Reduced white matter connectivity in the corpus callosum of children with Tourette syndrome

Center for Child and Adolescent Mental Health, University of Bergen, Bergen, Norway.
Journal of Child Psychology and Psychiatry (Impact Factor: 5.67). 11/2006; 47(10):1013-22. DOI: 10.1111/j.1469-7610.2006.01639.x
Source: PubMed

ABSTRACT Brain imaging studies have revealed anatomical anomalies in the brains of individuals with Tourette syndrome (TS). Prefrontal regions have been found to be larger and the corpus callosum (CC) area smaller in children and young adults with TS compared with healthy control subjects, and these anatomical features have been understood to reflect neural plasticity that helps to attenuate the severity of tics.
CC white matter connectivity, as measured by the Fractional Anisotropy (FA) index from diffusion tensor images, was assessed in 20 clinically well-defined boys with Tourette syndrome and 20 age- and gender-matched controls.
The hypothesis that children with TS would show reduced measures of connectivity in CC fibers was confirmed for all subregions of the CC. There was no significant interaction of TS and region. Reductions in FA in CC regions may reflect either fewer interhemispheric fibers or reduced axonal myelination. FA values did not correlate significantly with the severity of tic symptoms. Group differences in measures of connectivity did not seem to be attributable to the presence of comorbid ADHD or OCD, to medication exposure, or group differences in IQ.
Our findings of a reduced interhemispheral white matter connectivity add to the understanding of neural connectivity and plasticity in the brains of children who have TS.

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Available from: Dongrong Xu, Aug 26, 2015
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    • "This may be explained by the fact that the CC is the main path for coordinating syntactic information in the left hemisphere and prosodic information in the right hemisphere. Moreover, structural CC abnormalities have been noticed in some patients with schizophrenia, autism, Tourette's syndrome and attention deficit hyperactivity disorder, even though definitive association with these disorders still remains to be demonstrated (Hardan et al., 2000; Seidman et al., 2005; Plessen et al., 2006; Hallak et al., 2007; Paul et al., 2007). "
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    ABSTRACT: The corpus callosum (CC) plays a crucial role in interhemispheric communication. It has been shown that CC formation relies on the guidepost cells located in the midline region that include glutamatergic and GABAergic neurons as well as glial cells. However, the origin of these guidepost GABAergic neurons and their precise function in callosal axon pathfinding remain to be investigated. Here, we show that two distinct GABAergic neuronal subpopulations converge towards the midline prior to the arrival of callosal axons. Using in vivo and ex vivo fate mapping we show that CC GABAergic neurons originate in the caudal and medial ganglionic eminences (CGE and MGE) but not in the lateral ganglionic eminence (LGE). Time lapse imaging on organotypic slices and in vivo analyses further revealed that CC GABAergic neurons contribute to the normal navigation of callosal axons. The use of Nkx2.1 knockout (KO) mice confirmed a role of these neurons in the maintenance of proper behavior of callosal axons while growing through the CC. Indeed, using in vitro transplantation assays, we demonstrated that both MGE- and CGE-derived GABAergic neurons exert an attractive activity on callosal axons. Furthermore, by combining a sensitive RT-PCR technique with in situ hybridization, we demonstrate that CC neurons express multiple short and long range guidance cues. This study strongly suggests that MGE- and CGE-derived interneurons may guide CC axons by multiple guidance mechanisms and signaling pathways. © 2013 Wiley Periodicals, Inc. Develop Neurobiol, 2013.
    Developmental Neurobiology 09/2013; 73(9). DOI:10.1002/dneu.22075 · 4.19 Impact Factor
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    • "Combined DTI and TMS in a sample of 15 " pure " adult GTS patients showed reduced left to right interhemispheric inhibition measured with TMS and an abnormal correlation between the amount of interhemispheric inhibition and fractional anisotropy assessments (reflecting the levels of white matter organization and integrity) across the motor part of the corpus callosum (Baumer et al., 2010). Previously, the corpus callosum was found to be reduced in size (n GTS = 158) in children but not adults with GTS with an inverse correlation of tic severity and size (Plessen et al., 2004) and reduced FA values in both GTS children and adults (total n GTS = 39) in two further studies reflecting altered interhemispheric connectivity (Neuner et al., 2010; Plessen et al., 2006). Again, disentangling " primary " and adaptive changes is not possible on the basis of the data available. "
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    ABSTRACT: Gilles de la Tourette syndrome (GTS) holds a prime position as a disorder transgressing the brittle boundaries of neurology and psychiatry with an entangling web of motor and behavioural problems. With tics as the disorder's hallmark and myriads of related signs such as echo-, pali- and coprophenomena, paralleled by a broad neuropsychiatric spectrum of comorbidities encompassing attention deficit hyperactivity disorder, obsessive-compulsive disorder but also self-injurious behaviour and depression, GTS pathophysiology remains enigmatic. In this review, in the light of GTS phenomenology, we will focus on current theories of tic-emergence related to aberrant activity in the basal ganglia and abnormal basal ganglia - cortex interplay through cortico-striato-thalamocortical loops from an anatomical, neurophysiological and functional-neuroimaging perspective. We will attempt a holistic view to the countless major and minor drawbacks of the GTS brain and comment on future directions of neuroscientific research to elucidate this common and complex neuropsychiatric syndrome, which merits scientific understanding and social acceptance.
    Neuroscience & Biobehavioral Reviews 12/2012; 37(6). DOI:10.1016/j.neubiorev.2012.11.004 · 10.28 Impact Factor
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    • "However, these effects may be modulated by compensatory, neuroplastic, changes in the structure and function of longer range cortical circuits, including inter-hemispheric connectivity and connections between frontal and motor areas. Examples may include alterations in the white-matter microstructure of neural pathways linked to motor areas (Jackson et al., 2011; Neuner et al., 2010; Plessen et al., 2004, 2006); and recruitment of additional cortical regions (e.g., prefrontal cortex) to aid in the control of motor outputs (Jackson et al., 2011), perhaps by 'dampening' the hyper-excitability of motor areas. Evidence in support of this idea comes from a recent fMRI study in which the Blood Oxygenation Level Dependent (BOLD) signal recorded in the motor cortex of individuals with TS was significantly reduced relative to controls (who were performing at the same level on a behavioural task), whereas the BOLD signal recording in the right prefrontal cortex of the TS group was significantly increased relative to controls, and, in the TS group only, was significantly correlated with performance on the behavioural task (Jackson et al., 2011). "
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    ABSTRACT: Tourette syndrome (TS) is a neuro-developmental disorder characterized by the occurrence of motor and vocal tics: involuntary, repetitive, stereotyped behaviours that occur with a limited duration, often typically many times in a single day. Previous studies suggest that children and adolescents with TS may undergo compensatory, neuroplastic changes in brain structure and function that help them gain control over their tics. In the current study we used single-pulse and dual-site paired-pulse transcranial magnetic stimulation (TMS), in conjunction with a manual choice reaction time task that induces high levels of inter-manual conflict, to investigate this conjecture in a group of children and adolescents with TS, but without co-morbid Attention Deficit Hyperactivity Disorder (ADHD). We found that performance on the behavioural response-conflict task did not differ between the adolescents with TS and a group of age-matched typically developing individuals. By contrast, our study demonstrated that cortical excitability, as measured by TMS-induced motor-evoked potentials (MEPs), was significantly reduced in the TS group in the period immediately preceding a finger movement. This effect is interpreted as consistent with previous suggestions that the cortical hyper-excitability that may give rise to tics in TS is actively suppressed by cognitive control mechanisms. Finally, we found no reliable evidence for altered patterns of functional inter-hemispheric connectivity in TS. These results provide evidence for compensatory brain reorganization that may underlie the increased self-regulation mechanisms that have been hypothesized to bring about the control of tics during adolescence.
    Journal of Neuropsychology 07/2012; 7(1). DOI:10.1111/j.1748-6653.2012.02033.x · 3.82 Impact Factor
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