Prior intention can locally tune inhibitory processes in the primary motor cortex: direct evidence from combined TMS-EEG.

Human subjects are able to prepare cognitively to resist an involuntary movement evoked by a suprathreshold transcranial magnetic stimulation (TMS) applied over the primary motor cortex (M1) by anticipatory selective modulation of corticospinal excitability. Uncovering how the sensorimotor cortical network is involved in this process could reveal directly how a prior intention can tune the intrinsic dynamics of M1 before any peripheral intervention. Here, we used combined TMS-EEG to study the cortical integrative processes that are engaged both in the preparation to react to TMS (Resist vs. Assist) and in the subsequent response to it. During the preparatory period, the contingent negative variation (CNV) amplitude was found to be smaller over central electrodes (FC1, C1, Cz) when preparing to resist compared with preparing to assist the evoked movement whereas alpha-oscillation power was similar in the two conditions. Following TMS, the amplitude of the TMS evoked-N100 component was higher in the Resist than in the Assist condition for some central electrodes (FCz, C1, Cz, CP1, CP3). Moreover, for six out of eight subjects, a single-trial-based analysis revealed a negative correlation between CNV amplitude and N100 amplitude. In conclusion, prior intention can tune the excitability of M1. When subjects prepare to resist a TMS-evoked movement, the anticipatory processes cause a decreased cortical excitability by locally increasing the inhibitory processes.

Corticospinal control of the thumb-index grip depends on precision of force control: a transcranial magnetic stimulation and functional magnetic resonance imagery study in humans.

The corticospinal system (CS) is well known to be of major importance for controlling the thumb-index grip, in particular for force grading. However, for a given force level, the way in which the involvement of this system could vary with increasing demands on precise force control is not well-known. Using transcranial magnetic stimulation and functional magnetic resonance imagery, the present experiments investigated whether increasing the precision demands while keeping the averaged force level similar during an isometric dynamic low-force control task, involving the thumb-index grip, does affect the corticospinal excitability to the thumb-index muscles and the activation of the motor cortices, primary and non-primary (supplementary motor area, dorsal and ventral premotor and in the contralateral area), at the origin of the CS. With transcranial magnetic stimulation, we showed that, when precision demands increased, the CS excitability increased to either the first dorsal interosseus or the opponens pollicis, and never to both, for similar ongoing electromyographic activation patterns of these muscles. With functional magnetic resonance imagery, we demonstrated that, for the same averaged force level, the amplitude of blood oxygen level-dependent signal increased in relation to the precision demands in the hand area of the contralateral primary motor cortex in the contralateral supplementary motor area, ventral and dorsal premotor area. Together these results show that, during the course of force generation, the CS integrates online top-down information to precisely fit the motor output to the task's constraints and that its multiple cortical origins are involved in this process, with the ventral premotor area appearing to have a special role.

Stride variability in human gait: the effect of stride frequency and stride length.

This study focused on spatial and temporal variability of the stride in human gait. We determined the role of stride frequency (F) and stride length (L) on those parameters. Eight healthy subjects walked on a treadmill using 25 different FL combinations (0.95

Adaptation of neuromuscular synergies during intentional constraints of space-time relationships in human gait.

Tight frequency-to-amplitude relationships are observed in spontaneous human steady gait. They can be modified, if required; that flexibility forms a fundamental basis of the intentional adaptive capabilities of locomotion. In the present experiments, the processes underlying that flexibility were investigated at both the level of joint kinematics and the level of neuromuscular synergies. Subjects (N = 4) walked at the same speed either with a preferred or a nonpreferred frequency-to-amplitude relationship (i.e., constrained, short steps at a high frequency [COS condition] or constrained, long steps at a low frequency [COL condition]); their swing and stance phases were separately analyzed. In the COS condition, increases in EMG activity were specifically required during the swing phase. In the COL condition, several muscles required increases in EMG activity during the stance phase, but decreases of the hamstring muscles were needed during the swing phase. Whereas, in preferred walking, modification of the frequency affects the EMG patterns globally (the gain increasing with the frequency in both the stance and swing phases), the present results show that changing the frequency in a constrained manner either affects the swing phase specifically or affects both phases, but in the opposite direction. That finding indicates that a separate control is needed in both the swing and the stance phases.

Intentional on-line adaptation of stride length in human walking.

The intentional control of stride length is a fundamental basis for the adaptation of the stride to environmental constraints (obstacle avoidance, for example). Controlling the propulsive forces during the stance and/or controlling the pendular movement of the oscillating leg constitute the two potential and non-exclusive mechanisms underlying intentional stride length modulation. The present experiment was conducted in order to determine if these two mechanisms contribute to voluntary length modulation and, if so, how they cooperate according to whether the subject has to lengthen or shorten a stride and how these mechanisms are implemented at the neuromuscular level. Subjects had to produce a temporarily modulated stride of the same length, but originating from two different initial steady-states: one from shorter stride length and one from longer stride length. We found that the shortening was essentially realized by a swing-duration decrease (an increased activity in the hip extensor--biceps femoris--during the swing of the ipsilaterally shortened stride stopped the pendular leg movement earlier). The lengthening was realized by two mechanisms: (1) an increase in the propulsive forces (via an increased activity of the ankle extensor muscles--soleus--and the hip extensors--biceps femoris--from the stance of the ipsilaterally modulated stride, which was prolonged during the following stance of the contralateral leg), and (2) an increase in swing duration on the ipsilateral leg (an increased activity in hip and ankle flexors--rectus femoris and tibialis anterior--maintained the ipsilateral leg in flexion during the lengthened swing so that the foot landed later). In this experiment, the subjects were faced with a spatial constraint of the same magnitude in the direction of stride lengthening and stride shortening. However, under these conditions, subjects used a different balance between swing control (that directly modifies the foot trajectory without affecting the trajectory of the head-arm-trunk system) and/or the control of propulsive forces (that indirectly influences foot trajectory by modifying the trajectory of the head-arm-trunk system). In the first case, this concerns a voluntary control of gesture produced by the legs and usually implicated in the locomotor pointing; in the second case, this concerns a voluntary control of propulsive forces.

Contribution of proprioceptive information to preferred versus constrained space-time behavior in rhythmical movements.

Rhythmical movements are well-known to exhibit spontaneous and well-defined relationships between frequency and amplitude (preferred behavior). However, if required, these relationships can be modified (constrained behavior). This flexibility constitutes a fundamental basis for adapting motor functions to the subject's intentions in a given environment. In order to assess the role of proprioceptive information in the stabilization of preferred versus constrained rhythmical movements, we compared both cases in a deafferented patient and in a control group. Initially, the subjects were given as much time as they needed to adopt different, steady rhythmical movements in the presence of external feedback. Afterwards, the feedback was suppressed and the subjects had to maintain the same oscillating regimes for one additional minute. In the absence of feedback, the deafferented patient was able to stabilize the timing of both the preferred and the constrained movements. The spatial properties remained stationary for the preferred movements; however, large effects were observed in the constrained movements. By contrast, the control subjects were able to keep both the preferred and the constrained behaviors stationary. Our results show that, when reaching preferred regimes, the behavior remains stationary even in the absence of proprioceptive information. By contrast, proprioceptive feedbacks were shown to be necessary in order to maintain non-preferred regimes. In this case, error-correction mechanisms based on proprioceptive information allows for compensation of the natural tendency of the system to return to its preferred behavior.

Dynamic instability of visuospatial images.

Five experiments using a visuospatial task were conducted to study memory accuracy and variability and to identify the origin of variations in steady states. This research was conducted from a dynamical perspective, that is, by analyzing the temporal course of discrepancies between the perceptual configuration and its memory (accuracy) and the temporal course of discrepancies between 2 successive memories (variability). In Experiment 1 the stimulus (12 black dots randomly disposed) was presented repeatedly to assess the general evolution of accuracy and variability. In Experiments 2 and 3 memory accuracy and memory variability were separated to identify their relationship. In Experiments 4 and 5 memory variability was studied to determinate the origin of steady state variations. Results show that memory accuracy and memory variability evolved independently and that memory variability reached a threshold that was subject-dependent. The dynamic properties of image construction and stability are discussed.

Intentional on-line control of propulsive forces in human gait.

In locomotion, the capability to control and modulate intentionally the propulsive forces is fundamental for the adaptation of the body's progression, both in speed and direction. The purpose of this experiment was to determine how human beings can achieve such control on-line. To answer this question, four subjects walking steadily were faced with a linear increase in resistance (impeding forward displacement), lasting 3 s, once per minute. At the end of the variation, the new resistance was maintained. There were two tasks; in both tasks, in the initial steady state, the subjects had to walk steadily at 1.3 m s-1. As the resistance increased, subjects were either required to maintain their walking speed (compensation task) or to let the walking speed and amplitude adapt freely (no-intervention task). This provided an estimate of the effects of the perturbation alone. Throughout the experiment, the stride frequency (114 step min-1) was fixed by a metronome. Subjects maintained their stride frequency on both tasks. In the no-intervention task, walking speed was 1.3 and 1 m s-1 under normal and high resistance respectively. In the compensation task, under high steady resistance, walking speed was maintained by an increase in the activation gain of the neuromuscular synergy: all recorded muscles increased their EMG activity, but without any change in the shape of their activation profile throughout the cycle. During the transitional phases, however, as the resistance began to increase, the walking speed decreased temporarily (-2%) before returning rapidly to its initial value. By contrast, at the end of the resistance increase, no such changes in speed were observed. During the transitional phases, the on-line compensation for the resistance increase induced modifications in the shape of the activation burst in the medial gastrocnemius such that the transitional cycles clearly differed from the steady state cycles. The results observed in the compensation task suggest that the subjects used two different modes of control during steady states and transitional phases. In stable dynamic conditions, there appears to be an "intermittent control" mode, where propulsive forces are globally managed for the entire stance phase. As a result, no compensation occurred at the beginning of the perturbation. During the resistance increase, subjects appeared to switch to an "on-line control" mode in order to continuously adapt the propulsive forces to the time course of the external force, resulting in an observable compensation at the end of the resistance change.

Autonomy versus forcing in the organization of human rhythmic forearm movements.

In biological systems, obviously dissipative, some injection of muscle force is required in order to sustain rhythmic movement. As the movement frequency increases, the way the muscle-force-to-movement relationship evolves (in timing and amplitude) can be used to characterize some fundamental control properties, including whether the observed system is autonomous or forced. In the case of a simple rhythmic, biological movement (single-joint horizontal forearm movement), this question can be addressed by assuming that the processed electromyographic activity (EMG) is related to the muscle torques. In this case, 2 interesting phenomena can be observed as the frequency increases. The first is that the phase lag between the force and movement remains constant (40 degrees), and the second is that the co-contraction of the agonist and antagonist muscle groups increases with the square of the frequency. These results showed that the contribution of muscle forces to movement organization cannot be regarded in terms of an escapement in an autonomous system, nor in terms of a forcing function in a forced system.

Joint-dependent mechanisms to adapt to an imbalance between flexion and extension forces in human gait.

In human gait, alternating leg flexion/extension movements essentially require the production of extension muscle forces due to the large contribution of passive forces to leg flexion. In this experiment, we studied the adaptive capabilities of walking subjects constrained with elastic cords which further facilitated leg flexion and impeded leg extension. In order to walk, the subjects let the moments created by the elastic cords increase the ankle flexion during the whole cycle, which allowed them to reduce part of these moments. By contrast, at the knee level, they increased their extension muscle activity to compensate for the remaining constraint moments during the swing phase, which resulted in unchanged kinematics. Although neuromuscular locomotor synergy is often considered to control the lower limb as a unit, we showed here that different adaptive mechanisms can act at different joints of the same leg.

Effects of the spatio-temporal structure of optical flow on postural readjustments in man.

How does the spatio-temporal structure of an oscillating radial optical flow affect postural stability? In order to investigate this problem, two different types of stimulus pattern were presented to human subjects. These stimuli were generated either with a constant spatial frequency or with a spatial frequency gradient providing monocular depth cues. When the stimulation was set in motion, the gain response of the antero-posterior postural changes depended upon the oscillation frequency of the visual scene. The amplitude of the postural response did not change with the amplitude of the visual scene motion. The spatial orientation of the postural sway (major axis of sway) depended strictly and solely on the structure of the visual scene. In static conditions, depth information resulting from the presence of a spatial frequency gradient enhanced postural stability. When set in motion, a visual scene with a spatial frequency gradient induced an organization of postural sway in the direction of the visual motion. Considering visual dynamic cues, postural instability depended linearly both on the logarithm of the velocity and on the logarithm of the temporal frequency. A nonlinear relationship existed between the amplitude of the fore-aft postural sway at the driving frequency and the temporal frequency, with a peak around 2-4 Hz. These results are discussed in terms of their implications for the separation of visual and biomechanical factors influencing visuo-postural control.

Low luminance contrast sensitivity: effects of training on psychophysical and optokinetic nystagmus thresholds in man.

We compared psychophysical contrast sensitivity function (psi-CSF) and optokinetic contrast sensitivity function (OKN-CSF) in man, for the combination of three spatial and three temporal frequencies. psi-CSF was defined as the inverse of the contrast threshold, that is the contrast value of a sinusoidal grating for which a subject was able to identify the width of a drifting grating. OKN-CSF was defined as the inverse of the contrast value of the grating which triggered an involuntary optokinetic nystagmus. In highly experienced subjects, OKN-CSF was overall higher than psi-CSF. More precisely, differences between both contrast sensitivity functions occurred mainly in the low spatio-temporal frequency range (below 4 c/deg and 9 Hz). In naive subjects, psi-CSF reached the level of OKN-CSF after two consecutive test sessions. OKN-CSF did not change with training. Similarly, high spatio-temporal frequency psychophysical thresholds did not change with training and, moreover, approximated OKN-CSF thresholds. Low spatio-temporal frequency psychophysical sensitivity was initially lower than corresponding OKN-CSF sensitivity; however, after only two training sessions, the two functions were indistinguishable due to a selective increase in psychophysical low spatio-temporal frequency sensitivity.

Modulations of the optical flow did not induce locomotor pattern fluctuations in treadmill walking in man.

We report an analysis of gait during human treadmill walking when visual information from the self-displacement velocity was modulated. Removing or sinusoidally modulating the frequency edge information in the optical flow did not induce significant changes in the walking velocity as analyzed using Fast Fourier Transform or in the spatiotemporal gait parameters. While low-frequency fluctuations in displacement speed increased, there was no significant change in locomotor cycle stability, When a constant frequency edge was provided, i.e., when a backward optical flow was added, stride length decreased as compared to the no-optical-flow condition and instantaneous fluctuations in stride amplitude increased. Temporal gait parameters did not change. These partial effects might be better explained by modifications in trunk balance. In humans, modulation of velocity information on self-motion cannot induce unintentional modulation of walking velocity and did not enhance fluctuations in the locomotor pattern. These results argue against the proprioceptive role of sagittal visual-motion information in control of stability of rhythmic leg movement, at least when other proprioceptive feedback sources are available.

Distortions and fluctuations in topographic memory.

Two experiments dealing with the learning of a space by map or by navigation approached the questions of equivalency of the cognitive processes involved in spatial information and of response fluctuation. In the first experiment, 11 subjects were asked to situate, six times, 18 locations on a blank map. In the second experiment, the subjects were first given 3 min to learn a map with 12 locations marked, and then asked to reproduce it. The task was repeated six times, using three different maps. This gave us several trials per subject, so that distortion could be distinguished from response fluctuation. In Experiment 1, the range of values was the same for response inaccuracy and response fluctuation; in Experiment 2, the range was greater for response inaccuracy than for response fluctuation. The results showed that space learning by navigation and space learning by map involve different cognitive processes.

Intentionality in human gait control: modifying the frequency-to-amplitude relationship.

Tight frequency-to-amplitude relationships are observed in spontaneous human steady gait. If required, however, they can be modified. The following experiments were aimed at the processes underlying this flexibility, which forms the fundamental basis of the intentional adaptive capabilities of locomotion. In Experiment 1, Ss had to intentionally modify the frequency-to-amplitude relationship (leading to preferred or nonpreferred steady states). In Experiment 2, they had to temporarily perturbate the stride-frequency-to-amplitude relationship to intentionally shorten or lengthen 1 stride. Within the important constraints exerted by the head-arm-trunk system on leg movement, the results pointed out 2 main strategies that allow the S to intentionally adapt stride organization on-line: adjustment of the tonic properties of the oscillating leg to achieve nonpreferred steady states and phasic action to ensure temporary movement away from a steady state.

Steady-state fluctuations of human walking.

In steady-state walking, fluctuations in space-time behavior are observed for normal adult subjects. In the present study, the intrinsic fluctuations of gait have been analyzed when walking on a subject-driven treadmill (with adjustable inertial forces). Furthermore, these intrinsic fluctuations have been compared with those observed in natural overground locomotion which involves a real subject's displacement and thus an optical flow. Four adult subjects participated in both experimental sessions. It was found that the frequency and amplitude of the instantaneous fluctuations of leg movement were weak and of equal magnitude with or without optical flow. This was also the case for instantaneous fluctuations in displacement speed. Secondly, a low-frequency fluctuation in walking speed was observed when no optical flow information was available to the subject. This fluctuation results from the addition of a series of leg-movement fluctuations, whose values are all either positive or negative. As the optical flow provides information about the displacement speed, it allows the subject to avoid such addition, and thus plays a role in maintaining steady leg movement. Theoretical models linking space-time behavior of rhythmic movement with stiffness strongly suggest that the observed low-frequency fluctuations in speed result from fluctuations in stiffness.

Dopa-sensitive and dopa-resistant gait parameters in Parkinson's disease.

Quantitative analysis of gait was performed in 20 parkinsonians before and 1 h after the acute administration of L-Dopa in order to discriminate between the Dopa-sensitive and the Dopa-resistant kinematic gait parameters. The stride length and the kinematic parameters (swing velocity, peak velocity) related to the energy were Dopa-sensitive. The improvement of the bent forward posture by L-Dopa may explain the stride length increase. Temporal parameters (stride and swing duration, stride duration variability), related to rhythm, were Dopa-resistant. Experimental data argue for the importance of force control in maintaining the posture. The stride length variability, possibly related to the variability of force production shown to exist in parkinsonians was not significantly improved by L-Dopa. In Parkinson's disease different hypotheses might explain the inexorable aggravation of gait disorders along the course of the disease: (1) an advancing disorder of coordination between postural control and locomotion, (2) if some gait parameters like stride length and kinematic parameters are Dopa-sensitive, the others are Dopa-resistant and thus may involve other mechanisms than dopamine deficiency.

Intentional compensation for selective loading affecting human gait phases.

The locomotor strategies used by 12 subjects, instructed to hold their walking speed constant, were examined under various dynamic conditions in order to determine the means by which subjects can act upon their basic locomotor synergy. The dynamic conditions were modified either by adding a load or applying an impeding force. These modifications were designed to selectively affect either the stance phase or the swing phase. The results show that (a) subjects were able to rapidly calibrate their efforts to hold their walking speed constant, (b) in all conditions, the same walking speed was achieved with the same stride lengths and durations, and (c) at the within-cycle level, a change in duration synergically affected both phases and not just the perturbed one. The above results are discussed in terms of intentionally controlled parameters. Because cadence is closely linked to walking speed, it can be used as feedback; the control of walking speed in our experiments may thus be achieved simply by increasing the exerted force until the same cadence is produced.

Quantitative analysis of walking in patients with knee osteoarthritis: a method of assessing the effectiveness of non-steroidal anti-inflammatory treatment.

Most therapeutic tests of osteoarthritis treatments are assessed by criteria based either on fundamental data or on clinical data, which is often subjective. A quantified analysis of locomotion can be used to determine the spatiotemporal indices (stride length and duration), kinematic indices (walking speed, velocity peak), and symmetry criteria that are relevant to the assessment of locomotor handicaps in patients with osteoarthritis. This study examined the progression of locomotor abilities in 11 subjects aged 49-69 (mean 60.9) years with knee osteoarthritis before and after treatment with a non-steroidal anti-inflammatory drug. Naproxen sodium (1100 mg) was given once a day for seven days. The condition before and after treatment was evaluated by quantitative analysis of locomotion, estimation of pain on a visual analogue scale, and assessment of the degree of functional disability. Significant improvement in locomotor indices (proportional increase in walking speed 17.8%) and in degree of pain (proportional decrease 27%) as estimated on the analogue scale was found after non-steroidal anti-inflammatory drug treatment. The lack of a significant correlation between the decrease in pain experienced by the patients and the objective improvement of their functional capabilities emphasises the need in further studies of new treatments to accompany the patients' own assessments of self improvement with a quantitative analysis of the way in which they walk.

Spatiotemporal contrast sensitivity differs in normal aging and Parkinson's disease.

We measured contrast sensitivity for static and laterally drifting vertical gratings in 12 young adults, 7 normal elderly adults, and 8 patients with Parkinson's disease (PD). We compared static and motion contrast sensitivity for spatial frequencies of 0.25, 1, and 4 cycles per degree (cpd), and temporal frequencies of 1, 3, and 9 Hz. Results show that normal aging leads to a reduction of motion sensitivity for the spatial frequency of 0.25 cpd. Compared with elderly controls, PD patients do not present specific abnormalities in this domain. However, for spatial frequencies of 1 and 4 cpd and temporal frequencies of 1 and 3 Hz, motion sensitivity is worse than static sensitivity in PD patients and not in elderly controls. These findings suggest a specific deficit of motion perception in PD, and possible dopaminergic involvement in the control of visuospatial behavior.