BrainStat: A toolbox for brain-wide statistics and multimodal feature associations

Analysis and interpretation of neuroimaging datasets has become a multidisciplinary endeavor, relying not only on statistical methods, but increasingly on associations with respect to other brain-derived features such as gene expression, histological data, and functional as well as cognitive architectures. Here, we introduce BrainStat - a toolbox for (i) univariate and multivariate linear models in volumetric and surface-based brain imaging datasets, and (ii) multidomain feature association of results with respect to spatial maps of post-mortem gene expression and histology, task-based fMRI meta-analysis, as well as resting-state fMRI motifs across several common surface templates. The combination of statistics and feature associations into a turnkey toolbox streamlines analytical processes and accelerates cross-modal research. The toolbox is implemented in both Python and MATLAB, two widely used programming languages in the neuroimaging and neuroinformatics communities. BrainStat is openly available and complemented by an expandable documentation

Temporal lobe epilepsy perturbs the brain‐wide excitation‐inhibition balance: Associations with microcircuit organization, clinical parameters, and cognitive dysfunction

Excitation-inhibition (E/I) imbalance is theorized as a key mechanism in the pathophysiology of epilepsy, with ample research focusing on elucidating its cellular manifestations. However, few studies investigate E/I imbalance at the macroscale, whole-brain level, and its microcircuit-level mechanisms and clinical significance remain incompletely understood. Here, the Hurst exponent, an index of the E/I ratio, is computed from resting-state fMRI time series, and microcircuit parameters are simulated using biophysical models. A broad decrease in the Hurst exponent is observed in pharmaco-resistant temporal lobe epilepsy (TLE), suggesting more excitable network dynamics. Connectome decoders point to temporolimbic and frontocentral cortices as plausible network epicenters of E/I imbalance. Furthermore, computational simulations reveal that enhancing cortical excitability in TLE reflects atypical increases in recurrent connection strength of local neuronal ensembles. Mixed cross-sectional and longitudinal analyses show stronger E/I ratio elevation in patients with longer disease duration, more frequent electroclinical seizures as well as interictal epileptic spikes, and worse cognitive functioning. Hurst exponent-informed classifiers discriminate patients from healthy controls with high accuracy (72.4% [57.5%-82.5%]). Replicated in an independent dataset, this work provides in vivo evidence of a macroscale shift in E/I balance in TLE patients and points to progressive functional imbalances that relate to cognitive decline

The unique cytoarchitecture and wiring of the human default mode network

The default mode network (DMN), a set of brain regions in parietal, temporal and frontal cortex, is implicated in many aspects of complex thought and behavior. However, understanding the role of the DMN is complicated because is implicated in functional states that bridge traditional psychological categories and that may have antagonistic features, notably perceptually-decoupled mind-wandering vs perceptually-driven decision making. Here, we leverage post mortem histology and high field in vivo neuroimaging to show how the anatomy of the DMN helps to explain its broad functional associations. The DMN contains cytoarchitecture associated with unimodal, heteromodal, and memory-related processing, an architecture that can enable complex behaviours dependent on integration of perception and memory. Anatomically, the DMN contains regions receptive to input from sensory cortex and a core that is relatively insulated from environmental input, a division that may explain the network’s role in internally- and externally-focussed states. Finally, the DMN is unique amongst cortical networks in balancing its output across the levels of sensory processing hierarchies, a pattern that may help coordinate and homogenise distributed neural function. Together, our study establishes an anatomical foundation for mechanistic accounts of how the DMN contributes to human thought and behaviour by integrating experiences of the inner and outer worlds

Pharmaco-resistant temporal lobe epilepsy gradually perturbs the cortex-wide excitation-inhibition balance

Excitation-inhibition (E/I) imbalance is theorized as a key mechanism in the pathophysiology of epilepsy, with a mounting body of previous research focusing on elucidating its cellular manifestations. However, there are limited studies into E/I imbalance at macroscale and its microcircuit-level mechanisms and clinical associations. In our current work, we computed the Hurst exponent—a previously validated index of the E/I ratio—from resting-state fMRI time series, and simulated microcircuit parameters using biophysical computational models. We found a broad reduction in the Hurst exponent in pharmaco-resistant temporal lobe epilepsy (TLE), indicative of a shift towards more excitable network dynamics. Connectome decoders pointed to temporolimbic and frontocentral areas as plausible network epicenters of E/I imbalance. Computational simulations further revealed that enhancing cortical excitability in patients likely reflected atypical increases in recurrent connection strength of local neuronal ensembles. Moreover, mixed cross-sectional and longitudinal analyses revealed heightened E/I elevation in patients with longer disease duration, more frequent electroclinical seizures and inter-ictal epileptic spikes, and worse cognitive functioning. Replicated in an independent dataset, our work provides compelling in-vivo evidence of a macroscale shift in E/I balance in TLE patients that undergoes progressive changes and underpins cognitive impairments, potentially informing treatment strategies targeting E/I mechanisms

HippoMaps: Multiscale cartography of human hippocampal organization

The hippocampus has a specialized microarchitecture, is situated at the nexus of multiple macroscale functional networks, contributes to numerous cognitive as well as affective processes and is highly susceptible to brain pathology across common disorders. These features make the hippocampus a model to understand how brain structure covaries with function, in both health and disease. Here we introduce HippoMaps, an open access toolbox and online data warehouse for the mapping and contextualization of subregional hippocampal data in the human brain ( http://hippomaps.readthedocs.io ). HippoMaps capitalizes on a unified hippocampal unfolding approach as well as shape intrinsic registration capabilities to allow for cross-participant and cross-modal data aggregation. We initialize this repository with a combination of hippocampal data spanning three-dimensional ex vivo histology, ex vivo 9.4-Tesla magnetic resonance imaging (MRI), as well as in vivo structural MRI and resting-state functional MRI obtained at 3 Tesla and 7 Tesla, together with intracranial encephalography recordings in patients with epilepsy. All code, data and tools are openly available online, with the aim of fostering further community contributions

Multimodal gradients unify local and global cortical organization

Functional specialization of brain areas and subregions, as well as their integration into large-scale networks, are key principles in neuroscience. Consolidating both local and global perspectives on cortical organization, however, remains challenging. Here, we present an approach to integrate inter- and intra-areal similarities of microstructure, structural connectivity, and functional interactions. Using high-field in-vivo 7 tesla (7 T) Magnetic Resonance Imaging (MRI) data and a probabilistic post-mortem atlas of cortical cytoarchitecture, we derive multimodal gradients that capture cortex-wide organization. Inter-areal similarities follow a canonical sensory-fugal gradient, linking cortical integration with functional diversity across tasks. However, intra-areal heterogeneity does not follow this pattern, with greater variability in association cortices. Findings are replicated in an independent 7 T dataset and a 100-subject 3 tesla (3 T) cohort. These results highlight a robust coupling between local arealization and global cortical motifs, advancing our understanding of how specialization and integration shape human brain function

Network-based atrophy modeling in the common epilepsies: A worldwide ENIGMA study

Copyright \ua9 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).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

Sexual Relationships in Hispanic Countries: a Literature Review

This is a pre-print of an article published in Current Sexual Health Reports. The final authenticated version is available online at: https://doi.org/10.1007/s11930-020-00272-6Purpose of Review: Sexuality is a complex dimension for which culture seems to play an important role, particularly in countries that are more traditional. This review summarizes the knowledge about sexual relationships in Hispanic countries, considering sexual debut, attitudes, behaviors, and satisfaction. Recent Findings: In line with the literature reviewed, the sexual double standard seems to be continuing to influence sexual relationships. Some countries show more open expressions of sexuality based on the level of gender inequality or sexualized context, and within countries, variables such as religious commitment, family characteristics, and access to resources may play important roles in sexuality. Summary: Future research, policies, and interventions should consider these specific characteristics, including these forms of expression of sexuality, in the adjustment of cross-cultural and cross-national strategies

Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study

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 = \ue2 '0.24 to \ue2 '0.73; P < 1.49 7 10 \ue2 '4), and lower thickness in the precentral gyri bilaterally (d = \ue2 '0.34 to \ue2 '0.52; P < 4.31 7 10 \ue2 '6). Both MTLE subgroups showed profound volume reduction in the ipsilateral hippocampus (d = \ue2 '1.73 to \ue2 '1.91, P < 1.4 7 10 \ue2 '19), and lower thickness in extrahippocampal cortical regions, including the precentral and paracentral gyri, compared to controls (d = \ue2 '0.36 to \ue2 '0.52; P < 1.49 7 10 \ue2 '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 = \ue2 '0.29 to \ue2 '0.54; P < 1.49 7 10 \ue2 '4). Contrastingly, thickness differences of the ipsilateral pars opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = \ue2 '0.27 to \ue2 '0.51; P < 1.49 7 10 \ue2 '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 < \ue2 '0.0018; P < 1.49 7 10 \ue2 '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

Brain‐age prediction: Systematic evaluation of site effects, and sample age range and size

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5–90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8–80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9–25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5–40 and 40–90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open-science, web-based platform for individualized neuroimaging metrics