Pallidal activity related to posture and movement during reaching in the cat.

We tested the hypothesis that the pallidum contributes to the control of both posture and movement. We recorded neuronal activity from the pallidum in a task in which male cats reached forward from a standing posture to depress a lever. In agreement with previous studies, we found that a majority of pallidal cells (91/116 78%), including neurons in both the entopeduncular nucleus and the globus pallidus, showed significant modulations of their activity during reaching with the contralateral limb. Mostly different populations of cells were active during the transport (flexion) and lever press (extension) phase of the task. Most cells showed dynamic patterns of activity related to the movement. However, a modest proportion of modulated cells (18/91, 20%) showed properties consistent with a contribution to the control of anticipatory postural responses while a further 10% showed activity consistent with a contribution to postural support during the movement. While some cells that showed modified activity only during reaches with the contralateral forelimb, many cells (65/91, 71%) were also activated during reaches with the ipsilateral forelimb. This was particularly true for cells related to the lever press, many of which discharged similarly during reaches of either limb. This suggests a context-dependent control of movement and posture in which the same muscles are used for different functions during contralateral and ipsilateral reach. Comparison with the results from recordings made previously from the motor cortex and the pontomedullary reticular formation in the same task show more similarities with the former than the latter. Significance statement: Pathological changes in basal ganglia function frequently lead to problems with postural stability and gait initiation. Here we show that some neurons in one of the output regions of the basal ganglia, the pallidum, show discharge activity compatible with a contribution to postural control. At the same time, we note that such cells are a minority in this region with most cells being related to movement, rather than posture. We also show that many neurons are active during movements of both the contralateral and ipsilateral limbs, sometimes with identical discharge patterns. We suggest that this indicates a context-dependent regulation of movement and posture in the pallidum.

Stimulation of the pedunculopontine and cuneiform nuclei for freezing of gait and falls in Parkinson disease: Cross-over single-blinded study and long-term follow-up.

INTRODUCTION: Deep brain stimulation (DBS) of the mesencephalic locomotor region, composed of the pedunculopontine (PPN) and cuneiform (CuN) nuclei, has been proposed to treat dopa-resistant gait and balance disorders in Parkinson's disease (PD). Here, we report the long-term effects of PPN- or CuN-DBS on these axial disorders. METHODS: In 6 PD patients operated for mesencephalic locomotor region DBS and prospectively followed for more than 2 years, we assessed the effects of both PPN- and CuN-DBS (On-dopa) in a cross-over single-blind study by using clinical scales and recording gait parameters. Patients were also examined Off-DBS. RESULTS: More than 2 years after surgery, axial and Tinetti scores were significantly aggravated with both PPN- or CuN-DBS relative to before and one year after surgery. Gait recordings revealed an increased double-stance duration with both PPN- or CuN-DBS, higher swing phase duration with CuN-DBS and step width with PPN-DBS. With PPN- versus CuN-DBS, the step length, velocity and cadence were significantly higher; and the double-stance and turn durations significantly lower. Irrespective the target, we found no significant change in clinical scores Off-DBS compared to On-DBS. The duration of anticipatory postural adjustments as well as step length were lower with versus without PPN-DBS. We found no other significant changes in motor, cognitive or psychiatric scores, except an increased anxiety severity. CONCLUSION: In this long-term follow-up study with controlled assessments, PPN- or CuN-DBS did not improve dopa-resistant gait and balance disorders with a worsening of these axial motor signs with time, thus indicating no significant clinical effect.

Pedunculopontine and Cuneiform Nuclei Deep Brain Stimulation for Severe Gait and Balance Disorders in Parkinson's Disease: Interim Results from a Randomized Double-Blind Clinical Trial.

BACKGROUND: Dopa-resistant freezing of gait (FOG) and falls represent the dominant motor disabilities in advanced Parkinson's disease (PD). OBJECTIVE: We investigate the effects of deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR), comprised of the pedunculopontine (PPN) and cuneiform (CuN) nuclei, for treating gait and balance disorders, in a randomized double-blind cross-over trial. METHODS: Six PD patients with dopa-resistant FOG and/or falls were operated for MLR-DBS. Patients received three DBS conditions, PPN, CuN, or Sham, in a randomized order for 2-months each, followed by an open-label phase. The primary outcome was the change in anteroposterior anticipatory-postural-adjustments (APAs) during gait initiation on a force platformResults:The anteroposterior APAs were not significantly different between the DBS conditions (median displacement [1st-3rd quartile] of 3.07 [3.12-4.62] cm with sham-DBS, 1.95 [2.29-3.85] cm with PPN-DBS and 2.78 [1.66-4.04] cm with CuN-DBS; p = 0.25). Step length and velocity were significantly higher with CuN-DBS vs. both sham-DBS and PPN-DBS. Conversely, step length and velocity were lower with PPN-DBS vs. sham-DBS, with greater double stance and gait initiation durations. One year after surgery, step length was significantly lower with PPN-DBS vs. inclusion. We did not find any significant change in clinical scales between DBS conditions or one year after surgery. CONCLUSION: Two months of PPN-DBS or CuN-DBS does not effectively improve clinically dopa-resistant gait and balance disorders in PD patients.

Contribution of the Entopeduncular Nucleus and the Globus Pallidus to the Control of Locomotion and Visually Guided Gait Modifications in the Cat.

We tested the hypothesis that the entopeduncular (EP) nucleus (feline equivalent of the primate GPi) and the globus pallidus (GPe) contribute to both the planning and execution of locomotion and voluntary gait modifications in the cat. We recorded from 414 cells distributed throughout these two nuclei (referred to together as the pallidum) while cats walked on a treadmill and stepped over an obstacle that advanced towards them. Neuronal activity in many cells in both structures was modulated on a step-by-step basis during unobstructed locomotion and was modified in the step over the obstacle. On a population basis, the most frequently observed change, in both the EP and the GPe, was an increase in activity prior to and/or during the swing phase of the step over the obstacle by the contralateral forelimb, when it was the first limb to pass over the obstacle. Our results support a contribution of the pallidum, in concert with cortical structures, to the control of both the planning and the execution of the gait modifications. We discuss the results in the context of current models of pallidal action on thalamic activity, including the possibility that cells in the EP with increased activity may sculpt thalamo-cortical activity.

Role of proprioceptive information to control balance during gait in healthy and hemiparetic individuals.

Proprioceptive information is important for balance control yet little is known about how it is used during gait or how a stroke affects its use. The aim of this study was to evaluate the role of proprioception in controlling balance during gait in healthy participants and after stroke. Twelve healthy and 9 hemiparetic participants walked on an instrumented treadmill in a fully lit room, while whole-body, three-dimensional kinematics were quantified. Vibration was applied continuously or during the stance phase only, on the posterior neck muscles and triceps surae tendon on the non-dominant/paretic side. Difficulty in maintaining dynamic and postural balance was evaluated using stabilizing and destabilizing forces, respectively. Continuous and stance phase vibration of the triceps surae reduced the difficulty in maintaining both dynamic and postural balance in healthy participants (p<.05), with a greater distance between the center of pressure and the limit of the potential base of support, a more backward body position, and no change in spatio-temporal gait parameters. No effect of neck muscle vibration was observed on balance (p=.63 and above). None of the vibration conditions affected balance or gait parameters among stroke participants. The results confirmed that proprioceptive information was not used to control balance during gait in stroke participants. The importance of proprioceptive information may depend on other factors such as walking and visual conditions. Changes in sensory integration ability likely explain the results after stroke. Further study is needed to understand the integration of proprioceptive and visual information to control balance during gait after stroke.