Non-invasive brain stimulation for negative symptoms in schizophrenia: an updated systematic review and meta-analysis

Background: Schizophrenia is a mental disorder with significant social and economic burden. Although current pharmacological treatments are effective for controlling the positive symptoms, medications have small-to-no effect for the treatment of negative symptoms. Noninvasive Brain Stimulation (NIBS) techniques, such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and trigeminal nerve stimulation (TNS) are emerging as neuroplasticity enhancer, boosting treatment response for refractory symptoms in Schizophrenia. Objective: To assess the efficacy of non-invasive brain stimulation for negative symptoms in schizophrenia in randomized clinical trials (RCTs). Methods: A systematic review in the Medline and Cochrane Library databases was performed up to May 31, 2017. The primary outcome was the Hedges’ g for continuous scores in a random effects model. Heterogeneity was evaluated with the I 2 and the χ2 test. Publication bias was assessed using the Begg’s funnel plot. Meta-regression was performed usingthe random-effects model modified by Knapp and Hartung. Results: We included 31 RCTs (n=1272); most with small-to-modest sample sizes. Active stimulation was significantly superior over sham for negative symptoms (Hedges’ g = 0.23; 95% CI 0.11 – 0.34). The funnel plot and the Eggers test showed that heterogeneity and the risk of publication bias were low (I2 =2.3%, p=0.429 for the χ2 test; p=0.179 for the Egger’s test). Meta-regression showed no influence of any variable on the results found. Both transcranial magnetic stimulation and transcranial direct current stimulation were superior to sham. In a subgroup analysis, no trial was alone responsible for the positive results observed. Conclusion: NIBS active was superior to sham stimulation for the amelioration of negative symptoms in schizophrenia. We found no considerable heterogeneity or publication bias in our analysis, corroborating to the strength of our findings. Further RCTs with larger sample sizes are needed to clarify the precise impact of NIBS in negative symptoms in schizophrenia.Keywords: Schizophrenia; Brain stimulation; Noninvasive brain stimulation; Randomized clinical trials

Toward personalized circuit-based closed-loop brain-interventions in psychiatry: using symptom provocation to extract EEG-markers of brain circuit activity

Symptom provocation is a well-established component of psychiatric research and therapy. It is hypothesized that specific activation of those brain circuits involved in the symptomatic expression of a brain pathology makes the relevant neural substrate accessible as a target for therapeutic interventions. For example, in the treatment of obsessive-compulsive disorder (OCD), symptom provocation is an important part of psychotherapy and is also performed prior to therapeutic brain stimulation with transcranial magnetic stimulation (TMS). Here, we discuss the potential of symptom provocation to isolate neurophysiological biomarkers reflecting the fluctuating activity of relevant brain networks with the goal of subsequently using these markers as targets to guide therapy. We put forward a general experimental framework based on the rapid switching between psychiatric symptom states. This enable neurophysiological measures to be derived from EEG and/or TMS-evoked EEG measures of brain activity during both states. By subtracting the data recorded during the baseline state from that recorded during the provoked state, the resulting contrast would ideally isolate the specific neural circuits differentially activated during the expression of symptoms. A similar approach enables the design of effective classifiers of brain activity from EEG data in Brain-Computer Interfaces (BCI). To obtain reliable contrast data, psychiatric state switching needs to be achieved multiple times during a continuous recording so that slow changes of brain activity affect both conditions equally. This is achieved easily for conditions that can be controlled intentionally, such as motor imagery, attention, or memory retention. With regard to psychiatric symptoms, an increase can often be provoked effectively relatively easily, however, it can be difficult to reliably and rapidly return to a baseline state. Here, we review different approaches to return from a provoked state to a baseline state and how these may be applied to different symptoms occurring in different psychiatric disorders

Cognitive impact in children with “benign” childhood focal epilepsy with centrotemporal spikes

Background Cognitive alterations are associated with benign childhood focal epilepsy with centrotemporal spikes (BCECTS) including aspects of executive functions. Objectives This study presents the performance profile on attention and executive function tests of fifty-eight children (BCECTS, n = 30 and controls, n = 28) aged 8-13 years. Methods The following tools were employed: Vocabulary and Block Design subtests from the Wechsler Intelligence Scale for Children III, Stroop Test, Modified Card Sorting Test, Controlled Oral Word Association – FAS and Tower of London. Results Children with BCECTS presented average IQ measure, although their performance was statistically worse when compared to the control group. Children with BCECTS showed significantly lower performance compared to the control group in the following variables: total number of recollected words on the oral fluency test, total number of categories, categorization effect and total number of errors in MCST; and execution time for the Stroop Test Card 1. After controlling for the IQ effect, the total number of errors in the MCST did not show any significant difference between the groups. Discussion Children with BCECTS showed lower performance in attention and executive functions when compared to healthy children. The results suggest that the concept of “benign” BCECTS should be reconsidered

Trigeminal nerve stimulation for the treatment of major depressive disorder and obsessive-compulsive disorder: a case study

<div>Neuromodulation techniques have been proposed as add-on strategies for modulating brain areas involved in obsessive-compulsive disorder symptoms. Trigeminal nerve stimulation is a novel neuromodulation technique, which, to date, has not yet been explored for obsessive-compulsive disorder treatment. In this report, we describe a 52-year-old female patient suffering from major depressive disorder</div><div>and obsessive-compulsive disorder for 18 and 32 years, respectively and successfully undergoing a trigeminal nerve stimulation intervention protocol (10 consecutive daily trigeminal nerve stimulation sessions), with amelioration of symptoms. Cognitive function was not obviously altered as assessed by the Montreal Cognitive Assessment. Major depressive disorder and obsessive-compulsive disorder symptoms assessed using the Yale-Brown Obsessive-Compulsive Scale and the 17-item Hamilton Depression Rating Scale substantially improved after the 10-day treatment course and remained stable after 1-month follow-up (30 days after final trigeminal nerve stimulation). The patient reported significant global clinical gains and mild diurnal sleepiness without severe adverse effects. Trigeminal nerve stimulation has been studied for the treatment of various neuropsychiatric disorders that share common functional alterations at the frontal cortex and subcortical areas, usually altered in obsessive-compulsive disorder. We present the first case report on trigeminal nerve stimulation for co-morbid obsessive-compulsive disorder and major depressive disorder. These encouraging results should be seen as hypothesis-driving for further controlled randomized trials exploring the impact of trigeminal nerve stimulation in the treatment of obsessive-compulsive disorder.</div><div><div>doi: 10.4103/2542-3932.198962</div><div>How to cite this article: Trevizol AP, Sato IA, Cordeiro Q (2017) Trigeminal nerve stimulation for the treatment of major depressive disorder and obsessive-compulsive disorder: a case study. Asia Pac J Clin Trials Nerv Syst Dis 2(1):30-32.</div></div