Hypertonia in childhood secondary dystonia due to cerebral palsy is associated with reflex muscle activation

It is often assumed that co‐contraction of antagonist muscles is responsible for increased resistance to passive movement in hypertonic dystonia. Although co‐contraction may certainly contribute to hypertonia in some patients, the role of reflex activation has never been investigated. We measured joint torque and surface electromyographic activity during passive flexion and extension movements of the elbow in 8 children with hypertonic arm dystonia due to dyskinetic cerebral palsy. In all cases, we found significant phasic electromyographic activity in the lengthening muscle, consistent with reflex activity. By correlating activation with position or velocity of the limb, we determined that some children exhibit position‐dependent activation, some exhibit velocity‐dependent activation, and some exhibit a mixed pattern of activation. We conclude that involuntary or reflex muscle activation in response to stretch may be a significant contributor to increased tone in hypertonic dystonia, and we conjecture that this activation may be more important than co‐contraction for determining the resistance to passive movement. © 2009 Movement Disorder Society     

Task-dependent modulation of silent period duration in focal hand dystonia.

Focal hand dystonia (FHD) is a movement disorder that is also associated with impaired sensory function and sensorimotor integration. The aim of this study was to assess the modulation of inhibitory function in the motor cortex during the performance of four motor tasks (isometric pinch grip, writing, texture discrimination, and a phasic control task) in 8 FHD and 8 control subjects. The affected hands of the FHD subjects and the dominant hands of the control subjects were tested. Inhibitory function was assessed using transcranial magnetic stimulation to evoke a silent period in the ongoing electromyographic activity of the target muscle (first dorsal interosseous). There was no difference between FHD subjects and control subjects in silent period duration, which was significantly longer during the phasic texture discrimination and phasic control task than during the isometric pinch or writing. This finding suggests that the phasic nature of the task may increase cortical inhibitory function, rather than the sensory discrimination task itself. The accuracy of texture discrimination was significantly lower in FHD subjects than in control subjects. Sensory discrimination tasks do not appear to directly modulate the inhibitory processes responsible for the duration of the silent period.     

Changes of muscle excitability of the hand contralateral to a task performing one: a transcranial magnetic stimulation study]

It used to be considered that unilateral movements of distal limb parts are associated only with contralateral motor cortical activity. Recent neuroimaging studies, however, suggest that the motor cortex ipsilateral to a task-performing hand is also activated, and that motor patterns in one hand affect the degree of the activity of the ipsilateral motor cortex. If so, muscles of the hand contralateral to a task-performing one may change those excitability depending on types of tasks. We studied eight subjects who performed three different finger tasks by one hand: (a) pinch, (b) sequential finger opposition, and (c) tactile discrimination. Transcranial magnetic stimulation was delivered by a figure eight coil over the hemisphere ipsilateral to a task-performing hand. Motor evoked potentials and background electromyographic activities were recorded from the opponens pollicis muscle contralateral to the stimulated hemisphere. On average, the motor evoked potentials were larger during tactile discrimination task than those at rest in either hand (p < 0.01). Background electromyographic activities in the left hand increased significantly during right hand tactile discrimination task (p < 0.01), whilst those in the right hand did not change during the left hand performance (p > 0.05). These findings suggest the followings: (1) the hand muscle contralateral to a task performing one changes its excitability depending on types of tasks; and (2) increment of excitability of the left hand muscle associated with right hand tactile discrimination is greater than that of the right hand one in association with the same task by the left hand, thus supporting the idea that there is a functional asymmetry between the right and left motor cortex in respect of motor performance.     

Topographic differences in task-dependent facilitation of magnetic motor evoked potentials

OBJECTIVE: To look for differences in task-dependent facilitation of magnetic motor evoked potentials (MEPs) in proximal and distal upper extremity muscles. BACKGROUND: Postexercise facilitation of MEPs has been demonstrated repeatedly in forearm muscles. Proximal muscles are prominently involved in limb stabilization, a largely isometric activity. In contrast, distal hand muscles specialize in precision movements. Based on these functional differences between proximal and distal muscles, we postulated that there might be topographic differences in task-dependent facilitation of MEPs. METHODS: We studied the effects of isometric exercise and a precision grip task on MEPs in proximal and distal upper extremity muscles. RESULTS: Isometric exercise of the target muscle was associated with significant facilitation of MEPs in biceps and extensor carpi radialis muscles, but not in first dorsal interosseous or abductor digiti minimi muscles. In contrast, a precision grip task was associated with significant post-task facilitation of MEPs in first dorsal interosseous, but not in extensor carpi radialis. CONCLUSIONS: These differences in the facilitation of MEPs depending on the motor task and whether the muscle is proximal or distal may reflect the relative importance of proximal muscles in maintaining posture.     

Abnormalities of inhibitory neuronal mechanisms in the motor cortex of patients with schizophrenia

BACKGROUND: Focal transcranial magnetic stimulation (TMS) of the motor cortex was used to study two cortically activated inhibitory neuronal mechanisms that suppress ongoing tonic voluntary electromyographic activity in contralateral (postexcitatory inhibition [PI]) and ipsilateral (transcallosal inhibition [TI]) hand muscles. The PI follows the corticospinally mediated excitatory motor response (MEP) and is influenced by dopaminergic neurotransmission. TI reflects transcallosally mediated inhibition of the contralateral motor cortex, leading to motor inhibition in muscles ipsilateral to stimulation. PI and TI were studied to explore whether dopaminergic neurotransmission or interhemispheric transfers are altered in schizophrenia. METHODS: TMS was performed in 16 patients with this disease and in 16 healthy control subjects. Surface electromyographic activity was recorded bilaterally from the first dorsal interosseous muscle during a sustained strong isometric contraction. RESULTS: When compared with the findings in healthy subjects, patients with schizophrenia had a significantly longer PI and TI. The changes of the PI support the notion of an overactivity of the central dopaminergic system in schizophrenia. CONCLUSION: The prolonged TI suggests an abnormal activation of interhemispheric connections between the motor cortices and may be related to previously reported pathology of the corpus callosum in schizophrenic patients.     

Focal hand dystonia, mirror dystonia and motor overflow

Focal hand dystonia (FHD) is a syndrome of sustained muscle contraction, frequently causing twisting and repetitive movements or abnormal postures of the hand. Motor overflow, defined as unintentional muscle contraction that accompanies but is anatomically distinct from the primary dystonic movement, is a frequent but often unrecognized feature of FHD. In this series of eight patients with FHD, we describe two patterns of motor overflow, termed "ipsilateral overflow" and "contralateral overflow", and contrast it with the phenomenon termed "mirror dystonia". These findings extend the phenomenology and provide evidence for widespread abnormalities of motor control in patients with focal hand dystonia.     

Stumbling reactions in man: influence of corticospinal input

The aim of this study was to evaluate the degree of contribution of supraspinal input to the generation of the compensatory leg muscle activation following stance perturbation. Therefore, evoked motor response (EMR) input–output relations of two different motor tasks were compared at 3 distinct periods: (1) the basic period of muscular activity during standing, i.e. when no additional cortical or spinal activity due to the different tasks is to be expected, (2) the pre-movement period with low background activity, when different spinal and cortical inputs to the motoneuronal pool can be assumed and (3) the period of plateau EMG activity of compensatory and voluntary motor task. Transcranial magnetic stimulation (TMS) just below the motor threshold was applied randomly at 19 different time-intervals before and during the onset of stance perturbation and for comparison during an equivalent voluntary foot-dorsiflexion task. Recordings of electromyographic (EMG) activity from the tibialis anterior (TA) and corresponding ankle-joint movements were made from both legs. Forward-directed displacements were induced by randomly-timed ramp impulses of constant acceleration upon a moveable platform. For comparison, leg muscle EMG was recorded during isometric foot dorsiflexion during stance while leaning back against a support. The stance perturbations were followed by a compensatory response (CR) in the TA with a mean onset time of 81 ms. During the basic period of muscular activity and the period of plateau EMG activity there was no significant difference of the input–output relation between stance perturbation and the voluntary motor task. However, in the voluntary task compared with the CR, there was significantly greater input–output relation (facilitation) of the EMR in the TA following TMS, which may be related to an increased cortical influence. In contrast to this result of the CR following stance perturbation, a facilitation of the EMR was described for hand muscles under corresponding conditions of automatic compensation for muscle stretch, suggesting a transcortical reflex loop. This difference in the results from upper and lower extremity muscles favors the assumption of a predominantly spinal generation of the TA-CR following stance perturbation.     

Central motor conduction studies and diagnostic magnetic resonance imaging in children with severe primary and secondary dystonia

Aim Dystonia in childhood has many causes. Imaging may suggest corticospinal tract dysfunction with or without coexistent basal ganglia damage. There are very few published neurophysiological studies on children with dystonia; one previous study has focused on primary dystonia. We investigated central motor conduction in 62 children (34 males, 28 females; age range 3–19y, mean age 10y 8mo, SD 4y 8mo) with severe dystonia to evaluate corticospinal tract integrity before consideration for deep brain stimulation. Method Distal motor and F‐wave latencies were measured in the ulnar and/or posterior tibial nerves. Transcranial magnetic stimulation was applied over the motor cortex and motor‐evoked potentials were recorded in the activated abductor digiti minimi and/or abductor hallucis muscles. Central motor conduction time (CMCT) was calculated using the F‐wave method. Results CMCT was normal in 50 out of 62 patients; 12 patients showed prolonged CMCT to upper and/or lower limbs. Most children with severe primary and secondary dystonia had normal CMCT, indicating corticospinal tract integrity despite abnormal imaging in 42 out of 50 patients. Abnormal CMCT was found in two out of 12 patients with normal imaging. Interpretation This study provides new CMCT data for children with severe primary and secondary dystonia. Over 50% of children with evidence of periventricular white‐matter damage from magnetic resonance imaging had normal CMCT, challenging traditional pathophysiological models. This is consistent with recent diffusion tensor imaging in children with periventricular white‐matter damage, showing disruption of sensory connections rather than corticospinal tract damage. CMCT helps refine our understanding of imaging changes in complex motor disorders of childhood.     

Cerebellar TMS Evokes a Long Latency Motor Response in the Hand during a Visually Guided Manual Tracking Task

Previous studies showed that transcranial magnetic stimulation (TMS) to the cerebellum evokes a long latency motor response in the soleus muscle during a postural task. The cerebellum is activated not only during postural tasks but also during motor tasks for which eye–hand coordination is required. The purpose of this study was to investigate whether TMS over the cerebellum evokes long latency motor responses in the hand during a visually guided manual tracking task. Eight healthy humans tracked an oscillatory moving target with the right index finger or pointed the finger at a stationary target, and TMS was delivered to the scalp over the cerebellum during the motor tasks. Trials with sham TMS were inserted between the trials with cerebellar TMS. The trajectory of finger movement fluctuated 92 ms after cerebellar TMS with a 24% probability during tracking of a moving target. The fluctuation was preceded by an electromyographic burst in the first dorsal interosseous muscle starting at 65 ms after TMS. The probability of fluctuation evoked by cerebellar TMS was significantly larger than that evoked by sham TMS during tracking of a moving target. This significant difference was absent in trials during which subjects pointed their index finger at a stationary target. These findings indicate that cerebellar TMS evokes a long latency motor response during a visually guided manual tracking task. The long latency motor response may be related to cerebellar activity associated with eye–hand coordination or to the detection of and correction for visuomotor errors.     

The effect of cutaneous input on intracortical inhibition in focal task‐specific dystonia

In normal subjects short interval intracortical inhibition (SICI) is topographically modulated by cutaneous input, which may be important for focusing muscle activation during tasks. In patients with writer's cramp, a task‐specific focal dystonia characterized by inappropriate and excessive muscle activation of the upper limb during certain motor tasks, intracortical inhibition is reduced at rest and lacks the normal topographically‐specific modulation during motor tasks. In the present study we investigated whether cutaneous input modulated SICI in a group of patients with writer's cramp and a control group of subjects. Electromyographic recordings were made from the right first dorsal interosseous (FDI), abductor pollicis brevis (APB), and abductor digiti minimi (ADM) muscles. Brief electrical stimuli were applied to either digit II or digit V with ring electrodes. SICI was investigated using a paired transcranial magnetic stimulation paradigm employing interstimulus intervals of 1–15 ms. Cutaneous input from both digit II and digit V modulated motor evoked potentials and SICI in a topographically‐specific manner in control subjects. In contrast, cutaneous input failed to modulate motor evoked potentials or SICI in the focal hand dystonia patients. These results provide further evidence of abnormal sensorimotor integration in focal hand dystonia. © 2007 Movement Disorder Society     

Hand cramps: clinical features and electromyographic patterns in a focal dystonia

We studied 19 patients with hand cramps, including writer's cramp, typist's cramp, piano, and guitar player's cramp. EMGs were recorded while patients performed the task triggering the cramps. Ten patients with dystonic cramps had EMGs with generalized muscle spasms with co-contraction of agonist and antagonist muscles. In three patients with simple cramps that involved one to three fingers, specific muscle groups showed co-contracting bursts that lasted longer than normal. The physiological abnormalities support the interpretation that hand cramp is a focal dystonia, characterized by both excessive muscle activity and defective fine motor control.     

Reversal of handedness effects on bimanual coordination in adults with Down syndrome

Background Research on unimanual tasks suggested that motor asymmetries between hands may be reduced in people with Down syndrome. Our study examined handedness (as assessed by hand performance) and perceptual–motor integration effects on bimanual coordination. Methods Adults with Down syndrome (13 non‐right‐handed, 22 right‐handed), along with comparison groups of adults (16 non‐right‐handed, 21 right‐handed) and children (15 non‐right‐handed, 22 right‐handed) without Down syndrome, drummed with auditory, verbal and visual instructions. Results In contrast to handedness effects in the children and adults without Down syndrome, right‐handed participants with Down syndrome led more with the left hand, and had lower coordination stability than non‐right‐handed participants with Down syndrome. Conclusions The reversed handedness effect during bimanual coordination suggests a complex relationship between handedness and task requirements in adults with Down syndrome.     

The influence of task characteristics on the intermanual asymmetry of motor overflow.

The two studies reported here were designed to test the proposition that greater motor overflow occurs when movements are performed by the non-dominant hand. Unlike previous studies using normal adults, the task in these studies did not require force production. In the first study, a group of 19 right-handed participants performed unweighted finger lifting. That the frequency of motor overflow occurrence was the same regardless of which hand performed the task, did not support findings from other studies where tasks involving force production resulted in more overflow when performed by the non-dominant hand. To investigate further the influence of task characteristics on motor overflow occurrence, in the second study participants were required to remember and reproduce a prescribed sequence of four finger lifts. Left- and right-handed participants (N = 30) performed both single and sequenced finger lifting. The relative frequency of motor overflow (unintended lifts of fingers of the passive hand) was compared between hand preference groups, active hand and task type (single/sequenced). Contrary to the expectation that motor overflow would be greater for the sequenced finger lifting task, overflow was exhibited with a significantly greater frequency on single finger lifting. This finding indicates that task characteristics influence the pattern of overflow occurrence in normal adults. The task used in this study did not involve force production and did not result in an intermanual asymmetry of motor overflow. This contrasts with findings from other studies requiring adults to exert forces where greater overflow occurred when the non-dominant hand was active. However, this study confirms previous findings which show that left-handers produce greater overflow compared to right-handers regardless of the task being performed and the hand performing the task.     

Corticospinal excitability accompanying ballistic wrist movements in primary dystonia.

Current models of basal ganglia dysfunction in primary dystonia propose that the excessive muscle activity results from an increase in the excitability of the primary motor cortex. Neurophysiological and neuroimaging studies, however, have shown consistently reduced movement-related sensorimotor cortical activity. To explore this paradox, we used transcranial magnetic stimulation (TMS) to examine changes in corticospinal excitability preceding and during ballistic movements of the wrist in 9 patients with primary dystonia affecting the arm and 9 matched control subjects. The onset time, rate of rise, and duration of changes in the excitability of corticospinal projections to the agonist muscle were normal in the patients with dystonia. Increases in excitability were selective to the initial agonist muscle, suggesting that the spatial recruitment of corticospinal neurons was normal. Nonetheless, movements were slower in the patients by an average of 26%. The onset of the first agonist muscle burst was normal in magnitude and timing but the activity in this muscle subsequently became attenuated as movement progressed. Muscle activity in antagonist and proximal muscles of the upper arm was reduced significantly in the dystonia patients. These findings support the view that movement preparation and initiation at the level of the primary motor cortex is normal in patients with dystonia. Bradykinesia could not be attributed to co-contraction or overflow of activity and was associated with reduced rather than excessive muscle activity.     

Motor ‘surround inhibition’ is not correlated with activity in surround muscles

Surround inhibition (SI) is a neural process that has been extensively investigated in the sensory system and has been recently probed in the motor system. Muscle‐specific modulation of corticospinal excitability at the onset of an isolated finger movement has been assumed to reflect the presence of SI in the motor system. This study attempted to characterise this phenomenon in a large cohort of normal volunteers and investigate its relationship with muscle activity in the hand. Corticospinal excitability of the pathways projecting to three hand muscles [first dorsal interosseus (FDI), abductor pollicis brevis (APB) and abductor digiti minimi (ADM)] and electromyographic (EMG) activity of the same muscles were assessed in 31 healthy volunteers during an isolated index finger movement. In the agonist FDI muscle both corticospinal excitability and EMG activity were found to be increased at the onset of the movement (P < 0.001 and P < 0.001, respectively). On the contrary, in the surround ADM, there was dissociation between the corticospinal excitability (decreased: P < 0.001) and EMG activity (increased: P < 0.001). Cross‐correlation analysis of the EMG activity showed that neuronal signals driving the agonist and surround muscles are not synchronised when SI is present. The results suggest a distinctive origin of the neuronal signals driving the agonist and surround muscles. In addition, they indicate that cortical output might be simultaneously modulated by voluntary and non‐voluntary activity, generated in cortical and subcortical structures, respectively.     

The Influence of Task Characteristics on the Intermanual Asymmetry of Motor Overflow

The two studies reported here were designed to test the proposition that greater motor overflow occurs when movements are performed by the non-dominant hand. Unlike previous studies using normal adults, the task in these studies did not require force production. In the first study, a group of 19 right-handed participants performed unweighted finger lifting. That the frequency of motor overflow occurrence was the same regardless of which hand performed the task, did not support findings from other studies where tasks involving force production resulted in more overflow when performed by the non-dominant hand. To investigate further the influence of task characteristics on motor overflow occurrence, in the second study participants were required to remember and reproduce a prescribed sequence of four finger lifts. Left- and right-handed participants (N =30) performed both single and sequenced finger lifting. The relative frequency of motor overflow (unintended lifts of fingers of the passive hand) was compared between hand preference groups, active hand and task type (single/sequenced). Contrary to the expectation that motor overflow would be greater for the sequenced finger lifting task, overflow was exhibited with a significantly greater frequency on single finger lifting. This finding indicates that task characteristics influence the pattern of overflow occurrence in normal adults. The task used in this study did not involve force production and did not result in an intermanual asymmetry of motor overflow. This contrasts with findings from other studies requiring adults to exert forces where greater overflow occurred when the non-dominant hand was active. However, this study confirms previous findings which show that left-handers produce greater overflow compared to right-handers regardless of the task being performed and the hand performing the task.     

Disturbances of grip force behaviour in focal hand dystonia: evidence for a generalised impairment of sensory-motor integration?

BACKGROUND: Focal task specific dystonia occurs preferentially during performance of a specific task. There may be an inefficiently high grip force when doing manipulative tasks other than the trigger task, possibly reflecting a generalised impairment of sensory-motor integration. OBJECTIVE: To examine how well subjects with writer's cramp (n = 4) or musician's cramp (n = 5) adapted their grip force when lifting a new object or catching a weight. METHODS: Nine patients with focal hand dystonia and 10 controls were studied. Experiments addressed different motor behaviours: (A) lifting and holding an object; (B) adjusting grip force in anticipation of or in reaction to a change in load force by catching a small weight dropped expectedly or unexpectedly into a hand held receptacle. RESULTS: In (A), patients produced a grip force overshoot during the initial lifts; force overflow was most pronounced in those with writer's cramp. Patients and controls adjusted their grip force to object weight within one or two lifts, though patients settled to a steady force level above normal. In (B), patients with focal hand dystonia and normal controls showed similar predictive grip force adjustments to expected changes in object load, suggesting that this aspect of sensory-motor integration was normal. Patients had a shorter latency of grip force response than controls after an unexpected load increase, reflecting either a greater level of preparatory motor activity or a disinhibited spinal reflex response. CONCLUSIONS: The overall increased grip force in patients with focal hand dystonia is likely to be a prelearned phenomenon rather than a primary disorder of sensory-motor integration.     

Altered sensorimotor activation patterns in idiopathic dystonia—an activation likelihood estimation meta‐analysis of functional brain imaging studies

Dystonia is characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements or postures. Functional neuroimaging studies have yielded abnormal task‐related sensorimotor activation in dystonia, but the results appear to be rather variable across studies. Further, study size was usually small including different types of dystonia. Here we performed an activation likelihood estimation (ALE) meta‐analysis of functional neuroimaging studies in patients with primary dystonia to test for convergence of dystonia‐related alterations in task‐related activity across studies. Activation likelihood estimates were based on previously reported regional maxima of task‐related increases or decreases in dystonia patients compared to healthy controls. The meta‐analyses encompassed data from 179 patients with dystonia reported in 18 functional neuroimaging studies using a range of sensorimotor tasks. Patients with dystonia showed bilateral increases in task‐related activation in the parietal operculum and ventral postcentral gyrus as well as right middle temporal gyrus. Decreases in task‐related activation converged in left supplementary motor area and left postcentral gyrus, right superior temporal gyrus and dorsal midbrain. Apart from the midbrain cluster, all between‐group differences in task‐related activity were retrieved in a sub‐analysis including only the 14 studies on patients with focal dystonia. For focal dystonia, an additional cluster of increased sensorimotor activation emerged in the caudal cingulate motor zone. The results show that dystonia is consistently associated with abnormal somatosensory processing in the primary and secondary somatosensory cortex along with abnormal sensorimotor activation of mesial premotor and right lateral temporal cortex. Hum Brain Mapp 37:547–557, 2016. © 2015 Wiley Periodicals, Inc.     

Shortened cortical silent period in facial muscles of patients with cranial dystonia

OBJECTIVE: To study the cortical silent period (SP) in the orbicularis oculi and perioral muscles in 23 patients with cranial dystonia and 10 age-matched control subjects. METHODS: High-intensity magnetic stimuli were delivered with a round coil centered at the vertex during a maximal muscle contraction. Electromyographic (EMG) responses were recorded from surface electrodes placed over the orbicularis oculi and perioral muscles. RESULTS: SPs elicited in upper and lower facial muscles had a similar duration. Facial muscle SPs were significantly shorter in patients than in control subjects. Patients with blepharospasm plus oromandibular dystonia had shorter SPs than patients with blepharospasm alone. Although patients' recordings showed reduced voluntary and evoked EMG activity, neither activities correlated with the duration of the SP. CONCLUSIONS: Silent period (SP) shortening depends neither on the level of electromyographic activity nor on segmentary mechanisms. The shortened SP in facial muscles reflects hypoexcitability of cortical inhibitory neurons in cranial dystonia.     

Embouchure dystonia—Portrait of a task‐specific cranial dystonia

Focal task‐specific dystonia (FTSD) is an unusual disorder of motor control, which typically affects the hand but may also involve the face, jaw, and tongue. We report 89 musicians with dystonia of the embouchure (ED), the muscles of the lower face, jaw, and tongue used to control the flow of air into the mouthpiece of a woodwind or brass instrument. Symptoms of ED began at an average age of 36, were typically painless and only rarely were preceded by trauma. Specific musical techniques commonly triggered dystonia, often in one instrumental register. Task‐specific embouchure tremor and lip‐pulling ED phenotypes were common among high‐register brass players (trumpet and French horn), whereas lip‐locking occurred exclusively in low‐register brass players (trombone and tuba). Jaw and tongue ED phenotypes occurred predominantly in woodwind players, and once present, frequently spread to speaking or eating. Six percent of all ED patients had coincident writer's cramp, suggesting a possible genetic predisposition to develop dystonia. We assessed two‐point sensory discrimination in the upper lip, lower lip, and hand in ED patients, normal musicians, and nonmusician age‐matched controls—there were no differences between groups. Once present, symptoms of ED did not remit and often disrupted careers and livelihoods. Better treatments are urgently needed for this unusual disorder of oral motor control. © 2009 Movement Disorder Society