The Amsterdam Ultra-high field adult lifespan database (AHEAD): A freely available multimodal 7 Tesla submillimeter magnetic resonance imaging database.

Normative databases allow testing of novel hypotheses without the costly collection of magnetic resonance imaging (MRI) data. Here we present the Amsterdam Ultra-high field adult lifespan database (AHEAD). The AHEAD consists of 105 7 Tesla (T) whole-brain structural MRI scans tailored specifically to imaging of the human subcortex, including both male and female participants and covering the entire adult life span (18-80 yrs). We used these data to create probability maps for the subthalamic nucleus, substantia nigra, internal and external segment of the globus pallidus, and the red nucleus. Data was acquired at a submillimeter resolution using a multi-echo (ME) extension of the second gradient-echo image of the MP2RAGE sequence (MP2RAGEME) sequence, resulting in complete anatomical alignment of quantitative, R1-maps, R2*-maps, T1-maps, T1-weighted images, T2*-maps, and quantitative susceptibility mapping (QSM). Quantitative MRI maps, and derived probability maps of basal ganglia structures are freely available for further analyses.

Mapping Cytoarchitectonics and Receptor Architectonics to Understand Brain Function and Connectivity.

This review focuses on cytoarchitectonics and receptor architectonics as biological correlates of function and connectivity. It introduces the 3-dimensional cytoarchitectonic probabilistic maps of cortical areas and nuclei of the Julich-Brain Atlas, available at EBRAINS, to study structure-function relationships. The maps are linked to the BigBrain as microanatomical reference model and template space. The siibra software tool suite enables programmatic access to the maps and to receptor architectonic data that are anchored to brain areas. Such cellular and molecular data are tools for studying magnetic resonance connectivity including modeling and simulation. At the end, we highlight perspectives of the Julich-Brain as well as methodological considerations. Thus, microstructural maps as part of a multimodal atlas help elucidate the biological correlates of large-scale networks and brain function with a high level of anatomical detail, which provides a basis to study brains of patients with psychiatric disorders.

Manual delineation approaches for direct imaging of the subcortex.

The growing interest in the human subcortex is accompanied by an increasing number of parcellation procedures to identify deep brain structures in magnetic resonance imaging (MRI) contrasts. Manual procedures continue to form the gold standard for parcellating brain structures and is used for the validation of automated approaches. Performing manual parcellations is a tedious process which requires a systematic and reproducible approach. For this purpose, we created a series of protocols for the anatomical delineation of 21 individual subcortical structures. The intelligibility of the protocols was assessed by calculating Dice similarity coefficients for ten healthy volunteers. In addition, dilated Dice coefficients showed that manual parcellations created using these protocols can provide high-quality training data for automated algorithms. Here, we share the protocols, together with three example MRI datasets and the created manual delineations. The protocols can be applied to create high-quality training data for automated parcellation procedures, as well as for further validation of existing procedures and are shared without restrictions with the research community.

Multimodal mapping and analysis of the cyto- and receptorarchitecture of the human hippocampus.

The human hippocampal formation is relevant for various aspects of memory and learning, and the different hippocampal regions are differentially affected by neuropsychiatric disorders. Therefore, the hippocampal formation has been subject of numerous cytoarchitectonic and other mapping studies, which resulted in divergent parcellation schemes. To understand the principles of hippocampal architecture, it is necessary to integrate different levels of hippocampal organisation, going beyond one modality. We here applied a multimodal mapping approach combining cyto- and multi-receptorarchitectonic analyses, and generated probabilistic maps in stereotaxic space of the identified regions. Cytoarchitecture in combination with the regional and laminar distribution of 15 neurotransmitter receptors visualized by in vitro receptor autoradiography were analysed in seven hemispheres from 6 unfixed shock frozen and serially sectioned brains. Cytoarchitectonic delineations for generation of probabilistic maps were carried out on histological sections from ten fixed, paraffin embedded and serially sectioned brains. Nine cyto- and receptorarchitectonically distinct regions were identified within the hippocampal formation (i.e., fascia dentata, cornu Ammonis (CA) regions 1-4, prosubiculum, subiculum proper, presubiculum and parasubiculum), as well as the hippocampal-amygdaloid transition area and the periallocortical transsubiculum. Subsequently generated probabilistic maps quantify intersubject variability in the size and extent of these cyto- and receptorarchitectonically distinct regions. The regions did not differ in their volume between the hemispheres and gender. Receptor mapping revealed additional subdivisions which could not be detected by cytoarchitectonic analysis alone. They correspond to parcellations previously found in immunohistochemical and connectivity studies. The multimodal approach enabled the definition of regions not consistently reported, e.g., CA4 region or prosubiculum. The ensuing detailed probabilistic maps of the hippocampal formation constitute the basis for future architectonically informed analyses of in vivo neuroimaging studies.

Three-Dimensional Probabilistic Maps of Mesial Temporal Lobe Structures in Children and Adolescents' Brains.

The hippocampus and the adjacent perirhinal, entorhinal, temporopolar, and parahippocampal cortices are interconnected in a hierarchical MTL system crucial for memory processes. A probabilistic description of the anatomical location and spatial variability of MTL cortices in the child and adolescent brain would help to assess structure-function relationships. The rhinal sulcus (RS) and the collateral sulcus (CS) that border MTL cortices and influence their morphology have never been described in these populations. In this study, we identified the aforementioned structures on magnetic resonance images of 38 healthy subjects aged 7-17 years old. Relative to sulcal morphometry in the MTL, we showed RS-CS conformation is an additional factor of variability in the MTL that is not explained by other variables such as age, sex and brain volume; with an innovative method using permutation testing of the extrema of structures of interest, we showed that RS-SC conformation was not associated with differences of location of MTL sulci. Relative to probabilistic maps, we offered for the first time a systematic mapping of MTL structures in children and adolescent, mapping all the structures of the MTL system while taking sulcal morphology into account. Our results, with the probabilistic maps described here being freely available for download, will help to understand the anatomy of this region and help functional and clinical studies to accurately test structure-function hypotheses in the MTL during development. Free access to MTL pediatric atlas: http://neurovault.org/collections/2381/.

Amygdala-based intrinsic functional connectivity and anxiety disorders in adolescents and young adults.

Anxiety disorders (AD) are the most prevalent group of psychiatric disorders in adolescents and young adults. Nevertheless, the pathophysiology of anxiety disorders is still poorly understood. This study investigated differences in the functional connectivity of intrinsic amygdala-based networks of participants with and without AD. Resting state fMRI data were obtained from 18 participants with an AD and 19 healthy comparison individuals. Psychiatric diagnosis was assessed using standardized structured interviews. The comparison between groups was carried out using functional connectivity maps from six seed regions defined using probabilistic maps bilaterally within the amygdala (basolateral, superficial and centromedial amygdala). We found significant between-group differences in five clusters, which showed aberrant functional connectivity with the left basolateral amygdala: right precentral gyrus, right cingulate gyrus, bilateral precuneus, and right superior frontal gyrus in subjects with AD as compared with the comparison subjects. For the comparison subjects, the correlations between the amygdala and the five clusters were either non-significant, or negative. The present study suggests there is an intrinsic disruption in the communication between left basolateral amygdala and a network of brain regions involved with emotion regulation, and with the default mode network in adolescents and young adults with anxiety disorders.

Cytoarchitecture and probability maps of the human medial orbitofrontal cortex.

Previous architectonical studies of human orbitofrontal cortex (OFC) provided divergent maps regarding number, location, and extent of areas. To solve this controversy, an observer-independent cytoarchitectonical mapping of medial OFC (mOFC) was performed. Borders of cortical areas were detected in histological sections of ten human post-mortem brains using a quantitative, statistically testable method, and their stereotaxic localization and intersubject variability were determined. Three areas were identified: granular Fo1 mainly on the rostral Gyrus rectus and medial of the olfactory sulcus; granular to dysgranular Fo2, mainly on the posterior part of the ventromedial Gyrus rectus and the medial and lateral banks of the olfactory sulcus; granular Fo3 between the olfactory and medial or intermediate orbital sulci. Fo3 was bordered medially by Fo1 and Fo2 and laterally by the lateral OFC (lOFC). A cluster analysis of the cytoarchitectonical features of Fo1-Fo3, subgenual cingulate areas, BA12, lateral and medial areas of the frontopolar cortex, lOFC and areas of Broca's region demonstrated the cytoarchitectonical similarity between the mOFC areas in contrast to all other frontal areas. Probabilistic maps of mOFC areas show a considerable intersubject variability in extent and position in stereotaxic space, and provide spatial templates for anatomical localization of in vivo neuroimaging data via the JuBrain atlas and the Anatomy Toolbox.

Cytoarchitecture of the human lateral occipital cortex: mapping of two extrastriate areas hOc4la and hOc4lp.

The microstructural correlates of the functional segregation of the human lateral occipital cortex are largely unknown. Therefore, we analyzed the cytoarchitecture of this region in ten human post-mortem brains using an observer-independent and statistically testable parcellation method to define the position and extent of areas in the lateral occipital cortex. Two new cytoarchitectonic areas were found: an anterior area hOc4la and a posterior area hOc4lp. hOc4la was located behind the anterior occipital sulcus in rostral and ventral portions of this region where it occupies the anterior third of the middle and inferior lateral occipital gyri. hOc4lp was found in caudal and dorsal portions of this region where it extends along the superior and middle lateral occipital gyri. The cytoarchitectonic areas were registered to 3D reconstructions of the corresponding brains, which were subsequently spatially normalized to the Montreal Neurological Institute reference space. Continuous probabilistic maps of both areas based on the analysis of ten brains were generated to characterize their inter-subject variability in location and size. The maps of hOc4la and hOc4lp were then used as seeds for meta-analytic connectivity modeling and quantitative functional decoding to identify their co-activation patterns and assignment to functional domains. Convergent evidence from their location, topography, size, functional domains and connectivity indicates that hOc4la and hOc4lp are the potential anatomical correlates of the functionally defined lateral occipital areas LO-1 and LO-2.

A probabilistic map of the human ventral sensorimotor cortex using electrical stimulation.

OBJECT: The human ventral sensorimotor cortex (vSMC) is involved in facial expression, mastication, and swallowing, as well as the dynamic and highly coordinated movements of human speech production. However, vSMC organization remains poorly understood, and previously published population-driven maps of its somatotopy do not accurately reflect the variability across individuals in a quantitative, probabilistic fashion. The goal of this study was to describe the responses to electrical stimulation of the vSMC, generate probabilistic maps of function in the vSMC, and quantify the variability across individuals. METHODS: Photographic, video, and stereotactic MRI data of intraoperative electrical stimulation of the vSMC were collected for 33 patients undergoing awake craniotomy. Stimulation sites were converted to a 2D coordinate system based on anatomical landmarks. Motor, sensory, and speech stimulation responses were reviewed and classified. Probabilistic maps of stimulation responses were generated, and spatial variance was quantified. RESULTS: In 33 patients, the authors identified 194 motor, 212 sensory, 61 speech-arrest, and 27 mixed responses. Responses were complex, stereotyped, and mostly nonphysiological movements, involving hand, orofacial, and laryngeal musculature. Within individuals, the presence of oral movement representations varied; however, the dorsal-ventral order was always preserved. The most robust motor responses were jaw (probability 0.85), tongue (0.64), lips (0.58), and throat (0.52). Vocalizations were seen in 6 patients (0.18), more dorsally near lip and dorsal throat areas. Sensory responses were spatially dispersed; however, patients' subjective reports were highly precise in localization within the mouth. The most robust responses included tongue (0.82) and lips (0.42). The probability of speech arrest was 0.85, highest 15-20 mm anterior to the central sulcus and just dorsal to the sylvian fissure, in the anterior precentral gyrus or pars opercularis. CONCLUSIONS: The authors report probabilistic maps of function in the human vSMC based on intraoperative cortical electrical stimulation. These results define the expected range of mapping outcomes in the vSMC of a single individual and shed light on the functional organization of the vSMC supporting speech motor control and nonspeech functions.