Atypical connectome topography and signal flow in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common pharmaco-resistant epilepsy in adults. While primarily associated with mesiotemporal pathology, recent evidence suggests that brain alterations in TLE extend beyond the paralimbic epicenter and impact macroscale function and cognitive functions, particularly memory. Using connectome-wide manifold learning and generative models of effective connectivity, we examined functional topography and directional signal flow patterns between large-scale neural circuits in TLE at rest. Studying a multisite cohort of 95 patients with TLE and 95 healthy controls, we observed atypical functional topographies in the former group, characterized by reduced differentiation between sensory and transmodal association cortices, with most marked effects in bilateral temporo-limbic and ventromedial prefrontal cortices. These findings were consistent across all study sites, present in left and right lateralized patients, and validated in a subgroup of patients with histopathological validation of mesiotemporal sclerosis and post-surgical seizure freedom. Moreover, they were replicated in an independent cohort of 30 TLE patients and 40 healthy controls. Further analyses demonstrated that reduced differentiation related to decreased functional signal flow into and out of temporolimbic cortical systems and other brain networks. Parallel analyses of structural and diffusion-weighted MRI data revealed that topographic alterations were independent of TLE-related cortical thinning but partially mediated by white matter microstructural changes that radiated away from paralimbic circuits. Finally, we found a strong association between the degree of functional alterations and behavioral markers of memory dysfunction. Our work illustrates the complex landscape of macroscale functional imbalances in TLE, which can serve as intermediate markers bridging microstructural changes and cognitive impairment.

A WORLDWIDE ENIGMA STUDY ON EPILEPSY-RELATED GRAY AND WHITE MATTER COMPROMISE ACROSS THE ADULT LIFESPAN.

Objectives: Temporal lobe epilepsy (TLE) is commonly associated with mesiotemporal pathology and widespread alterations of grey and white matter structures. Evidence supports a progressive condition although the temporal evolution of TLE is poorly defined. This ENIGMA-Epilepsy study utilized multimodal magnetic resonance imaging (MRI) data to investigate structural alterations in TLE patients across the adult lifespan. We charted both grey and white matter changes and explored the covariance of age-related alterations in both compartments. Methods: We studied 769 TLE patients and 885 healthy controls across an age range of 17-73 years, from multiple international sites. To assess potentially non-linear lifespan changes in TLE, we harmonized data and combined median split assessments with cross-sectional sliding window analyses of grey and white matter age-related changes. Covariance analyses examined the coupling of grey and white matter lifespan curves. Results: In TLE, age was associated with a robust grey matter thickness/volume decline across a broad cortico-subcortical territory, extending beyond the mesiotemporal disease epicentre. White matter changes were also widespread across multiple tracts with peak effects in temporo-limbic fibers. While changes spanned the adult time window, changes accelerated in cortical thickness, subcortical volume, and fractional anisotropy (all decreased), and mean diffusivity (increased) after age 55 years. Covariance analyses revealed strong limbic associations between white matter tracts and subcortical structures with cortical regions. Conclusions: This study highlights the profound impact of TLE on lifespan changes in grey and white matter structures, with an acceleration of aging-related processes in later decades of life. Our findings motivate future longitudinal studies across the lifespan and emphasize the importance of prompt diagnosis as well as intervention in patients.

Selective Medial Septum Lesions in Healthy Rats Induce Longitudinal Changes in Microstructure of Limbic Regions, Behavioral Alterations, and Increased Susceptibility to Status Epilepticus.

Septo-hippocampal pathway, crucial for physiological functions and involved in epilepsy. Clinical monitoring during epileptogenesis is complicated. We aim to evaluate tissue changes after lesioning the medial septum (MS) of normal rats and assess how the depletion of specific neuronal populations alters the animals' behavior and susceptibility to establishing a pilocarpine-induced status epilepticus. Male Sprague-Dawley rats were injected into the MS with vehicle or saporins (to deplete GABAergic or cholinergic neurons; n = 16 per group). Thirty-two animals were used for diffusion tensor imaging (DTI); scanned before surgery and 14 and 49 days post-injection. Fractional anisotropy and apparent diffusion coefficient were evaluated in the fimbria, dorsal hippocampus, ventral hippocampus, dorso-medial thalamus, and amygdala. Between scans 2 and 3, animals were submitted to diverse behavioral tasks. Stainings were used to analyze tissue alterations. Twenty-four different animals received pilocarpine to evaluate the latency and severity of the status epilepticus 2 weeks after surgery. Additionally, eight different animals were only used to evaluate the neuronal damage inflicted on the MS 1 week after the molecular surgery. Progressive changes in DTI parameters in both white and gray matter structures of the four evaluated groups were observed. Behaviorally, the GAT1-saporin injection impacted spatial memory formation, while 192-IgG-saporin triggered anxiety-like behaviors. Histologically, the GABAergic toxin also induced aberrant mossy fiber sprouting, tissue damage, and neuronal death. Regarding the pilocarpine-induced status epilepticus, this agent provoked an increased mortality rate. Selective septo-hippocampal modulation impacts the integrity of limbic regions crucial for certain behavioral skills and could represent a precursor for epilepsy development.

Functional correlates of cognitive performance and working memory in temporal lobe epilepsy: Insights from task-based and resting-state fMRI.

Temporal lobe epilepsy (TLE) is a common form of medically intractable epilepsy. Although seizures originate in mesial temporal structures, there are widespread abnormalities of gray and white matter beyond the temporal lobes that negatively impact functional networks and cognition. Previous studies have focused either on the global impact on functional networks, or on the functional correlates of specific cognitive abilities. Here, we use a two-pronged approach to evaluate the link between whole-brain functional connectivity (FC) anomalies to overall cognitive performance, and how such abnormal connectivity alters the fronto-parietal brain regions involved in working memory (WMem), a cognitive disability often reported by TLE patients. We evaluated 31 TLE patients and 35 healthy subjects through extensive cognitive testing, resting-state functional magnetic resonance imaging (RS-fMRI), and task-based fMRI using Sternberg's task to evaluate WMem. As a group, TLE patients displayed cognitive abnormalities across different domains, although considerable within-group variability was identified. TLE patients showed disruptions of functional networks between and within the default mode network (DMN) and task-positive networks (TPN) resulting in associations with cognitive performance. Furthermore, during the WMem task, TLE patients showed abnormal activity of fronto-parietal regions that were associated with other forms of memory, and alterations of seed-based connectivity analyses. Our results show that different degrees of abnormal functional brain activity and connectivity are related to the severity of disabilities across cognitive spheres. Differential co-activation patterns between patients and healthy subjects suggest potential compensatory mechanisms to preserve adequate cognitive performance.

ILAE neuroimaging task force highlight: Subcortical laminar heterotopia.

The ILAE Neuroimaging Task Force publishes educational case reports that highlight basic aspects of neuroimaging in epilepsy consistent with the ILAE's educational mission. Subcortical laminar heterotopia, also known as subcortical band heterotopia (SBH) or "double cortex," is an intriguing and rare congenital malformation of cortical development. SBH lesions are part of a continuum best designated as agyria-pachygyria-band-spectrum. The malformation is associated with epilepsy that is often refractory, as well as variable degrees of developmental delay. Moreover, in an increasing proportion of cases, a distinct molecular-genetic background can be found. Diagnosing SBH can be a major challenge for many reasons, including more subtle lesions, and "non-classic" or unusual MRI-appearances. By presenting an illustrative case, we address the challenges and needs of diagnosing and treating SBH patients in epilepsy, especially the value of high-resolution imaging and specialized MRI-protocols.

Pre-supplementary Motor Cortex Mediates Learning Transfer from Perceptual to Motor Timing.

When we intensively train a timing skill, such as learning to play the piano, we not only produce brain changes associated with task-specific learning but also improve our performance in other temporal behaviors that depend on these tuned neural resources. Since the neural basis of time learning and generalization is still unknown, we measured the changes in neural activity associated with the transfer of learning from perceptual to motor timing in a large sample of subjects (n = 65; 39 women). We found that intense training in an interval discrimination task increased the acuity of time perception in a group of subjects that also exhibited learning transfer, expressed as a reduction in inter-tap interval variability during an internally driven periodic motor task. In addition, we found subjects with no learning and/or generalization effects. Notably, functional imaging showed an increase in pre-supplementary motor area and caudate-putamen activity between the post- and pre-training sessions of the tapping task. This increase was specific to the subjects that generalized their timing acuity from the perceptual to the motor context. These results emphasize the central role of the cortico-basal ganglia circuit in the generalization of timing abilities between tasks.

The neurovascular unit of capillary blood vessels in the rat nervous system. A rapid-Golgi electron microscopy study.

We describe a pericapillary organ in the rat forebrain and cerebellar cortex. It consists of a series of tripartite synapses with synaptic extensions enveloped by astrocytic endfeet that are linked to the capillary wall by synaptic extensions. Reciprocal specializations of the pericyte-capillary blood vessel (CBV) with such specialized synapses suggest a mechanoreceptor role. In Golgi-impregnated and 3D reconstructions of the cerebral cortex and thalamus, a series of TSs appear to be sequentially ordered in a common dendrite, paralleled by synaptic outgrowths termed golf club synaptic extensions (GCE) opposed to a longitudinal crest (LC) from the capillary basal lamina (BL). Our results show that, in the cerebellar cortex, afferent fibers and interneurons display microanatomical structures that strongly suggest an interaction with the capillary wall. Afferent mossy fiber (MF) rosettes and ascending granule cell axons and their dendrites define the pericapillary passage interactions that are entangled by endfeet. The presence of mRNA of the mechanosensitive channel Piezo1 in the MF rosettes, together with the surrounding end-feet and the capillary wall form mechanosensory units. The ubiquity of such units to modulate synaptic transmission is also supported by Piezo1 mRNA expressing pyramidal isocortical and thalamic neurons. This scenario suggests that ascending impulses to the cerebellar and cortical targets are presynaptically modulated by the reciprocal interaction with the mechanosensory pericapillary organ that ultimately modulates the vasomotor response.

Simultaneous and independent electroencephalography and magnetic resonance imaging: A multimodal neuroimaging dataset.

We introduce an open access, multimodal neuroimaging dataset comprising simultaneously and independently collected Electroencephalography (EEG) and Magnetic Resonance Imaging (MRI) data from twenty healthy, young male individuals (mean age = 26 years; SD = 3.8 years). The dataset adheres to the BIDS standard specification and is structured into two components: 1) EEG data recorded outside the Magnetic Resonance (MR) environment, inside the MR scanner without image collection and during simultaneous functional MRI acquisition (EEG-fMRI) and 2) Functional MRI data acquired with and without simultaneous EEG recording and structural MRI data obtained with and without the participants wearing the EEG cap. EEG data were recorded with an MR-compatible EEG recording system (GES 400 MR, Electrical Geodesics Inc.) using a 32-channel sponge-based EEG cap (Geodesic Sensor Net). Eyes-closed resting-state EEG data were recorded for two minutes in both the outside and inside scanner conditions and for ten minutes during simultaneous EEG-fMRI. Eyes-open resting-state EEG data were recorded for two minutes under each condition. Participants also performed an eyes opening-eyes closure block-design task outside the scanner (two minutes) and during simultaneous EEG-fMRI (four minutes). The EEG data recorded outside the scanner provides a reference signal devoid of MR-related artifacts. The data collected inside the scanner without image acquisition captures the contribution of the ballistocardiographic (BCG) without the gradient artifact, making it suitable for testing and validating BCG artifact correction methods. The EEG-fMRI data is affected by both the gradient and BCG artifacts. Brain images were acquired using a 3T GE MR750-Discovery MR scanner equipped with a 32-channel head coil. Whole-brain functional images were obtained using a GRE-EPI T2* weighted sequence (TR = 2000 ms, TE = 40 ms, 35 interleaved axial slices with 4 mm isometric voxels). Structural images were acquired using an SPGR sequence (TR = 8.1 ms, TE = 3.2 ms, flip angle = 12°, 176 sagittal slices with 1 mm isometric voxels). This stands as one of the largest open access EEG-fMRI datasets available, which allows researchers to: 1) Assess the impact of gradient and BCG artifacts on EEG data, 2) Evaluate the effectiveness of novel artifact removal techniques to minimize artifact contribution and preserve EEG signal integrity, 3) Conduct hardware/setup comparison studies, 4) Evaluate the quality of structural and functional MRI data obtained with this particular EEG system, and 5) Implement and validate multimodal integrative analysis approaches on simultaneous EEG-fMRI data.

Standardizing an Experimental Murine Model of Extraparenchymal Neurocysticercosis That Immunologically Resembles Human Infection.

BACKGROUND: Neurocysticercosis (NCC) is endemic in non-developed regions of the world. Two forms of NCC have been described, for which neurological morbidity depends on the location of the lesion, which can be either within the cerebral parenchyma or in extraparenchymal spaces. The extraparenchymal form (EXP-NCC) is considered the most severe form of NCC. EXP-NCC often requires several cycles of cysticidal treatment and the concomitant use of glucocorticoids to prevent increased inflammation, which could lead to intracranial hypertension and, in rare cases, to death. Thus, the improvement of EXP-NCC treatment is greatly needed. METHODS: An experimental murine model of EXP-NCC, as an adequate model to evaluate new therapeutic approaches, and the parameters that support it are described. EXP-NCC was established by injecting 30 Taenia crassiceps cysticerci, which are less than 0.5 mm in diameter, into the cisterna magna of male and female Wistar rats. RESULTS: Cyst implantation and infection progression were monitored by detecting the HP10 antigen and anti-cysticercal antibodies in the serum and cerebral spinal fluid (CSF) of infected rats and by magnetic resonance imaging. Higher HP10 levels were observed in CSF than in the sera, as in the case of human EXP-NCC. Low cell recruitment levels were observed surrounding established cysticerci in histological analysis, with a modest increase in GFAP and Iba1 expression in the parenchyma of female animals. Low cellularity in CSF and low levels of C-reactive protein are consistent with a weak inflammatory response to this infection. After 150 days of infection, EXP-NCC is accompanied by reduced levels of mononuclear cell proliferation, resembling the human disease. EXP-NCC does not affect the behavior or general status of the rats. CONCLUSIONS: This model will allow the evaluation of new approaches to control neuroinflammation and immunomodulatory treatments to restore and improve the specific anti-cysticercal immunity in EXP-NCC.

Atypical connectome topography and signal flow in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is one of the most common pharmaco-resistant epilepsies in adults. While hippocampal pathology is the hallmark of this condition, emerging evidence indicates that brain alterations extend beyond the mesiotemporal epicenter and affect macroscale brain function and cognition. We studied macroscale functional reorganization in TLE, explored structural substrates, and examined cognitive associations. We investigated a multisite cohort of 95 patients with pharmaco-resistant TLE and 95 healthy controls using state-of-the-art multimodal 3T magnetic resonance imaging (MRI). We quantified macroscale functional topographic organization using connectome dimensionality reduction techniques and estimated directional functional flow using generative models of effective connectivity. We observed atypical functional topographies in patients with TLE relative to controls, manifesting as reduced functional differentiation between sensory/motor networks and transmodal systems such as the default mode network, with peak alterations in bilateral temporal and ventromedial prefrontal cortices. TLE-related topographic changes were consistent in all three included sites and reflected reductions in hierarchical flow patterns between cortical systems. Integration of parallel multimodal MRI data indicated that these findings were independent of TLE-related cortical grey matter atrophy, but mediated by microstructural alterations in the superficial white matter immediately beneath the cortex. The magnitude of functional perturbations was robustly associated with behavioral markers of memory function. Overall, this work provides converging evidence for macroscale functional imbalances, contributing microstructural alterations, and their associations with cognitive dysfunction in TLE.

Tractography passes the test: Results from the diffusion-simulated connectivity (disco) challenge.

Estimating structural connectivity from diffusion-weighted magnetic resonance imaging is a challenging task, partly due to the presence of false-positive connections and the misestimation of connection weights. Building on previous efforts, the MICCAI-CDMRI Diffusion-Simulated Connectivity (DiSCo) challenge was carried out to evaluate state-of-the-art connectivity methods using novel large-scale numerical phantoms. The diffusion signal for the phantoms was obtained from Monte Carlo simulations. The results of the challenge suggest that methods selected by the 14 teams participating in the challenge can provide high correlations between estimated and ground-truth connectivity weights, in complex numerical environments. Additionally, the methods used by the participating teams were able to accurately identify the binary connectivity of the numerical dataset. However, specific false positive and false negative connections were consistently estimated across all methods. Although the challenge dataset doesn't capture the complexity of a real brain, it provided unique data with known macrostructure and microstructure ground-truth properties to facilitate the development of connectivity estimation methods.

Multi-tensor diffusion abnormalities of gray matter in an animal model of cortical dysplasia.

Focal cortical dysplasias are a type of malformations of cortical development that are a common cause of drug-resistant focal epilepsy. Surgical treatment is a viable option for some of these patients, with their outcome being highly related to complete surgical resection of lesions visible in magnetic resonance imaging (MRI). However, subtle lesions often go undetected on conventional imaging. Several methods to analyze MRI have been proposed, with the common goal of rendering subtle cortical lesions visible. However, most image-processing methods are targeted to detect the macroscopic characteristics of cortical dysplasias, which do not always correspond to the microstructural disarrangement of these cortical malformations. Quantitative analysis of diffusion-weighted MRI (dMRI) enables the inference of tissue characteristics, and novel methods provide valuable microstructural features of complex tissue, including gray matter. We investigated the ability of advanced dMRI descriptors to detect diffusion abnormalities in an animal model of cortical dysplasia. For this purpose, we induced cortical dysplasia in 18 animals that were scanned at 30 postnatal days (along with 19 control animals). We obtained multi-shell dMRI, to which we fitted single and multi-tensor representations. Quantitative dMRI parameters derived from these methods were queried using a curvilinear coordinate system to sample the cortical mantle, providing inter-subject anatomical correspondence. We found region- and layer-specific diffusion abnormalities in experimental animals. Moreover, we were able to distinguish diffusion abnormalities related to altered intra-cortical tangential fibers from those associated with radial cortical fibers. Histological examinations revealed myelo-architectural abnormalities that explain the alterations observed through dMRI. The methods for dMRI acquisition and analysis used here are available in clinical settings and our work shows their clinical relevance to detect subtle cortical dysplasias through analysis of their microstructural properties.

Differentiation of white matter histopathology using b-tensor encoding and machine learning.

Diffusion-weighted magnetic resonance imaging (DW-MRI) is a non-invasive technique that is sensitive to microstructural geometry in neural tissue and is useful for the detection of neuropathology in research and clinical settings. Tensor-valued diffusion encoding schemes (b-tensor) have been developed to enrich the microstructural data that can be obtained through DW-MRI. These advanced methods have proven to be more specific to microstructural properties than conventional DW-MRI acquisitions. Additionally, machine learning methods are particularly useful for the study of multidimensional data sets. In this work, we have tested the reach of b-tensor encoding data analyses with machine learning in different histopathological scenarios. We achieved this in three steps: 1) We induced different levels of white matter damage in rodent optic nerves. 2) We obtained ex vivo DW-MRI data with b-tensor encoding schemes and calculated quantitative metrics using Q-space trajectory imaging. 3) We used a machine learning model to identify the main contributing features and built a voxel-wise probabilistic classification map of histological damage. Our results show that this model is sensitive to characteristics of microstructural damage. In conclusion, b-tensor encoded DW-MRI data analyzed with machine learning methods, have the potential to be further developed for the detection of histopathology and neurodegeneration.

Neurocysticercosis and epilepsy: Imaging and clinical characteristics.

The ILAE Neuroimaging Task Force aimed to publish educational case reports highlighting basic aspects related to neuroimaging in epilepsy consistent with the educational mission of the ILAE. Neurocysticercosis (NCC) is highly endemic in resource-limited countries and increasingly more often seen in non-endemic regions due to migration. Cysts with larva of the tapeworm Taenia solium lodge in the brain and cause several neurological conditions, of which seizures are the most common. There is great heterogeneity in the clinical presentation of neurocysticercosis because cysts vary in number, larval stage, and location among patients. We here present two illustrative cases with different clinical features to highlight the varying severity of symptoms secondary to this parasitic infestation. We also present several examples of imaging characteristics of the disease at various stages, which emphasize the central role of neuroimaging in the diagnosis of neurocysticercosis.

Atypical intrinsic neural timescales in temporal lobe epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) is the most common pharmacoresistant epilepsy in adults. Here we profiled local neural function in TLE in vivo, building on prior evidence that has identified widespread structural alterations. Using resting-state functional magnetic resonance imaging (rs-fMRI), we mapped the whole-brain intrinsic neural timescales (INT), which reflect temporal hierarchies of neural processing. Parallel analysis of structural and diffusion MRI data examined associations with TLE-related structural compromise. Finally, we evaluated the clinical utility of INT. METHODS: We studied 46 patients with TLE and 44 healthy controls from two independent sites, and mapped INT changes in patients relative to controls across hippocampal, subcortical, and neocortical regions. We examined region-specific associations to structural alterations and explored the effects of age and epilepsy duration. Supervised machine learning assessed the utility of INT for identifying patients with TLE vs controls and left- vs right-sided seizure onset. RESULTS: Relative to controls, TLE showed marked INT reductions across multiple regions bilaterally, indexing faster changing resting activity, with strongest effects in the ipsilateral medial and lateral temporal regions, and bilateral sensorimotor cortices as well as thalamus and hippocampus. Findings were similar, albeit with reduced effect sizes, when correcting for structural alterations. INT reductions in TLE increased with advancing disease duration, yet findings differed from the aging effects seen in controls. INT-derived classifiers discriminated patients vs controls (balanced accuracy, 5-fold: 76% ± 2.65%; cross-site, 72%-83%) and lateralized the focus in TLE (balanced accuracy, 5-fold: 96% ± 2.10%; cross-site, 95%-97%), with high accuracy and cross-site generalizability. Findings were consistent across both acquisition sites and robust when controlling for motion and several methodological confounds. SIGNIFICANCE: Our findings demonstrate atypical macroscale function in TLE in a topography that extends beyond mesiotemporal epicenters. INT measurements can assist in TLE diagnosis, seizure focus lateralization, and monitoring of disease progression, which emphasizes promising clinical utility.

Prenatal Cafeteria Diet Primes Anxiety-like Behavior Associated to Defects in Volume and Diffusion in the Fimbria-fornix of Mice Offspring.

Prenatal exposure to high-energy diets primes brain alterations that increase the risk of developing behavioral and cognitive failures. Alterations in the structure and connectivity of brain involved in learning and memory performance are found in adult obese murine models and in humans. However, the role of prenatal exposure to high-energy diets in the modulation of the brain's structure and function during cognitive decline remains unknown. We used female C57BL6 mice (n = 10) exposed to a high-energy diets (Cafeteria diet (CAF)) or Chow diet for 9 weeks (before, during and after pregnancy) to characterize their effect on brain structural organization and learning and memory performance in the offspring at two-month-old (n = 17). Memory and learning performance were evaluated using the Y-maze test including forced and spontaneous alternation, novel object recognition (NORT), open field and Barnes maze tests. We found no alterations in the short- or long-time spatial memory performance in male offspring prenatally exposed to CAF diet when compared to the control, but they increased time spent in the edges resembling anxiety-like behavior. By using deformation-based morphometry and diffusion tensor imaging analysis we found that male offspring exposed to CAF diet showed increased volume in primary somatosensory cortex and a reduced volume of fimbria-fornix, which correlate with alterations in its white matter integrity. Biological modeling revealed that prenatal exposure to CAF diet predicts low volume in the fimbria-fornix, which was associated with anxiety in the offspring. The findings suggest that prenatal exposure to high-energy diets prime brain structural alterations related to anxiety in the offspring.

Micapipe: A pipeline for multimodal neuroimaging and connectome analysis.

Multimodal magnetic resonance imaging (MRI) has accelerated human neuroscience by fostering the analysis of brain microstructure, geometry, function, and connectivity across multiple scales and in living brains. The richness and complexity of multimodal neuroimaging, however, demands processing methods to integrate information across modalities and to consolidate findings across different spatial scales. Here, we present micapipe, an open processing pipeline for multimodal MRI datasets. Based on BIDS-conform input data, micapipe can generate i) structural connectomes derived from diffusion tractography, ii) functional connectomes derived from resting-state signal correlations, iii) geodesic distance matrices that quantify cortico-cortical proximity, and iv) microstructural profile covariance matrices that assess inter-regional similarity in cortical myelin proxies. The above matrices can be automatically generated across established 18 cortical parcellations (100-1000 parcels), in addition to subcortical and cerebellar parcellations, allowing researchers to replicate findings easily across different spatial scales. Results are represented on three different surface spaces (native, conte69, fsaverage5), and outputs are BIDS-conform. Processed outputs can be quality controlled at the individual and group level. micapipe was tested on several datasets and is available at https://github.com/MICA-MNI/micapipe, documented at https://micapipe.readthedocs.io/, and containerized as a BIDS App http://bids-apps.neuroimaging.io/apps/. We hope that micapipe will foster robust and integrative studies of human brain microstructure, morphology, function, cand connectivity.

Brain circuits activated by female sexual behavior evaluated by manganese enhanced magnetic resonance imaging.

Magnetic resonance imaging (MRI) allows obtaining anatomical and functional information of the brain in the same subject at different times. Manganese-enhanced MRI (MEMRI) uses manganese ions to identify brain activity, although in high doses it might produce neurotoxic effects. Our aims were to identify a manganese dose that does not affect motivated behaviors such as sexual behavior, running wheel and the rotarod test. The second goal was to determine the optimal dose of chloride manganese (MnCl2) that will allow us to evaluate activation of brain regions after females mated controlling (pacing) the sexual interaction. To achieve that, two experiments were performed. In experiment 1 we evaluated the effects of two doses of MnCl2, 8 and 16 mg/kg. Subjects were injected with one of the doses of MnCl2 24 hours before the test on sessions 1, 5 and 10 and immediately thereafter scanned. Female sexual behavior, running wheel and the rotarod were evaluated once a week for 10 weeks. In experiment 2 we followed a similar procedure, but females paced the sexual interaction once a week for 10 weeks and were injected with one of the doses of MnCl2 24 hours before the test and immediately thereafter scanned on sessions 1, 5 and 10. The results of experiment 1 show that neither dose of MnCl2 induces alterations on sexual behavior, running wheel and rotarod. Experiment 2 demonstrated that MEMRI allow us to detect activation of different brain regions after sexual behavior, including the olfactory bulb (OB), the bed nucleus of the stria terminalis (BNST), the amygdala (AMG), the medial preoptic area (MPOA), the ventromedial hypothalamus (VMH), the nucleus accumbens (NAcc), the striatum (STR) and the hippocampus (Hipp) allowing the identification of changes in brain circuits activated by sexual behavior. The socio sexual circuit showed a higher signal intensity on session 5 than the reward circuit and the control groups indicating that even with sexual experience the activation of the reward circuit requires the activation of the socio sexual circuit. Our study demonstrates that MEMRI can be used repeatedly in the same subject to evaluate the activation of brain circuits after motivated behaviors and how can this activation change with experience.

Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression.

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.

Event-based modeling in temporal lobe epilepsy demonstrates progressive atrophy from cross-sectional data.

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.