Katja Biermann-Ruben

Structural Changes in the Somatosensory System Correlate with Tic Severity in Gilles de la Tourette Syndrome.

Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder characterized by multiple motor and vocal tics. Previous structural MRI studies have identified regional abnormalities in grey matter, especially in the basal ganglia. These findings are consistent with the assumption of alterations in cortico-striato-thalamo-cortical circuits and dopaminergic neurotransmission playing a major role in the pathophysiology of GTS. Additionally, recent imaging studies suggested an involvement of sensory-motor cortices in the pathophysiology of GTS. However, little is known about the role of white matter changes in GTS. In this study, we aimed to examine whether GTS is associated with abnormalities in white matter microstructure and whether these changes are correlated with tic severity. In a morphometric study based on diffusion tensor MRI of the whole brain, we compared brain tissue diffusion characteristics between 15 unmedicated adults with GTS without psychiatric co-morbidity and 15 healthy age- and sex-matched controls. We performed voxel-based morphometry (VBM) of regional fractional anisotropy (FA) values to identify regional differences in white matter microstructure between the groups. We also tested for a linear relationship between regional FA values and clinical scores of tic severity. Probabilistic fibre tracking was applied to characterize anatomical connectivity of those areas showing differences in regional FA. Compared with healthy controls, GTS patients showed bilateral FA increases in white matter underlying the post- and precentral gyrus, below the left supplementary motor area, and in the right ventro-postero-lateral part of the thalamus. The peak increase in FA was located below the left postcentral gyrus. Probabilistic tractography identified transcallosal and ipsilateral cerebello-thalamo-cortical pathways of the somatosensory system passing through this subcortical region. In patients, regional FA in this region showed an inverse linear relationship with tic severity. These findings demonstrate, for the first time, structural alterations in somatosensory pathways in GTS. Changes of water diffusion characteristics point towards reduced branching in somatosensory pathways in GTS patients. The negative correlation between higher regional FA values and fewer tics suggests that these alterations of white matter microstructure represent adaptive reorganization of somatosensory processing in GTS.

Investigating the human mirror neuron system by means of cortical synchronization during the imitation of biological movements

The human mirror neuron system (MNS) has recently been a major topic of research in cognitive neuroscience. As a very basic reflection of the MNS, human observers are faster at imitating a biological as compared with a non-biological movement. However, it is unclear which cortical areas and their interactions (synchronization) are responsible for this behavioural advantage. We investigated the time course of long-range synchronization within cortical networks during an imitation task in 10 healthy participants by means of whole-head magnetoencephalography (MEG). Extending previous work, we conclude that left ventrolateral premotor, bilateral temporal and parietal areas mediate the observed behavioural advantage of biological movements in close interaction with the basal ganglia and other motor areas (cerebellum, sensorimotor cortex). Besides left ventrolateral premotor cortex, we identified the right temporal pole and the posterior parietal cortex as important junctions for the integration of information from different sources in imitation tasks that are controlled for movement (biological vs. non-biological) and that involve a certain amount of spatial orienting of attention. Finally, we also found the basal ganglia to participate at an early stage in the processing of biological movement, possibly by selecting suitable motor programs that match the stimulus.

Right rolandic activation during speech perception in stutterers: a MEG study

The focus of our magnetoencephalographic (MEG) study was to obtain further insight into the neuronal organization of language processing in stutterers. We recorded neuronal activity of 10 male developmental stutterers and 10 male controls, while they listened to pure tones, to words in order to repeat them, and to sentences in order to either repeat or transform them into passive form. Stimulation with pure tones resulted in similar activation patterns in the two groups, but differences emerged in the more complex auditory language tasks. In the stutterers, the left inferior frontal cortex was activated for a short while from 95 to 145 ms after sentence onset, which was not evident in the controls nor in either group during the word task. In both subject groups, the left rolandic area was activated when listening to the speech stimuli, but in the stutterers, there was an additional activation of the right rolandic area from 315 ms onwards, which was more pronounced in the sentence than word task. Activation of areas typically associated with language production was thus observed also during speech perception both in controls and in stutterers. Previous research on speech production in stutterers has found abnormalities in both the amount and timing of activation in these areas. The present data suggest that activation in the left inferior frontal and right rolandic areas in stutterers differs from that in controls also during speech perception.

Altered intrahemispheric structural connectivity in Gilles de la Tourette syndrome

Gilles de la Tourette syndrome (GTS) is a common developmental neuropsychiatric disorder characterized by tics and frequent psychiatric comorbidities, often causing significant disability. Tic generation has been linked to disturbed networks of brain areas involved in planning, controlling and execution of actions, particularly structural and functional disorders in the striatum and cortico–striato–thalamo–cortical loops. We therefore applied structural diffusion tensor imaging (DTI) to characterize changes in intrahemispheric white matter connectivity in cortico-subcortical circuits engaged in motor control in 15 GTS patients without psychiatric comorbidities. White matter connectivity was analyzed by probabilistic fiber tractography between 12 predefined cortical and subcortical regions of interest. Connectivity values were combined with measures of clinical severity rated by the Yale Global Tic Severity Scale (YGTSS). GTS patients showed widespread structural connectivity deficits. Lower connectivity values were found specifically in tracts connecting the supplementary motor areas (SMA) with basal ganglia (pre-SMA–putamen, SMA–putamen) and in frontal cortico-cortical circuits. There was an overall trend towards negative correlations between structural connectivity in these tracts and YGTSS scores. Structural connectivity of frontal brain networks involved in planning, controlling and executing actions is reduced in adult GTS patients which is associated with tic severity. These findings are in line with the concept of GTS as a neurodevelopmental disorder of brain immaturity.

Coherence in consciousness: Paralimbic gamma synchrony of self-reference links conscious experiences

A coherent and meaningful percept of the world is essential for human nature. Consequently, much speculation has focused on how this is achieved in the brain. It is thought that all conscious experiences have reference to the self. Self‐reference may either be minimal or extended, i.e., autonoetic. In minimal self‐reference subjective experiences are self‐aware in the weak sense that there is something it feels like for the subject to experience something. In autonoetic consciousness, consciousness emerges, by definition, by retrieval of memories of personally experienced events (episodic memory). It has been shown with transcranial magnetic stimulation (TMS) that a medial paralimbic circuitry is critical for self‐reference. This circuitry includes anterior cingulate/medial prefrontal and posterior cingulate/medial parietal cortices, connected directly and via thalamus. We here hypothesized that interaction in the circuitry may bind conscious experiences with widely different degrees of self‐reference through synchrony of high frequency oscillations as a common neural event. This hypothesis was confirmed with magneto‐encephalography (MEG). The observed coupling between the neural events in conscious experience may explain the sense of unity of consciousness and the severe symptoms associated with paralimbic dysfunction. Hum Brain Mapp, 2010.

Motor-Cortical Interaction in Gilles de la Tourette Syndrome

Background In Gilles de la Tourette syndrome (GTS) increased activation of the primary motor cortex (M1) before and during movement execution followed by increased inhibition after movement termination was reported. The present study aimed at investigating, whether this activation pattern is due to altered functional interaction between motor cortical areas. Methodology/Principal Findings 10 GTS-patients and 10 control subjects performed a self-paced finger movement task while neuromagnetic brain activity was recorded using Magnetoencephalography (MEG). Cerebro-cerebral coherence as a measure of functional interaction was calculated. During movement preparation and execution coherence between contralateral M1 and supplementary motor area (SMA) was significantly increased at beta-frequency in GTS-patients. After movement termination no significant differences between groups were evident. Conclusions/Significance The present data suggest that increased M1 activation in GTS-patients might be due to increased functional interaction between SMA and M1 most likely reflecting a pathophysiological marker of GTS. The data extend previous findings of motor-cortical alterations in GTS by showing that local activation changes are associated with alterations of functional networks between premotor and primary motor areas. Interestingly enough, alterations were evident during preparation and execution of voluntary movements, which implies a general theme of increased motor-cortical interaction in GTS.

Increased sensory feedback in Tourette syndrome

Tourette syndrome (TS) is a neuro-psychiatric disorder being characterized by motor and phonic tics typically preceded by sensory urges. Given the latter the role of the sensory system and sensorimotor interaction in TS has recently gained increased attention. 12 TS patients and 12 matched control subjects performed two tasks, requiring simple finger movements: a Go/NoGo task and a self paced movement task. Neurophysiological data was recorded using magnetoencephalography (MEG). Event related responses around movement onset, i.e. motor field (MF) occurring directly prior to the movement and movement evoked field (MEF) immediately after movement onset were analyzed using dipole modeling. MF peak amplitudes did not differ between groups in either task. In contrast, in both tasks MEF peak amplitudes were increased in TS patients. Moreover, larger MEF amplitudes during self paced movements were inversely correlated with motor tic frequency and severity. Enlarged MEF amplitudes as a marker of early sensory feedback of ones own movements probably represent enlarged sensory input from the periphery resulting from altered subcortical gating. We conclude that TS patients exhibit altered sensory-motor processing involved in voluntary movement control, which might also be successful in tic control.

Right hemisphere contributions to imitation tasks

Humans imitate biological movements faster than non‐biological movements. The faster response has been attributed to an activation of the human mirror neuron system, which is thought to match observation and execution of actions. However, it is unclear which cortical areas are responsible for this behavioural advantage. Also, little is known about the timing of activations. Using whole‐head magnetoencephalography we recorded neuronal responses to single biological finger movements and non‐biological dot movements while the subjects were required to perform an imitation task or an observation task, respectively. Previous imaging studies on the human mirror neurone system suggested that activation in response to biological movements would be stronger in ventral premotor, parietal and superior temporal regions. In accordance with previous studies, reaction times to biological movements were faster than those to dot movements in all subjects. The analysis of evoked magnetic fields revealed that the reaction time benefit was paralleled by stronger and earlier activation of the left temporo‐occipital cortex, right superior temporal area and right ventral motor/premotor area. The activity patterns suggest that the latter areas mediate the observed behavioural advantage of biological movements and indicate a predominant contribution of the right temporo‐frontal hemisphere to action observation–execution matching processes in intransitive movements, which has not been reported previously.

Altered pattern of motor cortical activation-inhibition during voluntary movements in Tourette syndrome.

In patients with Gilles de la Tourette syndrome (GTS) alterations of motor cortex (M1) excitability at rest have been evidenced. In contrast, there has so far been little research into changes of motor cortical reactivity during the time course of voluntary movements in GTS patients. The present study investigates neuromagnetic event‐related desynchronization (ERD) and event‐related synchronization (ERS) of bilateral M1 in 11 GTS patients and 11 healthy control subjects. ERD represents motor cortical activation, whereas ERS most likely indicates its inhibition. Subjects performed a self‐paced finger movement task while magnetoencephalography was used to record neuromagnetic activity. In GTS patients, ERD at beta frequency was significantly increased in the contralateral hemisphere before and during movements, whereas ERS following movement termination was increased in M1 ipsilateral. Ipsilateral ERS was inversely correlated with tic severity as determined by the Yale Global Tic Severity Rating Scale. The data of the present study support the hypothesis that during voluntary movements, motor cortical reactivity is pathologically altered in GTS patients. The observed pattern of increased activation (ERD) prior to and during movement execution followed by increased inhibition (ERS) after movement termination at beta frequency suggests abnormally increased motor cortical activation, possibly driving stronger inhibition. The stronger this inhibition is, the better symptoms appear to be controlled.

Echoes from childhood--imitation in Gilles de la Tourette Syndrome.

Tourette syndrome patients are reported to show automatic imitation (echopraxia), but this has not yet been proven experimentally.