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Noninvasive brain stimulation has emerged in the last three decades as a promising treatment for patients with antipsychotic-resistant symptoms of schizophrenia. This review updates the latest progress in the use of noninvasive brain stimulation to treat schizophrenia symptoms.Several recently published randomized-controlled trials support a long-lasting clinical effect of stimulation techniques on schizophrenia symptoms. In addition, efforts have been made in recent months to improve efficacy through several optimization strategies. Studies have tested new parameters of stimulation, such as theta burst stimulation, and alternative cortical or subcortical targets and have reported encouraging results. New forms of electrical stimulations such as alternating and random noise stimulation, have also been studied and have shown clinical and cognitive usefulness for patients. Accelerated stimulation protocols, and prospects could arise with deeper stimulation strategies.Using brain stimulation to treat symptoms of schizophrenia seems promising and the great flexibility of the stimulation parameters leaves much room for developing optimization strategies and improving its effectiveness. Further studies need to identify the optimal parameters to maximize response rate.

Stress is an adaptive response with repercussions on the human health. The dorsolateral prefrontal cortex (DLPFC) is thought to be involved in stress regulation by contributing to limit its biological and behavioral pejorative consequences. Here, to investigate the contribution of the DLPFC in stress response, we applied transcranial Direct Current Stimulation (tDCS) over the DLPFC during acute stress exposure in healthy participants. We hypothesized that active tDCS compared to sham would impact top-down control of the DLPFC on goal-directed behavior and hypothalamo–pituitary–adrenal (HPA) axis activity. In a double-blind sham-controlled study, 30 healthy subjects were randomly allocated to receive either active (2 mA, n = 15) or sham tDCS (n = 15) with the anode over the left DLPFC and the cathode over the right DLFPC. During the 30-min stimulation period, participants faced an experimental acute stress paradigm. Changes in goal-directed behavior were measured with a decision-making task. HPA axis reactivity was assessed by repeated measures of salivary cortisol. Acute stress decreased appetite for immediate reward in the sham group (mean - 4.40%; p = 0.017) whereas no significant effect of stress was observed in the active group. During stress exposure, we observed a significant larger elevation of salivary cortisol (p = 0.045; Cohen's d = 0.431) in the sham tDCS group (+179.8%; Standard error of the mean (SEM) = 20.6) than in the active group (+138.5%; SEM = 14.2). Stimulating the DLPFC using bifrontal tDCS may prevent stress-induced acute effects on both biological and behavioral outcomes.

In recent years noninvasive brain stimulation (NIBS) applications have emerged as a third and novel treatment option alongside psychopharmacology and psychotherapy in the treatment of mental diseases. It is assumed that NIBS could represent a supplement or (in some indications) even replacement to established therapeutic strategies, e.g. in disorders with high resistance to current treatment regimens, such as negative symptoms or cognitive impairments in schizophrenia. Although positive symptoms in schizophrenia can be treated sufficiently with antipsychotic drugs, patients with negative symptoms frequently suffer from persistent lack of impetus, cognitive decline, social withdrawal and loss of global functioning in the activities of daily life; however, in these cases, current treatment strategies exert only moderate effects, and new treatment options are urgently needed. This review article provides a summary of the clinical effects of new electrical NIBS methods, e.g. transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS) for the treatment of negative symptoms in schizophrenia. These new NIBS methods could help restore the disrupted neuronal networks and improve disturbed connectivity, especially of the left dorsolateral prefrontal cortex and left temporoparietal junction. Promising results are reported for the treatment of negative symptoms with tDCS, tACS and tRNS and could thus represent new therapeutic options in the treatment of schizophrenia.Über die letzten Jahre entwickelten sich Neuromodulationsverfahren zu einer dritten Säule neben Pharmakotherapie und Psychotherapie in der Behandlung psychischer Erkrankungen. Besonders in der Behandlung von Menschen mit einer Schizophrenie könnten Hirnstimulationsverfahren eine Alternative oder Ergänzung zu den etablierten Therapiestrategien darstellen. Die meist vorhandenen Positivsymptome können zumeist mit Antipsychotika adäquat behandelt werden. Gerade bei Patienten mit Schizophrenie besitzen jedoch Negativsymptome einen überdauernden Krankheitswert und beeinflussen den Verlauf durch globale Antriebsverarmung und beeinträchtigte Kognition im alltäglichen Leben negativ. Dieser Übersichtsartikel stellt eine Zusammenfassung über die verschiedenen nichtinvasiven Hirnstimulationsverfahren transkranielle Gleichstromstimulation (transcranial direct current stimulation, tDCS), Wechselstromstimulation (transcranial alternating current stimulation, tACS) sowie Rauschstromstimulation (transcranial random noise stimulation, tRNS) zur Behandlung der Negativsymptomatik bei Schizophrenie dar. Die neuen transkraniellen Hirnstimulationsverfahren könnten dabei helfen, gestörte neuronale Vernetzungen wieder herzustellen und die Konnektivität vor allem der dorsolateralen präfrontalen Anteile des Kortex zu verbessern. Einige Studien weisen auf eine Verbesserung der Negativsymptome durch Behandlung mit tDCS, tACS bzw. tRNS hin und könnten so neue Therapiemöglichkeiten in der Behandlung der Schizophrenie darstellen.

Objective: Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. The study aims are to discuss the implementation of tES digital trials by performing a systematic scoping review and strategic process mapping, evaluate methodological aspects of tES digital trial designs, and provide Delphi-based recommendations for implementing digital trials using tES.Methods: We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided.Results: The main strengths/opportunities of tES were: (i) non-pharmacological nature (92% of agreement), safety of these techniques (80%), affordability (88%), and potential scalability (78%). As for weaknesses/threats, we listed insufficient supervision (76%) and unclear regulatory status (69%). Many issues related to methodological biases did not reach consensus. Device appraisal showed moderate digitalization readiness, with high safety and potential for trial implementation, but low connectivity.Conclusions: Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; with no consensus about aspects regarding methodological biases. Significance: We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials. (C) 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Background One out of three patients with schizophrenia failed to respond adequately to antipsychotics and continue to experience debilitating symptoms such as auditory hallucinations and negative symptoms. The development of additional therapeutic approaches for these persistent symptoms constitutes a major goal for patients. Here, we develop a randomized-controlled trial testing the efficacy of high-frequency transcranial random noise stimulation (hf-tRNS) for the treatment of resistant/persistent symptoms of schizophrenia in patients with various profiles of symptoms, cognitive deficits and illness duration. We also aim to investigate the biological and cognitive effects of hf-tRNS and to identify the predictors of clinical response. Methods In a randomized, double-blind, 2-arm parallel-group, controlled, multicentre study, 144 patients with schizophrenia and persistent symptoms despite the prescription of at least one antipsychotic treatment will be randomly allocated to receive either active (n = 72) or sham (n = 72) hf-tRNS. hf-tRNS (100–500 Hz) will be delivered for 20 min with a current intensity of 2 mA and a 1-mA offset twice a day on 5 consecutive weekdays. The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left temporoparietal junction. Patients’ symptoms will be assessed prior to hf-tRNS (baseline), after the 10 sessions, and at 1-, 3- and 6-month follow-up. The primary outcome will be the number of responders defined as a reduction of at least 25% from the baseline scores on the Positive and Negative Syndrome Scale (PANSS) after the 10 sessions. Secondary outcomes will include brain activity and connectivity, source monitoring performances, social cognition, other clinical (including auditory hallucinations) and biological variables, and attitude toward treatment. Discussion The results of this trial will constitute a first step toward establishing the usefulness of hf-tRNS in schizophrenia whatever the stage of the illness and the level of treatment resistance. We hypothesize a long-lasting effect of active hf-tRNS on the severity of schizophrenia symptoms as compared to sham. This trial will also have implications for the use of hf-tRNS as a preventive intervention of relapse in patients with schizophrenia. Trial registration ClinicalTrials.gov NCT02744989. Prospectively registered on 20 April 2016

International audience; No abstract available

The safety and efficacy of neuronavigated intermittent theta burst stimulation (iTBS) in patients with bipolar depression has not yet been investigated. We hypothesized the superiority of active iTBS over sham. Twenty-six patients were randomly allocated to receive either active (n=12) or sham (n=14) iTBS. Response and remission rates according to changes in depression MADRS score were high following active iTBS (72% and 42% for response and remission rates, respectively), but no significant difference was found after sham stimulation (42%and 25%). No adverse events were observed. This study revealed the safety and tolerability of twice daily iTBS in patients with bipolar depression. Larger controlled studies are warranted to prove iTBS superiority in treatment-resistant bipolar depression.

Auditory and visual dysfunctions are key pathophysiological features of schizophrenia (Sz). Therefore, remedial interventions that directly target such impairments could potentially drive gains in higher-order cognition (e.g., memory, executive functions, emotion processing), symptoms and functional outcome, in addition to improving sensory abilities in this population. Here, we reviewed available sensory-targeted cognitive training (S-TCT) programs that were investigated so far in Sz patients. Area covered: A systematic review of the literature was conducted following PRISMA guidelines. Twenty-seven relevant records were included. The superiority of S-TCT over control conditions on higher-order cognition measures was repeatedly demonstrated, but mostly lost significance at later endpoints of evaluation. Clinical symptoms and functional outcome were improved in a minority of studies. S-TCT interventions were associated with the relative normalization of several neurobiological biomarkers of neuroplasticity and sensory mechanisms. Expert commentary: S-TCT, although time-intensive, is a cost-efficient, safe and promising technique for Sz treatment. Its efficacy on higher-order cognition opens a critical window for clinical and functional improvement. The biological impact of S-TCT may allow for the identification of therapeutic biomarkers to further precision-medicine. Additional research is required to investigate the long-term effects of S-TCT, optimal training parameters and potential confounding factors associated with the illness.

Background Suicide is a major public health issue and the majority of those who attempt suicide suffer from mental disorders. Beyond psychopharmacotherapy, seizure therapies and noninvasive brain stimulation interventions have been used to treat such patients. However, the effect of these nonpharmacological treatments on the suicidal ideation and incidence of suicidality remains unclear. Here, we aimed to provide an update on the effects of seizure therapies and noninvasive brain stimulation on suicidality. Methods We conducted a systematic review of the literature in the PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Elsevier ScienceDirect, and Wiley Online Library databases using the MeSH terms “Electroconvulsive Therapy”, “Magnetic Seizure Stimulation”, “repetitive Transcranial Magnetic Stimulation”, “transcranial Direct Current Stimulation”, “Cranial Electrostimulation” and “suicide”. We included studies using seizure therapies and noninvasive brain stimulation as a main intervention that evaluated suicidality, regardless of diagnosis. Results Among 1,019 records screened, 26 studies met the inclusion criteria using either electroconvulsive therapy (n = 14), magnetic seizure therapy (n = 2), repetitive transcranial magnetic stimulation (n = 9), or transcranial direct current stimulation (n = 1). We observed that studies reported significant results, suggesting these techniques can be effective on the suicidal dimension of mental health pathologies, but a general statement regarding their efficacy is premature due to limitations. Conclusions Future enquiry is necessary to address methodological limitations and evaluate the long‐term efficacy of these methods both alone and in combination with pharmacotherapy and/or psychotherapy., We provided an update of current evidence on the effects of seizure therapies (electroconvulsive therapy and magnetic seizure therapy) and noninvasive brain stimulations (repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and transcranial electrostimulation) on suicidality. The antisuicidal effect of ECT could be supported, but magnetic seizure therapy, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and transcranial electrostimulation were not consistently recommended for treating suicidality. Long‐term antisuicidal effect of seizure therapies and noninvasive brain stimulations should be further investigated both alone and in combination with pharmacotherapy or psychotherapy.

Background Reality-monitoring process enables to discriminate memories of internally generated information from memories of externally derived information. Studies have reported impaired reality-monitoring abilities in schizophrenia patients with auditory hallucinations (AHs), specifically with an exacerbated externalization bias, as well as alterations in neural activity within frontotemporoparietal areas. In healthy subjects, impaired reality-monitoring abilities have been associated with reduction of the paracingulate sulcus (PCS). The current study aimed to identify neuroanatomical correlates of reality monitoring in patients with schizophrenia. Methods Thirty-five patients with schizophrenia and AHs underwent a reality-monitoring task and a 3D anatomical MRI scan at 1.5 T. PCS lengths were measured separately for each hemisphere, and whole-brain voxel-based morphometry analyses were performed using the Computational Anatomy Toolbox (version 12.6) to evaluate the gray-matter volume (GMV). Partial correlation analyses were used to investigate the relationship between reality-monitoring and neuroanatomical outcomes (PCS length and GMV), with age and intracranial volume as covariates. Results The right PCS length was positively correlated with reality-monitoring accuracy (Spearman’s ρ = 0.431, p = 0.012) and negatively with the externalization bias (Spearman’s ρ = −0.379, p = 0.029). Reality-monitoring accuracy was positively correlated with GMV in the right angular gyrus, whereas externalization bias was negatively correlated with GMV in the left supramarginal gyrus/superior temporal gyrus, in the right lingual gyrus and in the bilateral inferior temporal/fusiform gyri (voxel-level p p Conclusions Reduced reality-monitoring abilities were significantly associated with shorter right PCS and reduced GMV in temporal and parietal regions of the reality-monitoring network in schizophrenia patients with AHs.

The current COVID-19 pandemic is the most severe pandemic of the 21st century, on track to having a rising death toll. Beyond causing respiratory distress, COVID-19 may also cause mortality by way of suicide. The pathways by which emerging viral disease outbreaks (EVDOs) and suicide are related are complex and not entirely understood. We aimed to systematically review the evidence on the association between EVDOs and suicidal behaviors and/or ideation. An electronic search was conducted using five databases: Medline, Embase, Web of Science, PsycINFO and Scopus in April 2020. A rapid systematic review was carried out, which involved separately and independently extracting quantitative data of selected articles. The electronic search yielded 2480 articles, of which 9 met the inclusion criteria. Most of the data were collected in Hong Kong (n = 3) and the USA (n = 3). Four studies reported a slight but significant increase in deaths by suicide during EVDOs. The increase in deaths by suicide was mainly reported during the peak epidemic and in older adults. Psychosocial factors such as the fear of being infected by the virus or social isolation related to quarantine measures were the most prominent factors associated with deaths by suicide during EVDOs. Overall, we found scarce and weak evidence for an increased risk of deaths by suicide during EVDOs. Our results inform the need to orient public health policies toward suicide prevention strategies targeting the psychosocial effects of EVDOs. High-quality research on suicide risk and prevention are warranted during the current pandemic., Highlights • Few studies assessed the association between suicidal behaviors or ideation and emerging viral outbreaks. • The literature reports weak evidence for increased suicide rates during emerging viral outbreaks. • Psychosocial factors are associated with deaths by suicide during emerging viral outbreaks. • Suicide prevention strategies are needed during emerging viral outbreaks.

International audience; Nicotine use, which is mostly done through smoking tobacco, is among the most burdensome comorbidities of schizophrenia. However, the ways in which nicotine affects the cognitive and early sensory alterations found in this illness are still debated. After conducting a systematic literature search, 29 studies were selected. These studies involve individuals with schizophrenia who underwent cognitive and/or early sensory function assessments after acute nicotine administration and include 560 schizophrenia subjects and 346 non-schizophrenia controls. The findings highlight that a single dose of nicotine can improve a range of cognitive functions in schizophrenia subjects, such as attention, working memory, and executive functions, with attention being the most responsive domain. In addition, nicotine can modulate early detection of changes in the sensory environment at both the auditory and visual levels. Nevertheless, effects vary strongly depending on the type of neuropsychological assessment and nicotine intake conditions used in each study. The current findings suggest the need to consider a potential decrease of cognitive and early sensory performance when patients with schizophrenia quit smoking.

International audience; Objective: DSM-5 Substance Use Disorders (SUD) are frequent and debilitating comorbidities displayed by patients with schizophrenia spectrum disorders (SZ). One crucial feature of SUD is drug craving, an intense desire to consume a substance, commonly divided into reward and relief dimensions. Here, we conducted a meta-analysis of studies investigating craving in individuals with both SUD and SZ in order to examine whether these patients exhibit a distinct pattern of craving as compared to patients with SUD without SZ.Method: Meta-analysis based on the PRISMA guidelines.Results: Sixteen relevant publications were identified by a systematic search of databases, which included 1219 individuals (589 SUD-SZ and 630 SUD-without-SZ). Of the 16 studies, 11 focused on tobacco, 3 on cannabis and 2 on cocaine. When considered across all studies, SUD-SZ had significantly higher scores than SUD-without-SZ for global craving with medium effect size (knumber of studies = 16, Zr = 0.20 [0.15, 0.26], equivalent d = 0.41, P < 0.001). Discrete patterns emerged for reward (k = 7, Zr = 0.10 [0.02, 0.17], equivalent d = 0.20, P < 0.05) and relief (k = 7, Zr = 0.25 [0.17, 0.33], d = 0.52, P < 0.001) craving, and the direct comparison revealed a significantly greater effect for relief than reward (χ2(1) = 7.40 P = 0.007).Conclusion: These results suggest that SUD-SZ cases experience higher craving, more specifically for relief, in comparison to patients with SUD-without-SZ. These clinical findings can foster the development of tailored addiction therapies for this specific comorbid population.

Background Transcranial direct current stimulation has shown promising clinical results, leading to increased demand for an evidence-based review on its clinical effects. Objective We convened a team of transcranial direct current stimulation experts to conduct a systematic review of clinical trials with more than 1 session of stimulation testing: pain, Parkinson’s disease motor function and cognition, stroke motor function and language, epilepsy, major depressive disorder, obsessive compulsive disorder, Tourette syndrome, schizophrenia, and drug addiction. Methods Experts were asked to conduct this systematic review according to the search methodology from PRISMA guidelines. Recommendations on efficacy were categorized into Levels A (definitely effective), B (probably effective), C (possibly effective), or no recommendation. We assessed risk of bias for all included studies to confirm whether results were driven by potentially biased studies. Results Although most of the clinical trials have been designed as proof-of-concept trials, some of the indications analyzed in this review can be considered as definitely effective (Level A), such as depression, and probably effective (Level B), such as neuropathic pain, fibromyalgia, migraine, post-operative patient-controlled analgesia and pain, Parkinson’s disease (motor and cognition), stroke (motor), epilepsy, schizophrenia, and alcohol addiction. Assessment of bias showed that most of the studies had low risk of biases, and sensitivity analysis for bias did not change these results. Effect sizes vary from 0.01 to 0.70 and were significant in about 8 conditions, with the largest effect size being in postoperative acute pain and smaller in stroke motor recovery (nonsignificant when combined with robotic therapy). Conclusion All recommendations listed here are based on current published PubMed-indexed data. Despite high levels of evidence in some conditions, it must be underscored that effect sizes and duration of effects are often limited; thus, real clinical impact needs to be further determined with different study designs.

International audience; Background: Evidence suggests that individuals with psychopathy display difficulties to adapt their behavior in accordance with the demands of the environment and show altered performance monitoring. However, studies investigating electrophysiological markers of error monitoring (e.g., the error-related negativity (ERN) and the error-positivity (Pe)) in this population reported mixed results. To explain discrepancies observed between studies, we hypothesized that psychopathy dimensions influence electrophysiological outcomes and we predicted that individuals with impulsive-antisocial features would display abnormal ERN compared to individuals with interpersonal-affective features. Methods: Based on the PRISMA guidelines, we conducted a systematic review and meta-analysis of studies investigating ERN and Pe components in individuals with psychopathy compared to controls. A factorial analysis was undertaken to investigate the role of psychopathy dimensions on ERN. Results: Among the 206 retrieved studies, 15 were included in the meta- analysis. Individuals with psychopathy (n = 817) showed a reduced ERN (Cohen's d = 0.18) and Pe amplitude (d = -0.22) compared to control. The factorial analysis indicates a dissociation regarding the dimensional construct of psychopathy. The impulsive-antisocial dimension was linked to reduced ERN amplitude (d = 0.22) whereas the interpersonal-affective dimension was related to increased ERN amplitude compare to controls (d = -0.17). Conclusion: Individuals with psychopathy displayed abnormal ERN and Pe amplitudes following error commission. In addition, models reported that individuals with psychopathic traits relating more specifically to the interpersonal-affective dimension shows efficient error-monitoring systems and increased ERN component while those with marked impulsive-antisocial dimension displayed decreased ERN and altered performance monitoring.

BackgroundImpairments in self-recognition (i.e. recognition of own thoughts and actions) have been repeatedly shown in individuals with schizophrenia. According to classical clinical characterizations, schizophrenia is included in a continuum encompassing a large range of genetic statuses, psychotic states and symptoms. The current meta-analysis aims to determine whether self-recognition is affected by individuals within the psychosis continuum.MethodThree populations were considered: people with an at-risk mental state for psychosis (ARMS), hallucination-prone individuals and unaffected relatives of patients with schizophrenia. Eleven studies contrasted self-recognition between these three populations (n = 386) and healthy controls (n = 315) and four studies used correlational analysis to estimate comparable effects (n = 629). Eligible studies used experimental paradigms including source-monitoring and self-monitoring.ResultsWe observed significantly reduced self-recognition accuracy in these populations [g = −0.44 (−0.71 to −0.17), p = 0.002] compared to controls. No influence of the type of population, experimental paradigm or study design was observed.ConclusionThe present analysis argues for self-recognition deficits in populations with no full-blown psychotic symptoms represented across the continuum of psychosis.

Background:Based on the observed clinical overlap between obsessive–compulsive disorder (OCD) and schizophrenia (SCZ), both conditions may share, at least in part, common cognitive underpinnings. Among the cognitive deficits that could be involved, it has been hypothesized that patients share a failure in their abilities to monitor their own thoughts (source monitoring), leading to confusion between what they actually did or perceived and what they imagined. Although little is known regarding source-monitoring performances in patients with OCD, numerous studies in patients with SCZ have observed a relationship between delusions and/or hallucinations and deficits in both internal source- and reality-monitoring abilities.Methods:The present work compared source-monitoring performances (internal source and reality monitoring) between patients with OCD (n= 32), patients with SCZ (n= 38), and healthy controls (HC;n= 29).Results:We observed that patients with OCD and patients with SCZ displayed abnormal internal source-monitoring abilities compared to HC. Only patients with SCZ displayed abnormalities in reality monitoring compared to both patients with OCD and HC.Conclusions:Internal source-monitoring deficits are shared by patients with OCD and SCZ and may contribute to the shared cognitive deficits that lead to obsessions and delusions. In contrast, reality-monitoring performance seems to differentiate patients with OCD from patients with SCZ.

BackgroundPrevious studies have shown an elevated risk of psychotic symptoms (PS) and experiences (PEs) among ethnic minority groups, with significant variation between groups. This pattern may be partially attributable to the unfavorable socio-environmental conditions that surround ethnic minority groups. Perceived ethnic discrimination (PED) in particular has been a salient putative risk factor to explain the increased risk.MethodsWe conducted a systematic literature review and meta-analysis to assess the impact of PED on reporting PS/PEs in ethnic minorities. This review abides by the guidelines set forth by Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The included studies were obtained from the databases: Medline, PsycINFO, and Web Of Science. Sub-group analyses were performed assessing the effect of PED in different subtypes of PS, the influence of ethnicity and moderating/mediating factors.ResultsSeventeen studies met the inclusion criteria, and nine were used to conduct the meta-analysis. We found a positive association between PED and the occurrence of PS/PEs among ethnic minorities. The combined odds ratio were 1.77 (95% CI 1.26–2.49) for PS and 1.94 (95% CI 1.42–2.67) for PEs. We found that the association was similar across ethnic groups and did not depend on the ethnic origin of individuals. Weak evidence supported the buffering effects of ethnic identity, collective self-esteem and social support; and no evidence supported the moderating effect of ethnic density. Sensitivity to race-based rejection significantly but only slightly mediated the association.ConclusionThese findings suggest that PED is involved in the increased risk of PS/PEs in ethnic minority populations.

Background Although electroconvulsive therapy (ECT) is a highly effective, safe, and well-tolerated antidepressant treatment for late-life depression (LLD), there is large variability in response rates across individuals. We hypothesized that these variations would be in part explained by the level of vascular risk in this population. We therefore compared response rates to ECT in patients with LLD presenting with or without vascular risk factors (VRF). Methods 52 patients with LLD (age > 55) who received a course of ECT were separated into 2 groups according to the presence of VRF (n = 20) or not (n = 32). Framingham score (10-year risk for developing a coronary heart disease) was calculated for each patient. Our primary outcome was the number of responders to ECT in each group (defined as at least 50% decrease of the Montgomery–Asberg Depression Rating Scale score following ECT course). Scores at the self-rated Beck Depression Inventory are also reported. Results Patients with VRF presented significant lower response rates to ECT (12 out of 20; 60%) than patients without VRF (30 out of 32; 94%; p = 0.004). A negative correlation was found between Framingham score and changes in depression scores pre/post ECT (r = -0.42; p = 0.0039). Limitations Our study was limited by sample size and retrospective design. Conclusion Patients with LLD and VRF showed lower response rates to ECT than those without VRF. The more the VRF increased, the less the antidepressant effect of ECT was observed. Results are discussed in light of the role of apathy in clinical response to ECT.

Objectives: Biological strategies to improve treatment efficacy in clozapine-treated patients are urgently needed. Repetitive transcranial magnetic stimulation (rTMS) merits consideration as intervention for patients with persistent auditory hallucinations (AH) or negative symptoms (NS) not responding sufficiently to clozapine treatment. Methods: Data from 10 international RCTs of rTMS for patients being treated with clozapine were pooled. Two levels of symptomatic response were defined: improvement of >= 20% and >= 50% on study-specific primary endpoint scales. Changes in the positive and negative syndrome scale (PANSS) from baseline to endpoint assessment were also analysed. Results: Analyses of 131 patients did not reveal a significant difference for >= 20% and >= 50% response thresholds for improvement of AH, negative or total symptoms between active and sham rTMS groups. The number needed to treat (NNT) for an improvement in persistent AH was nine following active rTMS. PANSS scores did not improve significantly from baseline to endpoint between active and sham groups in studies investigating NS and AH. Conclusions: rTMS as a treatment for persistent symptoms in clozapine-treated patients did not show a beneficial effect of active compared to sham treatment. For AH, the size of the NNTs indicates a possible beneficial effect of rTMS.

We report here the case of a transcranial magnetic stimulation (TMS)-related seizure observed after an accelerated TMS protocol in a young patient with major depressive disorder. The protocol consisted of delivering 5 sessions per day during 4 consecutive working days over the left dorsolateral prefrontal cortex. Stimulations were delivered at 20 Hz, with 40 trains, train duration of 1.9 seconds, intertrain interval of 12 seconds, and 1560 pulses per session. The event occurred during the third session (out of 5) of the second day (out of 4) into the 26th train (out of 40). Twelve days after the event, new sessions of stimulation (30 sessions of 1 Hz, 6 trains, train duration of 60 seconds, intertrain 30 seconds, 360 stimulations per session) followed by a maintenance protocol (1 session every 2 weeks) were proposed to the patient. This strategy allows us to achieve and maintain remission.

AIM To compare cognitive insight abilities measured with the Beck Cognitive Insight Scale (BCIS) between individuals with an at-risk mental state (ARMS) and healthy controls. METHOD Review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS A search for articles investigating cognitive insight in ARMS in the MEDLINE and ScienceDirect databases revealed five studies including 303 ARMS and 376 controls. Regarding BCIS subscales, ARMS individuals displayed significant higher scores for self-certainty than controls with a small-to-moderate effect size (ESg = 0.45 [0.23;0.67], P

A group of European experts reappraised the guidelines on the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) previously published in 2014 [Lefaucheur et al., Clin Neurophysiol 2014;125:2150-206]. These updated recommendations take into account all rTMS publications, including data prior to 2014, as well as currently reviewed literature until the end of 2018. Level A evidence (definite efficacy) was reached for: high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the painful side for neuropathic pain; HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC) using a figure-of-8 or a Hl-coil for depression; low-frequency (LF) rTMS of contralesional M1 for hand motor recovery in the post-acute stage of stroke. Level B evidence (probable efficacy) was reached for: HF-rTMS of the left M1 or DLPFC for improving quality of life or pain, respectively, in fibromyalgia; HF-rTMS of bilateral M1 regions or the left DLPFC for improving motor impairment or depression, respectively, in Parkinson's disease; HF-rTMS of ipsilesional M1 for promoting motor recovery at the post-acute stage of stroke; intermittent theta burst stimulation targeted to the leg motor cortex for lower limb spasticity in multiple sclerosis; HF-rTMS of the right DLPFC in posttraumatic stress disorder; LF-rTMS of the right inferior frontal gyrus in chronic post-stroke non-fluent aphasia; LF-rTMS of the right DLPFC in depression; and bihemispheric stimulation of the DLPFC combining right-sided LF-rTMS (or continuous theta burst stimulation) and left-sided HF-rTMS (or intermittent theta burst stimulation) in depression. Level A/B evidence is not reached concerning efficacy of rTMS in any other condition. The current recommendations are based on the differences reached in therapeutic efficacy of real vs. sham rTMS protocols, replicated in a sufficient number of independent studies. This does not mean that the benefit produced by rTMS inevitably reaches a level of clinical relevance. (C) 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.

Non-invasive transcranial brain stimulation therapies, such as transcranial direct current stimulation, have been found to improve negative symptoms in schizophrenia. Another new technique is transcranial alternating current stimulation (tACS). Here we report a series of three patient treated with twice-daily 10min prefrontal 40Hz tACS stimulation over ten days. Patients showed an improvement in the Positive and Negative Syndrome Scale, Scale for the Assessment of Negative Symptoms, and subjective well-being. Furthermore, there was an improvement in the Trail Making Test and word fluency. ytACS merits further investigation in the treatment of schizophrenia symptoms.

Auditory hallucinations (AHs) are certainly the most emblematic experiences in schizophrenia, but visual hallucinations (VHs) are also commonly observed in this developmental psychiatric disorder. Notably, several studies have suggested a possible relationship between the clinical variability in hallucinations′ phenomenology and differences in brain development/maturation. In schizophrenia, impairments of the hippocampus, a medial temporal structure involved in mnesic and neuroplastic processes, have been repeatedly associated with hallucinations, particularly in the visual modality. However, the possible neurodevelopmental origin of hippocampal impairments in VHs has never been directly investigated. A classic marker of early atypical hippocampal development is incomplete hippocampal inversion (IHI). In this study, we compared IHI patterns in healthy volunteers, and two subgroups of carefully selected schizophrenia patients experiencing frequent hallucinations: (a) those with pure AHs and (b) those with audio–visual hallucinations (A+VH). We found that VHs were associated with a specific IHI pattern. Schizophrenia patients with A+VH exhibited flatter left hippocampi than patients with pure AHs or healthy controls. This result first confirms that the greater clinical impairment observed in A+VH patients may relate to an increased neurodevelopmental weight in this subpopulation. More importantly, these findings bring crucial hints to better specify the sensitivity period of A+VH-related IHI during early brain development.

OBJECTIVES Depression is a frequent but potentially treatable clinical dimension in patients with schizophrenia spectrum disorders (PWS). However, there is a lack of consensual recommendations regarding the optimal strategy to manage depression in PWS. In this study, we aimed to compare the various proposed strategies to define a core set of valid care recommendations for depression management in PWS. METHODS After a systematic search of the literature, the methodological quality of 10 international guidelines from four continents was compared using a validated guideline appraisal instrument (AGREE II). Key recommendations for the management of depression in PWS were subsequently reviewed and discussed. RESULTS The methodological quality of the guidelines was heterogeneous. Although all guidelines proposed pharmacotherapy, psychosocial interventions were a minor concern. Waiting for antipsychotic effects mostly was recommended during the acute phase of schizophrenia. During the postpsychotic phase of the illness, a switch to a second-generation antipsychotic and/or the adjunction of an antidepressant were the primary recommendations. Cognitive behavioural therapy and other medications were considered with strong variations. CONCLUSIONS Further studies are needed to strengthen the level of evidence for antidepressive approaches in PWS. The inclusion of PWS as stakeholders is also considered to be a major issue for future guideline development.

Most individuals with schizophrenia (SZ) have little to no insight regarding the presence of their illness. Psychoeducational programs are state-of-the-art interventions that consist in delivering stabilized patients with accurate knowledge about their illness and its treatment. Evidence suggests a significant relationship between levels of illness-related knowledge and insight in SZ patients. However, the effect of psychoeducation on these related outcomes needs to be explored further.In this open label study involving 30 French-speaking patients with SZ, we propose to compare levels of knowledge and insight before and after the French P.A.C.T.® psychoeducation program to investigate how this approach affects both outcomes. Knowledge levels were measured with the self-questionnaire "What do I know?". Insight levels were measured using the Scale to Assess Unawareness of Mental Disorder (SUMD). Symptoms were assessed with the Positive And Negative Syndrome Scale (PANSS).A large significant improvement of knowledge was observed (p 0.001; d = 0.77). By contrast, the analysis reported no significant effect of psychoeducation on insight (p = 0.86; d = 0.07). PANSS total scores were significantly decreased after treatment (p = 0.001; d = 0.66).Although the P.A.C.T.® program is a promising tool for improving illness-related knowledge in SZ patients, its use is not sufficient to significantly improve insight levels.

Transcranial direct current stimulation (tDCS) has been proposed as a therapeutic option for treatment-resistant auditory verbal hallucinations (AVH) in schizophrenia. In such cases, repeated sessions of tDCS are delivered with the anode over the left prefrontal cortex and the cathode over the left temporoparietal junction. Despite promising findings, the clinical response to tDCS is highly heterogeneous among patients. Here, we explored baseline differences between responders and nonresponders to frontotemporal tDCS using electric field modeling. We hypothesized that responders would display different tDCS-induced electric field strength in the brain areas involved in AVH compared to nonresponders.Using baseline structural MRI scans of 17 patients with schizophrenia and daily AVH who received 10 sessions of active frontotemporal tDCS, we constructed individual realistic whole brain models estimating electric field strength. Electric field maps were compared between responders (n = 6) and nonresponders to tDCS (n = 11) using an independent two-sample t test. Clinical response was defined as at least a 50% decrease of AVH 1 month after the last tDCS session.Results from the electric field map comparison showed that responders to tDCS displayed higher electric field strength in the left transverse temporal gyrus at baseline compared to nonresponders (T = 2.37; p = 0.016; 32 voxels).These preliminary findings suggested that the strength of the tDCS-induced electric field reaching the left transverse temporal gyrus could play an important role in the response to frontotemporal tDCS. In addition, this work suggests the interest of using electric field modeling to individualize tDCS and increase response rate.

Background: Obsessive-compulsive disorder (OCD) is a severe mental disorder with poor response to the available treatments. Neuroimaging studies have identified dysfunctions within the orbito-fronto-striato-pallido-thalamic network in patients with OCD. Here, we assessed the efficacy and safety of transcranial direct current stimulation (tDCS) applied with the cathode over the orbitofrontal cortex (OFC) and the anode over the right cerebellum to decrease OCD symptoms in patients with treatment-resistant OCD. Methods: In a randomized sham-controlled double-blind study, 21 patients with OCD were assigned to receive ten 20-min sessions (two sessions per day) of either active (2 mA) or sham tDCS. The clinical symptoms were measured using the Yale-Brown Obsessive and Compulsive Scale (YBOCS). Acute effects on the symptoms were measured from baseline to immediately after the 10 tDCS sessions. Long-lasting effects were measured 1 and 3 months after the 10th tDCS session. Results: Compared with the sham tDCS, active tDCS significantly decreased OCD symptoms immediately after the 10th tDCS session (F(1,19) = 5.26, p = 0.03). However, no significant differences were observed between the active and sham groups in terms of changes in YBOCS score or the number of responders one and 3 months after tDCS. Conclusion: Despite significant acute effects, tDCS with the cathode placed over the left OFC and the anode placed over the right cerebellum was not significantly effective in inducing a long-lasting reduction of symptoms in patients with treatment-resistant OCD.

The presence of visual hallucinations in addition to auditory hallucinations (V + AH) is associated with poor prognosis in patients with schizophrenia. However, little consideration has been given to these symptoms and their underlying cognitive bases remain unclear. Based on cognitive models of hallucinations, we hypothesized that V + AH are underpinned by an impairment in reality-monitoring processes. The objective of the present study was to test whether reality-monitoring deficits were associated with V + AH in schizophrenia. This study examined reality-monitoring abilities in two groups of patients with schizophrenia: a group of patients with V + AH (n = 24) and a group of patients with AH only (n = 22). Patients with V + AH were significantly more likely to misremember imagined words as being perceived from an external source, compared to patients with AH only (p = 0.008, d = -0.82). In other words, V + AH patients display a larger externalization bias than patients with AH only. One explanation for these results could be that experiencing hallucinations in two sensory modalities may contribute to increased vividness of mental imagery and, in turn, lead to disruption in reality-monitoring processes. This study helps to refine our understanding of the cognitive processes underlying the presence of both auditory and visual hallucinations in patients with schizophrenia.

BackgroundIndividuals with psychopathic traits display deficits in emotional processing. A key event-related potential component involved in emotional processing is the late positive potential (LPP). In healthy controls, LPP amplitude is greater in response to negative stimuli than to positive or neutral stimuli. In the current study, we aimed to compare LPP amplitudes between individuals with psychopathic traits and control subjects when presented with negative, positive or neutral stimuli. We hypothesized that LPP amplitude evoked by emotional stimuli would be reduced in individuals with psychopathic traits compared to healthy controls.MethodsAfter a systematic review of the literature, we conducted a meta-analysis to compare LPP amplitude elicited by emotional stimuli in individuals with psychopathic traits and healthy controls.ResultsIndividuals with psychopathic traits showed significantly reduced LPP amplitude evoked by negative stimuli (mean effect size = −0.47; 95% CI −0.60 to −0.33; p < 0.005) compared to healthy controls. No significant differences between groups were observed for the processing of positive (mean effect size = −0.15; 95% CI −0.42 to 0.12; p = 0.28) and neutral stimuli (mean effect size = −0.12; 95% CI 0.31 to 0.07; p = 0.21).ConclusionsMeasured by LPP amplitude, individuals with psychopathic traits displayed abnormalities in the processing of emotional stimuli with negative valence whereas processing of stimuli with positive and neutral valence was unchanged as compared with healthy controls.

International audience; Patients with schizophrenia (SZ) display deficits in both basic non-verbal auditory processing and source-monitoring of speech. To date, the contributions of basic auditory deficits to higher-order cognitive impairments, such as source-monitoring, and to clinical symptoms have yet to be elucidated. The aim of this study was to investigate the deficits and relationships between basic auditory functions, source-monitoring performances, and clinical symptom severity in SZ. Auditory processing of 4 psychoacoustic features (pitch, intensity, amplitude, length) and 2 types of source-monitoring (internal and reality monitoring) performances were assessed in 29 SZ and 29 healthy controls. Clinical symptoms were evaluated in patients with the Positive And Negative Syndrome Scale. Compared to the controls, SZ individuals in showed significant reductions in both global basic auditory processing (p < .0005, d = 1.16) and source-monitoring (p < .0005, d = 1.24) abilities. Both deficits correlated significantly in patients and across groups (all p < .05). Pitch processing skills were negatively correlated with positive symptom severity (r = -0.4, p < .05). A step-wise regression analysis showed that pitch discrimination was a significant predictor of source-monitoring performance. These results suggest that cognitive mechanisms associated with the discrimination of basic auditory features are most compromised in patients with source-monitoring disability. Basic auditory processing may index pathophysiological processes that are critical for optimal source-monitoring in schizophrenia and that are involved in positive symptoms.

Summary Objective The Stroop effect performance reflects cognitive resistance to interference. We aimed to investigate the effect of a single transcranial random noise stimulation session (tRNS) applied over the dorsolateral prefrontal cortex (DLPFC) on the semantic Stroop effect and its resting electroencephalography (EEG) correlates (β/α ratio). Methods In a randomized, double-blind study, healthy volunteers were allocated to receive either one session of active tRNS (n = 8) or one session of sham tRNS (n = 11). The anode pad was placed on the scalp over the right-DLPFC and the cathode pad was placed over the left-DLPFC. A computerized adaptation of the French Stroop Color-Word Test (Victoria version) and a resting-state continuous EEG recording were administered before and after the tRNS. Results No significant difference were observed for either Stroop Interference/Congruent (F(1,15) = 0.5, P = .5, BF = .19) or Interference/Cross (F(1,14) = 3.2, P = .1, BF = 0.25) ratios. No significant effect of tRNS was observed on EEG β/α ratios across electrodes (F(5,95) = 0.6, P = .7, BF = 0.59e−05). Under active stimulation, Pearson's tests showed significant correlations with moderate evidence between post–pre differences of Stroop Interference/Congruent and Fz-β/α ratios (r = 0.88, P = .02, BF = 4.05), and Stroop Interference/Crosses and Cz-β/α ratios (r = 0.89, P = .008, BF = 8.25), while the same correlations did not reach significance under sham conditions. Discussion We observed no significant changes in either semantic Stroop task reaction time or its EEG correlates after tRNS. However, we provide the original finding that fronto-central β/α activity becomes related to cognitive resistance to interference when the DLPFC is stimulated with random noise current. The results suggest a potential resynchronization of relevant brain frequency patterns into Stroop-related cortical involvement.

International audience; BACKGROUND: Electroconvulsive therapy (ECT) is one of the most effective treatments for major depressive disorder (MDD), especially in cases of treatment-resistant MDD. Because of their pharmacological profiles, benzodiazepines (BZDs) are suspected to decrease the efficacy of ECT. This study investigated the effect of BZDs on ECT-induced clinical outcomes and ECT course parameters in patients with MDD.METHOD: The impact of BZDs on severity of depression (Montgomery-Asberg Depression Rating Scale scores) and on ECT course parameters (seizure threshold, clinical and electroencephalographic seizure duration) was investigated in 70 patients with MDD who received an ECT course using dose-titration method (22 received concomitant BZDs).RESULTS: Lower remission rates (52.0%) and smaller decreases in Montgomery-Asberg Depression Rating Scale scores were observed in the non-BZD group than in the BZD group (81.2%, P = 0.02). There were no significant differences between the 2 groups regarding seizure duration and seizure threshold.LIMITATIONS: This was a retrospective study. Impact of BZDs on anxiety and cognition was not assessed.CONCLUSIONS: Benzodiazepines increased the clinical efficacy of ECT when delivered using dose-titration method and bitemporal stimulation. Further studied are needed to understand the interaction between BZDs and ECT on clinical outcomes.

Background Obsessive–compulsive disorder (OCD) is a severe mental illness. OCD symptoms are often resistant to available treatments. Abnormalities within the orbitofronto-striato-pallido-thalamic circuitry, especially orbitofrontal cortex (OFC) hyperactivity and cerebellar hypoactivity have been observed in patients. Non-invasive brain stimulation studies have indicated that transcranial direct current stimulation (tDCS) may be a useful alternative to alleviate treatment-resistant symptoms in various neuropsychiatric conditions. Methods In an open-label pilot study, 8 patients with treatment-resistant OCD received 10 sessions (twice a day) of 2 mA tDCS applied with the cathode over the left OFC and the anode over the right cerebellum. OCD (Y-BOCS and OCD-VAS) as well as depressive (MADRS) symptoms were measured 4 times: one time before tDCS and 3 times after (immediately after, 1 and 3 months after the 10th tDCS session). Results We reported a significant 26.4% (± 15.8) decrease of Y-BOCS score (p = 0.002). The beneficial effect lasted during the 3 month follow-up. No effect of tDCS was observed on depressive symptoms. At end point, 5 out of 8 patients had a decrease of ≥ 25%; and 3 out of 8 patients had a decrease of ≥ 35% in Y-BOCS score. tDCS was well tolerated. Conclusion tDCS with the cathode placed over the left OFC combined with the anode placed over the right cerebellum is a suitable and safe approach to decrease OCD symptoms in patients with treatment-resistant OCD. Large scale randomized controlled studies are needed to confirm this promising result.

Some 25% to 30% of patients with schizophrenia report auditory verbal hallucinations (AVHs) that fail to respond adequately to antipsychotic treatments. In such cases, transcranial direct current stimulation (tDCS) has been proposed as a therapeutic option. Here, we aim to provide an exhaustive review of the literature examining the clinical effects of tDCS on AVH in patients with schizophrenia. A systematic search in the PubMed and Web of Science databases yielded 14 results, 7 randomized controlled trials (RCTs) and 7 open-label studies. Among them, 4 RCTs and 7 open-label studies reported a significant reduction of AVH after repeated sessions of tDCS, whereas 3 RCTs did not show any advantage of active tDCS over sham tDCS. Altogether, current studies showed an overall decrease of approximately 26% of AVH after active tDCS and 11% after sham tDCS. One suitable approach to decreasing AVH was to deliver twice-daily sessions of tDCS over 5 consecutive days (10 sessions at 20 minutes each, 2 mA) with the anode over the left dorsolateral prefrontal cortex and the cathode over the left temporoparietal junction. Demographic and clinical parameters such as young age, nonsmoking status, and higher frequencies of AVH occurrence seemed to be predictors of clinical improvement. Further RCTs, with larger sample sizes, are needed to confirm the usefulness of tDCS for AVH.

Recent studies have shown that transcranial direct current stimulation (tDCS) may reduce craving and smoking. However, little is known regarding brain correlates of these behavioral changes. We aimed to evaluate whether 10 sessions of tDCS modulate cigarette consumption, craving and brain reactivity to smoking cues in subjects with tobacco use disorder (TUD). In a double blind parallel-arms study, 29 subjects with TUD who wished to quit smoking were randomly assigned to receive 10 sessions of either active or sham tDCS applied with the anode over the right dorsolateral prefrontal cortex (DLPFC) and a large cathode over the left occipital region. As compared to sham, active tDCS significantly reduced smoking craving and increased brain reactivity to smoking-cues within the right posterior cingulate, as measured with a functional magnetic resonance imaging event-related paradigm. However, we failed to find a significant difference between active and sham groups regarding the self-reported number of cigarettes smoked and the exhaled carbon monoxide during one month. These findings suggested that 10 sessions of tDCS over the right DLPFC may reduce craving by modulating activity within the resisting-to-smoke network but might not be significantly more effective than sham to decrease cigarette consumption.

Summary Objective We aimed to investigate whether the number of sessions delivered within one day influences the acute and long-term effects of transcranial random noise stimulation (tRNS) applied over the dorsolateral prefrontal cortex (DLPFC) on inhibitory control. Methods Thirty-six healthy participants were randomly assigned to receive either (i) 3 active (3A), (ii) 1 active and 2 sham (1A2S) or (iii) 3 sham (3S) tRNS sessions. The 3 tRNS were delivered consecutively in the same half-day separated by 30 min with the anode over the right and the cathode over the left DLPFC. The effects of tRNS on inhibitory control were assessed 5 times using a Go/No Go task: at baseline (T0), after one tRNS session (T1), after the 3 sessions (T3), 1 (D1) and 8 (D8) days after. Results As compared to sham, active tRNS did not acutely modulate accuracy in the Go/No Go task but decreased reaction times at Go trials. At D1, participants who received at least one active tRNS sessions (3A and 1A2S groups) were faster than those who received 3 sessions of sham. At D8, only the participants who received 3 active tRNS sessions were faster to successfully respond to Go trials as compared to sham. Discussion Three active tRNS sessions induced longer effects on reaction times than a single session of active tRNS, compared to sham. These findings suggested that delivering repeated tRNS sessions on the same day induces more sustained effects than delivering a single session.

A single transcranial direct current stimulation (tDCS) session applied over the dorsolateral prefrontal cortex (DLFPC) can be associated with procognitive effects. Furthermore, repeated DLPFC tDCS sessions are under investigation as a new therapeutic tool for a range of neuropsychiatric conditions. A possible mechanism explaining such beneficial effects is a modulation of meso-cortico-limbic dopamine transmission. We explored the spatial and temporal neurobiological effects of bifrontal tDCS on subcortical dopamine transmission during and immediately after the stimulation. In a double blind sham-controlled study, 32 healthy subjects randomly received a single session of either active (20 min, 2 mA; n = 14) or sham (n = 18) tDCS during a dynamic positron emission tomography scan using [11C]raclopride binding. During the stimulation period, no significant effect of tDCS was observed. After the stimulation period, compared with sham tDCS, active tDCS induced a significant decrease in [11C]raclopride binding potential ratio in the striatum, suggesting an increase in extracellular dopamine in a part of the striatum involved in the reward-motivation network. The present study provides the first evidence that bifrontal tDCS induces neurotransmitter release in polysynaptic connected subcortical areas. Therefore, levels of dopamine activity and reactivity should be a new element to consider for a general hypothesis of brain modulation by bifrontal tDCS.

Auditory verbal hallucinations (AVH) in patients with schizophrenia are linked to abnormalities within a large cerebral network including frontal and temporal regions. Whilst abnormalities of frontal speech production and temporal speech perception regions have been extensively studied, alterations of the dorsolateral prefrontal cortex (DLPFC), a region critically involved in the pathophysiology of schizophrenia, have rarely been studied in relation to AVH. Using 1.5 T proton magnetic resonance spectroscopy, this study examined the relationship between right and left DLPFCs N-AcetylAspartate (NAA) levels and the severity of AVH in patients with schizophrenia. Twenty-seven male patients with schizophrenia were enrolled in this study, 15 presented daily treatment-resistant AVH (AVH+) and 12 reported no AVH (no-AVH). AVH+ patients displayed higher NAA levels in the right DLPFC than no-AVH patients (p = 0.033). In AVH+ patients, NAA levels were higher in the right DLPFC than in the left (p = 0.024). No difference between the right and left DLPFC was observed in no-AVH patients. There was a positive correlation between NAA levels in the right DLPFC and the severity of AVH (r = 0.404, p = 0.037). Despite limited by magnetic field strength, these results suggest that AVH may be associated with increased NAA levels in the right DLPFC in schizophrenia.

Auditory verbal hallucinations (AVH) in patients with schizophrenia are associated with abnormal hyperactivity in the left temporo-parietal junction (TPJ) and abnormal connectivity between frontal and temporal areas. Recent findings suggest that fronto-temporal transcranial Direct Current stimulation (tDCS) with the cathode placed over the left TPJ and the anode over the left prefrontal cortex can alleviate treatment-resistant AVH in patients with schizophrenia. However, brain correlates of the AVH reduction are unclear. Here, we investigated the effect of tDCS on the resting-state functional connectivity (rs-FC) of the left TPJ. Twenty-three patients with schizophrenia and treatment-resistant AVH were randomly allocated to receive 10 sessions of active (2 mA, 20 min) or sham tDCS (2 sessions/d for 5 d). We compared the rs-FC of the left TPJ between patients before and after they received active or sham tDCS. Relative to sham tDCS, active tDCS significantly reduced AVH as well as the negative symptoms. Active tDCS also reduced rs-FC of the left TPJ with the left anterior insula and the right inferior frontal gyrus and increased rs-FC of the left TPJ with the left angular gyrus, the left dorsolateral prefrontal cortex and the precuneus. The reduction of AVH severity was correlated with the reduction of the rs-FC between the left TPJ and the left anterior insula. These findings suggest that the reduction of AVH induced by tDCS is associated with a modulation of the rs-FC within an AVH-related brain network, including brain areas involved in inner speech production and monitoring. 42;2

Recent studies have shown heterogeneous results regarding the influence of intensity and duration of motor transcranial direct current stimulation (tDCS) on cortical excitability. In this pilot crossover study including 14 healthy participants, we compared the effects of a single session of anodal-tDCS set with two commonly used durations (20 and 30minutes) and intensities (1 and 2mA) on short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Regardless of the current intensity, 20minutes of tDCS increased SICI (3ms inter-stimulus interval ISI) and decreased ICF (7ms ISI); 30minutes of tDCS did not affect cortical excitability.

Growing evidence has suggested that mindfulness-based interventions (MBIs) could have beneficial effects on the acute phase of depression and on the prevention of depressive relapse or recurrence. Despite growing clinical interest, the effects of MBIs on brain functioning in patients with MDD remain unclear. The aim of this systematic review was to assess the changes in brain functioning associated with MBIs in patients with MDD. A systematic search was conducted, and of the 56 articles found, 8 were eligible. MBIs have modulatory effects on several brain regions implicated in the pathophysiology of MDD, such as the prefrontal cortex, the basal ganglia, the anterior and posterior cingulate cortices, and the parietal cortex. These regions have been implicated in self-awareness, attention and emotion regulation. Some of these findings were consistent with the effects of MBIs observed in healthy subjects and patients with other psychiatric disorders, especially enhanced activity in the frontal and subcortical regions related to the improved somatosensory awareness. Further studies are needed to elucidate the mechanisms of MBIs in MDD.

Background Schizophrenia is a mental disorder with significant socioeconomic burden. Although current pharmacological treatments are effective for treating positive symptoms, medications have little-to-no effect in the treatment of negative symptoms. Objective To assess the efficacy of non-invasive brain stimulation (NIBS) for negative symptoms in schizophrenia in randomized clinical trials (RCTs). Methods A systematic review in Medline and Cochrane Library databases was performed up to May 31, 2017. The primary outcome was Hedges' g for continuous scores in a random-effects model. Heterogeneity was evaluated with the I 2 and χ 2 tests. Publication bias was assessed using Begg's funnel plot. Results 31 RCTs ( n = 1272) were included, most with small-to-modest sample sizes. Both repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) were superior to sham (Hedges' g = 0.19; 95% CI 0.07–0.32; and 0.5; 0.02–0.97, respectively). Only one study evaluated the use of transcutaneous auricular vagus nerve stimulation (taVNS). The funnel plot and Eggers test showed that the risk of publication bias was low. In relation to heterogeneity, we found an I 2 of 0% (p = 0.749) and 51.3% (0.055) for rTMS and tDCS, respectively. Conclusion Both rTMS and tDCS were superior to sham stimulation for ameliorating negative symptoms in schizophrenia. We found no considerable heterogeneity or publication bias in our analysis, corroborating the strength of our findings. Not enough studies on other NIBS techniques, such as taVNS, were found for an isolated analysis. Further RCTs with larger sample sizes are needed to clarify the specific impact of NIBS on negative symptoms in schizophrenia.

There is a lack of consensual tools for evaluating the cognitive side-effects in patients with depression who are treated with electroconvulsive therapy (ECT). The objective of this study was to evaluate the usefulness of the Montreal Cognitive Assessment (MoCA) and of the Mini Mental State Examination (MMSE) to monitor cognitive changes in patients with depression receiving ECT. Cognitive functioning was assessed prospectively in 48 patients with unipolar or bipolar depression before and after an ECT course. ECT-induced cognitive impairments were defined as a decrease of at least 2 points on the MoCA and the MMSE total scores and of at least one point on each sub-score. At baseline, the MoCA detected a higher number of patients with cognitive deficits than the MMSE. After ECT, the MoCA and MMSE total scores were comparable, but the MoCA detected more impairments than did the MMSE for visuo-executive, memory and language subscores. ECT significantly decreased the language capacities but improved the visuo-executive and abstraction performances measured by MoCA. In remitters, the MoCA total score and visuo-executive and abstraction performances were significantly improved, while other cognitive functions remained unchanged. The MoCA is a useful screening tool for monitoring cognitive functioning during an ECT course.