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In India, Holstein and its crosses are being used extensively in breeding programmes and all these breeding bulls are screened for autosomal recessive genes. Blood samples are collected in ethylenediaminetetraacetic acid (EDTA) coated tubes and DNA was isolated by using phenol-chloroform method. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) were performed by using bovine leukocyte adhesion deficiency (BLAD) specific primers and TaqI restriction enzyme for diagnosis of bovine leukocyte adhesion deficiency (BLAD) syndrome. The bull was found to be heterozygous for BLAD allele. The PCR product was sequenced by automated sequencer using the ABI big dye Ver 3.1 for detection of mutation at position 383 bp (A/G). Sequence analysis comparison was performed using the codon code aligner 4.0.4 software. The sequence of carrier animal confirmed polymorphism at 383 bp position. The sequence was also compared with sequence of normal Holstein as a control and the sequence available with NCBI (accession No. NC-007299). The comparison of sequences revealed a heterozygous polymorphism at 348 position (T>C) in a carrier animal whereas in homozygous in a control Holstein which was normal for BLAD. The new polymorphism at 348 position was found to be silent as it does not change amino acid (asparagine, AAT>AAC) within exon 4 of CD18 gene. The partial sequence of new polymorphism / silent mutation has already been submitted to NCBI (accession No. KF840683). Further studies have to be carried out to elucidate the possible association of the CD18 silent point mutation at 348 bp position as a potential molecular marker for milk production traits. [ABSTRACT FROM AUTHOR]

Abstract: Sensitivity to pain shows a remarkable interindividual variance that has been reported to both forecast and accompany various clinical pain conditions. Although pain thresholds have been reported to be associated to brain morphology, it is still unclear how well these findings replicate in independent data and whether they are powerful enough to provide reliable pain sensitivity predictions on the individual level. In this study, we constructed a predictive model of pain sensitivity (as measured with pain thresholds) using structural magnetic resonance imaging-based cortical thickness data from a multicentre data set (3 centres and 131 healthy participants). Cross-validated estimates revealed a statistically significant and clinically relevant predictive performance (Pearson r = 0.36, P < 0.0002, R2 = 0.13). The predictions were found to be specific to physical pain thresholds and not biased towards potential confounding effects (eg, anxiety, stress, depression, centre effects, and pain self-evaluation). Analysis of model coefficients suggests that the most robust cortical thickness predictors of pain sensitivity are the right rostral anterior cingulate gyrus, left parahippocampal gyrus, and left temporal pole. Cortical thickness in these regions was negatively correlated to pain sensitivity. Our results can be considered as a proof-of-concept for the capacity of brain morphology to predict pain sensitivity, paving the way towards future multimodal brain-based biomarkers of pain., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Genetic generalized epilepsy (GGE) is conceptualized as a brain disorder involving distributed bilateral networks. To study these networks, simultaneous EEG-fMRI measurements can be used. However, inside-MRI EEG suffers from strong MR-related artifacts; it is not established whether EEG-based metrics in EEG-fMRI resting-state measurements are suitable for the analysis of group differences at source-level. We evaluated the impact of the inside-MR measurement condition on statistical group comparisons of EEG on source-level power and functional connectivity in patients with GGE versus healthy controls. We studied the cross-modal spatial relation of statistical group differences in seed-based FC derived from EEG and parallel fMRI. We found a significant increase in power and a frequency-specific change in functional connectivity for the inside MR-scanner compared to the outside MR-scanner condition. For power, we found reduced group difference between GGE and controls both in terms of statistical significance as well as effect size. Group differences for ImCoh remained similar both in terms of statistical significance as well as effect size. We found increased seed-based FC for GGE patients from the thalamus to the precuneus cortex region in fMRI, and in the theta band of simultaneous EEG. Our findings suggest that the analysis of EEG functional connectivity based on ImCoh is suitable for MR-EEG, and that relative group difference in a comparison of patients with GGE against controls are preserved. Spatial correspondence of seed-based FC group differences between the two modalities was found for the thalamus., (© 2023. The Author(s).)

Optimism bias is the tendency to believe desirable events are more likely to happen than undesirable ones. People often display optimistic biases for themselves (personal optimism), but also for members of groups they like or identify with (social optimism). However, the neural bases of and connections between these two concepts are poorly understood. The present study hence used both questionnaires and a social optimism task performed during magnetic resonance imaging to investigate how network connectivity associates with personal and social optimism biases. Using sparse canonical correlation analysis, we found that a behavioral dimension that included both in-group optimism bias and personal optimism bias was positively associated with a dimension of network connectivity. This dimension comprised two networks with positive weights (dorsal precuneus-related default mode network and dorsal sensorimotor network), and three with negative weights (including parts of the salience and central executive networks). Our findings indicate that connectivity in networks adjacent to the temporoparietal junction favors propagation of both personal and social optimism biases. Meanwhile, low connectivity in more frontal networks associated with more complex cognition may also further such propagation., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Image templates are a common tool for neuroscience research. Often, they are used for spatial normalization of magnetic resonance imaging (MRI) data, which is a necessary procedure for analyzing brain morphology and function via voxel-based analysis. This allows the researcher to reduce individual shape differences across images and make inferences across multiple subjects. Many templates have a small field-of-view typically focussed on the brain, limiting the use for applications requiring detailed information about other extra-cranial structures in the head and neck area. However, there are several applications where such information is important, for example source reconstruction of electroencephalography (EEG) and/or magnetoencephalography (MEG). We have constructed a new template based on 225 T1w and FLAIR images with a big field-of-view that can serve both as target for across subject spatial normalization as well as a basis to build high-resolution head models. This template is based on and iteratively re-registered to the MNI152 space to provide maximal compatibility with the most commonly used brain MRI template., (© 2023. The Author(s).)

People have been shown to be optimistically biased when their future outcome expectancies are assessed. In fact, we display optimism bias (OB) toward our own success when compared to a rival individual's (personal OB [POB]). Similarly, success expectancies for social groups we like reliably exceed those we mention for a rival group (social OB [SOB]). Recent findings suggest the existence of neural underpinnings for OB. Mostly using structural/functional MRI, these findings rely on voxel-based mass-univariate analyses. While these results remain associative in nature, an open question abides whether MRI information can accurately predict OB. In this study, we hence used predictive modelling to forecast the two OBs. The biases were quantified using a validated soccer paradigm, where personal (self versus rival) and social (in-group versus out-group) forms of OB were extracted at the participant level. Later, using gray matter cortical thickness, we predicted POB and SOB via machine-learning. Our model explained 17% variance (R 2  = 0.17) in individual variability for POB (but not SOB). Key predictors involved the rostral-caudal anterior cingulate cortex, pars orbitalis and entorhinal cortex-areas that have been associated with OB before. We need such predictive models on a larger scale, to help us better understand positive psychology and individual well-being., (© 2023. The Author(s).)

Background and Objectives: Genetic generalized epilepsy (GGE) is the most common form of generalized epilepsy. Although individual patients with GGE typically present without structural alterations, group differences have been demonstrated in GGE and some GGE subtypes like juvenile myoclonic epilepsy (GGE-JME). Previous studies usually involved only small cohorts from single centers and therefore could not assess imaging markers of multiple GGE subtypes., Methods: We performed a diffusion MRI mega-analysis in 192 participants consisting of 126 controls and 66 patients with GGE from four different cohorts and two different epilepsy centers. We applied whole-brain multi-site harmonization and analyzed fractional anisotropy (FA), as well as mean, radial and axial diffusivity (MD/RD/AD) to assess differences between controls, patients with GGE and the common GGE subtypes, i.e. GGE with generalized tonic-clonic seizures only (GGE-GTCS), GGE-JME and absence epilepsy (GGE-AE). We also analyzed relationships with patients' response to anti-seizure-medication (ASM)., Results: Relative to controls, we identified decreased anisotropy and increased RD in patients with GGE. We found no significant effects of disease duration, age of onset or seizure frequency on diffusion metrics. Patients with JME had increased MD and RD when compared to controls, while patients with GGE-GTCS showed decreased MD/AD when compared to controls. Compared to patients with GGE-AE, patients with GGE-GTCS had lower AD/MD. Compared to patients with GGE-GTCS, patients with GGE-JME had higher MD/RD and AD. Moreover, we found lower FA in patients with refractory when compared to patients with non-refractory GGE in the right cortico-spinal tract, but no significant differences in patients with active versus controlled epilepsy., Discussion: We provide evidence that clinically defined GGE as a whole and GGE-subtypes harbor marked microstructural differences detectable with diffusion MRI. Moreover, we found an association between microstructural changes and treatment resistance. Our findings have important implications for future full-resolution multi-site studies when assessing GGE, its subtypes and ASM refractoriness., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem epilepsy risk gene expression patterns. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-transcriptomic signatures could potentially guide diagnosis or tailor therapeutic approaches to specific epilepsy syndromes., (© 2022. The Author(s).)

Objective: Genetic generalized epilepsy (GGE) is characterized by aberrant neuronal dynamics and subtle structural alterations. We evaluated whether a combination of magnetic and electrical neuronal signals and cortical thickness would provide complementary information about network pathology in GGE. We also investigated whether these imaging phenotypes were present in healthy siblings of the patients to test for genetic influence., Methods: In this cross-sectional study, we analyzed 5 min of resting state data acquired using electroencephalography (EEG) and magnetoencephalography (MEG) in patients, their siblings, and controls, matched for age and sex. We computed source-reconstructed power and connectivity in six frequency bands (1-40 Hz) and cortical thickness (derived from magnetic resonance imaging). Group differences were assessed using permutation analysis of linear models for each modality separately and jointly for all modalities using a nonparametric combination., Results: Patients with GGE (n = 23) had higher power than controls (n = 35) in all frequencies, with a more posterior focus in MEG than EEG. Connectivity was also increased, particularly in frontotemporal and central regions in theta (strongest in EEG) and low beta frequencies (strongest in MEG), which was eminent in the joint EEG/MEG analysis. EEG showed weaker connectivity differences in higher frequencies, possibly related to drug effects. The inclusion of cortical thickness reinforced group differences in connectivity and power. Siblings (n = 18) had functional and structural patterns intermediate between those of patients and controls., Significance: EEG detected increased connectivity and power in GGE similar to MEG, but with different spectral sensitivity, highlighting the importance of theta and beta oscillations. Cortical thickness reductions in GGE corresponded to functional imaging patterns. Our multimodal approach extends the understanding of the resting state in GGE and points to genetic underpinnings of the imaging markers studied, providing new insights into the causes and consequences of epilepsy., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Temporal lobe epilepsy, a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter structural alterations in temporal lobe epilepsy relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry; or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multisite ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 temporal lobe epilepsy patients and 1418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in temporal lobe epilepsy, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity calculated using 207 healthy controls obtained from Human Connectome Project and an independent dataset containing 23 temporal lobe epilepsy patients and 53 healthy controls and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of temporal lobe epilepsy-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of temporal lobe epilepsy and may inform future discovery and validation of complementary MRI biomarkers in temporal lobe epilepsy., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

We investigated the white matter correlates of personality profiles predictive of subjective well-being. Using principal component analysis to first determine the possible personality profiles onto which core personality measures would load, we subsequently searched for whole-brain white matter correlations with these profiles. We found three personality profiles that correlated with the integrity of white matter tracts. The correlates of an "optimistic" personality profile suggest (a) an intricate network for self-referential processing that helps regulate negative affect and maintain a positive outlook on life, (b) a sustained capacity for visually tracking rewards in the environment and (c) a motor readiness to act upon the conviction that desired rewards are imminent. The correlates of a "short-term approach behavior" profile was indicative of minimal loss of integrity in white matter tracts supportive of lifting certain behavioral barriers, possibly allowing individuals to act more outgoing and carefree in approaching people and rewards. Lastly, a "long-term approach behavior" profile's association with white matter tracts suggests lowered sensitivity to transient updates of stimulus-based associations of rewards and setbacks, thus facilitating the successful long-term pursuit of goals. Together, our findings yield convincing evidence that subjective well-being has its manifestations in the brain., (© 2022. The Author(s).)

Individuals often anticipate an unrealistically favorable future for themselves (personal optimism bias) or others (social optimism bias). While such biases are well established, little is known about their neuroanatomy. In this study, participants engaged in a soccer task and estimated the likelihood of successful passes in personal and social scenarios. Voxel-based morphometry revealed that personal optimism bias varied as a positive function of gray matter volume (GMV) in the putamen, frontal pole, hippocampus, temporal pole, inferior temporal gyrus, visual association areas, and mid-superior temporal gyrus. Social optimism bias correlated positively with GMV in the temporoparietal junction and negatively with GMV in the inferior temporal gyrus and pre-supplementary motor areas. Together, these findings suggest that parts of our optimistic outlook are biologically rooted. Moreover, while the two biases looked similar at the behavioral level, they were related to distinct gray matter structures, proposing that their underlying mechanisms are not identical.

Sex hormones such as estradiol (E2) have long-lasting influence on brain architecture. Recent studies indicate further structural changes during hormonal transition periods including pregnancy, when women experience the greatest increase in sex hormone levels across their life span. In the present study, three groups of women (n = 44) with different levels of E2 underwent structural magnetic resonance imaging: (1) first-time pregnant women (n = 13, 'extreme E2 group'); (2), nulliparous, naturally cycling women who received 12 mg of E2 valerate (n = 16, 'high E2 group'); and (3) nulliparous, naturally cycling women receiving a placebo and hence low E2 (n = 15, 'low E2 group'). Blood samples were taken to assess hormonal levels. Moreover, parameters for cognition, emotion regulation and affect were assessed. On the neuronal level, the extreme E2 compared to the high E2 group showed a reduced gray matter volume in the left putamen. However, no significant differences were found between the low vs. high E2 groups, nor between the low E2 and extreme E2 groups. Cognitive performance was reduced in the extreme E2 group, although a positive affect was increased compared to the high E2 and low E2 groups. Furthermore, regression analyses revealed several associations between cognition, subjective measures of affect, emotion regulation and gray matter volume. A volume reduction of the left putamen during pregnancy further supports the notion that the female brain is shaped by hormonal transition phases, possibly preparing women for their future roles (e.g., pregnant women for their role as mothers)., (© 2021 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.)

Aims: The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems-level analysis., Methods: Imaging-based cortical structural maps from a large-scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell-type deconvolution, differential expression analysis and cell-type enrichment analyses were used to identify differences in cell-type distribution. These differences were followed up in post-mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell-type-specific depletion was used in a murine model of acquired epilepsy., Results: We identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers and, in particular, activated microglial states. Analysis of post-mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non-spatial memory test seen in epileptic mice not depleted of microglia., Conclusions: These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control., (© 2021 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.)

Recent research shows that congruent outcomes are more rapidly (and incongruent less rapidly) detected when individuals receive optimistic rather than pessimistic cues, an effect that was termed optimism robustness. In the current voxel-based morphometry study, we examined whether optimism robustness has a counterpart in the brain structure. The participants' task was to detect two different letters (symbolizing monetary gain or loss) in a visual search matrix. Prior to each onset of the search matrix, two different verbal cues informed our participants about a high probability to gain (optimistic expectancy) or lose (pessimistic expectancy) money. The target presented was either congruent or incongruent with these induced expectancies. Optimism robustness revealed in the participants' reaction times correlated positively with gray matter volume (GMV) in brain regions involved in selective attention (medial visual association area, intraparietal sulcus), emphasizing the strong intertwinement of optimistic expectancies and attention deployment. In addition, GMV in the primary visual cortex diminished with increasing optimism robustness, in line with the interpretation of optimism robustness arising from a global, context-oriented perception. Future studies should address the malleability of these structural correlates of optimism robustness. Our results may assist in the identification of treatment targets in depression., (© The Author(s) 2021. Published by Oxford University Press.)

Objective: To assess whether neuronal signals in patients with genetic generalized epilepsy (GGE) are heritable, we examined magnetoencephalography resting-state recordings in patients and their healthy siblings., Methods: In a prospective, cross-sectional design, we investigated source-reconstructed power and functional connectivity in patients, siblings, and controls. We analyzed 5 minutes of cleaned and awake data without epileptiform discharges in 6 frequency bands (1-40 Hz). We further calculated intraclass correlations to estimate heritability for the imaging patterns within families., Results: Compared with controls (n = 45), patients with GGE (n = 25) showed widespread increased functional connectivity (θ to γ frequency bands) and power (δ to γ frequency bands) across the spectrum. Siblings (n = 18) fell between the levels of patients and controls. Heritability of the imaging metrics was observed in regions where patients strongly differed from controls, mainly in β frequencies, but also for δ and θ power. Network connectivity in GGE was heritable in frontal, central, and inferior parietal brain areas and power in central, temporo-parietal, and subcortical structures. Presence of generalized spike-wave activity during recordings and medication were associated with the network patterns, whereas other clinical factors such as age at onset, disease duration, or seizure control were not., Conclusion: Metrics of brain oscillations are well suited to characterize GGE and likely relate to genetic factors rather than the active disease or treatment. High power and connectivity levels co-segregated in patients with GGE and healthy siblings, predominantly in the β band, representing an endophenotype of GGE., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

An optimism bias refers to the belief in good things happening to oneself in the future with a higher likelihood than is justified. Social optimism biases extend this concept to groups that one identifies with. Previous literature has found that both personal and social optimism biases are linked to brain structure and task-related brain function. Less is known about whether optimism biases are also expressed in resting-state functional connectivity (RSFC). Forty-two participants completed questionnaires on dispositional personal optimism (which is not necessarily unjustified) and comparative optimism (i.e., whether we see our own future as being rosier than a comparison person's future) and underwent a resting-state functional magnetic resonance imaging scan. They further undertook an imaginative soccer task in order to assess both their personal and social optimism bias. We tested associations of these data with RSFC within and between 13 networks, using sparse canonical correlation analyses (sCCAs). We found that the primary sCCA component was positively connected to personal and social optimism bias and negatively connected to dispositional personal pessimism. This component was associated with (a) reduced integration of the default mode network, (b) reduced integration of the central executive and salience networks, and (c) reduced segregation between the default mode network and the central executive network. Our finding that optimism biases are linked to RSFC indicates that they may be rooted in neurobiology that exists outside of concurrent tasks. This poses questions as to what the limits of the malleability of such biases may be., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Artificial intelligence has recently gained popularity across different medical fields to aid in the detection of diseases based on pathology samples or medical imaging findings. Brain magnetic resonance imaging (MRI) is a key assessment tool for patients with temporal lobe epilepsy (TLE). The role of machine learning and artificial intelligence to increase detection of brain abnormalities in TLE remains inconclusive. We used support vector machine (SV) and deep learning (DL) models based on region of interest (ROI-based) structural (n = 336) and diffusion (n = 863) brain MRI data from patients with TLE with ("lesional") and without ("non-lesional") radiographic features suggestive of underlying hippocampal sclerosis from the multinational (multi-center) ENIGMA-Epilepsy consortium. Our data showed that models to identify TLE performed better or similar (68-75%) compared to models to lateralize the side of TLE (56-73%, except structural-based) based on diffusion data with the opposite pattern seen for structural data (67-75% to diagnose vs. 83% to lateralize). In other aspects, structural and diffusion-based models showed similar classification accuracies. Our classification models for patients with hippocampal sclerosis were more accurate (68-76%) than models that stratified non-lesional patients (53-62%). Overall, SV and DL models performed similarly with several instances in which SV mildly outperformed DL. We discuss the relative performance of these models with ROI-level data and the implications for future applications of machine learning and artificial intelligence in epilepsy care., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Epilepsy is increasingly conceptualized as a network disorder. In this cross-sectional mega-analysis, we integrated neuroimaging and connectome analysis to identify network associations with atrophy patterns in 1021 adults with epilepsy compared to 1564 healthy controls from 19 international sites. In temporal lobe epilepsy, areas of atrophy colocalized with highly interconnected cortical hub regions, whereas idiopathic generalized epilepsy showed preferential subcortical hub involvement. These morphological abnormalities were anchored to the connectivity profiles of distinct disease epicenters, pointing to temporo-limbic cortices in temporal lobe epilepsy and fronto-central cortices in idiopathic generalized epilepsy. Negative effects of age on atrophy further revealed a strong influence of connectome architecture in temporal lobe, but not idiopathic generalized, epilepsy. Our findings were reproduced across individual sites and single patients and were robust across different analytical methods. Through worldwide collaboration in ENIGMA-Epilepsy, we provided deeper insights into the macroscale features that shape the pathophysiology of common epilepsies., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n = 182) and non-lesional extratemporal epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P < 0.001). Across 'all epilepsies' lower fractional anisotropy was observed in most fibre tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. There were also less robust increases in mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Individuals with temporal lobe epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced reductions in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and increased mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of diffusion abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibres in a large multicentre study of epilepsy. Overall, patients with epilepsy showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across epilepsy syndromes. These data further define the spectrum of white matter abnormalities in common epilepsy syndromes, yielding more detailed insights into pathological substrates that may explain cognitive and psychiatric co-morbidities and be used to guide biomarker studies of treatment outcomes and/or genetic research., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

We assessed the applicability of MP2RAGE for voxel-based morphometry. To this end, we analyzed its brain tissue segmentation characteristics in healthy subjects and the potential for detecting focal epileptogenic lesions (previously visible and nonvisible). Automated results and expert visual interpretations were compared with conventional VBM variants (i.e., T1 and T1 + FLAIR). Thirty-one healthy controls and 21 patients with focal epilepsy were recruited. 3D T1-, T2-FLAIR, and MP2RAGE images (consisting of INV1, INV2, and MP2 maps) were acquired on a 3T MRI. The effects of brain tissue segmentation and lesion detection rates were analyzed among single- and multispectral VBM variants. MP2-single-contrast gave better delineation of deep, subcortical nuclei but was prone to misclassification of dura/vessels as gray matter, even more than conventional-T1. The addition of multispectral combinations (INV1, INV2, or FLAIR) could markedly reduce such misclassifications. MP2 + INV1 yielded generally clearer gray matter segmentation allowing better differentiation of white matter and neighboring gyri. Different models detected known lesions with a sensitivity between 60 and 100%. In non lesional cases, MP2 + INV1 was found to be best with a concordant rate of 37.5%, specificity of 51.6% and concordant to discordant ratio of 0.60. In summary, we show that multispectral MP2RAGE VBM (e.g., MP2 + INV1, MP2 + INV2) can improve brain tissue segmentation and lesion detection in epilepsy., (© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Background and Purpose: Voxel-based morphometry is widely used for detecting gray matter abnormalities in epilepsy. However, its performance with changing parameters, smoothing and statistical threshold, is debatable. More important, the potential yield of combining multiple MR imaging contrasts (multispectral voxel-based morphometry) is still unclear. Our aim was to objectify smoothing and statistical cutoffs and systematically compare the performance of multispectral voxel-based morphometry with existing T1 voxel-based morphometry in patients with focal epilepsy and previously negative MRI., Materials and Methods: 3D T1-, T2-, and T2-weighted FLAIR scans were acquired for 62 healthy volunteers and 13 patients with MR imaging negative for focal epilepsy on a Magnetom Skyra 3T scanner with an isotropic resolution of 0.9 mm 3 . We systematically optimized the main voxel-based morphometry parameters, smoothing level and statistical cutoff, with T1 voxel-based morphometry as a reference. As a next step, the performance of multispectral voxel-based morphometry models, T1+T2, T1+FLAIR, and T1+T2+FLAIR, was compared with that of T1 voxel-based morphometry using gray matter concentration and gray matter volume analysis., Results: We found the best performance of T1 at 12 mm and a T-threshold (statistical cutoff) of 3.7 for gray matter concentration analysis. When we incorporated these parameters, after expert visual interpretation of concordant and discordant findings, we identified T1+FLAIR as the best model with a concordant rate of 46.2% and a concordant rate/discordant rate of 1.20 compared with T1 with 30.8% and 0.67, respectively. Visual interpretation of voxel-based morphometry findings decreased concordant rates from 38.5%-46.2% to 15.4%-46.2% and discordant rates from 53.8%-84.6% to 30.8%-46.2% and increased specificity across models from 33.9%-40.3% to 46.8%-54.8%., Conclusions: Multispectral voxel-based morphometry, especially T1+FLAIR, can yield superior results over single-channel T1 in focal epilepsy patients with a negative conventional MR imaging., (© 2018 by American Journal of Neuroradiology.)

Voxel-based morphometry is still mainly based on T1-weighted MRI scans. Misclassification of vessels and dura mater as gray matter has been previously reported. Goal of the present work was to evaluate the effect of multimodal segmentation methods available in SPM12, and their influence on identification of age related atrophy and lesion detection in epilepsy patients. 3D T1-, T2- and FLAIR-images of 77 healthy adults (mean age 35.8 years, 19-66 years, 45 females), 7 patients with malformation of cortical development (MCD) (mean age 28.1 years,19-40 years, 3 females), and 5 patients with left hippocampal sclerosis (LHS) (mean age 49.0 years, 25-67 years, 3 females) from a 3T scanner were evaluated. Segmentation based on T1-only, T1+T2, T1+FLAIR, T2+FLAIR, and T1+T2+FLAIR were compared in the healthy subjects. Clinical VBM results based on the different segmentation approaches for MCD and for LHS were compared. T1-only segmentation overestimated total intracranial volume by about 80ml compared to the other segmentation methods. This was due to misclassification of dura mater and vessels as GM and CSF. Significant differences were found for several anatomical regions: the occipital lobe, the basal ganglia/thalamus, the pre- and postcentral gyrus, the cerebellum, and the brainstem. None of the segmentation methods yielded completely satisfying results for the basal ganglia/thalamus and the brainstem. The best correlation with age could be found for the multimodal T1+T2+FLAIR segmentation. Highest T-scores for identification of LHS were found for T1+T2 segmentation, while highest T-scores for MCD were dependent on lesion and anatomical location. Multimodal segmentation is superior to T1-only segmentation and reduces the misclassification of dura mater and vessels as GM and CSF. Depending on the anatomical region and the pathology of interest (atrophy, lesion detection, etc.), different combinations of T1, T2 and FLAIR yield optimal results., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls. We ranked brain structures in order of greatest differences between patients and controls, by meta-analysing effect sizes across 16 subcortical and 68 cortical brain regions. We also tested effects of duration of disease, age at onset, and age-by-diagnosis interactions on structural measures. We observed widespread patterns of altered subcortical volume and reduced cortical grey matter thickness. Compared to controls, all epilepsy groups showed lower volume in the right thalamus (Cohen's d = -0.24 to -0.73; P < 1.49 × 10-4), and lower thickness in the precentral gyri bilaterally (d = -0.34 to -0.52; P < 4.31 × 10-6). Both MTLE subgroups showed profound volume reduction in the ipsilateral hippocampus (d = -1.73 to -1.91, P < 1.4 × 10-19), and lower thickness in extrahippocampal cortical regions, including the precentral and paracentral gyri, compared to controls (d = -0.36 to -0.52; P < 1.49 × 10-4). Thickness differences of the ipsilateral temporopolar, parahippocampal, entorhinal, and fusiform gyri, contralateral pars triangularis, and bilateral precuneus, superior frontal and caudal middle frontal gyri were observed in left, but not right, MTLE (d = -0.29 to -0.54; P < 1.49 × 10-4). Contrastingly, thickness differences of the ipsilateral pars opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = -0.27 to -0.51; P < 1.49 × 10-4). Lower subcortical volume and cortical thickness associated with a longer duration of epilepsy in the all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b < -0.0018; P < 1.49 × 10-4). In the largest neuroimaging study of epilepsy to date, we provide information on the common epilepsies that could not be realistically acquired in any other way. Our study provides a robust ranking of brain measures that can be further targeted for study in genetic and neuropathological studies. This worldwide initiative identifies patterns of shared grey matter reduction across epilepsy syndromes, and distinctive abnormalities between epilepsy syndromes, which inform our understanding of epilepsy as a network disorder, and indicate that certain epilepsy syndromes involve more widespread structural compromise than previously assumed., (© The Author(s) (2018). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Writer's cramp (WC) is one of the commonly observed focal dystonias. The pathophysiology of WC has not been fully understood. The role of the cerebellum has been increasingly recognized in the pathogenesis of dystonia. As the cerebellum is crucial for maintaining accurate eye-hand coordination (EHC), its role in the pathogenesis of WC can be investigated by studying the EHC in patients with WC., Methods: Fifteen patients with WC (women:men, 3:12) and 15 age- and gender-matched controls performed oculomotor and EHC tasks. A visually guided stimulus (VGS) task was first performed with eye-only condition (EOC) and then with EHC., Results: A significant interaction between the groups (controls and patients) and tasks (EOC and EHC) with age as a covariate confirmed that the two groups reacted differently to the tasks in saccadic latency (F(1,27) = 4.8; p = 0.039) and average saccade acceleration (F(1,27) = 10.6; p = 0.003). The curvature index of acceleration of the hand was significantly more in patients compared to controls (patients vs. controls, 2.4±0.4 vs. 1.8±0.2, p = 0.01). While performing the EHC task, there was a significant correlation of the Writer's Cramp Rating Score with the average saccadic speed (-0.61, p = 0.016), peak saccadic deceleration (0.59, p = 0.019) and average saccadic acceleration (-0.63, p = 0.012)., Discussion: Saccadic acceleration and latency are abnormal while performing EHC tasks in patients with WC. Our study gives further insights into the possible role of the cerebellum in the pathogenesis of WC., Competing Interests: Funding: This study was funded by a grant from the Department of Biotechnology, India (No. BT/PR4986/MED/30/753/2012). Conflicts of interest: The authors report no conflict of interest. Ethics Statement: This study was performed in accordance with the ethical standards detailed in the Declaration of Helsinki. The authors’ institutional ethics committee has approved this study and all patients have provided written informed consent.

Introduction: To explore the neuroanatomical correlates of primary writing tremor (PWT) and the role of cerebellum, using advanced structural neuroimaging. Till date, there are no studies exploring the gray and white matter changes using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) in PWT., Methods: Ten male patients with PWT were evaluated clinically and with magnetic resonance imaging. VBM and DTI images of patients were compared with that of 10 healthy male subjects. Spatially unbiased infra-tentorial template (SUIT) analysis was done to investigate the alterations of cerebellar gray matter. Region-of-interest analysis was performed on regions observed to be significantly different on DTI analysis., Results: The mean duration of illness and mean age of the patients were 3.5 ± 1.9 and 51.7 ± 8.6 years, respectively. On VBM analysis, the cluster of gray matter atrophy was found in bilateral cerebellar areas of culmen and left declive, right superior and medial frontal gyrus, bilateral middle frontal gyrus, bilateral anterior cingulate gyrus, and bilateral parahippocampal gyrus. DTI showed significantly reduced fractional anisotrophy of the anterior thalamic radiation, cingulum, and inferior fronto-occipital fasciculus in PWT patients compared to controls. The axial diffusivity, mean diffusivity, and radial diffusivity maps did not reveal any significant differences. On SUIT analysis, significant atrophy was found in right uvula and semilunar lobule in patients with PWT compared to controls., Conclusions: Our study found that patients with PWT had predominant gray matter atrophy in parts of cerebellum and frontal lobe along with white matter changes of the cingulum and frontal lobe connections.

An unprecedented Pd-catalyzed cascade Wacker-Heck lactonization-cyclization sequence is reported. The process provides a facile approach to bi- and tricyclic spiranoid lactones in good yields. The reaction shows general substrate scope and a broad functional group tolerability. In addition, a rare 4-exo trig Heck-type cyclization is demonstrated.

A general, parallel, and collective synthesis of 5/5/5- and 5/5/6-ring fusion topologies of tricyclic spiranoid lactones through the controlled cyclizations of easily accessible, common key precursors is described. The rapid composition of key cycloalkyl methylene precursors yielded an assembly of bicyclic diastereoisomeric iodolactones, which were individually converted into a wide range of tricyclic, angularly fused spiranoid lactones in a regioselective and stereodirected fashion through the diastereoisomeric differentiation of a collective key precursor. The critical stereochemical assignment of the bicyclic starting materials, as well as the tricyclic targets, was confirmed by X-ray crystal structure determination., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Blood collection in heparin tubes for cytogenetic, and ethylenediaminetetraacetic acid (EDTA) tubes for molecular genetics applications respectively, are routine practices everywhere. If blood samples are required for cytogenetics as well as DNA work, two samples from each animal are usually collected, which leads to wastage of time and money. The present study tried to explore the possibilities of collecting a single blood sample in a heparinised tube for use in both applications. Two blood samples were collected from the same animals; one in a heparin tube and the other in an EDTA tube. DNA was extracted and stored at the same temperature and for the same durations. Comparative studies revealed that the DNA samples extracted from blood using these two different coagulants give more or less the same quality of results especially for polymerase chain reaction (PCR) based applications in cattle. The purpose of the present study was to establish the possibility of using heparin blood for chromosomal studies as well as for molecular biology. Such a practice will obviously save time and money in collecting samples in duplicate.

A range of phosphinoylindoles was prepared in one-pot from functionalized propargyl alcohols and a suitable P(III) precursor via a base-mediated reaction. The reaction proceeds via the intermediacy of allenylphosphine oxides. Similarly, phosphinoylisocoumarins were prepared from allenylphosphine oxides in a trifluoroacetic acid-mediated reaction; the latter also acts as a solvent. Interestingly, in the presence of wet trifluoroacetic acid, in addition to phosphinoylisocoumarins, phosphorus-free isocoumarins were also obtained. Key products were characterized by single crystal X-ray crystallography.

The aim of the study is to standardize the simple method for extracting DNA from cells fixed in fixative (3:1 ratio of methanol and acetic acid glacial) mostly used for chromosomal studies in cattle and buffaloes. These fixed cells were stored for more than 6 months at refrigerated temperature. The fixed cells were washed 2-3 times by the ice cold 1x Phosphate Buffer Saline (PBS) with pH 7.4, so that effect of fixative may be eliminated. The genomic DNA was extracted by adding cell lysis and nucleus lysis buffers. The quality and quantity of DNA were estimated. The readings of nano drop and agarose gel electrophoresis indicate good quality DNA isolated with a rapid and simple protocol routinely using in our laboratory. The method enables us to study the DNA of a cattle and buffaloes after completing cytogenetic investigation or in cases where DNA samples are otherwise not available. This protocol may be useful for molecular analysis of DNA from fixed cells palettes.

Cycloaddition reactions of allenylphosphonates [(RO)(2)P(O)[(R(1))C═C═CR(2)(2)] with dialkyl acetylenedicarboxylates, 1,3-diphenylisobenzofuran, and anthracene have been investigated and compared with those of allenoates [(EtO(2)C)RC═C═CH(2)] and allenylphosphine oxides [Ph(2)P(O)(R(1))C═C═CR(2)(2)] in selected cases. Allenylphosphonates (RO)(2)P(O)(Ar)C═C═CH(2) with an α-aryl group preferentially undergo [4 + 2] cycloaddition with DMAD/DEAD under thermal activation, but in addition to the expected 1:1 (allene: DMAD) product, the reaction also leads to 1:2 as well as 2:1 products that were not reported before. When an extra vinyl group is present at the γ-carbon of allenylphosphonate [e.g., (OCH(2)CMe(2)CH(2)O)P(O)(Ph)C═C═CH(C═CHMe)], [4 + 2] cycloaddition takes place utilizing either the vinylic or the aryl end, but additionally a novel cyclization wherein complete opening of the [β,γ] carbon-carbon double bond of the allene is realized. In contrast to these, the reaction of allenylphosphonate (OCH(2)CMe(2)CH(2)O)P(O)(H)C═C═CMe(2) possessing a terminal ═CMe(2) group with DMAD occurs by both [2 + 2] cycloaddition and ene reaction. While the reaction of ═CH(2) terminal allenylphosphonates as well as allenylphosphine oxides with 1,3-diphenylisobenzofuran afforded preferentially endo-[4 + 2] cycloaddition products via [α,β] attack, the analogous allenoates [(EtO(2)C)RC═C═CH(2)] underwent exo-[4 + 2] cyclization. Under similar conditions, allenylphosphonates with a terminal ═CR(2) group gave only [β,γ]-cycloaddition products. An unusual ring-opening of a [4 + 2] cycloaddition product followed by ring-closing via [4 + 4] cycloaddition, as revealed by (31)P NMR spectroscopy, is reported. Anthracene reacted in a manner similar to 1,3-diphenylisobenzofuran, albeit with lower reactivity. Key products, including a set of exo- and endo- [4 + 2] cycloaddition products, have been characterized by single crystal X-ray crystallography.