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Abstract Successful epilepsy surgery depends on localizing 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, hypothesizing a greater overlap in seizure‐free patients. Thirty‐four individuals with refractory focal epilepsy underwent pre‐surgical resting‐state interictal magnetoencephalography (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 (a) a data‐driven framework to validate current hypotheses of the epileptogenic zone localization or (b) to guide further investigation.

Abstract A normative electrographic activity map could be a powerful resource to understand normal brain function and identify abnormal activity. Here, we present a normative brain map using scalp EEG in terms of relative band power. In this exploratory study we investigate its temporal stability, its similarity to other imaging modalities, and explore a potential clinical application. We constructed scalp EEG normative maps of brain dynamics from 17 healthy controls using source-localised resting-state scalp recordings. We then correlated these maps with those acquired from MEG and intracranial EEG to investigate their similarity. Lastly, we use the normative maps to lateralise abnormal regions in epilepsy. Spatial patterns of band powers were broadly consistent with previous literature and stable across recordings. Scalp EEG normative maps were most similar to other modalities in the alpha band, and relatively similar across most bands. Towards a clinical application in epilepsy, we found abnormal temporal regions ipsilateral to the epileptogenic hemisphere. Scalp EEG relative band power normative maps are spatially stable across time, in keeping with MEG and intracranial EEG results. Normative mapping is feasible and may be potentially clinically useful in epilepsy. Future studies with larger sample sizes and high-density EEG are now required for validation.

Structural covariance analysis is a widely used structural MRI analysis method which characterises the co-relations of morphology between brain regions over a group of subjects. To our knowledge, little has been investigated in terms of the comparability of results between different data sets of healthy human subjects, as well as the reliability of results over the same subjects in different rescan sessions, image resolutions, or FreeSurfer versions.In terms of comparability, our results show substantial differences in the structural covariance matrix between data sets of age- and sex-matched healthy human adults. These differences persist after univariate site correction, they are exacerbated by low sample sizes, and they are most pronounced when using average cortical thickness as a morphological measure. Down-stream graph theoretic analyses further show statistically significant differences.In terms of reliability, substantial differences were also found when comparing repeated scan sessions of the same subjects, image resolutions, and even FreeSurfer versions of the same image. We could further estimate the relative measurement error and showed that it is largest when using cortical thickness as a morphological measure. Using simulated data, we argue that cortical thickness is least reliable because of larger relative measurement errors.Practically, we make the following recommendations (1) combining subjects across sites into one group should be avoided, particularly if sites differ in image resolutions, subject demographics, or preprocessing steps; (2) surface area and volume should be preferred as morphological measures over cortical thickness; (3) a large number of subjects (n≫30 for the Desikan-Killiany parcellation) should be used to estimate structural covariance; (4) measurement error should be assessed where repeated measurements are available; (5) if combining sites is critical, univariate (per ROI) site-correction is insufficient, but error covariance (between ROIs) should be explicitly measured and modelled.

A normative electrographic activity map could be a powerful resource to understand normal brain function and identify abnormal activity. Here, we present a normative brain map using scalp EEG in terms of relative band power. In this exploratory study we investigate its temporal stability, its similarity to other imaging modalities, and explore a potential clinical application. We constructed scalp EEG normative maps of brain dynamics from 17 healthy controls using source-localised resting-state scalp recordings. We then correlated these maps with those acquired from MEG and intracranial EEG to investigate their similarity. Lastly, we use the normative maps to lateralise abnormal regions in epilepsy. Spatial patterns of band powers were broadly consistent with previous literature and stable across recordings. Scalp EEG normative maps were most similar to other modalities in the alpha band, and relatively similar across most bands. Towards a clinical application in epilepsy, we found abnormal temporal regions ipsilateral to the epileptogenic hemisphere. Scalp EEG relative band power normative maps are spatially stable across time, in keeping with MEG and intracranial EEG results. Normative mapping is feasible and may be potentially clinically useful in epilepsy. Future studies with larger sample sizes and high-density EEG are now required for validation. [ABSTRACT FROM AUTHOR]

Successful epilepsy surgery depends on localizing 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, hypothesizing a greater overlap in seizure‐free patients. Thirty‐four individuals with refractory focal epilepsy underwent pre‐surgical resting‐state interictal magnetoencephalography (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 (a) a data‐driven framework to validate current hypotheses of the epileptogenic zone localization or (b) to guide further investigation. [ABSTRACT FROM AUTHOR]

Objective: Epilepsy surgery fails to achieve seizure freedom in 30%–40% of cases. It is not fully understood why some surgeries are unsuccessful. By comparing interictal magnetoencephalography (MEG) band power from patient data to normative maps, which describe healthy spatial and population variability, we identify patient‐specific abnormalities relating to surgical failure. We propose three mechanisms contributing to poor surgical outcome: (1) not resecting the epileptogenic abnormalities (mislocalization), (2) failing to remove all epileptogenic abnormalities (partial resection), and (3) insufficiently impacting the overall cortical abnormality. Herein we develop markers of these mechanisms, validating them against patient outcomes. Methods: Resting‐state MEG recordings were acquired for 70 healthy controls and 32 patients with refractory neocortical epilepsy. Relative band‐power spatial maps were computed using source‐localized recordings. Patient and region‐specific band‐power abnormalities were estimated as the maximum absolute z‐score across five frequency bands using healthy data as a baseline. Resected regions were identified using postoperative magnetic resonance imaging (MRI). We hypothesized that our mechanistically interpretable markers would discriminate patients with and without postoperative seizure freedom. Results: Our markers discriminated surgical outcome groups (abnormalities not targeted: area under the curve [AUC] = 0.80, p =.003; partial resection of epileptogenic zone: AUC = 0.68, p =.053; and insufficient cortical abnormality impact: AUC = 0.64, p =.096). Furthermore, 95% of those patients who were not seizure‐free had markers of surgical failure for at least one of the three proposed mechanisms. In contrast, of those patients without markers for any mechanism, 80% were ultimately seizure‐free. Significance: The mapping of abnormalities across the brain is important for a wide range of neurological conditions. Here we have demonstrated that interictal MEG band‐power mapping has merit for the localization of pathology and improving our mechanistic understanding of epilepsy. Our markers for mechanisms of surgical failure could be used in the future to construct predictive models of surgical outcome, aiding clinical teams during patient pre‐surgical evaluations. [ABSTRACT FROM AUTHOR]

The Flynn effect refers to increases over time in measured (particularly fluid) intelligence of approximately 3 IQ points per decade. We define the Flynn effect at the family level, using longitudinal data and two new family-level cohort definitions. Multilevel growth curve analyses of the National Longitudinal Survey of Youth 1979 data showed that children in families with later-born mothers had higher average PIAT math scores, and lower average reading comprehension scores and growth, in young and middle childhood. Children in families where the first child was born later had higher average PIAT math, reading recognition, and reading comprehension scores, as well as larger developmental growth. The latter family-level Flynn effects were of higher magnitudes than the usual individual-level Flynn effect found in previous studies. Our results, showing family level-intercept and slope Flynn effects for both maternal birthyear and first child birthyear, have implications for research aiming to explain the Flynn effect. [ABSTRACT FROM AUTHOR]

Objective: Recent work has shown that people with common epilepsies have characteristic patterns of cortical thinning, and that these changes may be progressive over time. Leveraging a large multicenter cross‐sectional cohort, we investigated whether regional morphometric changes occur in a sequential manner, and whether these changes in people with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE‐HS) correlate with clinical features. Methods: We extracted regional measures of cortical thickness, surface area, and subcortical brain volumes from T1‐weighted (T1W) magnetic resonance imaging (MRI) scans collected by the ENIGMA‐Epilepsy consortium, comprising 804 people with MTLE‐HS and 1625 healthy controls from 25 centers. Features with a moderate case–control effect size (Cohen d ≥.5) were used to train an event‐based model (EBM), which estimates a sequence of disease‐specific biomarker changes from cross‐sectional data and assigns a biomarker‐based fine‐grained disease stage to individual patients. We tested for associations between EBM disease stage and duration of epilepsy, age at onset, and antiseizure medicine (ASM) resistance. Results: In MTLE‐HS, decrease in ipsilateral hippocampal volume along with increased asymmetry in hippocampal volume was followed by reduced thickness in neocortical regions, reduction in ipsilateral thalamus volume, and finally, increase in ipsilateral lateral ventricle volume. EBM stage was correlated with duration of illness (Spearman ρ =.293, p = 7.03 × 10−16), age at onset (ρ = −.18, p = 9.82 × 10−7), and ASM resistance (area under the curve =.59, p =.043, Mann–Whitney U test). However, associations were driven by cases assigned to EBM Stage 0, which represents MTLE‐HS with mild or nondetectable abnormality on T1W MRI. Significance: From cross‐sectional MRI, we reconstructed a disease progression model that highlights a sequence of MRI changes that aligns with previous longitudinal studies. This model could be used to stage MTLE‐HS subjects in other cohorts and help establish connections between imaging‐based progression staging and clinical features. [ABSTRACT FROM AUTHOR]

The identification of abnormal electrographic activity is important in a wide range of neurological disorders, including epilepsy for localizing epileptogenic tissue. However, this identification may be challenging during non-seizure (interictal) periods, especially if abnormalities are subtle compared to the repertoire of possible healthy brain dynamics. Here, we investigate if such interictal abnormalities become more salient by quantitatively accounting for the range of healthy brain dynamics in a location-specific manner. To this end, we constructed a normative map of brain dynamics, in terms of relative band power, from interictal intracranial recordings from 234 participants (21 598 electrode contacts). We then compared interictal recordings from 62 patients with epilepsy to the normative map to identify abnormal regions. We proposed that if the most abnormal regions were spared by surgery, then patients would be more likely to experience continued seizures postoperatively. We first confirmed that the spatial variations of band power in the normative map across brain regions were consistent with healthy variations reported in the literature. Second, when accounting for the normative variations, regions that were spared by surgery were more abnormal than those resected only in patients with persistent postoperative seizures (t = -3.6, P = 0.0003), confirming our hypothesis. Third, we found that this effect discriminated patient outcomes (area under curve 0.75 P = 0.0003). Normative mapping is a well-established practice in neuroscientific research. Our study suggests that this approach is feasible to detect interictal abnormalities in intracranial EEG, and of potential clinical value to identify pathological tissue in epilepsy. Finally, we make our normative intracranial map publicly available to facilitate future investigations in epilepsy and beyond. [ABSTRACT FROM AUTHOR]

With populations rapidly aging, the development over time in the cognitive function among the elderly approaching or reaching retirement is important for successful aging at work and planning pension policies. However, few studies in this field focus on this age group. This study characterizes time trends in cognitive function among 55-69-year-old Europeans from 2006 to 2015, and compares these trends by region, gender, and education. This study analyzes 40,689 subjects in Waves 2, 4, 5 and 6 of the Survey of Health, Aging and Retirement in Europe (SHARE) covering ten countries. Cognitive function was measured by Recall and Verbal Fluency. Educational levels were classified by quartiles. A Generalized Estimating Equation (GEE) model was used to explore the association between cognitive function and development over time after controlling for confounders. Further stratification analysis using GEE models was conducted, stratified by region, gender and education. Cognitive function improved significantly in southern and central Europe over the observed timeframe, whereas it did not in northern Europe. Those with relative low levels of formal education displayed the most rapid increases in cognitive function in southern and central Europe. Among those with lower education in southern Europe, males' cognitive function improved more quickly than females'. The improvement of cognitive function at ages 55-69 in southern and central Europe may contribute to continuing engagement with productive activities in old age. Educational interventions for people with lower levels of education may be most effective in achieving such engagement. This paper extends the literature on the development over time in the cognitive function among the elderly close to retirement age in Europe by analysing southern, central and northern Europe, as well as differences by region, gender and education. The results may provide evidence for planning pension policies and educational interventions. [ABSTRACT FROM AUTHOR]

Previous studies investigating associations between white matter alterations and duration of temporal lobe epilepsy (TLE) have shown differing results, and were typically limited to univariate analyses of tracts in isolation. In this study, we apply a multivariate measure (the Mahalanobis distance), which captures the distinct ways white matter may differ in individual patients, and relate this to epilepsy duration. Diffusion MRI, from a cohort of 94 subjects (28 healthy controls, 33 left‐TLE and 33 right‐TLE), was used to assess the association between tract fractional anisotropy (FA) and epilepsy duration. Using ten white matter tracts, we analysed associations using the traditional univariate analysis (z‐scores) and a complementary multivariate approach (Mahalanobis distance), incorporating multiple white matter tracts into a single unified analysis. For patients with right‐TLE, FA was not significantly associated with epilepsy duration for any tract studied in isolation. For patients with left‐TLE, the FA of two limbic tracts (ipsilateral fornix, contralateral cingulum gyrus) were significantly negatively associated with epilepsy duration (Bonferonni corrected p <.05). Using a multivariate approach we found significant ipsilateral positive associations with duration in both left, and right‐TLE cohorts (left‐TLE: Spearman's ρ = 0.487, right‐TLE: Spearman's ρ = 0.422). Extrapolating our multivariate results to duration equals zero (i.e., at onset) we found no significant difference between patients and controls. Associations using the multivariate approach were more robust than univariate methods. The multivariate Mahalanobis distance measure provides non‐overlapping and more robust results than traditional univariate analyses. Future studies should consider adopting both frameworks into their analysis in order to ascertain a more complete understanding of epilepsy progression, regardless of laterality. [ABSTRACT FROM AUTHOR]