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Multispectral brain morphometry in Tourette syndrome persisting into adulthood.

ABSTRACT: Tourette syndrome is a childhood-onset neuropsychiatric disorder with a high prevalence of attention deficit hyperactivity and obsessive-compulsive disorder co-morbidities. Structural changes have been found in frontal cortex and striatum in children and adolescents. A limited number of morphometric studies in Tourette syndrome persisting into adulthood suggest ongoing structural alterations affecting frontostriatal circuits. Using cortical thickness estimation and voxel-based analysis of T1- and diffusion-weighted structural magnetic resonance images, we examined 40 adults with Tourette syndrome in comparison with 40 age- and gender-matched healthy controls. Patients with Tourette syndrome showed relative grey matter volume reduction in orbitofrontal, anterior cingulate and ventrolateral prefrontal cortices bilaterally. Cortical thinning extended into the limbic mesial temporal lobe. The grey matter changes were modulated additionally by the presence of co-morbidities and symptom severity. Prefrontal cortical thickness reduction correlated negatively with tic severity, while volume increase in primary somatosensory cortex depended on the intensity of premonitory sensations. Orbitofrontal cortex volume changes were further associated with abnormal water diffusivity within grey matter. White matter analysis revealed changes in fibre coherence in patients with Tourette syndrome within anterior parts of the corpus callosum. The severity of motor tics and premonitory urges had an impact on the integrity of tracts corresponding to cortico-cortical and cortico-subcortical connections. Our results provide empirical support for a patho-aetiological model of Tourette syndrome based on developmental abnormalities, with perturbation of compensatory systems marking persistence of symptoms into adulthood. We interpret the symptom severity related grey matter volume increase in distinct functional brain areas as evidence of ongoing structural plasticity. The convergence of evidence from volume and water diffusivity imaging strengthens the validity of our findings and attests to the value of a novel multimodal combination of volume and cortical thickness estimations that provides unique and complementary information by exploiting their differential sensitivity to structural change.

SUBMITTER: Draganski B

PROVIDER: S-EPMC2995885 | biostudies-other | 2010 Dec

REPOSITORIES: biostudies-other

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Multispectral brain morphometry in Tourette syndrome persisting into adulthood.

Draganski Bogdan B Martino Davide D Cavanna Andrea E AE Hutton Chloe C Orth Michael M Robertson Mary M MM Critchley Hugo D HD Frackowiak Richard S RS

Brain : a journal of neurology 20101110 Pt 12

Tourette syndrome is a childhood-onset neuropsychiatric disorder with a high prevalence of attention deficit hyperactivity and obsessive-compulsive disorder co-morbidities. Structural changes have been found in frontal cortex and striatum in children and adolescents. A limited number of morphometric studies in Tourette syndrome persisting into adulthood suggest ongoing structural alterations affecting frontostriatal circuits. Using cortical thickness estimation and voxel-based analysis of T1- an ...[more]

PMID: 21071387

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Project description:Youth with Tourette syndrome (TS) exhibit, compared to healthy, abnormal ability to lateralize digital sequential tasks. It is unknown whether this trait is related to inter-hemispheric connections, and whether it is preserved or lost in patients with TS persisting through adult life. We studied 13 adult TS patients and 15 age-matched healthy volunteers. All participants undertook: 1) a finger opposition task, performed with the right hand (RH) only or with both hands, using a sensor-engineered glove in synchrony with a metronome at 2 Hz; we calculated a lateralization index [(single RH-bimanual RH)/single RH X 100) for percentage of correct movements (%CORR); 2) MRI-based diffusion tensor imaging and probabilistic tractography of inter-hemispheric corpus callosum (CC) connections between supplementary motor areas (SMA) and primary motor cortices (M1). We confirmed a significant increase in the %CORR in RH in the bimanual vs. single task in TS patients (p<0.001), coupled to an abnormal ability to lateralize finger movements (significantly lower lateralization index for %CORR in TS patients, p = 0.04). The %CORR lateralization index correlated positively with tic severity measured with the Yale Global Tic Severity Scale (R = 0.55;p = 0.04). We detected a significantly higher fractional anisotropy (FA) in both the M1-M1 (p = 0.036) and the SMA-SMA (p = 0.018) callosal fibre tracts in TS patients. In healthy subjects, the %CORR lateralization index correlated positively with fractional anisotropy of SMA-SMA fibre tracts (R = 0.63, p = 0.02); this correlation was not significant in TS patients. TS patients exhibited an abnormal ability to lateralize finger movements in sequential tasks, which increased in accuracy when the task was performed bimanually. This abnormality persists throughout different age periods and appears dissociated from the transcallosal connectivity of motor cortical regions. The altered interhemispheric transfer of motor abilities in TS may be the result of compensatory processes linked to self-regulation of motor control.

Project description:To report the results of 'responsive' deep brain stimulation (DBS) for Tourette syndrome (TS) in a National Institutes of Health funded experimental cohort. The use of 'brain derived physiology' as a method to trigger DBS devices to deliver trains of electrical stimulation is a proposed approach to address the paroxysmal motor and vocal tic symptoms which appear as part of TS. Ten subjects underwent bilateral staged DBS surgery and each was implanted with bilateral centromedian thalamic (CM) region DBS leads and bilateral M1 region cortical strips. A series of identical experiments and data collections were conducted on three groups of consecutively recruited subjects. Group 1 (n = 2) underwent acute responsive DBS using deep and superficial leads. Group 2 (n = 4) underwent chronic responsive DBS using deep and superficial leads. Group 3 (n = 4) underwent responsive DBS using only the deep leads. The primary outcome measure for each of the 8 subjects with chronic responsive DBS was calculated as the pre-operative baseline Yale Global Tic Severity Scale (YGTSS) motor subscore compared to the 6 month embedded responsive DBS setting. A responder for the study was defined as any subject manifesting a ≥ 30 points improvement on the YGTSS motor subscale. The videotaped Modified Rush Tic Rating Scale (MRVTRS) was a secondary outcome. Outcomes were collected at 6 months across three different device states: no stimulation, conventional open-loop stimulation, and embedded responsive stimulation. The experience programming each of the groups and the methods applied for programming were captured. There were 10 medication refractory TS subjects enrolled in the study (5 male and 5 female) and 4/8 (50%) in the chronic responsive eligible cohort met the primary outcome manifesting a reduction of the YGTSS motor scale of ≥ 30% when on responsive DBS settings. Proof of concept for the use of responsive stimulation was observed in all three groups (acute responsive, cortically triggered and deep DBS leads only). The responsive approach was safe and well tolerated. TS power spectral changes associated with tics occurred consistently in the low frequency 2-10 Hz delta-theta-low alpha oscillation range. The study highlighted the variety of programming strategies which were employed to achieve responsive DBS and those used to overcome stimulation induced artifacts. Proof of concept was also established for a single DBS lead triggering bi-hemispheric delivery of therapeutic stimulation. Responsive DBS was applied to treat TS related motor and vocal tics through the application of three different experimental paradigms. The approach was safe and effective in a subset of individuals. The use of different devices in this study was not aimed at making between device comparisons, but rather, the study was adapted to the current state of the art in technology. Overall, four of the chronic responsive eligible subjects met the primary outcome variable for clinical effectiveness. Cortical physiology was used to trigger responsive DBS when therapy was limited by stimulation induced artifacts.

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Multispectral brain morphometry in Tourette syndrome persisting into adulthood.

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Multispectral brain morphometry in Tourette syndrome persisting into adulthood.

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