Reduced Contralateral Cerebello-Cortical Functional Connectivity in 22q11.2 Deletion Syndrome
Poster No:
882
Submission Type:
Abstract Submission
Authors:
Hoki Fung1, Charles Schleifer1, Leila Kushan1, Elizabeth Bondy1, Carrie Bearden1,2
Institutions:
1Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, 2Department of Psychology, University of California, Los Angeles, Los Angeles, CA
First Author:
Hoki Fung
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles
Los Angeles, CA
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles
Los Angeles, CA
Co-Author(s):
Charles Schleifer
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles
Los Angeles, CA
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles
Los Angeles, CA
Leila Kushan
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles
Los Angeles, CA
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles
Los Angeles, CA
Elizabeth Bondy
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles
Los Angeles, CA
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles
Los Angeles, CA
Carrie Bearden, PhD
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles|Department of Psychology, University of California, Los Angeles
Los Angeles, CA|Los Angeles, CA
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles|Department of Psychology, University of California, Los Angeles
Los Angeles, CA|Los Angeles, CA
Introduction:
22q11.2 Deletion Syndrome (22qDel) is a genetic disorder resulting from a microdeletion on the long arm of chromosome 22. It occurs in approximately 1 in 4000 live births, and is associated with a wide range of clinical manifestations including heart defects, immune dysfunction, and developmental delay. It is also linked to elevated risks for neurodevelopmental and neuropsychiatric disorders including schizophrenia, autism spectrum disorder, and attention-deficit/hyperactivity disorder [1]. 22qDel is highly pleiotropic, offering a valuable framework for elucidating the links between genes, brain development, and transdiagnostic psychiatric phenotypes [2]. Previous studies have reported structural and functional alterations in cortical and subcortical regions, as well as their associations with cognitive deficits and neuropsychiatric symptoms in 22qDel [3-6]. However, the cerebellum - a region traditionally associated with motor control but increasingly recognized for its involvement in higher cognitive functions - remains an understudied neuroendophenotype in 22qDel research [7]. This study sought to address this gap by examining network-specific resting-state cerebello-cortical functional connectivity (FC) in individuals with 22qDel.
Methods:
Resting-state functional magnetic resonance imaging (rs-fMRI) and high-resolution T1-weighted structural images were acquired on two scanners (Siemens 3T MAGNETOM Trio and Prisma) in 77 participants with 22qDel (M=17.1y, SD=8.26y; 59.7% F) and 74 demographically comparable typically developing (TD) control participants (M=14.7y, SD=6.76y; 54.0% F). The images were preprocessed using the Quantitative Neuroimaging Environment & Toolbox with the Human Connectome Project minimal preprocessing pipeline. Additional processing of the rs-fMRI data included bandpass filtering, motion scrubbing, and spatial smoothing. The whole brain, including the cerebellum, was parcellated into 718 parcels using the Cole-Anticevic brain-wide network partition [8], where each parcel was assigned to one of the 12 large-scale brain networks (Figure 1). Network cerebello-cortical FC was calculated as the Fisher z-transformed pairwise Pearson correlation between the cortical and cerebellar parcels from the frontoparietal cognitive control (FPN), default-mode (DMN), and dorsal attention (DAN) networks. Differences in FC between the control and 22qDel groups were investigated using linear regression models. All models included age, sex, and scanner as covariates, and the results were corrected with a false-discovery rate threshold of q<.05.
·Fig 1. Cole-Anticevic brain-wide network partition (CAB-NP). Extracted from Figure 1 in Ji et al., 2019 [8].
Results:
In comparison to TD controls, 22qDel exhibited significantly reduced FC in three distinct cerebello-cortical pairs (FDR q<.05; see Figure 2). Specifically: 1. Dorsal-Attention-R-Cerebellum and Dorsal-Attention-L-Cortex (β = - .25, p = .002, 95% CI [-0.40, -0.10]), 2. Frontoparietal-L-Cerebellum and Frontoparietal-R-Cortex (β = - .25, p = .002, 95% CI [-0.40, -0.10]), and 3. Default-R-Cerebellum and Frontoparietal-L-Cortex (β = - .23, p = .004, 95% CI [-0.23, -0.07]).
·Fig 2. Cerebellar-Cortical FC in TD and 22q11.2 Deletion Syndrome. Red bounding box indicates the z’ difference between TD controls and 22qDel is significant at FDR q<.05.
Conclusions:
To our knowledge, this study is the first to examine cerebello-cortical FC in individuals with 22qDel. Using a novel functional parcellation approach, our study revealed disruptions in network-specific FC between the cerebellum and cortex in individuals with 22qDel. Specifically, three cerebello-cortical pairs from the DAN, FPN, and DMN exhibited significantly reduced FC in 22qDel relative to controls. Notably, all three pairs displayed a contralateral pattern. While anatomical and tractography studies [9-10] have previously established that structural cerebello-cortical connections are contralateral, the implications for functional connectivity remain unclear. This prompts further exploration into the concept of laterality in cerebello-cortical FC research and an investigation into how disruptions in contralateral connectivity may be linked to cognitive outcomes and psychiatric symptoms in 22qDel.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism)
Psychiatric (eg. Depression, Anxiety, Schizophrenia)
Genetics:
Neurogenetic Syndromes 1
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 2
Task-Independent and Resting-State Analysis
Keywords:
Cerebellum
Cortex
MRI
Other - Genetic Disorders; 22q11.2 Deletion Syndrome; Cerebello-Cortical Functional Connectivity
1|2Indicates the priority used for review
Provide references using author date format
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