Accepted Manuscript Cortical activation during visual illusory walking in persons with spinal cord injury: A pilot study John Eick , B.S, Elizabeth J. Richardson , Ph.D., MSPH PII:
S0003-9993(14)01222-2
DOI:
10.1016/j.apmr.2014.10.020
Reference:
YAPMR 56028
To appear in:
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
Received Date: 8 September 2014 Revised Date:
24 October 2014
Accepted Date: 25 October 2014
Please cite this article as: Eick J, Richardson EJ, Cortical activation during visual illusory walking in persons with spinal cord injury: A pilot study, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2014), doi: 10.1016/j.apmr.2014.10.020. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Cortical activation in illusory walking 1
Cortical activation during visual illusory walking in persons with spinal cord injury:
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A pilot study
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John Eick, B.S.1 & Elizabeth J. Richardson, Ph.D., MSPH2
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1. University of Alabama at Birmingham, School of Medicine
2. University of Alabama at Birmingham, Department of Physical Medicine and Rehabilitation
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A portion of these data were presented at the Association of Academic Physiatrists annual conference in New Orleans, LA. March 6-10, 2013 and at the 2014 Academy of Spinal Cord
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Injury Professionals annual conference in St. Louis, MO.
Acknowledgments: This study was made possible by the Rehabilitation Research Experience for
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Medical Students (RREMS) Program of the Association of Academic Physiatrists, NIDRR grant #H133N110008 and by NIH grant #1 K23 HD073680-01A1. There are no known conflicts of interest.
Corresponding author: E. J. Richardson, 1717 6th Avenue S, Birmingham, AL, 35249. Phone: 205.934.3454. Email:
[email protected].
ACCEPTED MANUSCRIPT Cortical activation in illusory walking 1 1
Cortical activation during visual illusory walking in persons with spinal cord injury: A pilot
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study
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Abstract Objective: To determine the location of cortical activation during a visual illusion
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walking paradigm, a recently proposed treatment for spinal cord injury (SCI)-related neuropathic
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pain, in persons with SCI compared to able-bodied controls. Design: Pilot experimental fMRI
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trial. Setting: Outpatient rehabilitation clinic. Participants: Three persons with paraplegia and
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five able bodied participants were included in this study. Interventions: Not applicable. Main
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Outcome Measures: Cortical activation as measured by blood oxygenation-level dependent
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(BOLD) method of fMRI. Results: During visually illusory walking, there was significant
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activation in the somatosensory cortex among those with SCI. In contrast, able-bodied
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participants showed little to no significant activation in this area, but rather, in the frontal and
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pre-motor areas. Conclusions: Treatment modalities for SCI-related neuropathic pain that are
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based on sensory input paradigms such as virtual or visual illusory walking may work by
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targeting somatosensory cortex, an area that has been previously found to functionally reorganize
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following SCI.
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Key words: spinal cord injuries, neuropathic pain, somatosensory cortex, fMRI
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Abbreviations: SCI = spinal cord injury, fMRI = functional magnetic resonance imaging, BOLD
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= blood oxygen level dependent, MNI = Montreal Neurologic Institute
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Introduction
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Approximately 70% of persons report pain following spinal cord injury (SCI).1 Neuropathic pain is one form of post-SCI pain that is experienced in a region of sensory
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disturbance around or below the zone of injury. SCI-related neuropathic pain is often refractory,
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with many individuals experiencing only modest to minimal responsiveness to currently
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available treatments.2 It is for this reason that novel treatment approaches to address SCI-related
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neuropathic pain are now being explored with promising initial results.
Novel treatments for SCI-related neuropathic pain are based on the assumption that
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cortical activity is continuously modulated by afferent, intersensory processes.3 When
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disruptions in this cortical-afferent operating feedback system occur, such as in amputation, the
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brain can functionally reorganize – a phenomenon thought to underlie the pain that is
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experienced.4 Reinstating sensory input, via visual illusion (e.g., mirror box therapy for phantom
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limb pain) has been found to promote pain relief5,6 and, moreover, some sensory input paradigms
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have been shown to reverse the reorganization thought to underlie phantom pain.7 Similarly,
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functional cortical reorganization in the somatosensory cortex has been linked to SCI and to a
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greater degree among those with SCI-related pain.8 Additionally, existing evidence suggests that
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when persons with SCI-related neuropathic pain are provided the visual illusion that they are
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walking, the severity of their pain is reduced.9,10
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If in fact SCI-related neuropathic pain is alleviated by reinstating sensory input through
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visual illusion walking paradigms, then it remains to be understood how these treatments affect
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the cortical correlates of SCI-related neuropathic pain and perhaps reverse maladaptive
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functional reorganization. It has been shown that mirror box therapy results in sensorimotor
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activation contralateral to the virtual hand, supporting the theory that perception plays a large
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role in sensorimotor cortical activity.11 Providing the visual illusion of walking may have a
ACCEPTED MANUSCRIPT Cortical activation in illusory walking 3 similar effect as mirror box therapy, yet the cortical region of activation has not been
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characterized. Therefore, the aim of this study was to determine the location of cortical activation
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during a visual illusory walking paradigm in persons with SCI compared to able-bodied controls.
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We hypothesized that the visual illusion of walking would activate the sensorimotor cortex in
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persons with SCI and that the patterns of activation would be different than that of able-bodied
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participants.
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Methods
Subjects: Three persons with SCI (2 male, 1 female) who were non ambulatory, manual
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wheelchair users were recruited from an outpatient rehabilitation center (Table 1). Additionally,
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data from five able-bodied controls (2 male, 3 female) were used for comparison. The study was
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approved by the institution’s IRB and informed written consent was obtained from all
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participants for all of the procedures.
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MRI scanning and image processing: Whole brain images were acquired using a Philips Achieva 3 Tesla MRI systema and the blood oxygenation-level dependent (BOLD) method of
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fMRI was used to measure change in cerebral blood flow during presentation of each stimulus.
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A block design was used, such that participants viewed separate 30-second blocks of fixation
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point (resting state), visual illusion of walking, and visual illusion of wheelchair use. The stimuli
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were projected to each participant on an MRI-compatible screen while lying on the scanner. The
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sequence of stimuli was repeated four times for a total of eight minutes.
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Visual illusory walking: The visual illusory walking paradigm was adapted from an
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ongoing, larger study examining the effects of an immersive, simulated walking experience
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presented in 3D video to participants. Due to constraints of MR scanning and the necessity to
ACCEPTED MANUSCRIPT Cortical activation in illusory walking 4 have demagnetized video display equipment, the walking stimuli could only be presented in 2D
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format during scanning. The walking stimuli consisted of a video of an actor, in first person
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view, walking along a path. The control stimuli consisted of the same actor, in first person view,
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propelling a manual wheelchair along the same path for the same length of time (Figure 1). Prior
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to the presentation of the stimuli during scanning, participants were instructed to imagine that
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they themselves were performing the movements of the actor, but without actual movement of
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limbs. They were instructed to gaze at a fixation point during resting state scanning.
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After scanning, participants were asked to rate how immersive/realistic the fMRI-adapted virtual scenes were on a 5-point Likert scale (1 =Not at all, 2 = Slightly, 3 = Moderately, 4 =
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Very Much So, 5 = Extremely). Participants were also asked to rate, using the same scale, how
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adequately they were able to imagine that they were performing the movements.
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Analysis: fMRI images were processed using SPM8 software,12,b correcting for motion artifact, normalized to the Montreal Neurological Institute (MNI) template and smoothed using a
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8mm full-width half-max Gaussian filter. Using general linear modeling, a contrast was modeled
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between the walk and wheel conditions so that significant activations (p < .01) during the
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illusory walking condition, above and beyond that of the illusory wheeling condition, could be
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observed. Differences in the average signal intensity during walking, while controlling for
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wheeling, were then determined for each group.
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Results
When the pattern of activation in the contrast (cortical activation during walking
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condition minus the wheeling condition) was examined, differences emerged. Among persons
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with SCI, there was significant activation along the bilateral somatosensory cortex and the
ACCEPTED MANUSCRIPT Cortical activation in illusory walking 5 paracentral lobule (right > left), and to a lesser extent, although still present, medial motor areas
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(Fig. 2). In contrast, able-bodied participants experienced significant activation in the bilateral
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frontal and premotor cortex. When examining individual scans of the participants, each
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participant with SCI consistently showed activation in the somatosensory cortex. The participant
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with incomplete SCI additionally showed premotor activation, similar to the able-bodied group.
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Questionnaire data revealed that both walking and wheeling visual illusory stimuli were
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experienced as more immersive among able-bodied participants compared to persons with SCI
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(M = 3.6 and 2.0, respectively), a difference that was significant (t = 3.0; p