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Background: Structural and functional neuroimaging studies often overlook lower basal ganglia structures located in and adjacent to the midbrain due to poor contrast on clinically acquired T1-weighted scans. Here, we acquired T1-weighted, T2-weighted, and resting-state fMRI scans to investigate differences in volume, estimated myelin content and functional connectivity of the substantia nigra (SN), subthalamic nuclei (SubTN) and red nuclei (RN) of the midbrain in IGE., Methods: Thirty-three patients with IGE (23 refractory, 10 non-refractory) and 39 age and sex-matched healthy controls underwent MR imaging. Midbrain structures were automatically segmented from T2-weighted images and structural volumes were calculated. The estimated myelin content for each structure was determined using a T1-weighted/T2-weighted ratio method. Resting-state functional connectivity analysis of midbrain structures (seed-based) was performed using the CONN toolbox., Results: An increased volume of the right RN was found in IGE and structural volumes of the right SubTN differed between patients with non-refractory and refractory IGE. However, no volume findings survived corrections for multiple comparisons. No myelin alterations of midbrain structures were found for any subject groups. We found functional connectivity alterations including significantly decreased connectivity between the left SN and the thalamus and significantly increased connectivity between the right SubTN and the superior frontal gyrus in IGE., Conclusions: We report volumetric and functional connectivity alterations of the midbrain in patients with IGE. We postulate that potential increases in structural volumes are due to increased iron deposition that impacts T2-weighted contrast. These findings are consistent with previous studies demonstrating pathophysiological abnormalities of the lower basal ganglia in animal models of generalised epilepsy., 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 Author(s). Published by 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.)

The Wada test remains the traditional test for lateralizing language and memory function prior to epilepsy surgery. Functional imaging, particularly functional MRI (fMRI), has made progress in the language domain, but less so in the memory domain. Magnetoencephalography (MEG) has received less research attention, but shows promise, particularly for language lateralization. We recruited a consecutive sample of 19 patients with epilepsy who had completed presurgical work-up, including the Wada test, and compared fMRI (memory) and MEG (language and memory) with Wada test results. The main research question was the concordance between Wada and these two imaging techniques as preepilepsy surgery investigations. We were also interested in the acceptability of the three techniques to patients. Concordance rates (N=16) were nonsignificant (Cohen's Kappa) between fMRI and Wada test (memory) and between MEG and Wada test (memory and language). The Wada test was a well-established protocol used at several epilepsy surgery centers in the UK. Patients generally found the Wada test an odd, but not aversive procedure. Sixteen (84%) patients who were scanned reported some level of obtundation in MEG. We present these discordant findings in support of the position that functional imaging and the Wada test are distinctive procedures, with little in the way of overlapping mechanisms, and that patient's experience should be taken into account when procedures are selected and offered to them., (Copyright © 2017 Elsevier Inc. All rights reserved.)

There is an increasing awareness of the involvement of thalamic connectivity on higher level cortical functioning in the human brain. This is reflected by the influence of thalamic stimulation on cortical activity and behavior as well as apparently cortical lesion syndromes occurring as a function of small thalamic insults. Here, we attempt to noninvasively test the correspondence of structural and functional connectivity of the human thalamus using diffusion-weighted and resting-state functional MRI. Using a large sample of 102 adults, we apply tensor independent component analysis to diffusion MRI tractography data to blindly parcellate bilateral thalamus according to diffusion tractography-defined structural connectivity. Using resting-state functional MRI collected in the same subjects, we show that the resulting structurally defined thalamic regions map to spatially distinct, and anatomically predictable, whole-brain functional networks in the same subjects. Although there was significant variability in the functional connectivity patterns, the resulting 51 structural and functional patterns could broadly be reduced to a subset of 7 similar core network types. These networks were distinct from typical cortical resting-state networks. Importantly, these networks were distributed across the brain and, in a subset, map extremely well to known thalamocortico-basal-ganglial loops., (© The Author 2015. Published by Oxford University Press.)

A particularly popular automated magnetic resonance imaging (MRI) hippocampal subfield mapping technique is the one described by Van Leemput et al. (2009: Hippocampus 19:549-557) that is currently distributed with FreeSurfer software. This method assesses the probabilistic locations of subfields based on a priori knowledge of subfield topology determined from high-field MRI. Many studies have applied this technique to conventionally acquired T1-weighted MRI data. In the present study, we investigated the relationship between this technique applied to conventional T1-weighted MRI data acquired at 3 T and postsurgical hippocampal histology in patients with medically intractable mesial temporal lobe epilepsy (mTLE) and hippocampal sclerosis (HS). Patients with mTLE (n = 82) exhibited significant volume loss of ipsilateral CA1, CA2-3, CA4-dentate gyrus (DG), subiculum, and fimbria relative to controls (n = 81). Histopathological analysis indicated that the most significant neuronal loss was observed in CA1, then CA4 and CA3, and more subtle neuronal loss in CA2, consistent with classical HS. Neuronal density of CA1 significantly correlated with MRI-determined volume of CA1, and increasingly so with CA2-3 and CA4-DG. Patients with increased HS based on histopathology had greater volume loss of the ipsilateral hippocampal regions on MRI. We conclude by suggesting that whilst time efficient and fully reproducible when applied to conventional single acquisition sequences, the use of the automated subfield technique described here may necessitate the application to multiacquisition high-resolution MR sequences for accurate delineation of hippocampal subfields., (Copyright © 2014 Wiley Periodicals, Inc.)

Individual differences in executive functioning and brain morphology are considerable. In this study, we investigated their interrelation in a large sample of healthy older individuals. Digit span, trail-making, and Stroop tasks were used to assess different executive subfunctions in 367 nondemented community-dwelling individuals (50-81 years). Task performance was analyzed relative to brain structure using voxel-based morphometry, corrected for age and sex. Improved task performance was associated with increased local gray matter volume in task-specific patterns that showed partial, but not complete overlap with known task-specific functional imaging patterns. While all three tasks showed associations with prefrontal gray matter volume as expected for executive functioning, the strongest overlap between the three tasks was found in insular cortex, suggesting that it has a previously underestimated role for executive functions. The association between the insular cortex and executive functioning was corroborated using stereological region-of-interest measurement of insular volume in a subgroup of 93 subjects. Quantitatively, the volume of the single most strongly related region explained 2.4 ± 1.1% of the variance in executive performance over and above the variance explained by age, which amounted to 7.4 ± 4.1%. The age-independent peak associations between executive performance and gray matter described here occurred in regions that were also strongly affected by age-related gray matter atrophy, consistent with the hypothesis that age-related regional brain volume loss and age-related cognitive changes are linked., (Copyright © 2012 Wiley Periodicals, Inc.)

Purpose: Patients with juvenile myoclonic epilepsy (JME) show evidence of microstructural white matter (WM) damage of thalamocortical fiber tracts and changes of blood oxygen level dependent (BOLD) signal in a striatothalamocortical network. The objective of the present study was to investigate microstructural and volumetric alterations of the putamen in patients with JME using diffusion tensor imaging (DTI) and conventional magnetic resonance imaging (MRI)., Methods: We performed DTI and MRI for 10 patients with JME and 59 age-matched neurologically healthy volunteers. Evaluation of microstructural damage was investigated using calculation of mean fractional anisotropy (FA) values in a priori regions of interest (ROIs) for the putamen, frontal lobe, and a thalamocortical region, after application of an improved eddy current correction method and a new statistical parametric mapping (SPM)-compatible toolbox incorporating intensive multicontrast FA image registration. Stereologic analysis on MRI was performed to estimate macroscopic volume of the putamen in both cerebral hemispheres for all subjects., Key Findings: Relative to controls, patients had significantly reduced FA in the frontal lobe (p = 0.01) and thalamocortical fiber WM (p < 0.001). In contrast, putamen FA was bilaterally increased (p = 0.01) and correlated with decreasing putamen volume (r(2) = -0.63, p = 0.004) in patients only. Putamen FA correlated negatively with onset of JME (total: r(2) = -0.50, p = 0.01), duration of JME (r(2) = 0.52, p = 0.01), and thalamocortical fiber FA (r(2) = -0.47, p = 0.01)., Significance: This is the first evidence of combined microstructural and macrostructural putamen abnormalities in patients with JME, with early age of onset and a longer duration of epilepsy being significant predictors for greater architectural alterations. These findings are consistent with studies indicating neurophysiologic abnormalities of frontostriatal networks in patients with JME, and may contribute to explain the frequent presentation of executive dysfunction in these patients. Confirmation and further exploration of the increase in putamen FA in patients with JME is required in larger samples., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

It has long been suspected that cortical interhemispheric asymmetries may underlie hemispheric language dominance (HLD). To test this hypothesis, we determined interhemispheric asymmetries using stereology and MRI of three cortical regions hypothesized to be related to HLD (Broca's area, planum temporale, and insula) in healthy adults in whom HLD was determined using functional transcranial Doppler sonography and functional MRI (15 left HLD, 10 right HLD). We observed no relationship between volume asymmetry of the gyral correlates of Broca's area or planum temporale and HLD. However, we observed a robust relationship between volume asymmetry of the insula and HLD (p = .008), which predicted unilateral HLD in 88% individuals (86.7% left HDL and 90% right HLD). There was also a subtle but significant positive correlation between the extent of HLD and insula volume asymmetry (p = .02), indicating that a larger insula predicted functional lateralization to the same hemispheric side for the majority of subjects. We found no visual evidence of basic anatomical markers of HLD other than that the termination of the right posterior sylvian fissure was more likely to be vertical than horizontal in right HLD subjects (p = .02). Predicting HLD by virtue of gross brain anatomy is complicated by interindividual variability in sulcal contours, and the possibility remains that morphological and cytoarchitectural organization of the classical language regions may underlie HLD when analyses are not constrained by the natural limits imposed by measurement of gyral volume. Although the anatomical correlates of HLD will most likely be found to include complex intra- and interhemispheric connections, there is the possibility that such connectivity may correlate with gray matter morphology. We suggest that the potential significance of insular morphology should be considered in future studies addressing the anatomical correlates of human language lateralization.

This study examined interactive effects of sex and age on prefrontal brain anatomy in humans. It specifically targeted ranges of the adult life span and regions of cortex that previously showed male-female differences. Participants were 68 healthy human males and females aged 20-72 years. Data collection and analysis were conducted in parallel across two cohorts (laboratories) to investigate reproducibility of effects in relation to sex and age. Volumes for four regional prefrontal subfields per hemisphere were obtained from high-resolution MRI. Regional sex by age interactions were replicated across cohorts. In men, age effects were greatest in medial prefrontal volume, with decreases in dorsal medial and orbital medial regions. In women, age-related changes in medial prefrontal regions were limited to the dorsal volume, with additional decreases observed in lateral subfields. Cohort and Cohort x Age effects in total brain and total prefrontal volume were linked to a combination of methodological and sampling-related factors. Findings indicated that neuroanatomical changes throughout adulthood unfold along different time scales in men and women. Results also showed that sex differences in ageing localized to medial prefrontal regions were particularly robust to variation across cohorts.