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

Abstract

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.

Impaired structural connectivity between dorsal attention network and pulvinar mediates the impact of premature birth on adult visual–spatial abilities

“…To define corticothalamic functional connectivity, we relied on previously applied partial correlation approach of our group on functional connectivity as described in (Avram, Brandl, Bauml, & Sorg, 2018 To relate between group differences in DAN-thalamus iFC to POindices, we used the following approach: voxels whose iFC differed significantly between groups were saved as images in SPM 8. In order to control whether structural connectivity changes between DAN and pulvinar in the VPB group were specific for modality, we analyzed the functional connectivity between DAN and thalamus and compared it across MB and VPB groups.…”

“…In order to control whether structural connectivity changes between DAN and pulvinar in the VPB group were specific for modality, we analyzed the functional connectivity between DAN and thalamus and compared it across MB and VPB groups. To define corticothalamic functional connectivity, we relied on previously applied partial correlation approach of our group on functional connectivity as described in (Avram, Brandl, Bauml, & Sorg, 2018 To relate between group differences in DAN-thalamus iFC to POindices, we used the following approach: voxels whose iFC differed significantly between groups were saved as images in SPM 8. After binarization, ROI-restricted network-specific iFC was extracted and averaged subject-wise with Matlab-based in-house software.…”

Cortico-thalamic dysconnectivity links with aberrant striatal dopamine in schizophreniaA simultaneous18F-DOPA-PET/resting-state fMRI study

“…Both aberrant dopamine transmission in the striatum 1-8 and aberrant intrinsic functional connectivity (iFC) between distinct cortical networks and thalamic nuclei 9-17 are among the most consistent findings of brain alterations in schizophrenia. As basal ganglia circuits, including the striatum and midbrain-based dopaminergic projections into the striatum, modulate cortico-thalamic-iFC, it has been suggested that these brain changes are pathophysiologically related.…”

“…As basal ganglia circuits, including the striatum and midbrain-based dopaminergic projections into the striatum, modulate cortico-thalamic-iFC, it has been suggested that these brain changes are pathophysiologically related. 9, 17-20 The current study investigated this proposed relationship in patients with schizophrenia using simultaneous Fluorodihydroxyphenyl-L-alanine positron emission tomography ( 18 F-DOPA-PET) to assess dopamine transmission and blood oxygenation level-dependent resting-state functional magnetic resonance imaging (rs-fMRI) to evaluate cortico-thalamic-iFC.…”

“…27-29 Both decreased iFC between frontal cortices (i.e., salience-network (SAL) – covering cingulo-opercular-insular-mediofrontal cortices) and ventral anterior/mediodorsal thalamus and increased iFC between primary-sensorimotor cortices (i.e., auditory-sensorimotor-network (ASM) – covering lateral somatomotor-temporal cortices) and posterior/ventrolateral thalamus have been reported in at-risk, first-episode, and chronic patients with schizophrenia and first-degree relatives of patients. 10, 13,14, 17, 30, 31…”