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The brainstem is one of the most densely packed areas of the central nervous system in terms of gray, but also white, matter structures and, therefore, is a highly functional hub. It has mainly been studied by the means of histological techniques, which requires several hundreds of slices with a loss of the 3D coherence of the whole specimen. Access to the inner structure of the brainstem is possible using Magnetic Resonance Imaging (MRI), but this method has a limited spatial resolution and contrast in vivo. Here, we scanned an ex vivo specimen using an ultra-high field (11.7T) preclinical MRI scanner providing data at a mesoscopic scale for anatomical T2-weighted (100 µm and 185 µm isotropic) and diffusion-weighted imaging (300 µm isotropic). We then proposed a hierarchical segmentation of the inner gray matter of the brainstem and defined a set of rules for each segmented anatomical class. These rules were gathered in a freely accessible web-based application, WIKIBrainStem (https://fibratlas.univ-tours.fr/brainstems/index.html), for 99 structures, from which 13 were subdivided into 29 substructures.This segmentation is, to date, the most detailed one developed from ex vivo MRI of the brainstem. This should be regarded as a tool that will be complemented by future results of alternative methods, such as Optical Coherence Tomography, Polarized Light Imaging or histology… This is a mandatory step prior to segmenting multiple specimens, which will be used to create a probabilistic automated segmentation method of ex vivo, but also in vivo, brainstem and may be used for targeting anatomical structures of interest in managing some degenerative or psychiatric disorders.

In humans and non-humans primates, extensive evidence supports the existence of subcortico-cortical circuits for cognition and behavior. Lesions studies are critical to understand the clinical significance of these functionally segregated circuits. Mapping these circuits from lesion studies is difficult given the heterogeneous etiology of the lesions, the lack of long-term and systematic testing of cognitive and behavioral disturbances, as well as the scarcity of neuroimaging data for identifying the precise location and extent of subcortical lesions. Here, we report the long-term follow-up study of a patient who developed a loss of psychic self-activation associated to a dysexecutive syndrome following resuscitation from cardiac arrest. Neuroimaging revealed extensive bilateral lesions in the putamen, with a relative spare of the caudate, and exhibiting a dorsoventral gradient that was predominantly rostrally to the anterior commissure and spared most of the ventral striatum. In comprehensive neuropsychological and neuropsychiatric assessments, we observed dissociation between the improvement of the self-activation deficits and the stability of the dysexecutive syndrome. The pattern of recovery after this lesion lends support to current models proposing the existence of two main subcortico-cortical circuits: a dorsal circuit, mostly mediating cognitive processes, and a ventral circuit, implicated in motivation.

White matter is composed of irregularly packed axons leading to a structural disorder in the extra-axonal space. Diffusion MRI experiments using oscillating gradient spin echo sequences have shown that the diffusivity transverse to axons in this extra-axonal space is dependent on the frequency of the employed sequence. In this study, we observe the same frequency-dependence using 3D simulations of the diffusion process in disordered media. We design a novel white matter numerical phantom generation algorithm which constructs biomimicking geometric configurations with few design parameters, and enables to control the level of disorder of the generated phantoms. The influence of various geometrical parameters present in white matter, such as global angular dispersion, tortuosity, presence of Ranvier nodes, beading, on the extra-cellular perpendicular diffusivity frequency dependence was investigated by simulating the diffusion process in numerical phantoms of increasing complexity and fitting the resulting simulated diffusion MR signal attenuation with an adequate analytical model designed for trapezoidal OGSE sequences.This work suggests that angular dispersion and especially beading have non-negligible effects on this extracellular diffusion metrics that may be measured using standard OGSE DW-MRI clinical protocols.

Huntington disease (HD) is associated with early and severe damage to the basal ganglia and particularly the striatum. We investigated cortico-striatal connectivity modifications occurring in HD patients using a novel approach which focuses on the projection of the connectivity profile of the basal ganglia onto the cortex. This approach consists in computing, for each subcortical structure, surface connectivity measures representing its strength of connections to the cortex and comparing these measures across groups. In this study, we focused on Huntington disease as an application of this new approach. First, surface cortico-striatal connectivity measures of a group of healthy subjects were averaged in order to infer the "normal" connectivity profile of the striatum to the cortex. Second, a statistical analysis was performed from the surface connectivity measures of healthy subjects and HD patients in order to detect the cortical gyri presenting altered cortico-striatal connectivity in HD. Lastly, percentage differences of connectivity between healthy subjects and patients were inferred, for each nucleus of the striatum, from the connectivity measures of the cortical gyri presenting a significant connectivity difference between the two groups. These percentage differences characterize the axonal disruptions between the striatum and the cortex occurring in HD. We found selective region-specific degeneration of cortical connections predominating for associative and primary sensorimotor connections and with relative preservation of limbic connections. Our method can be used to infer novel connectivity-based markers of HD pathological process.