R. G. Querry

Changes in supraspinal activation patterns following robotic locomotor therapy in motor-incomplete spinal cord injury.

Objectives. Body weight-supported treadmill training (BWSTT) is a task-specific rehabilitation strategy that enhances functional locomotion in patients following spinal cord injury (SCI). Supraspinal centers may play an important role in the recovery of over-ground locomotor function in patients with motor-incomplete SCI. The purpose of this study was to evaluate the potential for supraspinal reorganization associated with 12 weeks of robotic BWSTT using functional magnetic resonance imaging (fMRI). Methods. Four men with motor-incomplete SCI participated in this study. Time since onset ranged from 14 weeks to 48 months post-SCI injury. All subjects were trained with BWSTT 3 times weekly for 12 weeks. This training was preceded and followed by fMRI study of supraspinal activity during a movement task. Testing of locomotor disability included the Walking Index for Spinal Cord Injury (WISCI II) and over-ground gait speed. Results. All subjects demonstrated some degree of change in the blood-oxygen-level-dependent (BOLD) signal following BWSTT. fMRI results demonstrated greater activation in sensorimotor cortical regions (S1, S2) and cerebellar regions following BWSTT. Conclusions. Intensive task-specific rehabilitative training, such as robotic BWSTT, can promote supraspinal plasticity in the motor centers known to be involved in locomotion. Furthermore, improvement in over-ground locomotion is accompanied by an increased activation of the cerebellum.

Effects of partial neuromuscular blockade on carotid baroreflex function during exercise in humans

1 This investigation was designed to determine the contribution of central command to the resetting of the carotid baroreflex during static and dynamic exercise in humans. 2 Thirteen subjects performed 3.5 min of static one‐legged exercise (20 % maximal voluntary contraction) and 7 min dynamic cycling (20 % maximal oxygen uptake) under two conditions: control (no intervention) and with partial neuromuscular blockade (to increase central command influence) using Norcuron (curare). Carotid baroreflex function was determined at rest and during steady‐state exercise using a rapid neck pressure/neck suction technique. Whole‐body Norcuron was repeatedly administered to effectively reduce hand‐grip strength by approximately 50 % of control. 3 Partial neuromuscular blockade increased heart rate, mean arterial pressure, perceived exertion, lactate concentration and plasma noradrenaline concentration during both static and dynamic exercise when compared to control (P < 0.05). No effect was seen at rest. Carotid baroreflex resetting was augmented from control static and dynamic exercise by partial neuromuscular blockade without alterations in gain (P < 0.05). In addition, the operating point of the reflex was relocated away from the centring point (i.e. closer to threshold) during exercise by partial neuromuscular blockade (P < 0.05). 4 These findings suggest that central command actively resets the carotid baroreflex during dynamic and static exercise.

Effects of exercise pressor reflex activation on carotid baroreflex function during exercise in humans

1 This investigation was designed to determine the contribution of the exercise pressor reflex to the resetting of the carotid baroreflex during exercise. 2 Ten subjects performed 3.5 min of static one‐legged exercise (20 % maximal voluntary contraction) and 7 min dynamic cycling (20 % maximal oxygen uptake) under two conditions: control (no intervention) and with the application of medical anti‐shock (MAS) trousers inflated to 100 mmHg (to activate the exercise pressor reflex). Carotid baroreflex function was determined at rest and during exercise using a rapid neck pressure/neck suction technique. 3 During exercise, the application of MAS trousers (MAS condition) increased mean arterial pressure (MAP), plasma noradrenaline concentration (dynamic exercise only) and perceived exertion (dynamic exercise only) when compared to control (P < 0.05). No effect of the MAS condition was evident at rest. The MAS condition had no effect on heart rate (HR), plasma lactate and adrenaline concentrations or oxygen uptake at rest and during exercise. The carotid baroreflex stimulus‐response curve was reset upward on the response arm and rightward to a higher operating pressure by control exercise without alterations in gain. Activation of the exercise pressor reflex by MAS trousers further reset carotid baroreflex control of MAP, as indicated by the upward and rightward relocation of the curve. However, carotid baroreflex control of HR was only shifted rightward to higher operating pressures by MAS trousers. The sensitivity of the carotid baroreflex was unaltered by exercise pressor reflex activation. 4 These findings suggest that during dynamic and static exercise the exercise pressor reflex is capable of actively resetting carotid baroreflex control of mean arterial pressure; however, it would appear only to modulate carotid baroreflex control of heart rate.

Partial blockade of skeletal muscle somatosensory afferents attenuates baroreflex resetting during exercise in humans

During exercise, the carotid baroreflex is reset to operate around the higher arterial pressures evoked by physical exertion. The purpose of this investigation was to evaluate the contribution of somatosensory input from the exercise pressor reflex to this resetting during exercise. Nine subjects performed seven minutes of dynamic cycling at 30 % of maximal work load and three minutes of static one‐legged contraction at 25 % maximal voluntary contraction before (control) and after partial blockade of skeletal muscle afferents with epidural anaesthesia. Carotid baroreflex function was assessed by applying rapid pulses of hyper‐ and hypotensive stimuli to the neck via a customised collar. Using a logistic model, heart rate (HR) and mean arterial pressure (MAP) responses to carotid sinus stimulation were used to develop reflex function stimulus‐response curves. Compared with rest, control dynamic and static exercise reset carotid baroreflex‐HR and carotid baroreflex‐MAP curves vertically upward on the response arm and laterally rightward to higher operating pressures. Inhibition of exercise pressor reflex input by epidural anaesthesia attenuated the bi‐directional resetting of the carotid baroreflex‐MAP curve during both exercise protocols. In contrast, the effect of epidural anaesthesia on the resetting of the carotid baroreflex‐HR curve was negligible during dynamic cycling whereas it relocated the curve in a laterally leftward direction during static contraction. The data suggest that afferent input from skeletal muscle is requisite for the complete resetting of the carotid baroreflex during exercise. However, this neural input appears to modify baroreflex control of blood pressure to a greater extent than heart rate.

Differential baroreflex control of heart rate in sedentary and aerobically fit individuals

PURPOSE We compared arterial, aortic, and carotid-cardiac baroreflex sensitivity in eight average fit (maximal oxygen uptake, VO2max = 42.2+/-1.9 mL x kg(-1) x min(-1)) and eight high fit (VO2max = 61.9+/-2.2 mL x kg(-1) x min(-1)) healthy young adults. METHODS Arterial and aortic (ABR) baroreflex functions were assessed utilizing hypo- and hyper-tensive challenges induced by graded bolus injections of sodium nitroprusside (SN) and phenylephrine (PE), respectively. Carotid baroreflex (CBR) sensitivity was determined using ramped 5-s pulses of both pressure and suction delivered to the carotid sinus via a neck chamber collar, independent of drug administration. RESULTS During vasoactive drug injection, mean arterial pressure (MAP) was similarly altered in average fit (AF) and high fit (HF) groups. However, the heart rate (HR) response range of the arterial baroreflex was significantly attenuated (P < 0.05) in HF (31+/-4 beats x min(-1)) compared with AF individuals (46+/-4 beats x min(-1)). When sustained neck suction and pressure were applied to counteract altered carotid sinus pressure during SN and PE administration, isolating the ABR response, the response range remained diminished (P < 0.05) in the HF population (24+/-3 beats x min(-1)) compared with the AF group (41+/-4 beats x min(-1)). During CBR perturbation, the HF (14+/-1 beats-min(-1)) and AF (16+/-1 beats-min(-1)) response ranges were similar. The arterial baroreflex response range was significantly less than the simple sum of the CBR and ABR (HF, 38+/-3 beats x min(-1) and AF, 57+/-4 beats x min(-1)) in both fitness groups. CONCLUSIONS These data confirm that reductions in arterial-cardiac reflex sensitivity are mediated by diminished ABR function. More importantly, these data suggest that the integrative relationship between the ABR and CBR contributing to arterial baroreflex control of HR is inhibitory in nature and not altered by exercise training.

A prediction model for determining over ground walking speed after locomotor training in persons with motor incomplete spinal cord injury.

Abstract Background/Objective: To develop and test a clinically relevant model for predicting the recovery of over ground walking speed after 36 sessions of progressive body weight-supported treadmill training (BWSTT) in individuals with motor incomplete spinal cord injury (SCI). Design: A retrospective review and stepwise regression analysis of a SCI clinical outcomes data set. Setting: Outpatient SCI laboratory. Subjects: Thirty individuals with a motor incomplete SCI who had participated in locomotor training with BWSTT. Eight individuals with similar diagnoses were used to prospectively test the prediction model. Main Outcome Measures: Over ground walking speed was assessed using the 10-m walking test. Methods: The locomotor training program consisted of 36 sessions of sequential comprehensive training comprised of robotic assisted BWSTT, followed by manual assisted BWSTT, and over ground walking. The dose of locomotor training was standardized throughout the protocol. Results: Clinical characteristics with predictive value for walking speed were time from injury onset, the presence or absence of voluntary bowel and bladder voiding, a functional spasticity assessment, and over ground walking speed before locomotor training. The model identified that these characteristics accounted for 78.3% of the variability in the actual final over ground walking speed after 36 sessions of locomotor training. The model was successful in prospectively predicting over ground walking speed in the 8 test participants within 4.15 ± 2.22 cm/s in their recovered walking speed. Conclusions: This prediction model can identify individuals who are most likely to experience success using locomotor training by determining an expected magnitude of training effect, thereby allowing individualized decisions regarding the use of this intensive approach to rehabilitation.

Automated Gait and Balance Parameters Diagnose and Correlate with Severity in Parkinson Disease

OBJECTIVE To assess the suitability of instrumented gait and balance measures for diagnosis and estimation of disease severity in PD. METHODS Each subject performed iTUG (instrumented Timed-Up-and-Go) and iSway (instrumented Sway) using the APDM(®) Mobility Lab. MDS-UPDRS parts II and III, a postural instability and gait disorder (PIGD) score, the mobility subscale of the PDQ-39, and Hoehn & Yahr stage were measured in the PD cohort. Two sets of gait and balance variables were defined by high correlation with diagnosis or disease severity and were evaluated using multiple linear and logistic regressions, ROC analyses, and t-tests. RESULTS 135 PD subjects and 66 age-matched controls were evaluated in this prospective cohort study. We found that both iTUG and iSway variables differentiated PD subjects from controls (area under the ROC curve was 0.82 and 0.75 respectively) and correlated with all PD severity measures (R(2) ranging from 0.18 to 0.61). Objective exam-based scores correlated more strongly with iTUG than iSway. The chosen set of iTUG variables was abnormal in very mild disease. Age and gender influenced gait and balance parameters and were therefore controlled in all analyses. INTERPRETATION Our study identified sets of iTUG and iSway variables which correlate with PD severity measures and differentiate PD subjects from controls. These gait and balance measures could potentially serve as markers of PD progression and are under evaluation for this purpose in the ongoing NIH Parkinson Disease Biomarker Program.

Synchronous stimulation and monitoring of soleus H reflex during robotic body weight-supported ambulation in subjects with spinal cord injury.

We evaluated the accuracy of a novel method for recording the soleus H reflex at specific points in the gait cycle during robotic locomotor training in subjects with spinal cord injury (SCI). Hip goniometric information from the Lokomat system defined midstance and midswing points within the gait cycle. Soleus H reflex stimulation was synchronized to these points during robotic-assisted ambulation at 1.8 and 2.5 km/h. Motor stimulus intensity was monitored and adjusted in real time. Analysis of 50 H reflex cycles during each speed and gait phase showed that stimulation accuracy was within 0.5 degrees of the defined hip joint position and that >85% of the H reflex cycles met the +/-10% M wave criterion that was established during quiet standing. This method allows increased consistency of afferent information into the segmental spinal and supraspinal circuitry and, thus, evaluation of H reflex characteristics during robotic ambulation in subjects with SCI.

Ventilatory responses to dynamic exercise elicited by intramuscular sensors.

PURPOSE Eight subjects, aged 27.0+/-1.6 yr, performed incremental workload cycling to investigate the contribution of skeletal muscle mechano- and metaboreceptors to ventilatory control during dynamic exercise. METHODS Each subject performed four bouts of exercise: exercise with no intervention (CON); exercise with bilateral thigh cuffs inflated to 90 mm Hg (CUFF); exercise with application of lower-body positive pressure (LBPP) to 45 torr (PP); and exercise with 90 mm Hg thigh cuff inflation and 45 torr LBPP (CUFF+PP). Ventilatory responses and pulmonary gas exchange variables were collected breath-by-breath with concomitant measurement of leg intramuscular pressure. RESULTS Ventilation (VE) was significantly elevated from CON during PP and CUFF+PP at workloads corresponding to > or = 60% CON peak oxygen uptake (VO2peak) and during CUFF at workloads > or = 80% CON VO2peak, P < 0.05. The VO2 at which ventilatory threshold occurred was significantly reduced from CON (2.17+/-0.28 L x min(-1)) to 1.60+/-0.19 L x min(-1), 1.45+/-0.15 L x min(-1), and 1.15+/-0.11 L x min(-1) during CUFF, PP, and CUFF+PP, respectively. The slope of the linear regression describing the VE/CO2 output relationship was increased from CON by approximately 22% during CUFF, 40% during PP, and 41% during CUFF+PP. CONCLUSIONS As intramuscular pressure was significantly elevated immediately upon application of LBPP during PP and CUFF+PP without a concomitant increase in VE, it seems unlikely that LBPP-induced increases in VE can be attributed to activation of the mechanoreflex. These findings suggest that LBPP-induced reductions in perfusion pressure and decreases in venous outflow resulting from inflation of bilateral thigh cuffs may generate a metabolite sensitive intramuscular ventilatory stimulus.

Are Decreases in Insular Regional Cerebral Blood Flow Sustained during Postexercise Hypotension

UNLABELLED Regional cerebral blood flow (rCBF) in the insular cortex (IC), a well-recognized site for central blood pressure (BP) modulation, is decreased at minute 10 during postexercise hypotension (PEH). PURPOSE To determine whether exercise-induced decreases in IC rCBF are associated with BP changes throughout PEH. METHODS Ten subjects were studied on three different days using a counterbalanced design with a randomized order for conditions; all were tested during a resting baseline and then at two of three time points postexercise: 10, 30, and 60 min. Data were collected for HR, mean BP, and rCBF using single-photon emission computed tomography as an index of brain activation. RESULTS Using ANOVA across conditions, there were differences (P < 0.05; mean +/- SD) for HR from baseline at minute 10 (+15 +/- 4 bpm) and minute 30 (+6 +/- 3 bpm) and for mean BP at minute 10 (-11 +/- 4 mm Hg) and minute 30 (-5 +/- 3 mm Hg). There were significant decreases (P < 0.05) in rCBF at both minutes 10 and 30 after exercise in the inferior thalamus and the right inferior IC regions. Although there were no decreases in BP or IC activity at minute 60, changes in right inferior posterior IC activity and BP were strongly correlated (r2 = 0.74; P < 0.05) postexercise. CONCLUSIONS Findings show that exercise-induced decreases in IC and thalamic activity may be a significant neural factor contributing to at least the first 30 min of PEH.