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The hippocampus is a uniquely infolded allocortical structure in the medial temporal lobe that consists of the microstructurally and functionally distinct subregions: subiculum, cornu ammonis, and dentate gyrus. The hippocampus is a remarkably plastic region that is implicated in learning and memory. At the same time it has been shown that hippocampal subregion volumes are heritable, and that genetic expression varies along a posterior to anterior axis. Here, we studied how a heritable, stable, hippocampal organisation may support its flexible function in healthy adults. Leveraging the twin set-up of the Human Connectome Project with multimodal neuroimaging, we observed that the functional connectivity between hippocampus and cortex was heritable and that microstructure of the hippocampus genetically correlated with cortical microstructure. Moreover, both functional and microstructural organisation could be consistently captured by anterior-to-posterior and medial-to-lateral axes across individuals. However, heritability of functional, relative to microstructural, organisation was found reduced, suggesting individual variation in functional organisation may be explained by experience-driven factors. Last, we demonstrate that structure and function couple along an inherited macroscale organisation, suggesting an interplay of stability and plasticity within the hippocampus. Our study provides new insights on the heritability of the hippocampal of the structure and function within the hippocampal organisation., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Building precise and detailed parcellations of anatomically and functionally distinct brain areas has been a major focus in Neuroscience. Pioneer anatomists parcellated the cortical manifold based on extensive histological studies of post-mortem brain, harnessing local variations in cortical cyto- and myeloarchitecture to define areal boundaries. Compared to the cytoarchitectonic field, where multiple neuroimaging studies have recently translated this old legacy data into useful analytical resources, myeloarchitectonics, which parcellate the cortex based on the organization of myelinated fibers, has received less attention. Here, we present the neocortical surface-based myeloarchitectonic atlas based on the histology-derived maps of the Vogt-Vogt school and its 2D translation by Nieuwenhuys. In addition to a myeloarchitectonic parcellation, our package includes intracortical laminar profiles of myelin content based on Vogt-Vogt-Hopf original publications. Histology-derived myelin density mapped on our atlas demonstrated a close overlap with in vivo quantitative MRI markers for myelin and relates to cytoarchitectural features. Complementing the existing battery of approaches for digital cartography, the whole-brain myeloarchitectonic atlas offers an opportunity to validate imaging surrogate markers of myelin in both health and disease., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest related to this manuscript., (Copyright © 2022. Published by Elsevier Inc.)

The majority of MRI studies in temporal lobe epilepsy (TLE) have utilized morphometry to map widespread cortical alterations. Morphological markers, such as cortical thickness or grey matter density, reflect combinations of biological events largely driven by overall cortical geometry rather than intracortical tissue properties. Because of its sensitivity to intracortical myelin, quantitative measurement of longitudinal relaxation time (qT 1 ) provides and an in vivo proxy for cortical microstructure. Here, we mapped the regional distribution of qT 1 in a consecutive cohort of 24 TLE patients and 20 healthy controls. Compared to controls, patients presented with a strictly ipsilateral distribution of qT 1 increases in temporopolar, parahippocampal and orbitofrontal cortices. Supervised statistical learning applied to qT 1 maps could lateralize the seizure focus in 92% of patients. Intracortical profiling of qT 1 along streamlines perpendicular to the cortical mantle revealed marked effects in upper levels that tapered off at the white matter interface. Findings remained robust after correction for cortical thickness and interface blurring, suggesting independence from previously reported morphological anomalies in this disorder. Mapping of qT 1 along hippocampal subfield surfaces revealed marked increases in anterior portions of the ipsilateral CA1-3 and DG that were also robust against correction for atrophy. Notably, in operated patients, qualitative histopathological analysis of myelin stains in resected hippocampal specimens confirmed disrupted internal architecture and fiber organization. Both hippocampal and neocortical qT 1 anomalies were more severe in patients with early disease onset. Finally, analysis of resting-state connectivity from regions of qT 1 increases revealed altered intrinsic functional network embedding in patients, particularly to prefrontal networks. Analysis of qT 1 suggests a preferential susceptibility of ipsilateral limbic cortices to microstructural damage, possibly related to disrupted myeloarchitecture. These alterations may reflect atypical neurodevelopment and affect the integrity of fronto-limbic functional networks., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The hippocampus contributes to episodic, spatial and semantic aspects of memory, yet individual differences within and between these functions are not well-understood. In 136 healthy individuals, we investigated whether these differences reflect variation in the strength of connections between functionally-specialised segments of the hippocampus and diverse cortical regions that participate in different aspects of memory. Better topographical memory was associated with stronger connectivity between lingual gyrus and left anterior, rather than posterior, hippocampus. Better semantic memory was associated with increased connectivity between the intracalcarine/cuneus and left, rather than right, posterior hippocampus. Notably, we observed a double dissociation between semantic and topographical memory: better semantic memory was associated with stronger connectivity between left temporoparietal cortex and left anterior hippocampus, while better topographic memory was linked to stronger connectivity with right anterior hippocampus. Together these data support a division-of-labour account of hippocampal functioning: at the population level, differences in connectivity across the hippocampus reflect functional specialisation for different facets of memory, while variation in these connectivity patterns across individuals is associated with differences in the capacity to retrieve different types of information. In particular, within-hemisphere connectivity between hippocampus and left temporoparietal cortex supports conceptual processing at the expense of spatial ability., (Copyright © 2017. Published by Elsevier Inc.)

In drug-resistant temporal lobe epilepsy (TLE), detecting hippocampal atrophy on MRI is important as it allows defining the surgical target. The performance of automatic segmentation in TLE has so far been considered unsatisfactory. In addition to atrophy, about 40% of patients present with developmental abnormalities (referred to as malrotation) characterized by atypical morphologies of the hippocampus and collateral sulcus. Our purpose was to evaluate the impact of malrotation and atrophy on the performance of three state-of-the-art automated algorithms. We segmented the hippocampus in 66 patients and 35 sex- and age-matched healthy subjects using a region-growing algorithm constrained by anatomical priors (SACHA), a freely available atlas-based software (FreeSurfer) and a multi-atlas approach (ANIMAL-multi). To quantify malrotation, we generated 3D models from manual hippocampal labels and automatically extracted collateral sulci. The accuracy of automated techniques was evaluated relative to manual labeling using the Dice similarity index and surface-based shape mapping, for which we computed vertex-wise displacement vectors between automated and manual segmentations. We then correlated segmentation accuracy with malrotation features and atrophy. ANIMAL-multi demonstrated similar accuracy in patients and healthy controls (p > 0.1), whereas SACHA and FreeSurfer were less accurate in patients (p < 0.05). Surface-based analysis of contour accuracy revealed that SACHA over-estimated the lateral border of malrotated hippocampi (r = 0.61; p < 0.0001), but performed well in the presence of atrophy (|r |< 0.34; p > 0.2). Conversely, FreeSurfer and ANIMAL-multi were affected by both malrotation (FreeSurfer: r = 0.57; p = 0.02, ANIMAL-multi: r = 0.50; p = 0.05) and atrophy (FreeSurfer: r = 0.78, p < 0.0001, ANIMAL-multi: r = 0.61; p < 0.0001). Compared to manual volumetry, automated procedures underestimated the magnitude of atrophy (Cohen's d: manual: 1.68; ANIMAL-multi: 1.11; SACHA: 1.10; FreeSurfer: 0.90, p < 0.0001). In addition, they tended to lateralize the seizure focus less accurately in the presence of malrotation (manual: 64%; ANIMAL-multi: 55%, p = 0.4; SACHA: 50%, p = 0.1; FreeSurfer: 41%, p = 0.05). Hippocampal developmental anomalies and atrophy had a negative impact on the segmentation performance of three state-of-the-art automated methods. These shape variants should be taken into account when designing segmentation algorithms., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Epileptic activity underlying idiopathic generalized epilepsy (IGE) is related to abnormal thalamo-cortical interactions. Our purpose was to map in vivo the organization of the thalamo-cortical network in IGE. We measured cortical thickness and thalamic volumes on MRI in 23 IGE patients with generalized tonic-clonic seizures only and 46 healthy controls. Significant correlations between thalamic volumes and cortical thickness were interpreted as thalamo-cortical network connections. In controls, thickness of frontal, limbic, and occipital regions was positively correlated with the thalamic volumes, corresponding to known anatomical connections from sacrificial tracer studies in primates and human in vivo DTI data. In patients, thalamo-cortical network correlations increased in fronto-central and parietal regions, but decreased in limbic areas. Group analysis revealed that, compared to controls, IGE patients had bilateral thalamic atrophy and widespread cortical thinning that was most prominent in fronto-central areas, with a prevalence of up to 40%. Duration of epilepsy affected negatively thalamic volumes and thickness of fronto-central and limbic cortices. These effects were significantly different from aging in controls. Patients with poorly controlled seizures showed an even faster progression in these neocortical regions. Fronto-centro-parietal atrophy in IGE is likely the effect of generalized seizure activity inducing thalamo-cortical network remodeling. On the other hand, limbic abnormalities may take place secondary to thalamic disconnection.

Temporal lobe epilepsy (TLE) is considered primarily a limbic disorder. Our purpose was to map limbic network organization in TLE and to statistically relate it to neocortical atrophy. We performed MRI-based cortical thickness analysis in 110 TLE patients (including 68 patients with hippocampal atrophy and 42 patients with normal hippocampal volume) and 46 healthy controls. Limbic connectivity was statistically inferred by correlating mean thickness of the entorhinal cortex (EC) with thickness at each vertex across the entire neocortex. The EC was chosen as seed region since it is the link between the neocortex and the hippocampal formation. Patients showed cortical thinning mainly in temporal and fronto-central neocortices, with a prevalence of atrophy in up to 35%. In controls, EC networks corresponded closely to known anatomical connections. In TLE the pattern of correlations was similar to controls, suggesting that pathological processes in the EC affect the same networks that co-vary with the EC in the healthy brain. Nevertheless, we found decreases in correlations mainly in the temporal lobe and increases mainly in orbitofrontal cortices. Although our analysis indicated alterations in the temporo-limbic network in TLE, there was no association between mesiotemporal connectivity and atrophy across the entire cortical surface. This divergence underlines the complexity of the pathophysiological mechanisms leading to neocortical atrophy in TLE.

The objective of this study was to assess temporal lobe white matter (WM) quantitatively using T2 relaxometry in patients with pharmacologically intractable temporal lobe epilepsy (TLE). T2 relaxometry was performed using a dual-echo sequence with 23 contiguous oblique coronal slices in 56 consecutive TLE patients and in 30 healthy subjects. Averages of six slices were chosen to calculate T2 relaxation time in the temporal lobe WM (WM-T2) and the hippocampus (Hippo-T2). Twenty-seven patients had unilateral hippocampal atrophy (HA), and twenty-nine patients had normal hippocampal volumes (NV) on volumetric MRI. Mean WM-T2 was increased ipsilateral to the seizure focus in TLE patients with HA and those with NV (P < 0.001). Contralateral mean WM-T2 was increased in left and right TLE with HA (P < 0.001) and in right TLE with NV (P = 0.001). There was a positive correlation between WM-T2 and Hippo-T2. Individual analysis showed a prolongation of WM-T2 in about 70% of TLE patients with HA and NV. In half of the patients, WM-T2 increase was bilateral and symmetric. However, in 33% of patients with NV and bilateral symmetric increase in Hippo-T2, WM-T2 provided a correct lateralization of the seizure focus. Regardless of the pattern of T2 abnormalities, that is, bilateral symmetric or ipsilateral, the majority of patients with HA became seizure-free after surgery, while those with NV did not have a favorable outcome. In patients with NV, WM-T2 measurement may provide additional lateralizing information compared to Hippo-T2.

Focal cortical dysplasia (FCD), a malformation of cortical development, is a frequent cause of pharmacologically intractable epilepsy. FCD is characterized on Tl-weighted MRI by cortical thickening, blurring of the gray-matter/white-matter interface, and gray-level hyperintensity. We have previously used computational models of these characteristics to enhance visual lesion detection. In the present study we seek to improve our methods by combining these models with features derived from texture analysis of MRI, which allows measurement of image properties not readily accessible by visual analysis. These computational models and texture features were used to develop a two-stage Bayesian classifier to perform automated FCD lesion detection. Eighteen patients with histologically confirmed FCD and 14 normal controls were studied. On the MRI volumes of the 18 patients, 20 FCD lesions were manually labeled by an expert observer. Three-dimensional maps of the computational models and texture features were constructed for all subjects. A Bayesian classifier was trained on the computational models to classify voxels as cerebrospinal fluid, gray-matter, white-matter, transitional, or lesional. Voxels classified as lesional were subsequently reclassified based on the texture features. This process produced a 3D lesion map, which was compared to the manual lesion labels. The automated classifier identified 17/20 manually labeled lesions. No lesions were identified in controls. Thus, combining models of the T1-weighted MRI characteristics of FCD with texture analysis enabled successful construction of a classifier. This computer-based, automated method may be useful in the presurgical evaluation of patients with severe epilepsy related to FCD.

In many patients, focal cortical dysplasia (FCD) is characterized by minor structural changes that may go unrecognized by standard radiological analysis. We previously demonstrated that visual analysis of a composite map based on three simple models of MRI features of FCD increased the sensitivity of FCD lesion detection, compared to visual analysis of conventional MRI. Here we report on the use of improved methods for characterizing FCD which improve contrast in the composite maps: a Laplacian-based metric for measuring cortical thickness, a convolutional kernel to model blurring of the GM-WM interface, and an operator to measure hyperintense T1 signal. To validate these methods, we processed the MRIs of 14 FCD patients with our original set of image processing operators and an improved set of image processing operators. Comparison of the composite maps associated with the two sets of operators revealed that contrast between lesional tissue and nonlesional cortex was significantly increased in the composite maps associated with the set of improved operators. Increasing this contrast is an important step toward the goal of automated FCD lesion detection.

In unselected patients with intractable temporal lobe epilepsy (TLE), approximately 15% do not have detectable hippocampal atrophy on MRI. The purpose of this study was to evaluate whether T2 relaxometry can identify hippocampal pathology and lateralize the epileptic focus in patients with intractable TLE, who do not demonstrate hippocampal atrophy on volumetric MRI (MRIV). We selected 14 patients with unilateral TLE who had unilateral atrophy and 11 patients with unilateral TLE who had no evidence of atrophy on MRIV. Images were acquired on a 1.5 T MR scan using a dual echo sequence with 23 contiguous oblique coronal slices in all patients and in 14 healthy subjects. Fitting a single exponential decay equation to the imaging data generated T2 maps. Averages of six slices containing the head, body, and tail of the hippocampus were used to calculate hippocampal T2 relaxation times (HT2). The epileptic focus was defined by history, video-EEG, and surgical response. All TLE patients with hippocampal atrophy and 9/11 (82%) patients with normal MRI had abnormally high HT2 ipsilateral to the epileptic focus. Bilateral abnormal HT2 were found in 6/14 (43%) of patients with unilateral hippocampal atrophy and 2/11 (18%) of patients with normal MRI. However, this increase was always greater ipsilateral to the epileptic focus. Qualitative hippocampal pathology showed gliosis and neuronal loss in 10/14 operated patients with hippocampal atrophy on MRIV and in 5/7 operated patients with normal MRI. In conclusion, hippocampal T2 mapping provides evidence of hippocampal damage in the majority of patients with intractable TLE who have no evidence of atrophy on MRI and can correctly lateralize the epileptic focus in most patients., (Copyright 2000 Academic Press.)