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Katja Biermann-Ruben,
Anastasia Miller, Stephanie Franzkowiak,
Jennifer Finis,
Bettina Pollok,
Claudia Wach,
Martin Südmeyer,
Melanie Jonas,
Götz Thomalla,
Kirsten Müller-Vahl,
Alexander Münchau,
Alfons Schnitzler
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ABSTRACT: 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 one's 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.
NeuroImage 07/2012; 63(1):119-25. · 5.89 Impact Factor
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ABSTRACT: 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.
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.
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.
PLoS ONE 01/2012; 7(1):e27850. · 4.09 Impact Factor
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Stephanie Franzkowiak,
Bettina Pollok,
Katja Biermann-Ruben,
Martin Südmeyer,
Jennifer Paszek,
Melanie Jonas,
Götz Thomalla,
Tobias Bäumer,
Michael Orth,
Alexander Münchau,
Alfons Schnitzler
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ABSTRACT: 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.
Movement Disorders 09/2010; 25(12):1960-6. · 4.51 Impact Factor
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ABSTRACT: Long-term potentiation (LTP) and long-term depression (LTD) play important roles in mediating activity-dependent changes in synaptic transmission and are believed to be crucial mechanisms underlying learning and cortical plasticity. In human subjects, however, the lack of adequate input stimuli for the induction of LTP and LTD makes it difficult to study directly the impact of such protocols on behavior.
Using tactile high- and low-frequency stimulation protocols in humans, we explored the potential of such protocols for the induction of perceptual changes. We delivered tactile high-frequency and low-frequency stimuli (t-HFS, t-LFS) to skin sites of approximately 50 mm2 on the tip of the index finger. As assessed by 2-point discrimination, we demonstrate that 20 minutes of t-HFS improved tactile discrimination, while t-LFS impaired performance. T-HFS-effects were stable for at least 24 hours whereas t-LFS-induced changes recovered faster. While t-HFS changes were spatially very specific with no changes on the neighboring fingers, impaired tactile performance after t-LFS was also observed on the right middle-finger. A central finding was that for both t-LFS and t-HFS perceptual changes were dependent on the size of the stimulated skin area. No changes were observed when the stimulated area was very small (< 1 mm2) indicating special requirements for spatial summation.
Our results demonstrate differential effects of such protocols in a frequency specific manner that might be related to LTP- and LTD-like changes in human subjects.
BMC Neuroscience 02/2008; 9:9. · 3.04 Impact Factor
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ABSTRACT: Adopting the patterns of theta burst stimulation (TBS) used in brain-slice preparations, a novel and rapid method of conditioning the human brain has recently been introduced. Using short bursts of high-frequency (50 Hz) repetitive transcranial magnetic stimulation (rTMS) has been shown to induce lasting changes in brain physiology of the motor cortex. In the present study, we tested whether a few minutes of intermittent theta burst stimulation (iTBS) over left primary somatosensory cortex (SI) evokes excitability changes within the stimulated brain area and whether such changes are accompanied by changes in tactile discrimination behavior. As a measure of altered perception we assessed tactile discrimination thresholds on the right and left index fingers (d2) before and after iTBS. We found an improved discrimination performance on the right d2 that was present for at least 30 min after termination of iTBS. Similar improvements were found for the ring finger, while left d2 remained unaffected in all cases. As a control, iTBS over the tibialis anterior muscle representation within primary motor cortex had no effects on tactile discrimination. Recording somatosensory evoked potentials over left SI after median nerve stimulation revealed a reduction in paired-pulse inhibition after iTBS that was associated but not correlated with improved discrimination performance. No excitability changes could be found for SI contralateral to iTBS. Testing the performance of simple motor tasks revealed no alterations after iTBS was applied over left SI. Our results demonstrate that iTBS protocols resembling those used in slice preparations for the induction of long-term potentiation are also effective in driving lasting improvements of the perception of touch in human subjects together with an enhancement of cortical excitability.
Experimental Brain Research 02/2008; 184(1):1-11. · 2.39 Impact Factor
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ABSTRACT: Abstract
Background
Long-term potentiation (LTP) and long-term depression (LTD) play important roles in mediating activity-dependent changes in synaptic transmission and are believed to be crucial mechanisms underlying learning and cortical plasticity. In human subjects, however, the lack of adequate input stimuli for the induction of LTP and LTD makes it difficult to study directly the impact of such protocols on behavior.
Results
Using tactile high- and low-frequency stimulation protocols in humans, we explored the potential of such protocols for the induction of perceptual changes. We delivered tactile high-frequency and low-frequency stimuli (t-HFS, t-LFS) to skin sites of approximately 50 mm<sup>2 </sup>on the tip of the index finger. As assessed by 2-point discrimination, we demonstrate that 20 minutes of t-HFS improved tactile discrimination, while t-LFS impaired performance. T-HFS-effects were stable for at least 24 hours whereas t-LFS-induced changes recovered faster. While t-HFS changes were spatially very specific with no changes on the neighboring fingers, impaired tactile performance after t-LFS was also observed on the right middle-finger. A central finding was that for both t-LFS and t-HFS perceptual changes were dependent on the size of the stimulated skin area. No changes were observed when the stimulated area was very small (< 1 mm<sup>2</sup>) indicating special requirements for spatial summation.
Conclusion
Our results demonstrate differential effects of such protocols in a frequency specific manner that might be related to LTP- and LTD-like changes in human subjects.
BMC Neuroscience. 01/2008;
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Stephanie Franzkowiak
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ABSTRACT: Das Gilles de la Tourette Syndrom (GTS) ist eine neuropsychiatrische Erkrankung, die durch das Auftreten von motorischen und vokalen Tics gekennzeichnet ist. Es gibt Hinweise darauf, dass motorische Regelkreise bei GTS-Patienten gestört sind. Als Hauptursache von GTS wird eine abnorme Basalganglienaktivität angenom-men, die möglicherweise zu einer Überaktivierung kortikaler Areale führt. Vo-rausgehende Studien zeigten eine verstärkte Exzitabilitität des primären Motor-kortex (M1) bei GTS-Patienten in Ruhe, die möglicherweise mit der Tic-Entstehung in Zusammenhang steht. Der Aktivitätsverlauf während der Ausfüh-rung einfacher voluntarischer Bewegungen wurde bisher kaum untersucht. Wei-terhin wurden eine erhöhte Sensitivität gegenüber externen Stimuli sowie eine veränderte sensomotorische Integration bei GTS-Patienten nachgewiesen. In der vorliegenden Arbeit wurde die kortikale oszillatorische Aktivität bei GTS-Patienten und gesunden Kontrollprobanden während motorischer und sensori-scher Verarbeitung mittels Magnetenzephalographie (MEG) untersucht. Von be-sonderem Interesse war die oszillatorische Aktivität im Alpha- und Beta-Frequenzband, da diese Rhythmen im primären sensomotorischen Kortex (S1/M1) auftreten. Alpha-Oszillationen (8-12 Hz) werden insbesondere im primä-ren somatosensorischen Kortex (S1) generiert und sind somit eher mit sensorischer Verarbeitung assoziiert, Beta-Oszillationen (13-24 Hz) dagegen sind in M1 lokali-siert und. Im ersten Versuchsteil führten beide Gruppen voluntarische Fingerbe-wegungen aus, während die Gehirnaktivität mittels MEG aufgezeichnet wurde. Die Analyse der lokalen oszillatorischen Aktivität erbrachte einen signifikanten Unterschied in der zeitlichen Modulation der rhythmischen Beta-Aktivität. Vor Bewegungsbeginn und während Bewegungsausführung war die Amplitude der ereigniskorrelierten Desynchronisation (event-related-desynchronization; ERD), die einen Zustand motorkortikaler Aktivität darstellt, im kontralateralen M1 in der Patientengruppe signifikant erhöht. Nach Bewegungstermination zeigte sich in der Patientengruppe eine signifikant stärkere Inhibition im ipsilateralen M1, die durch das Maß der ereigniskorrelierten Synchronisation (event-related-synchronization; ERS) gemessen wurde. Diese Maße korrelierten in der Patienten-gruppe miteinander, jedoch nicht in der Kontrollgruppe. Des Weiteren zeigte sich eine negative Korrelation zwischen der ipsilateralen Inhibition und der Tic-Schwere. Diese Daten deuten auf ein abnormes Aktivitätsmuster von erhöhter Aktivität gefolgt von erhöhter Inhibition bei GTS-Patienten hin. Die erhöhte M1-Aktivität im kontralateralen M1 spiegelt möglicherweise ein pathophysiologisches Korrelat von GTS wider. Im Gegensatz dazu deutet die inverse Korrelation zwi-schen der gesteigerten ipsilateralen Inhibition und der Tic-Schwere auf einen Kompensationsmechanismus hin. Patienten, die eine stärkere Inhibition aufwie-sen, waren geringer von Tics betroffen. Die Analyse der kortiko-kortikalen Kohä-renz als Maß der funktionellen Interaktion zeigte eine erhöhte funktionelle Inter-aktion zwischen dem kontralateralen M1 und dem supplementären motorischen Areal (SMA) besonders in der Bewegungsvorbereitungs und -ausführungsphase in der Patientengruppe. Dieser Befund könnte einen Hinweis auf die bei Patienten vermutete abnorm verstärkte Afferenz aus den Basalganglien liefern, die schließ-lich zu einer Aktivitätssteigerung motorkortikaler Aktivität führt. Alternativ könn-te es sich um eine adaptive Änderung des motorischen Systems handeln, die der Tic-Entstehung entgegenwirkt. Im zweiten Versuchsteil wurde eine elektrische Stimulation am Nervus medianus appliziert und die lokale oszillatorische Aktivi-tät in S1 und in M1 untersucht. Die Ergebnisse zeigten eine signifikante Abnahme der Modulation des Alpha-Rhythmus bei GTS-Patienten. Sowohl ERD als auch ERS waren signifikant reduziert. Dieser Befund deutet auf eine Beteiligung des somatosensorischen Systems bei GTS-Patienten hin und könnte als Hinweis auf einen Kompensationsmechanismus von S1 erklärt werden, um starke sensorische Afferenzen zu unterdrücken. Dies könnte verhindern, dass durch eine verstärkte Weiterleitung der Informationen von S1 zu M1 Tics als Reaktion auf externe Reize ausgelöst werden.
Zusammenfassend zeigen die Daten der vorliegenden Arbeit Aktivitätsverände-rungen in S1/M1 von GTS-Patienten. Während sich bei der Verarbeitung volunta-rischer Bewegungen bei GTS-Patienten ein Muster von verstärkter Aktivierung gefolgt von verstärkter Inhibition zeigt, sind nach sensorischer Stimulation die Aktivierung sowie die Inhibition bei GTS-Patienten verringert. Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder characterized by multiple motor and vocal tics. There is evidence for an abnormal processing of motor and sensory information which is mainly due to alterations of cortico-striato-thalamo-cortical circuits rising within the basal ganglia. Using magnetoen-cephalography (MEG), a non-invasive method to record neuromagnetic brain ac-tivity, cortical oscillatory activity was investigated in GTS-patients and healthy control subjects during voluntary finger movements and during electrical stimula-tion of the median nerve. Typically, voluntary movements are accompanied by a modulation of cortical rhythms of the primary sensorimotor cortex (S1/M1) indi-cated by event-related-desynchronization (ERD) and event-related-synchroni-zation (ERS). ERD has been associated with increased excitability of S1/M1, whereas ERS most likely represents its deactivation. ERD and ERS occur at alpha- and beta-frequency. The alpha-rhythm (8-12 Hz) is generated mainly in the pri-mary somatosensory cortex (S1) and is related to sensory processing whereas the beta-rhythm (13-24 Hz) is generated mainly in the primary motor cortex (M1). In the first study, participants performed simple voluntary movements. The results of the first analyses indicate increased activation of the contralateral M1 and a sig-nificantly stronger inhibition of the ipsilateral M1 at beta-frequency. Furthermore, the contralateral activation and the ipsilateral inhibition were significantly corre-lated with each other in GTS-patients but not in controls. Additionally, amplitudes of ipsilateral ERS and tic severity were inversely correlated. The observed pattern of increased activation prior to and during movement execution followed by in-creased inhibition after movement termination at beta-frequency in GTS suggests abnormally increased motor cortical activation possibly driving stronger inhibi-tion. While increased activation might reflect a pathophysiological correlate of GTS increased inhibition most likely represents a compensatory mechanism to suppress tics. The more efficient such inhibition is the better symptoms appear to be controlled.
The analyses of cerebro-cerebral coherence as a measurement of functional connec-tivity between brain areas revealed a significantly increased coherence between SMA and contralateral M1 in GTS-patients particularly during movement prepara-tion and execution. The increased functional connectivity might be driven by basal ganglia dysfunction possibly reflecting a pathophysiological marker of GTS. Al-ternatively, the increased coherence might represent an adaptive mechanism of the motor system to prevent tics.
In the second experiment, the oscillatory activity induced by sensory stimulation was investigated in GTS-patients compared to healthy control subjects. To this end, electrical stimulation was applied to the median nerve and local oscillatory activity within S1 and M1 was analyzed. The analysis showed a reduced ERD and ERS-amplitude at alpha-frequency while no differences at beta-frequency were evident. Therefore, one might speculate that the observed differences between GTS-patients and controls reflect an adaptation of the somatosensory system to compensate strong sensory input. Inhibiting sensory input to S1 might suppress exaggerated input to M1, thereby minimizing the number of tics initiated in re-sponse to external stimuli.
To summarize, the present studies indicate alterations of sensorimotor cortical activity in GTS-patients. During the performance of voluntary movements the data show a pattern of increased activation followed by increased inhibition in GTS-patients. In contrast, during processing of sensory information both activa-tion and inhibition were decreased in GTS-patients.
