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: 6.46). 11/2006; 47(10):1013-22. DOI: 10.1111/j.1469-7610.2006.01639.x
Source: PubMed


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, Sep 29, 2015
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    • "Our data further corroborate an involvement of the CC in the generation of tics in adult TS patients as suggested earlier: in both children and adults, larger CC volumes [17-19] and reduced FA [2,9,13,14] have been reported as well as an altered structure-function relationship in the motor CC in adults with TS “only” using a combined TMS-DTI approach [10]. Since we found a positive correlation between tic severity and FA values in the CC, it can be speculated that CC alterations are correlated to neurodevelopmental abnormalities - resulting in reduced transcallosal inhibition of cortical neurons - rather than adaptive mechanisms to compensate for impairments in other brain regions [9]. "
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    ABSTRACT: Despite strong evidence that the pathophysiology of Tourette syndrome (TS) involves structural and functional disturbances of the basal ganglia and cortical frontal areas, findings from in vivo imaging studies have provided conflicting results. In this study we used whole brain diffusion tensor imaging (DTI) to investigate the microstructural integrity of white matter pathways and brain tissue in 19 unmedicated, adult, male patients with TS "only" (without comorbid psychiatric disorders) and 20 age- and sex-matched control subjects. Compared to normal controls, TS patients showed a decrease in the fractional anisotropy index (FA) bilaterally in the medial frontal gyrus, the pars opercularis of the left inferior frontal gyrus, the middle occipital gyrus, the right cingulate gyrus, and the medial premotor cortex. Increased apparent diffusion coefficient (ADC) maps were detected in the left cingulate gyrus, prefrontal areas, left precentral gyrus, and left putamen. There was a negative correlation between tic severity and FA values in the left superior frontal gyrus, medial frontal gyrus bilaterally, cingulate gyrus bilaterally, and ventral posterior lateral nucleus of the right thalamus, and a positive correlation in the body of the corpus callosum, left thalamus, right superior temporal gyrus, and left parahippocampal gyrus. There was also a positive correlation between regional ADC values and tic severity in the left cingulate gyrus, putamen bilaterally, medial frontal gyrus bilaterally, left precentral gyrus, and ventral anterior nucleus of the left thalamus. Our results confirm prior studies suggesting that tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus seem to reflect secondary compensatory mechanisms. Due to the study design, influences from comorbidities, gender, medication and age can be excluded.
    BMC Neuroscience 01/2014; 15(1):6. DOI:10.1186/1471-2202-15-6 · 2.67 Impact Factor
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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 · 3.37 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 · 8.80 Impact Factor
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