Susan K. Patrick

Quantification of the UPDRS rigidity scale

In the clinical setting, Parkinsonian rigidity is assessed using subjective rating scales such as that of the Unified Parkinsons Disease Rating System (UPDRS). However, such scales are susceptible to problems of sensitivity and reliability. Here, we evaluate the reliability and validity of a device designed to quantify Parkinsonian rigidity at the elbow and the wrist. The method essentially quantifies the clinical examination and employs small sensors to monitor forces and angular displacements imposed by the clinician onto the limb segment distal to the joint being evaluated. Force and displacement data are used to calculate elastic and viscous stiffnesses and their vectorial sum, mechanical impedance. Interexaminer agreement of measures of mechanical impedance in subjects with Parkinsons disease was comparable to that of clinical UPDRS scores. Examiners tended to overrate rigidity on the UPDRS scale during reinforcement manoeuvres. Mechanical impedance was nonlinearly related to UPDRS ratings of rigidity at the elbow and wrist; characterization of such relationships allows interpretation of impedance measurements in terms of the clinical rating scales.

Interlimb Coordination in Human Crawling Reveals Similarities in Development and Neural Control With Quadrupeds

The study of quadrupeds has furnished most of our understanding of mammalian locomotion. To allow a more direct comparison of coordination between the four limbs in humans and quadrupeds, we studied crawling in the human, a behavior that is part of normal human development and mechanically more similar to quadrupedal locomotion than is bipedal walking. Interlimb coordination during hands-and-knees crawling is compared between humans and quadrupeds and between human infants and adults. Mechanical factors were manipulated during crawling to understand the relative contributions of mechanics and neural control. Twenty-six infants and seven adults were studied. Video, force plate, and electrogoniometer data were collected. Belt speed of the treadmill, width of base, and limb length were manipulated in adults. Influences of unweighting and limb length were explored in infants. Infants tended to move diagonal limbs together (trot-like). Adults additionally moved ipsilateral limbs together (pace-like). At lower speeds, movements of the four limbs were more equally spaced in time, with no clear pairing of limbs. At higher speeds, running symmetrical gaits were never observed, although one adult galloped. Widening stance prevented adults from using the pace-like gait, whereas lengthening the hind limbs (hands-and-feet crawling) largely prevented the trot-like gait. Limb length and unweighting had no effect on coordination in infants. We conclude that human crawling shares features both with other primates and with nonprimate quadrupeds, suggesting similar underlying mechanisms. The greater restriction in coordination patterns used by infants suggests their nervous system has less flexibility.

Unique characteristics of motor adaptation during walking in young children

Children show precocious ability in the learning of languages; is this the case with motor learning? We used split-belt walking to probe motor adaptation (a form of motor learning) in children. Data from 27 children (ages 8-36 mo) were compared with those from 10 adults. Children walked with the treadmill belts at the same speed (tied belt), followed by walking with the belts moving at different speeds (split belt) for 8-10 min, followed again by tied-belt walking (postsplit). Initial asymmetries in temporal coordination (i.e., double support time) induced by split-belt walking were slowly reduced, with most children showing an aftereffect (i.e., asymmetry in the opposite direction to the initial) in the early postsplit period, indicative of learning. In contrast, asymmetries in spatial coordination (i.e., center of oscillation) persisted during split-belt walking and no aftereffect was seen. Step length, a measure of both spatial and temporal coordination, showed intermediate effects. The time course of learning in double support and step length was slower in children than in adults. Moreover, there was a significant negative correlation between the size of the initial asymmetry during early split-belt walking (called error) and the aftereffect for step length. Hence, children may have more difficulty learning when the errors are large. The findings further suggest that the mechanisms controlling temporal and spatial adaptation are different and mature at different times.

Developmental constraints of quadrupedal coordination across crawling styles in human infants

Human infants can crawl using several very different styles; this diversity appears at first glance to contradict our previous findings from hands-and-knees crawling, which suggested that there were strict limitations on coordination, imposed either mechanically or by the developing nervous system. To determine whether coordination was similarly restricted across crawling styles, we studied free crawling overground in 22 infants who used a number of different locomotor strategies. Despite the wide variety in the use of individual limbs and even the number of limbs used, the duration of the stance phase increased with duration of cycle, whereas the duration of the swing phase remained more constant. Additionally, all infants showed organized, rhythmic interlimb coordination. Alternating patterns (e.g., trotlike) predominated (86% of infants). Alternatively, yet much less frequently, all limbs used could work in synchrony (14% of infants). Pacelike patterns were never observed, even in infants that crawled with the belly remaining in contact with the ground so that stability was not a factor. To explore the robustness of the interlimb coordination, a perturbation that prolonged swing of the leg was imposed on 14 additional infants crawling on hands and knees overground or on the treadmill. The perturbation led to a resetting of the crawling pattern, but never to a change in the coordination of the limbs. The findings concur with those regarding other infant animals, together suggesting that the nervous system itself limits the coordination patterns available at a young age.

Training to Enhance Walking in Children With Cerebral Palsy: Are We Missing the Window of Opportunity?

The objective of this paper is to (1) identify from the literature a potential critical period for the maturation of the corticospinal tract (CST) and (2) report pilot data on an intensive, activity-based therapy applied during this period, in children with lesions to the CST. The best estimate of the CST critical period for the legs is when the child is younger than 2 years of age. Previous interventions for walking in children with CST damage were mainly applied after this age. Our preliminary results with training children younger than 2 years showed improvements in walking that exceeded all previous reports. Further, we refined techniques for measuring motor and sensory pathways to and from the legs, so that changes can be measured at this young age. Previous activity-based therapies may have been applied too late in development. A randomized controlled trial is now underway to determine if intensive leg therapy improves the outcome of children with early stroke.

Effects of Chronic Treatment with Losartan and Enalaprilat on [3H]-Norepinephrine Release from Isolated Atria of Wistar-Kyoto and Spontaneously Hypertensive Rats

The present study was designed to evaluate the effect of chronic treatment with losartan, an AT1 angiotensin II receptor antagonist, and enalaprilat, an angiotensin converting enzyme inhibitor, on the presynaptic modulation of [3H]-norepinephrine release from isolated atria of spontaneously hypertensive rats (SHR) and their respective control, the Wistar-Kyoto rats (WKY). The rats received either losartan (5 mg/kg/day) or enalaprilat (1 mg/kg/day) for 12 days by means of osmotic minipumps. The atria were isolated and incubated with [3H]-norepinephrine and the release of radioactivity was used as an index of norepinephrine release. The experimental protocol consisted of two electrical stimulations and the drugs were administered 20 min before the second stimulation. The modulatory action of angiotensin II (0.01 and 1 mumol/L), the alpha 2-adrenoceptor agonist, oxymetazoline (1 mumol/L), the alpha 2-adrenoceptor antagonist, idazoxan (1 mumol/L) and the beta 2-adrenoceptor agonist fenoterol (1 mumol/L) were tested. The results show that losartan or enalaprilat both similarly reduced the blood pressure in SHR. However, only the chronic losartan treatment, and not enalaprilat, abolished the facilitatory effect of exogenously administered angiotensin II on the release of radioactivity. The prejunctional alpha 2- and beta 2-adrenoceptor modulatory mechanisms were not altered by either chronic treatments. Similarly, the facilitatory effect of angiotensin II was blocked by acute administration of losartan but not by enalaprilat. Finally, the facilitatory action of bradykinin on the release of radioactivity was unchanged by chronic enalaprilat treatment. These results confirm the presence of facilitatory AT1 angiotensin II receptors on sympathetic nerve terminals of rat atria. These results also confirm that sympathetic nerve terminal blockade by losartan or the blockade of endogenous angiotensin II formation by enalaprilat are likely to participate in the antihypertensive action of AT1 angiotensin II receptor antagonists and angiotensin converting enzyme.

A nonlinear model of step responses in the cockroach tactile spine neuron

Rapid sensory adaptation in the cockroach tactile spine neuron has previously been associated with a labile threshold for action potentials, which changes with the membrane potential by a process involving two time constants. A feed-forward, variable-threshold model has previously been used to account for the frequency response function of the neuron when stimulated with small-signal, white-noise currents. Here, we used a range of accurately controlled steps of extracellular current to stimulate the neuron. The same model was able to predict the individual step responses and could also fit the entire set of step responses from a single neuron if an initial, saturating, static nonlinearity was included. These results indicate that the two-time-constant, variable-threshold model can account for most of the rapidly adapting behavior of the tactile spine neuron.

Prior Experience but Not Size of Error Improves Motor Learning on the Split-Belt Treadmill in Young Children

Children can modify learned motor skills, such as walking, to adapt to new environments. Movement errors in these new situations drive the learning. We used split-belt walking to determine whether size of the error affects the degree of learning. Twenty-two children (aged 2–5 y) walked on the split-belt treadmill on two separate days spaced 1 week apart. Twenty-eight adults served as controls. On Day 1, children experienced an abrupt change in belt speeds (from 1∶1 to 2∶1 differential) resulting in large errors, or a gradual change (same change in speed over 12–15 min), resulting in small errors. Learning was measured by the size of the aftereffect upon return to a 1∶1 differential. On Day 2 (1 week later), the leg on the fast belt was reversed, as was the method of introducing the speed differential. We found that the error size did not affect learning. Unexpectedly, learning was greater on Day 2 compared to Day 1, especially for children under 4 y of age, despite the fact that the task was opposite to that of Day 1, and did not influence learning in adults. Hence, 11 additional children under 4 y of age were tested with belts running at the same speed on Day 1, and with a 2∶1 speed differential (abrupt introduction) on Day 2. Surprisingly, learning was again greater on Day 2. We conclude that size of error during split-belt walking does not affect learning, but experience on a treadmill does, especially for younger children.

Characteristics of the developing human locomotor system: Similarities to other mammals

Similarities in the development of locomotion between young children and other mammals are explored by reanalysis of data accrued over ~18 years. Supported stepping in children was tested on a treadmill. Although the time course of development is more protracted in humans compared to other mammals, the same trends are seen. For example, the duration of the stepping cycle shortens rapidly in the first 5 months of life. Hypermetric flexion of the hip and knee during stepping is seen in children <3 mo old. Stability of the locomotor rhythm both with respect to cycle duration within a limb and coupling between limbs improves slowly. Finally, coordination between the left and right legs can be manipulated with training, indicating experience-dependent learning at a young age. The possible reasons for these remarkably similar trends in development are explored as a function of maturational time tables for neural structures.

Training-Specific Neural Plasticity in Spinal Reflexes after Incomplete Spinal Cord Injury

The neural plasticity of spinal reflexes after two contrasting forms of walking training was determined in individuals with chronic, motor-incomplete spinal cord injury (SCI). Endurance Training involved treadmill walking for as long as possible, and Precision Training involved walking precisely over obstacles and onto targets overground. Twenty participants started either Endurance or Precision Training for 2 months and then crossed over after a 2-month rest period to the other form of training for 2 months. Measures were taken before and after each phase of training and rest. The cutaneomuscular reflex (CMR) during walking was evoked in the soleus (SOL) and tibialis anterior muscles by stimulating the posterior tibial nerve at the ankle. Clonus was estimated from the EMG power in the SOL during unperturbed walking. The inhibitory component of the SOL CMR was enhanced after Endurance but not Precision Training. Clonus did not change after either form of training. Participants with lower reflex excitability tended to be better walkers (i.e., faster walking speeds) prior to training, and the reduction in clonus was significantly correlated with the improvement in walking speed and distance. Thus, reflex excitability responded in a training-specific way, with the reduction in reflex excitability related to improvements in walking function. Trial registration number is NCT01765153.