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We consider the theoretical constraints on interactions between coupled cortical columns. Each column comprises a set of neural populations, where each population is modelled as a neural mass. The existence of semi-stable states within a cortical column has been shown to be dependent on the type of interaction between the constituent neuronal subpopulations, i.e., the form of the implicit synaptic convolution kernels. Current-to-current coupling has been shown, in contrast to potential-to-current coupling, to create semi-stable states within a cortical column. In this analytic and numerical study, the interaction between semi-stable states is characterized by equations of motion for ensemble activity. We show that for small excitations, the dynamics follow the Kuramoto model. However, in contrast to previous work, we derive coupled equations between phase and amplitude dynamics. This affords the possibility of defining connectivity as a dynamic variable. The turbulent flow of phase dynamics found in networks of Kuramoto oscillators indicate turbulent changes in dynamic connectivity for coupled cortical columns. Crucially, this is something that has been recorded in epileptic seizures. We used the results we derived to estimate a seizure propagation model, which allowed for relatively straightforward inversions using variational Laplace (a.k.a., Dynamic Causal Modelling). The face validity of the ensuing seizure propagation model was established using simulated data as a prelude to future work; which will investigate dynamic connectivity from empirical data. This model also allows predictions of seizure evolution, induced by virtual lesions to synaptic connectivity: something that could be of clinical use, when applied to epilepsy surgical cases.

Background Disturbances in N-methyl-D-aspartate receptors (NMDARs)—as implicated in patients with schizophrenia—can cause regionally specific electrophysiological effects. Both animal models of NMDAR blockade and clinical studies in patients with schizophrenia have suggested that behavioral phenotypes are associated with reduction in inhibition within the frontal cortex. Methods Here we investigate event-related potentials to a roving auditory oddball paradigm under ketamine in healthy human volunteers (N= 18; double-blind, placebo-controlled, crossover design). Using recent advances in Bayesian modeling of group effects in dynamic causal modeling, we fit biophysically plausible network models of the auditory processing hierarchy to whole-scalp event-related potential recordings. This allowed us to identify regionally specific effects of ketamine in a distributed network of interacting cortical sources. Results We show that the effect of ketamine is best explained as a selective change in intrinsic inhibition, with a pronounced ketamine-induced reduction of inhibitory interneuron connectivity in frontal sources, compared with temporal sources. Simulations of these changes in an integrated microcircuit model shows that they are associated with a reduction in superficial pyramidal cell activity that can explain drug effects observed in the event-related potential. Conclusions These results are consistent with findings from invasive recordings in animal models exposed to NMDAR blockers, and provide evidence that inhibitory interneuron–specific NMDAR dysfunction may be sufficient to explain electrophysiological abnormalities induced by NMDAR blockade in human subjects.

Narcolepsy with cataplexy is a rare, but important differential diagnosis for daytime sleepiness and atonic paroxysms in an adolescent. A recent increase in incidence in the pediatric age group probably linked to the use of the Pandemrix influenza vaccine in 2009, has increased awareness that different environmental factors can "trigger" narcolepsy with cataplexy in a genetically susceptible population. Here, we describe the case of a 13-year-old boy with narcolepsy following yellow fever vaccination. He carries the HLA DQB1*0602 haplotype strongly associated with narcolepsy and cataplexy. Polysomnography showed rapid sleep onset with rapid eye movement (REM) latency of 47 min, significant sleep fragmentation and a mean sleep latency of 1.6 min with sleep onset REM in four out of four nap periods. Together with the clinical history, these findings are diagnostic of narcolepsy type 1. The envelope protein E of the yellow fever vaccine strain 17D has significant amino acid sequence overlap with both hypocretin and the hypocretin receptor 2 receptors in protein regions that are predicted to act as epitopes for antibody production. These findings raise the question whether the yellow fever vaccine strain may, through a potential molecular mimicry mechanism, be another infectious trigger for this neuro-immunological disorder.

Zusammenfassung Hintergrund Die Epilepsiechirurgie hat sich als wirksame Behandlungsmethode für pharmakoresistente, strukturelle Epilepsien erwiesen. Läsionen im posterioren Kortex stellen dabei – gerade bei Kindern – eine besondere Herausforderung dar. Fragestellung Wirksamkeit der epilepsiechirurgischen Eingriffe bei Kindern und Jugendlichen mit posterioren strukturellen Läsionen. Material und Methoden Literaturüberblick und Zusammenfassung der hauptsächlichen Befunde publizierter Studien zu pädiatrischen Kohorten nach epilepsiechirurgischer Behandlung posteriorer Epilepsien. Ergebnisse Epilepsien aufgrund posteriorer Läsionen sind bei Kindern häufiger als bei Erwachsenen und sind oft weniger klar lokalisiert und weniger deutlich von eloquentem Kortex abgrenzbar. Dennoch haben sich die postoperativen Verläufe in den letzten Jahrzehnten auf Grund von Fortschritten in der Abklärung deutlich verbessert. Schlussfolgerung Auch bei posterioren epileptogenen Läsionen ist die Epilepsiechirurgie oft eine wirksame Behandlungsmethode. Dabei bestehen die besten Aussichten auf Anfallsfreiheit nach frühzeitigen, ausreichend ausgedehnten Eingriffen. Das heißt, diese Kinder und Jugendlichen müssen für ein optimales Outcome umfangreich und v. a. frühzeitig abgeklärt werden.