Jordan W. Squair

First trial and StartReact effects induced by balance perturbations to upright stance

Postural responses (PR) to a balance perturbation differ between the first and subsequent perturbations. One explanation for this first trial effect is that perturbations act as startling stimuli that initiate a generalized startle response (GSR) as well as the PR. Startling stimuli, such as startling acoustic stimuli (SAS), are known to elicit GSRs, as well as a StartReact effect, in which prepared movements are initiated earlier by a startling stimulus. In this study, a StartReact effect paradigm was used to determine if balance perturbations can also act as startle stimuli. Subjects completed two blocks of simple reaction time trials involving wrist extension to a visual imperative stimulus (IS). Each block included 15 CONTROL trials that involved a warning cue and subsequent IS, followed by 10 repeated TEST trials, where either a SAS (TESTSAS) or a toes-up support-surface rotation (TESTPERT) was presented coincident with the IS. StartReact effects were observed during the first trial in both TESTSAS and TESTPERT conditions as evidenced by significantly earlier wrist movement and muscle onsets compared with CONTROL. Likewise, StartReact effects were observed in all repeated TESTSAS and TESTPERT trials. In contrast, GSRs in sternocleidomastoid and PRs were large in the first trial, but significantly attenuated over repeated presentation of the TESTPERT trials. Results suggest that balance perturbations can act as startling stimuli. Thus first trial effects are likely PRs which are superimposed with a GSR that is initially large, but habituates over time with repeated exposure to the startling influence of the balance perturbation.

Are increases in COP variability observed when participants are provided explicit verbal cues prior to COM stabilization

Previous research has shown that when the COM is stabilized without participant awareness, COP displacements increase. This finding suggests that postural sway under normal conditions may be exploratory and used as a means of acquiring sensory information. However, based on the theory that posture is controlled using internal models, it could be argued that increases in COP displacement reflect errors that arise as the central nervous system attempts to adapt the internal model used to control posture to the new conditions. The current study provided an explicit verbal cue to the participants indicating how and when COM stabilization would occur. Based on evidence suggesting that explicit verbal cues can reduce errors when the dynamics of the task are altered, we hypothesized that when participants were aware of COM stabilization, COP displacements would be reduced. However, we found that anterior-posterior COP displacements increased independent of cueing, suggesting that increases in COP displacements with locking were not the result of an attempt to adapt the internal model of postural control. The results provide further support for an exploratory role of postural sway.

The Canadian clinician-scientist training program must be reinstated

Clinical investigators within the Canadian and international communities were shocked when the Canadian Institutes of Health Research (CIHR) announced that their funding for the MD/PhD program would be terminated after the 2015-2016 academic year. The program has trained Canadian clinician-scientists for more than two decades. The cancellation of the program is at odds with the CIHRs mandate, which stresses the translation of new knowledge into improved health for Canadians, as well as with a series of internal reports that have recommended expanding the program. Although substantial evidence supports the analogous Medical Scientist Training Program in the United States, no parallel analysis of the MD/PhD program has been performed in Canada. Here, we highlight the long-term consequences of the programs cancellation in the context of increased emphasis on translational research. We argue that alternative funding sources cannot ensure continuous support for students in clinician-scientist training programs and that platform funding of the MD/PhD program is necessary to ensure leadership in translational research.

Spinal cord perfusion pressure predicts neurologic recovery in acute spinal cord injury

Objective: To determine whether spinal cord perfusion pressure (SCPP) as measured with a lumbar intrathecal catheter is a more predictive measure of neurologic outcome than the conventionally measured mean arterial pressure (MAP). Methods: A total of 92 individuals with acute spinal cord injury were enrolled in this multicenter prospective observational clinical trial. MAP and CSF pressure (CSFP) were monitored during the first week postinjury. Neurologic impairment was assessed at baseline and at 6 months postinjury. We used logistic regression, systematic iterations of relative risk, and Cox proportional hazard models to examine hemodynamic patterns commensurate with neurologic outcome. Results: We found that SCPP (odds ratio 1.039, p = 0.002) is independently associated with positive neurologic recovery. The relative risk for not recovering neurologic function continually increased as individuals were exposed to SCPP below 50 mm Hg. Individuals who improved in neurologic grade dropped below SCPP of 50 mm Hg fewer times than those who did not improve (p = 0.012). This effect was not observed for MAP or CSFP. Those who were exposed to SCPP below 50 mm Hg were less likely to improve from their baseline neurologic impairment grade (p = 0.0056). Conclusions: We demonstrate that maintaining SCPP above 50 mm Hg is a strong predictor of improved neurologic recovery following spinal cord injury. This suggests that SCPP (the difference between MAP and CSFP) can provide useful information to guide the hemodynamic management of patients with acute spinal cord injury.

Cardiac Consequences of Autonomic Dysreflexia in Spinal Cord Injury

Autonomic dysreflexia (AD), which describes episodic hypertension, is highly prevalent in people with spinal cord injury (SCI). In non-SCI, primary hypertension depresses cardiac contractile reserve via &bgr;-adrenergic mechanisms. In this study, we investigated whether AD contributes to the impairment in cardiac contractile function that accompanies SCI. We induced SCI in rodents and stratified them into sham, SCI, or SCI plus repetitive induction of AD. At 6-week post-SCI, we assessed cardiac function using in vivo (speckle-tracking echocardiography), ex vivo (working heart), and molecular approaches (Western blot). We also provide unique translational insight by comparing the relationship between the number of daily AD events and cardiac function in 14 individuals with cervical SCI. We found SCI and SCI plus repetitive induction of AD exhibited a reduction in left ventricular dimensions at 6-week post-SCI versus preinjury (P<0.049). Compared with sham, SCI exhibited a reduction in peak radial strain along with a down and rightward shift in the Starling curve (P<0.037), both of which were further depressed in SCI plus repetitive induction of AD (P<0.042). In response to &bgr;-adrenergic stimulation, SCI plus repetitive induction of AD exhibited an attenuated increase in contractile indices (P<0.001), despite no differences in &bgr;-receptor expression within the left ventricle. Our clinical data confirm our experimental findings by demonstrating significant associations between the number of daily AD events and markers of systolic and diastolic function along with left ventricular mechanics. Here, we provide the first evidence from a translational perspective that AD exerts insidious effects on cardiac function in rodents and humans with SCI.

Cortical and vestibular stimulation reveal preserved descending motor pathways in individuals with motor-complete spinal cord injury.

OBJECTIVE To use a combination of electrophysiological techniques to determine the extent of preserved muscle activity below the clinically-defined level of motor-complete spinal cord injury. METHODS Transcranial magnetic stimulation and vestibular-evoked myogenic potentials were used to investigate whether there was any preserved muscle activity in trunk, hip and leg muscles of 16 individuals with motor-complete spinal cord injury (C4-T12) and 16 able-bodied matched controls. RESULTS Most individuals (14/16) with motor-complete spinal cord injury were found to have transcranial magnetic stimulation evoked, and/or voluntary evoked muscle activity in muscles innervated below the clinically classified lesion level. In most cases voluntary muscle activation was accompanied by a present transcranial magnetic stimulation response. Furthermore, motor-evoked potentials to transcranial magnetic stimulation could be observed in muscles that could not be voluntarily activated. Vestibular-evoked myogenic potentials responses were also observed in a small number of subjects, indicating the potential preservation of other descending pathways. CONCLUSION These results highlight the importance of using multiple electrophysiological techniques to assist in determining the potential preservation of muscle activity below the clinically-defined level of injury in individuals with a motor-complete spinal cord injury. These techniques may provide clinicians with more accurate information about the state of various motor pathways, and could offer a method to more accurately target rehabilitation.

Emergency management of autonomic dysreflexia with neurologic complications.

A 59-year-old man with a complete (American Spinal Injury Association Impairment Scale A) spinal cord injury at the fourth thoracic vertebra (T4), secondary to a motor vehicle crash 42 years earlier, presented to the emergency department with a 12-hour history of headaches, loss of vision and nausea

Diagnostic accuracy of common clinical tests for assessing abdominal muscle function after motor-complete spinal cord injury above T6

Study design:Diagnostic study.Objectives:The objective of this study was to compare patterns of electromyography (EMG) recordings of abdominal muscle function in persons with motor-complete spinal cord injury (SCI) above T6 and in able-bodied controls, and to determine whether manual examination or ultrasound measures of muscle activation can be accurate alternatives to EMG.Setting:Research center focused on SCI and University laboratory, Vancouver, Canada.Methods:Thirteen people with SCI (11 with American Spinal Injury Association Impairment Scale (AIS) A and 2 AIS B; C4-T5), and 13 matched able-bodied participants volunteered for the study. Participants completed trunk tasks during manual examination of the abdominal muscles and then performed maximal voluntary isometric contractions, while EMG activity and muscle thickness changes were recorded. The frequency of muscle responses detected by manual examination and ultrasound were compared with detection by EMG (sensitivity and specificity).Results:All individuals with SCI were able to elicit EMG activity above resting levels in at least one abdominal muscle during one task. In general, the activation pattern was task specific, confirming voluntary control of the muscles. Ultrasound, when compared with EMG, showed low sensitivity but was highly specific in its ability to detect preserved abdominal muscle function in persons with SCI. Conversely, manual examination was more sensitive than ultrasound but showed lower specificity.Conclusion:The results from this study confirm preserved voluntary abdominal muscle function in individuals classified with motor-complete SCI above T6 and highlight the need for further research in developing more accurate clinical measures to diagnose the level of trunk muscle preservation in individuals with SCI.

Journal Club: Relationship between carotid arterial properties and cerebral white matter hyperintensities

White matter hyperintensities (WMH) are generally diagnosed on brain MRI and are associated with risk of stroke, dementia, death, and functional impairment.1,2 Their progression appears to be insidious, and the detection of preclinical disease could provide the opportunity to aggressively manage risk factors (i.e., reduced thresholds to begin hypertension treatment, lowering blood pressure targets), increase monitoring frequency, and begin secondary prevention strategies in the case of silent infarcts (i.e., initiation of antiplatelet therapy with silent strokes, CT angiography as needed). Given that most people do not receive neuroimaging in the presymptomatic stage, an inexpensive, noninvasive test could help to identify those at risk. To date, potential vascular markers of cerebrovascular disease have focused on central arterial stiffness3; however, directly assessing the carotid arteries may be more relevant to cerebrovascular disease as this vessel serves as the primary conduit responsible for delivering blood to the brain.

Predictors of sustained research involvement among MD/PhD programme graduates

MD/PhD programmes provide structured paths for physician‐scientist training. However, considerable proportions of graduates of these programmes do not pursue careers in research consistent with their training.