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The article presents an analysis of the pharmacology of clozapine in relation to schizophrenia. It as well discusses the existing evidence associating clozapine to GABAergic neurotransmission, and highlights alternative treatment methods that may deliver better outcomes through the GABAergic system. It indicates that schizophrenia is a neuropsychiatric disorder implicating disturbances of perception, cognition, and behavior

Background: Non-response to repetitive transcranial magnetic stimulation (rTMS) treatment for depression is costly for both patients and clinics. Simple and cheap methods to predict response would reduce this burden. Resting EEG measures differentiate responders from non-responders, so may have utility for response prediction.Methods: Fifty patients with treatment resistant depression and 21 controls had resting electroencephalography (EEG) recorded at baseline (BL). Patients underwent 5-8 weeks of rTMS treatment, with EEG recordings repeated at week 1 (W1). Forty-two participants had valid BL and W1 EEG data, and 12 were responders. Responders and non-responders were compared at BL and W1 in measures of theta (4-8 Hz) and alpha (8-13 Hz) power and connectivity, frontal theta cordance and alpha peak frequency. Control group comparisons were made for measures that differed between responders and non-responders. A machine learning algorithm assessed the potential to differentiate responders from non-responders using EEG measures in combination with change in depression scores from BL to W1.Results: Responders showed elevated theta connectivity across BL and W1. No other EEG measures differed between groups. Responders could be distinguished from non-responders with a mean sensitivity of 0.84 (p = 0.001) and specificity of 0.89 (p = 0.002) using cross-validated machine learning classification on the combination of all EEG and mood measures.Limitations: The low response rate limited our sample size to only 12 responders.Conclusion: Resting theta connectivity at BL and W1 differ between responders and non-responders, and show potential for predicting response to rTMS treatment for depression. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Working memory is associated with gamma oscillations (30-50Hz). Previous studies have demonstrated altered gamma oscillations in the elderly population that may be related to general cognitive decline. However, it is unknown how gamma oscillations change with age or if there is an age when gamma oscillations optimally mediate working memory performance. That is, gamma oscillations may be maximal in middle-aged adults compared to younger and elderly adults. The objective of this study was to evaluate working memory evoked gamma oscillations in adults aged 19-29 years (mean 23.32±2.85 1SD) compared to adults aged 30-60 years (mean 39.10±8.11 1SD). METHODS: Subjects completed the verbal N-back task administered at four working loads (0, 1, 2, 3), while electroencephalography (EEG) was collected. Gamma power was measured during correct responses. RESULTS: Reduced gamma oscillations were observed in the adults aged 19-29 compared to those aged 30-60 years. Age was found to be positively related to the power of gamma oscillations. No differences were found on N-Back accuracy. CONCLUSIONS: Increased working memory evoked gamma oscillatory activity may provide a neurophysiological marker in the healthy aging brain. [ABSTRACT FROM AUTHOR]

Objective: While previous studies showed that the single nucleotide polymorphism (Val66Met) of brain-derived neurotrophic factor (BDNF) can impact neuroplasticity, the influence of BDNF genotype on cortical circuitry and relationship to neuroplasticity remain relatively unexplored in human., Methods: Using individualised transcranial magnetic stimulation (TMS) parameters, we explored the influence of the BDNF Val66Met polymorphism on excitatory and inhibitory neural circuitry, its relation to I-wave TMS (ITMS) plasticity and effect on the excitatory/inhibitory (E/I) balance in 18 healthy individuals., Results: Excitatory and inhibitory indexes of neurotransmission were reduced in Met allele carriers. An E/I balance was evident, which was influenced by BDNF with higher E/I ratios in Val/Val homozygotes. Both long-term potentiation (LTP-) and depression (LTD-) like ITMS plasticity were greater in Val/Val homozygotes. LTP- but not LTD-like effects were restored in Met allele carriers by increasing stimulus intensity to compensate for reduced excitatory transmission., Conclusions: The influence of BDNF genotype may extend beyond neuroplasticity to neurotransmission. The E/I balance was evident in human motor cortex, modulated by BDNF and measurable using TMS. Given the limited sample, these preliminary findings warrant further investigation., Significance: These novel findings suggest a broader role of BDNF genotype on neurocircuitry in human motor cortex., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression, but only some individuals respond. Predicting response could reduce patient and clinical burden. Neural activity related to working memory (WM) has been related to mood improvements, so may represent a biomarker for response prediction., Primary Hypotheses: We expected higher theta and alpha activity in responders compared to non-responders to rTMS., Methods: Fifty patients with treatment resistant depression and twenty controls performed a WM task while electroencephalography (EEG) was recorded. Patients underwent 5-8 weeks of rTMS treatment, repeating the EEG at week 1 (W1). Of the 39 participants with valid WM-related EEG data from baseline and W1, 10 were responders. Comparisons between responders and non-responders were made at baseline and W1 for measures of theta (4-8 Hz), upper alpha (10-12.5 Hz), and gamma (30-45 Hz) power, connectivity, and theta-gamma coupling. The control group's measures were compared to the depression group's baseline measures separately., Results: Responders showed higher levels of WM-related fronto-midline theta power and theta connectivity compared to non-responders at baseline and W1. Responder's fronto-midline theta power and connectivity was similar to controls. Responders also showed an increase in gamma connectivity from baseline to W1, with a concurrent improvement in mood and WM reaction times. An unbiased combination of all measures provided mean sensitivity of 0.90 at predicting responders and specificity of 0.92 in a predictive machine learning algorithm., Conclusion: Baseline and W1 fronto-midline theta power and theta connectivity show good potential for predicting response to rTMS treatment for depression., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Several meta-analyses considering repetitive transcranial magnetic stimulation (rTMS) for auditory verbal hallucinations (AVH) have been performed with moderate to high mean weighted effect sizes. Since then several negative findings were reported in relatively large samples. The aim of this study was to provide an update of the literature on the efficacy of rTMS for AVH and to investigate the effect of rTMS one month after the end of treatment., Data Sources: A literature search was performed from 1966 through August 2012 using Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Embase Psychiatry, Ovid Medline, PsycINFO and PubMed. Randomized, double blind, sham-controlled studies with severity of AVH or severity of psychosis as an outcome measure were included., Study Selection: Data were obtained from 17 randomized studies of rTMS for AVH. Five studies fulfilled the criteria for the meta-analysis on the effect of rTMS one month after the end of treatment., Data Extraction: Standardized mean weighted effect sizes of rTMS versus sham were computed on pre- and posttreatment comparisons., Data Synthesis: The mean weighted effect size of rTMS directed at the left temporoparietal area was 0.44 (95% CI 0.19-0.68). A separate meta-analysis including studies directing rTMS at other brain regions revealed a mean weighted effect size of 0.33 (95% CI 0.17-0.50) in favor of real TMS. The effect of rTMS was no longer significant at one month of follow-up (mean weighted effect size=0.40, 95% CI -0.23-0.102). Side effects were mild and the number of dropouts in the real TMS group was not significantly higher than in the sham group., Conclusions: With the inclusion of studies with larger patient samples, the mean weighted effect size of rTMS directed at the left temporoparietal area for AVH has decreased, although the effect is still significant. The duration of the effect of rTMS may be less than one month. More research is needed in order to optimize parameters and further evaluate the clinical relevance of this intervention., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Gamma (gamma) oscillations (30-50 Hz) elicited during working memory (WM) are altered in schizophrenia (SCZ). However, the nature of the relationship between evoked frontal oscillatory activity, WM performance and symptom severity has yet to be ascertained. This study had two objectives. First, to extend previous studies by examining delta, theta, alpha, beta, and gamma (delta, theta, alpha, beta, and gamma) oscillatory activities during the N-back task in SCZ patients compared to healthy subjects; second, to evaluate the relationship between oscillatory activities elicited during the N-back, performance, and clinical symptoms in SCZ patients. Patients with SCZ elicited excessive frontal gamma oscillatory activity that was most pronounced in the 3-back condition compared to healthy subjects. Reduced frontal beta activity at all WM loads was also observed in patients with SCZ compared to healthy subjects. Task performance was inversely correlated with negative symptoms but not with positive symptoms. Our findings suggest that evoked frontal oscillatory activities during WM are selectively altered in the gamma and beta frequency bands that may contribute to WM impairment in SCZ patients. These findings may provide important insights into the pathophysiology underlying WM deficits, its relationship to negative symptoms and may represent a potential neurobiological marker for cognitive enhancing strategies in SCZ., (Copyright 2010 Elsevier B.V. All rights reserved.)

The objective of this study was to explore the effects of 1Hz repetitive transcranial magnetic stimulation (rTMS) applied to dorsal lateral prefrontal cortex (DLPFC) on both an EEG index of cortical excitation and inhibition, event-related desynchronization/ synchronization (ERDIS) and on the P300 component of an auditory oddball-induced ERP. Eight normal participants received 15 minutes of 1Hz rTMS at 110% of the resting motor threshold to right DLPFC. ERDIS of alpha and beta bands was measured during an auditory oddball task immediately before and after stimulation. There was significantly less alpha desynchronization post-TMS, and this effect was widespread excepting posterior midline sites. No changes were found to oddball-P300 amplitudes or latencies. In conclusion, the findings of less alpha desynchronization post-TMS are compatible with notions of slow rTMS causing a decrease in cortical excitation.

A considerable body of imaging research has demonstrated morphological changes in the corpus callosum (CC) of patients with schizophrenia. Transcranial magnetic stimulation (TMS) allows the possibility for the in vivo investigation of a variety of aspects of brain function including the spread of information across the CC. We aimed to investigate whether patients with schizophrenia demonstrate abnormalities of transcallosal inhibition (TCI), a TMS parameter measured with both single and paired pulse experiments. 25 patients with DSM-IV schizophrenia and 20 normal volunteers participated in the study. Electromyographic (EMG) recordings from the bilateral abductor pollicis brevis (APB) muscle were made during focal TMS stimulation to the motor cortex. Experimental paradigms were utilised to measure both the timing and degree of the effect of TCI. The patient group demonstrated a reduction in the degree of TCI at rest and during a sustained muscle contraction. TCI commenced at the same time in the patient and the control group but was of prolonged duration in the patient group although the length of TCI correlated with medication dose. Patients with schizophrenia demonstrate a reduction in the degree of TCI that appeared independent of medication dose. The latency of TCI is not altered in the patient group suggesting that cortical inhibitory mechanisms, rather than corpus callosal ones, are likely to be the cause of these TCI alterations.