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Agarwal S.M.,National Institute of Mental Health and Neuro Sciences | Agarwal S.M.,National Health Research Institute | Bose A.,National Institute of Mental Health and Neuro Sciences | Bose A.,National Health Research Institute | And 17 more authors.
Psychiatry Research | Year: 2016

Transcranial direct current stimulation (tDCS) has generated interest as a treatment modality for schizophrenia. Dopamine, a critical pathogenetic link in schizophrenia, is also known to influence tDCS effects. We evaluated the influence of antipsychotic drug type (as defined by dopamine D2 receptor affinity) on the impact of tDCS in schizophrenia. DSM-IV-TR-diagnosed schizophrenia patients [N=36] with persistent auditory hallucinations despite adequate antipsychotic treatment were administered add-on tDCS. Patients were divided into three groups based on the antipsychotic's affinity to D2 receptors. An auditory hallucinations score (AHS) was measured using the auditory hallucinations subscale of the Psychotic Symptom Rating Scales (PSYRATS). Add-on tDCS resulted in a significant reduction inAHS. Antipsychotic drug type had a significant effect on AHS reduction. Patients treated with high affinity antipsychotics showed significantly lesser improvement compared to patients on low affinity antipsychotics or a mixture of the two. Furthermore, a significant sex-by-group interaction occurred; type of medication had an impact on tDCS effects only in women. Improvement differences could be due to the larger availability of the dopamine receptor system in patients taking antipsychotics with low D2 affinity. Sex-specific differences suggest potential estrogen-mediated effects. This study reports a first-time observation on the clinical utility of antipsychotic drug type in predicting tDCS effects in schizophrenia. © 2015 Elsevier Ireland Ltd.

Kuo H.-I.,University of Gottingen | Paulus W.,University of Gottingen | Batsikadze G.,University of Gottingen | Jamil A.,University of Gottingen | And 4 more authors.
Neuropsychopharmacology | Year: 2016

Serotonin affects memory formation via modulating long-term potentiation (LTP) and depression (LTD). Accordingly, acute selective serotonin reuptake inhibitor (SSRI) administration enhanced LTP-like plasticity induced by transcranial direct current stimulation (tDCS) in humans. However, it usually takes some time for SSRI to reduce clinical symptoms such as anxiety, negative mood, and related symptoms of depression and anxiety disorders. This might be related to an at least partially different effect of chronic serotonergic enhancement on plasticity, as compared with single-dose medication. Here we explored the impact of chronic application of the SSRI citalopram (CIT) on plasticity induced by tDCS in healthy humans in a partially double-blinded, placebo (PLC)-controlled, randomized crossover study. Furthermore, we explored the dependency of plasticity induction from the glutamatergic system via N-methyl-D-aspartate receptor antagonism. Twelve healthy subjects received PLC medication, combined with anodal or cathodal tDCS of the primary motor cortex. Afterwards, the same subjects took CIT (20 mg/day) consecutively for 35 days. During this period, four additional interventions were performed (CIT and PLC medication with anodal/cathodal tDCS, CIT and dextromethorphan (150 mg) with anodal/cathodal tDCS). Plasticity was monitored by motor-evoked potential amplitudes elicited by transcranial magnetic stimulation. Chronic application of CIT increased and prolonged the LTP-like plasticity induced by anodal tDCS for over 24 h, and converted cathodal tDCS-induced LTD-like plasticity into facilitation. These effects were abolished by dextromethorphan. Chronic serotonergic enhancement results in a strengthening of LTP-like glutamatergic plasticity, which might partially explain the therapeutic impact of SSRIs in depression and other neuropsychiatric diseases. © 2016 American College of Neuropsychopharmacology. All rights reserved.

Sellaro R.,Leiden University | Nitsche M.A.,University of Gottingen | Nitsche M.A.,Leibniz Research Center for Working Environment and Human Resources | Nitsche M.A.,University Medical Hospital Bergmannsheil | Colzato L.S.,Leiden University
Annals of the New York Academy of Sciences | Year: 2016

Transcranial direct current stimulation (tDCS) is an increasingly popular noninvasive neuromodulatory tool in the fields of cognitive and clinical neuroscience and psychiatry. It is an inexpensive, painless, and safe brain-stimulation technique that has proven to be effective in modulating cognitive and sensory-perceptual functioning in healthy individuals and clinical populations. Importantly, recent findings have shown that tDCS may also be an effective and promising tool for probing the neural mechanisms of social cognition. In this review, we present the state-of-the-art of the field of tDCS research in social cognition. By doing so, we aim to gather knowledge of the potential of tDCS to modulate social functioning and social decision making in healthy humans, and to inspire future research investigations. © 2016 The New York Academy of Sciences.

Otal B.,Neuroelectrics Barcelona | Dutta A.,Montpellier University | Foerster A.,University of Gottingen | Ripolles O.,Neuroelectrics Barcelona | And 7 more authors.
Frontiers in Neurology | Year: 2016

Stroke is a leading cause of serious long-term disability worldwide. Functional outcome depends on stroke location, severity, and early intervention. Conventional rehabilitation strategies have limited effectiveness, and new treatments still fail to keep pace, in part due to a lack of understanding of the different stages in brain recovery and the vast heterogeneity in the poststroke population. Innovative methodologies for restorative neurorehabilitation are required to reduce long-term disability and socioeconomic burden. Neuroplasticity is involved in poststroke functional disturbances and also during rehabilitation. Tackling poststroke neuroplasticity by non-invasive brain stimulation is regarded as promising, but efficacy might be limited because of rather uniform application across patients despite individual heterogeneity of lesions, symptoms, and other factors. Transcranial direct current stimulation (tDCS) induces and modulates neuroplasticity, and has been shown to be able to improve motor and cognitive functions. tDCS is suited to improve poststroke rehabilitation outcomes, but effect sizes are often moderate and suffer from variability. Indeed, the location, extent, and pattern of functional network connectivity disruption should be considered when determining the optimal location sites for tDCS therapies. Here, we present potential opportunities for neuroimaging-guided tDCS-based rehabilitation strategies after stroke that could be personalized. We introduce innovative multimodal intervention protocols based on multichannel tDCS montages, neuroimaging methods, and real-time closed-loop systems to guide therapy. This might help to overcome current treatment limitations in poststroke rehabilitation and increase our general understanding of adaptive neuroplasticity leading to neural reorganization after stroke. © 2016 Otal, Dutta, Foerster, Ripolles, Kuceyeski, Miranda, Edwards, Ilic, Nitsche and Ruffini.

Batista E.K.,Federal University of Espirito Santo | Klauss J.,Federal University of Espirito Santo | Fregni F.,Harvard University | Fregni F.,Beth Israel Deaconess Medical Center | And 4 more authors.
International Journal of Neuropsychopharmacology | Year: 2015

Background: Transcranial direct current stimulation over the dorsolateral prefrontal cortex has been shown to be clinically useful in the treatment of drug addiction. Methods: We conducted a double-blind randomized clinical trial aiming to assess the effects of bilateral dorsolateral prefrontal cortex transcranial direct current stimulation (left cathodal/right anodal) on crack-cocaine addiction. We defined craving as the primary outcome, and other clinical measurements, including depressive and anxiety symtoms, and quality of life, as secondary outcomes. Seventeen male crack-cocaine users (mean age 30.4 ± 9.8 SD) were randomized to receive 5 sessions of active transcranial direct current stimulation (2 mA, 35 cm2, for 20 minutes), every other day, and 19 males (mean age 30.3 ± 8.4 SD) to receive sham-transcranial direct current stimulation (placebo) as control group. Results: Craving scores were significantly reduced in the transcranial direct current stimulation group after treatment when compared with sham-transcranial direct current stimulation (P = .028) and baseline values (P = .003), and decreased linearly over 4 weeks (before, during, and after treatment) in the transcranial direct current stimulation group only (P = .047). Changes of anxiety scores towards increase in the sham-transcranial direct current stimulation and decrease in the transcranial direct current stimulation group (P = .03), and of the overall perception of quality of life (P = .031) and of health (P = .048) towards decrease in the sham-transcranial direct current stimulation group and increase in the transcranial direct current stimulation group differed significantly between groups. Conclusions: Repetitive bilateral transcranial direct current stimulation over the dorsolateral prefrontal cortex reduced craving for crack-cocaine use, decreased anxiety, and improved quality of life. We hypothesize that transcranial direct current stimulation effects may be associated with increased prefrontal processing and regulation of craving behavior. © The Author 2015.

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