Cerebral networks involved in internal scaling of spatial dimensions.

Motor information needs to be coupled to visual information of an object to
grasp that object. Apart from spatial information about the location of the
object, it is necessary to make an estimation about the size of the object to
grasp it. To do this, sensory input and motor output must be integrated. The
parietal cortex is involved in both the processing of spatial information and
the generation of task-related movements. Furthermore the parietal cortex is
part of the so-called 'dorsal stream', positioned between the primary and
secondary visual areas and the premotor cortex. This network supports
visually-guided actions, spatial navigation and spatial working memory. In a
previous experiment we created selective dyscongruence in axial orientation,
which showed that there is perceptual and executive specialization of
visuomotor control in movements. During the transformation with dominance of
motor information there was activation of the left premotor cortex, while
during transformation of dominant visual information there was activation of
the right dorsal premotor cortex and the right posterior parietal cortex. In a
behavioural experiment patients with Parkinson's disease (PD) were not able to
perform these tasks. They followed the visual example instead of the instructed
direction of drawing, which suggests a disturbance in maintaining the own
internal spatial system in PD. An other component of visuomotor transformation
is the scaling of the size of objects. It is reasonable to assume that there is
an internal reference system for scaling of size of subjects. Prediction of
size of an object without holding it is based on visual information about the
distance of the object with reference to other objects in the direct
environment and/or the size with reference to one's own body. The underlying
cerebral mechanisms, in which premotor and parietal cortex undoubtedly have a
clear role are currently unknown.

In our earlier experiment patients with PD drew figures with the same
orientation bigger, after leaving out direct visual feedback on their own
drawings. This points to a problem with the maintenance of an internal
reference system of spatial dimensions, This also seems to play a role in
micrographia, which is an early symptom in this disease, with a prevalence
varying from 15% to 50%. Micrographia is characterized by a decrease in the
movement amplitude during writing. Different explanations have been given for
this phenomenon. Van Gemmert et al. proposed that micrographia in PD is caused
by an increased complexity of the task at cerebral level. Apart from that,
there is a strong correlation between micrographia and hypophonia and
bradykinesia, although this does not have to be a causal relation because all
three factors are influenced by the severity of the disease. PD patients can
increase their size of writing when encouraged to do so, but this persists only
for a short time. Furthermore, it has been shown that PD patients write bigger
without visual feedback, which is consistent with the observation of de Jong et
al. (1999). It can be questioned which cortical mechanisms are responsible for
the fact that the size of writing is seemingly easily changeable. The
possibility to change the size of writing with external stimuli suggests that
there is a problem with internal scaling of size in PD. We hypothesize that
there is a shift from medial to lateral premotor cortex involvement when an
external stimulus is presented. This can explain the improvement in size of
writing in the presence of an external stimulus or by an increase in attention.
From functional imaging studies it is known that there is dysfunction of the
medial premotor cortex in PD patients, while the lateral premotor cortex is
spared. The lateral premotor cortex is activated during the selection of
movements evoked by external stimuli, while the supplementary motor area (SMA)
is activated in the absence of external stimuli. A comparable dichotomy between
these areas is created during motor learning with SMA activation during learned
motor sequences, while the lateral premotor cortex is activated during learning
of new motor sequences. This shift can explain why patients change the size of
writing when reminded to write bigger, because a different (attention-related)
neuronal network is used with activation of the lateral premotor cortex.

It is necessary to gain insight in the cerebral networks involved in internal
scaling of size at a more basal level. To do so we will do a functional MRI
(fMRI) study with 16 healthy volunteers. We expect that copying of figures
causes activation of the cerebral network involving the medial premotor cortex,
apart from visual and parietal areas. When presenting the same reference object
with the task to draw it two times bigger or smaller, this extern object causes
a change in the use of the internal defined spatial system. The expectation is
that more lateral premotor cortex areas will be activated, in particular the
left dorsal premotor cortex, and also the left ventral premotor cortex together
with activation of the antero-inferior parietal cortex. We expect that drawing
the original reference object at presentation of the same object of a different
size causes activation of the right lateral premotor cortex and
postero-superior parietal cortex. This is comparable to the earlier described
executive and perceptual specialization of visuomotor control of movements.
Apart from these specific effect in the lateral premotor cortex we expect a
general effect of increased activation in the SMA in every dyscongruence
between stimuli and motor action, in comparison with exact copying of the
example. By gaining insight in the functional balance between medial and
lateral premotor areas in the described tasks, we expect to gain more insight
in the fundamental organization of motor actions and visuomotor disturbances in
PD.

Primary goal: Identification with fMRI of specific cerebral activations during
drawing of figures in different conditions.

3T fMRI is used to measure task-induced blood oxygen level dependent (BOLD)
responses, that are caused by an increase in regional perfusion. This measure
gives an index of the distribution of local neuronal activations. Before
scanning handedness is quantified using the Edinburgh Handedness Inventory.
During the fMRI measurements subjects are presented with 6 different conditions
via a beamer. The following experimental conditions are distinguished: (1:
total visuomotor congruence) drawing the reference figure (square, circle,
diamond or triangle), with variations in the figures to keep one's attention,
(2: total visuomotor congruence, different sizes) the reference figure is
presented in different sizes and must be copied, (3: visual dyscongruence, but
also motor memory) the reference figure is presented in different sizes, but
subjects must draw the original reference figure, (4: motor dyscongruence) A:
the reference figure is presented in different sizes and must be copied two
times bigger, B:the reference figure is presented in different sizes and must
be copied two times smaller, (5: visuomotor congruence, different sizes,
control for motor memory) the reference figure is shown and needs to be drawn
in different sizes, but the presented figures are a different figure than the
reference figure (6) a rest condition during which subjects will fixate on a
point on the screen.
A condition takes 20 seconds (2 seconds instruction and 6 times 3 seconds
drawing), the rest condition takes 17 seconds (2 seconds instruction, 15
seconds fixating on the screen). A block consists of 3 times the 6 conditions
(about 6 minutes). A run consists of 4 blocks (total 23.4 minutes). Two runs of
experimental conditions will be performed by the subjects. Between the two runs
an anatomical (T1-weighted) scan will be made. Each condition is thus presented
24 times. A subject lies in the scanner for about 50 minutes.
Subjects draw on a specially designed writing case which lies in their lap.
This writing case has also been used during a previous fMRI experiment
investigating writing in healthy subjects.
A voxel-based analysis of differences between task-related cerebral activations
will be performed using 'Statistical Parametric Mapping' (version SPM8). The
differences between the experimental conditions will be quantified.

Use of MRI is very safe, especially when precaution is taken to evaluate
contraindications for the MRI scan. Subjects will be asked for
contraindications during a telephone conversation. Before the MRI scan this
will be checked again.The risks are nihil and the burden is considered small (1
hour time), which is why we think this study can be justified.