Randomized placebo-controlled crossover trial of memantine in children with epileptic encephalopathy.

Memantine is an N-methyl-D-aspartate receptor antagonist, approved for dementia treatment. There is limited evidence of memantine showing benefit for paediatric neurodevelopmental phenotypes, but no randomized placebo-controlled trials in children with developmental and epileptic encephalopathy. In this randomized double-blind placebo-controlled crossover trial (Trial registration: https://clinicaltrials.gov/ct2/show/NCT03779672), patients with developmental and epileptic encephalopathy received memantine and placebo, each for a 6-week period separated by a 2-week washout phase. Electroencephalography, seizure diary, patient caregivers' global impression, serum inflammatory markers and neuropsychological evaluation were performed at baseline and after each treatment phase. The primary outcome measure was classification as a 'responder', defined as ≥2 of: >50% seizure frequency reduction, electroencephalography improvement, caregiver clinical impression improvement or clear neuropsychological testing improvement. Thirty-one patients (13 females) enrolled. Two patients withdrew prior to initiating medication and two (twins) had to be removed from analysis. Of the remaining 27 patients, nine (33%) were classified as responders to memantine versus two (7%) in the placebo group (P < 0.02). Electroencephalography improvement was seen in eight patients on memantine compared to two on placebo (P < 0.04). Seizure improvement was observed in eight patients on memantine and two on placebo (P < 0.04). Caregivers reported overall clinical improvement in 10 patients on memantine compared to seven on placebo (not significant). Statistical analysis of neuropsychological evaluation suggested improvements in symptoms of attention-deficit hyperactivity disorder and autism. Memantine is a safe and effective treatment for children with developmental and epileptic encephalopathy, having the potential to improve both seizure control and cognitive function.

Task-irrelevant filler items alter the dynamics of electrical brain activity during visual search.

In electroencephalography (EEG) studies of visual search, task-irrelevant fillers are included in displays to balance bottom-up stimulation across the visual field and generally considered as inconsequential for performance or EEG results. We examined the impact of fillers on target and distractor processing using lateralised event-related potentials (ERPs). Two task-relevant items (TRIs) were presented, with or without fillers. One TRI (target or target-colour distractor) was on the vertical midline and the other in a lateral position (left or right visual field) on an imaginary circle around fixation. An N2pc was elicited by lateral targets and task-relevant distractors, suggesting that attention was allocated to the lateral TRI because it possessed a target defining feature (colour). A Ptc was only elicited by lateral task-relevant distractors, in line with previous research suggesting that this component is associated with distractor processing. When fillers were also in the circular arrangement, alterations in performance and neural activity occurred. Fillers enhanced and delayed attentional deployment (N2pc) and delayed distractor processing (Ptc). Critically, we observed no difference in Ptc amplitude according to filler presence. Thus, if the Ptc reflects active suppression (or attentional disengagement), it was not required for fillers. ERPs were also modulated by the distance between TRIs (which could be separated by one or four filler positions), but differently according to the colour scheme (blue TRIs with grey fillers or vice versa). Our results suggest that fillers affect lateralised electrophysiological activity at multiple loci during visual search and should not be considered inconsequential.

Awake Craniotomy Language Mapping in Children With Drug-Resistant Epilepsy due to Focal Cortical Dysplasia.

BACKGROUND: Language mapping during awake craniotomy can allow for precise resection of epileptogenic lesions, while reducing the risk of damage to eloquent cortex. There are few reports in the literature of language mapping during awake craniotomy in children with epilepsy. Some centers may avoid awake craniotomy in the pediatric age group due to concerns that children are unable to cooperate with such procedures. METHODS: We reviewed pediatric patients from our center with drug-resistant focal epilepsy who underwent language mapping during awake craniotomy and subsequent resection of the epileptogenic lesion. RESULTS: Two patients were identified, both female, aged 17 years and 11 years at the time of surgery. Both patients had frequent and disabling focal seizures despite trials of multiple antiseizure medications. Both patients had resection of their epileptogenic lesions with the aid of intraoperative language mapping; in both cases pathology was consistent with focal cortical dysplasia. Both patients had transient language difficulties in the immediate postoperative period but no deficits at six-month follow-up. Both patients are now seizure-free. CONCLUSIONS: Awake craniotomy should be considered in pediatric patients with drug-resistant epilepsy in whom the suspected epileptogenic lesion is in close proximity to cortical language areas.

Effects of task-irrelevant or filler items on brain mechanisms of visual spatial attention.

Many visual search paradigms use color to distinguish task-relevant items from those considered fillers (e.g., blue task-relevant items and grey fillers). Hilimire and colleagues suggested that the N2pc, a lateralized electrophysiological component typically observed in visual attention, is a neural correlate for localized attentional interference, which postulates that target selection is degraded by nearby competing stimuli. In their study, N2pc amplitude decreased with decreasing distance between task-relevant items presented among fillers. With an increase in distance, however, there was also an increase in the number of fillers between task-relevant items. We tested whether this distance effect could be explained by the presence of fillers near task-relevant items rather than their proximity per se. We manipulated the distance between task-relevant items (adjacent, separated by two, or by four positions) and the presence/absence of fillers orthogonally. We used two color schemes: blue task-relevant items and grey fillers or grey task-relevant items and blue fillers (manipulated between-subjects) to control for color interactions. N2pc amplitude increased with increasing distance, but only when fillers were present, suggesting that the results of Hilimire et al. may be due to increasing fillers interference. Exploratory analyses also suggested that the colors selected to be task-relevant and task-irrelevant could play a role in our ability to filter task-irrelevant information. Our results suggest that fillers are not as inconsequential as sometimes assumed and generally support the Ambiguity Resolution Theory, where nearby items increase N2pc amplitude because of a greater need for focused attention.

Colour-specific differences in attentional deployment for equiluminant pop-out colours: evidence from lateralised potentials.

We investigated how target colour affected behavioural and electrophysiological results in a visual search task. Perceptual and attentional mechanisms were tracked using the N2pc component of the event-related potential and other lateralised components. Four colours (red, green, blue, or yellow) were calibrated for each participant for luminance through heterochromatic flicker photometry and equated to the luminance of grey distracters. Each visual display contained 10 circles, 1 colored and 9 grey, each of which contained an oriented line segment. The task required deploying attention to the colored circle, which was either in the left or right visual hemifield. Three lateralised ERP components relative to the side of the lateral coloured circle were examined: a posterior contralateral positivity (Ppc) prior to N2pc, the N2pc, reflecting the deployment of visual spatial attention, and a temporal and contralateral positivity (Ptc) following N2pc. Red or blue stimuli, as compared to green or yellow, had an earlier N2pc. Both the Ppc and Ptc had higher amplitudes to red stimuli, suggesting particular selectivity for red. The results suggest that attention may be deployed to red and blue more quickly than to other colours and suggests special caution when designing ERP experiments involving stimuli in different colours, even when all colours are equiluminant.

The attentional blink freezes spatial attention allocation to targets, not distractors: evidence from human electrophysiology.

Previous work found a significant reduction of the amplitude of the N2pc ERP component during the attentional blink in response to lateral visual targets, suggesting that the allocation of attention to visual targets is impaired during the attentional blink. Recent theorizing on the processes reflected by the N2pc suggests the possibility of distinct sets of neural mechanisms underlying its generation, one responsible for target activation, and one for distractor inhibition. To disentangle whether either or both of these mechanisms are impaired during the attentional blink, an RSVP sequence of circles, equidistant from fixation was used. The first target frame (T1) contained the same repeated target colour circle and target whereas the second target frame (T2) contained a distractor colour singleton as well as a target colour singleton. Only the target or only the distractor was presented at a lateral position; the other singleton was presented on the vertical midline so as not to elicit any event-related lateralization. Impaired T2 report accuracy at a short stimulus-onset asynchrony (SOA) was accompanied by a significant delay of the N2pc to lateral T2 targets when compared to a long SOA condition. No such delay was found when the lateralized stimulus was a distractor, suggesting that the attentional blink impacts attention allocation to targets, not distractors. We also observed a lateralized component earlier than the N2pc, a posterior contralateral positivity (Ppc) that did not depend on T1-T2 SOA and that was elicited by both lateral targets and distractors. We conclude that, contrary to N2pc, the Ppc likely reflects activity of bottom-up mechanisms responding unselectively to asymmetrical visual displays.

Electrophysiological evidence of multitasking impairment of attentional deployment reflects target-specific processing, not distractor inhibition.

We studied the interaction between the control mechanisms subserving spatial attention and central attention using the psychological refractory period (PRP) paradigm. Two stimuli, a pure tone (T(1)) and a circular visual array (T(2)), including a salient target and a salient distractor, were presented at varying stimulus onset asynchronies, each requiring a speeded response. Target-specific and distractor-specific lateralized event-related potentials were isolated by placing one of them at a lateral position and the other on the vertical midline. As SOA was decreased, a progressive reduction and postponement of a T(2)-locked N2pc component was observed with a lateral target and a central distractor. No lateralized potentials were associated with a lateral distractor and a central target. The sustained posterior contralateral negativity (SPCN) was observed independently of SOA modulation, only with a lateral target. We also observed an earlier positive deflection, the Ppc (positivity posterior contralateral), that was contralateral to both lateral targets and distractors, whose amplitude and latency were not affected by SOA variations. We conclude that central processing interferes specifically with target processing reflected by the N2pc and SPCN. We propose that the Ppc reflects an initial, bottom-up response to the presence of a salient stimulus, whereas the N2pc and SPCN reflect the controlled deployment of spatial attention to targets and maintenance of target information in visual short-term memory, respectively.