Aperiodic MEG abnormality in patients with focal to bilateral tonic-clonic seizures

Aperiodic activity is a physiologically distinct component of the electrophysiological power spectrum. It is suggested to reflect the balance of excitation and inhibition in the brain, within selected frequency bands. However, the impact of recurrent seizures on aperiodic activity remains unknown, particularly in patients with severe bilateral seizures. Here, we hypothesised greater aperiodic abnormality in the epileptogenic zone, in patients with focal to bilateral tonic clonic (FBTC) seizures, and earlier age of seizure onset. Pre-operative magnetoencephalography (MEG) recordings were acquired from 36 patients who achieved complete seizure freedom (Engel I outcome) post-surgical resection. A normative whole brain map of the aperiodic exponent was computed by averaging across subjects for each region in the hemisphere contralateral to the side of resection. Selected regions of interest were then tested for abnormality using deviations from the normative map in terms of z-scores. Resection masks drawn from postoperative structural imaging were used as an approximation of the epileptogenic zone. Patients with FBTC seizures had greater abnormality compared to patients with focal onset seizures alone in the resection volume (p=0.003, area under the ROC curve = 0.78 ). Earlier age of seizure onset was correlated with greater abnormality of the aperiodic exponent in the resection volume (correlation coefficient = -0.3, p= 0.04)) as well as the whole cortex (rho = -0.33, p=0.03). The abnormality of the aperiodic exponent did not significantly differ between the resected and non-resected regions of the brain. Abnormalities in aperiodic components relate to important clinical characteristics such as severity and age of seizure onset. This suggests the potential use of the aperiodic band power component as a marker for severity of epilepsy

Volumetric and structural connectivity abnormalities co-localise in TLE

Patients with temporal lobe epilepsy (TLE) exhibit both volumetric and structural connectivity abnormalities relative to healthy controls. How these abnormalities inter-relate and their mechanisms are unclear. We computed grey matter volumetric changes and white matter structural connectivity abnormalities in 144 patients with unilateral TLE and 96 healthy controls. Regional volumes were calculated using T1-weighted MRI, while structural connectivity was derived using white matter fibre tractography from diffusion-weighted MRI. For each regional volume and each connection strength, we calculated the effect size between patient and control groups in a group-level analysis. We then applied hierarchical regression to investigate the relationship between volumetric and structural connectivity abnormalities in individuals. Additionally, we quantified whether abnormalities co-localised within individual patients by computing Dice similarity scores. In TLE, white matter connectivity abnormalities were greater when joining two grey matter regions with abnormal volumes. Similarly, grey matter volumetric abnormalities were greater when joined by abnormal white matter connections. The extent of volumetric and connectivity abnormalities related to epilepsy duration, but co-localisation did not. Co-localisation was primarily driven by neighbouring abnormalities in the ipsilateral hemisphere. Overall, volumetric and structural connectivity abnormalities were related in TLE. Our results suggest that shared mechanisms may underlie changes in both volume and connectivity alterations in patients with TLE

Learning to Teach Argumentation: Research and development in the science classroom

The research reported in this study focuses on an investigation into the teaching of argumentation in secondary science classrooms. Over a one-year period, a group of 12 teachers from schools in the greater London area attended a series of workshops to develop materials and strategies to support the teaching of argumentation in scientific contexts. Data were collected at the beginning and end of the year by audio and video recording lessons where the teachers attempted to implement argumentation. To assess the quality of argumentation, analytical tools derived from Toulmin's argument pattern (TAP) were developed and applied to classroom transcripts. Analysis shows there was development in teachers' use of argumentation across the year. Results indicate that the pattern of use of argumentation is teacher-specific, as is the nature of change. To inform future professional development programmes, transcripts of five teachers, three showing a significant change and two no change, were analysed in more detail to identify features of teachers' oral contributions that facilitated and supported argumentation. The analysis showed that all teachers attempted to encourage a variety of processes involved in argumentation and that the teachers whose lessons included the highest quality of argumentation (TAP analysis) also encouraged higher order processes in their teaching. The analysis of teachers' facilitation of argumentation has helped to guide the development of in-service materials and to identify the barriers to learning in the professional development of less experienced teachers

Identifying epileptogenic abnormalities through spatial clustering of MEG interictal band power

Successful epilepsy surgery depends on localising and resecting cerebral abnormalities and networks that generate seizures. Abnormalities, however, may be widely distributed across multiple discontiguous areas. We propose spatially constrained clusters as candidate areas for further investigation, and potential resection. We quantified the spatial overlap between the abnormality cluster and subsequent resection, hypothesising a greater overlap in seizure-free patients. Thirty-four individuals with refractory focal epilepsy underwent pre-surgical resting-state interictal MEG recording. Fourteen individuals were totally seizure free (ILAE 1) after surgery and 20 continued to have some seizures post-operatively (ILAE 2+). Band power abnormality maps were derived using controls as a baseline. Patient abnormalities were spatially clustered using the k-means algorithm. The tissue within the cluster containing the most abnormal region was compared with the resection volume using the dice score. The proposed abnormality cluster overlapped with the resection in 71% of ILAE 1 patients. Conversely, an overlap only occurred in 15% of ILAE 2+ patients. This effect discriminated outcome groups well (AUC=0.82). Our novel approach identifies clusters of spatially similar tissue with high abnormality. This is clinically valuable, providing (i) a data-driven framework to validate current hypotheses of the epileptogenic zone localisation or (ii) to guide further investigation.Comment: 16 pages, 3 figure

Identifying epileptogenic abnormalities through spatial clustering of MEG interictal band power

Successful epilepsy surgery depends on localising and resecting cerebral abnormalities and networks that generate seizures. Abnormalities, however, may be widely distributed across multiple discontiguous areas. We propose spatially constrained clusters as candidate areas for further investigation, and potential resection. We quantified the spatial overlap between the abnormality cluster and subsequent resection, hypothesising a greater overlap in seizure-free patients. Thirty-four individuals with refractory focal epilepsy underwent pre-surgical resting-state interictal MEG recording. Fourteen individuals were totally seizure free (ILAE 1) after surgery and 20 continued to have some seizures post-operatively (ILAE 2+). Band power abnormality maps were derived using controls as a baseline. Patient abnormalities were spatially clustered using the k-means algorithm. The tissue within the cluster containing the most abnormal region was compared with the resection volume using the dice score. The proposed abnormality cluster overlapped with the resection in 71% of ILAE 1 patients. Conversely, an overlap only occurred in 15% of ILAE 2+ patients. This effect discriminated outcome groups well (AUC=0.82). Our novel approach identifies clusters of spatially similar tissue with high abnormality. This is clinically valuable, providing (i) a data-driven framework to validate current hypotheses of the epileptogenic zone localisation or (ii) to guide further investigation

Complementary structural and functional abnormalities to localise epileptogenic tissue

BACKGROUND: When investigating suitability for epilepsy surgery, people with drug-refractory focal epilepsy may have intracranial EEG (iEEG) electrodes implanted to localise seizure onset. Diffusion-weighted magnetic resonance imaging (dMRI) may be acquired to identify key white matter tracts for surgical avoidance. Here, we investigate whether structural connectivity abnormalities, inferred from dMRI, may be used in conjunction with functional iEEG abnormalities to aid localisation of the epileptogenic zone (EZ), improving surgical outcomes in epilepsy. METHODS: We retrospectively investigated data from 43 patients (42% female) with epilepsy who had surgery following iEEG. Twenty-five patients (58%) were free from disabling seizures (ILAE 1 or 2) at one year. Interictal iEEG functional, and dMRI structural connectivity abnormalities were quantified by comparison to a normative map and healthy controls. We explored whether the resection of maximal abnormalities related to improved surgical outcomes, in both modalities individually and concurrently. Additionally, we suggest how connectivity abnormalities may inform the placement of iEEG electrodes pre-surgically using a patient case study. FINDINGS: Seizure freedom was 15 times more likely in patients with resection of maximal connectivity and iEEG abnormalities (p = 0.008). Both modalities separately distinguished patient surgical outcome groups and when used simultaneously, a decision tree correctly separated 36 of 43 (84%) patients. INTERPRETATION: Our results suggest that both connectivity and iEEG abnormalities may localise epileptogenic tissue, and that these two modalities may provide complementary information in pre-surgical evaluations. FUNDING: This research was funded by UKRI, CDT in Cloud Computing for Big Data, NIH, MRC, Wellcome Trust and Epilepsy Research UK

Complementary structural and functional abnormalities to localise epileptogenic tissue

When investigating suitability for surgery, people with drug-refractory focal epilepsy may have intracranial EEG (iEEG) electrodes implanted to localise seizure onset. Diffusion-weighted magnetic resonance imaging (dMRI) may be acquired to identify key white matter tracts for surgical avoidance. Here, we investigate whether structural connectivity abnormalities, inferred from dMRI, may be used in conjunction with functional iEEG abnormalities to aid localisation and resection of the epileptogenic zone (EZ), and improve surgical outcomes in epilepsy. We retrospectively investigated data from 43 patients with epilepsy who had surgery following iEEG. Twenty five patients (58%) were free from disabling seizures (ILAE 1 or 2) at one year. For all patients, T1-weighted and diffusion-weighted MRIs were acquired prior to iEEG implantation. Interictal iEEG functional, and dMRI structural connectivity abnormalities were quantified by comparison to a normative map and healthy controls respectively. First, we explored whether the resection of maximal (dMRI and iEEG) abnormalities related to improved surgical outcomes. Second, we investigated whether the modalities provided complementary information for improved prediction of surgical outcome. Third, we suggest how dMRI abnormalities may be useful to inform the placement of iEEG electrodes as part of the pre-surgical evaluation using a patient case study. Seizure freedom was 15 times more likely in those patients with resection of maximal dMRI and iEEG abnormalities (p=0.008). Both modalities were separately able to distinguish patient outcome groups and when combined, a decision tree correctly separated 36 out of 43 (84%) patients based on surgical outcome. Structural dMRI could be used in pre-surgical evaluations, particularly when localisation of the EZ is uncertain, to inform personalised iEEG implantation and resection.Comment: 5 figure

Changes in intraocular pressure in study and fellow eyes in the IVAN trial

PURPOSE: To describe changes in intraocular pressure (IOP) in the 'alternative treatments to Inhibit VEGF in Age-related choroidal Neovascularisation (IVAN)' trial (registered as ISRCTN92166560). DESIGN: Randomised controlled clinical trial with factorial design. PARTICIPANTS: Patients (n=610) with treatment naïve neovascular age-related macular degeneration were enrolled and randomly assigned to receive either ranibizumab or bevacizumab and to two regimens, namely monthly (continuous) or as needed (discontinuous) treatment. METHODS: At monthly visits, IOP was measured preinjection in both eyes, and postinjection in the study eye. OUTCOME MEASURES: The effects of 10 prespecified covariates on preinjection IOP, change in IOP (postinjection minus preinjection) and the difference in preinjection IOP between the two eyes were examined. RESULTS: For every month in trial, there was a statistically significant rise in both the preinjection IOP and the change in IOP postinjection during the time in the trial (estimate 0.02 mm Hg, 95% CI 0.01 to 0.03, p<0.001 and 0.03 mm Hg, 95% CI 0.01 to 0.04, p=0.002, respectively). There was also a small but significant increase during the time in trial in the difference in IOP between the two eyes (estimate 0.01 mm Hg, 95% CI 0.005 to 0.02, p<0.001). There were no differences between bevacizumab and ranibizumab for any of the three outcomes (p=0.93, p=0.22 and p=0.87, respectively). CONCLUSIONS: Anti-vascular endothelial growth factor agents induce increases in IOP of small and uncertain clinical significance

Increased diversification rates follow shifts to bisexuality in liverworts

Shifts in sexual systems are one of the key drivers of species diversification. In contrast to angiosperms, unisexuality prevails in bryophytes. Here, we test the hypotheses that bisexuality evolved from an ancestral unisexual condition and is a key innovation in liverworts. We investigate whether shifts in sexual systems influence diversification using hidden state speciation and extinction analysis (HiSSE). This new method compares the effects of the variable of interest to the best-fitting latent variable, yielding robust and conservative tests. We find that the transitions in sexual systems are significantly biased toward unisexuality, even though bisexuality is coupled with increased diversification. Sexual systems are strongly conserved deep within the liverwort tree but become much more labile toward the present. Bisexuality appears to be a key innovation in liverworts. Its effects on diversification are presumably mediated by the interplay of high fertilization rates, massive spore production and long-distance dispersal, which may separately or together have facilitated liverwort speciation, suppressed their extinction, or both. Importantly, shifts in liverwort sexual systems have the opposite effect when compared to angiosperms, leading to contrasting diversification patterns between the two groups. The high prevalence of unisexuality among liverworts suggests, however, a strong selection for sexual dimorphism