BATRAC indicates bilateral arm training with rhythmic auditory cueing;
DMTE, dose-matched therapeutic exercises; fMRI, functional magnetic resonance
*In a secondary analysis on arm function data, 3 patients without fMRI
response were excluded.
Two axial sections at different z coordinates representing changes of
activation are shown. Areas of yellow-orange indicate increased activation
after bilateral arm training with rhythmic auditory cueing (BATRAC); areas
of green would indicate increased activation in control patients but none
were detected (probability threshold P <.05, corrected for
multiple comparisons). In neither group were any areas of decreased activation
identified after the intervention. Left panel, Talairach coordinates x, y,
z (foci from anterior to posterior): contralesional: −5/4/61 (Brodmann
area [BA] 6), −17/−7/61 (BA 6), −15/−60/61 (BA 7);
ipsilesional: 12/14/61 (BA 6), 13/−13/61 (BA 6). Right panel, ipsilesional:
29/−77/−29 (posterior lobe of cerebellum). DMTE indicates dose-matched
therapeutic exercises (control).
Lesions are on the right side of the brain, probability threshold P<.001, uncorrected; green-blue indicates decreased
activation; yellow-orange, increased. A-F, In 6 of 9 patients, increased activation
was seen in the precentral and postcentral gyri (orange-yellow). In a few
cases (blue) there was decreased activation. G-I, In 3 patients there was
no change in activation of precentral, postcentral, or premotor areas. BATRAC
indicates bilateral arm training with rhythmic auditory cueing.
Customize your JAMA Network experience by selecting one or more topics from the list below.
Luft AR, McCombe-Waller S, Whitall J, et al. Repetitive Bilateral Arm Training and Motor Cortex Activation in Chronic StrokeA Randomized Controlled Trial. JAMA. 2004;292(15):1853–1861. doi:10.1001/jama.292.15.1853
Context Reorganization in central motor networks occurs during early recovery
from hemiparetic stroke. In chronic stroke survivors, specific rehabilitation
therapy can improve upper extremity function.
Objective To test the hypothesis that in patients who have chronic motor impairment
following stroke, specific rehabilitation therapy that improves arm function
is associated with reorganization of cortical networks.
Design, Setting, and Patients A randomized controlled clinical trial conducted in a US ambulatory
rehabilitation program with 21 patients (median [IQR], 50.3 [34.8-77.3] months
after unilateral stroke). Data were collected between 2001 and 2004.
Interventions Patients were randomly assigned to bilateral arm training with rhythmic
auditory cueing (BATRAC) (n = 9) or standardized dose-matched therapeutic
exercises (DMTE) (n = 12). Both were conducted for 1 hour, 3 times
a week, for 6 weeks.
Main Outcome Measures Within 2 weeks before and after the intervention, brain activation during
elbow movement assessed by functional magnetic resonance imaging (fMRI) and
functional outcome assessed using arm function scores.
Results Patients in the BATRAC group but not in the DMTE group increased hemispheric
activation during paretic arm movement (P = .03).
Changes in activation were observed in the contralesional cerebrum and ipsilesional
cerebellum (P = .009). BATRAC was associated
with significant increases in activation in precentral (P<.001) and postcentral gyri (P = .03)
and the cerebellum (P<.001), although 3 BATRAC
patients showed no fMRI changes. Considering all patients, there were no differences
in functional outcome between groups. When only BATRAC patients with fMRI
response were included (n = 6), BATRAC improved arm function more
than DMTE did (P = .02).
Conclusions These preliminary findings suggest that BATRAC induces reorganization
in contralesional motor networks and provide biological plausibility for repetitive
bilateral training as a potential therapy for upper extremity rehabilitation
in hemiparetic stroke.
Hemiparesis represents the dominant functionally limiting symptom in
80% of patients with acute stroke.1 Within
2 to 5 months after a stroke, patients recover a variable degree of function,
depending on the magnitude of the initial deficit.1 Several
studies have demonstrated that recovery is associated with reorganization
of central nervous system networks.2,3 Functional
brain imaging of paretic movement during the recovery period has shown recruitment
of cortex immediately adjacent to the stroke cavity along with intact cortical
areas within the lesioned and in the uninjured contralesional hemisphere.4,5 The pattern of recruitment depends
on the severity of impairment,6 lesion location,7 and time since stroke.8 The
factors that initiate and maintain cortical reorganization are not known.
Imaging data suggest that circuitry in motor cortices on both sides of the
brain is modified during recovery.2
Even with traditional rehabilitation therapy, 50% to 95% of stroke survivors
remain impaired.9-11 For
some patients, recently developed repetitive active training therapies provide
additional benefit.12 Bilateral arm training
with rhythmic auditory cueing (BATRAC), a rehabilitation therapy based on
the concept that bilateral movement permits interhemispheric facilitation
of the limbs,13 is one such intervention. We
previously showed that BATRAC improves arm function in chronic stroke survivors
with fixed upper extremity deficits.14
We hypothesized that BATRAC may be associated with reorganization of
brain regions involved in motor control.
This study was conducted as part of the University of Maryland School
of Medicine, National Institute on Aging–Claude D. Pepper Older Americans
Independence Center in collaboration with the Johns Hopkins University Division
of Brain Injury Outcomes. All study participants provided informed written
consent. The study was approved by the ethics committees of the participating
institutions (the University of Maryland School of Medicine, the Baltimore
Veterans Affairs Medical Center, and the Johns Hopkins University School of
Eligible participants had residual upper extremity spastic hemiparesis
following a single cortical or subcortical ischemic stroke. All patients had
the ability to move the affected limb (at least partial range antigravity
movement) and had completed 3 to 6 months of conventional rehabilitation therapy.
Inclusion criteria were adequate language and neurocognitive function to understand
instructions. Patients with multiple clinical strokes, a history of other
neurological disease, chronic pain, or emotional disorders were excluded.
This article reports findings from a substudy of a larger study designed
to examine the effect of BATRAC on function and the retention of functional
improvement 4 months after the last training session. Participants in the
larger study were randomized to receive either BATRAC or the control intervention
(dose-matched therapeutic exercises [DMTE]) using a stratified block allocation
scheme (variable block size, allocation ratio 1:1). All participants included
in the larger study were entered into the functional magnetic resonance imaging
(fMRI) substudy if they were eligible to undergo MRI (absence of metal implants
and claustrophobia). When the fMRI substudy was designed, we were unable to
estimate the sample size needed; we knew of no data that could be used to
estimate the fMRI activation changes brought about by the BATRAC intervention.
We chose to analyze our data at this time based on recent fMRI studies from
our group7,15,16 that
indicate that a sample size of approximately 10 patients per group is sufficient
to show fMRI activation changes. Data were collected between 2001 and 2004.
The investigators performing training or analyses of fMRI and functional
data were blinded to group assignment. Patients were aware of the differences
in treatment but were not specifically aware that one treatment was a control
because neither the consent forms nor verbal explanations referred to DMTE
as a control treatment. Thus, patients could reasonably expect an improvement
regardless of treatment group. Baseline fMRI data from 13 patients in the
current sample were reported as part of another study.7
BATRAC training consisted of hour-long therapy sessions (four 5-minute
movement periods interspersed with 10-minute rest periods) 3 times per week
for 6 weeks. Upon auditory cues at individually determined rates of 0.67 to
0.97 Hz, participants pushed and pulled bilaterally, in synchrony or alternation,
2 T-bar handles sliding in the transverse plane.14 DMTE
was based on neurodevelopmental principles17 and
included thoracic spine mobilization, scapular mobilization, weight bearing
with the paretic arm, and opening a closed fist. DMTEs were administered in
standardized format equal to the time used for BATRAC.
Within 2 weeks before and afterBATRAC or DMTE, patients underwent fMRI
of nonparetic and paretic elbow movement, electromyography of biceps and deltoid
muscles during elbow movement, and a battery of arm function tests.
Functional Magnetic Resonance Imaging. Scanning
was performed at the Kirby Center for Functional Brain Imaging, Kennedy Krieger
Institute, Baltimore, Md. Before fMRI scanning, there was a 5-minute period
of accommodation to the scanning environment when several cycles of arm movement
were performed. A total of 60 coronal blood oxygenation–level dependent
(BOLD) weighted scans (echo planar imaging; repetition time, 3 seconds; echo
time, 40 milliseconds; slice thickness, 5 mm; 30 scans) covering the entire
brain were acquired to access brain activation first from the nonparetic arm
and then from the paretic arm. The 60 scans were obtained during 3 cycles
of rest (10 images) followed by arm movement (10 images). During imaging,
the arm was strapped to a device that limited the movement to a single plane
and a defined range of motion. Flexion began at 45° relative to the standard
anatomical position, ending at 60° to 75°, and was followed by extension.
The range was selected by adjusting the end position according to the patient’s
movement ability. It was held constant for all tests on an individual patient.
Movement was performed in response to a beep given via headsets once every
The participants kept their eyes closed during scanning. Video monitoring
and taping with 2 cameras (one focused on the head, the other on the elbows)
allowed us to assess compliance with the requested movement, any mirror movement
of the opposite limb, and head motion. No patient showed any overt head movements
in these recordings.
A T1-weighted image set was acquired for anatomical localization (3D-MPRAGE
sequence; resolution, 1 × 1×1 mm3). Data
from fMRI were processed using the BrainVoyager Software (Brain Innovation
BV, Maastricht, the Netherlands). Images were corrected for minimal head motion
and changes in image intensity. To allow analyses across individuals, each
patient’s image set was normalized to the Talairach coordinate space
by applying translation, rotation, and scaling in 12 subvolumes. The subvolumes
were defined by the Talairach landmarks, anterior and posterior commissures,
rostral, caudal, ventral, dorsal, and lateral boundaries of the brain (reference
points were selected manually). To facilitate image analyses, all image data
from patients with left-sided lesions were flipped about the mid-sagittal
plane, such that the affected hemisphere was always the right hemisphere.
When combining individual images to obtain a composite functional map, image
data were smoothed using a full width–half maximum algorithm with a
kernel of 8 mm.
Statistical analysis to identify activated voxels was performed using
standard linear regression methods (boxcar design with hemodynamic response
modification, independent variable: elbow motion vs rest).18 Uniform
probability thresholds commonly used in comparable studies6,8 were
applied when identifying activated voxels (individual patient: P<.001, uncorrected for multiple comparisons; composite image maps
of multiple patients: P<.05 with Bonferroni correction).
The number of activated voxels in 9 regions of interest was automatically
determined using software we developed using Matlab (Mathworks Inc, Natick,
Mass). The 9 regions of interest were selected by manually identifying the
following anatomical landmarks: medial part of the precentral gyrus, lateral
part of the precentral gyrus, postcentral gyrus, cerebellar hemispheres, supramarginal
gyrus, supplementary motor area (caudal supplementary motor area between medial
precentral gyrus and a coronal plane through the anterior commissure19), and superior, middle, and inferior frontal gyri.
Difference maps identifying voxels activated after, but not before,
the intervention were constructed for each patient7,20 and
were combined into composite maps by treatment group (BATRAC and DMTE).
Motor Function. Upper extremity motor function
was measured with the upper-extremity portion of the Fugl-Meyer Motor Performance
Test21 and the Wolf Motor Arm Test22 (WMAT), during which Wolf time and Wolf weight were
measured, and the University of Maryland Arm Questionnaire for Stroke14 (UMAQS). Additionally, we used dynamometry to measure
elbow and shoulder strength (peak force in 3 consecutive trials). The Fugl-Meyer
test assesses the ability to isolate movements at each joint and the influence
of unwanted synergies on movement. Although there are no published cutoffs,
based on our observations patients who are severely impaired score below 25,
and those who are moderately impaired score between 26 and 50 out of 66. The
WMAT measures functional ability. The Wolf time is the mean time required
to perform 14 functional tasks with the paretic arm and hand. Maximum Wolf
time is 120 seconds; moderate and severe impairment results in times above
80 and 120 seconds, respectively (S.M.-W., S. Harding, J.W.,unpublished data,
2004). The Wolf weight assesses functional strength as the weight that the
paretic arm can lift. Moderate and severe impairment correspond to 1 to 2
and 0 kg, respectively. The UMAQS is a self-reported questionnaire that assesses
the daily use of the paretic arm in accomplishing activities of daily living
on the basis of a 5-point ordinal scale. Moderate and severe impairment correspond
to below 35 and 25 out of 50, respectively.
Electromyography. To screen for cocontraction
or mirror movement of the unimpaired limb, biceps and deltoid activity were
recorded bilaterally from surface electrodes while the patient isometrically
contracted the hemiparetic limb with either low (force needed to oppose gravity)
or maximal force. Electromyographic (EMG) testing was performed within 2 weeks
of each fMRI examination. A synkinesia index was
computed based on root mean square (RMS) amplitudes:
[(RMSparetic – RMSnonparetic) /
(RMSparetic + RMSnonparetic)].
A series of 6 unpaired t tests was used to
compare the changes (value after treatment minus baseline) in functional outcome
following BATRAC vs DMTE. A comparison of the changes in brain activation
induced by BATRAC vs DMTE was performed using repeated-measures analysis of
variance (proc MIXED with a REPEATED statement, SAS version 9.1; SAS Institute
Inc, Cary, NC).
Separate analyses were performed for the paretic and nonparetic arms.
This analysis was designed to test for differences in activation between the
arms. Change (value after treatment minus baseline) in volume of brain activation
(voxels) was the dependent variable; independent variables included voxel
count at baseline, side of brain from which voxel count was obtained (ipsilesional
vs contralesional), area of brain scanned (cerebellum, supplementary motor
area, and inferior frontal, mid frontal, postcentral, precentral [medial part],
precentral [lateral part], superior frontal, and supramarginal gyri), and
treatment (BATRAC vs DMTE).
In addition to these main effects, all 2-way and all 3-way interactions
(except those including initial voxel count) were included in the model. All
3-way interactions were nonsignificant and were dropped from the models. Because
the cerebral cortex is interconnected with the contralateral cerebellum, the
designations ipsilesional and contralesional were flipped for the data obtained
from the cerebellum to allow for an analysis of activation changes in corticocerebellar
networks. P≤.05 was considered statistically significant.
Akaike information criterion and Schwarz’s Bayesian information
criterion were used to choose among the 3 covariance structures (none, unstructured,
and compound symmetry) used to account for the serial autocorrelation among
observations from the same individual. All patients included in the analyses
completed either the 6-weekBATRAC or 6-week DMTE interventions.
Twenty-six patients were enrolled after a single cortical or subcortical
ischemic stroke. Initially, 11 and 15 patients were randomized to BATRAC and
control (DMTE) groups, respectively. Four patients (1 in the BATRAC group
and 3 in the DMTE group) discontinued the intervention and 1 BATRAC patient
cancelled baseline MRI due to claustrophobia, leaving 9 patients in the BATRAC
group and 12 in the DMTE group for analysis (12 men and 9 women; mean [SD]
age, 61.5 [12.6] years) a median (interquartile range [IQR]) of 50.3 (34.8-77.3)
months (range, 10 months–39 years) after stroke (Figure 1). There were no significant differences between BATRAC
and DMTE groups with respect to age, time since stroke, or baseline functional
scores. There were more women in the DMTE group (Table 1).
At baseline, there was no difference between voxel counts in the BATRAC
and DMTE groups (mean [SE] within-person difference, 11 , P = .92).
Movement of the paretic arm, but not the unaffected arm, resulted in
differential change in the activation of brain regions according to treatment
group (treatment group × brain area interaction, P = .03 in the paretic arm and P = .19
in the non-paretic arm; Table 2). In
the paretic arm, for BATRAC significant changes in the number of activated
voxels were seen in the cerebellum, the postcentral, and the precentral gyri
(medial and lateral parts) (Table 3).
The changes in the cerebellum and medial precentral gyrus remained significant
after adjustment for multiple comparisons (critical Bonferroni for 9 comparisons,
0.05/9; P=.006) and were different from the changes
in the DMTE group.
There was a suggestion of differential lateralization of brain activation
with movement of the paretic arm but not the nonparetic arm (treatment group
× side of brain, P = .06 for
paretic arm and P = .99 for nonparetic
arm; Table 2). Movement of the paretic
arm in the BATRAC group led to a significant increase in the activation in
the contralesional hemisphere (P = .009; Table 3) without any change in the ipsilesional
hemisphere (because of the data coding, “contralesional hemisphere”
includes the contralesional cerebrum and ipsilesional cerebellum). In the
control group, there were no significant changes in the activation of either
side of the brain.
The activation maps representing the difference between postintervention
and baseline time points visually confirmed significant activation changes
in the BATRAC group but not in the DMTE group (Figure 2). Six of 9 patients in the BATRAC group showed recruitment
of precentral regions (primary motor cortex and premotor area) with and without
the postcentral gyri (Figure 3). The
remaining 3 patients demonstrated no change in activation of precentral, postcentral,
premotor areas (Figure 3), and cerebellum
(data not shown).
To determine if changes in contralesional activation patterns were due
to involuntary cocontraction in the nonparetic limb when the paretic arm was
moved, the synkinesia index obtained from EMG recordings was analyzed. The
index was unchanged (within-group mean [SE] baseline, 0.68 [0.06]; post-BATRAC,
0.82 [0.05]; paired t test with 8 df, P = .08). Additionally, continuous
video recordings of elbow movement performed during fMRI scanning did not
show any overt mirror movements.
A comparison of the changes in functional outcome including all patients
revealed no significant differences between the groups (Table 4). Prior to these analyses we noted that 3BATRAC patients
showed no before-after differences in fMRI activation and we analyzed the
functional data with and without these 3 BATRAC patients. Excluding them,
we found a significantly greater increase in Fugl-Meyer scores in the BATRAC
than in the DMTE group (Table 4). The
inferences concerning functional outcome were unchanged when the comparisons
were performed using the nonparametric Kruskal-Wallis test.
Bilateral repetitive arm training (BATRAC) over 6 weeks induced changes
in movement-related cortical activation patterns in chronic stroke survivors,
suggesting cortical reorganization. Increased recruitment was observed in
sensorimotor areas of the contralesional hemisphere (precentral gyrus, postcentral
gyrus) and in the ipsilesional cerebellum. In patients with such changes arm
function improved, supporting our previous observation regarding BATRAC.23
Activation in the contralesional hemisphere is frequently seen acutely
after stroke in patients without exposure to rehabilitation.4,5,24-28 The
recruitment is commonly explained by an unmasking of uncrossed corticospinal
projections,2 which are silent or latent in
the healthy state. Serial functional imaging studies show that contralesional
recruitment is demonstrable early after stroke and then declines as spontaneous
recovery progresses.8,26,29-31 The
functional relevance of contralesional recruitment is unclear.2,32 Temporary
inhibition of the contralesional motor cortex by repetitive transcranial magnetic
stimulation does not interfere with paretic hand movement.33 However,
the opposite is reported for contralesional premotor areas.34 The
presence of evoked muscle responses after stimulation of the contralesional
motor cortex may occur more often in patients with poor recovery.35,36 Our data suggest functional relevance
to contralesional hemisphere recruitment possibly brought about by BATRAC
therapy. These findings indicate that prior work, describing only the natural
history of acute recovery, may have underestimated the role of contralesional
sensorimotor cortex in recovery.
Other rehabilitation interventions that focus on the paretic limb (unilateral)
are associated with reorganization in the ipsilesional cortices.37-42 Constraint-induced
(forced use) training, in which the nonparetic arm is restrained to enforce
task-oriented exercises with the paretic limb, is one such intervention. Although
the numerical analysis of voxel counts was not significant, the difference
composite map of BATRAC patients—which is more sensitive to small alterations—shows
activation changes in the ipsilesional hemisphere. Therefore, this study provides
some evidence that BATRAC also recruits ipsilesional motor areas.
Reorganization in the cerebellum is reported to occur after constraint-induced
training.42 We observed a significant increase
in cerebellar activation after BATRAC. Extensive cerebellar recruitment seems
to predict better hand function in stroke patients.43 Cerebellar
recruitment during motor cortex reorganization may occur as a consequence
of pathways connecting the cerebrum to the contralateral cerebellum. Therefore,
reorganization of corticocerebellar circuits involving contralesional motor
cortex and ipsilesional cerebellum may be an important mechanism of BATRAC
We developed the BATRAC therapy based on the concepts of bilaterality
and rhythmicity. Rhythmic training improves spatiotemporal arm control when
compared with nonrhythmic training.44 The rationale
for bilaterality is the induction of disinhibition in bihemispheric motor
cortices via transcallosal projections.45 During
isolated voluntary movement of the paretic hand, the contralesional motor
cortex imposes an abnormally high inhibitory drive onto the ipsilesional cortex,46 which may contribute to motor impairment.47 Disinhibition may render cortex in both hemispheres
more susceptible to reorganization. After reorganization has occurred (or
while it is occurring), its traces are detectable by fMRI activation in response
to unilateral movement.
It would be premature to speculate which feature of BATRAC—the
bilaterality, rhythmicity, or intensity—is associated with cortical
reorganization while DMTE is not. The intensity of elbow training was lower
in the DMTE group because this intervention included time devoted to non-elbow
tasks such as weight shifting of the trunk and movement of the fingers and
wrist. Therefore, the number of repetitions for muscles involved in elbow
flexion and extension, the movement assessed in fMRI, was less for DMTE thanBATRAC
and may be below the threshold to induce measurable reorganization. Additionally,
DMTE was mainly based on passive movement (such as mobilization, opening a
closed fist with help of the therapist), which might also be a factor contributing
to the absence of cortical reorganization in this group.
We previously reported thatBATRAC improves arm function.14 Similarly,
the current BATRAC sample (all 9 patients) showed a significant improvement
in the Fugl-Meyer score in within-group analysis (12% improvement; P = .04). This within-group effect is modest and, while larger
than the effect in the DMTE group, it is not statistically different from
the within-group change in the DMTE group (P<.26).
The 9 patients in whom the modest effect in BATRAC was seen included 3 patients
who did not exhibit cortical reorganization and who did not improve in any
of the functional measures. Based on the lack of evidence of cortical reorganization,
we excluded the 3 patients from the between-group comparison and found a significant
between-group effect on the Fugl-Meyer score in favor of BATRAC. This suggests
that BATRAC may induce cortical reorganization, and that it does no help every
patient. In addition, the DMTE regimen may also be of some benefit (our failure
to show a significant effect may be a type II error because our sample size
was small), but if so, this improvement does not appear to be mediated by
cortical reorganization. This is only conjecture; studies with larger sample
sizes will be necessary not only to evaluate functional benefits but also
to understand precisely which factors predict successful BATRAC therapy.
This preliminary study has several limitations. Because our hypothesis
was that BATRAC induces brain reorganization, the sample size was chosen based
on our experience analyzing fMRI data; it was therefore small to detect changes
in arm function that had been demonstrated in a previous study.14 Second,
we do not know the optimal dose ofBATRAC or the number of joints and movements
that need to be practiced to maximize functional benefits, and therefore,
we selected an arbitrary administration schedule. Third, to identify brain
activation changes specifically related toBATRAC with its features of bilaterality
and repetition, we used a dose-matched active control intervention (DMTE)
as opposed to placebo treatment (giving the patient attention but no training)
that may have led us to overestimateBATRAC-related activation changes. However,
comparingBATRAC to DMTE may result in our underestimating the effect of BATRAC
on functional outcome. Our sample size does not allow us to exclude the hypothesis
that DMTE may have a salutary effect on some functional outcomes. Another
limitation is not having EMG tracking of mirror muscle contractions during
fMRI. A change in the degree of mirror contraction or movement of the unimpaired
limb during fMRI testing may account for activation changes in the contralesional
hemisphere. Because EMG during fMRI is technically difficult and therefore
increases patient burden (time and instrumentation), we performed only video
recordings during scanning. In these recordings, no overt mirror movements
were detected in any of the patients, either before or after the intervention.
In patients with chronic motor impairment after stroke, specific bilateral
repetitive upper extremity rehabilitation therapy appears to induce reorganization
in bilateral, but mainly in contralesional, hemisphere networks and in cerebellum,
and may operate by recruiting these brain areas to provide functional benefits.
This association supports the hypothesis thatBATRAC improves arm function
by inducing reorganization of contralesional motor cortex networks, but it
needs to be tested in future studies. The maximal activation of these networks
should be evaluated thoroughly to produce the best possible recovery after
Corresponding Author: Jill Whitall, PhD,
Department of Physical Therapy and Rehabilitation Science, University of Maryland,
School of Medicine, 100 Penn St, Baltimore, MD 21201 (Jwhitall@som.umaryland.edu).
Author Contributions: Drs Luft, Whitall, and
Hanley had full access to all of the data in the study and take responsibility
for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Luft, Waller, Whitall,
Macko, Goldberg, Hanley.
Acquisition of data: Luft, Waller, Whitall,
Analysis and interpretation of data: Luft,
Macko,Sorkin, Schulz, Goldberg, Waller, Whitall, Hanley.
Drafting of the manuscript: Luft, Macko, Waller,
Whitall, Macko, Goldberg, Hanley.
Critical revision of the manuscript for important
intellectual content: Luft, Waller, Whitall, Forrester, Macko, Sorkin,
Schulz, Goldberg, Hanley.
Statistical analysis: Luft, Sorkin.
Obtained funding: Luft, Whitall, Goldberg,
Administrative, technical, or material support:
Waller, Whitall, Forrester, Sorkin, Hanley.
Study supervision: Luft, Waller, Whitall, Forrester.
Funding/Support: This study was funded by National
Institutes of Health grants from the National Institute on Aging (P60AG 12583);
University of Maryland Claude D. Pepper Older Americans Independence Center,
National Institute on Disability and Rehabilitation Research (H133G010111);
the Baltimore Department of Veterans Affairs Geriatrics Research, Education
and Clinical Center (GRECC); National Institute of Neurological Disorders
and Stroke 1RO1 NS 24282-08; the France-Merrick Foundation; the Johns Hopkins
GCRC (NCRR MO1-00052); and the Eleanor Naylor Dana Charitable Trust, Deutsche
Forschungsgemeinschaft (Lu 748/2, 748/3).
Role of the Sponsors: None of the funding agencies
had any role in the design and conduct of the study; the collection, management,
analysis, and interpretation of the data; or in the preparation of the manuscript.
Acknowledgment: We thank Jim Boyd, BA, Christina
Stephenson, MPT, and Jill England, PTA, BS, for their support. We thank the
F. M. Kirby Centre for Functional Brain Imaging, Kennedy Krieger Institute,
and its staff, especially Terry Brawner, BS, and James Pekar, PhD.