Balance control systems in Parkinson’s disease and the impact of pedunculopontine area stimulation

Abstract

Impaired balance is a major contributor to falls and diminished quality of life in Parkinson’s disease, yet the pathophysiology is poorly understood. Here, we assessed if patients with Parkinson’s disease and severe clinical balance impairment have deficits in the intermittent and continuous control systems proposed to maintain upright stance, and furthermore, whether such deficits are potentially reversible, with the experimental therapy of pedunculopontine nucleus deep brain stimulation. Two subject groups were assessed: (i) 13 patients with Parkinson’s disease and severe clinical balance impairment, implanted with pedunculopontine nucleus deep brain stimulators; and (ii) 13 healthy control subjects. Patients were assessed in the OFF medication state and blinded to two conditions; off and on pedunculopontine nucleus stimulation. Postural sway data (deviations in centre of pressure) were collected during quiet stance using posturography. Intermittent control of sway was assessed by calculating the frequency of intermittent switching behaviour (discontinuities), derived using a wavelet-based transformation of the sway time series. Continuous control of sway was assessed with a proportional–integral–derivative (PID) controller model using ballistic reaction time as a measure of feedback delay. Clinical balance impairment was assessed using the ‘pull test’ to rate postural reflexes and by rating attempts to arise from sitting to standing. Patients with Parkinson’s disease demonstrated reduced intermittent switching of postural sway compared with healthy controls. Patients also had abnormal feedback gains in postural sway according to the PID model. Pedunculopontine nucleus stimulation improved intermittent switching of postural sway, feedback gains in the PID model and clinical balance impairment. Clinical balance impairment correlated with intermittent switching of postural sway (rho = − 0.705, P < 0.001) and feedback gains in the PID model (rho = 0.619, P = 0.011). These results suggest that dysfunctional intermittent and continuous control systems may contribute to the pathophysiology of clinical balance impairment in Parkinson’s disease. Clinical balance impairment and their related control system deficits are potentially reversible, as demonstrated by their improvement with pedunculopontine nucleus deep brain stimulation.

Long-lasting event-related beta synchronizations of electroencephalographic activity in response to support-surface perturbations during upright stance

“…Supraspinal contributions to postural stabilization during human upright stance have been demonstrated by postural instability in patients with neurological disorders such as Parkinson's disease (PD), multiple sclerosis, and stroke (Horak et al 1992;Yamamoto et al 2011;Perera et al 2018;Visser et al 2008;Frzovic et al 2000;Geurts et al 2005). Alterations in patterns of postural sway and postural responses to perturbations induced by a cognitive load (Woollacott and Shumway-Cook 2002) and by motor learning during adapting to novel environmental demands (Horak and Nashner 1986) also provide a glimpse into the roles played by the supraspinal networks in the control of upright posture.…”

Neurophysiological analysis of the clinical pull test

“…Clinicians do not have the benefit of a pull force meter and a mixed linear model to adjust for such confounds. Although the pull test remains a very useful clinical test, these findings help explain why reliability has been an issue and supports the call to develop more objective measures or biomarkers of postural instability (Perera et al 2018).…”

Anatomo‐Functional Mapping of the Primate Mesencephalic Locomotor Region Using Stereotactic Lesions

“…A target location is then variable from one team to another, which increases the difficulty of interpretation of the potential effect of PPN DBS. Although some teams target the PPN itself, other have proposed the sub‐CuN or a more ventral region in the pons . However, the specific target that should be modulated in the mesencephalon to alleviate gait disorders remains unknown, as the normal function of the primate PPN and CuN in the control of locomotion is still poorly understood.…”