Search

Cognitive dysfunction is suggested to be the best predictor of functional outcome in schizophrenia. Therefore, new diagnostic and treatment strategies are needed to both ascertain the biological underpinning of cognitive deficits and to restore them. Modulation of gamma oscillations (30-50 Hz) has been associated with cognitive performance, particularly in the dorsolateral prefrontal cortex (DLPFC). In this manuscript, we review evidence for gamma modulation deficits during cognitive performance in schizophrenia. We demonstrate that transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) is a reliable method that permits systematic quantification of gamma modulation in the cortex. Using TMS-EEG, we show that patients with schizophrenia have selective gamma inhibition deficits in the DLPFC. Finally, we demonstrate that repetitive TMS therapy over the DLPFC can normalize excessive gamma oscillations and ultimately cognitive performance in patients. We suggest that restoring gamma impairments in the DLPFC may be a potential strategy for improving cognitive deficits in schizophrenia., (© 2012 New York Academy of Sciences.)

Schizophrenia (SCZ) is a serious mental disorder, and its pathogenesis is complex. Recently, the glutamate hypothesis and the excitatory/inhibitory (E/I) imbalance hypothesis have been proposed as new pathological hypotheses for SCZ. Combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) is a non-invasive novel method that enables us to investigate the cortical activity in humans, and this modality is a suitable approach to evaluate these hypotheses. In this study, we systematically reviewed TMS-EEG studies that investigated the cortical dysfunction of SCZ to examine the emerging hypotheses for SCZ. The following search terms were set in this systematic review: (TMS or 'transcranial magnetic stimulation') and (EEG or electroencephalog*) and (schizophrenia). We inspected the articles written in English that examined humans and were published by March 2020 via MEDLINE, Embase, PsycINFO, and PubMed. The initial search generated 379 studies, and 14 articles were finally identified. The current review noted that patients with SCZ demonstrated the E/I deficits in the prefrontal cortex, whose dysfunctions were also associated with cognitive impairment and clinical severity. Moreover, TMS-induced gamma activity in the prefrontal cortex was related to positive symptoms, while theta/delta band activities were associated with negative symptoms in SCZ. Thus, this systematic review discusses aspects of the pathophysiological neural basis of SCZ that are not explained by the traditional dopamine hypothesis exclusively, based on the findings of previous TMS-EEG research, mainly in terms of the E/I imbalance hypothesis. In conclusion, TMS-EEG neurophysiology can be applied to establish objective biomarkers for better diagnosis as well as to develop new therapeutic strategies for patients with SCZ. [ABSTRACT FROM AUTHOR]

• Interhemispheric signal propagation was elevated in schizophrenia and depression patients relative to healthy controls. • Interhemispheric signal propagation did not differ between patient groups. • There were no medication effects on interhemispheric signaling from inter-individual comparisons and no significant correlation with symptom severity. Altered interhemispheric connectivity is implicated in the pathophysiology of schizophrenia (SCZ) and major depressive disorder (MDD) and may account for deficits in lateralized cognitive processes. We measured transcranial magnetic stimulation evoked interhemispheric signal propagation (ISP), a non-invasive measure of transcallosal connectivity, and hypothesized that the SCZ and MDD groups will have increased ISP compared to healthy controls. We evaluated ISP over the dorsolateral prefrontal cortex in 34 patients with SCZ and 34 patients with MDD compared to 32 age and sex-matched healthy controls. ISP was significantly increased in patients with SCZ and patients with MDD compared to healthy controls but did not differ between patient groups. There were no effects of antidepressant, antipsychotic, and benzodiazepine medications on ISP and our results remained unchanged after re-analysis with a region of interest method. Altered ISP was found in both SCZ and MDD patient groups. This indicates that disruptions of interhemispheric signaling processes can be indexed with ISP across psychiatric populations. These findings enhance our knowledge of the physiological mechanisms of interhemispheric imbalances in SCZ and MDD, which may serve as potential treatment targets in future patients. [ABSTRACT FROM AUTHOR]

Background: Working memory deficits represent a core feature of schizophrenia. These deficits have been associated with dysfunctional dorsolateral prefrontal cortex (DLPFC) cortical oscillations. Theta-gamma coupling describes the modulation of gamma oscillations by theta phasic activity that has been directly associated with the ordering of information during working memory performance. Evaluating theta-gamma coupling may provide greater insight into the neural mechanisms mediating working memory deficits in this disorder.Methods: Thirty-eight patients diagnosed with schizophrenia or schizoaffective disorder and 38 healthy controls performed the verbal N-Back task administered at 4 levels, while EEG was recorded. Theta (4-7Hz)-gamma (30-50Hz) coupling was calculated for target and non-target correct trials for each working memory load. The relationship between theta-gamma coupling and accuracy was determined.Results: Theta-gamma coupling was significantly and selectively impaired during correct responses to target letters among schizophrenia patients compared to healthy controls. A significant and positive relationship was found between theta-gamma coupling and 3-Back accuracy in controls, while this relationship was not observed in patients.Conclusions: These findings suggest that impaired theta-gamma coupling contribute to working memory dysfunction in schizophrenia. Future work is needed to evaluate the predictive utility of theta-gamma coupling as a neurophysiological marker for functional outcomes in this disorder. [ABSTRACT FROM AUTHOR]