Structural Connectivity-Based Parcellation of the Dopaminergic Midbrain in Healthy Subjects and Schizophrenic Patients

Abstract

Background and objectives: Functional deregulation of dopaminergic midbrain regions is a core feature of schizophrenia pathophysiology. Anatomical research on primates suggests that these regions may be subdivided into distinct, topographically organized functional territories according to their connectivity to the striatum. The aim of the present work was the reconstruction of dopaminergic midbrain subregions in healthy subjects and schizophrenic patients and the evaluation of their structural connectivity profiles. Materials and Methods: A hypothesis-driven connectivity-based parcellation derived from diffusion tractography was applied on 24 healthy subjects and 30 schizophrenic patients to identify distinct territories within the human dopaminergic midbrain in vivo and non-invasively. Results: We identified a tripartite subdivision of dopaminergic midbrain, including limbic, prefrontal and sensorimotor territories. No significant differences in structural features or connectivity were found between subjects and patients. Conclusions: The parcellation scheme proposed herein may help to achieve detailed characterization of structural and functional anomalies of the dopaminergic midbrain in schizophrenic patients.

Magnetic resonance imaging of the dopamine system in schizophrenia – A scoping review

“…First, DWI is typically of low spatial resolution (i.e., about 2 × 2 × 2 mm), which makes tractography of small regions such as VTA difficult. Therefore, some studies have opted for manually delineating these structures ( 92 ) or drawing small spheres around brain coordinates of VTA/substantia nigra with subsequent tractography from there ( 93 , 94 ). Second, tractography is unspecific to the type of neuronal projections, i.e., one cannot differentiate, for example, between dopaminergic and glutamatergic connections from VTA.…”

“…Finally, there is a wide range of distinct measures obtained from both DWI and DTI-based tractography, which are – confusingly – “lumped together” under the label “structural connectivity,” making comparisons across studies challenging. Examples of outcome measures comprise the number of streamlines per voxel; the percentage of streamlines starting from the seed region (for example VTA) that reach the target region (for example orbitofrontal cortex), also referred to as connectivity index; the volume of streamlines in the seed region divided by the total volume of the seed region [also called the streamline density index ( 92 )]; or the probability for a given voxel to be part of an a priori defined tract connecting two regions ( 93 ). Changes in any of these measures for the pathway connecting VTA and orbitofrontal cortex, for example, would indicate alterations in this pathway; however, the exact underlying biological process (number of axons, degree of compaction of axons, etc.)…”

Striatal topographical organization: Bridging the gap between molecules, connectivity and behavior

“…In summary, the currently expanding fields of studies bringing together human neuroimaging to transcriptomics may add novel insight on striatal functional organization and may guide towards a better comprehension of molecular mechanisms underlying complex behavior. Understanding the molecular correlates of corticostriatal circuitry is of uttermost importance as striatal subregions may be differentially affected in neurodevelopmental, psychiatric and movement disorders including autism spectrum disorders, 157 addiction, 158 schizophrenia, 159 , 160 obsessive-compulsive disorder (OCD), 161 Parkinson’s disease (PD) and Huntington’s disease. 162 In line with this perspective, it is not surprising that some of the genes which expression was related to different structural or functional territories of striatum were found to be associated with high risk of autism, neurodevelopmental syndromes, PD and schizophrenia.…”

Unsupervised clustering of track-weighted dynamic functional connectivity reveals white matter substrates of functional connectivity dynamics

“…At the most detailed dimensionality scale (ICA100), ICA decomposition of tw-dFC data reveals a fine-grained, anatomically meaningful functional parcellation of the white matter into long-or short-range connectivity patterns, adding further insights on the functional organization of white matter circuits at the macroscale. As an example, fine-grained ICA was able to reveal subtle anatomical details of white matter connectivity such as the dense, tightly-organized U-fibers system connecting somatotopically analogous regions of precentral and postcentral gyri, the contribution of the cerebellar white matter to intrinsic lobule-specific cerebellar circuitry 34,35 , or again, parallel white matter components corresponding to topographically organized cortico-basal ganglia-thalamic circuitry [36][37][38][39] (Figure 3).…”

“…Percentage overlap between white matter parcellations derived from the ICA10, ICA20 and ICA100 and known white and gray matter components is reported in Supplementary File 2. right anterior; IC18; posterior, IC20, n=20) and increasingly detailed white matter sub-units ( ICs 12,30,49,50,56,68,81,n=100). B) Cortico-basal ganglia-thalamocortical loops as revealed by ICA100 ( ICs 72,84,38,42,87). Fine-grained ICA unsupervised decomposition identifies a ventromedialorbitofrontal component (red) which extends to the basal forebrain, a ventrolateral component (orange) and dorsolateral (yellow) component involving prefrontal white matter, and two lateralized sensorimotor components (light blue) which also include part of the pyramidal tract.…”