Gamma Oscillations and Potassium Channel Modulation in Schizophrenia: Targeting GABAergic Dysfunction.

Impairments in gamma-aminobutyric acid (GABAergic) interneuron function lead to gamma power abnormalities and are thought to underlie symptoms in people with schizophrenia. Voltage-gated potassium 3.1 (Kv3.1) and 3.2 (Kv3.2) channels on GABAergic interneurons are critical to the generation of gamma oscillations suggesting that targeting Kv3.1/3.2 could augment GABAergic function and modulate gamma oscillation generation. Here, we studied the effect of a novel potassium Kv3.1/3.2 channel modulator, AUT00206, on resting state frontal gamma power in people with schizophrenia. We found a significant positive correlation between frontal resting gamma (35-45 Hz) power (n = 22, r = 0.613, P < .002) and positive and negative syndrome scale (PANSS) positive symptom severity. We also found a significant reduction in frontal gamma power (t13 = 3.635, P = .003) from baseline in patients who received AUT00206. This provides initial evidence that the Kv3.1/3.2 potassium channel modulator, AUT00206, may address gamma oscillation abnormalities in schizophrenia.

Alpha3/alpha2 power ratios relate to performance on a virtual reality shopping task in ageing adults.

Background: Aspects of cognitive function decline with age. This phenomenon is referred to as age-related cognitive decline (ARCD). Improving the understanding of these changes that occur as part of the ageing process can serve to enhance the detection of the more incapacitating neurodegenerative disorders such as Alzheimer's disease (AD). In this study, we employ novel methods to assess ARCD by exploring the utility of the alpha3/alpha2 electroencephalogram (EEG) power ratio - a marker of AD, and a novel virtual reality (VR) functional cognition task - VStore, in discriminating between young and ageing healthy adults. Materials and methods: Twenty young individuals aged 20-30, and 20 older adults aged 60-70 took part in the study. Participants underwent resting-state EEG and completed VStore and the Cogstate Computerised Cognitive Battery. The difference in alpha3/alpha2 power ratios between the age groups was tested using t-test. In addition, the discriminatory accuracy of VStore and Cogstate were compared using logistic regression and overlying receiver operating characteristic (ROC) curves. Youden's J statistic was used to establish the optimal threshold for sensitivity and specificity and model performance was evaluated with the DeLong's test. Finally, alpha3/alpha2 power ratios were correlated with VStote and Cogstate performance. Results: The difference in alpha3/alpha2 power ratios between age cohorts was not statistically significant. On the other hand, VStore discriminated between age groups with high sensitivity (94%) and specificity (95%) The Cogstate Pre-clinical Alzheimer's Battery achieved a sensitivity of 89% and specificity of 60%, and Cogstate Composite Score achieved a sensitivity of 83% and specificity of 85%. The differences between the discriminatory accuracy of VStore and Cogstate models were statistically significant. Finally, high alpha3/alpha2 power ratios correlated strongly with VStore (r = 0.73), the Cogstate Pre-clinical Alzheimer's Battery (r = -0.67), and Cogstate Composite Score (r = -0.76). Conclusion: While we did not find evidence that the alpha3/alpha2 power ratio is elevated in healthy ageing individuals compared to young individuals, we demonstrated that VStore can classify age cohorts with high accuracy, supporting its utility in the assessment of ARCD. In addition, we found preliminary evidence that elevated alpha3/alpha2 power ratio may be linked to lower cognitive performance.

Gamma band oscillations in the early phase of psychosis: A systematic review.

Abnormal gamma oscillations, measured by electroencephalography (EEG), have been associated with chronic psychotic disorders, but their prevalence in the early phase of psychosis is less clear. We sought to address this by systematically reviewing the relevant literature. We searched for EEG studies of gamma band oscillations in subjects at high risk for psychosis and in patients with first episode psychosis. The following measures of gamma oscillations were extracted: resting power, evoked power, induced power, connectivity and peak frequency. Forty-five studies with a total of 3099 participants were included. There were potential sources of bias in the study designs and potential artefacts. Although there were few consistent findings, several studies reported decreased evoked or induced power in both high risk subjects and first episode patients. Studies using larger samples with serial EEG measurements, and designs that minimise artefacts that occur at the gamma frequency may advance work in this area.

State-of-the-Art Analysis of High-Frequency (Gamma Range) Electroencephalography in Humans.

Gamma oscillations (>30 Hz) in the brain are involved in attention, perception and memory. They are altered in various pathological states, as well as by neuropharmaceuticals, so that they are of interest in drug and clinical investigations. However, when the human electroencephalogram is recorded on the scalp, this neural high-frequency signal is buried under a range of other electrical signals such that, without careful handling, recordings of the high-frequency electroencephalogram cannot be considered reliable. The artefacts of concern originate from: power line noise, saccade-associated contraction of the extra-ocular muscles, activity of muscles in the scalp, face and neck, screen refresh artefacts and activity of the muscles associated with blinking. Recent progress in dealing with these artefacts is described, including either noise cancellation or phased noise template subtraction for power line noise, regression or independent component analysis for correcting extra-ocular muscle activity and mathematical modelling for reducing scalp, face and neck muscle activity. If the artefacts are properly addressed, the neural gamma signal can be uncovered.

Delta-9-tetrahydrocannabinol, neural oscillations above 20 Hz and induced acute psychosis.

RATIONALE: An acute challenge with delta-9-tetrahydrocannabinol (THC) can induce psychotic symptoms including delusions. High electroencephalography (EEG) frequencies, above 20 Hz, have previously been implicated in psychosis and schizophrenia. OBJECTIVES: The objective of this study is to determine the effect of intravenous THC compared to placebo on high-frequency EEG. METHODS: A double-blind cross-over study design was used. In the resting state, the high-beta to low-gamma magnitude (21-45 Hz) was investigated (n = 13 pairs + 4 THC only). Also, the event-related synchronisation (ERS) of motor-associated high gamma was studied using a self-paced button press task (n = 15). RESULTS: In the resting state, there was a significant condition × frequency interaction (p = 0.00017), consisting of a shift towards higher frequencies under THC conditions (reduced high beta [21-27 Hz] and increased low gamma [27-45 Hz]). There was also a condition × frequency × location interaction (p = 0.006), such that the reduction in 21-27-Hz magnitude tended to be more prominent in anterior regions, whilst posterior areas tended to show greater 27-45-Hz increases. This effect was correlated with positive symptoms, as assessed on the Positive and Negative Syndrome Scale (PANSS) (r = 0.429, p = 0.042). In the motor task, there was a main effect of THC to increase 65-130-Hz ERS (p = 0.035) over contra-lateral sensorimotor areas, which was driven by increased magnitude in the higher, 85-130-Hz band (p = 0.02) and not the 65-85-Hz band. CONCLUSIONS: The THC-induced shift to faster gamma oscillations may represent an over-activation of the cortex, possibly related to saliency misattribution in the delusional state.

A novel method for reducing the effect of tonic muscle activity on the gamma band of the scalp EEG.

Neural oscillations in the gamma band are of increasing interest, but separating them from myogenic electrical activity has proved difficult. A novel algorithm has been developed to reduce the effect of tonic scalp and neck muscle activity on the gamma band of the EEG. This uses mathematical modelling to fit individual muscle spikes and then subtracts them from the data. The method was applied to the detection of motor associated gamma in two separate groups of eight subjects using different sampling rates. A reproducible increase in high gamma (65-85 Hz) magnitude occurred immediately after the motor action in the left central area (p = 0.02 and p = 0.0002 for the two cohorts with individually optimized algorithm parameters, compared to p = 0.03 and p = 0.16 before correction). Whilst the magnitude of this event-related gamma synchronisation was not reduced by the application of the EMG reduction algorithm, the baseline left central gamma magnitude was significantly reduced by an average of 23 % with a faster sampling rate (p < 0.05). In comparison, at left and right temporo-parietal locations the gamma amplitude was reduced by 60 and 54 % respectively (p < 0.05). The reduction of EMG contamination by fitting and subtraction of individual spikes shows promise as a method of improving the signal to noise ratio of high frequency neural oscillations in scalp EEG.

Uncovering gamma in visual tasks.

Gamma is an important frequency band of the electroencephalogram (EEG), but its study has been impaired by problems with artefacts. This paper focuses on the artefacts caused by contraction of the extra-ocular muscles at the start of a saccade, which produces spurious gamma oscillations in the EEG. An algorithm was written and tested which detects and reduces the effect of this artefact. It involves novel adaptations of standard regression techniques which have traditionally been used to reduce blink artefacts, so as to render them applicable to the gamma band ocular artefact. Before the algorithm can be applied any power-line noise must be removed by noise cancellation and not notch filtering. The sharp, broadband gamma peak at around 200 ms was substantially reduced by the algorithm in all three subjects tested. However, there may be lower amplitude, task related, modulations in gamma which are uncovered when the artefact is reduced. The amplitude of the artefact had its largest positive value at the most anterior electrodes and its largest negative value at midline central and parietal electrodes, and these two sets of locations also showed the greatest reductions in gamma band magnitude after application of the algorithm. This study demonstrates the feasibility of reducing the saccade linked gamma band artefact.