Intrinsic cerebellar functional connectivity of social cognition and theory of mind in first-episode psychosis patients

Neuroimaging studies have revealed how intrinsic dysconnectivity among cortical regions of the mentalizing network (MENT) and the mirror neuron system (MNS) could explain the theory of mind (ToM) deficit in schizophrenia patients. However, despite the concurrent involvement of the cerebellum with the cortex in social cognition, the dysfunction in intrinsic interplay between the cerebellar nodes of MENT/MNS and the cortex in schizophrenia patients remains unknown. Thus, we aimed to investigate whether resting-state cerebello–cortical dysconnectivity exists in first-episode psychosis (FEP) patients in relationship with their ToM deficit. A total of 37 FEP patients and 80 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. Using a priori-defined cerebellar seeds that functionally connect to the MENT (right crus II) and MNS (right crus I), we compared cerebello–cortical functional connectivities (FCs) in FEP patients and HCs. Correlations between cerebello–parietal connectivities and ToM performance were investigated in FEP patients. FEP patients showed hyperconnectivity between the right crus II and anterior cingulate gyrus and between the right crus I and supplementary motor area, bilateral postcentral gyrus, and right central/parietal operculum (CO/PO). Hypoconnectivity was found between the right crus II and left supramarginal gyrus (SMG) in FEP patients. FCs between the right crus II and left SMG and between the right crus I and right CO/PO were significantly correlated with ToM scores in FEP patients. In accordance with the “cognitive dysmetria” hypothesis, our results highlight the importance of cerbello-cortical dysconnectivities in understanding social cognitive deficits in schizophrenia patients.


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We require information from authors about some types of materials, experimental systems and methods used in many studies. Here, indicate whether each material, system or method listed is relevant to your study. If you are not sure if a list item applies to your research, read the appropriate section before selecting a response. Forty first-episode psychosis (FEP) patients were recruited from the Seoul Youth Clinic of Seoul National University Hospital (SNUH). Using the Structured Clinical Interview for DSM, fourth edition (DSM-IV), Axis I (SCID-I), experienced psychiatrists interviewed all FEP individuals who met the following inclusion criteria: between the age of 15 to 40; diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder according to the DSM-IV criteria; and symptom presence for less than 2 years. A total of 110 healthy controls (HCs) were recruited from internet advertisements, screened, and confirmed using the SCID Nonpatient Edition (SCID-NP).
From 40 FEP and 110 HC participants, we only included participants with ToM task scores (excluding 2 FEP patients and 21 HCs) and structural and functional MRI data with intact cerebella (excluding 1 FEP patient and 9 HCs). In total, 117 participants (FEP patients, n = 37; HCs, n=80) were included in the current study.
All MR images were acquired with a Siemens 3T Trio scanner (Siemens, Erlangen, Germany) using a 12-channel head coil. For each participant, a high-resolution 3D T1-weighted image was obtained using a magnetization-prepared rapid gradient echo sequence (TR/ echo time (TE) = 1670/1.89 ms, field of view (FOV) = 250 mm, flip angle (FA) = 9°, voxel size = 1.0×1.0×1.0 mm3, and sagittal slices = 208) for anatomical reference. Using an echo planar imaging sequence (TR/TE = 3500/30 ms, FOV = 240 mm, FA = 90°, voxel size = 1.9×1.9×3.5 mm3, 35 axial slices), rs-fMRI data were collected for 6 min and 58 seconds. The phase-encoding direction for all images was anterior to posterior. During rest, participants were instructed to keep their eyes closed and relax but to not fall asleep. To ensure that participants had not fallen asleep, they completed a questionnaire after the scan.
Data were collected from June 2010 to August 2016.
From 40 FEP and 110 HC participants, we only included participants with ToM task scores (excluding 2 FEP patients and 21 HCs) and structural and functional MRI data with intact cerebella (excluding 1 FEP patient and 9 HCs). In total, 117 participants (FEP patients, n = 37; HCs, n=80) were included in the current study. Exclusion criteria were pre-established.
No participants dropped out.
Allocation was not random, but participants were age-, sex-, and handed-matched. Forty first-episode psychosis (FEP) patients were recruited from the Seoul Youth Clinic of Seoul National University Hospital (SNUH). A total of 110 healthy controls (HCs) were recruited from internet advertisements, screened, and confirmed using the SCID Nonpatient Edition (SCID-NP).
The study was conducted in accordance with the Declaration of Helsinki and was approved by the IRB of the SNUH (IRB no. H-2104(IRB no. H- -223-1216 ARtifact detection Tools (ART)-based outlier detection was performed. The signals from white matter, cerebrospinal fluid, motion realignment parameters, and their first derivatives were regressed out (aCompCor strategy).

N/A. general linear model
The coefficients of Pearson's bivariate correlation were subsequently converted into normally distributed z scores via Fisher r-to-z transformation.
To study cerebellar FC with socially relevant cerebral regions, five social cerebellar ROIs were chosen according to the MNI coordinates revealed by the automated meta-analysis of NeuroSynth with the keywords "action" and "mirror" for the MNS seeds and "mentalizing" for the MENT seeds8. Spherical ROIs (5 mm) were created, centered around these coordinates. The centers of the two MENT cerebellar ROIs were located at the right crus II (+26, -84, -32) and its left mirror location (-26, -84, -32), while those of the three MNS cerebellar ROIs were at the right crus I (+40, -48, -32) and lobule VIII (+15, -75, -50),