A novel and simple test of gait adaptability predicts gold standard measures of functional mobility in stroke survivors.

BACKGROUND: Although there is evidence that stroke survivors have reduced gait adaptability, the underlying mechanisms and the relationship to functional recovery are largely unknown. We explored the relationships between walking adaptability and clinical measures of balance, motor recovery and functional ability in stroke survivors. METHODS: Stroke survivors (n=42) stepped to targets, on a 6m walkway, placed to elicit step lengthening, shortening and narrowing on paretic and non-paretic sides. The number of targets missed during six walks and target stepping speed was recorded. Fugl-Meyer (FM), Berg Balance Scale (BBS), self-selected walking speed (SWWS) and single support (SS) and step length (SL) symmetry (using GaitRite when not walking to targets) were also assessed. Stepwise multiple-linear regression was used to model the relationships between: total targets missed, number missed with paretic and non-paretic legs, target stepping speed, and each clinical measure. RESULTS: Regression revealed a significant model for each outcome variable that included only one independent variable. Targets missed by the paretic limb, was a significant predictor of FM (F(1,40)=6.54, p=0.014,). Speed of target stepping was a significant predictor of each of BBS (F(1,40)=26.36, p<0.0001), SSWS (F(1,40)=37.00, p<0.0001). No variables were significant predictors of SL or SS asymmetry. DISCUSSION: Speed of target stepping was significantly predictive of BBS and SSWS and paretic targets missed predicted FM, suggesting that fast target stepping requires good balance and accurate stepping demands good paretic leg function. The relationships between these parameters indicate gait adaptability is a clinically meaningful target for measurement and treatment of functionally adaptive walking ability in stroke survivors.

Foot rotation contribution to trunk and gaze stability during whole-body mediated gaze shifts: a principal component analysis study.

Large gaze displacements are mediated by combined motion of the eye, head, trunk, and foot. We applied principal component analysis (PCA) to examine the degree of variability and linearity in the angular velocity pattern of the various segments involved that participate in this task. Ten normal subjects stood up and had to visually fixate and realign their bodies with LED targets separated 45 degrees apart, ranging from +/-45 to 360 degrees. The outbound movement in this paradigm is unpredictable whereas the return (inbound) movement occurs under spatially predictable conditions. Under such predictable conditions, subjects generate in approximately 15% of the trials gaze shifts, with periods of fairly constant high gaze velocity (single-step gaze shifts). PCA showed that gaze velocity variability did not change if the feet were rotating or not. Foot velocity was variable and showed additional PCs suggestive of non-linear motion components. Trunk and head-in-space velocity showed intermediate levels of variability but its variability decreased during the foot stepping movements. The results suggest that the feet, trunk, and head are less tightly controlled by the central nervous system than gaze velocity. Movements of the feet seem to aid trunk stability and motion rather than gaze control.

Evidence that older adult fallers prioritise the planning of future stepping actions over the accurate execution of ongoing steps during complex locomotor tasks.

Previous research has highlighted differences between older adults determined to be at a low-risk of falling (low-risk) and older adults prone to falling (high-risk) in both where and when they look at stepping targets and the precision with which they subsequently step. On the basis of these findings, we proposed that high-risk older adults prioritise the planning of future stepping actions over the accurate execution of ongoing movements and that adoption of this strategy contributes to increased likelihood of falls. The present experiment was designed to test this hypothesis by manipulating the complexity of the required walking conditions and comparing gaze and stepping performance between young, high-risk and low-risk older adults. Participants walked at a self-selected pace along a 7-m pathway and encountered one of three obstacle conditions: (1) a single stepping target, (2) two stepping targets, (3) two stepping targets separated by a raised obstacle. On average, when there was a single target (Target 1) in the travel path, all groups fixated the target until after heel contact. However, when challenged with additional impending stepping constraints, high-risk older adults transferred their gaze significantly sooner from Target 1 prior to heel contact. On average, low-risk older adults and younger adults maintained gaze on Target 1 until after heel contact, irrespective of future constraints. Premature gaze transfer was associated with decline in stepping accuracy and precision. Our findings suggest that high-risk older adults choose a potentially hazardous gaze strategy when challenged with multiple obstacles. Putative mechanisms underlying this behaviour are discussed.

Age-related differences in stepping performance during step cycle-related removal of vision.

The aim of the present study was to investigate whether there are age-related changes in the ability of individuals to use vision to plan (feedforward control) and guide (on-line control) foot placement during locomotion. This aim was achieved by constraining the availability of vision and comparing the effects on the stepping performances of older and young adults during a precision stepping task. We experimentally controlled the availability of visual information such that: (1) vision was only available during each stance phase of the targeting limb, (2) vision was only available during each swing phase of the targeting limb or (3) vision was always available. Our visual manipulations had relatively little effect on younger adults' stepping performance as demonstrated by their missing the target on less than 10% of occasions. However, there were clear visual condition-related differences in older adults' stepping performance. When vision was only available during the stance phase of the targeting limb, older adults demonstrated significantly larger foot placement error and associated task failure rate (23%) than trials in which vision was always available (10%). There was an even greater increase in older adults' foot placement error and task failure rate (42%) during trials in which vision was only available in the swing phase than the other visual conditions. These findings suggest that older adults need vision at particular times during the step cycle, to effectively pre-plan future stepping movements. We discuss the evidence that these age-related changes in performance reflect decline in visual and visuomotor CNS pathways.

Evidence for a link between changes to gaze behaviour and risk of falling in older adults during adaptive locomotion.

There is increasing evidence that gaze stabilization with respect to footfall targets plays a crucial role in the control of visually guided stepping and that there are significant changes to gaze behaviour as we age. However, past research has not measured if age-related changes in gaze behaviour are associated with changes to stepping performance. This paper aims to identify differences in gaze behaviour between young (n=8) adults, older adults determined to be at a low-risk of falling (low-risk, n=4) and older adults prone to falling (high-risk, n=4) performing an adaptive locomotor task and attempts to relate observed differences in gaze behaviour to decline in stepping performance. Participants walked at a self-selected pace along a 9m pathway stepping into two footfall target locations en route. Gaze behaviour and lower limb kinematics were recorded using an ASL 500 gaze tracker interfaced with a Vicon motion analysis system. Results showed that older adults looked significantly sooner to targets, and fixated the targets for longer, than younger adults. There were also significant differences in these measures between high and low-risk older adults. On average, high-risk older adults looked away from targets significantly sooner and demonstrated less accurate and more variable foot placements than younger adults and low-risk older adults. These findings suggest that, as we age, we need more time to plan precise stepping movements and clearly demonstrate that there are differences between low-risk and high-risk older adults in both where and when they look at future stepping targets and the precision with which they subsequently step. We propose that high-risk older adults may prioritize the planning of future actions over the accurate execution of ongoing movements and that adoption of this strategy may contribute to an increased likelihood of falls.

"Look where you're going!": gaze behaviour associated with maintaining and changing the direction of locomotion.

In order to fully understand how vision is used to guide locomotion it is necessary to know what people look at as they move through the environment. This study provides information, hitherto lacking, regarding gaze behaviour associated with both maintaining and changing the direction of locomotion: activities that are essential for efficient navigation through our cluttered environment. Participants' spatiotemporal gaze patterns were recorded whilst they performed a task requiring that they either maintained a straight walking trajectory or changed their direction of walking by 30 degrees or 60 degrees, left or right, at the midpoint of a 9-m path. Participants were either visually cued to turn when they stepped on a trigger mat placed one step before the mid-point of the walkway (cued trials) or given verbal instruction about the required route prior to the start of each trial (advance knowledge trials). Our clear finding was that for the large majority of the time participants' gaze was aligned with environmental features lying in their current plane of progression both prior to and following the onset of the transition stride during which the direction change was implemented. This gaze behaviour was observed both during cued trials (78% of total fixation time prior to the transition stride onset and 89% following the transition stride onset) and advance knowledge trials (67% prior to transition stride onset, 92% following transition stride onset). When not aligned with the plane of progression, gaze was normally fixated on environmental features related to either known or potential future routes. Prior to changing the direction of walking, individuals invariably made saccadic eye movements in order to align gaze with the end-point of the required travel path. This gaze realignment was invariably accompanied by head reorientation, which was initiated, on average, at the same time as the saccade. On average, participants fixated gaze on their goal (represented by the cue light at the travel path end-point) until after head realignment with the new path was achieved. Additionally, the head was consistently aligned with participants' current walking direction prior to and following the transition stride even on the minority of occasions when they were looking elsewhere. These findings challenge the ecological validity of existing theories of how visual information is used to determine heading direction and are consistent with the proposal that aligning the head with the desired travel direction through coordinated eye and head movements provides the CNS with an allocentric frame of reference that is used to control the movement of the body in space.

Effects of head immobilization on the coordination and control of head and body reorientation and translation during steering.

Changing the direction of locomotion involves lateral translation of the body in addition to body reorientation to align with the new travel direction. We designed this study to investigate the CNS control of these postural adjustments. The specific aims of the study were: first, to test the hypothesis that anticipatory head movements towards the new travel path are proactively controlled by the CNS to provide a stable frame of reference for body reorientation and, second, to investigate the relative contribution of foot placement and other mechanisms to the control of lateral body translation during steering. We achieved these aims by carrying out a comprehensive biomechanical analysis of participants performing a steering paradigm and observing the effects of immobilizing the head (by fixing it to the trunk) on postural control and the sequencing of body segment reorientation. Participants performed a task whereby they were visually cued to change their direction of walking by 30 degrees or 60 degrees, left or right, at the midpoint of a 9-m path. The temporal sequence of body reorientation was consistent with previous findings that the head starts to turn in the direction of travel before the rest of the body. Translation of the centre of mass (COM) in the new travel direction was achieved both through alternate placement of the contralateral foot prior to the turn step and use of a hip strategy to control the body pendulum during swing. Immobilizing the head resulted in the following significant changes: earlier onset of trunk yaw with respect to cue delivery, later trunk roll onset and a reduction in trunk roll amplitude. These results provide valuable information regarding the biomechanics of steering and support the hypothesis that aligning the head with motor or locomotor goals using vision provides the CNS with a stable frame of reference, independent of gaze, that can be used to control the repositioning of the body in space.

Coordination of eye and leg movements during visually guided stepping.

In the present study, 2 related hypotheses were tested: first, that vision is used in a feedforward control mode during precision stepping onto visual targets and, second, that the oculomotor and locomotor control centers interact to produce coordinated eye and leg movements during that task. Participants' (N = 4) eye movements and step cycle transition events were monitored while they performed a task requiring precise foot placement at every step onto irregularly placed stepping stones under conditions in which the availability of visual information was either restricted or intermittently removed altogether. Accurate saccades, followed by accurate steps, to the next footfall target were almost always made even when the information had been invisible for as long as 500 ms. Despite delays in footlift caused by the temporary removal (and subsequent reinstatement) of visual information, the mean interval between the start of the eye movement and the start of the swing toward a target did not vary significantly (p >.05). In contrast, the mean interval between saccade onset away from a target and a foot landing on that target (stance onset) did vary significantly (p <.05) under the different experimental conditions. Those results support the stated hypotheses.

Evidence for interactive locomotor and oculomotor deficits in cerebellar patients during visually guided stepping.

Eight patients suffering from primary cerebellar degenerative diseases undertook a walkway task, demanding precise foot placement at each step, and a visual fixation task, requiring only eye movements. Step cycle and horizontal eye movements were recorded throughout the tasks and compared to those of healthy adults (including age- and sex-matched controls). Cerebellar patients displayed both locomotor and oculomotor deficits. Increases in duration of the stance, swing and double support phases of the step cycle were all shown to contribute to ataxic gait. Dysmetric saccades to fixate the footfall targets were seen more frequently in patients than in controls. These hypometric saccades were followed by one or more corrective saccades (patients: >45% accompanied by one or more corrective saccades; controls: <10% accompanied by a single corrective saccade). Similarities between the oculomotor deficits displayed by patients during the visual fixation task and when walking indicate that the latter are not merely a consequence of ataxic gait. The existence of several links between these locomotor and oculomotor deficits provides evidence for considerable interaction between the two control systems in the production of patterned eye and stepping movements. These results also suggest that the cerebellum plays an active role in the co-ordination of visually guided eye and limb movements during visually guided stepping.

A method for automatic identification of saccades from eye movement recordings.

We describe a technique for reliable and rapid automatic identification of saccades in eye movement records. The signal processing that we describe will be useful to anyone wanting to analyse large numbers (thousands) of eye movements. We describe a transform that is derived from the differentiated eye movement record, and which is related to a transform previously used to automate analysis of EMG recordings.

Visually guided stepping under conditions of step cycle-related denial of visual information.

We recently reported that subjects performing a task that requires visual guidance of each step onto irregularly placed "stepping stones" usually fixate the next target of footfall just before they lift the foot to be repositioned, i.e. towards the end of that limb's stance phase. When negotiating the same walkway without ambient lighting, and with each stone's location indicated by a central light spot (LED), stepping and eye movements were unchanged. Under conditions of intermittent visual denial, in which all LEDs (the only visual cues) were temporarily extinguished at irregular intervals, temporal changes in the normal stepping pattern were sometimes observed, but stepping was not always affected. The primary effect of visual denial was on the leg that was in stance (foot in place on a stepping stone) at the moment of LED extinction, rather than on the leg that was in swing, and was an increase in stance duration, suggesting an effect on planning during this stance of the next swing towards the next target rather than on execution of the ongoing swing of the other leg. Subjects rarely failed to step onto the targets. Prolongations of stance under visual denial lasting 400 or 500 ms were less than 200 ms, much less than the duration of denial; subjects did not simply wait for the footfall target to reappear. There was no effect for denial lasting 300 ms; subjects performed as well as with a constantly visible target. Under 400 and 500 ms denial, there was no effect when the targets disappeared in the first 100 ms of stance (of the foot to be repositioned); stance durations were indistinguishable from control. This suggests that there is no crucial visuomotor processing by the control system(s) for eye and limb guidance until the target reappeared near the usual end of stance, when feedforward planning of the next saccade and/or swing to a target reaches a crucial stage, and is affected by intrusion of the period of visual denial. With longer (800 ms) denial there was an effect regardless of when in stance it began. A smaller effect of 800 ms denial sometimes visible in swing duration is attributable to interlimb coordination. Accurate saccades, followed by accurate steps, to the next target are almost always made, even when the target is invisible. Our results demonstrate that uninterrupted on-line visual information is not necessary for accurate stepping even when (as here) each step requires visual guidance. Also, since stance prolongations did not always result, and they were always much shorter than the periods of denial, we conclude that the visuomotor control mechanism(s) are robust in the face of substantial denial of all visual information including normally preferred inputs (foveal or peripheral images) at the normally preferred times. The fact that a saccade is still made to an invisible target location implies that this is useful in itself, since it does not result in a visible foveal image. We propose that skilled, visually guided stepping onto irregularly placed targets is executed under predominantly feedforward visuomotor control mechanisms, and suggest that the ability to function effectively in this way is dependent upon the integrity of the lateral cerebellum.

Human Eye Movements During Visually Guided Stepping.

Visually guided locomotion was studied in an experiment in which human subjects (N = 8) had to accurately negotiate a series of irregularly spaced stepping-stones while infrared reflectometry and electrooculography were used to continuously record their eye movements. On average, 68% of saccades made toward the next target of footfall had been completed (visual target capture had occurred) while the foot to be positioned was still on the ground; the remainder were completed in the first 300 ms of the swing phase. The subjects' gaze remained fixed on a target, on average, until 51 ms after making contact with it, with little variation. A greater amount of variation was seen in the timing of trailing footlift relative to visual target capture. Assuming that subjects sampled the visual cues as and when they were required, visual information appeared most useful when the foot to be positioned was still on the ground.

Triazolam premedication. A comparison with lorazepam and placebo in gynaecological patients.

A randomised, double blind study, of 58 female patients undergoing laparoscopic investigation was carried out to compare triazolam 0.25 mg, lorazepam 2 mg, or placebo as oral premedication. Each patient was assessed by only one of the authors both pre- and postoperatively with regard to anxiolysis, sedation and rapidity of recovery. Triazolam and lorazepam were each associated with a significant reduction in anxiety compared to the initial assessment, whereas placebo had no anxiolytic effect. Sixty minutes after premedication, patients who had received triazolam were significantly more sleepy than patients given placebo or lorazepam. Two hours after the operation, the patients who had had triazolam or lorazepam were significantly more sleepy than those who received placebo. However, at 6 hours postoperatively there was no difference between triazolam and placebo, whilst those who had been given lorazepam were still significantly more sleepy than those given placebo. Triazolam appears to offer advantages over either lorazepam or placebo in patients who require rapid recovery, sedation and reduction in pre-operative anxiety.

A simple apparatus for comparative measurements of energy expenditure in human subjects: the thermic effect of caffeine.

A simple inexpensive indirect calorimeter that is suitable for the estimation of energy expenditure in man is described. Its usefulness is demonstrated by a study of the effect of coffee on energy expenditure. Caffeinated coffee increased energy expenditure by 16% over 1 2-h period compared with decaffeinated coffee.

Important sites of lipogenesis in the mouse other than liver and white adipose tissue.

The musculature of the shoulders and back has been identified as a major site of fatty acid synthesis in mice.

Experimental approach of activity and mechanism(s) of action of drugs used in cerebral metabolic insufficiency. Application to 1-eburnamonine.

The authors described an experimental approach, specially using oral administration, of drugs used in cerebral metabolic insufficiencies and its application to l-eburnamonine (l-EB). Administered orally, l-EB: (1) significantly increased the cerebral consumption of [14C]- deoxyglucose in normoxic mice; (2) decreased the fall in cerebral energy charge (ECP) of rats after an acute normobaric hypoxia, and (3) stimulated the glycolysis of red blood cells (RBC) in healthy volunteers (repeated administrations) as demonstrated by important increases in 2,3-DPG and ATP, i.e., in factors involved in the bioavailability of oxygen (oxygen transport activity and RBC deformability). The results therefore demonstrate oral activity of l-EB in animals and man. They are in agreement with previous data showing cerebral metabolic stimulant and antihypoxic effects following parenteral administration, in animals. They allow to propose that l-EB acts both at cerebral and extracerebral levels and constitute objective biochemical proof of the activity of l-EB in man. The study of new drugs may be done using the same experimental approach.