Much of our present understanding of the function and operation of the basal ganglia rests on models of anatomical connectivity derived from tract-tracing approaches in rodents and primates. However, the last years have been characterized by promising step forwards in the in vivo investigation and comprehension of brain connectivity in humans. The aim of this review is to revise the current knowledge on basal ganglia circuits, highlighting similarities and differences across species, in order to widen the current perspective on the intricate model of the basal ganglia system. This will allow us to explore the implications of additional direct pathways running from cortex to basal ganglia and between basal ganglia and cerebellum recently described in animals and humans.

The red nucleus (RN) is a large subcortical structure located in the ventral midbrain. Although it originated as a primitive relay between the cerebellum and the spinal cord, during its phylogenesis the RN shows a progressive segregation between a magnocellular part, involved in the rubrospinal system, and a parvocellular part, involved in the olivocerebellar system. Despite exhibiting distinct evolutionary trajectories, these two regions are strictly tied together and play a prominent role in motor and non-motor behavior in different animal species. However, little is known about their function in the human brain. This lack of knowledge may have been conditioned both by the notable differences between human and non-human RN and by inherent difficulties in studying this structure directly in the human brain, leading to a general decrease of interest in the last decades. In the present review, we identify the crucial issues in the current knowledge and summarize the results of several decades of research about the RN, ranging from animal models to human diseases. Connecting the dots between morphology, experimental physiology and neuroimaging, we try to draw a comprehensive overview on RN functional anatomy and bridge the gap between basic and translational research.

Background Understanding the topographical organization of the cortico‐basal ganglia circuitry is of pivotal importance because of the spreading of techniques such as DBS and, more recently, MR‐guided focused ultrasound for the treatment of movement disorders. A growing body of evidence has described both direct cortico‐ and dento‐pallidal connections, although the topographical organization in vivo of these pathways in the human brain has never been reported. Objective To investigate the topographical organization of cortico‐ and dento‐pallidal pathways by means of diffusion MRI tractography and connectivity based parcellation. Methods High‐quality data from 100 healthy subjects from the Human Connectome Project repository were utilized. Constrained spherical deconvolution–based tractography was used to reconstruct structural cortico‐ and dento‐pallidal connectivity. Connectivity‐based parcellation was performed with a hypothesis‐driven approach at three different levels: functional regions (limbic, associative, sensorimotor, and other), lobes, and gyral subareas. Results External globus pallidus segregated into a ventral associative cluster, a dorsal sensorimotor cluster, and a caudal “other” cluster on the base of its cortical connectivity. Dento‐pallidal connections clustered only in the internal globus pallidus, where also associative and sensorimotor clusters were identified. Lobar parcellation revealed the presence in the external globus pallidus of dissociable clusters for each cortical lobe (frontal, parietal, temporal, and occipital), whereas in internal globus pallidus only frontal and parietal clusters were found out. Conclusion We mapped the topographical organization of both internal and external globus pallidus according to cortical and cerebellar connections. These anatomical data could be useful in DBS, radiosurgery and MR‐guided focused ultrasound targeting for treating motor and nonmotor symptoms in movement disorders. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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Internal and external segments of globus pallidus (GP) exert different functions in basal ganglia circuitry, despite their main connectional systems share the same topographical organization, delineating limbic, associative, and sensorimotor territories. The identification of internal GP sensorimotor territory has therapeutic implications in functional neurosurgery settings. This study is aimed at assessing the spatial coherence of striatopallidal, subthalamopallidal, and pallidothalamic pathways by using tractography-derived connectivity-based parcellation (CBP) on high quality diffusion MRI data of 100 unrelated healthy subjects from the Human Connectome Project. A two-stage hypothesis-driven CBP approach has been carried out on the internal and external GP. Dice coefficient between functionally homologous pairs of pallidal maps has been computed. In addition, reproducibility of parcellation according to different pathways of interest has been investigated, as well as spatial relations between connectivity maps and existing optimal stimulation points for dystonic patients. The spatial organization of connectivity clusters revealed anterior limbic, intermediate associative and posterior sensorimotor maps within both internal and external GP. Dice coefficients showed high degree of coherence between functionally similar maps derived from the different bundles of interest. Sensorimotor maps derived from the subthalamopallidal pathway resulted to be the nearest to known optimal pallidal stimulation sites for dystonic patients. Our findings suggest that functionally homologous afferent and efferent connections may share similar spatial territory within the GP and that subcortical pallidal connectional systems may have distinct implications in the treatment of movement disorders.