Bed rest impairs the vestibular control of balance.

Prolonged bed rest impairs standing balance but the underlying mechanisms are uncertain. Previous research suggests strength loss is not the cause, leaving impaired sensorimotor control as an alternative. Here we examine vestibular control of posture in 18 male volunteers before and after 60 days of bed rest. Stochastic vestibular stimulation (SVS) was used to evoke sway responses before, 1 and 6 days after bed rest under different head yaw orientations. The directional accuracy and precision of these responses were calculated from ground reaction force vectors. Bed rest caused up to 63% increases in spontaneous standing sway and 31% reductions in leg strength, changes which were uncorrelated. The increase in sway was exacerbated when the eyes were closed. Mean directions of SVS-evoked sway responses were unaffected, being directed towards the anodal ear and rotating in line with head orientation in the same way before and after bed rest. However, individual trial analysis revealed 25%-30% increases in directional variability, which were significantly correlated with the increase in spontaneous sway (r = 0.48-0.71; P ≤ 0.044) and were still elevated on day 6 post-bed rest. This reveals that individual sway responses may be inappropriately oriented, a finding masked by the averaging process. Our results confirm that impaired balance following prolonged bedrest is not related to loss of strength. Rather, they demonstrate that the sensorimotor transformation process which converts vestibular feedback into appropriately directed balance responses is impaired. KEY POINTS: Prolonged inactivity impairs balance but previous research suggests this is not caused by loss of strength. Here we investigated vestibular control of balance before and after 60 days of bed rest using electrical vestibular stimulation (EVS) to evoke sway responses. Spontaneous sway significantly increased and muscle strength reduced following bed rest, but, in keeping with previous research, these two effects were not correlated. While the overall accuracy of EVS-evoked sway responses was unaffected, their directional variability significantly increased following bed rest, and this was correlated with the increases in spontaneous sway. We have shown that the ability to transform head-centred vestibular feedback into an appropriately directed body sway response is negatively affected by prolonged inactivity; this may contribute to the impaired balance commonly observed following bed rest.

Altered visual and haptic verticality perception in posterior cortical atrophy and Alzheimer's disease.

There is increasing theoretical and empirical support for the brain combining multisensory information to determine the direction of gravity and hence uprightness. A fundamental part of the process is the spatial transformation of sensory signals between reference frames: eye-centred, head-centred, body-centred, etc. The question 'Am I the right way up?' posed by a patient with posterior cortical atrophy (PCA) suggests disturbances in upright perception, subsequently investigated in PCA and typical Alzheimer's disease (tAD) based on what looks or feels upright. Participants repeatedly aligned to vertical a rod presented either visually (visual-vertical) or haptically (haptic-vertical). Visual-vertical involved orienting a projected rod presented without or with a visual orientation cue (circle, tilted square (±18°)). Haptic-vertical involved orientating a grasped rod with eyes closed using a combination of side (left, right) and hand (unimanual, bimanual) configurations. Intraindividual uncertainty and bias defined verticality perception. Uncertainty was consistently greater in both patient groups than in control groups, and greater in PCA than tAD. Bias in the frontal plane was strongly directionally affected by visual cue tilt (visual-vertical) and grip side (haptic-vertical). A model was developed that assumed verticality information from multiple sources is combined in a statistically optimal way to produce observed uncertainties and biases. Model results suggest the mechanism that spatially transforms graviceptive information between body parts is disturbed in both patient groups. Despite visual dysfunction being typically considered the primary feature of PCA, disturbances were greater in PCA than tAD particularly for haptic-vertical, and are considered in light of posterior parietal vulnerability. KEY POINTS: The perception of upright requires accurate and precise estimates of orientation based on multiple noisy sensory signals. The question 'Am I the right way up?' posed by a patient with posterior cortical atrophy (PCA; purported 'visual variant Alzheimer's') suggests disturbances in the perception of upright. What looks or feels upright in PCA and typical Alzheimer's disease (tAD) was investigated by asking participants to repeatedly align to vertical a rod presented visually (visual-vertical) or haptically (haptic-vertical). PCA and tAD groups exhibited not only greater perceptual uncertainty than controls, but also exaggerated bias induced by tilted visual orientation cues (visual-vertical) and grip side (haptic-vertical). When modelled, these abnormalities, which were particularly evident in PCA haptic-vertical performance, were compatible with disruption of a mechanism that spatially transforms verticality information between body parts. The findings suggest an important role of posterior parietal cortex in verticality perception, and have implications for understanding spatial disorientation in dementia.

Visual field motion during a body pull affects compensatory standing and stepping responses.

KEY POINTS: It is unclear whether the visual input that accompanies a perturbation of a standing person can affect whether a recovery step is taken. Visual motion speeds were manipulated during unexpected forward and backward shoulder pulls. Visual motion that appeared slower than actual body motion reduced the initial in-place resistance to the perturbation. As a result of the modulation of the in-place response, less pull force was needed to trigger a step when visual velocity appeared slower than normal. The visuomotor postural response occurred earlier and was larger when the full-field visual input was paired with a mechanical perturbation. ABSTRACT: The present study aimed to determine how visual motion evoked by an upper body perturbation during standing affects compensatory postural responses. This was investigated by rotating the visual field forwards or backwards about the ankle, time-locked to a forwards or backwards shoulder pull. Kinematic, kinetic and electromyographic responses were recorded to a range of pull forces over 160 trials in 12 healthy adults (mean ± SD = 31 ± 5.8 years). Stepping threshold forces and in-place postural responses were compared between conditions. When the visual field moved in the same direction as the pull, so that the apparent velocity of the body was reduced (SLOW condition), the pull-force required to induce a step was less than when the visual field either rotated in the opposite direction (FAST) or was unaltered (NATURAL). For in-place responses, the body was displaced further in the direction of the pull in the SLOW condition. This was the result of a reduction in the resistive force from lower leg muscles 130 ms after the visual motion onset. In trials with no pull, the visual motion induced postural responses that were later (290 ms) and had smaller amplitudes compared to when visual motion is paired with an unexpected perturbation of the body. The results suggest that the apparent speed of the visual environment during a perturbation does influence whether a compensatory step is taken, not via a direct effect on the decision to step but by modulating the initial in-place response.

Stepping in circles: how locomotor signals of rotation adapt over time.

KEY POINTS: While it has been well described that prolonged rotational stepping will adapt the podokinetic sense of rotation, the mechanisms involved are not clearly understood. By studying podokinetic after-rotations following conditioning rotations not previously reported we have shown that slower rotational velocities are more readily adapted than faster velocities and adaptation occurs more quickly than previously thought. We propose a dynamic feedback model of vestibular and podokinetic adaptation that can fit rotation trajectories across multiple conditions and data sets. Two adaptation processes were identified that may reflect central and peripheral processes and the discussion unifies prior findings in the podokinetic literature under this new framework. The findings show the technique is feasible for people with locomotor turning problems. ABSTRACT: After a prolonged period stepping in circles, people walk with a curved trajectory when attempting to walk in a straight line without vision. Podokinetic adaptation shows promise in clinical populations to improve locomotor turning; however, the adaptive mechanisms involved are poorly understood. The first phase of this study asks: how does the podokinetic conditioning velocity affect the response velocity and how quickly can adaptation occur? The second phase of the study asks: can a mathematical feedback model account for the rotation trajectories across different conditioning parameters and different datasets? Twelve healthy participants stepped in place on the axis of a rotating surface ranging from 4 to 20 deg s-1 for durations of 1-10 min, while using visual cues to maintain a constant heading direction. Afterward on solid ground, participants were blindfolded and attempted to step without rotating. Participants unknowingly stepped in circles opposite to the direction of the prior platform rotation for all conditions. The angular velocity of this response peaked within 1 min and the ratio of the stimulus-to-response peak velocity fitted a decreasing power function. The response then decayed exponentially. The feedback model of podokinetic and vestibular adaptive processes had a good fit with the data and suggested that podokinetic adaptation is explained by a short (141 s) and a long (27 min) time constant. The podokinetic system adapts more quickly than previously thought and subjects adapt more readily to slower rotation than to faster rotation. These findings will have implications for clinical applications of the technique.

Dual processing of visual rotation for bipedal stance control.

KEY POINTS: When standing, the gain of the body-movement response to a sinusoidally moving visual scene has been shown to get smaller with faster stimuli, possibly through changes in the apportioning of visual flow to self-motion or environment motion. We investigated whether visual-flow speed similarly influences the postural response to a discrete, unidirectional rotation of the visual scene in the frontal plane. Contrary to expectation, the evoked postural response consisted of two sequential components with opposite relationships to visual motion speed. With faster visual rotation the early component became smaller, not through a change in gain but by changes in its temporal structure, while the later component grew larger. We propose that the early component arises from the balance control system minimising apparent self-motion, while the later component stems from the postural system realigning the body with gravity. ABSTRACT: The source of visual motion is inherently ambiguous such that movement of objects in the environment can evoke self-motion illusions and postural adjustments. Theoretically, the brain can mitigate this problem by combining visual signals with other types of information. A Bayesian model that achieves this was previously proposed and predicts a decreasing gain of postural response with increasing visual motion speed. Here we test this prediction for discrete, unidirectional, full-field visual rotations in the frontal plane of standing subjects. The speed (0.75-48 deg s(-1) ) and direction of visual rotation was pseudo-randomly varied and mediolateral responses were measured from displacements of the trunk and horizontal ground reaction forces. The behaviour evoked by this visual rotation was more complex than has hitherto been reported, consisting broadly of two consecutive components with respective latencies of ∼190 ms and >0.7 s. Both components were sensitive to visual rotation speed, but with diametrically opposite relationships. Thus, the early component decreased with faster visual rotation, while the later component increased. Furthermore, the decrease in size of the early component was not achieved by a simple attenuation of gain, but by a change in its temporal structure. We conclude that the two components represent expressions of different motor functions, both pertinent to the control of bipedal stance. We propose that the early response stems from the balance control system attempting to minimise unintended body motion, while the later response arises from the postural control system attempting to align the body with gravity.

Effect of head pitch and roll orientations on magnetically induced vertigo.

KEY POINTS: Lying supine in a strong magnetic field, such as in magnetic resonance imaging scanners, can induce a perception of whole-body rotation. The leading hypothesis to explain this invokes a Lorentz force mechanism acting on vestibular endolymph that acts to stimulate semicircular canals. The hypothesis predicts that the perception of whole-body rotation will depend on head orientation in the field. Results showed that the direction and magnitude of apparent whole-body rotation while stationary in a 7 T magnetic field is influenced by head orientation. The data are compatible with the Lorentz force hypothesis of magnetic vestibular stimulation and furthermore demonstrate the operation of a spatial transformation process from head-referenced vestibular signals to Earth-referenced body motion. ABSTRACT: High strength static magnetic fields are known to induce vertigo, believed to be via stimulation of the vestibular system. The leading hypothesis (Lorentz forces) predicts that the induced vertigo should depend on the orientation of the magnetic field relative to the head. In this study we examined the effect of static head pitch (-80 to +40 deg; 12 participants) and roll (-40 to +40 deg; 11 participants) on qualitative and quantitative aspects of vertigo experienced in the dark by healthy humans when exposed to the static uniform magnetic field inside a 7 T MRI scanner. Three participants were additionally examined at 180 deg pitch and roll orientations. The effect of roll orientation on horizontal and vertical nystagmus was also measured and was found to affect only the vertical component. Vertigo was most discomforting when head pitch was around 60 deg extension and was mildest when it was around 20 deg flexion. Quantitative analysis of vertigo focused on the induced perception of horizontal-plane rotation reported online with the aid of hand-held switches. Head orientation had effects on both the magnitude and the direction of this perceived rotation. The data suggest sinusoidal relationships between head orientation and perception with spatial periods of 180 deg for pitch and 360 deg for roll, which we explain is consistent with the Lorentz force hypothesis. The effects of head pitch on vertigo and previously reported nystagmus are consistent with both effects being driven by a common vestibular signal. To explain all the observed effects, this common signal requires contributions from multiple semicircular canals.

Maintaining balance against force perturbations: impaired mechanisms unresponsive to levodopa in Parkinson's disease.

There is evidence that postural instability associated with Parkinson's disease (PD) is not adequately improved by levodopa, implying involvement of nondopaminergic pathways. However, the mechanisms contributing to postural instability have yet to be fully identified and tested for their levodopa responsiveness. In this report we investigate balance processes that resist external forces to the body when standing. These include in-place responses and the transition to protective stepping. Forward and backward shoulder pulls were delivered using two force-feedback-controlled motors and were randomized for direction, magnitude, and onset. Sixteen patients with PD were tested OFF and ON levodopa, and 16 healthy controls were tested twice. Response behavior was quantified from 3-dimensional ground reaction forces and kinematic measurements of body segments and total body center-of-mass (CoM) motion. In-place responses resisting the pull were significantly smaller in PD as reflected in reduced horizontal anteroposterior ground reaction force and increased CoM displacement. Ankle, knee, and hip moments contributing to this resistance were smaller in PD, with the knee extensor moment to backward pulls being the most affected. The threshold force needed to evoke a step was also smaller for PD in the forward direction. Protective steps evoked by suprathreshold pulls showed deficits in PD in the backward direction, with steps being shorter and more steps being required to arrest the body. Levodopa administration had no significant effect on either in-place or protective stepping deficits. We conclude that processes employed to maintain balance in the face of external forces show impairment in PD consistent with disruption to nondopaminergic systems.

Evidence for early neurodegeneration in the cervical cord of patients with primary progressive multiple sclerosis.

Spinal neurodegeneration is an important determinant of disability progression in patients with primary progressive multiple sclerosis. Advanced imaging techniques, such as single-voxel (1)H-magnetic resonance spectroscopy and q-space imaging, have increased pathological specificity for neurodegeneration, but are challenging to implement in the spinal cord and have yet to be applied in early primary progressive multiple sclerosis. By combining these imaging techniques with new clinical measures, which reflect spinal cord pathology more closely than conventional clinical tests, we explored the potential for spinal magnetic resonance spectroscopy and q-space imaging to detect early spinal neurodegeneration that may be responsible for clinical disability. Data from 21 patients with primary progressive multiple sclerosis within 6 years of disease onset, and 24 control subjects were analysed. Patients were clinically assessed on grip strength, vibration perception thresholds and postural stability, in addition to the Expanded Disability Status Scale, Nine Hole Peg Test, Timed 25-Foot Walk Test, Multiple Sclerosis Walking Scale-12, and Modified Ashworth Scale. All subjects underwent magnetic resonance spectroscopy and q-space imaging of the cervical cord and conventional brain and spinal magnetic resonance imaging at 3 T. Multivariate analyses and multiple regression models were used to assess the differences in imaging measures between groups and the relationship between magnetic resonance imaging measures and clinical scores, correcting for age, gender, spinal cord cross-sectional area, brain T2 lesion volume, and brain white matter and grey matter volume fractions. Although patients did not show significant cord atrophy when compared with healthy controls, they had significantly lower total N-acetyl-aspartate (mean 4.01 versus 5.31 mmol/l, P = 0.020) and glutamate-glutamine (mean 4.65 versus 5.93 mmol/l, P = 0.043) than controls. Patients showed an increase in q-space imaging-derived indices of perpendicular diffusivity in both the whole cord and major columns compared with controls (P < 0.05 for all indices). Lower total N-acetyl-aspartate was associated with higher disability, as assessed by the Expanded Disability Status Scale (coefficient = -0.41, 0.01 < P < 0.05), Modified Ashworth Scale (coefficient = -3.78, 0.01 < P < 0.05), vibration perception thresholds (coefficient = -4.37, P = 0.021) and postural sway (P < 0.001). Lower glutamate-glutamine predicted increased postural sway (P = 0.017). Increased perpendicular diffusivity in the whole cord and columns was associated with increased scores on the Modified Ashworth Scale, vibration perception thresholds and postural sway (P < 0.05 in all cases). These imaging findings indicate reduced structural integrity of neurons, demyelination, and abnormalities in the glutamatergic pathways in the cervical cord of early primary progressive multiple sclerosis, in the absence of extensive spinal cord atrophy. The observed relationship between imaging measures and disability suggests that early spinal neurodegeneration may underlie clinical impairment, and should be targeted in future clinical trials with neuroprotective agents to prevent the development of progressive disability.

Violation of the craniocentricity principle for vestibularly evoked balance responses under conditions of anisotropic stability.

The balance response direction to electrically evoked vestibular perturbation is closely tied to head orientation. Such craniocentric response organization is expected of a simple error correction process. Here we ask whether this is maintained when the body is made more stable, but with the stability being greater in one direction than another. Since it is known that vestibularly evoked balance responses become smaller as body stability increases, the following two outcomes are possible: (1) response magnitude is attenuated, but with craniocentricity maintained; and (2) anisotropy of stability is considered such that components of the response are differentially attenuated, which would violate a craniocentric organizing principle. We tested these alternatives by measuring the direction of balance responses to electrical vestibular stimulation across a range of head orientations and stance widths in healthy humans. With feet together, the response was highly craniocentric. However, when stance width was increased so that the body was more stable in the frontal plane, response direction became biased toward the sagittal direction. This resulted in a nonlinear relationship between head orientation and response direction. While stance width changes the mechanical state of the body, the effect was also present when lateral light touch was used to produce anisotropy in stability, demonstrating that a significantly altered mechanical state was not crucial. We conclude that the balance system does not simply act according to the direction of vestibular input. Instead, it appears to assign greater relevance to components of vestibular input acting in the plane of lesser body stability than the plane of greater body stability, and acts accordingly.

Sensorimotor processing for balance in spinocerebellar ataxia type 6.

BACKGROUND: We investigated whether balance impairments caused by cerebellar disease are associated with specific sensorimotor processing deficits that generalize across all sensory modalities. Experiments focused on the putative cerebellar functions of scaling and coordinate transformation of balance responses evoked by stimulation of single sensory channels. METHODS: Vestibular, visual, and proprioceptive sensory channels were stimulated in isolation using galvanic vestibular stimulation, moving visual scenery, and muscle vibration, respectively, in 16 subjects with spinocerebellar ataxia type 6 (SCA6) and 16 matched healthy controls. Two polarities of each stimulus type evoked postural responses of similar form in the forward and backward directions. Disease severity was assessed using the Scale for Assessment and Rating of Ataxia. RESULTS: Impaired balance of SCA6 subjects during unperturbed stance was reflected in faster than normal body sway (P = 0.009), which correlated with disease severity (r = 0.705, P < 0.001). Sensory perturbations revealed a sensorimotor processing abnormality that was specific to response scaling for the visual channel. This manifested as visually evoked postural responses that were approximately three times larger than normal (backward, P < 0.001; forward P = 0.005) and correlated with disease severity (r = 0.543, P = 0.03). Response direction and habituation properties were no different from controls for all three sensory modalities. CONCLUSION: Cerebellar degeneration disturbs the scaling of postural responses evoked by visual motion, possibly through disinhibition of extracerebellar visuomotor centers. The excessively high gain of the visuomotor channel without compensatory decreases in gains of other sensorimotor channels provides a potential mechanism for instability of the balance control system in cerebellar disease.

Training balance with opto-kinetic stimuli in the home: a randomized controlled feasibility study in people with pure cerebellar disease.

OBJECTIVE: To investigate the feasibility of a randomized controlled trial of a home-based balance intervention for people with cerebellar ataxia. DESIGN: A randomized controlled trial design. SETTING: Intervention and assessment took place in the home environment. PARTICIPANTS: A total of 12 people with spinocerebellar ataxia type 6 were randomized into a therapy or control group. Both groups received identical assessments at baseline, four and eight weeks. INTERVENTIONS: Therapy group participants undertook balance exercises in front of optokinetic stimuli during weeks 4-8, while control group participants received no intervention. MAIN MEASURES: Test-retest reliability was analysed from outcome measures collected twice at baseline and four weeks later. Feasibility issues were evaluated using daily diaries and end trial exit interviews. RESULTS: The home-based training intervention with opto-kinetic stimuli was feasible for people with pure ataxia, with one drop-out. Test-retest reliability is strong (intraclass correlation coefficient >0.7) for selected outcome measures evaluating balance at impairment and activity levels. Some measures reveal trends towards improvement for those in the therapy group. Sample size estimations indicate that Bal-SARA scores could detect a clinically significant change of 0.8 points in this functional balance score if 80 people per group were analysed in future trials. CONCLUSIONS: Home-based targeted training of functional balance for people with pure cerebellar ataxia is feasible and the outcome measures employed are reliable.

Neuromechanical interference of posture on movement: evidence from Alexander technique teachers rising from a chair.

While Alexander technique (AT) teachers have been reported to stand up by shifting weight gradually as they incline the trunk forward, healthy untrained (HU) adults appear unable to rise in this way. This study examines the hypothesis that HU have difficulty rising smoothly, and that this difficulty relates to reported differences in postural stiffness between groups. A wide range of movement durations (1-8 s) and anteroposterior foot placements were studied under the instruction to rise at a uniform rate. Before seat-off (SO) there were clear and profound performance differences between groups, particularly for slower movements, that could not be explained by strength differences. For each movement duration, HU used approximately twice the forward center-of-mass (CoM) velocity and vertical feet-loading rate as AT. For slow movements, HU violated task instruction by abruptly speeding up and rapidly shifting weight just before SO. In contrast, AT shifted weight gradually while smoothly advancing the CoM, achieving a more anterior CoM at SO. A neuromechanical model revealed a mechanism whereby stiffness affects standing up by exacerbating a conflict between postural and balance constraints. Thus activating leg extensors to take body weight hinders forward CoM progression toward the feet. HU's abrupt weight shift can be explained by reliance on momentum to stretch stiff leg extensors. AT's smooth rises can be explained by heightened dynamic tone control that reduces leg extensor resistance and improves force transmission across the trunk. Our results suggest postural control shapes movement coordination through a dynamic "postural frame" that affects the resistive behavior of the body.

Ambulatory intracranial pressure in humans: ICP increases during movement between body positions.

Introduction: Positional changes in intracranial pressure (ICP) have been described in humans when measured over minutes or hours in a static posture, with ICP higher when lying supine than when sitting or standing upright. However, humans are often ambulant with frequent changes in position self-generated by active movement. Research question: We explored how ICP changes during movement between body positions. Material and methods: Sixty-two patients undergoing clinical ICP monitoring were recruited. Patients were relatively well, ambulatory and of mixed age, body habitus and pathology. We instructed patients to move back and forth between sitting and standing or lying and sitting positions at 20 s intervals after an initial 60s at rest. We simultaneously measured body position kinematics from inertial measurement units and ICP from an intraparenchymal probe at 100 Hz. Results: ICP increased transiently during movements beyond the level expected by body position alone. The amplitude of the increase varied between participants but was on average ∼5 mmHg during sit-to-stand, stand-to-sit and sit-to-lie movements and 10.8 mmHg [95%CI: 9.3,12.4] during lie-to-sit movements. The amplitude increased slightly with age, was greater in males, and increased with median 24-h ICP. For lie-to-sit and sit-to-lie movements, higher BMI was associated with greater mid-movement increase (ß = 0.99 [0.78,1.20]; ß = 0.49 [0.34,0.64], respectively). Discussion and conclusion: ICP increases during movement between body positions. The amplitude of the increase in ICP varies with type of movement, age, sex, and BMI. This could be a marker of disturbed ICP dynamics and may be particularly relevant for patients with CSF-diverting shunts in situ.

Stance instability in spinocerebellar ataxia type 6.

Balance impairment is a principal symptom of cerebellar disease, but is poorly understood partly because subjects with heterogenous cerebellar and extracerebellar lesions have often been studied. Spinocerebellar ataxia type 6 (SCA6) provides an opportunity to understand balance dysfunction associated with a relatively homogenous cerebellar lesion. This study investigated stance instability in SCA6 and how it is affected by varying stance width. Body sway, as well as its directional preponderance and distribution across joints, was measured three-dimensionally in 17 SCA6 and 17 matched healthy control subjects. Subjects stood for 40 seconds on a stable surface with their eyes open and feet positioned at various stance widths (32, 16, 8, 4, and 0 cm). SCA6 subjects swayed faster than controls at every stance width. Decreasing the stance width produced a disproportionate increase in sway speed in SCA6 subjects, compared to controls. Directional preponderance of sway was dependent on stance width, but did not differ between groups. Joint instability was increased by reducing stance width in both groups, but there was greater instability of the ankle joint in the roll plane in the SCA6 group. Measures of global instability correlated strongly with disease severity measured with the Scale for the Assessment and Rating of Ataxia (r = 0.79). The sway characteristics suggest a disruption of sensorimotor processing for balance control in SCA6. The correlation with disease severity implies that balance impairment is a feature of progression of SCA6 clinical syndrome. With stance width standardized, the instability measures employed could provide sensitive, continuous outcome measures of longitudinal or therapeutic change.

Hypokinesia without decrement distinguishes progressive supranuclear palsy from Parkinson's disease.

Repetitive finger tapping is commonly used to assess bradykinesia in Parkinson's disease. The Queen Square Brain Bank diagnostic criterion of Parkinson's disease defines bradykinesia as 'slowness of initiation with progressive reduction in speed and amplitude of repetitive action'. Although progressive supranuclear palsy is considered an atypical parkinsonian syndrome, it is not known whether patients with progressive supranuclear palsy have criteria-defined bradykinesia. This study objectively assessed repetitive finger tap performance and handwriting in patients with Parkinson's disease (n = 15), progressive supranuclear palsy (n = 9) and healthy age- and gender-matched controls (n = 16). The motion of the hand and digits was recorded in 3D during 15-s repetitive index finger-to-thumb tapping trials. The main finding was hypokinesia without decrement in patients with progressive supranuclear palsy, which differed from the finger tap pattern in Parkinson's disease. Average finger separation amplitude in progressive supranuclear palsy was less than half of that in controls and Parkinson's disease (P < 0.001 in both cases). Change in tap amplitude over consecutive taps was computed by linear regression. The average amplitude slope in progressive supranuclear palsy was nearly zero (0.01°/cycle) indicating a lack of decrement, which differed from the negative slope in patients with Parkinson's disease OFF levodopa (-0.20°/cycle, P = 0.002). 'Hypokinesia', defined as <50% of control group's mean amplitude, combined with 'absence of decrement', defined as mean positive amplitude slope, were identified in 87% of finger tap trials in the progressive supranuclear palsy group and only 12% in the Parkinson's disease OFF levodopa group. In progressive supranuclear palsy, the mean amplitude was not correlated with disease duration or other clinimetric scores. In Parkinson's disease, finger tap pattern was compatible with criteria-defined bradykinesia, characterized by slowness with progressive reduction in amplitude and speed and increased variability in speed throughout the tap trial. In Parkinson's disease, smaller amplitude, slower speed and greater speed variability were all associated with a more severe Unified Parkinson's Disease Rating Scale motor score. Analyses of handwriting showed that micrographia, defined as smaller than 50% of the control group's mean script size, was present in 75% of patients with progressive supranuclear palsy and 15% of patients with Parkinson's disease (P = 0.022). Most scripts performed by patients with progressive supranuclear palsy did not exhibit decrements in script size. In conclusion, patients with progressive supranuclear palsy have a specific finger tap pattern of 'hypokinesia without decrement' and they do not have criteria-defined limb bradykinesia. Similarly, 'micrographia' and 'lack of decrement in script size' are also more common in progressive supranuclear palsy than in Parkinson's disease.

Doorway-provoked freezing of gait in Parkinson's disease.

Freezing of gait in Parkinson's disease can be difficult to study in the laboratory. Here we investigate the use of a variable-width doorway to provoke freeze behavior together with new objective methods to measure it. With this approach we compare the effects of anti-parkinsonian treatments (medications and deep-brain stimulation of the subthalamic nucleus) on freezing and other gait impairments. Ten "freezers" and 10 control participants were studied. Whole-body kinematics were measured while participants walked at preferred speed in each of 4 doorway conditions (no door present, door width at 100%, 125%, and 150% of shoulder width) and in 4 treatment states (offmeds/offstim, offmeds/onstim, onmeds/offstim, onmeds/onstim). With no doorway, the Parkinson's group showed characteristic gait disturbances including slow speed, short steps, and variable step timing. Treatments improved these disturbances. The Parkinson's group slowed further at doorways by an amount inversely proportional to door width, suggesting a visuomotor dysfunction. This was not improved by either treatment alone. Finally, freeze-like events were successfully provoked near the doorway and their prevalence significantly increased in narrower doorways. These were defined clinically and by 2 objective criteria that correlated well with clinical ratings. The risk of freeze-like events was reduced by medication but not by deep-brain stimulation. Freeze behavior can be provoked in a replicable experimental setting using the variable-width doorway paradigm, and measured objectively using 2 definitions introduced here. The differential effects of medication and deep-brain stimulation on the gait disturbances highlight the complexity of Parkinsonian gait disorders and their management.

Foot drop splints improve proximal as well as distal leg control during gait in Charcot-Marie-Tooth disease.

INTRODUCTION: During walking, people with Charcot-Marie-Tooth (CMT) disease may compensate for distal weakness by using proximal muscles. We investigated the effect of different AFOs on distal leg control and proximal compensatory actions. METHODS: Fourteen people with CMT were tested while wearing 3 types of ankle-foot orthosis (AFO) bilaterally compared with shoes alone. Walking was assessed using three-dimensional gait analysis. Stiffness of the splints was measured by applying controlled 5-degree ankle stretches using a motor. RESULTS: The results showed that each AFO significantly stiffened the ankle and increased ankle dorsiflexion at foot clearance compared with shoes alone. At push off, peak ankle power generation was reduced, but only with 1 type of AFO. A significant decrease in hip flexion amplitude during the swing phase was observed with all 3 AFOs. CONCLUSIONS: These results indicate that AFOs reduce foot drop and remove the need for some proximal compensatory action.

Adaptation of vestibular signals for self-motion perception.

A fundamental concern of the brain is to establish the spatial relationship between self and the world to allow purposeful action. Response adaptation to unvarying sensory stimuli is a common feature of neural processing, both peripherally and centrally. For the semicircular canals, peripheral adaptation of the canal-cupula system to constant angular-velocity stimuli dominates the picture and masks central adaptation. Here we ask whether galvanic vestibular stimulation circumvents peripheral adaptation and, if so, does it reveal central adaptive processes. Transmastoidal bipolar galvanic stimulation and platform rotation (20 deg s−1) were applied separately and held constant for 2 min while perceived rotation was measured by verbal report. During real rotation, the perception of turn decayed from the onset of constant velocity with a mean time constant of 15.8 s. During galvanic-evoked virtual rotation, the perception of rotation initially rose but then declined towards zero over a period of ∼100 s. For both stimuli, oppositely directed perceptions of similar amplitude were reported when stimulation ceased indicating signal adaptation at some level. From these data the time constants of three independent processes were estimated: (i) the peripheral canal-cupula adaptation with time constant 7.3 s, (ii) the central 'velocity-storage' process that extends the afferent signal with time constant 7.7 s, and (iii) a long-term adaptation with time constant 75.9 s. The first two agree with previous data based on constant-velocity stimuli. The third component decayed with the profile of a real constant angular acceleration stimulus, showing that the galvanic stimulus signal bypasses the peripheral transformation so that the brainstem sees the galvanic signal as angular acceleration. An adaptive process involving both peripheral and central processes is indicated. Signals evoked by most natural movements will decay peripherally before adaptation can exert an appreciable effect, making a specific vestibular behavioural role unlikely. This adaptation appears to be a general property of the internal coding of self-motion that receives information from multiple sensory sources and filters out the unvarying components regardless of their origin. In this instance of a pure vestibular sensation, it defines the afferent signal that represents the stationary or zero-rotation state.

The fusimotor and reafferent origin of the sense of force and weight.

Signals associated with the command the brain sends to muscles are thought to create the sensation of heaviness when we lift an object. Thus, as a muscle is weakened by fatigue or partial paralysis (neuromuscular blockade), the increase in the motor command needed to lift a weight is thought to explain the increasing subjective heaviness of the lifted object.With different fatiguing contractions we approximately halved the force output of the thumb flexor muscles, which were then used to lift an object. For two deafferented subjects the perceived heaviness of the lifted object approximately doubled, in keeping with the central-signal theory. However, for normal subjects this resulted in objects feeling the same or lighter, inconsistent with the central-signal theory but consistent with the expected effects of the conditioning contractions on the sensitivity of peripheral receptors. In separate experiments we subjected the forearm muscles to complete paralysis with a non-depolarising neuromuscular blocking agent and then allowed them to recover to approximately half-force output. This also resulted in objects feeling lighter when lifted by the semi-paralysed thumb, even though the motor command to the motoneurons must have been greater. This is readily explained by reduced lift-related reafference caused by the prolonged paralysis of muscle spindle intrafusal fibres.We conclude that peripheral signals, including a major contribution from muscle spindles, normally give rise to the sense of exerted force. In concept, however, reafference from peripheral receptors may also be considered a centrally generated signal that traverses efferent and then afferent pathways to feed perceptual centres rather than one confined entirely to the central nervous system. These results therefore challenge the distinction between central- and peripheral-based perception, and the concept that muscle spindles provide only information about limb position and movement.

Gait in SWEDDs patients: comparison with Parkinson's disease patients and healthy controls.

Patients diagnosed with Parkinson's disease on clinical grounds who subsequently turn out to have normal dopamine transporter imaging have been referred to as SWEDDs (scans without evidence of dopaminergic deficits). Despite having clinical features similar to those of Parkinson's disease, these patients seem to have different pathophysiology, prognosis, and treatment requirements. In this study we determined the similarities and differences in the gaits of SWEDDs and Parkinson's disease patients to investigate whether walking patterns can distinguish these entities. We used 3-D motion capture to analyze the gaits of 11 SWEDDs patients (who had unilateral or asymmetric upper limb tremor with a rest component), 12 tremor-dominant Parkinson's disease patients, and 13 healthy control participants. In common with Parkinson's disease patients, SWEDDs patients had a slow gait mainly because of a small stride length, as well as a reduced arm swing. However, several abnormal features of posture and gait in Parkinson's disease were normal in SWEDDs. Thus, SWEDDs patients had normal trunk and elbow posture, normal stride length variability, and normal bilateral step-phase coordination, all of which were abnormal in Parkinson's disease patients. We also searched for signs of ataxic movements during normal and tandem walking, but found no evidence that ataxic gait was a general feature in SWEDDs. These findings could aid the clinician in identification of potential tremulous SWEDDs cases. © 2011 Movement Disorder Society.