Individual differences in expert motor coordination associated with white matter microstructure in the cerebellum.

Recent investigations into the neural basis of elite sporting performance have focused on whether cortical activity might characterize individual differences in ability. However, very little is understood about how changes in brain structure might contribute to individual differences in expert motor control. We compared the behavior and brain structure of healthy controls with a group of karate black belts, an expert group who are able to perform rapid, complex movements that require years of training. Using 3D motion tracking, we investigated whether the ability to control ballistic arm movements was associated with differences in white matter microstructure. We found that karate experts are better able than novices to coordinate the timing of inter-segmental joint velocities. Diffusion tensor imaging revealed significant differences between the groups in the microstructure of white matter in the superior cerebellar peduncles (SCPs) and primary motor cortex-brain regions that are critical to the voluntary control of movement. Motor coordination, the amount of experience, and the age at which training began were all associated with individual differences in white matter integrity in the cerebellum within the karate groups. These findings suggest a role for the white matter pathways of the SCPs in motor expertise.

Magnetic field effects on the vestibular system: calculation of the pressure on the cupula due to ionic current-induced Lorentz force.

Large static magnetic fields may be employed in magnetic resonance imaging (MRI). At high magnetic field strengths (usually from about 3 T and above) it is possible for humans to perceive a number of effects. One such effect is mild vertigo. Recently, Roberts et al (2011 Current Biology 21 1635-40) proposed a Lorentz-force mechanism resulting from the ionic currents occurring naturally in the endolymph of the vestibular system. In the present work a more detailed calculation of the forces and resulting pressures in the vestibular system is carried out using a numerical model. Firstly, realistic 3D finite element conductivity and fluid maps of the utricle and a single semi-circular canal containing the current sources (dark cells) and sinks (hair cells) of the utricle and ampulla were constructed. Secondly, the electrical current densities in the fluid are calculated. Thirdly, the developed Lorentz force is used directly in the Navier-Stokes equation and the trans-cupular pressure is computed. Since the driving force field is relatively large in comparison with the advective acceleration, we demonstrate that it is possible to perform an approximation in the Navier-Stokes equations that reduces the problem to solving a simpler Poisson equation. This simplification allows rapid and easy calculation for many different directions of applied magnetic field. At 7 T a maximum cupula pressure difference of 1.6 mPa was calculated for the combined ampullar (0.7 µA) and utricular (3.31 µA) distributed current sources, assuming a hair-cell resting current of 100 pA per unit. These pressure values are up to an order of magnitude lower than those proposed by Roberts et al using a simplistic model and calculation, and are in good agreement with the estimated pressure values for nystagmus velocities in caloric experiments. This modeling work supports the hypothesis that the Lorentz force mechanism is a significant contributor to the perception of magnetic field induced vertigo.

Putaminal activity is related to perceptual certainty.

We have investigated the neural basis of perceptual certainty using a simple discrimination paradigm. Psychophysical experiments have shown that a pair of identical electrical stimuli to the skin or a pair of auditory clicks to the ears are consistently perceived as two separate events in time when the inter-stimulus interval (ISIs) is long, and perceived as simultaneous events when the ISIs are very short. The perceptual certainty of having received one or two stimuli decreases when the ISI lies between these two extremes and this is reflected in inconsistent reporting of the percept across trials. In two fMRI experiments, 14 healthy subjects received either paired electrical pulses delivered to the forearm (ISIs=5-110 ms) or paired auditory clicks presented binaurally (ISIs=1-20 ms). For each subject and modality, we calculated a consistency index (CI) representing the level of perceptual certainty. The task activated pre-SMA and anterior cingulate cortex, plus the cerebellum and the basal ganglia. Critically, activity in the right putamen was linearly dependent on CI for both tactile and auditory discrimination, with topographically distinct effects in the two modalities. These results support a role for the human putamen in the "automatic" perception of temporal features of tactile and auditory stimuli.

De-stabilizing and training effects of foot orthoses in multiple sclerosis.

This study evaluates the effects of dynamic foot orthoses (DFO) on walking and balance performance in people with multiple sclerosis (MS). Sixteen ambulant subjects with MS and ten age-matched healthy control subjects were studied on initial receipt of foot orthoses and after four weeks of daily wear. Walking speed, MS Walking Scale-12 (MSWS-12) and standing balance were assessed with and without orthoses at both these times. During standing, stance width and vision were varied, and performance was quantified using the velocity of the centre of pressure (COP), body sway velocity and the mean COP position relative to the shoe. People with MS walked slower (P <0.001) and showed increased sway when standing (P <0.001). At the first assessment, the foot orthoses caused an increase in sway and a medial and posterior shift of the COP position. At repeat measurement, the DFOs continued to increase sway compared to a shoe only condition. However, MS subjects reported an improvement in the MSWS-12 (P <0.05) and, compared to the initial session, showed decreased sway when eyes were closed both with and without DFOs. Dynamic foot orthoses may increase sway and change COP position by altering foot alignment and/or plantar afferent stimulation. Improvement in body sway over time may be an overall training effect of the DFOs, as MS subjects adapt to the initial de-stabilization.

The neural basis of temporal auditory discrimination.

When two identical stimuli, such as a pair of clicks, are presented with a sufficiently long time-interval between them they are readily perceived as two separate events. However, as they are presented progressively closer together, there comes a point when the two separate stimuli are perceived as one. This phenomenon applies not only to hearing but also to other sensory modalities. Damage to the basal ganglia disturbs this type of temporal discrimination irrespective of sensory modality, suggesting a multimodal process is involved. Our aim was to study the neural substrate of auditory temporal discrimination in healthy subjects and to compare it with structures previously associated with analogous tactile temporal discrimination. During fMRI scanning, paired-clicks separated by variable inter-stimulus intervals (1-50 ms) were delivered binaurally, with different intensities delivered to each ear, yielding a lateralised auditory percept. Subjects were required (a) to report whether they heard one or two stimuli (TD: temporal discrimination); or (b) to report whether the stimuli were located on the right or left side of the head mid-line (SD: spatial discrimination); or (c) simply to detect the presence of an auditory stimulus (control task). Our results showed that both types of auditory discrimination (TD and SD) compared to simple detection activated a network of brain areas including regions of prefrontal cortex and basal ganglia. Critically, two clusters in pre-SMA and the anterior cingulate cortex were specifically activated by TD. Furthermore, these clusters overlap with regions activated for similar judgments in the tactile modality suggesting that they fulfill a multimodal function in the temporal processing of sensory events.

The vestibular control of balance after stroke.

OBJECTIVES: To examine vestibular control of balance in those who recovered the ability to stand after middle cerebral artery (MCA) stroke. METHODS: Sixteen patients with MCA stroke were compared with 10 age matched controls. Two additional patients were studied with isolated corticospinal tract lesions, one each at the level of the pons and medulla. Vestibular evoked postural responses were obtained using galvanic vestibular stimulation (GVS) while patients stood with their eyes closed and head facing forwards, equally loading both legs. The GVS response was characterised by measuring the amplitude of the stimulus evoked lateral forces acting through each leg and the lateral displacement of the axial skeleton. RESULTS: Lateral displacement and net lateral force following GVS were significantly larger after stroke. Unlike controls, the lateral forces in the stroke group were asymmetrical, being enhanced on the side of the non-paretic limb and small on the side of the paretic limb. The degree of GVS evoked asymmetry correlated with corticospinal damage assessed using transcranial magnetic stimulation. A similar asymmetrical response was seen in the patient with the pontine lesion but not the patient with the medullary lesion. CONCLUSIONS: MCA stroke may disrupt corticobulbar projections to brainstem output pathways involved in vestibular control of balance. These projections are either collaterals of the corticospinal tract or lie close to that tract and terminate in the pons/upper medulla. This hypothesis accounts for the association between corticospinal tract damage and GVS response asymmetry, and the lack of GVS evoked asymmetry with corticospinal lesions below the rostral medulla.

Modulation of human vestibular-evoked postural responses by alterations in load.

The effects of body loading and unloading on human postural responses elicited by 1 mA bilateral, bipolar galvanic vestibular stimulation (GVS) were investigated. Subjects stood symmetrically, and in separate experiments were either loaded by 16, 33 and 50 % of their body weight with weights attached to the trunk, or unloaded by 10, 20 and 30 % using a whole-body harness that partially lifted the body but was free to translate horizontally. Randomised blocks of stimuli for each loading/unloading condition were compared to a non-loaded control condition. The rate of lateral reaction force development over the period 200-350 ms poststimulus increased in both legs with loading and decreased with unloading. The rate of force development was always larger from the leg on the side of cathodal stimulation. Vertical force responses were equal and opposite in the two legs, increasing on the side of the cathode and decreasing on the side of the anode. The rate of vertical force development over the period 200-350 ms after stimulus onset was increased with loading and decreased with unloading. In the frontal plane, the rate of head and trunk tilt in space was increased and decreased with loading and unloading, respectively. However, the relative rate of head tilt with respect to the trunk was not affected by loading conditions. These experiments provide further evidence that load-related afferent feedback influences the processing of vestibular information for the control of balance.

Bipedal distribution of human vestibular-evoked postural responses during asymmetrical standing.

Galvanic vestibular stimulation (GVS) evokes responses in muscles of both legs when bilateral stimuli are applied during normal stance. We have used this technique to assess whether asymmetrical standing alters the distribution of responses in the two legs. Subjects stood either asymmetrically with 75% of their body weight on one leg or symmetrically with each leg taking 50% of their body weight. The net response in each leg was taken from changes in ground reaction force measured from separate force plates under each foot. The net force profile consisted of a small initial force change that peaked at approximately 200 ms followed by an oppositely directed larger component that peaked at approximately 450 ms. We analysed the second force component since it was responsible for the kinematic response of lateral body sway and tilt towards the anode. In the horizontal plane, both legs produced lateral force responses that were in the same direction but larger in the leg ipsilateral to the cathodal ear. There were also vertical force responses that were of equal size in both legs but acted in opposite directions. When subjects stood asymmetrically the directions of the force responses remained the same but their magnitudes changed. The lateral force response became 2-3 times larger for the more loaded leg and the vertical forces increased 1.5 times on average for both legs. Control experiments showed that these changes could not be explained by either the consistent (< 5 deg) head tilt towards the side of the loaded leg or the changes in background muscle activity associated with the asymmetrical posture. We conclude that the redistribution of force responses in the two legs arises from a load-sensing mechanism. We suggest there is a central interaction between load-related afferent input from the periphery and descending motor signals from balance centres.

Evidence for subcortical involvement in the visual control of human reaching.

To test whether the most rapid visually evoked reach adjustments are cortically organized in humans, we have measured their latency in a healthy subject with complete agenesis of the corpus callosum. This condition precludes direct communication between left and right cerebral cortices and so, in this subject, a purely cortical visuomotor process would be expected to produce longer-latency responses to a target that appears in the visual hemifield contralateral to the responding limb (crossed) compared with the ipsilateral hemifield (uncrossed). As predicted, when performing simple reaction time tasks that involved lifting a finger or an arm in response to a visual stimulus presented to either hemifield, this acallosal subject showed a significant crossed-uncrossed latency difference (mean 35.8 ms) that was not present in control subjects (group mean 2.2 ms). In contrast, when she reached for a target that unexpectedly jumped into either visual hemifield, the latencies of mid-flight adjustment were the same (approximately 120 ms) irrespective of either the target jump direction or which hand was used. This was not due to an early movement of the eyes bringing the target back on to the fovea since this subject's finger always deviated towards the new target position in advance of her eyes. Neither could it be explained by the use of ipsilateral corticospinal projections since transcranial magnetic stimulation over the motor cortex failed to evoke ipsilateral responses in arm or hand muscles. These results suggest that, even in humans, subcortical structures are involved in the fastest adjustments of the reaching arm made in response to fresh visual information. An additional finding in this subject was that, when reaching, the eye saccadic latency was greater by 36 ms on average when the target jumped right compared with left, irrespective of which hand was being used. This is the same value as the mean interhemispheric transfer time obtained in the simple reaction time tasks and may indicate right-hemispheric dominance for saccadic eye movement control.

A dissociation between subjective and objective unsteadiness in primary orthostatic tremor.

Patients with primary orthostatic tremor (OT) experience a disabling sense of unsteadiness but rarely fall. In order to study the relationship between the development of subjective unsteadiness, objective unsteadiness and tremor, we recorded standing under four conditions (eyes open or closed, feet together or apart) in six patients with OT. Subjective unsteadiness was indicated by the patients on a four-point scale using a hand-held slider. Objective unsteadiness was assessed by measuring the path lengths of the centre of foot pressure and body motion at the level of the cervical spine. Tremor was measured by surface electromyography from leg and paraspinal muscles. OT patients were objectively more unsteady than controls. Objective unsteadiness also increased disproportionately in patients when standing with eyes closed. These findings suggest that balance control in OT is abnormal and shows increased visual dependence. Subjective unsteadiness increased from mild to severe over seconds to minutes. The increase was faster when standing with eyes closed or feet together. However, although escalating subjective unsteadiness was paralleled by an increase in leg tremor, there were no comparable changes in either paraspinal tremor or objective unsteadiness during the course of a stand. We conclude that there is a dissociation between subjective and objective unsteadiness. This implies that subjective unsteadiness does not arise simply from an awareness of increased body sway. We postulate that the sensation of unsteadiness arises from a tremulous disruption of proprioceptive afferent activity from the legs. This disturbance gives rise to increased co-contracting drive to the leg muscles in order to stiffen the joints and increase stability. Since muscle activity remains tremor-locked, the tremulous proprioceptive feedback is increased, which then further increases the sensation of unsteadiness, and so on in a vicious circle of escalating activity.

Voluntary modification of automatic arm movements evoked by motion of a visual target.

We have investigated whether the processes underlying the visually evoked, automatic adjustments to a reach are: (1) modifiable by the subject's intention, and (2) available to initiate movement of a stationary arm. Unpredictable movement of a target (80 m/s through 10 cm, left or right in a third of trials) either evoked a mid-flight adjustment of a reaching movement or else acted as a trigger to start an arm movement. Subjects were instructed to respond as rapidly as possible by moving their finger either in the same or in the opposite direction to the target. The target shift evoked an early (125-160 ms) and/or a later (> 160 ms) class of response in the reaching arm. The early response was highly automatic in that it could not be reversed (move opposite) by the subjects' intention. However, the subjects' intention did influence the frequency of occurrence and the size of this early response. The later response was totally modifiable in that it changed direction according to the subjects' intention. Similar classes of response were observed in stationary limbs, but the early, more automatic response was substantially weaker than that elicited during a reach. Two possible mechanisms are proposed to explain these results. The first is a dual-pathway model, which assumes that the two response classes are each generated by separate visuo-motor processes with different properties. The second model assumes both responses are generated by a single visuo-motor mechanism that is under the control of a higher, attentional process.

Vestibular hypersensitivity to clicks is characteristic of the Tullio phenomenon.

OBJECTIVES: The frequency of pathologically reduced click thresholds for vestibular activation was explored in patients with the Tullio phenomenon (sound induced vestibular activation). METHODS: Seven patients (eight affected ears) with symptoms of oscillopsia and unsteadiness in response to loud external sounds or to the patient's own voice were examined. In all but one patient, vestibular hypersensitivity to sound was confirmed by the fact that eye movements could be produced by pure tones of 110 dB intensity or less. Conventional diagnostic imaging was normal in all cases and three of the patients had normal middle ears at surgical exploration. Thresholds for click evoked vestibulocollic reflexes were compared with those of a group of normal subjects. Galvanic stimulation was used as a complementary method of examining the excitability of vestibular reflexes. RESULTS: All the patients showed a reduced threshold for click activation of vestibulocollic reflexes arising from the affected ear. Short latency EMG responses to clicks were also present in posterior neck and leg muscles, suggesting that these muscles receive vestibular projections. Galvanic stimulation produced a normal pattern of body sway in four of the five patients tested. CONCLUSIONS: A pathologically reduced threshold to click activation (< or = 70 dB NHL (average normal hearing level)) seems to be a consistent feature of the Tullio phenomenon and a useful diagnostic criterion. This in turn is most likely to be due to an increased effectiveness of the transmission of sound energy to saccular receptors. Activation of these receptors probably contributed to the vestibular symptoms experienced by the patients.

Galvanic vestibular stimulation modulates voluntary movement of the human upper body.

1. We have investigated whether vestibular information plays a role in the control of voluntary movement of the upper body. Movement consisted of a lateral tilt of the upper body in the frontal plane through an angle of about 8 deg. The influence of vestibular input was assessed from the effect of long duration (3-6 s), low-intensity (0.7 mA) galvanic vestibular stimulation (GVS) applied at different times relative to the movement. 2. GVS always produced a tilt of the body in the frontal plane but the response was larger and more prolonged when the onset of stimulation coincided with the cue to start moving compared with when it was applied some seconds after movement onset (i.e. while the subject was stationary in a tilted posture). 3. When the stimulus began 2 s before the voluntary movement the response consisted of two distinct components separated in time, one that was linked to the onset of GVS and another that was linked to onset of the voluntary movement. The large response observed when GVS onset coincided with the movement cue resembled the sum (after realignment in time) of these two separate components. 4. We suggest that these two components of the response to GVS relate to two different uses of vestibular information for whole-body control: first, to help maintain balance of the body, and second, to help guide and improve the accuracy of voluntary movements involving motion of the head in space.

Central motor conduction time in progressive multiple sclerosis. Correlations with MRI and disease activity.

The purpose of this study was to relate abnormalities of motor conduction time to the presence of spinal cord MRI lesions in progressive multiple sclerosis and to investigate the relationship between changes in motor conduction over time and clinical and MRI changes. Central motor conduction time (CMCT), serial MRI of the brain and spinal cord, and clinical evaluations were carried out in 20 patients with primary and secondary progressive multiple sclerosis. CMCT was carried out at the beginning and end of the study whilst the clinical and MRI examinations occurred at monthly intervals for 12 months. Median CMCT to abductor pollicis brevis was 14.8 ms (range 8.8-27.4 ms). The response latency to tibialis anterior correlated with disability measured on the Expanded Disability Status Scale. Latencies to upper limb muscles correlated with cervical MRI lesion load and the presence of atrophy of the cervical cord. Over the 12-month study period, 15 of 19 patients deteriorated clinically. However, an increase in motor response latencies occurred only in the four patients who had developed new cord lesions. The results suggest that prolonged CMCT is related to spinal cord lesion load and that, over time, changes in the CMCT occur only when spinal cord lesion load increases. Clinical change in progressive multiple sclerosis may therefore occur without either the development of new lesions on MRI scans or an increase in motor conduction time. This suggests that clinical deterioration in these patients may occur by a mechanism other than increasing demyelination. This may be progressive axonal degeneration.

Influence of vision on upper limb reaching movements in patients with cerebellar ataxia.

The effects of vision on spatial and temporal characteristics of free unrestrained reaching movements of the arm were examined in 17 patients with ataxic syndromes due to degenerative disease of the cerebellum and its connections. Subjects were required to reach out and touch a visually presented target either in the dark or with the target and their finger visible. Overall, patients had prolonged reaction times and their movements were performed slower than normal. The spatial paths described by their fingertips were more circuitous, being of greater length than normal, a characteristic that was uninfluenced by visual conditions. Ataxic movements were less accurate than normal in two ways. First, there was greater spatial variability between repeat paths to the same target. The increased variability was present very early in the movement trajectory and at that stage was not influenced by visual feedback. Secondly, there were large constant errors at the end of movement, but only when moving in darkness. Patients with Friedreich's ataxia as well as those with intrinsic cerebellar degeneration showed the above abnormalities, although there were some quantitative differences between the two groups. We suggest these spatial errors arise because the cerebellum contributes either directly or indirectly to preparatory motor processes which, based on limb proprioceptive and retinal information, compute the pattern of muscle activity required to launch the limb accurately towards a target. Patients were largely successful at using visual guidance to make midflight adjustments to their movements in order to improve accuracy. This manifested as a reduction in spatial variability between repeat paths as the target was approached and a reduction in constant error. However, the visual correction mechanism did not appear normal. Under visual guidance, the end-phase of movement was often prolonged and characterized by excessive deviations or direction changes in the path. These deviations may be the expression of a visual guidance system producing corrections which themselves contain error requiring further correction. Thus, this process may be abnormal for the same reason that the initial pattern of muscle activity is misjudged.

Control of frontal plane body motion in human stepping.

During a step the body's centre of mass (CoM) typically remains medial to the supporting foot and therefore the body is unstable and falling (sideways) under gravity. This may make it difficult to adjust the frontal-plane body motion appreciably once the step is under way. We have therefore investigated whether this motion could be controlled largely in a ballistic manner, that is by setting the initial (toe-off) position and velocity of the CoM such that the fall develops as required for the particular step without the need for appreciable mid-step adjustment. Subjects stepped in different directions and from different postures, and the resulting motion of their CoM in the frontal plane was compared with that of a single-segment mathematical model of the body which falls freely under the influence of gravity. The lateral position and velocity of subjects' CoM at toe-off varied across the different step types in a manner consistent with a ballistic mode of control. Furthermore the model, given these positions and velocities as initial conditions, closely predicted the subsequent CoM motion. The results suggest that subjects may produce the different body trajectories required for different types of step largely in a ballistic manner. This would imply that the central nervous system must judge in advance the size and direction of the initial "throw" given to the body-mass.

Human body-segment tilts induced by galvanic stimulation: a vestibularly driven balance protection mechanism.

1. We have studied the effects of changes in posture on the motor response to galvanic vestibular stimulation (GVS). The purpose of the experiments was to investigate whether the function of the GVS-evoked response is to stabilize the body or the head in space. Subjects faced forwards with eyes closed standing with various stance widths and sitting. In all cases the GVS-evoked response consisted of a sway of the body towards the anodal ear. 2. In the first set of experiments the response was measured from changes in (i) electromyographic activity of hip and ankle muscles, (ii) the lateral ground reaction force, and (iii) lateral motion of the body at the level of the neck (C7). For all measurements the response became smaller as the feet were placed further apart. 3. In the second set of experiments we measured the GVS-evoked tilts of the head, torso and pelvis. The basic response consisted of a tilt in space (anodal ear down) of all three segments. The head tilted more than the trunk and the trunk tilted more than the pelvis producing a leaning and bending of the body towards the anodal ear. This change in posture was sustained for the duration of the stimulus. 4. The tilt of all three segments was reduced by increasing the stance width. This was due to a reduction in evoked tilt of the pelvis, the bending of the upper body remaining relatively unchanged. Changing from a standing to a sitting posture produced additional reductions in tilt by reducing the degree of upper body bending. 5. The results indicate that the response is organized to stabilize the body rather than the head in space. We suggest that GVS produces a vestibular input akin to that experienced on an inclined support surface and that the function of the response is to counter any threat to balance by keeping the centre of mass of the body within safe limits.