This study will use electroencephalography (EEG) to examine how the brain prepares for
movement. It will look at 1) what changes occur in a person's brain just before voluntary
movement, 2) when the changes occur, 3) how consistent the changes are, and 4) how the
changes vary from person to person. The information from this study will be applied to other
studies, such as exploring how brain changes that signal movement can be used to control
prostheses in patients with spinal cord injuries or stroke.
Healthy normal volunteers 18 years of age and older may be eligible for this study. People
with neurologic or psychiatric disorders and people taking medicines that may affect brain
signals (e.g., Valium) may not participate.
Participants will come to the NIH Clinical Center on two separate days for testing sessions
of 2 to 3 hours each. At each session, an EEG cap will be placed on the head to record brain
signals, and electrodes will be placed on the arms to record movement. Subjects will perform
simple movements during the EEG recording, such as flexing their arm of clenching their
fist. Researchers will use the first recording to determine the pattern of how the brain
prepares for movement. During the second recording, they will try to predict the subjects'
movements, based on the patterns discerned in the first recording.
Human voluntary movement is associated with at least two distinct types of scalp
electroencephalographic (EEG) changes. Event-related potentials are slow, with DC signals
developing in the bifrontal region as early as 1.5 seconds prior to movement. They are
detected by averaging multiple events in the time domain and generally require at least
40-50 events to allow detection of the signal within the noise. Frequency changes however,
are more robust and may be seen reliably on individual traces. The frequency changes occur
in the alpha (8-13 Hz) range as well as beta (13-30 Hz) and may occur up to 2 seconds before
movement. This leads to the notion that real-time analysis of the EEG may allow one to
predict individual movement. If this could be done reliably, it may provide further insight
about how the brain prepares for movement, as well as potential therapeutic options such as
control of cortically based prosthetic device.
Our initial study, henceforth Phase 1, is an exploratory study using real-time EEG to
identify the factors that allow one to reliably predict normal human voluntary movement.
Subjects will be normal volunteers, studied in the EEG lab in the Human Motor Control
Section. Subjects will be asked to perform a simple motor task involving a sequence of
finger movements while undergoing a routine EEG recording with surface electromyography. The
EEG will then be processed using standard techniques to identify the location and time
course of EEG signals in response to movement. Once this has occurred, subjects will return
for a real-time study that will use their individually identified factors to predict their
movement. The effects of training on the accuracy of prediction will also be explored by
scheduling multiple real-time prediction sessions per subject over the course of several
weeks. The rate of successful movement prediction will be the primary outcome measure.
After we are able to accurately predict movement intention with healthy volunteers, i.e.,
the false positive rate is under 20% with the false negative rate under 50%, we will study
whether we can achieve the same prediction accuracy with stroke patients and patients with
primary lateral sclerosis (PLS) or amyotrophic lateral sclerosis (ALS). The stroke patients
and ALS/PLS patients will perform the same procedure as the subjects in the Phase 1 part of
Phase 2 of the investigation will extend to a different type of movement, reaching, and to
an additional parameter, the spatial field of the intended target of the movement. In
addition, Phase 2 will also include magnetoencephalography (MEG) as well as EEG methods to
classify the spatiotemporal features of these movement parameters. Successful prediction of
the intended goals of reaches to either ipsilateral or contralateral fields, prior to the
onset of movement will be the main outcome measure of phase 2 of the study.
In Phase 3 of the investigation, healthy volunteers will perform a simple finger movement
task which will be analyzed with special attention given to the timing of the intention to
move and to how the intention affects the EEG signal. In order to assess whether spontaneous
movements without prior instruction are associated with different physiological markers from
typical self-paced paradigms, a recording session will be performed after the EEG cap is
placed without instructing the subject.
Results from this study will then be used to design further protocols studying human
voluntary movement and clinical applications as appropriate.
- INCLUSION CRITERIA:
Healthy volunteers will be over 18, and willing to participate, and able to give informed
The stroke patients will have a clinically and radiologically documented stroke in the
sub-acute (2 weeks to 6 months to after onset) or the chronic state (more than 6 months
after onset), having a lesion in sub-cortical regions including the basal ganglia,
thalamus, internal capsule, or a combination of these structures, or cerebellum
unilaterally. These lesions can extend to the surrounding areas, however not including the
cortical areas. Patients will be over 18 years of age.
Patients must fulfill the diagnostic criteria proposed by Pringle (1992) for PLS and have
been diagnosed with PLS for at least 3 years. Criteria include onset of spasticity alone
in adulthood, slow progressive course, no family history, no lower motor neuron signs, and
exclusion of known causes of spasticity. ALS patients should have probable or definite ALS
by El Escorial criteria. Patients must have evidence of upper and lower motor neuron signs
in two or more defined regions: cranial, arms, legs, or torso. Only the PLS/ALS patients
who have recently participated in the study under protocol 06-N-0174 will be included.
Some subjects will be studied as inpatients.
Subjects who are unable to perform simple voluntary movement with both hands.
Subjects who have any neurological or psychiatric conditions.
Subjects who have any implanted metal in or on their bodies that cannot be removed prior
to the MRI and MEG scans.
We are investigating a particular EEG pattern associated with voluntary movement that we
believe may not be present in patients with multiple strokes that involve the cerebral
cortex; therefore, we will exclude this population of stroke patients. We will, however,
include patients with multiple strokes if the cerebral cortex was not involved because we
hypothesize that the EEG pattern that we are looking for will be preserved in patients
with sub-cortical stroke lesions.
A. Patients with MRI findings consistent with brain tumors, trauma or AVMs will be
B. Patients with multiple stroke lesions that involve the cerebral cortex will be
C. Subjects with a pre-stroke history of schizophrenia or bipolar disorders will be
D. Subjects with cancer will be excluded.
E. Patients not capable of giving an informed consent will be excluded.
PLS/ALS patients with a history or evidence of a coexisting or other neurological
disorder, such as stroke, epilepsy, Parkinson's disease, polio, ataxia or neuropathy, or a
history of traumatic brain injury, skull defects or neurosurgery will be excluded. PLS/ALS
patients will have neuropsychological tests of frontal cortex function under protocol
06-N-0174. Patients with scores below 133 (out of 144) on the Mattis dementia rating scale
will be classified as impaired patients who are unable to give their own informed consent
and will be excluded. PLS/ALS patients who are unable to travel will be excluded. PLS/ALS
patients who are respirator dependent will be excluded.