Development, validation and clinical utility of short-term adverse-effects of electroconvulsive therapy (SAVE) checklist.

Electroconvulsive therapy (ECT) is one of the most effective treatments in psychiatry. However, it has many cognitive and non-cognitive adverse effects (AEs). There are lacunae in the literature on systematic assessment of non-cognitive AEs. There is a need for a standard, comprehensive and specific clinical tool to evaluate this. Hence, a checklist of short-term AEs of ECT (SAVE) with a 2-phase assessment was developed. Content validation was done using 15 experts' ratings and predefined content validity ratio and index (CVR and CVI) in a two-stage modified Delphi method. The checklist had a good CVR and CVI with a final tool of 39 items. The tool was sensitive and identified the non-cognitive AEs after ECT. Cardiovascular and musculoskeletal systems displayed the highest incidence. Many participants exhibited delayed recovery in orientation, gait, and stance, highlighting a necessity for meticulous monitoring. SAVE is the first standardised tool to assess short-term ECT-related AEs systematically. This checklist likely identifies clinically significant incidences of adverse effects. Its regular use may enhance the safety of ECT and patient comfort by supporting early identification and intervention for AEs. However, given the transient nature of AEs, further studies are needed to determine their predictive validity for long-term consequences.

Effect of left temporoparietal transcranial direct current stimulation on self-bias effect and retrospective intentional binding paradigm: A randomised, double-blind, controlled study.

BACKGROUND: Self-bias effect is expressed as a preferential selection and accelerated perception of self-related sensory information. Intentional binding (IB) is a related phenomenon where the sensory outcome from a voluntary action and the voluntary action itself are perceived to be closer to each other in time in both predictive (voluntary action predicting sensory consequence) and retrospective (sensory consequence features triggering self-related inference) contexts. Recent evidence indicates that self-related visual stimuli can affect retrospective intentional binding (rIB). We aimed to 1) replicate rIB in the auditory context, and 2) investigate the potential role of left temporoparietal junction (l-TPJ), a crucial node for the self-monitoring process, in self-bias effect and intentional binding effect by manipulating l-TPJ activity with neuromodulation [using High-Definition Transcranial Direct Current Stimulation (HD-tDCS)]. We anticipated self-bias and rIB effects to increase with anodal stimulation of l-TPJ in comparison to cathodal-stimulation of l-TPJ. METHODS: Fourteen, right-handed, healthy participants performed sound-label matching (matching tones to self-and-other labels) and rIB (estimating time interval between a button press and a self/other labelled tone) tasks. Each participant underwent both anodal and cathodal stimulation of l-TPJ in separate sessions (at least 72 h apart). Assignment of HD-tDCS type was random and counter-balanced across participants. Behavioural data was collected at three time points: once at baseline (no-stimulation), and twice after stimulation with HD-tDCS. RESULTS: Strong self-bias effect was observed across all experimental conditions. Neuromodulation of l-TPJ affected processing of other-labelled tone in the sound-label matching task. rIB was noted in baseline and anodal-HD-tDCS conditions where participants exhibited stronger binding for self-associated stimuli compared to other-associated stimuli. CONCLUSION: l-TPJ may potentially play a critical role in self-other distinction. This may have possible implications for disorders of self-disturbances like psychosis.

Neurohemodynamic correlates of BDNF gene expression in schizophrenia patients with working memory deficits: A functional MRI study.

INTRODUCTION: Brain-derived neurotrophic factor (BDNF) is involved in neuroplasticity underlying cognitive deficits, including working memory deficits (WMD), in schizophrenia. Methodological challenges and inconsistencies are reported with peripheral BDNF levels. Left dorsolateral prefrontal cortex (DLPFC) is proposed to underlie WMD, though inconsistently. We aimed to explore the correlations between brain activation during working memory task-based functional Magnetic Resonance Imaging (fMRI) and BDNF gene expression in schizophrenia patients with WMD. METHODS: 26 patients with schizophrenia with established WMD were recruited for the study. Blood samples were collected to study lymphocyte BDNF gene expression. Patients underwent task-based fMRI to examine the working memory performance and related brain activation. Whole-brain analysis was performed with 2-back > 0-back and 2-back > rest contrast. The peak intensity values of the activation were used for correlation analysis. RESULTS: Whole brain analysis with 2-back > rest contrast revealed maximum activation in left DLPFC, Brodmann area 9 (t = 10.54, FWE corrected p < 0.05). The baseline BDNF gene expression correlated positively with the peak intensity of brain activation in left DLPFC (r = 0.365, p = 0.033). Negative symptom score negatively correlated with BDNF gene expression (r = -0.499, p = 0.005) and left DLPFC fMRI activation (r = -0.393, p = 0.023) respectively. CONCLUSION: We found a significant positive association between BDNF gene expression and the activation of the DLPFC during the working memory task. This novel observation needs further systematic evaluation to establish the potential role of peripheral BDNF expression in WMD in schizophrenia.

Superior temporal gyrus functional connectivity predicts transcranial direct current stimulation response in Schizophrenia: A machine learning study.

Transcranial direct current stimulation (tDCS) is a promising adjuvant treatment for persistent auditory verbal hallucinations (AVH) in Schizophrenia (SZ). Nonetheless, there is considerable inter-patient variability in the treatment response of AVH to tDCS in SZ. Machine-learned models have the potential to predict clinical response to tDCS in SZ. This study aims to examine the feasibility of identifying SZ patients with persistent AVH (SZ-AVH) who will respond to tDCS based on resting-state functional connectivity (rs-FC). Thirty-four SZ-AVH patients underwent resting-state functional MRI at baseline followed by add-on, twice-daily, 20-min sessions with tDCS (conventional/high-definition) for 5 days. A machine learning model was developed to identify tDCS treatment responders based on the rs-FC pattern, using the left superior temporal gyrus (LSTG) as the seed region. Functional connectivity between LSTG and brain regions involved in auditory and sensorimotor processing emerged as the important predictors of the tDCS treatment response. L1-regularized logistic regression model had an overall accuracy of 72.5% in classifying responders vs. non-responders. This model outperformed the state-of-the-art convolutional neural networks (CNN) model-both without (59.41%) and with pre-training (68.82%). It also outperformed the L1-logistic regression model trained with baseline demographic features and clinical scores of SZ patients. This study reports the first evidence that rs-fMRI-derived brain connectivity pattern can predict the clinical response of persistent AVH to add-on tDCS in SZ patients with 72.5% accuracy.

fNIRS study of prefrontal activation during emotion recognition-A Potential endophenotype for bipolar I disorder?

BACKGROUND: Facial emotion recognition (FER) deficit is documented in many psychiatric disorders, including bipolar disorder (BD). However, its role as a risk-marker in BD is not well researched. In the present study, we investigated the role of FER and the corresponding prefrontal neurohemodynamic changes (PNHC) with functional near infra-red spectroscopy (fNIRS) in patients with BD and subjects at high risk for BD compared to healthy subject. METHODS: Using a cross-sectional case-control design we compared 14 patients with first episode mania (FEM) in remission (BD group), 14 healthy siblings of BD patients (HR group), and 13 matched healthy subjects (HC group). FER was assessed using a computer-based task called Tool for Recognition of Emotions in Neuropsychiatric Disorders (TRENDS). Simultaneously, the corresponding PNHC was recorded with fNIRS. Kruskal Wallis H test was used to analyze between-group differences and Spearman's rho for correlation analysis. RESULTS: The three groups were comparable on socio-demographics (all p>0.09) except education (p = 0.03). HR group had the most hyper-activation in the bilateral DLPFC during the TRENDS task (all p<0.05). There was no significant between-group differences in the FER performance and no significant correlation between the FER performance and the PNHC in the HR and BD groups (all p>0.35). LIMITATIONS: The potential confounding effect of medications in the BD group. CONCLUSIONS: The hyper-activation of the DLPCF in HR group during FER could indicate an increased risk for BD. However, the lack of similar findings in the BD group might reflect a possible normalizing effect of medications. It is equally likely that differences in the PNHC are detectable earlier than the differences in FER task performance during the course of the illness. This requires further exploration.

High definition transcranial direct current stimulation (HD-tDCS): A systematic review on the treatment of neuropsychiatric disorders.

HD-tDCS (High-definition transcranial direct current stimulation) is a novel non-invasive brain stimulation (NIBS) technique based on the principle that when weak intensity electric currents are targeted on specific areas of the scalp, they cause underlying cortical stimulation. HD-tDCS shares its technical methodology with conventional tDCS (montage comprising of one anode and one cathode) except for a few modifications that are believed to have focal and longer-lasting neuromodulation effects. Although HD-tDCS is a recently available NIBS technique, impactful studies, case reports, and few controlled trials have been conducted in this context, facilitating an understanding of its neurobiological effects and the clinical translation of the same in health care set-up. The current article narratively reviews the mechanism of action of HD-tDCS, and it systematically examines the cognitive, clinical, and neurobiological effects of HD-tDCS in healthy volunteers as well as patients with neuropsychiatric conditions. Thus, this review attempts to explore the role of HD-tDCS in present-day practice and the future in the context of various neurological and psychiatric disorders.

Impact of NRG1 HapICE gene variants on digit ratio and dermatoglyphic measures in schizophrenia.

Multiple lines of evidence have suggested a potential role of Neuregulin-1 (NRG1) in the neurodevelopmental pathogenesis of schizophrenia. Interaction between genetic risk variants present within NRG1 locus and non-specific gestational putative insults can significantly impair crucial processes of brain development. Such genetic effects can be analyzed through the assessment of digit ratio and dermatoglyphic patterns. We examined the role of two well-replicated polymorphisms of NRG1 (SNP8NRG221533 and SNP8NRG243177) on schizophrenia risk and its probable impact on the digit ratio and dermatoglyphic measures in patients (N = 221) and healthy controls (N = 200). In schizophrenia patients, but not in healthy controls, a significant association between NRG1 SNP8NRG221533 C/C genotype with lower left 2D:4D ratio, as well as with higher FA_TbcRC and DA_TbcRC. The substantial effect of SNP8NRG221533 on both digit ratio and dermatoglyphic measures suggest a potential role for NRG1 gene variants on neurodevelopmental pathogenesis of schizophrenia.

Effect of add-on transcranial alternating current stimulation (tACS) on persistent delusions in schizophrenia.

The utility of non-invasive brain stimulation techniques to alleviate resistant delusions in schizophrenia is an under-researched area. In this study, we report the effectiveness of alpha transcranial alternating current stimulation (tACS) targeting the medial prefrontal cortex in ameliorating persistent delusions. Twelve Schizophrenia patients (N=12) with persistent delusions received add-on treatment with a twice-daily 20-minutes session of 10-Hz tACS. Significant reduction in severity of delusion was noted after 5th day (z=2.67, p<0.01, n=12) with further improvement after 10th day (z=2.52, p=0.01, n=9) of stimulation. Add-on treatment with 10-Hz tACS is a potential therapeutic option for treatment-resistant delusions, which requires further systematic research.

Target specific effects of direct current stimulation in schizo-obsessive disorder: A case report.

Transcranial direct current stimulation (tDCS) is a type of non-invasive brain stimulation technique that is explored as an add-on treatment for the alleviation of symptoms across the diverse symptom domains in neuropsychiatric disorders. In psychiatry, data is emerging on the effects of tDCS as an add-on treatment in schizophrenia as well as obsessive-compulsive disorder (OCD). But despite high prevalence, the effectiveness of tDCS in co-morbid schizophrenia and OCD is lacking. This case report for the first time examines the clinical utility with target-specific effects of the add-on tDCS in a patient diagnosed with schizo-obsessive disorder.

Tolerance of transcranial direct current stimulation in psychiatric disorders: An analysis of 2000+ sessions.

Transcranial direct current stimulation (tDCS), a non-invasive, neuromodulatory technique, is being increasingly applied to several psychiatric disorders. In this study, we describe the side-effect profile of repeated tDCS sessions (N = 2005) that were administered to 171 patients (156 adults and 15 adolescents) with different psychiatric disorders [schizophrenia [N = 109], obsessive-compulsive disorder [N = 28], alcohol dependence syndrome [N = 13], mild cognitive impairment [N = 10], depression [N = 6], dementia [N = 2] and other disorders [N = 3]]. tDCS was administered at a constant current strength of 2 mA with additional ramp-up and ramp-down phase of 20 s each at the beginning and end of the session, respectively. Other tDCS protocol parameters were: schizophrenia and obsessive-compulsive disorder: 5-days of twice-daily 20-min sessions with an inter-session interval of 3-h; Mild cognitive impairment/dementia and alcohol dependence syndrome: at least 5-days of once-daily 20-min session; Depression: 10-days of once-daily 30 min session. At the end of each tDCS session, any adverse event observed by the administrator and/or reported by the patient was systematically assessed using a comprehensive questionnaire. The commonly reported adverse events during tDCS included burning sensations (16.2%), skin redness (12.3%), scalp pain (10.1%), itching (6.7%), and tingling (6.3%). Most of the adverse events were noted to be mild, transient and well-tolerated. In summary, our observations suggest that tDCS is a safe mode for therapeutic non-invasive neuromodulation in psychiatric disorders in adults as well as the adolescent population.

Add-on HD-tDCS for obsessive-compulsive disorder with comorbid bipolar affective disorder: A case series.

Obsessive-compulsive disorder (OCD) with comorbid bipolar affective disorder (BPAD) is often faced with a therapeutic challenge. Pharmacological treatment strategy engaged towards alleviating symptoms in OCD has the propensity to precipitate a manic switch in patients with comorbid BPAD. Advanced non-invasive brain stimulation techniques like high definition transcranial direct current stimulation (HD-tDCS) may target the symptoms of OCD while preventing a probable manic switch in a vulnerable population. In this case series, we targeted OC symptoms in three patients by giving 2 mA of anodal HD-tDCS at their pre-SMA (localized using 10/10 EEG system) with 4 surrounding return electrodes of opposite polarity for 20 min of two sessions having an intersession gap of 20 min receiving a maximum of 20 sessions. We found that the patients showed significant improvement (more than 25%) in their OC symptoms while having no affective side effects and this effect was replicated in one of the two patients in repeating the treatment for relapse. This case series highlights the efficacy and durability of the effect of HD-tDCS as an add-on treatment modality in three patients who were treated for OC symptoms in the context of a comorbid bipolar disorder, two of them receiving repeat courses on relapse.

Schizophrenia and Corollary Discharge: A Neuroscientific Overview and Translational Implications.

Corollary discharge mechanism refers to the suppression of sensory consequences of self-generated actions; a process that serves to distinguish between self and non-self based on discrimination of origination of action. It explains, say for example, why we cannot tickle ourselves. This review discusses how corollary discharge model is an essential neural integration mechanism central to the motor functioning of animal kingdom. In this article, research conducted in the field of corollary discharge has been reviewed to understand the neuroanatomical and neurophysiological basis of corollary discharge and gain insight into the biochemical basis of its dysfunction. This review article also explores the role of corollary discharge and its dysfunction in the presentation of symptoms of schizophrenia, discussing the findings from corollary discharge studies on schizophrenia population. Lastly, the link between schizophrenia psychopathology and corollary discharge dysfunction has been highlighted, and an attempt has been made to establish a case for correction of corollary discharge deficit in schizophrenia through neuromodulation.

High-definition transcranial direct current simulation (HD-tDCS) for persistent auditory hallucinations in schizophrenia.

Conventional transcranial Direct Current Stimulation (tDCS) has been reported to alleviate persistent auditory hallucinations (AH) in schizophrenia as an add-on intervention. High-Definition tDCS (HD-tDCS), an optimized form of tDCS, has the potential for more focalized neuromodulation. In this study, add-on HD-tDCS (5 days twice daily session with 2-mA cathodal current on left temporo-parietal junction) using 4 × 1 ring montage significantly reduced persistent AH (t = 3.6;p < 0.01) in schizophrenia patients (N = 19). Add-on HD-tDCS has promising potential to treat persisting AH in schizophrenia. This needs further systematic research.