressiva da fala e da linguagem. A neuroimagem (estrutural e funcional), os biomarcadores e as avaliações neuropsicológicas permitem o diagnóstico precoce. No entanto, não há tratamento farmacológico para a doença. A terapia fonoaudiológica é a principal estratégia de reabilitação. Neste relato de caso, descrevemos uma paciente com diagnóstico de APP não fluente que foi submetida a sessões de estimulação magnética transcraniana de alta frequência no córtex pré-frontal dorsolateral esquerdo e apresentou melhora nos escores de depressão, nas tarefas de nomeação da fala oral e escrita e nas tarefas de compreensão da fala oral e escrita.

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Objective: Transcranial direct current stimulation (tDCS) has mixed effects for major depressive disorder (MDD) symptoms, partially owing to large inter-experimental variability in tDCS protocols and their correlated induced electric fields (E-fields). We investigated whether the E-field strength of distinct tDCS parameters was associated with antidepressant effect. Methods: A meta-analysis was performed with placebo-controlled clinical trials of tDCS enrolling MDD patients. PubMed, EMBASE, and Web of Science were searched from inception to March 10, 2023. Effect sizes of tDCS protocols were correlated with E-field simulations (SimNIBS) of brain regions of interest (bilateral dorsolateral prefrontal cortex [DLPFC] and bilateral subgenual anterior cingulate cortex [sgACC]). Moderators of tDCS responses were also investigated. Results: A total of 20 studies were included (21 datasets, 1,008 patients), using 11 distinct tDCS protocols. Results revealed a moderate effect for MDD (g = 0.41, 95%CI 0.18-0.64), while cathode position and treatment strategy were found to be moderators of response. A negative association between effect size and tDCS-induced E-field magnitude was seen, with stronger E-fields in the right frontal and medial parts of the DLPFC (targeted by the cathode) leading to smaller effects. No association was found for the left DLPFC and the bilateral sgACC. An optimized tDCS protocol is proposed. Conclusions: Our results highlight the need for a standardized tDCS protocol in MDD clinical trials. Registration number: PROSPERO CRD42022296246.

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OBJECTIVE: Transcranial direct current stimulation (tDCS) has mixed effects for major depressive disorder (MDD) symptoms, partially owing to large inter-experimental variability in tDCS protocols and their correlated induced electric fields (E-fields). We investigated whether the E-field strength of distinct tDCS parameters was associated with antidepressant effect. METHODS: A meta-analysis was performed with placebo-controlled clinical trials of tDCS enrolling MDD patients. PubMed, EMBASE, and Web of Science were searched from inception to March 10, 2023. Effect sizes of tDCS protocols were correlated with E-field simulations (SimNIBS) of brain regions of interest (bilateral dorsolateral prefrontal cortex [DLPFC] and bilateral subgenual anterior cingulate cortex [sgACC]). Moderators of tDCS responses were also investigated. RESULTS: A total of 20 studies were included (21 datasets, 1,008 patients), using 11 distinct tDCS protocols. Results revealed a moderate effect for MDD (g = 0.41, 95%CI 0.18-0.64), while cathode position and treatment strategy were found to be moderators of response. A negative association between effect size and tDCS-induced E-field magnitude was seen, with stronger E-fields in the right frontal and medial parts of the DLPFC (targeted by the cathode) leading to smaller effects. No association was found for the left DLPFC and the bilateral sgACC. An optimized tDCS protocol is proposed. CONCLUSION: Our results highlight the need for a standardized tDCS protocol in MDD clinical trials.

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Around 30% of the general population experience subjective tinnitus, characterized by conscious attended awareness perception of sound without an external source. Clinical distress tinnitus is more than just experiencing a phantom sound, as it can be highly disruptive and debilitating, leading those affected to seek clinical help. Effective tinnitus treatments are crucial for psychological well-being, but our limited understanding of the underlying neural mechanisms and a lack of a universal cure necessitate further treatment development. In light of the neurofunctional tinnitus model predictions and transcranial electrical stimulation, we conducted an open-label, single-arm, pilot study that utilized high-definition transcranial direct current stimulation (HD-tDCS) concurrent with positive emotion induction (PEI) techniques for ten consecutive sessions to down-regulate tinnitus negative valence in patients with clinical distress tinnitus. We acquired resting-state functional magnetic resonance imaging scans of 12 tinnitus patients (7 females, mean age = 51.25 ± 12.90 years) before and after the intervention to examine resting-state functional connectivity (rsFC) alterations in specific seed regions. The results showed reduced rsFC at post-intervention between the attention and emotion processing regions as follows: (1) bilateral amygdala and left superior parietal lobule (SPL), (2) left amygdala and right SPL, (3) bilateral dorsolateral prefrontal cortex (dlPFC) and bilateral pregenual anterior cingulate cortex (pgACC), and (4) left dlPFC and bilateral pgACC (FWE corrected p < 0.05). Furthermore, the post-intervention tinnitus handicap inventory scores were significantly lower than the pre-intervention scores (p < 0.05). We concluded that concurrent HD-tDCS and PEI might be effective in reducing tinnitus negative valence, thus alleviating tinnitus distress.

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Autism spectrum disorder (ASD) is manifested by abnormal cell numbers and patches of gene expression disruption in higher-order brain regions. Here, we investigated whether layer-specific changes in glia/neuron ratios (GNR) characterize patches in the dorsolateral prefrontal cortex (DL-PFC) of children with ASD. We analyzed high-resolution digital images of postmortem human brains from 11 ASD and 11 non-ASD children obtained from the Autism Study of the Allen Human Brain Atlas. We found the GNR is overall reduced in the ASD DL-PFC. Moreover, layers II-III belonging to patches presented a lower GNR in comparison with layers V-VI. We here provide a new insight into how brain cells are arranged within patches that contributes to elucidate how neurodevelopmental programs are altered in ASD.

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Introduction: Although pharmacological treatment for Attention-Deficit/Hyperactivity Disorder (ADHD) has demonstrated efficacy, several individuals persist in experiencing social and academic impairment. Additionally, the occurrence of significant side effects may render the use of psychotropic medications untenable. However, Transcranial Direct Current Stimulation (tDCS), a non-invasive brain stimulation technique, shows promising results in treating ADHD. Objectives: To investigate the efficacy and safety of tDCS on the performance of children and adolescents with ADHD in neuropsychological tests involving visual attention, visual and verbal working memory, and inhibitory control. Methodology: This study was a triple-blind, randomized, sham-controlled, crossover clinical trial. The intervention consisted of a daily session of tDCS (2 mA) or sham targeting the left dorsolateral prefrontal cortex (L-DLPFC), for 30 min, on five consecutive days. The primary outcome was change in the Visual Attention Test, Fourth Edition (TAVIS-4) before and after each intervention. Subjects were also evaluated pre and post-tDCS using the Digit Span subtest of the Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V), the Developmental Neuropsychological Assessment, Second Edition (NEPSY-II) Inhibiting Response (IR) subtest, and the Corsi Block-Tapping Task. Results: Fifteen individuals were included, and no statistically significant difference was observed when comparing the results of the TAVIS-4, the IR of NEPSY-II, and the intragroup Digit Span subtest of WISC-V undertaken before and after the procedure. Adverse events were mainly self-limiting and transient. The participants did not perceive any benefit from tDCS when measured on the Patient Global Impression of Improvement (PGI-I) Scale. Conclusion: This study did not meet its primary endpoint and found no performance enhancement in any investigated neuropsychological outcomes relating to the intervention group.

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ABSTRACT Primary progressive aphasia comprises a group of neurodegenerative diseases characterized by progressive speech and language dysfunction. Neuroimaging (structural and functional), biomarkers, and neuropsychological assessments allow for early diagnosis. However, there is no pharmacological treatment for the disease. Speech and language therapy is the main rehabilitation strategy. In this case report, we describe a female patient diagnosed with nonfluent primary progressive aphasia who underwent sessions of high-frequency transcranial magnetic stimulation in the left dorsolateral prefrontal cortex and showed improvement in depression scores, naming tasks in oral and written speech, and comprehension tasks in oral and written discourse.

RESUMO As afasias progressivas primárias (APP) representam um grupo de doenças neurodegenerativas caracterizadas por disfunção progressiva da fala e da linguagem. A neuroimagem (estrutural e funcional), os biomarcadores e as avaliações neuropsicológicas permitem o diagnóstico precoce. No entanto, não há tratamento farmacológico para a doença. A terapia fonoaudiológica é a principal estratégia de reabilitação. Neste relato de caso, descrevemos uma paciente com diagnóstico de APP não fluente que foi submetida a sessões de estimulação magnética transcraniana de alta frequência no córtex pré-frontal dorsolateral esquerdo e apresentou melhora nos escores de depressão, nas tarefas de nomeação da fala oral e escrita e nas tarefas de compreensão da fala oral e escrita.

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Non-invasive brain stimulation (NIBS) interventions are promising for the treatment of psychiatric disorders. Notwithstanding, the NIBS mechanisms of action over the dorsolateral prefrontal cortex (DLPFC), a hub that modulates affective and cognitive processes, have not been completely mapped. We aimed to investigate regional cerebral blood flow (rCBF) changes over the DLPFC and the subgenual anterior cingulate cortex (sgACC) of different NIBS protocols using Single-Photon Emission Computed Tomography (SPECT). A factorial, within-subjects, double-blinded study was performed. Twenty-three healthy subjects randomly underwent four sessions of NIBS applied once a week: transcranial direct current stimulation (tDCS), intermittent theta-burst stimulation (iTBS), combined tDCS + iTBS and placebo. The radiotracer 99m-Technetium-ethylene-cysteine-dimer was injected intravenously during the NIBS session, and SPECT neuroimages were acquired after the session. Results revealed that the combination of tDCS + iTBS increased right sgACC rCBF. Cathodal and anodal tDCS increased and decreased DLPFC rCBF, respectively, while iTBS showed no significant changes compared to the placebo. Our findings suggest that the combined protocol might optimize the activity in the right sgACC and encourage future trials with neuropsychiatric populations. Moreover, mechanistic studies to investigate the effects of tDCS and iTBS over the DLPFC are required.

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Empathic abilities have been shown to be linked with brain structural variations. Since psychotherapists constitute a population that tends to display greater empathic abilities, as shown in psychometric differences in cognitive empathy and emotional regulation, we aimed to identify cortical thickness (CT) differences between a group of professional psychotherapists and a control group. In line with the recently emphasized urge to employ more than a single workflow in cortical analyses, we utilized two cortical surface extraction and thickness estimation pipelines-CIVET and FreeSurfer. Eighteen psychotherapists and eighteen controls underwent MRI scanning and completed empathy-related psychometric assessments. We evaluated how CT measures differed between groups and if there was an association with individual empathy-related scores in a series of regions of interest (ROIs). Our analysis with CIVET shows that psychotherapists display a significantly greater CT at a ROI in the left dorsolateral prefrontal cortex (dlPFC; p < 0.05, FDR corrected). With FreeSurfer, a whole-brain vertex-wise analysis identified a statistically significant cluster in the left PFC that partially overlaps with the previous ROI. These results were reinforced by a structural covariance analysis revealing that, in psychotherapists, the left dlPFC ROI seemed to vary independently from the rest of the cortex. These findings are relevant because the dlPFC region importantly participates in the cognitive components of the empathic response, such as emotion regulation and perspective taking. Thus, our findings support the idea that empathic capacity is reflected by brain structural variations while also studying for the first time a sample of subjects for whom empathic responding is crucial in their profession.

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Competitive sports involve physical and cognitive skills. In traditional sports, there is a greater dependence on the development and performance of both motor and cognitive skills, unlike electronic sports (eSports), which depend much more on neurocognitive skills for success. However, little is known about neurocognitive functions and effective strategies designed to develop and optimize neurocognitive performance in eSports athletes. One such strategy is transcranial direct current stimulation (tDCS), characterized as a weak electric current applied on the scalp to induce prolonged changes in cortical excitability. Therefore, our objective is to propose anodal (a)-tDCS as a performance-enhancing tool for neurocognitive functions in eSports. In this manuscript, we discussed the neurocognitive processes that underlie exceptionally skilled performances in eSports and how tDCS could be used for acute modulation of these processes in eSports. Based on the results from tDCS studies in healthy people, professional athletes, and video game players, it seems that tDCS is applied over the left dorsolateral prefrontal cortex (DLPFC) as a potential performance-enhancing tool for neurocognition in eSports.

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Attention Deficit Hyperactivity Disorder (ADHD) is a common neuropsychiatric disorder in which children present prefrontal cortex (PFC) related functions deficit. Proactive cognitive control is a process that anticipates the requirement of cognitive control and crucially depends on the maturity of the PFC. Since this process is important to ADHD symptomatology, we here test the hypothesis that children with ADHD have proactive cognitive control impairments and that these impairments are reflected in the PFC oscillatory activity. We recorded EEG signals from 29 male children with ADHD and 25 typically developing (TD) male children while they performed a Go-Nogo task, where the likelihood of a Nogo stimulus increased while a sequence of consecutive Go stimuli elapsed. TD children showed proactive cognitive control by increasing their reaction time (RT) concerning the number of preceding Go stimuli, whereas children with ADHD did not. This adaptation was related to modulations in both P3a potential and lateral prefrontal theta oscillation for TD children. Children with ADHD as a group did not demonstrate either P3a or theta modulation. But, individual variation in theta activity was correlated with the ADHD symptomatology. The results depict a neurobiological mechanism of proactive cognitive control impairments in children with ADHD.

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Children with ADHD show significant deficits in response inhibition. A leading hypothesis suggests prefrontal hypoactivation as a possible cause, though, there is conflicting evidence. We tested the hypoactivation hypothesis by analyzing the response inhibition process within the oculomotor system. Twenty-two children diagnosed with ADHD and twenty control (CTRL) children performed the antisaccade task while undergoing an fMRI study with concurrent eye tracking. This task included a preparatory stage that cued a prosaccade (toward a stimuli) or an antisaccade (away from a stimuli) without an actual presentation of a peripheral target. This allowed testing inhibitory control without the confounding activation from an actual response. The ADHD group showed longer reaction times and more antisaccade direction errors. While both groups showed activations in saccade network areas, the ADHD showed significant hyperactivation in the dorsolateral prefrontal cortex during the preparatory stage. No other areas in the saccade network had significant activation differences between groups. Further ADHD group analysis OFF and ON stimulant medication did not show drug-related activation differences. However, they showed a significant correlation between the difference in OFF/ON preparatory activation in the precuneus, and a decrease in the number of antisaccade errors. These results do not support the hypoactivity hypothesis as an inhibitory control deficit general explanation, but instead suggest less efficiency during the inhibitory period of the antisaccade task in children. Our findings contrast with previous results in ADHD adults showing decreased preparatory antisaccade activity, suggesting a significant age-dependent maturation effect associated to the inhibitory response in the oculomotor system.

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Abstract Objectives Fibromyalgia Syndrome (FMS), is a chronic pain disorder with poorly understood pathophysiology. In recent years, repetitive transcranial magnetic stimulation (rTMS) has been recommended for pain relief in various chronic pain disorders. The objective of the present research was to study the effect of low frequency rTMS over the right dorsolateral prefrontal cortex (DLPFC) on pain status in FMS. Methods Ninety diagnosed cases of FMS were randomized into Sham-rTMS and Real-rTMS groups. Real rTMS (1 Hz/1200 pulses/8 trains/90% resting motor threshold) was delivered over the right DLPFC for 5 consecutive days/week for 4 weeks. Pain was assessed by subjective and objective methods along with oxidative stress markers. Patients were followed up for 6 months (post-rTMS;15 days, 3 months and 6 months). Results In Real-rTMS group, average pain ratings and associated symptoms showed significant improvement post rTMS. The beneficial effects of rTMS lasted up to 6 months in the follow-up phase. In Sham-rTMS group, no significant change in pain ratings was observed. Conclusion Right DLPFC rTMS can significantly reduce pain and associated symptoms of FMS probably through targeting spinal pain circuits and top-down pain modulation . Trial registration: Ref No: CTRI/2013/12/004228.(AU)

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BACKGROUND: Generalized anxiety disorder (GAD) is a common condition with current treatments being only moderately effective. Non-invasive brain stimulation techniques might provide a novel approach for treating GAD. Transcranial direct current stimulation (tDCS) has shown promising efficacy and tolerability for major depression but has not been investigated for GAD yet. Thus, we investigated the effects of tDCS on patients with GAD. METHODS: We conducted a pilot, double-blind, randomized, sham-controlled trial on 30 GAD patients. Five sessions of tDCS (2 mA, 20 min, anode over the left dorsolateral prefrontal cortex and cathode over the right supraorbital cortex) were performed. Anxiety was the primary outcome and it was measured by the Hamilton Anxiety Rating Scale and the Beck Anxiety Inventory. Secondary outcomes were accessed by the Lipp Inventory of Stress Symptoms for Adults, Positive and Negative Affect Schedule, and the Beck Depression Inventory (BDI). Data were examined at baseline, after the 5th day of intervention, and at 1-week follow-up. RESULTS: Thirty patients finished the study. There were no significant improvements in anxiety, mood symptoms of stress, affectivity or depression. Anodal stimulation of the left DLPFC showed significant improvements in physical symptoms of stress in GAD patients. LIMITATIONS: Additional tDCS sessions could have resulted in larger tDCS effects. CONCLUSION: Five sessions of anodal tDCS over the DLPFC did not improve the main outcomes for GAD patients, although physical symptoms of stress were improved. The role of tDCS in GAD should be explored in larger patient samples using different parameters.

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BACKGROUND/AIM: Although individuals with substance use disorder (SUD) are at high risk of committing suicide, most studies of postmortem gene expression exclude subjects with SUD due to the potential confounding effect of drugs in the transcriptome. Thus, little is known about the gene expression profile in suicides with SUD. The identification of altered biological processes in suicides with SUD is crucial in the comprehension of the interaction between both pathologies. METHODS: We evaluated the gene expression profile in the dorsolateral prefrontal area of suicides and nonsuicides with and without SUD by microarrays. RESULTS: We identified 222 differentially expressed genes, predominately enriched in cell proliferation in the comparison between suicides with and without SUD. When comparing the transcriptome of suicides with SUD to nonsuicides with SUD, we identified 550 differentially expressed genes, mainly enriched in oxidative phosphorylation. Differentially expressed genes (1,417) between suicides and nonsuicides without SUD were detected. Most of them were related to mitochondrial function. CONCLUSION: Interaction between suicide and SUD seems to influence the expression of genes involved in glial proliferation and glutamatergic neurotransmission. These results highlight, for the first time, that suicides with SUD have a gene expression profile distinct from that of subjects with only one of these disorders.

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AIM OF THE STUDY: Previous studies have shown that several cortical regions are involved in temporal tasks in multiple timescales. However, the hemispheric predominance of the dorsolateral prefrontal cortex (DLPFC) during time reproduction after repetitive low-frequency transcranial magnetic stimulation (rTMS) is relatively unexplored. Here, we study the effects of 1 Hz rTMS and sham stimulation applied medially over the superior parietal cortex (SPC) on the DLPFC alpha and beta band asymmetry and on time reproduction. MATERIALS AND METHODS: For this purpose, we have combined rTMS with electroencephalography in 20 healthy subjects who performed the time reproduction task in two conditions (sham and 1 Hz). RESULTS: The worst performance was observed in sham and 1Hz conditions for longer time intervals (p < .05), with the 1Hz condition subjects sub-reproducing the time interval, closer to the target interval (p < .05). The right DLPFC hemispheric predominance was found in both conditions, but after low-frequency rTMS, the right hemisphere predominance increased in the 1Hz condition (p < .05). CONCLUSIONS: Results of this study suggest that rTMS applied over the SPC influences time interval interpretation and the DLPFC functions. Future studies would explore the effects of the rTMS application to other cortical areas, and study how it influences time interval interpretation.

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Background: Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) has been investigated as additional therapeutic tool for drug use disorder. In a previous study, we showed that five sessions of tDCS applied bilaterally over the dorsolateral prefrontal cortex (dlPFC) reduced craving to the use of crack-cocaine in inpatients from a specialized clinic. In the present study, we examine if an extended number of sessions of the same intervention would reduce craving even further and affect also relapses to crack-cocaine use. Methods: A randomized, double-blind, sham-controlled, clinical trial with parallel arms was conducted (https://clinicaltrials.gov/ct2/show/NCT02091167). Crack-cocaine patients from two private and one public clinics for treatment of drug use disorder were randomly allocated to two groups: real tDCS (5 cm × 7 cm, 2 mA, for 20 min, cathodal over the left dlPFC and anodal over the right dlPFC, n = 19) and sham-tDCS (n = 16). Real or sham-tDCS was applied once a day, every other day, in a total of 10 sessions. Craving was monitored by a 5-item obsessive compulsive drinking scale once a week (one time before, three times during and once after brain stimulation) over about 5 weeks and relapse was monitored after their discharge from clinics for up to 60 days. Results: Craving scores progressively decreased over five measurements in both sham- and real tDCS groups. Corrected Hedges' within-group (initial and final) effect sizes of craving scores were of 0.77 for the sham-tDCS and of 0.97 for the real tDCS group. The between-groups effect size was of 0.34, in favor of the real tDCS group over sham-tDCS group. Relapse rates were high and quite similar between groups in the 30- and 60-days follow-up after discharge from the hospital. Conclusion: Extended repetitive bilateral tDCS over the dlPFC had no add-on effects over regular treatment when considering craving and relapses to the crack-cocaine use in a sample of crack-cocaine patients with severe use disorder. Different tDCS montages targeting other cortical regions and perhaps additional extension of sessions need to be investigated to reach more efficiency in managing craving and relapses to crack-cocaine use.

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Background: Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, has been studied as an adjunctive therapeutic agent for alcohol dependence. In a previous study, we showed that five consecutive sessions of tDCS applied bilaterally over the dorsolateral prefrontal cortex (dlPFC) reduced relapse to the use of alcohol in alcohol use disorder (AUD) outpatients. However, no changes on craving scores were observed. In the present study, we investigated if an extended number of sessions of the same intervention would reduce craving and relapses for alcohol use in AUD inpatients. Methods: Thus, a randomized, double-blind, sham-controlled, clinical trial with parallel arms was conducted (https://clinicaltrials.gov/ct2/show/NCT02091284). AUD patients from two private and one public clinics for treatment of drug dependence were randomly allocated to two groups: real tDCS (5 × 7 cm2, 2 mA, for 20 min, cathodal over the left dlPFC, and anodal over the right dlPFC) and sham-tDCS. Real or sham-tDCS was applied once a day, every other day, in a total of 10 sessions. Craving was monitored by a 5-item obsessive compulsive drinking scale once a week (one time before, three times during and once after brain stimulation) over about 5 weeks. Results: Craving scores progressively decreased over five measurements in both groups but were significantly reduced only in the real tDCS group after treatment. Corrected Hedges' within-group (initial and final) effect sizes of craving scores were of 0.3 for the sham-tDCS and of 1.1 for the real tDCS group. Effect size was 3-fold larger in the real tDCS group. In addition, the between-group analysis on craving score difference was nearly significant, and the effect size was 0.58, in favor for a larger effect in the real tDCS group when compared to sham-tDCS. Furthermore, in a 3-months follow-up after intervention, 72.2% of sham-tDCS group relapsed to the alcohol use whereas 72.7% of tDCS group were abstinent. Conclusions: Multiple sessions of bilateral prefrontal tDCS were well tolerated with no significant adverse events. Thus, extended repetitive bilateral tDCS over the dlPFC is a promising adjunctive clinical tool that could be used to reduce alcohol craving and relapses and facilitate alcoholism cessation.

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BACKGROUND: Bipolar depression (BD) is a highly prevalent condition associated with marked cognitive deficits that persist even in the euthymic phase of the illness. Pharmacological treatments for BD might further aggravate cognitive impairment, highlighting the need of developing interventions that present cognitive safety. In this study, we evaluated the cognitive effects of H1-coil (deep) transcranial magnetic stimulation (TMS) in patients with treatment-resistant bipolar depression. METHODS: Fourty-three patients were randomized to receive 20 sessions of active (55 trains, 18 Hz, 120% resting motor threshold intensity) or sham rTMS within a double-blind, sham-controlled trial. A battery of 20 neuropsychological assessments, grouped in 6 domains (attention and processing speed, working memory and executive function, inhibitory control, language, immediate verbal memory, and long-term verbal memory) was performed at baseline and after 4 and 8 weeks of trial onset. Depressive symptoms were assessed with the 17-item Hamilton Rating Scale for Depression. RESULTS: Cognitive improvement was shown for all cognitive domains. It occurred regardless of intervention group and depression improvement. For the language domain, greater improvement was observed in the sham group over time. No correlations between depression (at baseline or during treatment) and cognitive improvement were found. LIMITATIONS: Absence of healthy control group. CONCLUSION: The results of this exploratory study provide evidence on the cognitive safety of H1-coil TMS for BD patients. Putative pro-cognitive effects of rTMS in BD were not observed and thus should be further investigated.

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