Search

The ionotropic N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors of the glutamatergic neurotransmitter system are of fundamental importance to healthy brain function. Neuroimaging studies in humans have previously been conducted using various drugs that interact with N-methyl-D-aspartate glutamate receptors, but no such studies have investigated AMPA receptor signalling. The recent approval of perampanel (Fycompa) for use in humans provides a means to specifically study the role of AMPA receptors in the pharmacological basis of neuroimaging signals. Twenty male subjects participated in this placebo-controlled crossover study that consisted of two study days separated by a minimum two-week washout period. On one occasion participants ingested a 6 mg dose of perampanel, and on the other a placebo. Ten minutes of wakeful rest was recorded before and after each dose using magnetoencephalography. Subjective ratings of intoxication were significantly higher following drug than placebo. Cluster-based randomisation testing of sensor-level magnetoencephalography data showed significant drug-induced increases in low frequency power (1-4 Hz, 4-8 Hz, 8-13 Hz, 13-30 Hz), along with a significant decrease in the high gamma range (50-90 Hz). We also observed selective increases in functional connectivity in the alpha and beta bands. The findings are consistent with preclinical work and are similar to the spectral profile of other anti-epileptic drugs.

Background: Non-invasive in vivo neurophysiological recordings with EEG/MEG are key to the diagnosis, classification, and further understanding of epilepsy. Historically the emphasis of these recordings has been the localisation of the putative sources of epileptic discharges. More recent developments see new techniques studying oscillatory dynamics, connectivity and network properties., New Method: New analysis strategies for whole head MEG include the development of spatial filters or beamformers for source localisation, time-frequency analysis for cortical dynamics and graph theory applications for connectivity., Results: The idea of epilepsy as a network disorder is not new, and new applications of structural and functional brain imaging show differences in cortical and subcortical networks in patients with epilepsy compared to controls. Concepts of 'focal' and 'generalised' are challenged by evidence of focal onsets in generalised epileptic discharges, and widespread network changes in focal epilepsy. Spectral analyses can show differences in induced cortical response profiles, particularly in photosensitive epilepsy., Comparison With Existing Method: This review focuses on the application of MEG in the study of epilepsy, starting with a brief historical perspective, followed by novel applications of source localisation, time-frequency and connectivity analyses., Conclusion: Novel MEG analyses approaches show altered cortical dynamics and widespread network alterations in focal and generalised epilepsies, and identification of regional network abnormalities may have a role in epilepsy surgery evaluation., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: Magnetoencephalography (MEG) and a simple motor paradigm were used to study induced sensorimotor responses and their relationship to motor skills in children diagnosed with Benign Epilepsy with Centro-Temporal Spikes (BECTS)., Methods: Twenty-one children with BECTS and 15 age-matched controls completed a finger abduction task in MEG; movement-related oscillatory responses were derived and contrasted between groups. A subset of children also completed psycho-behavioural assessments. Regression analyses explored the relationship of MEG responses to manual dexterity performance, and dependence upon clinical characteristics., Results: In children with BECTS, manual dexterity was below the population mean (p=.002) and three showed severe impairment. Our main significant finding was of reduced ipsilateral movement related beta desynchrony (MRBDi) in BECTS relative to the control group (p=.03) and predicted by epileptic seizure recency (p=.02), but not age, medication status, or duration of epilepsy. Laterality scores across the entire cohort indicated that less lateralised MRBD predicted better manual dexterity (p=.04)., Conclusions: Altered movement-related oscillatory responses in ipsilateral motor cortex were associated with motor skill deficits in children with BECTS. These changes were more marked in those with more recent seizures., Significance: These findings may reflect differences in inter-hemispheric interactions during motor control in BECTS., (Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: We investigated differences in task induced responses in occipital and sensorimotor cortex between patients with juvenile myclonic epilepsy (JME) and healthy controls ., Methods: Twelve patients with JME and 12 age-matched non-epilepsy volunteers performed visual and motor tasks during MEG. We used synthetic aperture magnetometry to localise areas of task-related oscillatory modulations, performed time-frequency analyses on the locations of peak task related power changes and compared power and frequency modulation at these locations between patients and controls., Results: Patients with JME had significantly reduced pre-movement beta event-related desynchronisation in the motor task compared to controls. No significant differences were seen in other motor-related responses, or visual oscillatory responses., Conclusions: Altered beta event-related desynchronisation may represent network specific dysfunction in JME possibly through GABAergic dysfunction., Significance: Characterising task specific cortical responses in epilepsy offers the potential to understand the patho-physiological basis of seizures and provide a window on disease and treatment effects., (Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Abstract: The EEG/MEG signal is generated primarily by the summation of the post-synaptic potentials of cortical principal cells. At a microcircuit level, these glutamatergic principal cells are reciprocally connected to GABAergic interneurons and cortical oscillations are thought to be dependent on the balance of excitation and inhibition between these cell types. To investigate the dependence of movement-related cortical oscillations on excitation–inhibition balance, we pharmacologically manipulated the GABA system using tiagabine, which blocks GABA Transporter 1(GAT-1), the GABA uptake transporter and increases endogenous GABA activity. In a blinded, placebo-controlled, crossover design, in 15 healthy participants we administered either 15mg of tiagabine or a placebo. We recorded whole-head magnetoencephalograms, while the participants performed a movement task, prior to, one hour post, three hour post and five hour post tiagabine ingestion. Using time-frequency analysis of beamformer source reconstructions, we quantified the baseline level of beta activity (15–30Hz), the post-movement beta rebound (PMBR), beta event-related desynchronisation (beta-ERD) and movement-related gamma synchronisation (MRGS) (60–90Hz). Our results demonstrated that tiagabine, and hence elevated endogenous GABA levels causes, an elevation of baseline beta power, enhanced beta-ERD and reduced PMBR, but no modulation of MRGS. Comparing our results to recent literature (Hall et al., 2011) we suggest that beta-ERD may be a GABAA receptor mediated process while PMBR may be GABAB receptor mediated. [Copyright &y& Elsevier]

Larger size and higher spatial frequency of grating stimuli have been shown not only to maximally modulate early gamma-band visual cortical responses but also to provoke seizures in photosensitive epilepsy. Occipital brain magnetic field (MEG) oscillatory responses were evoked upon static grating pattern subthreshold stimuli in 12 patients with photosensitive epilepsy and 2 matched control groups, one with epilepsy but no photosensitivity and the other healthy controls. The continuous wavelet transform (CWT) was employed to characterize the time–frequency energy dynamics and phase-locking of the early evoked gamma-band oscillatory responses (eGBR). The photosensitive epilepsy group showed statistically significantly increased phase-locking of the gamma-band responses (eGBR) of the striate visual cortex in the (40–70 Hz) × (25–300 ms) and in the (25–30 Hz) × (300–600 ms) time–frequency windows with respect to the healthy controls. Photosensitive epilepsy seems to be characterized by altered phase synchronization dynamics at a higher frequency range (a-frequency band) compared to healthy controls. Our results indicate that photosensitive epilepsy is driven by the large-scale phase-locking of the underlying striatal visual cortical unit oscillators in specific “photosensitive” frequency components (dynamic phase-attractor theory of epilepsy). Our method could provide a novel diagnostic tool in safely detecting, investigating and assessing response to treatment in photosensitive epilepsy. [ABSTRACT FROM AUTHOR]