Aberrant striatal dopamine links topographically with cortico-thalamic dysconnectivity in schizophrenia.

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.

Cortico-thalamic hypo- and hyperconnectivity extend consistently to basal ganglia in schizophrenia.

Schizophrenia is characterized by hypoconnectivity or decreased intrinsic functional connectivity (iFC) between prefrontal-limbic cortices and thalamic nuclei, as well as hyperconnectivity or increased iFC between primary-sensorimotor cortices and thalamic nuclei. However, cortico-thalamic iFC overlaps with larger, structurally defined cortico-striato-pallido-thalamo-cortical (CSPTC) circuits. If such an overlap is relevant for intrinsic hypo-/hyperconnectivity, it suggests (i) that patterns of cortico-subcortical hypo-/hyperconnectivity extend consistently from thalamus to basal ganglia nuclei; and (ii) such consistent hypo-/hyperconnectivity might link distinctively but consonant with different symptom dimensions, namely cognitive and psychotic impairments. To test this hypothesis, 57 patients with schizophrenia and 61 healthy controls were assessed by resting-state functional magnetic resonance imaging (fMRI) and clinical-behavioral testing. IFC from intrinsic cortical networks into thalamus, striatum, and pallidum was estimated by partial correlations between fMRI time courses. In patients, the salience network covering prefrontal-limbic cortices was hypoconnected with the mediodorsal thalamus and ventral parts of striatum and pallidum; these iFC-hypoconnectivity patterns were correlated both among each other and specifically with patients' impaired cognition. In contrast, the auditory-sensorimotor network covering primary-sensorimotor cortices was hyperconnected with the anterior ventral nucleus of the thalamus and dorsal parts of striatum and pallidum; these iFC-hyperconnectivity patterns were likewise correlated among each other and specifically with patients' psychotic symptoms. The results demonstrate that prefrontal-limbic hypoconnectivity and primary-sensorimotor hyperconnectivity extend consistently across subcortical nuclei and specifically across distinct symptom dimensions. Data support the model of consistent cortico-subcortical hypo-/hyperconnectivity within CSPTC circuits in schizophrenia.

Frontoparietal areas link impairments of large-scale intrinsic brain networks with aberrant fronto-striatal interactions in OCD: a meta-analysis of resting-state functional connectivity.

Neuroimaging studies report evidence for two distinct pathophysiological models of obsessive-compulsive disorder (OCD): disrupted fronto-striatal circuits and impaired large-scale fronto-parietal-limbic intrinsic brain networks, defined by functionally connected (FC) infra-slow oscillations in ongoing brain activity. To synthesize this literature and overcome inconsistencies, we conducted a coordinate-based meta-analysis of 18 whole-brain resting-state functional magnetic resonance imaging (fMRI) studies (541 patients, 572 healthy controls) comparing seed-based FC between OCD patients and healthy controls. In patients, the meta-analysis revealed (1) consistent hypoconnectivity within frontoparietal and salience network, and between salience, frontoparietal and default-mode network, and (2) consistent general dysconnectivity (no specific direction of connectivity change) within default-mode and frontoparietal network, as well as between frontoparietal, default-mode, and salience networks. Between-network hypoconnectivity provides evidence for the triple-network model in OCD, while aberrant within-network connectivity of frontoparietal and striatal regions supports reports of aberrant fronto-striatal circuitry. Therefore, results corroborate both models of OCD pathophysiology and link them by underlining the importance of intrinsic connectivity of frontoparietal regions which are common to both models.