Dissociable Disruptions in Thalamic and Hippocampal Resting-State Functional Connectivity in Youth with 22q11.2 Deletions
| Autor: | Carrie E. Bearden, Alan Anticevic, Leila Kushan, Jie Lisa Ji, Charles Schleifer, Genevieve Yang, Amy Lin |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Aging hippocampus Hippocampal formation Medical and Health Sciences Hippocampus 0302 clinical medicine Thalamus Neural Pathways 2.1 Biological and endogenous factors Copy-number variation Aetiology Gray Matter Child Research Articles Pediatric 0303 health sciences Human Connectome Project General Neuroscience fMRI Cognition Magnetic Resonance Imaging Mental Health connectivity Neurological Female Sensorimotor Cortex Adult Adolescent 1.1 Normal biological development and functioning Sensory system Neuroimaging Biology Basic Behavioral and Social Science 03 medical and health sciences Young Adult Clinical Research Underpinning research Behavioral and Social Science Connectome DiGeorge Syndrome Humans 030304 developmental biology Neurology & Neurosurgery Resting state fMRI Psychology and Cognitive Sciences Neurosciences 22q11 Brain Disorders networks Schizophrenia Nerve Net Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience, vol 39, iss 7 |
| Popis: | The 22q11.2 deletion syndrome (22q11DS) is a recurrent copy number variant with high penetrance for developmental neuropsychiatric disorders. Study of individuals with 22q11DS therefore may offer key insights into neural mechanisms underlying such complex illnesses. Resting-state functional connectivity MRI studies in idiopathic schizophrenia have consistently revealed disruption of thalamic and hippocampal circuitry. Here, we sought to test whether this circuitry is similarly disrupted in the context of this genetic high-risk condition. To this end, resting-state functional connectivity patterns were assessed in a sample of human youth with 22q11DS (n= 42; 59.5% female) and demographically matched healthy controls (n= 39; 53.8% female). Neuroimaging data were acquired via single-band protocols and analyzed in line with methods provided by the Human Connectome Project. We computed functional relationships between individual-specific anatomically defined thalamic and hippocampal seeds and all gray matter voxels in the brain. Whole-brain Type I error protection was achieved through nonparametric permutation-based methods. The 22q11DS patients displayed dissociable disruptions in thalamic and hippocampal functional connectivity relative to control subjects. Thalamocortical coupling was increased in somatomotor regions and reduced across associative networks. The opposite effect was observed for the hippocampus in regards to somatomotor and associative network connectivity. The thalamic and hippocampal dysconnectivity observed in 22q11DS suggests that high genetic risk for psychiatric illness is linked with disruptions in large-scale corticosubcortical networks underlying higher-order cognitive functions. These effects highlight the translational importance of large-effect copy number variants for informing mechanisms underlying neural disruptions observed in idiopathic developmental neuropsychiatric disorders.SIGNIFICANCE STATEMENTInvestigation of neuroimaging biomarkers in highly penetrant genetic syndromes represents a more biologically tractable approach to identify neural circuit disruptions underlying developmental neuropsychiatric conditions. The 22q11.2 deletion syndrome confers particularly high risk for psychotic disorders and is thus an important translational model in which to investigate systems-level mechanisms implicated in idiopathic illness. Here, we show resting-state fMRI evidence of large-scale sensory and executive network disruptions in youth with 22q11DS. In particular, this study provides the first evidence that these networks are disrupted in a dissociable fashion with regard to the functional connectivity of the thalamus and hippocampus, suggesting circuit-level dysfunction. |
| Databáze: | OpenAIRE |
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