Aberrant Functional Network Recruitment of Posterior Parietal Cortex in Turner Syndrome

Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA, USA
Human Brain Mapping (Impact Factor: 5.97). 12/2013; 34(12). DOI: 10.1002/hbm.22131
Source: PubMed


Turner syndrome is a genetic disorder caused by the complete or partial absence of an X chromosome in affected women. Individuals with TS show characteristic difficulties with executive functions, visual-spatial and mathematical cognition, with relatively intact verbal skills, and congruent abnormalities in structural development of the posterior parietal cortex (PPC). The functionally heterogeneous PPC has recently been investigated using connectivity-based clustering methods, which sub-divide a given region into clusters of voxels showing similar structural or functional connectivity to other brain regions. In the present study, we extended this method to compare connectivity-based clustering between groups and investigate whether functional networks differentially recruit the PPC in TS. To this end, we parcellated the PPC into sub-regions based on temporal correlations with other regions of the brain. fMRI data were collected from 15 girls with TS and 14 typically developing (TD) girls, aged 7-14, while they performed a visual-spatial task. Temporal correlations between voxels in the PPC and a set of seed regions were calculated, and the PPC divided into clusters of voxels showing similar connectivity. It was found that in general the PPC parcellates similarly in TS and TD girls, but that regions in bilateral inferior parietal lobules, and posterior right superior parietal lobule, were reliably recruited by different networks in TS relative to TD participants. These regions showed weaker correlation in TS with a set of regions involved in visual processing. These results suggest that abnormal development of visuospatial functional networks in TS may relate to the well documented cognitive difficulties in this disorder. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.

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    • "Neuroanatomically, TS patients have been shown to have reduced parieto-occipital gray matter (GM) volume (Murphy et al. 1993; Reiss et al. 1995; Molko et al. 2004; Marzelli et al. 2011), aberrant thickness and/or surface area of temporal-parieto-occipital cortical regions (Raznahan et al. 2010; Lepage, Clouchoux, et al. 2013; Lepage, Hong, et al. 2013; Lepage, Mazaika, et al. 2013), and impaired microstructural integrity of white matter (WM) tracts such as the superior longitudinal fasciculus (Holzapfel et al. 2006; Yamagata et al. 2012). Furthermore , functional MRI studies have revealed that during visuospatial (Kesler et al. 2004; Bray et al. 2013), executive function (Tamm et al. 2003), working memory (Haberecht et al. 2001; Hart et al. 2006; Bray et al. 2011), or arithmetic tasks (Molko et al. 2003; Kesler et al. 2006), TS patients show abnormal profiles of functional activation or functional coupling/connectivity, predominantly in the frontal/parietal cortices and in subcortical regions such as the caudate. However, currently, the patterns of intrinsic FC in TS patients remain unexplored. "
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    ABSTRACT: Turner syndrome (TS), a disorder caused by the congenital absence of one of the 2 X chromosomes in female humans, provides a valuable human “knockout model” for studying the functions of the X chromosome. At present, it remains unknown whether and how the loss of the X chromosome influences intrinsic functional connectivity (FC), a fundamental phenotype of the human brain. To address this, we performed resting-state functional magnetic resonance imaging and specific cognitive assessments on 22 TS patients and 17 age-matched control girls. A novel data-driven approach was applied to identify the disrupted patterns of intrinsic FC in TS. The TS girls exhibited significantly reduced whole-brain FC strength within the bilateral postcentral gyrus/intraparietal sulcus, angular gyrus, and cuneus and the right cerebellum. Furthermore, a specific functional subnetwork was identified in which the intrinsic FC between nodes was mostly reduced in TS patients. Particularly, this subnetwork is composed of 3 functional modules, and the disruption of intrinsic FC within one of these modules was associated with the deficits of TS patients in math-related cognition. Taken together, these findings provide novel insight into how the X chromosome affects the human brain and cognition, and emphasize an important role of X-linked genes in intrinsic neural coupling.
    Full-text · Article · Oct 2015 · Cerebral Cortex
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    • "Moreover, we show that this flexibility may be predicted from moment-tomoment variability in resting connectivity patterns in these regions. Data-driven connectivity clustering has previously been applied to identify regions of differential functional connectivity in clinical conditions [Bray et al., 2013]. "
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    ABSTRACT: Remote brain regions show correlated spontaneous activity at rest within well described intrinsic connectivity networks (ICNs). Meta-analytic coactivation studies have uncovered networks similar to resting ICNs, suggesting that in task states connectivity modulations may occur principally within ICNs. However, it has also been suggested that specific “hub” regions dynamically link networks under different task conditions. Here, we used functional magnetic resonance imaging at rest and a continuous visual attention task in 16 participants to investigate whether a shift from rest to attention was reflected by within-network connectivity modulation, or changes in network topography. Our analyses revealed evidence for both modulation of connectivity within the default-mode (DMN) and dorsal attention networks (DAN) between conditions, and identified a set of regions including the temporoparietal junction (TPJ) and posterior middle frontal gyrus (MFG) that switched between the DMN and DAN depending on the task. We further investigated the temporal nonstationarity of flexible (TPJ and MFG) regions during both attention and rest. This showed that moment-to-moment differences in connectivity at rest mirrored the variation in connectivity between tasks. Task-dependent changes in functional connectivity of flexible regions may, therefore, be understood as shifts in the proportion of time specific connections are engaged, rather than a switch between networks per se. This ability of specific regions to dynamically link ICNs under different task conditions may play an important role in behavioral flexibility. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Sep 2014 · Human Brain Mapping
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    ABSTRACT: Recently, there has been a wealth of research into structural and functional brain connectivity, and how they change over development. While we are far from a complete understanding, these studies have yielded important insights into human brain development. There isan evergrowing variety of methods for assessing connectivity, each with its own advantages. Here we review research on the development of structural and/or functional brain connectivity in both typically developing subjects and subjects with neurodevelopmental disorders. Space limitations preclude an exhaustive review of brain connectivity across all developmental disorders, so we reviewa representative selection of recent findingson brain connectivity in autism, Fragile X, 22q11.2 deletion syndrome, Williams syndrome, Turner syndrome, and ADHD. Major strides have been made in understandingthe developmental trajectory of the human connectome, offering insight intocharacteristic features of brain development and biological processesinvolved in developmental brain disorders. We also discuss some common themes, includinghemispheric specialization - or asymmetry - and sex differences. We conclude by discussing some promising future directions in connectomics, including the merger of imaging and genetics, and a deeper investigation of the relationships between structural and functional connectivity.
    Full-text · Article · May 2013 · International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience
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