Elsevier

NeuroImage

Volume 48, Issue 4, December 2009, Pages 682-695
NeuroImage

fMRI activation during spike and wave discharges evoked by photic stimulation

https://doi.org/10.1016/j.neuroimage.2009.07.019Get rights and content

Abstract

Photoparoxysmal response (PPR) is an electroencephalographic (EEG) trait characterized by the occurrence of epileptiform discharges in response to visual stimulation. Studying this trait helps to learn about mechanisms of epileptogenicity. While simultaneous recordings of EEG and functional MRI (EEG–fMRI) in patients with spontaneous generalised spike-wave discharges (GSW) have revealed activation of the thalamus and deactivation in frontoparietal areas, EEG–fMRI studies on evoked GSW such as PPR are lacking. In this EEG–fMRI study, 30 subjects with reported generalised PPR underwent intermittent photic stimulation (IPS) in a 3 T MR scanner. PPR was elicited in 6 subjects, four diagnosed with idiopathic generalised epilepsy and two with tension-type headache. Because PPR is preceded by synchronization of cortical gamma oscillations, blood oxygenation level-dependent (BOLD) signal changes were analysed at the onset of the PPR (standard regressor) and 3 s before the onset of PPR (early regressor) in one model. In all subjects, IPS led to a significant activation of the visual cortex. Based on the early regressor, PPR associated activation was found in the parietal cortex adjacent to the intraparietal sulcus in five and in the premotor cortex in all 6 subjects. The standard regressor revealed deactivation in early activated areas in all subjects and thalamic activation in one subject. In contrast to spontaneous GSW, these results suggest that PPR is a cortical phenomenon with an involvement of the parietal and frontal cortices. Pronounced haemodynamic changes seen with the early regressor could mirror gamma activity that is known to precede PPR.

Introduction

Photosensitivity or photoparoxysmal response (PPR) is an abnormal, highly hereditary electroencephalographic (EEG) trait characterized by the occurrence of spikes or spike-wave discharges in response to visual stimulation (Fisher et al., 2005). Although PPR has been found in 0.5 to 7.6% subjects without epilepsy (Doose and Gerken, 1973, Trojaborg, 1992, Nagarajan et al., 2003), it is a more common feature of idiopathic generalised epilepsies (IGE), in which a PPR may be observed in 40–90% of the patients (Wolf and Goosses, 1986; Appleton et al., 2000; Lu et al., 2008). Sustained exposure to photic stimulation can induce epileptic seizures in photosensitive patients (Ferlazzo et al., 2005). Because of this close relationship between photosensitivity and epilepsy, studying mechanisms underlying PPR may shed light onto the pathophysiology of epilepsy in general. Several studies have shown that photosensitivity is characterized by an increased excitability of the occipital cortex (Porciatti et al., 2000, Siniatchkin et al., 2007). It has been demonstrated that a PPR occurs if normal physiological excitation in the occipital cortex exceeds a critical level (Wilkins et al., 2004) and if synchronization of gamma oscillations increases (Parra et al., 2003). However, these studies are only part of an incomplete puzzle and the pathophysiological mechanisms of the PPR are still insufficiently understood.

Simultaneous recording of EEG and blood oxygenation level-dependent (BOLD) functional MRI (EEG–fMRI) is a non-invasive imaging technique that allows to measure haemodynamic changes in the brain associated with GSW (Gotman et al., 2006, Laufs and Duncan, 2007). EEG–fMRI studies on spontaneous GSW have revealed a significant BOLD signal increase in the thalamus in the majority of patients, demonstrating an important role of this structure in the generation of this hypersynchronized activity (Aghakhani et al., 2004, Gotman et al., 2005, Hamandi et al., 2006, Moeller et al., 2008a, Moeller et al., 2008b). Moreover, these studies have shown a significant BOLD signal decrease in frontoparietal areas associated with GSW. These BOLD signal changes were interpreted in terms of the default mode theory which states that the parietal cortex, precuneus and frontal cortical areas are active at rest and support the state of consciousness in awake subjects (Raichle and Mintun, 2006). GSW-related BOLD signal decreases in those areas may indicate a disturbance of this physiological activity due to GSW (Gotman et al., 2005). A previous EEG–fMRI study on photosensitive patients failed to detect any PPR-related BOLD signal changes. It only showed an increased activation of the visual cortex during intermittent photic stimulation (IPS) when compared to controls, irrespectively of whether a PPR was elicited or not (Hill et al., 1999). The aim of this EEG–fMRI study was to investigate the pathophysiological mechanisms of PPRs by characterizing brain areas involved in their generation.

Section snippets

Subjects

From April 2006 to January 2008, 30 subjects with PPR were recruited from the Department of Neuropediatrics at the University Hospital Schleswig Holstein, Campus Kiel and the Northern German Epilepsy Centre for Children and Adolescents in Raisdorf, Germany. The mean age of subjects was 14 years (range: 8–22 years) at the time of the study. Neurological examination and structural MRI were normal. Visual acuity was normal or corrected-to-normal as assessed by the Snellen-chart. The study was

Results

Eight subjects had to be excluded from the study due to one of the following reasons: a) excessive movements, b) stopping of the investigation due to discomfort during IPS, c) technical problems, or d) frequent interictal generalised discharges. One other subject developed a photic induced seizure during the investigation and was reported elsewhere (Moeller et al., 2009). Six of the remaining 21 subjects showed reproducible PPR during the experiment and were included into the fMRI analysis. All

Discussion

This EEG–fMRI study describes BOLD signal changes associated with PPRs. All 6 subjects showed PPR-related increases in BOLD signal 3 s before the onset of the PPR (early regressor). In five subjects these early BOLD signal changes involved the parietal cortex in the in the vicinity of the intraparietal sulcus and the premotor cortex; in one subject, only bilateral frontal activation was found. In the analysis corresponding to the onset of PPR (standard regressor) deactivation in areas that had

Acknowledgments

We thank the subjects and their parents for participating in our study. This work was supported by grants from the BMBF (Bundesministerium für Bildung und Forschung) to H.R. Siebner (01GO 0511) and M. Siniatchkin and an intramural grant from the Medical Faculty of the University of Kiel to F. Moeller.

References (51)

  • PellegriniA. et al.

    Role of afferent input of subcortical origin in the genesis of bilaterally synchronous epileptic discharges of feline generalized penicillin epilepsy

    Exp. Neurol.

    (1979)
  • SrivastavaG. et al.

    ICA-based procedures for removing ballistocardiogram artifacts from EEG data acquired in the MRI scanner

    NeuroImage

    (2005)
  • TimofeevI. et al.

    Neocortical seizures: initiation, development and cessation

    Neuroscience

    (2004)
  • WaltzS. et al.

    The different patterns of the photoparoxysmal response—a genetic study

    Electroencephalogr. Clin. Neurophysiol.

    (1992)
  • AghakhaniY. et al.

    fMRI activation during spike and wave discharges in idiopathic generalized epilepsy

    Brain

    (2004)
  • AvoliM. et al.

    The effects of transient functional depression of the thalamus on spindles and on bilateral synchronous epileptic discharges of feline generalized penicillin epilepsy

    Epilepsia

    (1981)
  • BlumenfeldH

    Cellular and network mechanisms of spike-wave seizures. [Review]

    Epilepsia

    (2005)
  • DooseH. et al.

    On the genetics of EEG-anomalies in childhood. IV. Photoconvulsive reaction

    Neuropadiatrie

    (1973)
  • FerlazzoE. et al.

    Cortical triggers in generalized reflex seizures and epilepsies

    Brain

    (2005)
  • FisherR.S. et al.

    Epilepsy Foundation of America Working Group. Photic- and pattern-induced seizures: a review for the Epilepsy Foundation of America Working Group

    Epilepsia

    (2005)
  • FristonK.J. et al.

    Statistical parametric maps in functional imaging: a general linear approach

    Hum. Brain Map.

    (1995)
  • GotmanJ. et al.

    Generalized epileptic discharges show thalamocortical activation and suspension of the default state of the brain

    Proc. Natl. Acad. Sci. U. S. A.

    (2005)
  • GotmanJ. et al.

    Combining EEG and fMRI: a multimodal tool for epilepsy research

    J. Magn. Reson. Imaging

    (2006)
  • HardingG.F.A. et al.

    Two visual mechanisms of photosensitivity

    Epilepsia

    (1999)
  • HillR.A. et al.

    Hemodynamic and metabolic aspects of photosensitive epilepsy revealed by functional magnetic resonance imaging and magnetic resonance spectroscopy

    Epilepsia

    (1999)
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