Altered accelerator pedal control in a driving simulator in people with diabetic peripheral neuropathy.

AIM: To investigate whether the sensory-motor impairment attributable to diabetic peripheral neuropathy would affect control of the accelerator pedal during a driving simulator task. METHODS: A total of 32 active drivers, 11 with diabetic peripheral neuropathy (mean ± sd age 67±5.0 years), 10 with diabetes but no neuropathy (diabetes group; mean ± sd age 62±10 years), and 11 healthy individuals without diabetes (healthy group; mean ± sd age 60±11 years), undertook a test on a dynamometer to assess ankle plantar flexor muscle strength and ankle joint proprioception function of the right leg, in addition to a driving simulator task. The following variables were measured: maximal ankle plantar flexor muscle strength; speed of strength generation (Nm/s); and ankle joint proprioception (ankle repositioning error, degrees). In the driving simulator task, driving speed (mph), accelerator pedal signal (degrees) and the duration of specific 'loss-of-control events' (s) were measured during two drives (Drive 1, Drive 2). RESULTS: Participants with diabetic peripheral neuropathy had a lower speed of strength generation (P<0.001), lower maximal ankle plantar flexor muscle strength (P<0.001) and impaired ankle proprioception (P=0.034) compared to healthy participants. The diabetic peripheral neuropathy group drove more slowly compared with the healthy group (Drive 1 P=0.048; Drive 2 P=0.042) and showed marked differences in the use of the accelerator pedal compared to both the diabetes group (P=0.010) and the healthy group (P=0.002). Participants with diabetic peripheral neuropathy had the longest duration of loss-of-control events, but after one drive, this was greatly reduced (P=0.023). CONCLUSIONS: Muscle function, ankle proprioception and accelerator pedal control are all affected in people with diabetic peripheral neuropathy, adversely influencing driving performance, but potential for improvement with targeted practice remains possible.

People with diabetic peripheral neuropathy display a decreased stepping accuracy during walking: potential implications for risk of tripping.

AIM: To examine the stepping accuracy of people with diabetes and diabetic peripheral neuropathy. METHODS: Fourteen patients with diabetic peripheral neuropathy (DPN), 12 patients with diabetes but no neuropathy (D) and 10 healthy non-diabetic control participants (C). Accuracy of stepping was measured whilst the participants walked along a walkway consisting of 18 stepping targets. Preliminary data on visual gaze characteristics were also captured in a subset of participants (diabetic peripheral neuropathy group: n = 4; diabetes-alone group: n = 4; and control group: n = 4) during the same task. RESULTS: Patients in the diabetic peripheral neuropathy group, and patients in the diabetes-alone group were significantly less accurate at stepping on targets than were control subjects (P < 0.05). Preliminary visual gaze analysis identified that patients diabetic peripheral neuropathy were slower to look between targets, resulting in less time being spent looking at a target before foot-target contact. CONCLUSIONS: Impaired motor control is theorized to be a major factor underlying the changes in stepping accuracy, and potentially altered visual gaze behaviour may also play a role. Reduced stepping accuracy may indicate a decreased ability to control the placement of the lower limbs, leading to patients with neuropathy potentially being less able to avoid observed obstacles during walking.

The lateral cerebellum and visuomotor control.

The lateral cerebellum receives an abundance of visual input providing the link between visual and motor control centers. In this review we discuss experiments designed to increase our understanding of how visual inputs to the cerebellum are arranged in relation to the zonal organization of the cerebellar cortex, and how visual inputs are utilized to assist in the regulation of a visually guided movement. On the basis of anatomical and physiological characteristics our findings indicate that the medial-most folium in crus I of the cat lateral cerebellum can be subdivided into at least three functionally distinct zones; from lateral to medial along the length of the folium these correspond to zones D(1), lateral C(3) and C(2). Each zone displays clear differences in olivo-cortico-nuclear connectivity and in the anesthetized animal zones D(1) and C(2) both receive powerful visual inputs relayed via the climbing fiber system. Complementary experiments in awake behaving cats found that Purkinje cells located in the D(1) and D(2) zones of crus I exhibit changes in simple spike discharge time locked to target motion during a visually guided reaching task. These changes were unaffected by temporary visual denial of the target, raising the possibility that internally generated feedforward visuomotor control mechanisms are operating, in which a predictive model of the target's motion has been constructed by the CNS.

Direct visualisation of gaze and hypometric saccades in cerebellar patients during visually guided stepping.

Four patients suffering from primary cerebellar degeneration and healthy matched controls undertook a test of functional mobility that demanded precise foot placement at each step. Vertical and horizontal eye movements were measured (using a head mounted eye tracking system) together with footfall patterns. Healthy subjects stepped accurately onto all targets and produced a clear pattern of saccadic eye movements, fixating each target in the sequence just prior to footlift. Still video frames, showing direction of gaze while walking, provide direct visual confirmation that these saccades serve to transfer gaze between successive targets in the walkway sequence. The planning of the saccade to the next target probably provides the locomotor control system with information useful for planning the corresponding (and shortly following) step. Cerebellar patients showed characteristic locomotor and oculomotor deficits. Dysmetric saccades to fixate footfall targets were seen in 39% of steps. Analysis confirms that these multi-saccadic eye movements include an initial hypometric saccade, which undershoots the target, followed by one or more additional saccades in the same direction. Direct visualisation of gaze at the end of a saccadic sequence confirms that these additional saccades are indeed corrective resulting in a foveal image of the footfall target.

A method for automatic identification of periods of muscular activity from EMG recordings.

A computer-based method of identifying periods of activity in EMG recordings is described. Its application to the analysis of muscle activity patterns in freely moving human or animal subjects is illustrated and discussed.

A ladder paradigm for studying skilled and adaptive locomotion in the cat.

A circular horizontal ladder is described which is suitable for studying skilled and adaptive locomotion in the cat. Four mechanisms built into the ladder require the animal to adapt its normal walking by making either corrective manoeuvres following an unpredictable disturbance, or anticipatory changes informed by vision. In addition to these features, the ladder incorporates a servo-controlled boom to ensure that the cat is almost completely free of any restraint or drag which might otherwise be imposed by leads carrying foot contact, electromyographic and neuronal signals from the animal to the recording equipment. The apparatus is proving in use to be reliable and easy to operate, and our preliminary results clearly implicate supraspinal motor centres in controlling the skilled and adaptive behaviour which the ladder requires.

A lightweight hybrid microdrive for use with awake unrestrained animals.

A hybrid microdrive is described, comprising remote stepper motors connected by a hydraulic link to a slave electrode positioner which is light enough for use with freely walking cats. The system provides 18 mm of electrode movement in 2 or 10 microns steps.

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.

Changes in the discharge patterns of motor cortical neurones associated with volitional changes in stepping in the cat.

Extracellular recordings have been obtained from motor cortical neurones of cats walking along a horizontal ladder. We present responses obtained when the animal produced defined volitional changes in limb trajectory, and during different conditions of locomotion. Our results show substantial changes in discharge pattern of some cells under these different conditions. Encounters with displaced rungs produce marked changes in discharge pattern including some which precede foot contact and others graded to the magnitude and direction of displacement.

Responses of motor cortical neurones in the cat to unexpected perturbations of locomotion.

Extracellular recordings have been obtained from individual motor cortical neurones of cats walking along a horizontal ladder. We present responses obtained when selected rungs dropped unexpectedly by a small amount beneath the animal's weight. Our results show that forelimb motor cortex is rapidly and in graded fashion informed of such events, which may produce appreciable changes in impulse activity in the corticospinal tract.

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.

Eye-steering coordination in natural driving.

When driving along a winding road, eye movements and steering are tightly linked; the driver looks across to the inside kerb of an approaching bend some time before turning the steering wheel. With the eyes leading, the oculomotor controller assists the neural centres controlling steering; prevention of any eye movements correlated with steering impairs driving, so the coordination is crucial for safety. A key question is therefore what are the limits of acceptable variation in timing and degree of coordination. Over a period of continuous driving on the open road, how much does the relative timing and degree of coordination between eye and steering movements vary? A related question is how brief a period of driving will suffice to measure these coordination parameters. Drivers' eye movements and steering were measured over different time periods ranging from 15 s to 6 min epochs of natural driving along a winding country road to establish the variability in coordination and the minimum time period required to characterise it. We show here that brief periods of driving, 30 s or less, are inadequate for describing eye-steering coordination. But a minute of driving yields an accurate description much of the time; and 2 min is sufficient both to accurately describe this relationship and to show that it is highly consistent for a given individual, and for different people driving the same route.

Eye movements coordinated with steering benefit performance even when vision is denied.

When driving along a winding road, eye movements and steering are tightly linked. When approaching a bend, the driver looks across to the inside kerb (the tangent point) some time before turning the steering wheel. All drivers we have tested show this optimal coordination, without which driving is impaired. An intriguing question is how much of the benefit for steering arises just from moving the eyes in this coordinated way (ahead of steering and in the same direction), and how much from the visual information that the eyes move to acquire, in this instance the foveated tangent point. This can be answered by dissociating the two, by reducing visibility of the road ahead (and crucially of the tangent point) to a level at which drivers might or might not choose to move their eyes but, if they do, will not gain the information they seek. Twenty subjects repeatedly drove a simulated stage of the World Rally Championship. With full visibility, they exhibited the usual coordination of eye movements and steering. Subsequently, visibility was reduced on the left hand side. Drivers who persisted in making eye movements coordinated with steering to the left, despite the fact that they could no longer see the tangent point on that side, performed better than drivers who under the identical conditions did not look to the left. This confirms that the making of coordinated eye movements itself benefits steering, even when the eye movements do not yield the visual information sought.

Prevention of coordinated eye movements and steering impairs driving performance.

When approaching a bend in the road, a driver looks across to the inside kerb before turning the steering wheel. Eye movements and steering are tightly linked, with the eyes leading, which means that the oculomotor controller can assist the neural centres controlling steering. This optimum coordination is observed for all drivers; but despite being the preferred solution to the motor-control problem of successfully steering along a winding road, the question remains as to how crucial such coordinated eye and steering movements are for driving performance. Twenty subjects repeatedly drove a simulated stage of the World Rally Championship, aiming to complete the course in the fastest possible time. For the first six repetitions they used the usual coordination of eye movements and steering; for drives 7--12 they were instructed to fixate on a small spot in the centre of the screen (centre gaze). Prevention of coordination in this way impaired their performance (drives 6 and 7 compared), dramatically increasing their time taken to complete the course, equivalent to slipping 19 places down the leader board in the actual rally stage. This indicates that the usual pattern of eye movements correlated with steering is crucial for driving performance. Further experiments are suggested to reveal whether any attentional demand associated with keeping the eyes still contributes to the loss in performance.

Alcohol affects eye movements essential for visually guided stepping.

BACKGROUND: To understand how and why alcohol intoxication affects visually guided stepping, the eye movements and performance of 6 subjects (aged 22-35 years) were monitored as they progressed along a pathway of 18 irregularly placed stepping stones before and after consumption of an acute oral dose of alcohol. METHODS: Horizontal eye movements were measured with infrared reflectometry; footfall on or off target was monitored via copper fabric soles stuck to subjects' footwear. Breath alcohol concentration was monitored with an Alco-Sensor III breathalyzer. RESULTS: After alcohol loading, both locomotor and oculomotor deficits were evident. All subjects increased their step cycle duration-with prolonged stance, swing, and double support phases-and occasionally missed footfall targets. A large proportion of saccades made to fixate successive stepping stones were inaccurate and were accompanied by one or more corrective saccades. These problems with looking and stepping to footfall targets tended to occur together and were comparable to those seen previously in cerebellar patients undertaking the same task. CONCLUSIONS: The fact that healthy subjects acutely intoxicated by alcohol show symptoms of cerebellar dysfunction suggests that alcohol acutely and adversely affects the cerebellar contribution to performance of visually guided movements.

Cerebellar neuronal activity related to arm movements in trained rhesus monkeys.

1. The role of the paravermal cerebellum in controlling arm movements in monkeys trained to perform visually guided movements was investigated. Discharge patterns of extracellularly recorded Purkinje, Golgi, nuclear and unidentified cells were correlated with arm position, velocity and acceleration. 2. The discharge of thirty-seven out of fifty-two movement-related Purkinje cells and that of thirty-three out of forty-five other movement-related cerebellar neurones was more highly correlated with limb velocity (0.95 greater than r greater than 0.4) than with position or acceleration. Twelve out of fifty-two Purkinje cells and twelve out of forty-five other cells were related to both limb velocity and limb position. Three Purkinje cells were related to limb acceleration and position and no cell was related to position or acceleration alone. 3. Modulation of discharge of these cells usually preceded movement (range -240 ms, unit leading movement, to +180 ms, unit lagging; mode -36 ms; mean -15 ms). 4. Each movement-related neurone was tested for four directions of movement. All showed a preferred direction in which the correlation with arm movement velocity was highest. However, 43% (30/70) correlated at r greater than 0.4 with movements in a second direction, usually that opposite to their preferred direction. Sixty-three per cent of these neurones fired earlier during movements in the preferred than in the opposite direction. 5. It is concluded that the paravermal cerebellum may be involved in computing the velocity vectors required for achieving properly directed and co-ordinated movements of the whole arm.

Role of the cerebellum and motor cortex in the regulation of visually controlled locomotion.

An account is given of the current state of knowledge of the contributions of the cerebellum and the forelimb motor cortex (MC) to the neural control of walking movements in the cat. The main emphasis is on information obtained by recording from single MC and cerebellar neurones in chronically instrumented cats engaged in walking on the rungs of a horizontal ladder, a form of locomotion that is heavily dependent on visual input and for which the integrity of MC is essential. Evidence from the authors' laboratory and from other studies is presented which establishes that MC neurones, including pyramidal tract neurones, show higher levels of activity during ladder walking than during overground walking (i.e., when less constraint exists over the locus of footfall) and that this increase is greatest in late swing-early stance in the contralateral forelimb, consistent with one role of MC being to help determine the locus of footfall. However, many MC neurones develop peak activity at other times in the step cycle, and a comparison with recordings during treadmill walking suggests MC may also help regulate stance duration when walking speed is an important performance variable. Recordings from Purkinje cells and cerebellar nuclear neurones show that during ladder walking step-related activity is widespread in the vermal, paravermal, and crural regions of cortex and in the interposed and dentate nuclei. Nuclear cell activity is so timed that it could be contributing to producing the locomotor rhythms evident in MC cells, although this is not yet proven. Results are also presented and discussed relating to MC and cerebellar neuronal responses that occur when a step onto an unstable rung results in an unexpected external perturbation of the forelimb step cycle. MC responses begin with onset latency as short as 20 ms so that MC may assist spinal reflex mechanisms to produce a post hoc compensatory change in motor output. However, work in progress suggests that corresponding responses in paravermal cerebellum are weak and infrequent, so provisionally it seems that the MC responses are initiated via pathways that do not pass through the cerebellum. By contrast, current work involving a paradigm in which a ladder rung is motor driven to a new position as the animal approaches (thereby providing a visual cue that an adaptive change in gait will soon be required) is revealing in lateral cerebellar neurones, including dentate neurones, changes in discharge that are time locked to the execution of an adapted pace. In addition, there are prominent earlier responses, which begin at short latency after the onset of rung movement. These apparently visual responses have characteristics that encourage the speculation that they may represent a cerebellar signal that "primes for action" other more directly motor regions of the central nervous system.

Rhythmic neuronal activity in the lateral cerebellum of the cat during visually guided stepping.

1. The discharge patterns of 117 lateral cerebellar neurones were studied in cats during visually guided stepping on a horizontal circular ladder. Ninety per cent of both nuclear cells (53/59) and Purkinje cells (53/58) showed step-related rhythmic modulations of their discharge frequency (one or more periods of 'raised activity' per step cycle of the ipsilateral forelimb). 2. For 31% of nuclear cells (18/59) and 34% of Purkinje cells (20/58) the difference between the highest and lowest discharge rates in different parts of the step cycle was > 50 impulses s-1. 3. Individual neurones differed widely in the phasing of their discharges relative to the step cycle. Nevertheless, for both Purkinje cells and nuclear cells population activity was significantly greater in swing than in stance; the difference was more marked for the nuclear population. 4. Some cells exhibited both step-related rhythmicity and visual responsiveness (28 of 67 tested, 42%), whilst others were rhythmically active during locomotion and increased their discharge rate ahead of saccadic eye movements (11 of 54 tested, 20%). The rhythmicity of cells that were visually responsive was typical of the rhythmicity seen in the whole locomotor-related population. The step-related rhythmicity of cells that also discharged in relation to saccades was generally below average strength compared with the cortical and nuclear populations as a whole. 5. The possibility is discussed that the rhythmicity of dentate neurones acts as a powerful source of excitatory locomotor drive to motor cortex, and may thereby contribute to establishing the step-related rhythmicity of motor cortical (including pyramidal tract) neurones. More generally, the activity patterns of lateral cerebellar neurones provide for a role in the production of visually guided, co-ordinated eye and body movements.

Central regulation of motor cortex neuronal responses to forelimb nerve inputs during precision walking in the cat.

1. The responses of neurones in forelimb motor cortex to impulse volleys evoked by single pulse electrical stimulation (at 1.5 or 2 times the threshold for most excitable nerve fibres) of the superficial radial (SR) and ulnar (UL) nerves of the contralateral forelimb were studied in awake cats both resting quietly and walking on a horizontal ladder. Nerve volley amplitude was monitored by recording the compound action potential elicited by the stimulus. 2. In the resting animal 34/82 (41%) cells yielded statistically significant responses to SR stimulation, and 20/72 (28%) responded to UL stimulation. Some responses were confined to or began with an increase in firing probability ('excitatory' responses) and others with a decrease in firing ('inhibitory' responses), typically including a brief interruption of the spike train (zero rate). Cells responding to both nerves usually yielded responses similar in type. Most (78%) response onset latencies were less than 30 ms. Responses involved the addition or subtraction of from 3.4 to 0.1 impulses stimulus-1 (most <1 impulse stimulus-1). The distribution of response sizes was continuous down to the smallest values, i.e. there was no 'gap' which would represent a clear separation into 'responsive' and 'unresponsive' categories. Responses were commonest in the lateral part of the pericruciate cortex, and commoner among pyramidal tract neurones (PTNs) than non-PTNs. 3. During ladder walking most cells generated a rhythmic step-related discharge; in assessing the size of responses to nerve stimulation (20 studied, from 13 cells) this activity was first subtracted. Response onset latencies (90% <30 ms) and durations showed little or no change. Although most cells were overall more active than during rest both 'excitatory' and 'inhibitory' responses in both PTNs and non-PTNs were often markedly reduced in large parts of the step cycle; over some (usually brief) parts responses approached or exceeded their size during rest, i.e. response size was step phase dependent. Such variations occurred without parallel change in the nerve compound action potential, nor were they correlated with the level of background firing at the time that the response was evoked. When responses to both nerves were studied in the same neurone they differed in their patterns of phase dependence. 4. The findings are interpreted as evidence for central mechanisms that, during 'skilled', cortically controlled walking, powerfully regulate the excitability of the somatic afferent paths from forelimb mechanoreceptors (including low threshold cutaneous receptors) to motor cortex. Retention (or enhancement) of responsiveness often occurred (especially for ulnar nerve) around footfall, perhaps reflecting a behavioural requirement for sensory input signalling the quality of the contact established with the restricted surface available for support.