Structural connectivity‐based topography of the human globus pallidus: Implications for therapeutic targeting in movement disorders

Abstract

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.

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

“…More recently, Cacciola et al (2017b) provided a quantitative connectomic analysis revealing that the pallidal network mainly involves the sensorimotor areas (i.e., precentral and postcentral gyri), the superior frontal and paracentral gyri, with less representative widespread connectivity patterns with other important cortical areas (Cacciola et al, 2017b). These findings have been further corroborated by other diffusion tractography studies (da Silva et al, 2017; Grewal et al, 2018; Middlebrooks et al, 2018; Cacciola et al, 2019).…”

“…Recently, Cacciola et al (2019) by using whole-brain tractography-based segmentation unveiled that the basal ganglia system is topographically organized in functionally segregated and integrated circuits within the GPi and GPe. In particular, the topographical organization of the cortico-pallidal pathway within the GP resulted in an antero-dorsal associative region and a posterior sensorimotor region, despite it was not possible to identify a well-defined limbic territory, thus suggesting that the cortico-pallidal fibers may provide only a relative contribution to the limbic territories in the GP.…”

Mapping the structural connectivity between the periaqueductal gray and the cerebellum in humans

“…On the other hand, diffusion-weighted imaging (DWI) and tractography represent powerful tools to trace structural connections non-invasively and in vivo (Cacciola et al 2016, 2017a, c, d, 2018, 2019; Milardi et al 2016a, b, 2017; Arrigo et al 2018; Calamuneri et al 2018), by estimating diffusion properties of magnetically labeled water molecules along myelinated axons (Basser et al 1994; Henderson 2012). Several tractography studies explored the structural connectivity of PAG in humans (Sillery et al 2005; Hadjipavlou et al 2006; Owen et al 2007, 2008; Ezra et al 2015), though only a few characterized either direct or indirect pathways between the PAG and cerebellum (Sillery et al 2005; Hadjipavlou et al 2006; Owen et al 2008).…”

Anatomical Characterization of the Human Structural Connectivity between the Pedunculopontine Nucleus and Globus Pallidus via Multi-Shell Multi-Tissue Tractography

“…Primates studies revealed that the main connectional systems of both pallidal segments are topographically organized, delineating limbic, associative and sensorimotor territories [ 3 , 4 , 5 ]. This peculiarity is shared across basal ganglia nuclei and it has been confirmed in human imaging studies carried out via diffusion magnetic resonance imaging (dMRI) and tractography-related techniques [ 6 , 7 , 8 , 9 ]. Such a topographical organization has gained increasing attention in behavioral neuroscience, as the tripartite organization matches existing evidence for motivational, cognitive and motor roles of the GP [ 10 ], as well as in functional neurosurgery for its therapeutic implications in movement disorders [ 11 , 12 , 13 ].…”