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- Title
Aberrant striatal dopamine links topographically with cortico-thalamic dysconnectivity in schizophrenia.
- Authors
Avram, Mihai; Brandl, Felix; Knolle, Franziska; Cabello, Jorge; Leucht, Claudia; Scherr, Martin; Mustafa, Mona; Koutsouleris, Nikolaos; Leucht, Stefan; Ziegler, Sibylle; Sorg, Christian
- Abstract
Aberrant dopamine function in the dorsal striatum and aberrant intrinsic functional connectivity (iFC) between distinct cortical networks and thalamic nuclei are among the most consistent large-scale brain imaging findings in schizophrenia. A pathophysiological link between these two alterations is suggested by theoretical models based on striatal dopamine's topographic modulation of cortico-thalamic connectivity within cortico-basal-ganglia-thalamic circuits. We hypothesized that aberrant striatal dopamine links topographically with aberrant cortico-thalamic iFC, i.e. aberrant associative striatum dopamine is associated with aberrant iFC between the salience network and thalamus, and aberrant sensorimotor striatum dopamine with aberrant iFC between the auditory-sensorimotor network and thalamus. Nineteen patients with schizophrenia during remission of psychotic symptoms and 19 age- and sex-comparable control subjects underwent simultaneous fluorodihydroxyphenyl-l-alanine PET (18F-DOPA-PET) and resting state functional MRI (rs-fMRI). The influx constant kicer based on 18F-DOPA-PET was used to measure striatal dopamine synthesis capacity; correlation coefficients between rs-fMRI time series of cortical networks and thalamic regions of interest were used to measure iFC. In the salience network-centred system, patients had reduced associative striatum dopamine synthesis capacity, which correlated positively with decreased salience network-mediodorsal-thalamus iFC. This correlation was present in both patients and healthy controls. In the auditory-sensorimotor network-centred system, patients had reduced sensorimotor striatum dopamine synthesis capacity, which correlated positively with increased auditory-sensorimotor network-ventrolateral-thalamus iFC. This correlation was present in patients only. Results demonstrate that reduced striatal dopamine synthesis capacity links topographically with cortico-thalamic intrinsic dysconnectivity in schizophrenia. Data suggest that aberrant striatal dopamine and cortico-thalamic dysconnectivity are pathophysiologically related within dopamine-modulated cortico-basal ganglia-thalamic circuits in schizophrenia.
- Subjects
DOPAMINE; THALAMIC nuclei; FUNCTIONAL connectivity; FUNCTIONAL magnetic resonance imaging; BASAL ganglia; RESEARCH; NEURAL pathways; SCHIZOPHRENIA; RESEARCH methodology; MAGNETIC resonance imaging; DOPA; MEDICAL cooperation; EVALUATION research; THALAMUS; COMPARATIVE studies; RADIOPHARMACEUTICALS; CEREBRAL cortex
- Publication
Brain: A Journal of Neurology, 2020, Vol 143, Issue 11, p3495
- ISSN
0006-8950
- Publication type
journal article
- DOI
10.1093/brain/awaa296