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Motor Cortex in Voluntary Movements
2
Functional Magnetic
Resonance Imaging of
the Human Motor Cortex
Andreas Kleinschmidt and Ivan Toni
CONTENTS
2.1 INTRODUCTION
Using the title of this chapter as a search command in Medline gives more than
1000 hits, and the number of false negatives probably largely exceeds that of false
positives. This points to the vast number of functional neuroimaging studies that
have reported motor cortex activation, but it does not help to decide whether these
studies have advanced our knowledge of the functional organization and response
properties of motor cortex. In relation to findings from other techniques in the
neurosciences, the authors of this chapter are tempted to acknowledge that the
contribution to understanding the motor cortex that has come from neuroimaging is
small yet significant, in particular with respect to the human motor cortex. In
collating some of the findings that may be seen to provide such a contribution, it
has nonetheless been necessary to constrain somewhat arbitrarily the number and
type of studies that are considered in detail.
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Copyright © 2005 CRC Press LLC
 
A first major constraint that we decided to apply was to focus on studies that
used magnetic resonance as the functional imaging modality. This is not motivated
by the overwhelmingly greater number of studies using functional magnetic reso-
nance imaging (fMRI) techniques rather than others. In particular, and as a second
constraint, we will not cover the many studies in the wake of the fMRI avalanche
that have dealt with feasibility and methodological optimization. This first constraint
we introduced is motivated instead by the superior spatiotemporal resolution and
sensitivity of fMRI compared to other imaging modalities that can be applied
noninvasively in human subjects. In fact, the sensitivity of fMRI is even good enough
to permit analyses that invert the usual direction of inference, i.e., from the neuro-
physiological signal to behavior.
1
) or that allow for an interval between the activating paradigm
and data collection (such as positron emission tomography [PET] with slow tracers
like fluoro-deoxy-glucose
2
) offer distinct advantages in this respect although they
also fight artifacts and limitations of sensitivity and resolution. Second, within the
bore of the magnetic resonance scanner overt limb motion or even mere changes in
muscle tone readily translate into shifts of the brain relative to the machine’s imaging
coordinates. Even slight shifts result in devastating effects on image quality that are
far more complex than the mere displacement accounts for and thus not readily
compensated for by simple realignment algorithms. Accordingly, there have been
relatively few successful studies on movements of facial, proximal, or axial muscles.
There are some noteworthy studies on respiration
3
4,5
and facial functions such as
but most of the work with fMRI has dealt with movements
of the distal upper extremity that are associated with so little artifact that the existing
correction tools can handle it without compromising data quality. In other words,
and as a third constraint, our review will mostly cover hand function.
As a fourth constraint we will not consider in this review those many valuable
studies that have integrated the imaging of motor cortex activation into a clinical
context, be that the issue of presurgical mapping or that of postlesional plasticity,
or the influence of other disease conditions or pharmacological manipulations on
task-related motor cortex activity.
Finally, as a fifth constraint, and despite the multitude of “motor” areas in the
brain
6–8
we will focus on studies dealing with or involving effects on activity in the
primary motor cortex. The functional behavior of other motor areas will nonetheless
often be mentioned along these lines in the context of paradigms that are associated
with, but not only with, primary motor cortex activity.
Even when implementing all these constraints, we are certain to have missed
relevant studies in the abundant literature and we apologize for these omissions. The
Copyright © 2005 CRC Press LLC
Naturally, many of the issues previously addressed
by other imaging modalities have been revisited using fMRI, and in part this has
been merely confirmatory, but in part this has also resulted in more detailed findings.
Nonetheless, there is an important downside to this because fMRI is not only
exquisitely sensitive to the hemodynamic signals associated with the neural activity
related to movements, but unfortunately also to direct effects of motion. First, the
necessity of retaining the organ of interest within the rigid imaging grid precludes
studies with, for instance, free natural movements such as walking. Techniques that
can apply head-mounted or even telecommunicating devices (such as electrical or
optical recordings
swallowing or speaking,
9
purpose and hopefully the result of this chapter is to provide the reader with an
overview of the contribution of fMRI to some of the prevailing topics in the study
of motor control and of primary motor cortex function. In several points, the findings
with functional neuroimaging will seem to be in apparent disagreement with those
from other modalities. This cannot always be related to insufficient sensitivity of
this noninvasive modality. In part, it may reflect the indirect and spatio-temporally
imprecise nature of the fMRI signal, but these studies remain informative by virtue
of the fact that usually the whole brain is covered. This does not only provide a
plausibility control for localized effects, but the distribution of response foci and the
relation of effects observed at these different sites can assist the guidance of detailed
studies at the mesoscopic or microscopic spatio-temporal level. Even when denying
any single current neuroscience method a gold standard status, an adequately modest
view should probably conclude that fMRI currently is mostly a tool of exploratory
rather than explanatory value.
2.2 SIGNALS IN fMRI
The mainstream of functional activation studies by MRI relies on the blood-
oxygenation-level-dependent (BOLD) contrast although other techniques that measure
task-associated changes in blood flow or — via contrast agents — in blood volume
can also be used for functional imaging and can even offer distinct advantages in
some settings. Simply put, the basis of the BOLD contrast is that a neural activity
increase results in a blood flow increase that exceeds the concomitant increase in
oxygen consumption. This means that more blood flows through the capillaries
without that proportionately as much more oxygen is being extracted from it. As a
consequence, and somewhat counterintuitively, the blood in the postcapillary vas-
culature will become hyper-oxygenated during activation and thus will contain less
deoxyhemoglobin than before. As opposed to diamagnetic oxyhemoglobin, deoxy-
hemoglobin is paramagnetic and causes more and more signal loss the longer it
takes to record the echo. Accordingly, wherever in the brain this decrease in deoxy-
hemoglobin concentration occurs during an “activated” as opposed to a “resting”
state, there will be an image signal increase in the corresponding voxel, the so-called
BOLD response. Of course, the change in deoxyhemoglobin concentration is not
the only physiological effect occurring during activation, and BOLD contrast fMRI
sequences can also be sensitive to other effects, such as changes in blood volume
or flow velocity. However, a number of studies have used simultaneous transcranial
optical absorption measurements, so-called near-infrared spectroscopy (NIRS), dur-
ing fMRI to validate task-related deoxyhemoglobin concentration changes as the
physiological basis of the BOLD fMRI response.
11–13
Apart from the problem of confidently relating the signal changes observed in
fMRI to changes in a single physiological parameter, there remains the problem that
deoxyhemoglobin is only an indirect index of neural activity. The mechanisms that
link this parameter to neural activity are still not fully understood, although some
progress has been made in recent years. A more superficial but, for some purposes,
Copyright © 2005 CRC Press LLC
Along with visual stimulation, voluntary or paced movements have belonged to the
first experimental conditions used to evoke and observe fMRI responses in the human
brain.
10
Most of the work characterizing the coupling functions
between neural activity and blood flow and metabolism in man has used visual
stimulation as the functional challenge. This means that the related findings are
heavily dominated by the behavior of calcarine cortex, a cortical area with a peculiar
cyto- and myelo-architectonic organization that is not representative of other neo-
cortical or even primary sensory areas.
14
If one considers the huge neurochemical
and neurovascular heterogeneity in the central nervous system,
15–17
the usual assump-
tion of generic hemodynamic and metabolic response properties across different
brain regions needs to be taken with caution or even to be addressed analytically.
15
18
With these constraints in mind, it can be said that the BOLD response generally
occurs with 2 to 3 sec latency even after very brief neural events, peaks after
approximately 6 sec, and usually takes more than the rise time to decay back to
baseline level. This signal increase is often followed by an “undershoot” that may
take 10 or easily even more seconds before the signal asymptotically recovers
baseline level. Several laboratories have observed an “early dip,” i.e., an actual signal
decrease during the initial latency period, and this has also been shown for the motor
cortex.
Yet, many
laboratories have found it difficult to reproduce this dip at all, and even those that
have, consistently observed lower amplitudes in relation to the positive BOLD
response than seems to be the case in fMRI studies with laboratory animals. Con-
versely, it has been established in humans that the spatial specificity of the early
components of the positive BOLD response is sufficient to map, for instance, ocular
dominance columns in primary visual cortex.
20,21
Another hope related to the early dip
has been that since it occurs earlier than the positive response, it might also preserve
temporal information on a finer scale. Again, this is compromised by the overall
weakness of this signal, whereas there have been encouraging results from studying
in more detail the temporal information contained in the envelope of the positive
BOLD response.
22
It is therefore not surprising that the findings reviewed in the
following sections are almost entirely based on the positive BOLD response.
Over and above the uncertainties regarding the coupling between neural activity
and blood flow and metabolism, and between blood oxygenation changes and fMRI
signal, there remain open questions as to the precise nature or component out of the
orchestrated spectrum of neural activity that drives these effects. Both classical
studies and, in a more direct way, recent work with simultaneous fMRI and electro-
physiological recordings point to synaptic activity instead of action potentials as the
source underlying hemodynamic responses.
23
Synaptic activity arises mainly from
intracortical connectivity, with some contribution by afferents from distant neurons.
Synapses can be excitatory or inhibitory, and the metabolic demands from their
activity may be comparable in magnitude but the effect they have on their targets
is sign-inverted and probably often differs in efficiency. Although there has been
24
Copyright © 2005 CRC Press LLC
more relevant concern is to simply understand the coupling functions in terms of
the spatial and temporal dispersion that the BOLD signal change exhibits in relation
to neural activity changes.
Because this signal is also found in optical imaging studies and because in
animal fMRI studies it has been used to resolve functional architecture at the
columnar level, there has been considerable hope that it might be useful in human
fMRI studies to obtain mapping results at a higher spatial specificity.
19
some attempt to elucidate their relative contribution to blood flow regulation, this
issue remains far from resolved.
25
Despite all these uncertainties regarding the nature of the fMRI signal, it has
been widely used in the neurosciences in the past decade. There are conceptually
different ways of using the BOLD response to study brain function and they will
all be touched on in the following sections. At a first level, the response can be used
for the simple purpose of mapping, i.e., showing a responsiveness of neural tissue
in association with a task as opposed to rest. This approach has been used in the
context of studies on response lateralization and somatotopical representation (see
the next two sections). At a second level, the response can be used to determine
response properties, as related by analogy to stimulus–response functions. The rela-
tion between fMRI signal and movement parameters is covered in a section on motor
response properties. The sections thereafter deal with further aspects of the topic,
such as acute (attentional) or long-term modulation of responses (learning), other
sources of primary motor cortex activation than overt movement (sensation, imag-
ery), and findings related to cognitive states such as motor intention and preparation.
2.3 LATERALIZATION AND HANDEDNESS
quantified
this degree of lateralization. They studied predictably and unpredictably visually
cued finger movement sequences and computed for a given voxel significance
threshold the contra- and ipsilaterally activated volumes as well as their ratios, i.e.,
lateralization indices. With this analysis, they observed larger contralateral activation
volumes for dominant than for nondominant hand movements. This effect was only
significant in a region of interest covering M1 but not in other distant motor areas.
It was not accounted for by behavioral differences in that response times and error
rates were matched between hands. Interestingly, the degree of lateralization of
primary motor cortex activation during dominant hand usage was related to the
degree of handedness. This effect was driven by weaker ipsilateral activations in
those subjects with strong behavioral lateralization. A similar observation regarding
ipsilateral activation as a function of dominant vs. nondominant hand movements
was made by Singh et al.,
26
In a very detailed study, Dassonville et al.
27
although they pointed out that this effect was stronger
in regions presumably covering premotor rather than M1.
The study by Dassonville found no significant effect of handedness on contralat-
eral activation volume and no interaction of dominance with handedness. However,
an earlier study from the same laboratory had shown a handedness effect. Kim et al.
28
29
reported that while the right motor cortex was activated mostly during contralateral
finger movements in both right-handed and left-handed subjects, the left motor cortex
Copyright © 2005 CRC Press LLC
One of the basic observations in functional neuroimaging during simple unilateral
hand movements is that the strongest associated activation is observed in the con-
tralateral primary motor cortex (M1). This corresponds to the decussation of the
pyramidal tract as the main output of M1 and mirrors the clinical deficit observed
after lesions of this tract or its cortical origin. Yet, in addition to some PET studies
that have been conducted, early fMRI studies also observed activation in M1 ipsi-
lateral to the moving hand.

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