The Cortico-Basal Ganglia-Cerebellar Network: Past, Present and Future Perspectives

Abstract

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.

Red nucleus structure and function: from anatomy to clinical neurosciences

“…Taken together, functional neuroimaging studies are in line with animal literature, by suggesting that human RN could be involved in grasping, motor control, somatic tactile and pain perception; however, some works further extend the role of RN in cortico-cerebellar circuitry, suggesting its involvement in higher order functions ranging from sensory discrimination to salience detection, or executive functions. Noteworthy, resting state and task related fMRI studies reporting functional connectivity between RN, cerebellum and basal ganglia structures are in keeping with a growing line of research suggesting a strong interplay between these systems in the human brain (Cacciola et al 2017c ; Caligiore et al 2017 ; Milardi et al 2019 ; Quartarone et al 2020 ). The results of RN neuroimaging research in the last 20 years are summarized in Table 1 .…”

Opportunities of connectomic neuromodulation

“…On average every valid connection present in a typical single-subject diffusion MRI based tractogram is matched by four invalid (false positive) connections ( Maier-Hein et al, 2017 ). Thus, when using tractography to identify “novel” connections ( Hosp et al, 2019 ; Milardi et al, 2019 ; Quartarone et al, 2019 ), the chance of getting wrong answers is higher than of getting true answers ( Maier-Hein et al, 2017 ; Petersen et al, 2019 ). Moreover, myelinated long tracts are overrepresented and very short and thin bundles can be hardly reconstructed, if at all ( Edlow et al, 2019 ; Horn et al, 2019a ; Petersen et al, 2019 ).…”

How do adenosine A2A receptors regulate motor function?

“…Ultimately, GABAergic basal ganglia output activity depends on the balance between these GABAergic and glutamatergic input activities, and in turn regulates the inhibitory control of thalamocortical and brainstem motor systems. While the massive interconnectivity of the basal ganglia nuclei adds complexity to how we understand basal ganglia function [29][30][31], the direct pathway is still considered to provide motor facilitation, while the indirect pathway suppresses inappropriate/unwanted movements. This opposing and bidirectional distribution in function between the direct and the indirect pathway is called the basal ganglia Go/NoGo model with the direct 'Go' and the indirect 'NoGo' pathways controlling movement ( Fig.…”