Shifting perspectives on postural instability in Parkinson's disease

Postural instability and falls in Parkinson*s disease (PD) are both common and
devastating. Improved treatment strategies are urgently needed, but this
requires better insights in the underlying pathophysiology. Here, we propose a
new hypothesis, namely that a set-shifting deficit in the basal ganglia
underlies postural instability in PD. This idea was dictated by several
observations. Normal motor control under everyday circumstances requires the
ability to rapidly shift between motor programs. This so-called *set-shifting*
critically depends upon intact basal ganglia functioning.

Two types of set-shifting can be distinguished: cognitive (alternating between
different mental tasks) and motor (shifting between different motor tasks).
Both processes are clearly impaired in PD, but have never been linked to
balance impairment and falls. Such a relationship seems plausible: when balance
is jeopardized subjects must immediately choose from a repertoire of
compensatory strategies, in order to prevent a fall. A particularly crucial
strategy is the ability to take rapid corrective steps. This often requires
set-shifting, depending on what the subject was doing when the fall occurred.
For example, when a balance perturbation occurs during quiet standing, the
subject must shift away from the movement set *standing* to the movement set
*stepping*. Impairments in this motor shifting process would lead to either
delayed or even absent stepping responses, culminating in a fall. In addition,
cognitive set-shifting is required if the person is engaged in mental
activities when the balance perturbation occurs (e.g. holding a conversation).

Prior work already indicated that such *dual task* circumstances are the most
common circumstance under which falls occur in PD. However, no one has thus far
linked set-shifting difficulties to these falls under dual task circumstances.
Therefore, we will investigate the independent and interactive role of
cognitive and motor set-shifting in stepping responses in PD. Our primary aim
is to relate these set-shifting deficits to the ability to adequately react to
postural perturbations, and thereby assess the clinical relevance of these
findings. To be able to clarify the Parkinson specific deficits, healthy
controls are included in this study as well. Our long-term perspective is to
use this new knowledge for development of balance training programs in PD that
promote corrective stepping and help to prevent falls.

Primary Objective: To relate the ability to react in time to postural
perturbations to set-shifting performance in Parkinson*s disease patients.
Secondary Objective: To investigate the difference in set-shifting stepping
responses between PD and healthy controls.

Design: A prospective study consisting of two experimental tasks. The first
task will be carried out to assess cognitive and motor switching costs followed
by the second task in which we will assess the ability to adequately react to
postural perturbations.
Duration: Each participants is measured one one day. Inclusion of participants
is planned to start in November 2010 and to end in September 2011.
Setting: All measurements are performed in the Fall Simulator laboratory at the
department of Rehabilitation of the RUN-MC.

The burden for the subjects is limited to a visit to our laboratory to
participate in measurements with a duration of 1-2 hours, without preparation
time. In total we expect the visit to last maximum 3 hours. The experimental
procedures and measurement methods will not cause any harm to the patients. To
prevent falls due to balance perturbations, subjects will wear a safety harness
attached to the ceiling that moves in synchrony with the platform.