Anticipation of coming events in Parkinson*s Disease and Friedreich Ataxia: is timing more disturbed than spatial prediction?

To catch a ball implies that the brain needs to estimate *when* that flying
object is at a specific location, thus preparing the commands for the
appropriate movements. In a recent fMRI study (METc 2006/082), we used a novel
design that enabled contrasting the spatial and temporal characteristics of
such anticipation, with identical visual stimuli, motor responses and levels of
attention. In this experiment, subjects saw a ball moving on a monitor screen.
At the moment it stopped, they had to predict either where the ball would reach
the bottom of the screen, or how much time it would take to reach this bottom.
This study demonstrated the important role of the parietal cortex in both
spatial and temporal anticipation. In timing, additional involvement was seen
of pre-Supplementary Motor Area (preSMA), right prefrontal cortex and the
functionally inteconnected left side of the cerebellum. Coherent activition of
circuitry comprising these cerebral regions indicates that timing includes
sequential ordering of previous and future spatial compositions. The
contributions of preSMA and cerebellum to specifically timing, raises the
question whether dysfunction of these regions leads to disturbed time
prediction. In this respect, the behavioural effect of disturbed (pre)SMA
function may be assumed to occur in patients with Parkinson*s Disease (PD),
while the effect of cerebellar dysfunction can be tested in Friedreich Ataxia
(FA).

PD is a neurodegenerative disorder characterized by resting tremor, rigidity
and bradykinesia. Apart from simple movement dysfunction, additional symptoms
point at deficit in more complex sensorimotor interactions and cognitive
disturbances. Basal ganglia dysfunction caused by the loss of dopamine supply
from the degenerating substantia nigra is a hallmark in the pathophysiology of
PD. Both the reduction of dopaminergic innervations of the medial prefrontal
cortex and the decreased frontal cortical outflow of the basal ganglia may
explain the association with non-motor symptoms, and support the hypothesis
that timing may be more affected than spatial prediction in our paradigm. FA is
another slowly progressive neurodegenerative disorder dominated by the
manifestation of a cerebellar syndrome. Deterioration of particularly the
cerebellum is the reason to study the specificity of timing deficit (with
relative sparing of spatial prediction) in this patient group.

Is time prediction of a future event specifically disturbed, compared to
spatial prediction, in PD and FA, when compared to age-matched control
subjects? Do the 2 patient groups differ from each other?

Twelve PD patients, 8 FA patients and 12 age-matched healthy controls will be
included. The FA and PD patients will be selected from the database of the
movement disorders section our neurology department (UMCG). PD patients with
intermediate disease progression will be selected, based on the unified
Parkinson disease rating scale (UPDRS III), score >10, <30. (Age-matched)
partners from PD patients will be asked to participate in the research as
control population. The remaining healthy control subjects will be selected
from a database from the neuro-imaging centre and will be asked to participate.
Handedness is documented and a Mini Mental State Examination (MMSE), lasting
about 5 min, is taken to look for general cognitive ability. Subjects with
neurological or ophthalmologic disease other than PD / FA will be excluded. The
number of FA patients is smaller than that of PD because the disease is rare.
There is no personal advantage for the subjects. Participation of the subjects
takes approximately one hour, devided over two different days. In the first
meeting participants will be instructed, which is at least one week before the
actual experiment. They are allowed to withdraw from participation at any time.
The name and address of a non involved physician (J.J. de Vries) will be given
on the informed consent form.

Experimental paradigm.
Subjects will perform a psychophysical experiment on a computer. They watch the
computer screen, on which a ball successively starts moving, stops and
disappears from the screen. In 4 different conditions, different spatiotemporal
characteristics of the moving ball need to be determined. In the first
condition subjects have to indicate where the ball stopped moving, by
right-hand pushing one of two buttons of a response box. In the second
condition they have to determine whether the ball moved fast or slow. In the
third condition subjects have to infer from the preceding movements where the
ball would have touched the bottom of the screen. Finally, at the moment the
ball stops, subjects have to estimate whether it would have taken more or less
than three seconds to hit the bottom of the screen. The 4 conditions, with 9
stimulus fragments each, are randomly ordered in a block. Such blocks are
repeated four times within a run. The whole experiment is performed in two 10
min runs with a 5 min pause in between. In this way, 72 responses will be
obtained for each condition. The results of task performance will be quantified
by error measurements of the responses and ratings of perceived difficulty of
the 4 task conditions (scale 1-10, questionnaire). Although subjects are not
urged to give responsese as soon as possible, reaction times are documented.

Analysis.
Data analysis concerning the differences between timing and place prediction
within and between groups will be performed with statistical programs (MS
Excel, SPSS). External data presentation will be anonymous.

Burden is restricted to actually spending time to the study. There is no
specific risk.