GABA level, gamma oscillation, and working memory performance in schizophrenia

Abstract

A relationship between working memory impairment, disordered neuronal oscillations, and abnormal prefrontal GABA function has been hypothesized in schizophrenia; however, in vivo GABA measurements and gamma band neural synchrony have not yet been compared in schizophrenia. This case–control pilot study (N = 24) compared baseline and working memory task-induced neuronal oscillations acquired with high-density electroencephalograms (EEGs) to GABA levels measured in vivo with magnetic resonance spectroscopy. Working memory performance, baseline GABA level in the left dorsolateral prefrontal cortex (DLPFC), and measures of gamma oscillations from EEGs at baseline and during a working memory task were obtained. A major limitation of this study is a relatively small sample size for several analyses due to the integration of diverse methodologies and participant compliance. Working memory performance was significantly lower for patients than for controls. During the working memory task, patients (n = 7) had significantly lower amplitudes in gamma oscillations than controls (n = 9). However, both at rest and across working memory stages, there were significant correlations between gamma oscillation amplitude and left DLPFC GABA level. Peak gamma frequency during the encoding stage of the working memory task (n = 16) significantly correlated with GABA level and working memory performance. Despite gamma band amplitude deficits in patients across working memory stages, both baseline and working memory-induced gamma oscillations showed strong dependence on baseline GABA levels in patients and controls. These findings suggest a critical role for GABA function in gamma band oscillations, even under conditions of system and cognitive impairments as seen in schizophrenia.

An animal model of female adolescent cannabinoid exposure elicits a long-lasting deficit in presynaptic long-term plasticity

“…These latter studies demonstrated that chronic cannabis exposure alters the ability to generate neural oscillations in the gamma range (Skosnik et al, 2012). Alterations in gamma oscillation have long been thought to be associated with schizophrenic etiology (Chen et al, 2014; Uhlhaas and Singer, 2013). It is noteworthy that developmental NMDAR hypofunction animal models for psychosis have also shown dysregulation in gamma oscillations in the cortex (Anderson et al, 2014; Hunt and Kasicki, 2013) and loss of eCB-LTD, while mGluR2/3-LTD was spared (Lovelace et al, 2014).…”

Slow Gamma Activity of Local Field Potentials (LFP) in the Freely Moving Rat Relates to Movement

“…In this case a relationship was detected between this high gamma activity and the cannabinoid receptor CB1. Low gamma oscillations (30 -56 Hz) have been related in healthy subjects and schizophrenic patients to dorso-lateral prefrontal levels of GABA at rest and during a memory task [11].…”

Oscillations or Synchrony? Disruption of Neural Synchrony despite Enhanced Gamma Oscillations in a Model of Disrupted Perceptual Coherence

“…Furthermore, given that WS has a genetic basis, which is implicated in cortical circuit specification with a direct impact on the phenotype (Castelo-Branco et al, 2007), it is relevant to consider the molecular mechanisms underlying abnormal oscillatory patterning . It is known that high-frequency oscillatory activity in the cortex results from interactions between GABAergic inhibitory interneurons (Chen et al, 2014;Muthukumaraswamy et al, 2009) and is impaired in some neuropsychiatric disorders such as schizophrenia, epilepsy, and ADHD (Herrmann & Demiralp, 2005). Moreover, it has been shown that GABA concentration is positively correlated with stimulus-induced gamma-oscillations during a visual task (Muthukumaraswamy et al, 2009).…”