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Post mortem magnetic resonance imaging (MRI) studies on the human brain are of great interest for the validation of in vivo MRI. It facilitates a link between functional and anatomical information available from MRI in vivo and neuroanatomical knowledge available from histology/immunocytochemistry. However, linking in vivo and post mortem MRI to microscopy techniques poses substantial challenges. Fixation artifacts and tissue deformation of extracted brains, as well as co registration of 2D histology to 3D MRI volumes complicate direct comparison between modalities. Moreover, post mortem brain tissue does not have the same physical properties as in vivo tissue, and therefore MRI approaches need to be adjusted accordingly. Here, we present a pipeline in which whole-brain human post mortem in situ MRI is combined with subsequent tissue processing of the whole human brain, providing a 3-dimensional reconstruction via blockface imaging. To this end, we adapted tissue processing procedures to allow both post mortem MRI and subsequent histological and immunocytochemical processing. For MRI, tissue was packed in a susceptibility matched solution, tailored to fit the dimensions of the MRI coil. Additionally, MRI sequence parameters were adjusted to accommodate T1 and T2 ∗ shortening, and scan time was extended, thereby benefiting the signal-to-noise-ratio that can be achieved using extensive averaging without motion artifacts. After MRI, the brain was extracted from the skull and subsequently cut while performing optimized blockface imaging, thereby allowing three-dimensional reconstructions. Tissues were processed for Nissl and silver staining, and co-registered with the blockface images. The combination of these techniques allows direct comparisons across modalities., (Copyright © 2020 Alkemade, Pine, Kirilina, Keuken, Mulder, Balesar, Groot, Bleys, Trampel, Weiskopf, Herrler, Möller, Bazin and Forstmann.)

Within the cortico basal ganglia (BG)-thalamic network, the direct and indirect pathways comprise of projections from the cortex to the striatum (STR), whereas the hyperdirect pathway(s) consist of cortical projections toward the subthalamic nucleus (STN). Each pathway possesses a functionally distinct role for action selection. The current study quantified and compared the structural connectivity between 17 distinct cortical areas with the STN and STR using 7 Tesla diffusion weighted magnetic resonance imaging (dMRI) and resting-state functional MRI (rs-fMRI) in healthy young subjects. The selection of these cortical areas was based on a literature search focusing on animal tracer studies. The results indicate that, relative to other cortical areas, both the STN and STR showed markedly weaker structural connections to areas assumed to be essential for action inhibition such as the inferior frontal cortex pars opercularis. Additionally, the cortical connectivity fingerprint of the STN and STR indicated relatively strong connections to areas related to voluntary motor initiation such as the cingulate motor area and supplementary motor area. Overall the results indicated that the cortical-STN connections were sparser compared to the STR. There were two notable exceptions, namely for the orbitofrontal cortex and ventral medial prefrontal cortex, where a higher tract strength was found for the STN. These two areas are thought to be involved in reward processing and action bias.

In the recent perceptual decision-making literature, a fronto-parietal network is typically reported to primarily represent the neural substrate of human perceptual decision-making. However, the view that only cortical areas are involved in perceptual decision-making has been challenged by several neurocomputational models which all argue that the basal ganglia play an essential role in perceptual decisions. To consolidate these different views, we conducted an Activation Likelihood Estimation (ALE) meta-analysis on the existing neuroimaging literature. The results argue in favor of the involvement of a frontal-parietal network in general perceptual decision-making that is possibly complemented by the basal ganglia, and modulated in substantial parts by task difficulty. In contrast, expectation of reward, an important aspect of many decision-making processes, shows almost no overlap with the general perceptual decision-making network.

Recent exciting advancements in the field of in vivo neuroimaging allow for visualization of the living human brain with unprecedented anatomical detail. Large consortium studies will provide us with novel insights in the function and connectivity of the human brain. However, it is unlikely that the spatial resolution obtained using in vivo imaging will, in the near future, approximate the level of detail obtained in post-mortem anatomical studies. Initiatives such as the recently published Big Brain project (Amunts et al., 2013) herald a novel approach in post-mortem brain research. We feel that linking data from histological observations with in vivo imaging studies will greatly advance our understanding of the functional neuroanatomy of the human brain.

The prevailing academic opinion holds that the subthalamic nucleus (STN) consists of three parts, each anatomically distinct and selectively associated with cognitive, emotional, or motor functioning. We independently tested this assumption by summarizing the results from 33 studies on STN subdivisions in human and nonhuman primates. The studies were conducted from 1925 to 2010 and feature three different techniques: electrical lesions, anterograde and retrograde tracers, and classical cytoarchitectonics. Our results reveal scant evidence in support of a tripartite STN. Instead, our results show that the variability across studies is surprisingly large, both in the number of subdivisions and in their anatomical localization. We conclude that the number of subdivisions in the STN remains uncertain, and that academic consensus in support of a tripartite STN is presently unwarranted.