Efficacy of Transcranial Direct Current Stimulation to Improve Insight in Patients With Schizophrenia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND AND HYPOTHESIS: Impaired insight into the illness and its consequences is associated with poor outcomes in schizophrenia. While transcranial direct current stimulation (tDCS) may represent a potentially effective treatment strategy to relieve various symptoms of schizophrenia, its impact on insight remains unclear. To investigate whether tDCS would modulate insight in patients with schizophrenia, we undertook a meta-analysis based on results from previous RCTs that investigated the clinical efficacy of tDCS. We hypothesize that repeated sessions of tDCS will be associated with insight improvement among patients. STUDY DESIGN: PubMed and ScienceDirect databases were systematically searched to identify RCTs that delivered at least 10 tDCS sessions in patients with schizophrenia. The primary outcome was the change in insight score, assessed by the Positive and Negative Syndrome Scale (PANSS) item G12 following active tDCS sessions as opposed to sham stimulation. Effect sizes were calculated for all studies and pooled using a random-effects model. Meta-regression and subgroup analyses were conducted. STUDY RESULTS: Thirteen studies (587 patients with schizophrenia) were included. A significant pooled effect size (g) of -0.46 (95% CI [-0.78; -0.14]) in favor of active tDCS was observed. Age and G12 score at baseline were identified as significant moderators, while change in total PANSS score was not significant. CONCLUSIONS: Ten sessions of active tDCS with either frontotemporoparietal or bifrontal montage may improve insight into the illness in patients with schizophrenia. The effect of this treatment could contribute to the beneficial outcomes observed in patients following stimulation.

Cognitive outcomes after tDCS in schizophrenia patients with prominent negative symptoms: Results from the placebo-controlled STARTS trial.

Cognitive deficits and negative symptoms in schizophrenia are associated with poor functional outcomes and limited in terms of treatment. The Schizophrenia Treatment With Electric Transcranial Stimulation (STARTS) trial has shown efficacy of transcranial direct current stimulation (tDCS) for improving negative symptoms. In this secondary analysis, we investigate its effects on cognitive performance. In STARTS, a double-blinded, sham-controlled, randomized clinical trial, patients were treated with twice-daily, 20-min, 2-mA fronto-temporal tDCS over 5 days or sham-tDCS. In 90 patients, we evaluated the cognitive performance up to 12 weeks post-treatment. We found that active-tDCS showed no beneficial effects over sham-tDCS in any of the tests. Based on a 5-factor cognitive model, improvements of executive functions and delayed memory were observed in favor of sham-tDCS. Overall, the applied active-tDCS protocol, primarily designed to improve negative symptoms, did not promote cognitive improvement. We discuss possible protocol modification potentially required to increase tDCS effects on cognition. ClinicalTrials.gov identifier: NCT02535676.

Transcranial Direct Current Stimulation for Prader-Willi Syndrome.

BACKGROUND: Given the limited therapeutic options for Prader-Willi syndrome (PWS), we conducted an open-label clinical trial to evaluate the effects of transcranial direct current stimulation (tDCS) for hyperphagia, food craving, and aberrant behaviors on this population. METHODS: Twelve subjects with PWS (11-35 years old) were included. The subjects underwent 10 daily 20-minute sessions of tDCS in 2 weeks. The anode was positioned over the left dorsolateral prefrontal cortex, and the cathode over the contralateral region. RESULTS: We observed amelioration of hyperphagic and food craving symptoms (P < 0.05), as well as amelioration of behavioral symptoms measured with the Aberrant Behavior Checklist (P < 0.05). DISCUSSION: To our knowledge, this is the first proof-of-concept trial to report the positive effects of increasing excitability of the left dorsolateral prefrontal cortex, using tDCS, for the behavioral, hyperphagia, and food craving symptoms in PWS, which is a low-cost, well-studied, safe alternative for brain stimulation.

Neural Correlates of Preference: A Transmodal Validation Study.

Liking is one of the most important psychological processes associated with the reward system, being involved in affective processing and pleasure/displeasure encoding. Currently, there is no consensus regarding the combination of physiological indicators which best predict liking, especially when applied to dynamic stimuli such as videos. There is a lack of a standard methodology to assess likeability over time and therefore in assessing narrative and semantic aspects of the stimulus. We developed a time-dependent method to evaluate the physiological correlates of likeability for three different thematic categories, namely: adventure (AV), comedy (CM), and nature landscape (LS). Twenty-eight healthy adults with ages ranging from 18 to 35 years (average: 23.85 years) were enrolled in the study. The participants were asked to provide likeability ratings for videos as they watched them, using a response box. Three 60-s videos were presented, one for each category, in randomized order while the participant's physiological data [electroencephalogram (EEG), electrocardiogram (ECG) and eye tracking (ET)] was recorded. The comedy video (CM) presented the smallest minimum accumulated normalized rating (ANR; p = 0.013) and the LS video presented the highest maximum ANR (p = 0.039). The LS video presented the longest time for first response (p < 0.001) and the AV video presented the shortest time for maximum response (p = 0.016). The LS video had the highest mean likeability rating with 1.43 ± 2.31 points; and the CM video had the lowest with 0.57 ± 1.77. Multiple linear regression models were created to predict the likeability of each video using the following physiological indicators; AV: power in beta band at C4 and P4 (p = 0.004, adj. R 2 = 0.301); CM: alpha power in Fp2 (p = 0.001, adj. R 2 = 0.326) and LS: alpha power in P4, F8, and Fp2; beta power in C4 and P4 and pupil size, (p = 0.002, adj. R 2 = 0.489). Despite its limitations (e.g., using one 1-min video per category) our findings suggest that there is a considerable difference in the psychophysiological correlates of stimuli with different contextual properties and that the use of time-dependent methods to assess videos should be considered as best practices.

Evaluation of the efficacy of transcranial direct current stimulation in the treatment of cognitive symptomatology in the early stages of psychosis: study protocol for a double-blind randomized controlled trial.

BACKGROUND: Cognitive deficits are core symptoms of schizophrenia that occur from the early stages of the disorder. There is reliable evidence that cognitive deficits are associated with outcomes in schizophrenia; thus, early treatment could be particularly important. Studies with different neuromodulation techniques involving subjects with schizophrenia suggest that application of transcranial direct current stimulation (tDCS) with inhibitory stimulation over the left temporo-parietal cortex and excitatory stimulation over the left dorsolateral prefrontal cortex could ameliorate positive, negative, and cognitive symptoms. The aim of the present study protocol is to evaluate the efficacy of tDCS in the treatment of cognitive symptomatology in the early stages of psychosis. METHODS/DESIGN: Seventy patients in the early stages of psychosis will be randomly allocated to receive 20 min of active 2-mA tDCS or sham stimulation once a day for 10 consecutive weekdays. The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left temporo-parietal cortex. Neuropsychological and psychiatric assessments will be performed at baseline and at 1 and 3 months following the end of the intervention (sustained effect). DISCUSSION: The development and utilization of potentially effective neuroenhancement tools such as the non-invasive brain stimulation technique tDCS for the treatment and rehabilitation of cognitive impairment in the early stages of schizophrenia may contribute to improving outcomes of the disorder and eventually provide a further understanding of the nature of the complex and dynamic neural processes underlying those abnormalities. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03071484 . Registered on 7 March 2017.