Event-related potentials reveal preserved attention allocation but impaired emotion regulation in patients with epilepsy and comorbid negative affect

Patients with epilepsy have a high prevalence of comorbid mood disorders. This study aims to evaluate whether negative affect in epilepsy is associated with dysfunction of emotion regulation. Event-related potentials (ERPs) are used in order to unravel the exact electrophysiological time course and investigate whether a possible dysfunction arises during early (attention) and/or late (regulation) stages of emotion control. Fifty epileptic patients with (n = 25) versus without (n = 25) comorbid negative affect plus twenty-five matched controls were recruited. ERPs were recorded while subjects performed a face- or house-matching task in which fearful, sad or neutral faces were presented either at attended or unattended spatial locations. Two ERP components were analyzed: the early vertex positive potential (VPP) which is normally enhanced for faces, and the late positive potential (LPP) that is typically larger for emotional stimuli. All participants had larger amplitude of the early face-sensitive VPP for attended faces compared to houses, regardless of their emotional content. By contrast, in patients with negative affect only, the amplitude of the LPP was significantly increased for unattended negative emotional expressions. These VPP results indicate that epilepsy with or without negative affect does not interfere with the early structural encoding and attention selection of faces. However, the LPP results suggest abnormal regulation processes during the processing of unattended emotional faces in patients with epilepsy and comorbid negative affect. In conclusion, this ERP study reveals that early object-based attention processes are not compromised by epilepsy, but instead, when combined with negative affect, this neurological disease is associated with dysfunction during the later stages of emotion regulation. As such, these new neurophysiological findings shed light on the complex interplay of epilepsy with negative affect during the processing of emotional visual stimuli and in turn might help to better understand the etiology and maintenance of mood disorders in epilepsy

Neurophysiological investigations of drug resistant epilepsy patients treated with vagus nerve stimulation to differentiate responders from non-responders

Background and purpose In patients treated with vagus nerve stimulation (VNS) for drug resistant epilepsy (DRE), up to a third of patients will eventually not respond to the therapy. As VNS therapy requires surgery for device implantation, prediction of response prior to surgery is desirable. It is hypothesized that neurophysiological investigations related to the mechanisms of action of VNS may help to differentiate VNS responders from non-responders prior to the initiation of therapy. Methods In a prospective series of DRE patients, polysomnography, heart rate variability (HRV) and cognitive event related potentials were recorded. Polysomnography and HRV were repeated after 1 year of treatment with VNS. Polysomnography, HRV and cognitive event related potentials were compared between VNS responders (>= 50% reduction in seizure frequency) and non-responders. Results Fifteen out of 30 patients became VNS responders after 1 year of VNS treatment. Prior to treatment with VNS, the amount of deep sleep (NREM 3), the HRV high frequency (HF) power and the P3b amplitude were significantly different in responders compared to non-responders (P = 0.007; P = 0.001; P = 0.03). Conclusion Three neurophysiological parameters, NREM 3, HRV HF and P3b amplitude, were found to be significantly different in DRE patients who became responders to VNS treatment prior to initiation of their treatment with VNS. These non-invasive recordings may be used as characteristics for response in future studies and help avoid unsuccessful implantations. Mechanistically these findings may be related to changes in brain regions involved in the so-called vagal afferent network

EEG source connectivity to localize the seizure onset zone in patients with drug resistant epilepsy

Visual inspection of the EEG to determine the seizure onset zone (SOZ) in the context of the presurgical evaluation in epilepsy is time-consuming and often challenging or impossible. We offer an approach that uses EEG source imaging (ESI) in combination with functional connectivity analysis (FC) to localize the SOZ from ictal EEG. Ictal low-density-scalp EEG from 111 seizures in 27 patients who were rendered-seizure free after surgery was analyzed. For every seizure, ESI (LORETA) was applied on an artifact-free epoch selected around the seizure onset. Additionally, FC was applied on the reconstructed sources. We estimated the SOZ in two ways: (i)the source with highest power after ESI and (ii)the source with the most outgoing connections after ESI and FC. For both approaches, the distance between the estimated SOZ and the resected zone (RZ) of the patient were calculated. Using ESI alone, the SOZ was estimated inside the RZ in 31% of the seizures and within 10mm from the border of the RZ in 42%. For 18.5% of the patients, all seizures were estimated within 10mm of the RZ. Using ESI and FC, 72% of the seizures were estimated inside the RZ, and 94% within 10mm. For 85% of the patients, all seizures were estimated within 10mm of the RZ. FC provided a significant added value to ESI alone (p<0.001). ESI combined with subsequent FC is able to localize the SOZ in a non-invasive way with high accuracy. Therefore it could be a valuable tool in the presurgical evaluation of epilepsy

High-gamma oscillations precede visual steady-state responses : a human electrocorticography study

The robust steady-state cortical activation elicited by flickering visual stimulation has been exploited by a wide range of scientific studies. As the fundamental neural response inherits the spectral properties of the gazed flickering, the paradigm has been used to chart cortical characteristics and their relation to pathologies. However, despite its widespread adoption, the underlying neural mechanisms are not well understood. Here, we show that the fundamental response is preceded by high-gamma (55-125 Hz) oscillations which are also synchronised to the gazed frequency. Using a subdural recording of the primary and associative visual cortices of one human subject, we demonstrate that the latencies of the high-gamma and fundamental components are highly correlated on a single-trial basis albeit that the latter is consistently delayed by approximately 55 ms. These results corroborate previous reports that top-down feedback projections are involved in the generation of the fundamental response, but, in addition, we show that trial-to-trial variability in fundamental latency is paralleled by a highly similar variability in high-gamma latency. Pathology- or paradigm-induced alterations in steady-state responses could thus originate either from deviating visual gamma responses or from aberrations in the neural feedback mechanism. Experiments designed to tease apart the two processes are expected to provide deeper insights into the studied paradigm

A new insight into sentence comprehension : the impact of word associations in sentence processing as shown by invasive EEG recording

The effect of word association on sentence processing is still a matter of debate. Some studies observe no effect while others found a dependency on sentence congruity or an independent effect. In an attempt to separate the effects of sentence congruity and word association in the spatio-temporal domain, we jointly recorded scalp- and invasive-EEG (iEEG). The latter provides highly localized spatial (unlike scalp-EEG) and high temporal (unlike fMRI) resolutions. We recorded scalp- and iEEG in three patients with refractory epilepsy. The stimuli consisted of 280 sentences with crossed factors of sentence congruity and within sentence word-association. We mapped semantic retrieval processes involved in sentence comprehension onto the left temporal cortex and both hippocampi, and showed for the first time that certain localized regions participate in the processing of word association in sentence context. Furthermore, simultaneous recording of scalp- and iEEG gave us a direct overview of signal change due to its propagation across the head tissues

Decoding steady-state visual evoked potentials from electrocorticography

We report on a unique electrocorticography (ECoG) experiment in which Steady-State Visual Evoked Potentials (SSVEPs) to frequency-and phase-tagged stimuli were recorded from a large subdural grid covering the entire right occipital cortex of a human subject. The paradigm is popular in EEG-based Brain Computer Interfacing where selectable targets are encoded by different frequency-and/or phase-tagged stimuli. We compare the performance of two state-of-the-art SSVEP decoders on both ECoG-and scalp-recorded EEG signals, and show that ECoG-based decoding is more accurate for very short stimulation lengths (i.e., less than 1 s). Furthermore, whereas the accuracy of scalp-EEG decoding bene fi ts from a multi-electrode approach, to address interfering EEG responses and noise, ECoG decoding enjoys only a marginal improvement as even a single electrode, placed over the posterior part of the primary visual cortex, seems to suf fi ce. This study shows, for the fi rst time, that EEG-based SSVEP decoders can in principle be applied to ECoG, and can be expected to yield faster decoding speeds using less electrodes

Localization of deep brain activity with scalp and subdural EEG

To what extent electrocorticography (ECoG) and electroencephalography (scalp EEG) differ in their capability to locate sources of deep brain activity is far from evident. Compared to EEG, the spatial resolution and signal- to-noise ratio of ECoG is superior but its spatial coverage is more restricted, as is arguably the volume of tissue activity effectively measured from. Moreover, scalp EEG studies are providing evidence of locating activity from deep sources such as the hippocampus using high-density setups during quiet wakefulness. To address this question, we recorded a multimodal dataset from 4 patients with refractory epilepsy during quiet wakefulness. This data comprises simultaneous scalp, subdural and depth EEG electrode recordings. The latter was located in the hippocampus or insula and provided us with our "ground truth" for source localization of deep activity. We ap- plied independent component analysis (ICA) for the purpose of separating the independent sources in theta, alpha and beta frequency band activity. In all patients subdural- and scalp EEG components were observed which had a significant zero-lag correlation with one or more contacts of the depth electrodes. Subsequent dipole modeling of the correlating components revealed dipole locations that were significantly closer to the depth electrodes compared to the dipole location of non-correlating components. These findings support the idea that components found in both recording modalities originate from neural activity in close proximity to the depth electrodes. Sources localized with subdural electrodes were similar to 70% closer to the depth electrode than sources localized with EEG with an absolute improvement of around similar to 2cm. In our opinion, this is not a considerable improvement in source localization accuracy given that, for clinical purposes, ECoG electrodes were implanted in close proximity to the depth electrodes. Furthermore, the ECoG grid attenuates the scalp EEG, due to the electrically isolating silastic sheets in which the ECoG electrodes are embedded. Our results on dipole modeling show that the deep source localization accuracy of scalp EEG is comparable to that of ECoG. Significance Statement Deep and subcortical regions play an important role in brain function. However, as joint recordings at multiple spatial scales to study brain function in humans are still scarce, it is still unresolved to what extent ECoG and EEG differ in their capability to locate sources of deep brain activity. To the best of our knowledge, this is the first study presenting a dataset of simultaneously recorded EEG, ECoG and depth electrodes in the hippocampus or insula, with a focus on non-epileptiform activity (quiet wakefulness). Furthermore, we are the first study to provide experimental findings on the comparison of source localization of deep cortical structures between invasive and non-invasive brain activity measured from the cortical surface

Manchester triage system in paediatric emergency care: prospective observational study

Objective To validate use of the Manchester triage system in paediatric emergency care