Elsevier

Epilepsy Research

Volume 108, Issue 6, August 2014, Pages 1076-1086
Epilepsy Research

Evidence for increased visual gamma responses in photosensitive epilepsy

https://doi.org/10.1016/j.eplepsyres.2014.04.012Get rights and content

Highlights

  • We investigated graded gamma band visual responses in photosensitive epilepsy and controls.

  • Gamma response contrast tuning was consistent with results from invasive animal studies in all groups.

  • Gamma frequency response did not differ between photosensitive participants and controls.

  • A higher gamma amplitude response was more common in photosensitive participants compared to controls and may be a feature of photosensitivity.

Summary

Background

A sustained gamma (30–70 Hz) oscillation induced in occipital cortex by high-contrast visual stimulation has been well characterised in animal local field potential recordings and in healthy human participants using magnetoencephalography (MEG). The spatial frequency of a static grating stimulus that gives maximal gamma is also that most likely to provoke seizures in photosensitive epilepsy.

Methods

We used MEG to study visual responses induced by grating stimuli of varying contrast and size in twelve patients with photosensitive epilepsy and two matched control groups, one with epilepsy but no photosensitivity, the other healthy controls. We used a beamformer approach to localise cortical responses and to characterise the time–frequency dynamics of evoked and induced oscillatory responses.

Results

A greater number of patients with photosensitivity had particularly amplitude gamma responses compared to controls. Formal statistical testing failed to find a group difference. One photosensitive patient, tested before and after sodium valproate, had a peak gamma amplitude when drug naive over four times larger than the group mean for controls; this high amplitude was substantially decreased after treatment with sodium valproate. We found no difference in the frequency of the sustained gamma response between the three groups.

Discussion

Altered power, but not frequency, in induced cortical responses to a static grating stimulus may be a characteristic of photosensitive epilepsy. Our failure to find a group difference on statistical testing may have been due to a wide intersubject variability and heterogeneity of the photosensitive group. A high amplitude response would be in keeping with previous evidence of altered contrast gain and increased spatial recruitment in photosensitive epilepsy.

Introduction

Between 1 and 3% of people with epilepsy demonstrate photosensitivity, where epileptic seizures are provoked by visual stimuli and a photoparoxysmal response (PPR) is seen on EEG testing (Guerrini and Genton, 2004). High intensity visual flicker, alternating patterns and high contrast achromatic gratings are most likely to induce seizures or a PPR (Binnie et al., 1985, Wilkins et al., 1979b). Several lines of evidence from MEG (Parra et al., 2003), EEG (Porciatti et al., 2000), fMRI (Chiappa et al., 1999), transcranial magnetic stimulation (Siniatchkin et al., 2007), and psychophysical measures (Shepherd and Siniatchkin, 2009), point to the abnormal recruitment of large assemblies of synchronously firing neurons in photosensitive epilepsy (PSE), suggesting underlying neural network abnormalities.

The induced response to visual stimulation includes an emergent gamma oscillation (30–70 Hz) that has been well characterised with intracranial local field potential (LFP) recordings in animals (Gray et al., 1989, Kayser et al., 2003, Ray and Maunsell, 2010), and non-invasively using magnetoencephalography (MEG) in humans (Adjamian et al., 2004, Hall et al., 2005). Notably, the stimulus properties that produce the greatest visual gamma response, namely a high contrast achromatic grating, with spatial frequency of 3 cycles per degree (Adjamian et al., 2004) are also those most likely to induce a PPR in those individuals with photosensitive epilepsy (Wilkins et al., 1979a). Furthermore, a correlation exists between the oscillatory frequency of visually induced gamma and the concentration of GABA in occipital cortex (Muthukumaraswamy et al., 2009) as predicted by modelling of coupled excitatory and inhibitory networks (Brunel and Wang, 2003).

In this study, we used MEG to characterise evoked and induced visual cortical responses to static luminance-defined visual gratings in three groups: epilepsy patients with, and without, photosensitivity and in non-epilepsy controls. We hypothesised that the induced gamma frequency would differ in patients with photosensitive epilepsy and controls. Our further objective was to examine in detail the time–frequency dynamics of evoked and induced responses in the three groups.

Section snippets

Participants

We tested the following groups: (1) photosensitive group: 12 patients (8 female, aged 13–30, mean age 22) with a diagnosis of idiopathic generalised epilepsy, and recent clinical EEG showing a PPR (type 3/4 Waltz classification) to photic stimulation, without a change in medication since the PPR was recorded, all but 2 patients had a history of clinical seizures induced by visual stimulation; (2) epilepsy control group: 9 epilepsy control patients (7 female, mean age: 24 years, range: 12–31

Results

Table 1 summarises the clinical data for the epilepsy participants. Fig. 1 illustrates the key aspects of the evoked and induced response in group average spectrograms of the averaged MEG signal from the gamma-band virtual sensor in the 8° size, 100% contrast condition (see Supplementary Figs. S1–S3 for individual participant spectrograms). All three groups show a similar time–frequency response, which is consistent with those shown in previous studies (Muthukumaraswamy et al., 2010). The

Discussion

We characterised MEG evoked and induced occipital cortical responses to low level visual stimuli in 12 patients with photosensitive epilepsy (PSE) and in two age- and sex-matched control groups We made the following observations: (1) Our findings on contrast tuning of the sustained gamma response replicated those from LFP recordings in primates (Ray and Maunsell, 2010), with a monotonic increase in gamma frequency and amplitude with increased stimulus contrast in all 3 groups. (2) The main

Conclusions

Cortical oscillatory dynamics may be altered in patients with photosensitive epilepsy. Our study suggests that the amplitude, rather than peak frequency, of the induced occipital gamma response to visual stimuli might be a useful index of photosensitivity. An increased amplitude of the induced gamma response in photosensitivity may be due to one or both of greater spatial spread of neural activity or increased phase synchronisation of neural firing due to impaired inhibitory mechanisms in

Conflicts of interest

None of the authors has any conflict of interest to disclose.

Acknowledgements

This work was funded by a grant from Epilepsy Research UK. Khalid Hamandi received funding from NISCHR Allied Heath Science Collaboration Fellowship grant and is a member of the Wales Epilepsy Research Network. CUBRIC was funded by the Welsh Government, the UK Department of Trade and Industry and Cardiff University. We are grateful to Professor Phil Smith, Dr's Frances Gibbon, Ann Johnson, Johanne te Water Naude and Benny Thomas for referring patients, Ms Alison McQueen (NISCHR research support

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