EEG‐fMRI in atypical benign partial epilepsy

Atypical benign partial epilepsy (ABPE) is a subgroup among the idiopathic focal epilepsies of childhood. Aim of this study was to investigate neuronal networks underlying ABPE and compare the results with previous electroencephalography (EEG)–functional magnetic resonance imaging (fMRI) studies of related epilepsy syndromes. Ten patients with ABPE underwent simultaneous EEG‐fMRI recording. In all 10 patients several types of interictal epileptiform discharges (IEDs) were recorded. Individual IED‐associated blood oxygen level–dependent (BOLD) signal changes were analyzed in a single subject analysis for each IED type (33 studies). A group analysis was also performed to determine common BOLD signal changes across the patients. IED‐associated BOLD signal changes were found in 31 studies. Focal BOLD signal changes concordant with the spike field (21 studies) and distant cortical and subcortical BOLD signal changes (31 studies) were detected. The group analysis revealed a thalamic activation. This study demonstrated that ABPE is characterized by patterns similar to studies in rolandic epilepsy (focal BOLD signal changes in the spike field) as well as patterns observed in continuous spikes and waves during slow sleep (CSWS) (distant BOLD signal changes in cortical and subcortical structures), thereby underscoring that idiopathic focal epilepsies of childhood form a spectrum of overlapping syndromes.     

Complex discharge‐affecting networks in juvenile myoclonic epilepsy: A simultaneous EEG‐fMRI study

Juvenile myoclonic epilepsy (JME) is a common subtype of idiopathic generalized epilepsies (IGEs) and is characterized by myoclonic jerks, tonic‐clonic seizures and infrequent absence seizures. The network notion has been proposed to better characterize epilepsy. However, many issues remain not fully understood in JME, such as the associations between discharge‐affecting networks and the relationships among resting‐state networks. In this project, eigenspace maximal information canonical correlation analysis (emiCCA) and functional network connectivity (FNC) analysis were applied to simultaneous EEG‐fMRI data from JME patients. The main findings of our study are as follows: discharge‐affecting networks comprising the default model (DMN), self‐reference (SRN), basal ganglia (BGN) and frontal networks have linear and nonlinear relationships with epileptic discharge information in JME patients; the DMN, SRN and BGN have dense/specific associations with discharge‐affecting networks as well as resting‐state networks; and compared with controls, significantly increased FNCs between the salience network (SN) and resting‐state networks are found in JME patients. These findings suggest that the BGN, DMN and SRN may play intermediary roles in the modulation and propagation of epileptic discharges. These roles further tend to disturb the switching function of the SN in JME patients. We also postulate that emiCCA and FNC analysis may provide a potential analysis platform to provide insights into our understanding of the pathophysiological mechanism of epilepsy subtypes such as JME. Hum Brain Mapp 37:3515–3529, 2016. © 2016 Wiley Periodicals, Inc.     

Simultaneous EEG and fMRI recordings (EEG‐fMRI) in children with epilepsy

By combining electroencephalography (EEG) with functional magnetic resonance imaging (fMRI) it is possible to describe blood oxygenation level–dependent (BOLD) signal changes related to EEG patterns. This way, EEG‐pattern–associated networks of hemodynamic changes can be detected anywhere in the brain with good spatial resolution. This review summarizes EEG‐fMRI studies that have been performed in children with epilepsy. EEG‐fMRI studies in focal epilepsy (structural and nonlesional cases, benign epilepsy with centrotemporal spikes), generalized epilepsy (especially absence epilepsy), and epileptic encephalopathies (West syndrome, Lennox‐Gastaut syndrome, continuous spike and waves during slow sleep, and Dravet syndrome) are presented. Although EEG‐fMRI was applied mainly to localize the region presumably generating focal interictal discharges in focal epilepsies, EEG‐fMRI identified underlying networks in patients with generalized epilepsies and thereby contributed to a better understanding of these epilepsies. In epileptic encephalopathies a specific fingerprint of hemodynamic changes associated with the particular syndrome was detected. The value of the EEG‐fMRI technique for diagnosis and investigation of pathogenetic mechanisms of different forms of epilepsy is discussed.     

Absence seizures: Individual patterns revealed by EEG‐fMRI

Purpose: Absences are characterized by an abrupt onset and end of generalized 3–4 Hz spike and wave discharges (GSWs), accompanied by unresponsiveness. Although previous electroencephalography–functional magnetic resonance imaging (EEG–fMRI) studies showed that thalamus, default mode areas, and caudate nuclei are involved in absence seizures, the contribution of these regions throughout the ictal evolution of absences remains unclear. Furthermore, animal models provide evidence that absences are initiated by a cortical focus with a secondary involvement of the thalamus. The aim of this study was to investigate dynamic changes during absences. Methods: Seventeen absences from nine patients with absence epilepsy and classical pattern of 3–4 Hz GSWs during EEG‐fMRI recording were included in the study. The absences were studied in a sliding window analysis, providing a temporal sequence of blood oxygen–level dependent (BOLD) response maps. Results: Thalamic activation was found in 16 absences (94%), deactivation in default mode areas in 15 (88%), deactivation of the caudate nuclei in 10 (59%), and cortical activation in patient‐specific areas in 10 (59%) of the absences. Cortical activations and deactivations in default mode areas and caudate nucleus occurred significantly earlier than thalamic responses. Discussion: Like a fingerprint, patient‐specific BOLD signal changes were remarkably consistent in space and time across different absences of one patient but were quite different from patient to patient, despite having similar EEG pattern and clinical semiology. Early frontal activations could support the cortical focus theory, but with an addition: This early activation is patient specific.     

Electrophysiology meets fMRI: Neural correlates of the startle reflex assessed by simultaneous EMG–fMRI data acquisition

The startle reflex provides a unique tool for the investigation of sensorimotor gating and information processing. Simultaneous EMG–fMRI acquisition (i.e., online stimulation and recording in the MR environment) allows for the quantitative assessment of the neuronal correlates of the startle reflex and its modulations on a single trial level. This serves as the backbone for a startle response informed fMRI analysis, which is fed by data acquired in the same brain at the same time. We here present the first MR study using a single trial approach with simultaneous acquired EMG and fMRI data on the human startle response in 15 healthy young men. It investigates the neural correlates for isolated air puff startle pulses (PA), prepulse–pulse inhibition (PPI), and prepulse facilitation (PPF). We identified a common core network engaged by all three conditions (PA, PPI, and PPF), consisting of bilateral primary and secondary somatosensory cortices, right insula, right thalamus, right temporal pole, middle cingulate cortex, and cerebellum. The cerebellar vermis exhibits distinct activation patterns between the startle modifications. It is differentially activated with the highest amplitude for PPF, a lower activation for PA, and lowest for PPI. The orbital frontal cortex exhibits a differential activation pattern, not for the type of startle response but for the amplitude modification. For pulse alone it is close to zero; for PPI it is activated. This is in contrast to PPF where it shows deactivation. In addition, the thalamus, the cerebellum, and the anterior cingulate cortex add to the modulation of the startle reflex. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

BOLD signal changes preceding negative responses in EEG‐fMRI in patients with focal epilepsy

Purpose: In simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), increased neuronal activity from epileptiform spikes commonly elicits positive blood oxygenation level–dependent (BOLD) responses. Negative responses are also occasionally seen and have not been explained. Recent studies describe BOLD signal changes before focal EEG spikes. We aimed to systematically study if the undershoot of a preceding positive response might explain the negative BOLD seen in the focus. Methods: Eighty‐two patients with focal epilepsy who underwent EEG‐fMRI at 3T were retrospectively studied. Studies with a focal negative BOLD response in the region of the spike field were reanalyzed using models with hemodynamic response functions (HRFs) peaking from ?9 to +9 s around the spike. Results: Eight patients met the inclusion criteria, showing negative BOLD responses in the spike field on standard analysis. None had positive BOLD responses immediately adjacent to the areas of deactivation. Regions of deactivation were found to have congruent preceding positive responses in two cases. These early activations were seen at the combined maps of ?5 to ?9 s. Discussion: This study indicates that in a small proportion of patients with focal epilepsy in whom the standard analysis reveals focal negative responses, an earlier positive BOLD response is probably the cause. The origin of negative BOLD signal changes in the focus as a result of an epileptic event remains, however, unexplained in most of the patients in whom it occurs.     

Independent component analysis (ICA) of generalized spike wave discharges in fMRI: Comparison with general linear model‐based EEG‐fMRI

Most EEG‐fMRI studies in epileptic patients are analyzed using the general linear model (GLM), which assumes a known hemodynamic response function (HRF) to epileptic spikes. In contrast, independent component analysis (ICA) can extract blood‐oxygenation level dependent (BOLD) responses without imposing constraints on the HRF. ICA might therefore detect responses that vary in time and shape, and that are not detected in the GLM analysis. In this study, we compared the findings of ICA and GLM analyses in 12 patients with idiopathic generalized epilepsy. Spatial ICA was used to extract independent components from the functional magnetic resonance imaging (fMRI) data. A deconvolution method identified component time courses significantly related to the generalized EEG discharges, without constraining the shape of the HRF. The results from the ICA analysis were compared to those from the GLM analysis. GLM maps and ICA maps showed significant correlation and revealed BOLD responses in the thalamus, caudate nucleus, and default mode areas. In patients with a low rate of discharges per minute, the GLM analysis detected BOLD signal changes within the thalamus and the caudate nucleus that were not revealed by the ICA. In conclusion, ICA is a viable alternative technique to GLM analyses in EEG‐fMRI studies related to generalized discharges. This study demonstrated that the BOLD response largely resembles the standard HRF and that GLM analysis is adequate. However, ICA is more dependent on a sufficient number of events than GLM analysis. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Somatosensory reflex epilepsy: simultaneous video‐EEG monitoring and surface EMG

Somatosensory reflex epilepsy is induced by repetitive cutaneous contact of a circumscribed body area with a tight time‐lock between somatosensory stimulation and seizure. We describe the case of a 27‐year‐old man with seizures induced by repetitive tapping on the sole of the right foot. Simultaneous video‐EEG monitoring and surface electromyography was performed during a seizure triggered by repetitive tapping on the right sole aspect using a hammer. Stimulation produced a tingling sensation on the right sole that extended to the right lower leg. This was followed by motor Jacksonian march of the right leg. [Published with video sequence on www.epilepticdisorders.com ]     

Loss of frontal regulator of vigilance during sleep inertia: A simultaneous EEG‐fMRI study

Sleep inertia refers to a distinct physiological state of waking up from sleep accompanied by performance impairments and sleepiness. The neural substrates of sleep inertia are unknown, but growing evidence suggests that this inertia state maintains certain sleep features. To investigate the neurophysiological mechanisms of sleep inertia, a comparison of pre‐sleep and post‐sleep wakefulness with eyes‐open resting‐state was performed using simultaneous EEG‐fMRI, which has the potential to reveal the dynamic details of neuroelectric and hemodynamic responses with high temporal resolution. Our data suggested sleep‐like features of slow EEG power and decreased BOLD activity were persistent during sleep inertia. In the pre‐sleep phase, participants with stronger EEG vigilance showed stronger activity in the fronto‐parietal network (FPN), but this phenomenon disappeared during sleep inertia. A time course analysis confirmed a decreased correlation between EEG vigilance and the FPN activity during sleep inertia. This simultaneous EEG‐fMRI study advanced our understanding of sleep inertia and revealed the importance of the FPN in maintaining awareness. This is the first study to reveal the dynamic brain network changes from multi‐modalities perspective during sleep inertia.     

Hot water epilepsy

A 9‐year‐old Caucasian boy affected by hot water epilepsy, with positive family history, experienced complex partial seizures during contact with hot water. A video‐EEG recording was taken while hot water was poured onto his chest. Hot water epilepsy is rarely described in European countries, where bathing epilepsy in younger children is more common and often confused with this type of epilepsy. [Published with video sequences]     

Defecation reflex seizures: a case report with long‐term VEEG monitoring,neuroimaging and comprehensive epilepsy evaluation

Reflex seizures are consistently elicited by a specific afferent sensory stimulus or an activity undertaken by the patient. Among many known stimuli, defecation has rarely been reported. We describe the case of a child with reflex seizures triggered by defecation, considering the diagnostic challenge, epilepsy evaluation with video‐EEG monitoring, as well as impact on neuropsychology, behaviour and quality of life. The child was a 10‐year‐old boy with seizure onset at age four with epilepsy diagnosis established one and a half years later. Seizures were focal with impaired awareness triggered by defecation. Video‐EEG and structural and functional neuroimaging were performed and all pointed to the left temporal region. The patient became seizure‐free with carbamazepine and valproic acid. Neuropsychological and quality of life assessments suggested global impairment, both before and after seizure control. This is the third case of epilepsy induced by defecation reported in the literature. The rarity of this entity may be a diagnostic challenge and postpone specific treatment. Reporting of cases of defecation reflex epilepsy may provide a better understanding of its physiopathology and optimize effective treatment, avoiding cognitive, behavioural and poor social consequences. [Published with video sequence]     

ICA decomposition of EEG signal for fMRI processing in epilepsy

In this study, we introduce a new approach to process simultaneous Electroencephalography and functional Magnetic Resonance Imaging (EEG‐fMRI) data in epilepsy. The method is based on the decomposition of the EEG signal using independent component analysis (ICA) and the usage of the relevant components' time courses to define the event related model necessary to find the regions exhibiting fMRI signal changes related to interictal activity. This approach achieves a natural data‐driven differentiation of the role of distinct types of interictal activity with different amplitudes and durations in the epileptogenic process. Agreement between the conventional method and this new approach was obtained in 6 out of 9 patients that had interictal activity inside the scanner. In all cases, the maximum Z‐score was greater in the fMRI studies based on ICA component method and the extent of activation was increased in 5 out of the 6 cases in which overlap was found. Furthermore, the three cases where an agreement was not found were those in which no significant activation was found at all using the conventional approach. Hum Brain Mapp 2009. © 2009 Wiley‐Liss, Inc.     

Siblings with refractory occipital epilepsy showing localized network activity on EEG‐fMRI

The benign occipital epilepsies of childhood include Panayiotopoulos and Gastaut syndromes; a third syndrome, idiopathic photosensitive occipital epilepsy may also begin in childhood or adolescence. We describe siblings with occipital epilepsy characterized by refractory, frequent, brief visual seizures and normal magnetic resonance imaging (MRI). Electroencephalography (EEG) with functional MRI (fMRI) supports localization of interictal epileptiform activity to the occipital lobes. Our hypothesis is that the siblings share a genetic focal epilepsy arising from a localized occipital network. Although they share many features of Gastaut syndrome, their refractory ongoing seizures in adolescence is unusual and likely due to underlying genetic determinants.     

Investigation of the electrophysiological correlates of negative BOLD response during intermittent photic stimulation: An EEG‐fMRI study

Although the occurrence of concomitant positive BOLD responses (PBRs) and negative BOLD responses (NBRs) to visual stimuli is increasingly investigated in neuroscience, it still lacks a definite explanation. Multimodal imaging represents a powerful tool to study the determinants of negative BOLD responses: the integration of functional Magnetic Resonance Imaging (fMRI) and electroencephalographic (EEG) recordings is especially useful, since it can give information on the neurovascular coupling underlying this complex phenomenon. In the present study, the brain response to intermittent photic stimulation (IPS) was investigated in a group of healthy subjects using simultaneous EEG‐fMRI, with the main objective to study the electrophysiological mechanisms associated with the intense NBRs elicited by IPS in extra‐striate visual cortex. The EEG analysis showed that IPS induced a desynchronization of the basal rhythm, followed by the instauration of a novel rhythm driven by the visual stimulation. The most interesting results emerged from the EEG‐informed fMRI analysis, which suggested a relationship between the neuronal rhythms at 10 and 12 Hz and the BOLD dynamics in extra‐striate visual cortex. These findings support the hypothesis that NBRs to visual stimuli may be neuronal in origin rather than reflecting pure vascular phenomena. Hum Brain Mapp 37:2247–2262, 2016. © 2016 Wiley Periodicals, Inc.     

难治性癫痫致病灶术前定位EEG联合fMRI检查的临床研究

目的探讨对难治性癫痫患者术前进行EEG联合fMRI检查确定癫痫致病灶的准确性。方法选取行外科手术的难治性癫痫患者23例为研究对象,患者佩戴能在高场强MR室中使用的EEG高级电极帽,在MR扫描的同时采集EEG数据,记录棘波发生时间,并根据棘波的发放时间输入信号曲线,找出fMRI数据,求fMRI数据体与该曲线的相应关系,将相应程度高的区域(激活区)叠加在MRI的三维图像上,从而对癫痫致病灶进行定位。将该致病灶的位置、范围与手术中脑皮质电极及深部电极中显示的致痫灶进行比较。结果 13例(56.52%)EEG联合fMRI检查显示的癫痫致病灶与术中通过皮质电极及深部电极EEG所描记、确定的致病灶位置和范围完全相同。另外10例(43.48%)EEG联合fMRI检查显示的癫痫致病灶与术中通过皮质电极及深部电极EEG所描记、确定的致病灶位置相同,但是范围明显大于术中所确定的致病灶范围;对患者出院后进行随访6个月以上,其中15例(65.22%)癫痫未再发作,5例(14.29%)术后3周内出现癫痫发作1~4次,给予抗癫痫药物治疗后得到控制,3例(13.04%)仍有发作,给予药物控制后仍无法控制,但发作频率为每月(3.1±1.4)次,较术前发作次数明显降低。结论对难治性癫痫患者术前进行EEG联合fMRI检查定位致病灶,其定位准确,时间及空间分辨率均较高且是无创性的。     

Patient specific hemodynamic response functions associated with interictal discharges recorded via simultaneous intracranial EEG‐fMRI

Simultaneous collection of scalp EEG and fMRI has become an important tool for studying the hemodynamic changes associated with interictal epileptiform discharges (IEDs) in persons with epilepsy, and has become a standard presurgical assessment tool in some centres. We previously demonstrated that performing EEG‐fMRI using intracranial electrodes (iEEG‐fMRI) is of low risk to patients in our research centre, and offers unique insight into BOLD signal changes associated with IEDs recorded from very discrete sources. However, it is unknown whether the BOLD response corresponding to IEDs recorded by iEEG‐fMRI follows the canonical hemodynamic response. We therefore scanned 11 presurgical epilepsy patients using iEEG‐fMRI, and assessed the hemodynamic response associated with individual IEDs using two methods: assessment of BOLD signal changes associated with isolated IEDs at the location of the active intracranial electrode, and by estimating subject‐specific impulse response functions to isolated IEDs. We found that the hemodynamic response associated with the intracranially recorded discharges varied by patient and by spike location. The observed shape and timing differences also deviated from the canonical hemodynamic response function traditionally used in many fMRI experiments. It is recommended that future iEEG‐fMRI studies of IEDs use a flexible hemodynamic response model when performing parametric tests to accurately characterize these data. Hum Brain Mapp 36:5252–5264, 2015. © 2015 Wiley Periodicals, Inc.