Cortical activation patterns measured with functional near-infrared spectroscopy (fNIRS) during freezing of gait triggered by turning and passing doorways in Parkinson's disease.

Freezing of gait (FOG) is one of the most debilitating symptoms in Parkinson*s
disease (PD). Neuroimaging studies have tried to unravel it*s underlying neural
mechanism, but are hampered by severe limitations in study design because
subjects need to lay supine and still in scanners. This study proposes to study
FOG in real-time by using multichannel functional near-infrared spectroscopy
(fNIRS), a mobile neuroimaging technique that has been successfully applied in
other gait studies.

The main objective of this study is to identify cortical brain regions that
show significant altered fNIRS activity during FOG in patients with PD. This is
accomplished by considering four secondary objectives. First, we compare the
cortical activation patterns during normal walking, turning and passing
doorways (without FOG) between PD patients and healthy controls. Second, we
investigate whether activation patterns are different between freezing evoked
by a temporal trigger (turning) and freezing evoked by a spatial trigger
(passing a doorway). Third, we assess whether cortical activity change prior to
a FOG episode, compared to normal walking. Fourth, motor, cognitive and anxiety
scores, which may contribute to freezing, will be tested for association with
the cortical activity.

This is an explorative fNIRS-based imaging study measuring brain oxygenation
over 10 regions of interest in 25 PD patients OFF anti-Parkinson medication
(i.e. following an overnight withdrawal) and 25 healthy controls during a
walking task. The walking task will include 180 degree turns and passages
through a narrow doorway in order to trigger FOG in PD patients. Apart from
fNIRS measurements, motion data from motion sensors and video recordings are
collected during the walking tasks. The motion data and video recordings will
be used to label the fNIRS data with the different conditions (i.e. standing
still, walking, turning, passing doorway, FOG); and to calculate motor scores
(i.e. gait parameters and FOG severity). Cognitive and anxiety scores will be
calculated based on questionnaires.

A visit to Nijmegen to conduct the experiment will take 3 to 3.5 hours in
total. The gait task (including turns and passages through doorways) consists
of four sessions of 6,5 minutes each. Patients will be examined at the OFF
state, i.e. following an overnight withdrawal of their dopaminergic medication.
This is expected to yield more FOG episodes, thereby increasing the power of
the study and requiring fewer participants. The increase of PD symptoms
associated with the OFF state will resolve upon medication intake after the
experiments. Physical tiredness which might occur during the walking test is
minimalized by allowing participants to rest as long as needed between each
session. Persons with PD, and especially those with FOG, are, due to the nature
of their disease, at risk for falling. To reduce this risk of falling, a
researcher will continuously accompany the participant during walking. There
are no risks associated with the use of the fNIRS device or motion sensors and
the burden is considered low. The questionnaires are widely used in medical
research and are considered to place little burden on the participants.