C-STIM: Protocol for a randomized, single-blind, crossover study of cerebellar repetitive transcranial magnetic stimulation (rTMS) for postural instability in people with progressive supranuclear palsy (PSP).

Background: Methods for modulating the cerebellum with transcranial magnetic stimulation (TMS) are well established, and preliminary data from our group and others has shown evidence of transient improvements in balance after cerebellar repetitive transcranial magnetic stimulation (rTMS) in progressive suprancuclear palsy (PSP). This study examines extensive posturography measures before and after 10 sessions of cerebellar rTMS and sham TMS in PSP. Methods: Thirty subjects with PSP and postural instability will undergo cerebellar active and sham rTMS in a single-blind, crossover design with a randomized order of a 10-day intervention. Primary outcomes will be changes in sway area and medio-lateral range of sway with eyes open while standing on a stationary force-plate, and safety, tolerability, and blindedness. Secondary outcomes will include posturography and gait analysis with body-worn, triaxial inertial sensors, clinical balance scales and questionnaires, and a bedside test of vestibular function. Exploratory outcomes are changes in functional near infrared spectroscopy (fNIRS) signal over the prefrontal, supplementary motor, and primary motor cortices while standing and walking, and speech samples for future analysis. Discussion: The C-STIM crossover intervention study adds a longer duration of stimulation and extensive posturography measures to more finely measure the improvements in balance and exploratory functional near-infrared spectroscopy (fNIRS) over the prefronal, supplementary motor, and primary motor cortices during balance assessments before and after 10 sessions of cerebellar rTMS and 10 sessions of sham cerebellar TMS. This project will improve our understanding of the importance of the cerebellum for control of postural stability in PSP.

TURN-IT: a novel turning intervention program to improve quality of turning in daily life in people with Parkinson's disease.

BACKGROUND: People with Parkinson's disease (PD) have a high fall rate and many falls are associated with turns. Despite this, there is minimal research on effects of rehabilitation on the quality of turns. Further, quantifying turns in the home may have broader implications since rehabilitation of turns would ideally improve turning in real world mobility. METHODS: Sixty people with PD and a history of falls will be randomized to receive either a novel TURNing InTervention (TURN-IT) or no intervention (control group). The TURN-IT group will be seen for 6 weeks (18 visits) for an individualized, progressive program that is based on the specific constraints of turning in PD. Wearable sensors will be used to measure 7 days of mobility, including turns, before and after intervention or control period. In addition, blinded assessments of gait, mobility and turns will occur before and after intervention for both groups and falls will be monitored for twelve months post intervention with bimonthly email questionnaires. DISCUSSION: This study has the potential to change how we rehabilitate and assess turning in people with PD and falls. There are several novel aspects to our study including a comprehensive turning-focused intervention that is tailored to the underlying constraints that impair turning in people with PD. Further, our outcome measure of turning quality during 7 days of daily life is novel and has implications for determining real-life changes after rehabilitation. The ultimate goal of this rehabilitation intervention is to improve how patients turn in daily life and to reduce falls. TRIALS REGISTRATION: This protocol is registered at clinicaltrials.gov; #NCT04897256; https://clinicaltrials.gov/ct2/show/NCT04897256?term=Horak&cond=Parkinson+Disease&draw=2&rank=4 .

Consensus Paper: Neurophysiological Assessments of Ataxias in Daily Practice.

The purpose of this consensus paper is to review electrophysiological abnormalities and to provide a guideline of neurophysiological assessments in cerebellar ataxias. All authors agree that standard electrophysiological methods should be systematically applied in all cases of ataxia to reveal accompanying peripheral neuropathy, the involvement of the dorsal columns, pyramidal tracts and the brainstem. Electroencephalography should also be considered, although findings are frequently non-specific. Electrophysiology helps define the neuronal systems affected by the disease in an individual patient and to understand the phenotypes of the different types of ataxia on a more general level. As yet, there is no established electrophysiological measure which is sensitive and specific of cerebellar dysfunction in ataxias. The authors agree that cerebellar brain inhibition (CBI), which is based on a paired-pulse transcranial magnetic stimulation (TMS) paradigm assessing cerebellar-cortical connectivity, is likely a useful measure of cerebellar function. Although its role in the investigation and diagnoses of different types of ataxias is unclear, it will be of interest to study its utility in this type of conditions. The authors agree that detailed clinical examination reveals core features of ataxia (i.e., dysarthria, truncal, gait and limb ataxia, oculomotor dysfunction) and is sufficient for formulating a differential diagnosis. Clinical assessment of oculomotor function, especially saccades and the vestibulo-ocular reflex (VOR) which are most easily examined both at the bedside and with quantitative testing techniques, is of particular help for differential diagnosis in many cases. Pure clinical measures, however, are not sensitive enough to reveal minute fluctuations or early treatment response as most relevant for pre-clinical stages of disease which might be amenable to study in future intervention trials. The authors agree that quantitative measures of ataxia are desirable as biomarkers. Methods are discussed that allow quantification of ataxia in laboratory as well as in clinical and real-life settings, for instance at the patients' home. Future studies are needed to demonstrate their usefulness as biomarkers in pharmaceutical or rehabilitation trials.

Case Studies in Neuroscience: A dissociation of balance and posture demonstrated by camptocormia.

Upright stance in humans requires an intricate exchange between the neural mechanisms that control balance and those that control posture; however, the distinction between these control systems is hard to discern in healthy subjects. By studying balance and postural control of a participant with camptocormia - an involuntary flexion of the trunk during standing that resolves when supine - a divergence between balance and postural control was revealed. A kinematic and kinetic investigation of standing and walking showed a stereotyped flexion of the upper body by almost 80° over a few minutes, and yet the participant's ability to control center of mass within the base of support and to compensate for external perturbations remained intact. This unique case also revealed the involvement of automatic, tonic control of the paraspinal muscles during standing and the effects of attention. Although strength was reduced and MRI showed a reduction in muscle mass, there was sufficient strength to maintain an upright posture under voluntary control and when using geste antagoniste maneuvers or "sensory tricks" from visual, auditory, and haptic biofeedback. Dual tasks that either increased or decreased the attention given to postural alignment would decrease or increase the postural flexion, respectively. The custom-made "twister" device that measured axial resistance to slow passive rotation revealed abnormalities in axial muscle tone distribution during standing. The results suggest that the disorder in this case was due to a disruption in the automatic, tonic drive to the postural muscles and that myogenic changes were secondary. NEW & NOTEWORTHY By studying an idiopathic camptocormia case with a detailed biomechanical and sensorimotor approach, we have demonstrated unique insights into the neural control of human bipedalism 1) balance and postural control cannot be considered the same neural process, as there is a stereotyped abnormal flexed posture, without balance deficits, associated with camptocormia, and 2) posture during standing is controlled by automatic axial tone but "sensory tricks" involving sensory biofeedback to direct voluntary attention to postural alignment can override, when required.

Effects of freezing of gait on postural motor learning in people with Parkinson's disease.

Protective postural responses, including stepping, to recover equilibrium are critical for fall prevention and are impaired in people with Parkinson's disease (PD) with freezing of gait (FoG). Improving protective postural responses through training may reduce falls in this population. However, motor learning, the basis of neurorehabilitation, is also impaired in people with PD and, in particular, people with PD who experience freezing. It is unknown whether people with PD who freeze can improve protective postural responses, and whether these improvements are similar to nonfreezers. Our goal was to assess whether people with freezing can improve protective postural responses and retain these improvements similarly to nonfreezers. Twenty-eight people with PD (13 freezers, 15 nonfreezers) were enrolled. Improvement in protective postural responses was assessed over the course of 25 forward and 25 backward support surface translations (delivered in pseudo-random order). Postural responses were re-assessed 24h later to determine whether improvements were retained. People who freeze did not improve or retain improvement in protective postural responses as well as nonfreezers in our primary outcome variable, center of mass (COM) displacement after perturbations (post hoc across group assessments: freezers- p=0.14 and nonfreezers- p=0.001, respectively). However, other protective stepping outcomes, including margin of stability, step length, and step time, improved similarly across groups. Significant improvements were retained in both groups. In conclusion, people with PD who freeze exhibited reduced ability to improve protective postural responses in some, but not all, outcome variables. Additional training may be necessary to improve protective postural responses in people with PD who freeze.

Supraspinal control of automatic postural responses in people with multiple sclerosis.

The neural underpinnings of delayed automatic postural responses in people with multiple sclerosis (PwMS) are unclear. We assessed whether white matter pathways of two supraspinal regions (the cortical proprioceptive Broadman's Area-3; and the balance/locomotor-related pedunculopontine nucleus) were related to delayed postural muscle response latencies in response to external perturbations. 19 PwMS (48.8±11.4years; EDSS=3.5 (range: 2-4)) and 12 healthy adults (51.7±12.2years) underwent 20 discrete, backward translations of a support surface. Onset latency of agonist (medial-gastrocnemius) and antagonist (tibialis anterior) muscles were assessed. Diffusion tensor imaging assessed white-matter integrity (i.e. radial diffusivity) of cortical proprioceptive and balance/locomotor-related tracts. Latency of the tibialis anterior, but not medial gastrocnemius was larger in PwMS than control subjects (p=0.012 and 0.071, respectively). Radial diffusivity of balance/locomotor tracts was higher (worse) in PwMS than control subjects (p=0.004), and was significantly correlated with tibialis (p=0.002), but not gastrocnemius (p=0.06) onset latency. Diffusivity of cortical proprioceptive tracts was not correlated with muscle onset. Lesions in supraspinal structures including the pedunculopontine nucleus balance/locomotor network may contribute to delayed onset of postural muscle activity in PwMS, contributing to balance deficits in PwMS.

Identification of Balance Deficits in People with Parkinson Disease; is the Sensory Organization Test Enough?

BACKGROUND AND PURPOSE: Balance deficits in people with Parkinson's disease can affect any of the multiple systems encompassing balance control. Thus, identification of the specific deficit is crucial in customizing balance rehabilitation. The sensory organization test, a test of sensory integration for balance control, is sometimes used in isolation to identify balance deficits in people with Parkinson's disease. More recently, the Mini-Balance Evaluations Systems Test, a clinical scale that tests multiple domains of balance control, has begun to be used to assess balance in patients with Parkinson's disease. The purpose of our study was to compare the use of Sensory Organization Test and Mini-Balance Evaluations Systems Test in identifying balance deficits in people with Parkinson's disease. METHODS: 45 participants (27M, 18F; 65.2 ± 8.2 years) with idiopathic Parkinson's disease participated in the cross-sectional study. Balance assessment was performed using the Sensory Organization Test and the Mini-Balance Evaluations Systems Test. People were classified into normal and abnormal balance based on the established cutoff scores (normal balance: Sensory Organization Test >69; Mini-Balance Evaluations Systems Test >73). RESULTS: More subjects were classified as having abnormal balance with the Mini-Balance Evaluations Systems Test (71% abnormal) than with the Sensory Organization Test (24% abnormal) in our cohort of people with Parkinson's disease. There were no subjects with a normal Mini-Balance Evaluations Systems Test score but abnormal Sensory Organization Test score. In contrast, there were 21 subjects who had an abnormal Mini-Balance Evaluations Systems Test score but normal Sensory Organization Test scores. DISCUSSION AND CONCLUSIONS: Findings from this study suggest that investigation of sensory integration deficits, alone, may not be able to identify all types of balance deficits found in patients with Parkinson's disease. Thus, a comprehensive approach should be used to test of multiple balance systems to provide customized rehabilitation.

Neural Control of Walking in People with Parkinsonism.

People with Parkinson's disease exhibit debilitating gait impairments, including gait slowness, increased step variability, and poor postural control. A widespread supraspinal locomotor network including the cortex, cerebellum, basal ganglia, and brain stem contributes to the control of human locomotion, and altered activity of these structures underlies gait dysfunction due to Parkinson's disease.

Do cognitive measures and brain circuitry predict outcomes of exercise in Parkinson Disease: a randomized clinical trial.

BACKGROUND: There is emerging research detailing the relationship between balance/gait/falls and cognition. Imaging studies also suggest a link between structural and functional changes in the frontal lobe (a region commonly associated with cognitive function) and mobility. People with Parkinson's disease have important changes in cognitive function that may impact rehabilitation efficacy. Our underlying hypothesis is that cognitive function and frontal lobe connections with the basal ganglia and brainstem posture/locomotor centers are responsible for postural deficits in people with Parkinson's disease and play a role in rehabilitation efficacy. The purpose of this study is to 1) determine if people with Parkinson's disease can improve mobility and/or cognition after partaking in a cognitively challenging mobility exercise program and 2) determine if cognition and brain circuitry deficits predict responsiveness to exercise rehabilitation. METHODS/DESIGN: This study is a randomized cross-over controlled intervention to take place at a University Balance Disorders Laboratory. The study participants will be people with Parkinson's disease who meet inclusion criteria for the study. The intervention will be 6 weeks of group exercise (case) and 6 weeks of group education (control). The exercise is a cognitively challenging program based on the Agility Boot Camp for people with PD. The education program is a 6-week program to teach people how to better live with a chronic disease. The primary outcome measure is the MiniBESTest and the secondary outcomes are measures of mobility, cognition and neural imaging. DISCUSSION: The results from this study will further our understanding of the relationship between cognition and mobility with a focus on brain circuitry as it relates to rehabilitation potential. TRIAL REGISTRATION: This trial is registered at clinical trials.gov (NCT02231073).

Compensatory stepping in Parkinson's disease is still a problem after deep brain stimulation randomized to STN or GPi.

The effects of deep brain stimulation (DBS) on balance in people with Parkinson's disease (PD) are not well established. This study examined whether DBS randomized to the subthalamic nucleus (STN; n = 11) or globus pallidus interna (GPi; n = 10) improved compensatory stepping to recover balance after a perturbation. The standing surface translated backward, forcing subjects to take compensatory steps forward. Kinematic and kinetic responses were recorded. PD-DBS subjects were tested off and on their levodopa medication before bilateral DBS surgery and retested 6 mo later off and on DBS, combined with off and on levodopa medication. Responses were compared with PD-control subjects (n = 8) tested over the same timescale and 17 healthy control subjects. Neither DBS nor levodopa improved the stepping response. Compensatory stepping in the best-treated state after surgery (DBS+DOPA) was similar to the best-treated state before surgery (DOPA) for the PD-GPi group and the PD-control group. For the PD-STN group, there were more lateral weight shifts, a delayed foot-off, and a greater number of steps required to recover balance in DBS+DOPA after surgery compared with DOPA before surgery. Within the STN group five subjects who did not fall during the experiment before surgery fell at least once after surgery, whereas the number of falls in the GPi and PD-control groups were unchanged. DBS did not improve the compensatory step response needed to recover from balance perturbations in the GPi group and caused delays in the preparation phase of the step in the STN group.

Association of cognitive domains with postural instability/gait disturbance in Parkinson's disease.

INTRODUCTION: Research suggests an association between global cognition and postural instability/gait disturbance (PIGD) in Parkinson disease (PD), but the relationship between specific cognitive domains and PIGD symptoms is not clear. This study examined the association of cognition (global and specific cognitive domains) with PIGD symptoms in a large, well-characterized sample of individuals with PD. METHODS: Cognitive function was measured with a detailed neuropsychological assessment, including global cognition, executive function, memory, visuospatial function, and language. PIGD symptoms were measured using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, Motor Examination subscale. Multiple linear regression analyses were performed to assess the relationship between cognition and PIGD symptoms with models adjusting for age, sex, education, enrollment site, disease duration, and motor symptom severity. RESULTS: The analysis included 783 participants, with mean (standard deviation) age of 67.3 (9.7) years and median (interquartile range) MDS-UPDRS Motor Subscale score of 26 (17, 35). Deficits in global cognition, executive function, memory, and phonemic fluency were associated with more severe PIGD symptoms. Deficits in executive function were associated with impairments in gait, freezing, and postural stability, while visuospatial impairments were associated only with more severe freezing, and poorer memory function was associated only with greater postural instability. DISCUSSION: While impairments in global cognition and aspects of executive functioning were associated with more severe PIGD symptoms, specific cognitive domains were differentially related to distinct PIGD components, suggesting the presence of multiple neural pathways contributing to associations between cognition and PIGD symptoms in persons with PD.

Exploring outcome measures for exercise intervention in people with Parkinson's disease.

Background. It is widely believed that exercise improves mobility in people with Parkinson's disease (PD). However, it is difficult to determine whether a specific type of exercise is the most effective. The purpose of this study was to determine which outcome measures were sensitive to exercise intervention and to explore the effects of two different exercise programs for improving mobility in patients with PD. Methods. Participants were randomized into either the Agility Boot Camp (ABC) or treadmill training; 4x/week for 4 weeks. Outcome measures were grouped by the International Classification of Function/Disability (ICF). To determine the responsiveness to exercise, we calculated the standardized response means. t-tests were used to compare the relative benefits of each exercise program. Results. Four of five variables at the structure/function level changed after exercise: turn duration (P = 0.03), stride velocity (P = 0.001), peak arm speed (P = 0.001), and horizontal trunk ROM during gait (P = 0.02). Most measures improved similarly for both interventions. The only variable that detected a difference between groups was postural sway in ABC group (F = 4.95; P = 0.03). Conclusion. Outcome measures at ICF body structure/function level were most effective at detecting change after exercise and revealing differences in improvement between interventions.

Adaptation of gait termination on a slippery surface in Parkinson's disease.

Parkinson's disease (PD) causes instability and difficulty adapting to changing environmental and task demands. We examined the effects of PD on the adaptation of gait termination (GT) on a slippery surface under unexpected and cued circumstances. An unexpected slip perturbation during GT was followed by a slip perturbation during GT under two conditions: planned over multiple steps and cued one step prior to GT. Feed forward and feedback-based responses to the perturbation were compared to determine (1) how PD affects the ability to integrate adaptive feed forward and feedback-based GT strategies on a slippery surface, (2) if adaptations can be implemented when GT is required within one step, and (3) if behaviour changes with repeated exposure. Similar to the control group (n=10), the PD group (n=8) adapted and integrated feed forward and feedback-based components of GT under both stop conditions. Feed forward adaptations included a shorter, wider step, and appropriate stability margin modifications. Feedback-based adaptations included a longer, wider subsequent step. When cued to stop quickly, both groups maintained most of these adaptations: foot angle at contact increased in the first cued stop but adapted with practice. The group with PD differed in their ability to adapt GT with slower, wider steps and less stability.

Body-worn motion sensors detect balance and gait deficits in people with multiple sclerosis who have normal walking speed.

While balance and gait limitations are hallmarks of multiple sclerosis (MS), standard stopwatch-timed measures practical for use in the clinic are insensitive in minimally affected patients. This prevents early detection and intervention for mobility problems. The study sought to determine if body-worn sensors could detect differences in balance and gait between people with MS with normal walking speeds and healthy controls. Thirty-one MS and twenty-eight age- and sex-matched control subjects were tested using body-worn sensors both during quiet stance and gait (Timed Up and Go test, TUG). Results were compared to stopwatch-timed measures. Stopwatch durations of the TUG and Timed 25 Foot Walk tests were not significantly different between groups. However, during quiet stance with eyes closed, people with MS had significantly greater sway acceleration amplitude than controls (p=0.02). During gait, people with MS had greater trunk angular range of motion in roll (medio-lateral flexion, p=0.017) and yaw (axial rotation, p=0.026) planes. Turning duration through 180° was also longer in MS (p=0.031). Thus, body-worn motion sensors detected mobility differences between MS and healthy controls when traditional timed tests could not. This portable technology provides objective and quantitative mobility data previously not obtainable in the clinic, and may prove a useful outcome measure for early mobility changes in MS.

Walking in circles: navigation deficits from Parkinson's disease but not from cerebellar ataxia.

Little is known on the role of neuronal structures for spatial navigation. Our goal was to examine how Parkinson's disease (PD) and cerebellar ataxia, as human lesion models of the basal ganglia and cerebellum, affect spatial navigation round a circular walking path, blindfolded. Twelve subjects with idiopathic PD (ON and OFF medication), eight subjects with cerebellar ataxia and a control group of 20 age-matched healthy subjects participated. All groups performed well when walking around the circle with eyes open. In the eyes-closed condition, control subjects overshot the outlined trajectory but returned to their initial position, thus walking a further distance with eyes closed than with eyes open. When OFF medication, PD subjects navigated a larger radius than controls with eyes closed. When ON levodopa, PD subjects walked a similar distance as controls but with even larger errors in endpoint. Surprisingly, cerebellar patients navigated the circular walking task in the eyes closed condition with even more accuracy (i.e. following the outlined circle) than control and PD subjects. We conclude that blindfolded navigation around a previously seen circle requires intact basal ganglia, but not cerebellar input.

Increased dynamic regulation of postural tone through Alexander Technique training.

Gurfinkel and colleagues (2006) recently found that healthy adults dynamically modulate postural muscle tone in the body axis during anti-gravity postural maintenance and that this modulation is inversely correlated with axial stiffness. Our objective in the present study was to investigate whether dynamic modulation of axial postural tone can change through training. We examined whether teachers of the Alexander Technique (AT), who undergo "long-term" (3-year) training, have greater modulation of axial postural tone than matched control subjects. In addition, we performed a longitudinal study on the effect of "short-term" (10-week) AT training on the axial postural tone of individuals with low back pain (LBP), since short term AT training has previously been shown to reduce LBP. Axial postural tone was quantified by measuring the resistance of the neck, trunk and hips to small (±10°), slow (1°/s) torsional rotation during stance. Modulation of tone was determined by the torsional resistance to rotation (peak-to-peak, phase-advance, and variability of torque) and axial muscle activity (EMG). Peak-to-peak torque was lower (∼50%), while phase-advance and cycle-to-cycle variability were enhanced for AT teachers compared to matched control subjects at all levels of the axis. In addition, LBP subjects decreased trunk and hip stiffness following short-term AT training compared to a control intervention. While changes in static levels of postural tone may have contributed to the reduced stiffness observed with the AT, our results suggest that dynamic modulation of postural tone can be enhanced through long-term training in the AT, which may constitute an important direction for therapeutic intervention.

Haptic touch reduces sway by increasing axial tone.

It is unclear how haptic touch with a stable surface reduces postural sway. We hypothesized that haptic input enhances postural stability due to alterations in axial postural tone. We measured the influence of heavy and light touch (LT) of the hands on a stable bar on axial postural tone and postural sway during stance in 14 healthy adults. A unique "Twister" device measured hip torque by fixing the upper body in space while oscillating the surface in yaw ±10 at 1 deg/s. Subjects were tested while: (1) standing quietly with their arms at their sides, (2) lightly touching a rigid bar in front of them and (3) firmly gripping the bar. Horizontal and vertical sway was not restricted by the device's yaw fixation, therefore, the subjects remained in a state of active postural control during the three touch conditions. Haptic touch significantly increased hip postural tone by 44% during light touch, from 2.5±0.9 to 3.6±1.0 Nm (P=0.005), and by 40% during firm grip to 3.5±0.8 Nm (P=0.005). Increases in hip postural tone were associated with a reduction in postural sway (r=-0.55, P=0.001). This is the first study showing that axial postural tone can be modified by remote somatosensory input and provides a potential explanation for how light touch improves postural stability. Changes in subjects' perception from trunk to surface rotation when changing from no touch (NT) to haptic touch, suggests that the CNS changes from using a global, to a local, trunk reference frame for control of posture during touch. The increase of hip postural tone during touching and gripping can be explained as a suppression of hip muscle shortening reactions that normally assist axial rotation.

A meta-regression of the long-term effects of deep brain stimulation on balance and gait in PD.

OBJECTIVE: Deep brain stimulation (DBS) alleviates the cardinal Parkinson disease (PD) symptoms of tremor, rigidity, and bradykinesia. However, its effects on postural instability and gait disability (PIGD) are uncertain. Contradictory findings may be due to differences the in stimulation site and the length of time since DBS surgery. This prompted us to conduct the first meta-regression of long-term studies of bilateral DBS in the subthalamic nucleus (STN) and globus pallidus interna (GPi). RESULTS: Eleven articles reported a breakdown of the Unified Parkinson's Disease Rating Scale score before and beyond 3 years postsurgery (mean 4.5 years). Random effects meta-regression revealed that DBS initially improved PIGD compared to the OFF medicated state before surgery, but performance declined over time and extrapolation showed subjects would reach presurgery levels 9 years postsurgery. ON medication, DBS improved PIGD over and above the effect of medication before surgery. Nevertheless, for the STN group, PIGD progressively declined and was worse than presurgery function within 2 years. In contrast, GPi patients showed no significant long-term decline in PIGD in the medicated state. Improvements in cardinal signs with DBS at both sites were maintained across 5 years in the OFF and ON medication states. CONCLUSIONS: DBS alone does not offer the same improvement to PIGD as it does to the cardinal symptoms, suggesting axial and distal control are differentially affected by DBS. GPi DBS in combination with levodopa seemed to preserve PIGD better than did STN DBS, although more studies of GPi DBS and randomized controls are needed.

Axial kinesthesia is impaired in Parkinson's disease: effects of levodopa.

Integration of sensory and motor inputs has been shown to be impaired in appendicular muscles and joints of Parkinson's disease (PD) patients. As PD advances, axial symptoms such as gait and balance impairments appear, which often progresses to complete inability stand or walk unaided. The current study evaluates kinesthesia in the axial musculature of PD patients during active postural control to determine whether impairments similar to those found in the appendages are also present in the hip and trunk. Using axial twisting, we quantified the detection threshold and directional accuracy of the hip relative to the feet (i.e. Hip Kinesthesia) and the hip relative to the shoulders (i.e. Trunk Kinesthesia). The relation of kinesthetic threshold to disease progression as measured by UPDRS and the effect of levodopa treatment on kinesthesia were assessed in 12 PD compared to age-matched controls. Subjects stood unaided while passively twisted at a very low constant rotational velocity (1 degrees /s). The results showed that accuracy in determining the direction of axial twisting was reduced in PD relative to healthy control subjects in the hip (PD-ON: 81%; PD-OFF: 91%; CTL=96%) and trunk (PD-ON: 81%; PD-OFF: 88%; CTL=95%). Thresholds for perception of axial twisting were increased when PD subjects were ON levodopa versus OFF in both the hip (p<0.01) and the trunk (p<0.05). The magnitude of decrease in sensitivity due to being ON levodopa was significantly correlated with the increase in UPDRS motor scores (Hip: r=0.90, p<0.01 and Trunk: r=0.60, p<0.05). This effect was not significantly correlated with equivalent levodopa dosage. PD subjects with disease onset on the left side of their body showed significantly higher axial thresholds than subjects with right PD onset (p<0.05). In conclusion, deficits in axial kinesthesia seem to contribute to the functional impairments of posture and locomotion in PD. Although levodopa has been shown to improve appendicular kinesthesia, we observed the opposite in the body axis. These findings underscore the dissociable neurophysiological circuits and dopaminergic pathways that are known to innervate these functionally distinct muscle groups.

The relevance of clinical balance assessment tools to differentiate balance deficits.

Control of balance is complex and involves maintaining postures, facilitating movement, and recovering equilibrium. Balance control consists of controlling the body center of mass over its limits of stability. Clinical balance assessment can help to assess fall risk and/or determine the underlying reasons for balance disorders. Most functional balance assessment scales assess fall risk and the need for balance rehabilitation but do not differentiate types of balance deficits. A system approach to clinical balance assessment can differentiate different kinds of balance disorders and a physiological approach can determine underlying sensorimotor mechanisms contributing to balance disorders. Objective measures of balance using computerized systems and wearable inertial sensors can bring more sensitive, specific and responsive balance testing to clinical practice.