Antiepileptic effects of lacosamide loaded polymers implanted subdurally in GAERS

The current experiment investigated the ability of coaxial electrospun poly(D,L-lactide-co-glycolide) (PLGA) biodegradable polymer implants loaded with the antiepileptic drugs (AED) lacosamide to reduce seizures following implantation above the motor cortex in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS). In this prospective, randomized, masked experiments, GAERS underwent surgery for implantation of skull electrodes (n = 6), skull electrodes and blank polymers (n = 6), or skull electrodes and lacosamide loaded polymers (n = 6). Thirty-minute electroencephalogram (EEG) recordings were started at day 7 after surgery and continued for eight weeks. The number of SWDs and mean duration of one SWD were compared week-by-week between the three groups. There was no difference in the number of SWDs between any of the groups. However, the mean duration of one SWD was significantly lower in the lacosamide polymer group for up to 7 weeks when compared to the control group (0.004 \u3c p \u3c 0.038). The mean duration of one seizure was also lower at weeks 3, 5, 6, and 7 when compared to the blank polymer group (p = 0.016, 0.037, 0.025, and 0.025, resp.). We have demonstrated that AED loaded PLGA polymer sheets implanted on the surface of the cortex could affect seizure activity in GAERS for a sustained period

Matching pursuit based removal of cardiac pulse-related artifacts in EEG/fMRI

Cardiac pulse-related artifacts in the EEG recorded simultaneously with fMRI are complex and highly variable. Their effective removal is an unsolved problem. Our aim is to develop an adaptive removal algorithm based on the matching pursuit (MP) technique and to compare it to established methods using a visual evoked potential (VEP). We recorded the VEP inside the static magnetic field of an MR scanner (with artifacts) as well as in an electrically shielded room (artifact free). The MP-based artifact removal outperformed average artifact subtraction (AAS) and optimal basis set removal (OBS) in terms of restoring the EEG field map topography of the VEP. Subsequently, a dipole model was fitted to the VEP under each condition using a realistic boundary element head model. The source location of the VEP recorded inside the MR scanner was closest to that of the artifact free VEP after cleaning with the MP-based algorithm as well as with AAS. While none of the tested algorithms offered complete removal, MP showed promising results due to its ability to adapt to variations of latency, frequency and amplitude of individual artifact occurrences while still utilizing a common template

Bilateral volume reduction in posterior hippocampus in psychosis of epilepsy

Objective Psychosis of epilepsy (POE) occurs more frequently in temporal lobe epilepsy, raising the question as to whether abnormalities of the hippocampus are aetiologically important. Despite decades of investigation, it is unclear whether hippocampal volume is reduced in POE, perhaps due to small sample sizes and methodological limitations of past research. Methods In this study, we examined the volume of the total hippocampus, and the hippocampal head, body and tail, in a large cohort of patients with POE and patients with epilepsy without psychosis (EC). One hundred adults participated: 50 with POE and 50 EC. Total and subregional hippocampal volumes were manually traced and compared between (1) POE and EC; (2) POE with temporal lobe epilepsy, extratemporal lobe epilepsy and generalised epilepsy; and (3) patients with POE with postictal psychosis (PIP) and interictal psychosis (IP). Results Compared with EC the POE group had smaller total left hippocampus volume (13.5% decrease, p<0.001), and smaller left hippocampal body (13.3% decrease, p=0.002), and left (41.5% decrease, p<0.001) and right (36.4% decrease, p<0.001) hippocampal tail volumes. Hippocampal head volumes did not differ between groups. Conclusion Posterior hippocampal volumes are bilaterally reduced in POE. Volume loss was observed on a posteroanterior gradient, with severe decreases in the tail and moderate volume decreases in the body, with no difference in the hippocampal head. Posterior hippocampal atrophy is evident to a similar degree in PIP and IP. Our findings converge with those reported for the paradigmatic psychotic disorder, schizophrenia, and suggest that posterior hippocampal atrophy may serve as a biomarker of the risk for psychosis, including in patients with epilepsy.JA is supported by an Australian Postgraduate Award

Cerebral cortex : an MRI-based study of volume and variance with age and sex

The aim of the present study was to examine quantitative differences in lobar cerebral cortical volumes in a healthy adult population. Quantitative volumetric MRI of whole brain, cerebral and cerebellar volumes was performed in a cross-sectional analysis of 97 normal volunteers, with segmented frontal, temporal, parietal and occipital cortical volumes measured in a subgroup of 60 subjects, 30 male and 30 female, matched for age and sex. The right cerebral hemisphere was larger than the left across the study group with a small (&lt;1%) but significant difference in symmetry (P &lt; 0.001). No difference was found between volumes of right and left cerebellar hemispheres. Rightward cerebral cortical asymmetry (right larger than left) was found to be significant across all lobes except parietal. Males had greater cerebral, cerebellar and cerebral cortical lobar volumes than females. Larger male cerebral cortical volumes were seen in all lobes except for left parietal. Females had greater left parietal to left cerebral hemisphere and smaller left temporal to left cerebral hemisphere ratios. There was a mild reduction in cerebral volumes with age, more marked in males. This study confirms and augments past work indicating underlying structural asymmetries in the human brain, and provides further evidence that brain structures in humans are differentially sensitive to the effects of both age and sex.<br /

Virtual intracranial EEG signals reconstructed from MEG with potential for epilepsy surgery

Modelling the interactions that arise from neural dynamics in seizure genesis is challenging but important in the effort to improve the success of epilepsy surgery. Dynamical network models developed from physiological evidence offer insights into rapidly evolving brain networks in the epileptic seizure. A limitation of previous studies in this field is the dependence on invasive cortical recordings with constrained spatial sampling of brain regions that might be involved in seizure dynamics. Here, we propose virtual intracranial electroencephalography (ViEEG), which combines non-invasive ictal magnetoencephalographic imaging (MEG), dynamical network models and a virtual resection technique. In this proof-of-concept study, we show that ViEEG signals reconstructed from MEG alone preserve critical temporospatial characteristics for dynamical approaches to identify brain areas involved in seizure generation. We show the non-invasive ViEEG approach may have some advantage over intracranial electroencephalography (iEEG). Future work may be designed to test the potential of the virtual iEEG approach for use in surgical management of epilepsy

Implementation of a closed-loop BCI system for real-time speech synthesis under clinical constraints

Closed-loop brain-computer interface (BCI) systems that provide real-time feedback to their users are essential for the synthesis of attempted or imagined speech from intracranial recordings. Here, we describe the implementation of our BCI speech synthesis system, which can be trained with a limited amount of overt speech to produce a continuous stream of audio outputs during subsequent speech imagery tasks. We evaluate (1) the effect of parameter choices on the execution time of individual operations in the BCI loop and (2) the accuracy of predicted outputs. To confirm the feasibility of our approach, we conduct simulations in a pseudo-prospective fashion using recorded datasets from five patients undergoing intracranial epilepsy monitoring. We propose that our system can be used to synthesize different types of speech under specific clinical constraints.N

Extending communication for patients with disorders of consciousness

The difficulty of distinguishing disorders of consciousness from certain disorders of communication leads to the possibility of false diagnosis. Our aim is to communicate with patients with disorders of consciousness through asking them to answer questions with 'yes/no' by performing mental imagery tasks using functional magnetic resonance imaging (fMRI). A 1.5 T fMRI study with 5 patients and a control group is presented. Speech comprehension, mental imagery, and question-answer tests were performed. The imagery task of mental calculation produced equally distinct activation patterns when compared to navigation and motor imagery in controls. For controls, we could infer answers to questions based on imagery activations. Two patients produced activations in similar areas to controls for certain imagery tasks, however, no activations were observed for the question-answer task. The results from 2 patients provide independent support of similar work by others with 3 T fMRI, and demonstrate broader clinical utility for these tests at 1.5 T despite lower signal-to-noise ratio. Based on the control results, mental calculation adds a robust imagery task for use in future studies of this kind

Enlarged hippocampal fissure in psychosis of epilepsy

Psychosis of epilepsy (POE) can be a devastating condition, and its neurobiological basis remains unclear. In a previous study, we identified reduced posterior hippocampal volumes in patients with POE. The hippocampus can be further subdivided into anatomically and functionally distinct subfields that, along with the hippocampal fissure, have been shown to be selectively affected in other psychotic disorders and are not captured by gross measures of hippocampal volume. Therefore, in this study, we compared the volume of selected hippocampal subfields and the hippocampal fissure in 31 patients with POE with 31 patients with epilepsy without psychosis. Cortical reconstruction, volumetric segmentation, and calculation of hippocampal subfields and the hippocampal fissure were performed using FreeSurfer. The group with POE had larger hippocampal fissures bilaterally compared with controls with epilepsy, which was significant on the right. There were no significant differences in the volumes of the hippocampal subfields between the two groups. Our findings suggest abnormal development of the hippocampus in POE. They support and expand the neurodevelopmental model of psychosis, which holds that early life stressors lead to abnormal neurodevelopmental processes, which underpin the onset of psychosis in later life. In line with this model, the findings of the present study suggest that enlarged hippocampal fissures may be a biomarker of abnormal neurodevelopment and risk for psychosis in patients with epilepsy.James Allebone was supported by an Australian Postgraduate Award for this researc

A growth chart of brain function from infancy to adolescence based on EEG

Background: In children, objective, quantitative tools that determine functional neurodevelopment are scarce and rarely scalable for clinical use. Direct recordings of cortical activity using routinely acquired electroencephalography (EEG) offer reliable measures of brain function. Methods: We developed and validated a measure of functional brain age (FBA) using a residual neural network-based interpretation of the paediatric EEG. In this cross-sectional study, we included 1056 children with typical development ranging in age from 1 month to 18 years. We analysed a 10- to 15-min segment of 18-channel EEG recorded during light sleep (N1 and N2 states). Findings: The FBA had a weighted mean absolute error (wMAE) of 0.85 years (95% CI: 0.69–1.02; n = 1056). A two-channel version of the FBA had a wMAE of 1.51 years (95% CI: 1.30–1.73; n = 1056) and was validated on an independent set of EEG recordings (wMAE = 2.27 years, 95% CI: 1.90–2.65; n = 723). Group-level maturational delays were also detected in a small cohort of children with Trisomy 21 (Cohen's d = 0.36, p = 0.028). Interpretation: A FBA, based on EEG, is an accurate, practical and scalable automated tool to track brain function maturation throughout childhood with accuracy comparable to widely used physical growth charts. Funding: This research was supported by theNational Health and Medical Research Council, Australia, Helsinki University Diagnostic Center Research Funds, Finnish Academy, Finnish Paediatric Foundation, and Sigrid Juselius Foundation.Peer reviewe