***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Transcranial direct current stimulation ( tDCS ) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation . Anodal tDCS enhances and cathodal stimulation reduces excitability . Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation , while cathodal tDCS hyperpolarises cortical neurones . However , not much is known about the ion channels and receptors involved in these effects . Thus , the impact of the sodium channel blocker carbamazepine , the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested . tDCS- protocol s inducing excitability alterations ( 1 ) only during tDCS and ( 2 ) eliciting long-lasting after-effects were applied after drug administration . Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS . Flunarizine result ed in similar changes . Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation , which elicits no after-effects , but prevented the induction of long-lasting after-effects independent of their direction . These results suggest that , like in other animals , cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation , thus modulating the conductance of sodium and calcium channels . Moreover , they suggest that the after-effects may be NMDA receptor dependent . Since NMDA receptors are involved in neuroplastic changes , the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting . The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS , which may have important future clinical applications Background The lack of efficacy of pharmacological treatments for cognitive and negative symptoms in schizophrenia highlights the need for new interventions . We investigated the effects of tDCS on working memory and negative symptoms in patients with schizophrenia . Method Double-blinded , r and omized , sham-controlled clinical trial , investigating the effects of 10 sessions of tDCS in schizophrenia subjects .  Stimulation used 2 mA , for 20 min , with electrodes of 25 cm2 wrapped in cotton material soaked in saline solution . Anode was positioned over the left DLPFC and the cathode in the contralateral area . Twenty-four participants were assessed at baseline , after intervention and in a three-months follow-up . The primary outcome was the working memory score from MATRICS and the secondary outcome the negative score from PANSS . Data were analyzed using generalized estimating equations . Results We did not find group ∗ time interaction for the working memory ( p = 0.720 ) score or any other cognitive variable ( p > 0.05 ) . We found a significant group ∗ time interaction for PANSS negative ( p < 0.001 , d = 0.23 , CI.95 = −0.59–1.02 ) , general ( p = 0.011 ) and total scores ( p < 0.001 ) . Exploratory analysis of PANSS 5 factors suggests tDCS effect on PANSS negative ( p = 0.012 ) , cognitive ( p = 0.016 ) and depression factors ( p = 0.029 ) . Conclusion The results from this trial highlight the therapeutic effects of tDCS for treatment of persistent symptoms in schizophrenia , with reduction of negative symptoms . We were not able to confirm the superiority of active tDCS over sham to improve working memory performance . Larger sample size studies are needed to confirm these findings Working memory impairment in schizophrenia has been strongly associated with abnormalities in gamma oscillations within the dorsolateral prefrontal cortex ( DLFPC ) . We recently published the first ever study showing that anodal transcranial direct current stimulation ( tDCS ) to the left DLPFC was able to significantly improve working memory in schizophrenia and did so seemingly via restoring normal gamma oscillatory function . Transcranial alternating current stimulation ( tACS ) is a form of electrical brain stimulation that delivers stimulation at a specific frequency and has been shown to entrain endogenous cortical oscillations . Therefore , gamma ( γ ) tACS may be even more effective than tDCS in improving working memory in schizophrenia . In a r and omized repeated- measures study we compared the effects of γ-tACS , tDCS and sham stimulation on the performance of the two back working memory tasks in ten patients with schizophrenia . There was a significant time by stimulation interaction , with tDCS and sham showing trend-level improvements in working memory , while γ-tACS , contrary to our hypothesis , showed no change . The results are discussed in light of posited divergent effects of tACS and tDCS on the pathophysiology of working memory impairment in schizophrenia BACKGROUND Approximately 30 % of patients with schizophrenia experience auditory hallucinations that are refractory to antipsychotic medications . Here , we evaluated the feasibility and efficacy of transcranial alternating current stimulation ( tACS ) that we hypothesized would improve auditory hallucination symptoms by enhancing synchronization between the frontal and temporo-parietal areas of the left hemisphere . METHOD 22 participants were r and omized to one of three arms and received twice daily , 20 min sessions of sham , 10 Hz 2 mA peak-to-peak tACS , or 2 mA tDCS over the course of 5 consecutive days . Symptom improvement was assessed using the Auditory Hallucination Rating Scale ( AHRS ) as the primary outcome measure . The Positive and Negative Syndrome Scale ( PANSS ) and the Brief Assessment of Cognition in Schizophrenia ( BACS ) were secondary outcomes . RESULTS Primary and secondary behavioral outcomes were not significantly different between the three arms . However , effect size analyses show that tACS had the greatest effect based on the auditory hallucinations scale for the week of stimulation ( 1.31 for tACS ; 1.06 and 0.17 , for sham and tDCS , respectively ) . Effect size analysis for the secondary outcomes revealed heterogeneous results across measures and stimulation conditions . CONCLUSIONS To our knowledge , this is the first clinical trial of tACS for the treatment of symptoms of a psychiatric condition . Further studies with larger sample sizes are needed to better underst and the effect of tACS on auditory hallucinations Schizophrenia is characterized by cognitive deficits which persist after acute symptoms have been treated or resolved . Transcranial direct current stimulation ( tDCS ) has been reported to improve cognition and reduce smoking craving in healthy subjects but has not been as carefully evaluated in a r and omized controlled study for these effects in schizophrenia . We conducted a r and omized double-blind , sham-controlled study of the effects of 5 sessions of tDCS ( 2 milliamps for 20minutes ) on cognition , psychiatric symptoms , and smoking and cigarette craving in 37 out patients with schizophrenia or schizoaffective disorder who were current smokers . Thirty subjects provided evaluable data on the MATRICS Consensus Cognitive Battery ( MCCB ) , with the primary outcome measure , the MCCB Composite score . Active compared to sham tDCS subjects showed significant improvements after the fifth tDCS  session in MCCB Composite score ( p=0.008 ) and on the MCCB Working Memory ( p=0.002 ) and Attention-Vigilance ( p=0.027 ) domain scores , with large effect sizes . MCCB Composite and Working Memory domain scores remained significant at Benjamini-Hochberg corrected significance levels ( α=0.05 ) . There were no statistically significant effects on secondary outcome measures of psychiatric symptoms ( PANSS scores ) , hallucinations , cigarette craving , or cigarettes smoked . The positive effects of tDCS on cognitive performance suggest a potential efficacious treatment for cognitive deficits in partially recovered chronic schizophrenia out patients that should be further investigated Negative symptoms are highly relevant in the long-term course of schizophrenia and are an important target domain for the development of novel interventions . Recently , transcranial direct current stimulation ( tDCS ) of the prefrontal cortex has been investigated as a treatment option in schizophrenia . In this proof-of-concept study , 20 schizophrenia patients with predominantly negative symptoms were r and omized to either 10 sessions of add-on active ( 2 mA , 20min ) or sham tDCS ( anode : left DLPFC/F3 ; cathode : right supraorbital/F4 ) . Primary outcome measure was the change in the Scale for the Assessment of Negative Symptoms ( SANS ) sum score ; secondary outcomes included reduction in Positive and Negative Syndrome Scale ( PANSS ) scores and improvement of depressive symptoms , cognitive processing speed , and executive functioning .  Sixteen patients underwent 4 functional connectivity magnetic resonance imaging ( fcMRI ) scans ( pre and post 1st and pre and post 10th tDCS ) to investigate changes in resting state network connectivity after tDCS . Per- protocol analysis showed a significantly greater decrease in SANS score after active ( -36.1 % ) than after sham tDCS ( -0.7 % ) . PANSS sum scores decreased significantly more with active ( -23.4 % ) than with sham stimulation ( -2.2 % ) . Explorative analysis of fcMRI data indicated changes in subgenual cortex and dorsolateral prefrontal cortex ( DLPFC ) connectivity within frontal-thalamic-temporo-parietal networks . The results of this first proof-of-concept study indicate that prefrontal tDCS may be a promising intervention for treatment of schizophrenia with predominant negative symptoms . Large-scale r and omized controlled studies are needed to further establish prefrontal tDCS as novel treatment for negative symptoms in schizophrenia Non-technical summary Inter-individual differences in regional GABA as assessed by magnetic resonance spectroscopy ( MRS ) relate to behavioural variation in humans . However , it is not clear what the relationship is between MRS measures of the concentration of neurotransmitters in a region and synaptic activity . Transcranial magnetic stimulation ( TMS ) techniques provide physiological measures of cortical excitation or inhibition . Here , we investigated the relationship between  MRS and TMS measures of glutamatergic and GABAergic activity  within the same individuals . We demonstrated a relationship between MRS-assessed glutamate levels and a TMS measure of global cortical excitability , suggesting that MRS measures of glutamate do reflect glutamatergic activity . However , there was no clear relationship between MRS-assessed GABA levels and TMS measures of synaptic GABAA or GABAB activity . A relationship was found between MRS-assessed GABA and a TMS protocol with less clearly understood physiological underpinnings . We speculate that this protocol may therefore reflect extrasynaptic GABA tone Electrical brain stimulation ( EBS ) is a trendy new technique used to change brain function and treat neurological , psychiatric and psychological disorders . We were curious whether the published literature , which is dominated by positive results , reflects the experience of research ers using EBS . Specifically , we wanted to know whether research ers are able to reproduce published EBS effects and whether they engage in , but fail to report , question able research practice s. We invited 976 research ers to complete an online survey . We also audited 100 r and omly-selected published EBS papers . A total of 154 research ers completed the survey . Survey respondents had a median of 3 [ 1 to 6 , IQR ] published EBS papers ( 1180 total ) and 2 [ 1 to 3 ] unpublished ones ( 380 total ) . With anodal and cathodal EBS , the two most widely used techniques , 45–50 % of research ers reported being able to routinely reproduce published results . When asked about how study sample size was determined , 69 % of respondents reported using the sample size of published studies , while 61 % had used power calculations , and 32 % had based their decision on pilot data . In contrast , our audit found only 6 papers where power calculations were used and a single paper in which pilot data was used . When asked about question able research practice s , survey respondents were aware of other research ers who selectively reported study outcomes ( 41 % ) and experimental conditions ( 36 % ) , adjusted statistical analysis to optimise results ( 43 % ) , and engaged in other shady practice s ( 20 % ) . Fewer respondents admitted to engaging in these practice s themselves , although 25 % admitted to adjusting statistical analysis to optimize results . There was strong agreement that such practice s should be reported in research papers ; however , our audit found only two such admissions . The present survey confirms that question able research practice s and poor reproducibility are present in EBS studies . The belief that EBS is effective needs to be replaced by a more rigorous approach so that reproducible brain stimulation methods can be devised and applied Over the last decades , the treatment of schizophrenia has shifted fundamentally from a focus on symptom reduction to a focus on recovery and improving aspects of functioning . In this study , we examined the effect of transcranial direct current stimulation ( tDCS ) on social cognitive and nonsocial neurocognitive functions , as well as on electroencephalogram ( EEG ) measures , in individuals with schizophrenia . Thirty-seven individuals with schizophrenia were administered one of three different tDCS conditions ( cathodal , anodal , and sham ) per visit over the course of three visits , with approximately one week between each visit . Order of conditions was r 
    Output:
    
There is preliminary evidence for the possibility that tDCS may improve cognitive deficits in schizophrenia .