SUMMARYPurpose: To assess the extent of brain involvement during focal epileptic activity, we studied patterns of cortical and subcortical metabolic changes coinciding with interictal epileptic discharges (IEDs) using group analysis of simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) scans in patients with focal epilepsy. Methods: We selected patients with temporal lobe epilepsy (TLE, n = 32), frontal lobe epilepsy (FLE, n = 14), and posterior quadrant epilepsy (PQE, n = 20) from our 3 Tesla EEG-fMRI database. We applied group analysis upon the blood oxygen-level dependent (BOLD) response associated with focal IEDs. Key Findings: Patients with TLE and FLE showed activations and deactivations, whereas in PQE only deactivations occurred. In TLE and FLE, the largest activation was in the mid-cingulate gyri bilaterally. In FLE, activations were also found in the ipsilateral frontal operculum, thalamus, and internal capsule, and in the contralateral cerebellum, whereas in TLE, we found additional activations in the ipsilateral mesial and neocortical temporal regions, insula, and cerebellar cortex. All three groups showed deactivations in default mode network regions, the most widespread being in the TLE group, and less in PQE and FLE. Significance: These results indicate that different epileptic syndromes result in unique and widespread networks related to focal IEDs. Default mode regions are deactivated in response to focal discharges in all three groups with syndrome specific pattern. We conclude that focal IEDs are associated with specific networks of widespread metabolic changes that may cause more substantial disturbance to brain function than might be appreciated from the focal nature of the scalp EEG discharges.
SUMMARYPurpose: Simultaneous electroencephalography/functional magnetic resonance imaging (EEG/fMRI) recording can noninvasively map in the whole brain the hemodynamic response following an interictal epileptic discharge. EEG/fMRI is gaining interest as a presurgical evaluation tool. This study aims to determine how hemodynamic responses related to epileptic activity can help predict surgical outcome in patients considered for epilepsy surgery. Methods: Thirty-five consecutive patients with focal epilepsy who had significant hemodynamic responses and eventually surgical resection, were studied. The statistical map of hemodynamic responses were generated and coregistered to postoperative anatomic imaging. Patients were classified into four groups defined by the relative relationship between the location of the maximum hemodynamic response and the resection: group 1, fully concordant; group 2, partially concordant; group 3, partially discordant; and group 4, fully discordant. These findings were correlated with surgical outcome with at least 12-month follow-up. Key Findings: Ten patients in group 1 had the maximum t value (t-max) inside the resection; nine in group 2 had the t-max outside but close to the resection and the cluster with t-max overlapped the resection; five in group 3 had the t-max remote from resection, but with another less significant cluster in the resection; and 11 in group 4 had no response in the resection. The degree of concordance correlated largely with surgical outcome: a good surgical outcome (Engel's class I) was found in 7 of 10 patients of group 1, 4 of 9 of group 2, 3 of 5 of group 3, and only 1 of 11 of group 4. These results indicate that the partially concordant and partially discordant groups are best considered as inconclusive. In contrast, in the fully concordant and fully discordant groups, the sensitivity, specificity, positive predictive value, and negative predictive value were high, 87.5%, 76.9%, 70%, and 90.9%, respectively. Significance: This study demonstrates that hemodynamic responses related to epileptic activity can help delineate the epileptogenic region. Full concordance between maximum response and surgical resection is indicative of seizure freedom, whereas a resection leaving the maximum response intact is likely to lead to a poor outcome. EEG/fMRI is noninvasive but is limited to patients in whom interictal epileptic discharges can be recorded during the 60-90 min scan.
Vagus nerve stimulation (VNS) is widely used to treat drug-resistant epilepsy and depression.While the precise mechanisms mediating its long-term therapeutic effects are not fully resolved, they likely involve locus coeruleus (LC) stimulation via the nucleus of the solitary tract (NTS), which receives afferent vagal inputs. In rats, VNS elevates LC firing and forebrain noradrenaline levels, whereas LC lesions suppress VNS therapeutic efficacy. Non-invasive transcutaneous VNS (tVNS) employs electrical stimulation that targets the auricular branch of the vagus nerve at the cymba conchae of the ear. However, the extent that tVNS mimics VNS remains unclear. Here, we investigated the short-term effects of tVNS in healthy human male volunteers (n=24), using high-density EEG and pupillometry during visual fixation at rest. We compared short (3.4s) trials of tVNS to sham electrical stimulation at the earlobe (far from the vagus nerve branch) to control for somatosensory stimulation. Although tVNS and sham stimulation did not differ in subjective intensity ratings, tVNS led to robust pupil dilation (peaking 4-5s after trial onset) that was significantly higher than following sham stimulation.We further quantified, using parallel factor analysis, how tVNS modulates idle occipital alpha (8-13Hz) activity identified in each participant. We found greater attenuation of alpha oscillations by tVNS than by sham stimulation. This demonstrates that tVNS reliably induces pupillary and EEG markers of arousal beyond the effects of somatosensory stimulation, thus supporting the hypothesis that tVNS elevates noradrenaline and other arousal-promoting neuromodulatory signaling, and mimics invasive VNS.
Functional neuroimaging studies of epilepsy patients often show, at the time of epileptic activity, deactivation in default mode network (DMN) regions, which is hypothesized to reflect altered consciousness. We aimed to study the metabolic and electrophysiological correlates of these changes in the DMN regions. We studied six epilepsy patients that underwent scalp EEG-fMRI and later stereotaxic intracerebral EEG (SEEG) sampling regions of DMN (posterior cingulate cortex, Pre-cuneus, inferior parietal lobule, medial prefrontal cortex and dorsolateral frontal cortex) as well as non-DMN regions. SEEG recordings were subject to frequency analyses comparing sections with interictal epileptic discharges (IED) to IED-free baselines in the IED-generating region, DMN and non-DMN regions. EEG-fMRI and SEEG were obtained at rest. During IEDs, EEG-fMRI demonstrated deactivation in various DMN nodes in 5 of 6 patients, most frequently the pre-cuneus and inferior parietal lobule, and less frequently the other DMN nodes. SEEG analyses demonstrated decrease in gamma power (50–150 Hz), and increase in the power of lower frequencies (<30 Hz) at times of IEDs, in at least one DMN node in all patients. These changes were not apparent in the non-DMN regions. We demonstrate that, at the time of IEDs, DMN regions decrease their metabolic demand and undergo an EEG change consisting of decreased gamma and increased lower frequencies. These findings, specific to DMN regions, confirm in a pathological condition a direct relationship between DMN BOLD activity and EEG activity. They indicate that epileptic activity affects the DMN, and therefore may momentarily reduce the consciousness level and cognitive reserve.
Objective. Circadian and sleep dysfunction have long been symptomatic hallmarks of a variety of devastating neurodegenerative conditions. The gold standard for sleep monitoring is overnight sleep in a polysomnography (PSG) laboratory. However, this method has several limitations such as availability, cost and being labour-intensive. In recent years there has been a heightened interest in home-based sleep monitoring via wearable sensors. Our objective was to demonstrate the use of printed electrode technology as a novel platform for sleep monitoring. Approach. Printed electrode arrays offer exciting opportunities in the realm of wearable electrophysiology. In particular, soft electrodes can conform neatly to the wearer’s skin, allowing user convenience and stable recordings. As such, soft skin-adhesive non-gel-based electrodes offer a unique opportunity to combine electroencephalography (EEG), electromyography (EMG), electrooculography (EOG) and facial EMG capabilities to capture neural and motor functions in comfortable non-laboratory settings. In this investigation temporary-tattoo dry electrode system for sleep staging analysis was designed, implemented and tested. Main results. EMG, EOG and EEG were successfully recorded using a wireless system. Stable recordings were achieved both at a hospital environment and a home setting. Sleep monitoring during a 6 h session shows clear differentiation of sleep stages. Significance. The new system has great potential in monitoring sleep disorders in the home environment. Specifically, it may allow the identification of disorders associated with neurological disorders such as rapid eye movement (REM) sleep behavior disorder.
In EEG-fMRI studies, BOLD responses related to interictal epileptic discharges (IEDs) are most often the expected positive response (activation) but sometimes a surprising negative response (deactivation). The significance of deactivation in the region of IED generation is uncertain. The aim of this study was to determine if BOLD deactivation was caused by specific IED characteristics. Among focal epilepsy patients who underwent 3T EEG-fMRI from 2006 to 2011, those with negative BOLD having a maximum t-value in the IED generating region were selected.As controls, subjects with maximum activation in the IED generating region were selected. We established the relationship between the type of response (activation/deactivation) and (1) presence of slow wave in the IEDs, (2) lobe of epileptic focus, (3) occurrence as isolated events or bursts, (4) spatial extent of the EEG discharge. Fifteen patients with deactivation and 15 with activation were included. The IEDs were accompanied by a slow wave in 87 % of patients whose primary BOLD was a deactivation and only in 33 % of patients with activation. In the deactivation group, the epileptic focus was more frequently in the posterior quadrant and involved larger cortical areas, whereas in the activation group it was more frequently temporal. IEDs were more frequently of long duration in the deactivation group. The main factor responsible for focal deactivations is the Correspondence to: Jean Gotman. Electronic supplementary material The online version of this article
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