Multivariate Analysis of MRI Biomarkers for Predicting Neurologic Impairment in Cervical Spinal Cord Injury.

BACKGROUND AND PURPOSE: Acute markers of spinal cord injury are essential for both diagnostic and prognostic purposes. The goal of this study was to assess the relationship between early MR imaging biomarkers after acute cervical spinal cord injury and to evaluate their predictive validity of neurologic impairment. MATERIALS AND METHODS: We performed a retrospective cohort study of 95 patients with acute spinal cord injury and preoperative MR imaging within 24 hours of injury. The American Spinal Injury Association Impairment Scale was used as our primary outcome measure to define neurologic impairment. We assessed several MR imaging features of injury, including axial grade (Brain and Spinal Injury Center score), sagittal grade, length of injury, maximum canal compromise, and maximum spinal cord compression. Data-driven nonlinear principal component analysis was followed by correlation and optimal-scaled multiple variable regression to predict neurologic impairment. RESULTS: Nonlinear principal component analysis identified 2 clusters of MR imaging variables related to 1) measures of intrinsic cord signal abnormality and 2) measures of extrinsic cord compression. Neurologic impairment was best accounted for by MR imaging measures of intrinsic cord signal abnormality, with axial grade representing the most accurate predictor of short-term impairment, even when correcting for surgical decompression and degree of cord compression. CONCLUSIONS: This study demonstrates the utility of applying nonlinear principal component analysis for defining the relationship between MR imaging biomarkers in a complex clinical syndrome of cervical spinal cord injury. Of the assessed imaging biomarkers, the intrinsic measures of cord signal abnormality were most predictive of neurologic impairment in acute spinal cord injury, highlighting the value of axial T2 MR imaging.

Discrepancy between perceived pain and cortical processing: A voxel-based morphometry and contact heat evoked potential study.

OBJECTIVES: The purpose of this study was to determine if local gray and white matter volume variations between subjects could account for variability in responses to CHEP stimulation. METHODS: Structural magnetic resonance imaging was used to perform voxel-based morphometry (VBM) of gray and white matter in 30 neurologically healthy subjects. Contact heat stimulation was performed on the dorsum of the right hand at the base of the thumb. Evoked potentials were acquired from a vertex-recording electrode referenced to linked ears. RESULTS: Controlling for age, total intracranial volume, and skull/scalp thickness, CHEP amplitude and pain rating were not significantly correlated between subjects. A VBM region of interest approach demonstrated a significant interaction between pain rating and N2 amplitude in the right insular cortex (p<0.05, family-wise error corrected, FWE). In white matter, a significant interaction was localized in the right inferior frontal occipital fasciculus (IFOF, p<0.05 FWE). CONCLUSIONS: Accounting for gray matter volume in the right insular cortex, resulted in a significant relationship between CHEP amplitude and pain rating. SIGNIFICANCE: This finding suggests that the discrepancy between pain ratings and the amplitude of evoked potentials is not solely related to measurement artifact, but rather attributable, in part, to anatomical differences between subjects.

Heterotopic and homotopic nociceptive conditioning stimulation: distinct effects of pain modulation.

BACKGROUND: Within an area, habituation and sensitization represent well-established modulatory effects to repetitive noxious input. Less is known regarding the nociceptive conditioning effects between body sites - i.e., how stimulating one site may affect another. Therefore, we investigated the effects of nociceptive stimulation of anatomically distinct locations (shoulder and hand) on pain rating and evoked potentials (i.e., contact heat-evoked potentials). METHODS: The effect of stimulation order was assessed in eight healthy subjects. The shoulder was examined before the hand or the hand before the shoulder. All subjects underwent both conditions (shoulder before hand and hand before shoulder) on separate days. In an additional 30 subjects (total n = 38), between retesting the shoulder or the hand, conditioning stimulation in the respective other location (i.e., hand or shoulder) was applied. Both analyses focused upon changes in the magnitude of evoked pain responses in relation to the respective area being conditioned by heterotopic stimulation. RESULTS: When the shoulder was stimulated before the hand, N2P2 amplitude was significantly reduced. In contrast, stimulating the hand before the shoulder resulted in significant response increments (shorter N2 latency). Additionally, conditioning stimulation of the hand resulted in increased pain rating to shoulder stimulation. CONCLUSIONS: Overall, these findings indicate that response modulation to noxious contact heat stimulation depends upon conditioning stimulus location. These effects represent changes beyond conventional habituation due to repeated stimulation in the same area.

Increased baseline temperature improves the acquisition of contact heat evoked potentials after spinal cord injury.

OBJECTIVE: To investigate the effect of increasing the skin surface baseline temperature for contact heat evoked potentials (CHEPs). METHODS: CHEPs were studied in healthy subjects and subjects with chronic cervical spinal cord injury (SCI) using a conventional 35°C (condition 1) or increased 42-45°C baseline temperature (condition 2). A third condition was used to standardize the contact heat stimulus duration from the different baseline temperatures. Changes in peak latency and N2P2 amplitude of the CHEPs and rating of perceived intensity were examined between conditions. RESULTS: In healthy subjects, increasing the baseline temperature for contact heat stimulation significantly increased the rating of perceived intensity (conditions 2 and 3), as well as the amplitude of CHEPs (condition 2 only). Following SCI, an increased baseline temperature facilitated perception of contact heat stimulation and evoked potentials could be recorded from dermatomes that were insensitive to contact heat from a conventional baseline temperature. CONCLUSIONS: Enhancing the acquisition of CHEPs can be achieved by increasing the baseline temperature. This effect can be attributed, in part, to shortening the stimulation duration. SIGNIFICANCE: After SCI, increasing the baseline temperature for CHEPs in dermatomes with absent or diminished sensation improved the neurophysiological resolution of afferent sparing.

Temporal and spatial patterns of cortical activation during assisted lower limb movement.

Human gait is a complex process in the central nervous system that results from the integrity of various mechanisms, including different cortical and subcortical structures. In the present study, we investigated cortical activity during lower limb movement using EEG. Assisted by a dynamic tilt table, all subjects performed standardized stepping movements in an upright position. Source localization of the movement-related potential in relation to spontaneous EEG showed activity in brain regions classically associated with human gait such as the primary motor cortex, the premotor cortex, the supplementary motor cortex, the cingulate cortex, the primary somatosensory cortex and the somatosensory association cortex. Further, we observed a task-related power decrease in the alpha and beta frequency band at electrodes overlying the leg motor area. A temporal activation and deactivation of the involved brain regions as well as the chronological sequence of the movement-related potential could be mapped to specific phases of the gait-like leg movement. We showed that most cortical capacity is needed for changing the direction between the flexion and extension phase. An enhanced understanding of the human gait will provide a basis to improve applications in the field of neurorehabilitation and brain-computer interfaces.