Dataset Information

Effective Connectivity of the Hippocampus Can Differentiate Patients with Schizophrenia from Healthy Controls: A Spectral DCM Approach.

ABSTRACT: We applied spectral dynamic causal modelling (Friston et al. in Neuroimage 94:396-407. https://doi.org/10.1016/j.neuroimage.2013.12.009 , 2014) to analyze the effective connectivity differences between the nodes of three resting state networks (i.e. default mode network, salience network and dorsal attention network) in a dataset of 31 male healthy controls (HC) and 25 male patients with a diagnosis of schizophrenia (SZ). Patients showed increased directed connectivity from the left hippocampus (LHC) to the: dorsal anterior cingulate cortex (DACC), right anterior insula (RAI), left frontal eye fields and the bilateral inferior parietal sulcus (LIPS & RIPS), as well as increased connectivity from the right hippocampus (RHC) to the: bilateral anterior insula (LAI & RAI), right frontal eye fields and RIPS. In SZ, negative symptoms predicted the connectivity strengths from the LHC to: the DACC, the left inferior parietal sulcus (LIPAR) and the RHC, while positive symptoms predicted the connectivity strengths from the LHC to the LIPAR and from the RHC to the LHC. These results reinforce the crucial role of hippocampus dysconnectivity in SZ pathology and its potential as a biomarker of disease severity.

SUBMITTER: Uscatescu LC

PROVIDER: S-EPMC8556208 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Effective Connectivity of the Hippocampus Can Differentiate Patients with Schizophrenia from Healthy Controls: A Spectral DCM Approach.

Uscătescu Lavinia Carmen LC Kronbichler Lisa L Stelzig-Schöler Renate R Pearce Brandy-Gale BG Said-Yürekli Sarah S Reich Luise Antonia LA Weber Stefanie S Aichhorn Wolfgang W Kronbichler Martin M

Brain topography 20210904 6

We applied spectral dynamic causal modelling (Friston et al. in Neuroimage 94:396-407. https://doi.org/10.1016/j.neuroimage.2013.12.009 , 2014) to analyze the effective connectivity differences between the nodes of three resting state networks (i.e. default mode network, salience network and dorsal attention network) in a dataset of 31 male healthy controls (HC) and 25 male patients with a diagnosis of schizophrenia (SZ). Patients showed increased directed connectivity from the left hippocampus ...[more]

PMID: 34482503

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Project description:Alterations in cortical inter-areal functional connectivity, and aberrant glutamatergic signalling are implicated in the pathophysiology of schizophrenia but the relationship between the two is unclear. We used multimodal imaging to identify areas of convergence between the two systems. Two separate cohorts were examined, comprising 195 participants in total. All participants received resting state functional MRI to characterise functional brain networks and proton magnetic resonance spectroscopy (1H-MRS) to measure glutamate concentrations in the frontal cortex. Study A investigated the relationship between frontal cortex glutamate concentrations and network connectivity in individuals with schizophrenia and healthy controls. Study B also used 1H-MRS, and scanned individuals with schizophrenia and healthy controls before and after a challenge with the glutamatergic modulator riluzole, to investigate the relationship between changes in glutamate concentrations and changes in network connectivity. In both studies the network based statistic was used to probe associations between glutamate and connectivity, and glutamate associated networks were then characterised in terms of their overlap with canonical functional networks. Study A involved 76 individuals with schizophrenia and 82 controls, and identified a functional network negatively associated with glutamate concentrations that was concentrated within the salience network (p < 0.05) and did not differ significantly between patients and controls (p > 0.85). Study B involved 19 individuals with schizophrenia and 17 controls and found that increases in glutamate concentrations induced by riluzole were linked to increases in connectivity localised to the salience network (p < 0.05), and the relationship did not differ between patients and controls (p > 0.4). Frontal cortex glutamate concentrations are associated with inter-areal functional connectivity of a network that localises to the salience network. Changes in network connectivity in response to glutamate modulation show an opposite effect compared to the relationship observed at baseline, which may complicate pharmacological attempts to simultaneously correct glutamatergic and connectivity aberrations.

Project description:Background: The cognitive dysmetria theory of schizophrenia proposes that communication between the cerebellum and cerebral cortex is disrupted by structural and functional abnormalities, resulting in psychotic symptoms and cognitive deficits. Methods: Using publicly available data, resting-state functional connectivity (rsFC) was calculated from 20 hemispheric cerebellar lobules as seed regions of interest to the rest of the brain. Group differences in rsFC between individuals with schizophrenia (SZ) and healthy controls (HCs) were computed, and relationships between rsFC and symptom severity and cognitive functioning were explored. Results: HCs demonstrated stronger connectivity than SZ between several cerebellar lobules and cortical regions, most robustly between motor-related cerebellar lobules (V and VIIIa/b) and temporal and parietal cortices. In addition, seven of nine lobules in which reduced cerebellocortical connectivity was observed showed diagnosis × processing speed interactions; HC showed a positive relationship between connectivity and processing speed, whereas SZ did not show this relationship. Other cognitive domains and symptom severity did not show relationships with connectivity. Conclusions: These findings partially support the cognitive dysmetria theory, and suggest that disrupted cerebellocortical connectivity is associated with slowed processing speed in schizophrenia. Impact statement We show in this work that in chronic schizophrenia, there is weaker functional connectivity between previously unstudied inferior posterior cerebellar lobules and cortical association areas. These findings align and extend previous work showing abnormal connectivity of anterior cerebellar lobules. Further, we present a novel finding that these connectivity deficits are differentially associated with processing speed in the schizophrenia versus healthy control groups. Findings provide further evidence for cerebellocortical dysconnectivity and processing speed deficits as biomarkers of schizophrenia, which may have implications for downstream effects on higher order cognitive functions, in line with the cognitive dysmetria theory.

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Dataset Information

Effective Connectivity of the Hippocampus Can Differentiate Patients with Schizophrenia from Healthy Controls: A Spectral DCM Approach.

Publications

Effective Connectivity of the Hippocampus Can Differentiate Patients with Schizophrenia from Healthy Controls: A Spectral DCM Approach.

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