Repetition-Dependent Adaptation and Prediction Error Signalling in Schizophrenia Patients With Auditory Hallucinations: A Roving Mismatch Negativity Study.

BACKGROUND: Dysregulated prediction error-signalling may explain auditory hallucinations in schizophrenia (SZ-AH). Roving mismatch negativity (rMMN) is an event-related potential (ERP) index where the deviant tone becomes the new standard with repetitions. Longer repetitions of standard stimuli yield a more positive sensory-adaptation response (Repetition Positivity-RP), elicit a stronger deviance-detection when interrupted (deviant negativity-DN), and the difference waveform between them reflects the strength of prediction-error signalling (mismatch negativity-MMN). METHODS: Twenty-three SZ-AH patients and twenty-three healthy controls (HC) underwent rMMN assessment. Various standard stimuli were repeated in sets of 3, 8 and 33 yielding three components for RP (RP3, RP8, RP33), DN (DN3, DN8, DN33), and MMN (MMN3, MMN8, MMN33). Amplitudes and latencies were compared across groups. Correlation between (a) rMMN amplitudes and latencies, and clinical variables in SZ-AH, and (b) the RP-DN amplitude pair for all three repetition sets (3, 8, 33) were also examined. RESULTS: All DN and MMN33 amplitudes were significantly suppressed in SZ-AH, while RP amplitudes were not. MMN33 latency was significantly longer in SZ-AH than HC. A few amplitudes and latencies significantly correlated with the frequency of AH. HC showed a significant positive correlation between RP-DN amplitude pairs for sets of 3 and 8 but not for 33; SZ-AH group's correlation profile was opposite to this. DISCUSSION: The link between repetition-dependent sensory-adaptation and deviance-detection is perturbed in SZ-AH. The unimpaired RP profile in SZ-AH is due to potential interference of AH with auditory information processing, and does not indicate a preserved short-term plasticity of the echoic memory trace.

Home-based tDCS for schizophrenia: Exploring the feasibility of a standard operating procedure.

Transcranial Direct Current Stimulation (tDCS), a safe and easy-to-administer noninvasive brain stimulation technique, holds promise in managing auditory verbal hallucinations (AVH) in schizophrenia. However, its short-lasting effect often leads to frequent hospital visits for booster/maintenance sessions, posing logistical challenges. Home-based tDCS offers a potential solution that improves accessibility; however, careful standardisation is required to ensure safe and effective application. We present a case of schizophrenia, where add-on home-based tDCS was administered based on a standard operating procedure (SOP) developed to address challenges unique to home administration, like device-related factors, patient and caregiver-related factors, and comprehensive caregiver training protocol. As a part of training, caregivers underwent observational learning, mannequin-based training for electrode placement, and assisted live-patient sessions. Pre and post-training competency assessments were done to ensure proficiency and safe administration. Over ten days, home-based tDCS sustained improvements in AVH without adverse effects. This case report supports the feasibility of home-based tDCS and provides a detailed SOP for implementing a safe and effective home-based tDCS treatment regime. This comprehensive SOP with a training protocol is notedly efficient for enhancing the accessibility and affordability of tDCS treatment protocols.

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.

Feasibility of intermediate theta burst stimulation as sham control in therapeutic transcranial magnetic stimulation studies.

A major challenge in Transcranial Magnetic Stimulation trials is that of an inefficient sham protocol. This could potentially amplify the gap in behavioral outcomes following true and control treatments. Intermediate theta-burst stimulation (imTBS) is a promising sham alternative since it uses actual TMS pulses, thus mimicking the sensory effects of stimulation without producing physiological aftereffects. Here, we critically review controlled experiments that have examined physiological and behavioral aftereffects following imTBS with the intention to further investigate what appears to be a promising sham control modality for TBS studies.

Clinical efficacy and neurobiological correlates of electroconvulsive therapy in patients with clozapine-resistant/intolerant schizophrenia: study protocol of multi-site parallel arm double-blind randomized sham-controlled study.

Background: A substantial proportion of patients with treatment resistant schizophrenia do not respond well or partially to clozapine, with a subset that does not tolerate an adequate trial of clozapine. Electroconvulsive therapy (ECT) is regarded as one of the augmenting options, but there is a lack of high-quality evidence for this practice. This protocol describes a double-blind randomised sham-controlled modified-ECT trial to evaluate its efficacy in patients with clozapine resistant/intolerant schizophrenia. The study also involves multimodal investigations to identify the response predictors and the mechanistic basis of modified ECT in this population. Methods: One hundred consenting schizophrenia patients with resistance/intolerance to clozapine referred by clinicians for ECT would be randomly assigned to receive true ECT or sham ECT at three study centers. Sham ECT would mimic all the procedures of modified ECT including anaesthesia and muscle relaxation, except the electrical stimulation. After a blinded course, non-responders to sham ECT would be offered open-label true ECT. Clinical assessments, neurocognitive assessments and multimodal investigations (magnetic resonance imaging [MRI], electroencephalography, heart rate variability, investigative transcranial magnetic stimulation-transcranial direct current stimulation, gene polymorphism) would be conducted at baseline and repeated after the end of the trial, as well as open-label ECT course. The trial would evaluate the improvement in positive symptoms (scale for assessment of positive symptoms) of schizophrenia as the primary outcome measure with prediction of this change by resting-state functional-MRI based brain-connectivity as the second primary objective. Registration: Clinical Trial Registry of India (Reg no: CTRI/2021/05/033775) on 24 th May 2021.