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.
Highlights
Schizophrenia (SZ) is a common, invalidating mental disease with a huge social and economical burden, with still unknown etiology and pathogenesis [1]
We show that a similar topographical organization is reflected in midbrain-striatal connectivity patterns, that show a medio-lateral topography with medial portions mostly connected to limbic striatum and lateral portions mostly connected to sensorimotor striatum, while associative striatum occupies an intermediate portion
We described a tripartite parcellation of dopaminergic midbrain regions according to their structural connectivity to striatal territories
Summary
Schizophrenia (SZ) is a common, invalidating mental disease with a huge social and economical burden, with still unknown etiology and pathogenesis [1]. Substantia nigra pars compacta (SNc) and the nearby adjacent ventral tegmental area (VTA) are the most important dopaminergic brain regions implied in schizophrenia [7,8,9,10] While traditionally these regions are often regarded as clearly distinct in functional terms, being SNc mostly implied in motor control [11,12] and VTA in salience and reward processing [13,14], a growing line of research suggests that these regions can be considered as being part of a unified “midbrain dopaminergic complex” [15,16,17] with topographically organized, cytoarchitectonically distinct functional territories. Conclusions: The parcellation scheme proposed may help to achieve detailed characterization of structural and functional anomalies of the dopaminergic midbrain in schizophrenic patients
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