Motor excitability is reduced prior to voluntary movements in children and adolescents with Tourette syndrome

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.     

Examining the neural antecedents of tics in Tourette syndrome using electroencephalography

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the occurrence of motor and vocal tics. TS is associated with cortical–striatal–thalamic–cortical circuit dysfunction and hyper-excitability of cortical limbic and motor regions that lead to the occurrence of tics. Importantly, individuals with TS often report that their tics are preceded by premonitory sensory/urge phenomena (PU) that are described as uncomfortable bodily sensations that precede the execution of a tic and are experienced as an urge for motor discharge. While tics are most often referred to as involuntary movements, it has been argued by some that tics should be viewed as voluntary movements that are executed in response to the presence of PU. To investigate this issue further, we conducted a study using electroencephalography (EEG). We recorded movement-related EEG (mu- and beta-band oscillations) during (1) the immediate period leading up to the execution of voluntary movements by a group of individuals with TS and a group of matched healthy control participants, and (2) the immediate period leading up to the execution of a tic in a group of individuals with TS. We demonstrate that movement-related mu and beta oscillations are not reliably observed prior to tics in individuals with TS. We interpret this effect as reflecting the greater involvement of a network of brain areas, including the insular and cingulate cortices, the basal ganglia and the cerebellum, in the generation of tics in TS. We also show that beta-band desynchronization does occur when individuals with TS initiate voluntary movements, but, in contrast to healthy controls, desynchronization of mu-band oscillations is not observed during the execution of voluntary movements for individuals with TS. We interpret this finding as reflecting a dysfunction of physiological inhibition in TS, thereby contributing to an impaired ability to suppress neuronal populations that may compete with movement preparation processes.     

Premonitory urges are associated with decreased grey matter thickness within the insula and sensorimotor cortex in young people with Tourette syndrome

Tourette syndrome (TS) is a neurological disorder characterized by vocal and motor tics and is associated with cortical–striatal–thalamic–cortical circuit (CSTC) dysfunction and hyperexcitability of cortical limbic and motor regions, which are thought to lead to the occurrence of tics. Importantly, individuals with TS often report that their tics are preceded by ‘premonitory sensory phenomena’ (PSP) that are described as uncomfortable cognitive or bodily sensations that precede the execution of a tic, and are experienced as a strong urge for motor discharge. While the precise role played by PSP in the occurrence of tics is controversial, PSP are nonetheless of considerable theoretical and clinical importance in TS, not least because they form the core component in many of the behavioural therapies that are currently used in the treatment of tic disorders. In this study, we investigated the brain structure correlates of PSP. Specifically, we conducted a whole‐brain analysis of cortical (grey matter) thickness in 29 children and young adults with TS and investigated the association between grey matter thickness and PSP. We demonstrate for the first time that PSP are inversely associated with grey matter thickness measurements within the insula and sensorimotor cortex. We also demonstrate that grey matter thickness is significantly reduced in these areas in individuals with TS relative to a closely age‐ and gender‐matched group of typically developing individuals and that PSP ratings are significantly correlated with tic severity.     

Enhanced saccadic control in young people with Tourette syndrome despite slowed pro‐saccades

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics. Tics are repetitive and uncontrolled behaviours that have been associated with basal ganglia dysfunction. We investigated saccadic eye movements in a group of young people with TS but without co‐morbid ADHD. Participants performed two tasks. One required them to perform only pro‐saccade responses (pure pro‐saccade task). The other involved shifting, unpredictably, between executing pro‐ and anti‐saccades (mixed saccade task). We show that in the mixing saccade task, the TS group makes significantly fewer errors than an age‐matched control group, while responding equally fast. By contrast, on the pure pro‐saccade task, the TS group were shown to be significantly slower to initiate and to complete the saccades (longer movement duration and decreased peak velocity) than controls, while movement amplitude and direction accuracy were not different. These findings demonstrate enhanced shifting ability despite slower reflexive responding in TS and are discussed with respect to a disorder‐related adaptation for increased cognitive regulation of behaviour.     

Musical groove modulates motor cortex excitability: A TMS investigation

Groove is often described as a musical quality that can induce movement in a listener. This study examines the effects of listening to groove music on corticospinal excitability. Musicians and non-musicians listened to high-groove music, low-groove music, and spectrally matched noise, while receiving single-pulse transcranial magnetic stimulation (TMS) over the primary motor cortex either on-beat or off-beat. We examined changes in the amplitude of the motor-evoked potentials (MEPs), recorded from hand and arm muscles, as an index of activity within the motor system. Musicians and non-musicians rated groove similarly. MEP results showed that high-groove music modulated corticospinal excitability, whereas no difference occurred between low-groove music and noise. More specifically, musicians’ MEPs were larger with high-groove than low-groove music, and this effect was especially pronounced for on-beat compared to off-beat pulses. These results indicate that high-groove music increasingly engages the motor system, and the temporal modulation of corticospinal excitability with the beat could stem from tight auditory–motor links in musicians. Conversely, non-musicians’ MEPs were smaller for high-groove than low-groove music, and there was no effect of on- versus off-beat pulses, potentially stemming from suppression of overt movement. In sum, high-groove music engages the motor system, and previous training modulates how listening to music with a strong groove activates the motor system.     

Facilitation of corticospinal excitability during motor imagery of wrist movement with visual or quantitative inspection of EMG activity

The present study investigated facilitation of corticospinal excitability during motor imagery of wrist movement with visual or quantitative inspection of background electromyographic (EMG) activity. Ten healthy participants imagined wrist extension from a first-person perspective in response to a start cue. Transcranial magnetic stimulation was delivered to the motor cortex 2 sec. after the start cue. EMG signals were recorded from the extensor carpi radialis muscle. Trials with background EMG activity were discarded based on visual inspection. Both motor-evoked potential (MEP) and background EMG amplitudes increased during motor imagery. The amount of increase in MEP amplitude was positively correlated with the amount of increase in background EMG amplitude during motor imagery. The statistically significant increase in MEP amplitude during motor imagery disappeared when the effect of muscle activity was statistically eliminated or after trials with background EMG activity were discarded based on strict quantitative criteria. Facilitation of corticospinal excitability during motor imagery of wrist movement depends partially on muscle activity. Discarding background EMG activity during motor imagery based on visual inspection is not sufficient to equalize background EMG amplitude between resting and motor imagery. Discarding trials with background EMG activity through strict quantitative criteria is useful to equalize background EMG amplitude between at rest and during motor imagery.     

Cortico-spinal inhibition reflects time but not event preparation: neural mechanisms of preparation dissociated by transcranial magnetic stimulation.

Changes in cortico-spinal excitability related to time and event preparation were investigated by transcranial magnetic stimulation (TMS) of the motor cortex during the foreperiod of a movement-precuing task. Subjects performed a four alternative choice reaction time (RT) task involving a button-press with the index or middle finger (FI) of the left or right hand. Advance information about the to-be-signaled response was provided by a precue, which preceded the response signal by a 1 s foreperiod. The precue either indicated the hand (right or left) or FI (index or middle) with which the response would be executed or was uninformative. TMS was delivered to the left or right cortical hand area at one of five possible times during the foreperiod: -1000, -500, -333, -166 or 0 ms prior to the response signal. Surface EMG activity from a prime mover involved in flexion of the response FIs (Flexor digitorum superficialis) was used to measure the magnitude of the motor evoked potential (MEP) elicited by TMS. Cortico-spinal excitability--as assessed by the magnitude of the MEP evoked in the target muscle contralateral to the stimulated hemisphere--progressively decreased during the foreperiod. The identity of the precued responses, however, had no effect on MEP magnitude. These results suggest that preparation to respond at a particular time inhibited excitability of the cortico-spinal tract, while advance preparation to perform specific responses affected more central structures only.     

Transcranial magnetic stimulation in child psychiatry: disturbed motor system excitability in hypermotoric syndromes

Normal development and dysfunctions of motor system excitability can be investigated in vivo by means of single‐ and paired‐pulse transcranial magnetic stimulation (TMS). While different TMS‐parameters show different developmental time courses between 8 and 16 years of age, distinct dysfunctional patterns of motor system excitability can be demonstrated in child psychiatric disorders with hypermotoric behavior: in tic disorder, a shortened cortical silent period can be stated providing evidence for deficient inhibitory mechanisms within the sensorimotor loop, probably primarily at the level of the basal ganglia. In attention deficit hyperactivity disorder (ADHD), a decreased intracortical inhibition indicates deficient inhibitory mechanisms within the motor cortex (but enhancement of intracortical inhibition after oral intake of 10 mg methylphenidate). In children with comorbid ADHD and tic disorder, the findings of a reduced intracortical inhibition as well as a shortened cortical silent period provide evidence for additive effects at the level of motor system excitability. Thus, TMS allows us to obtain substantial insight into both the normal development and the neurobiological basis of hypermotoric syndromes in child psychiatry.     

Rapid plastic changes of human primary motor cortex with repetitive motor practice and transcranial magnetic stimulation

Excitability changes of human primary motor cortex are assumed to be associated with motor learning processes. To examine motor behavioral and neural mechanisms in these processes, the adaptive motor learning processes of the index finger abduction were investigated using motor evoked potential (MEP) elicited from the first dorsal interosseous and extensor carpi radialis muscles. Practice effects were examined on changes of MEP amplitudes elicited from these muscles during motor imagery. Given general consensus that the MEP amplitude change during motor imagery is a useful parameter reflecting changes in excitability of the human primary motor cortex, the present results, that MEP amplitudes of both muscles increased with repeated practice by the index finger abduction and that magnitudes of MEP amplitudes of both muscles (motor learning curves) were clearly different, suggested that participation of the muscles performing the index finger abduction gradually changed with practice. Short-term plastic changes of human primary motor cortex occur with repetitive practice and such adaptive change in human primary motor cortex is expressed in human voluntary movement that becomes more automatic.     

Interindividual Variability in Use-Dependent Plasticity Following Visuomotor Learning: The Effect of Handedness and Muscle Trained

Motor learning has been linked with increases in corticospinal excitability (CSE). However, the robustness of this link is unclear. In this study, changes in CSE associated with learning a visuomotor tracking task were mapped using transcranial magnetic stimulation (TMS). TMS maps were obtained before and after training with the first dorsal interosseous (FDI) of the dominant and nondominant hand, and for a distal (FDI) and proximal (biceps brachii) muscle. Tracking performance improved following 20 min of visuomotor training, while map area was unaffected. Large individual differences were observed with 18%–36% of the participants revealing an increase in TMS map area. This result highlights the complex relationship between motor learning and use-dependent plasticity of the motor cortex.     

Facilitation of motor evoked potentials and H-reflexes of flexor carpi radialis muscle induced by voluntary teeth clenching

In order to examine the effects of remote facilitation on cortical and spinal sites, we recorded motor evoked potentials (MEPs) and H-reflexes from the flexor carpi radialis muscle of 13 healthy subjects. The H-reflex was used to assess excitability changes at the spinal level, while the MEP following transcranial magnetic stimulation was used to study excitability changes at the cortical level. We induced remote facilitation by means of voluntary teeth clenching (VTC), the so-called Jendrassik maneuver, because this procedure is known to be effective and reliable. Although the facilitation induced by VTC was observed in both evoked potentials (i.e., H-reflex and MEP), which is consistent with previous reports, MEP onset latencies were shortened by VTC in proportion to an increased MEP amplitude, whereas the latencies of the H-reflex were not. Furthermore, statistically significant relationships between MEP latencies and amplitudes were observed in all subjects, whereas no such relationships were observed for the H-reflex. On the basis of these results, two neural pathways are presumed: one involving a release of pre-synaptic inhibition at the spinal level and the other involving an unmasking of lateral excitatory projections at the cortical level.     

Temporal aspects of passive movement-related corticomotor inhibition

We have previously shown that during rhythmic passive movement of the index finger, the amplitude of the motor evoke potential (MEP) of the first dorsal interosseous muscle (FDI) as the index finger moved through mid-range adduction, is significantly reduced compared to rest [Edwards, D. J., Thickbroom, G. W., Byrnes, M. L., Ghosh, S., & Mastaglia, F. L. (2002). Reduced corticomotor excitability with passive movement: A study using Transcranial Magnetic Stimulation. Human Movement Science 21, 533-540]. In the present study we have investigated the time-course of this phenomenon. We found that MEP amplitude was significantly reduced at the mid-range position in the first cycle of movement (50+/-6% of resting baseline values), and did not vary across subsequent cycles (10 cycles in 50 s), but that MEP amplitude returned to baseline values within 1s of cessation of movement. The results suggest that the pattern of afferent discharge set up by the kinematics of the movement acting at spinal or supraspinal levels underlies the inhibition observed, rather than an effect of central origin or a cumulative effect of ongoing cyclic movement.     

Effects of proprioceptive neuromuscular facilitation on the initiation of voluntary movement and motor evoked potentials in upper limb muscles

To better understand the mechanisms behind proprioceptive neuromuscular facilitation (PNF), an important method in motor rehabilitation, we investigated the effects of assuming a PNF posture relative to a neutral posture on the initiation of voluntary movement (Experiment 1) and the excitability of the motor cortex (Experiment 2) using a wrist extension task. The initiation of voluntary wrist movement was operationalized in terms of the electromyographic reaction time (EMG-RT), and the excitability of the motor cortex in terms of motor evoked potentials (MEPs). Compared to the neutral position, we found that (1) the facilitation position changed the muscle discharge order enhancing the movement efficiency of the joint, (2) the facilitation position led to a reduction in EMG-RT, the magnitude of which depended on the proximity of the muscle to the movement joint, and (3) MEP amplitude increased and MEP latency decreased in the facilitation position as a function of the proximity of the muscle to the joint. These findings corroborate the presumed effects of PNF and provide insights into the neurophysiological mechanisms underlying the PNF method.     

Negative emotional processing induced by spoken scenarios modulates corticospinal excitability

Emotion is assumed to facilitate the preparation of behavioral responses to environmental stimuli. In the present study, we examined whether emotional processing induced by spoken scenarios of positive and negative content, related to the self or to other people, modulates corticospinal excitability. Motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in 20 volunteers indicated that processing of negative emotional content increased MEP amplitude, regardless of the perspective taken in the scenario. By contrast, positive emotional processing did not reliably alter MEP amplitude. These results provide the first TMS evidence that the auditory processing of emotionally negative information triggers action preparation.     

The role of the cingulate cortex in the generation of motor tics and the experience of the premonitory urge-to-tic in Tourette syndrome

Tourette syndrome (TS) is a neurological disorder of childhood onset that is characterized by the occurrence of motor and vocal tics. TS is associated with cortical-striatal-thalamic-cortical circuit [CSTC] dysfunction and hyper-excitability of cortical limbic and motor regions that are thought to lead to the occurrence of tics. Individuals with TS often report that their tics are preceded by ‘premonitory sensory/urge phenomena’ (PU) that are described as uncomfortable bodily sensations that precede the execution of a tic and are experienced as a strong urge for motor discharge. While the precise role played by PU in the occurrence of tics is largely unknown, they are nonetheless of considerable theoretical and clinical importance as they form a core component of many behavioural therapies used in the treatment of tic disorders. Recent evidence indicates that the cingulate cortex may play an important role in the generation of PU in TS, and in ‘urges-for-action’ more generally. In the current study, we utilized voxel-based morphometry (VBM) techniques, together with ‘seed-to-voxel’ structural covariance network (SCN) mapping, to investigate the putative role played by the cingulate cortex in the generation of motor tics and the experience of PU in a relatively large group of young people with TS. Whole-brain VBM analysis revealed that TS was associated with clusters of significantly reduced grey matter volumes bilaterally within: the orbito-frontal cortex; the cerebellum; and the anterior and mid-cingulate cortex. Similarly, analysis of SCNs associated with bilateral mid- and anterior cingulate ‘seed’ regions demonstrated that TS is associated with increased structural covariance primarily with the bilateral motor cerebellum; the inferior frontal cortex; and the posterior cingulate cortex.     

The Premonitory Urge to Tic: Measurement,Characteristics, and Correlates in Older Adolescents and Adults

In addition to motor and/or vocal tics, many individuals with Tourette syndrome (TS) or chronic tic disorder (CTD) report frequent, uncomfortable sensory phenomena that immediately precede the tics. To date, examination of these premonitory sensations or urges has been limited by inconsistent assessment tools. In this paper, we examine the psychometric properties of a nine-item self-report measure, the Premonitory Urge to Tic Scale (PUTS) and examine the characteristics and correlates of the premonitory urge to tic in a clinical sample of 122 older adolescents and adults with TS or CTD. The PUTS demonstrated adequate internal consistency, temporal stability, and concurrent validity. Premonitory urges were endorsed by the majority of individuals. Most individuals reported some relief from the urges after completing a tic and being able to stop their tics even if only temporarily. Degree of premonitory urges was not significantly correlated with age, and we did not observe any gender differences. Degree of premonitory urges was significantly correlated with estimated IQ and tic severity, but not severity of comorbid obsessive–compulsive disorder or attention-deficit hyperactivity disorder. Also, it was not related to concomitant medication status. These findings represent another step forward in our understanding of the premonitory sensations associated with TS and CTD.     

Preparation and motor potentials in chronic tic and Tourette syndromes

Many studies have found that people with tic disorder show more difficulty when inhibiting an automated than a controlled response. Furthermore, although normal motor threshold and excitability are present, but reduced or impaired, motor inhibition seems manifest in patients with tic. In order to localize this inhibition impairment in tic disorder the present study examine two response-locked ERPs: the Bereitschaft (preparation BP) and the motor potentials (MP). The simple tic group showed faster BP latency and smaller amplitude than control and complex tic group and did not show a corresponding change in values with practice or with automated or controlled condition. The MP amplitudes revealed that whereas both controls and complex tic disorder showed a decrease in amplitude during control condition for both blocks, simple tic showed larger amplitude. Our ERP results are in agreement with RT results of a previous study. The explanation could lie with modulation in motor excitation inhibition circuits and seems worse in simple tics where the movements are more automatic and nonvoluntary.     

Impaired modulation of corticospinal excitability following subthreshold rTMS in focal hand dystonia

Previous studies have demonstrated that subthreshold 1 Hz repetitive transcranial magnetic stimulation (rTMS) causes a decrease in corticospinal excitability in neurologically normal subjects. The effects of subthreshold 1 Hz rTMS upon corticospinal excitability and intracortical inhibition in subjects with focal hand dystonia (FHD) is not yet clear. The purpose of this study was to examine the effects of low intensity 1 Hz rTMS upon these variables in control and FHD subjects. We recorded electromyographic (EMG) from the first dorsal interosseous (FDI) muscle of the dominant hands of seven control subjects, and seven affected hands of five FHD subjects. We used single and paired pulse TMS to examine motor evoked potential (MEP) amplitude, short interval intracortical inhibition (ICI) and silent period duration before, during and after 20 min of low intensity 1 Hz rTMS. MEP amplitude decreased significantly over the course of the rTMS in control subjects, but did not change in FHD subjects. Silent period duration was significantly longer in control subjects after rTMS, but there was no change in FHD subjects. There was no significant change in ICI after rTMS in either subject group, despite the rTMS intensity being set to preferentially activate intracortical inhibitory networks. This suggests that low intensity 1 Hz rTMS may have limited application in the normalisation of inhibitory function in FHD.     

Emotional stimuli modulate readiness for action: A transcranial magnetic stimulation study

Emotional stimuli may prime the motor system and facilitate action readiness. Direct evidence for this effect has been shown by recent studies using transcranial magnetic stimulation (TMS). When administered over the primary motor cortex involved in responding, TMS pulses elicit motor-evoked potentials (MEPs) in the represented muscles. The amplitudes of these MEPs reflect the state of corticospinal excitability. Here, we investigated the dynamic effects of induced emotions on action readiness, as reflected by corticospinal excitability. Subjects performed a choice task while viewing task-irrelevant emotional and neutral pictures. The pattern of MEP amplitudes showed a typical increase as the TMS pulse was presented closer in time to the imminent response. This dynamic pattern was amplified by both pleasant and unpleasant emotional stimuli, but more so when unpleasant pictures were viewed. These patterns present novel evidence in support of the notion that emotional stimuli modulate action readiness.     

Modulations of use-dependent excitability changes of human motor cortex (M1) by practice condition

Effects of repetitive index finger abductions on excitability changes in the human primary motor cortex (Ml) are assumed to be dependent on practice conditions of the task. To address how different effects occur dependent on various practice conditions, motor evoked potentials (MEPs) elicited from the first dorsal interosseous (FDI) muscle were investigated. Practice effects on the index finger abduction were examined for changes in excitability of first dorsal interosseous muscle under three forearm position changes (neutral vs prone) and two muscle contraction modes (isometric vs isotonic). Analysis showed that after practice MEP amplitude increased in the prone position but not in the neutral position and MEP increases in the isotonic contraction were larger than those in the isometric mode. These results suggest that use-dependent excitability changes are largely dependent on practice conditions because the amount of afferent input depends on the practice conditions.