Hema Nawani

Transcranial direct current stimulation in schizophrenia.

Transcranial direct current stimulation (tDCS) is an upcoming treatment modality for patients with schizophrenia. A series of recent observations have demonstrated improvement in clinical status of schizophrenia patients with tDCS. This review summarizes the research work that has examined the effects of tDCS in schizophrenia patients with respect to symptom amelioration, cognitive enhancement and neuroplasticity evaluation. tDCS is emerging as a safe, rapid and effective treatment for various aspects of schizophrenia symptoms ranging from auditory hallucinations-for which the effect is most marked, to negative symptoms and cognitive symptoms as well. An interesting line of investigation involves using tDCS for altering and examining neuroplasticity in patients and healthy subjects and is likely to lead to new insights into the neurological aberrations and pathophysiology of schizophrenia. The mechanistic aspects of the technique are discussed in brief. Future work should focus on establishing the clinical efficacy of this novel technique and on evaluating this modality as an adjunct to cognitive enhancement protocols. Understanding the mechanism of action of tDCS as well as the determinants and neurobiological correlates of clinical response to tDCS remains an important goal, which will help us expand the clinical applications of tDCS for the treatment of patients with schizophrenia.

Insight facilitation with add-on tDCS in schizophrenia

Impaired insight in schizophrenia patients has been linked with prefrontal deficits. In this open-label study, we examined for potential insight facilitation effects of add-on tDCS (with anodal stimulation of left DLPFC and cathodal stimulation over left temporo-parietal junction) in schizophrenia patients (N=21) with persistent auditory hallucinations despite adequate antipsychotic treatment. Following tDCS, there was a significant improvement in insight with concurrent significant reduction in auditory hallucination severity. Improvement in insight correlated significantly with improvement in severity of auditory hallucinations. These findings suggest improvement of insight with add-on tDCS in schizophrenia with persistent auditory hallucinations.

Monotherapy with tDCS for Schizophrenia: a case report.

positive response to cTBSmight have been related to the association of risperidonewith cTBS orwas primed bya course of low frequency rTMS completed a month before. However, the fact that this patient who suffered fromchronic persistentAVH responded to cTBSbut not to rTMS in addition to the fact that the improvements in her AHRS scores persisted with maintenance cTBS suggest that observed clinical changes were an effect of stimulation by cTBS. The encouraging findings of this case safely treated in a private practice setting aswell as those of the three previously published cases [8,9,10] should be further investigated and confirmed in sufficiently powered placebo-controlled, double-blind studies.

Neural basis of tDCS effects on auditory verbal hallucinations in schizophrenia: a case report evidence for cortical neuroplasticity modulation.

Transcranial direct current stimulation (tDCS) has been reported to ameliorate auditory hallucinations that are nonresponsive/minimally responsive to antipsychotic treatment in schizophrenia. The neurobiological basis of the tDCS effects in ameliorating auditory hallucinations is yet to be explored. In this case report, for the first time, using the novel method for noninvasive assessment of cortical plasticity, we demonstrate potential neuroplasticity effect of tDCS in improving treatment-resistant auditory hallucinations in a schizophrenic patient.

Rapid improvement of auditory verbal hallucinations in schizophrenia after add-on treatment with transcranial direct-current stimulation.

Abstract Treatment of nonresponsive auditory hallucinations in schizophrenia have been reported to improve with transcranial direct-current stimulation. This case description illustrates the use of add-on transcranial direct-current stimulation for rapid amelioration of auditory hallucinations in schizophrenia during the acute phase. Because transcranial direct-current stimulation is safe, largely well tolerated, and relatively inexpensive, this add-on treatment option is worth exploring through further rigorous studies.

S55. MECHANISTIC BASIS OF FRONTO-TEMPORAL TRANSCRANIAL DIRECT CURRENT STIMULATION ON AUDITORY VERBAL HALLUCINATION IN SCHIZOPHRENIA: A MEDIATION ANALYSIS OF COROLLARY DISCHARGE

Abstract Background Corollary discharge (CD), ubiquitous throughout the animal kingdom, refers to suppression of sensory consequences arising from self-generated actions. Complex motor acts like covert/overt speech are associated with corollary discharge that helps in ascertaining agency. Auditory verbal hallucinations (AVH) are hypothesized to originate due to failure of corollary discharge in auditory processing system. Transcranial Direct Current Stimulation (tDCS), as an add-on treatment, has been reported to significantly reduce severity of persistent AVH in schizophrenia patients. In this study, we describe mediation analysis findings that strongly support a role for amelioration of corollary discharge deficits as a mechanistic basis for tDCS effects on AVH in schizophrenia. Methods 27 DSM-IV-TR Schizophrenia patients (SCZ) with persistent AVH despite adequate antipsychotic treatment and 27 healthy controls (HC) underwent neurophysiological assessment for CD. In an event-related potential task, N1 component that reflects cortical responsiveness of auditory cortex to sounds, was elicited and examined in two conditions – i) Talk (with online auricular feedback of self-spoken speech sounds) and ii) Listen (passive playback of recorded self-spoken speech sounds). Corollary discharge index (CDI) was calculated by subtracting Listen condition N1 amplitude from Talk condition N1 amplitude (at FCz). Among these 27 patients, 13 patients participated in a randomized, double-blind, sham-controlled study examining the effect of add-on tDCS on AVH and CDI [5 consecutive days, twice-daily, 20-minute sessions; 2mA; anode: left dorsolateral prefrontal cortex; cathode: left temporo-parietal junction]. Mediation analysis was modelled with tDCS type (Verum vs. Sham) as independent variable, percent change in auditory hallucination rating scale score (AHRS) as dependent variable and percent change in CDI as the mediator. As recommended for small samples, bootstrap estimation approach with 5000 samples was used to examine the indirect effect of independent variable on dependent variable through proposed mediator for significance. Results SCZ (Mean±SD: -0.67 ± 1.93) had significantly deficient CDI than HC (1.36 ± 2.18) (t=3.62; p=0.001). Verum tDCS (32.24 ± 16.48) resulted in greater percentage reduction in AHRS than sham (4.79 ± 8.84) (t=3.64, p=0.004). There was a significant increase in CDI (t=2.48; p=0.03) with verum (0.85 ± 1.08) but not sham (-0.55 ± 0.98) tDCS. Percent change in CDI positively correlated with percent change in AHRS from pre-RCT to post-RCT time-point for the entire sample (N=13; ρ=0.55, p=0.05). Regression analysis showed that tDCS type (verum/sham) was a significant predictor of percent change in AHRS (β=-27.46, p=0.003) as well as percent change in CDI (β=-1.40, p=0.033). Percent change in CDI was a significant predictor of percent change in AHRS (β=8.87, p=0.014). When controlled for percent change in CDI, tDCS type ceased to be a significant predictor of percent change in AHRS (β=-15.0, p=0.063). The predictors accounted for approximately 75% of the variance (R2=0.756, p<0.001). Bootstrap estimation results indicate the coefficient of indirect effect to be significant, β=-12.46, SE=6.92, 95% CI=-31.20, -2.79, and significantly different from zero at p<0.05 (two tailed). Discussion Fronto-temporal tDCS reduces severity of auditory verbal hallucination in schizophrenia possibly through correction of the deficient corollary discharge. Fronto-temporal network is crucial to self-tagging component of auditory processing and has conspicuous implications for auditory verbal hallucination pathophysiology. Trial No. CTRI/2014/12/005307 (Clinical Trials Registry–India)

Enhanced error related negativity amplitude in medication-naïve, comorbidity-free obsessive compulsive disorder

Error monitoring and response inhibition is a key cognitive deficit in obsessive-compulsive disorder (OCD). Frontal midline regions such as the cingulate cortex and pre-supplementary motor area are considered critical brain substrates of this deficit. Electrophysiological equivalent of the above dysfunction is a fronto-central event related potential (ERP) which occurs after an error called the error related negativity (ERN). In this study, we sought to compare the ERN parameters between medication-naïve, comorbidity-free subjects with OCD and healthy controls (HC). Age, sex and handedness matched subjects with medication-naïve, comorbidity-free OCD (N = 16) and Healthy Controls (N = 17) performed a modified version of the flanker task while EEG was acquired for ERN. EEG signals were recorded from the electrodes FCz and Cz. Clinical severity of OCD was assessed using the Yale Brown Obsessive Compulsive Scale. The subjects with OCD had significantly greater ERN amplitude at Cz and FCz. There were no significant correlations between ERN measures and illness severity measures. Overactive performance monitoring as evidenced by enhanced ERN amplitude could be considered as a biomarker for OCD.

Feasibility of online neuromodulation using transcranial alternating current stimulation in schizophrenia

Abnormalities in resting and event-related brain oscillations are known to be associated with cognitive deficits in schizophrenia. Transcranial alternating current stimulation (tACS) modulates these rhythms across the neuronal circuits and could have a potential therapeutic role in psychiatric disorders. In this report, we describe, for the first time, application of online tACS in a schizophrenia patient with working memory deficits. This case report supports the feasibility and potential utility of online tACS in schizophrenia, which needs further systematic research.