An update on predicting motor recovery after stroke.

Being able to predict an individual's potential for recovery of motor function after stroke may facilitate the use of more effective targeted rehabilitation strategies, and management of patient expectations and goals. This review summarises developments since 2010 of approaches based on clinical, neurophysiological and neuroimaging measures for predicting individual patients' potential for upper limb recovery. Clinical assessments alone have low prognostic accuracy. Transcranial magnetic stimulation can be used to assess the functional integrity of the corticomotor pathway, and has some predictive value but is not superior when used in isolation due to its low negative predictive value. Neuroimaging measures can be used to assess the structural integrity of descending white matter tracts. Recent studies indicate that the integrity of corticospinal and alternate motor tracts in both hemispheres may be useful predictors of motor recovery after stroke. The PREP algorithm is currently the only sequential algorithm that combines clinical, neurophysiological and neuroimaging measures at the sub-acute stage to predict the potential for subsequent recovery of upper limb function. Future research could determine if a similar algorithmic approach may be useful for predicting the recovery of gait after stroke.

The fall and rise of corticomotor excitability with cancellation and reinitiation of prepared action.

The sudden cancellation of a motor action, known as response inhibition (RI), is fundamental to human motor behavior. The behavioral selectivity of RI can be studied by cueing cancellation of only a subset of a planned response, which markedly delays the remaining executed components. The present study examined neurophysiological mechanisms that may contribute to these delays. In two experiments, human participants received single- and paired-pulse transcranial magnetic stimulation while performing a bimanual anticipatory response task. Participants performed most trials bimanually (Go trials) and were sometimes cued to cancel the response with one hand while responding with the other (Partial trials). Motor evoked potentials were recorded from left first dorsal interosseous (FDI) as a measure of corticomotor excitability (CME) during Go and Partial trials. CME was temporally modulated during Partial trials in a manner that reflected anticipation, suppression, and subsequent initiation of a reprogrammed response. There was an initial increase in CME, followed by suppression 175 ms after the stop signal, even though the left hand was not cued to stop. A second increase in excitability occurred prior to the (delayed) response. We propose an activation threshold model to account for nonselective RI. To investigate the inhibitory component of our model, we investigated short-latency intracortical inhibition (sICI), but results indicated that sICI cannot fully explain the observed temporal modulation of CME. These neurophysiological and behavioural results indicate that the default mode for reactive partial cancellation is suppression of a unitary response, followed by response reinitiation with an inevitable time delay.

Conceptual binding: integrated visual cues reduce processing costs in bimanual movements.

In discrete reaction time (RT) tasks, it has been shown that nonsymmetric bimanual movements are initiated slower than symmetric movements in response to symbolic cues. By contrast, no such RT differences are found in response to direct cues ("direct cue effect"). Here, we report three experiments showing that the direct cue effect generalizes to rhythmical bimanual movements and that RT cost depends on different cue features: 1) symbolic versus direct or 2) integrated (i.e., action of both hands is indicated as one entity) versus dissociated (i.e., action of each hand is indicated separately). Our main finding was that dissociated symbolic cues were most likely processed serially, resulting in the longest RTs, which were substantially reduced with integrated symbolic cues. However, extra RT costs for switching to nonsymmetrical bimanual movements were overcome only when the integrated cues were direct. We conclude that computational resources might have been exceeded when the response needs to be determined for each hand separately, but not when a common response for both hands is selected. This supports the idea that bimanual control benefits from conceptual binding.

Ipsilateral corticospinal projections do not predict congenital mirror movements: a case report.

Congenital mirror movements (CMMs) are involuntary, symmetric movements of one hand during the production of voluntary movements with the other. CMMs have been attributed to a range of physiological mechanisms, including excessive ipsilateral projections from each motor cortex to distal extremities. We examined this hypothesis with an individual showing pronounced CMMs. Mirror movements were characterized for a set of hand muscles during a simple contraction task. Transcranial magnetic stimulation (TMS) was then used to map the relative input to each muscle from both motor cortices. Contrary to our expectations, CMMs were most prominent for muscles with the strongest contralateral representation rather than in muscles that were activated by stimulation of either hemisphere. These findings support a bilateral control hypothesis whereby CMMs result from the recruitment of both motor cortices during intended unimanual movements. Consistent with this hypothesis, bilateral motor cortex activity was evident during intended unimanual movements in an fMRI study. To assess the level at which bilateral recruitment occurs, motor cortex excitability during imagined unimanual movements was assessed with TMS. Facilitory excitation was only observed in the contralateral motor cortex. Thus, the bilateral recruitment of the hemispheres for unilateral actions in individuals with CMMs appears to occur during movement execution rather than motor planning.

Excitability changes in human forearm corticospinal projections and spinal reflex pathways during rhythmic voluntary movement of the opposite limb.

Rhythmic movements brought about by the contraction of muscles on one side of the body give rise to phase-locked changes in the excitability of the homologous motor pathways of the opposite limb. Such crossed facilitation should favour patterns of bimanual coordination in which homologous muscles are engaged simultaneously, and disrupt those in which the muscles are activated in an alternating fashion. In order to examine these issues, we obtained responses to transcranial magnetic stimulation (TMS), to stimulation of the cervicomedullary junction (cervicomedullary-evoked potentials, CMEPs), to peripheral nerve stimulation (H-reflexes and f-waves), and elicited stretch reflexes in the relaxed right flexor carpi radialis (FCR) muscle during rhythmic (2 Hz) flexion and extension movements of the opposite (left) wrist. The potentials evoked by TMS in right FCR were potentiated during the phases of movement in which the left FCR was most strongly engaged. In contrast, CMEPs were unaffected by the movements of the opposite limb. These results suggest that there was systematic variation of the excitability of the motor cortex ipsilateral to the moving limb. H-reflexes and stretch reflexes recorded in right FCR were modulated in phase with the activation of left FCR. As the f-waves did not vary in corresponding fashion, it appears that the phasic modulation of the H-reflex was mediated by presynaptic inhibition of Ia afferents. The observation that both H-reflexes and f-waves were depressed markedly during movements of the opposite indicates that there may also have been postsynaptic inhibition or disfacilitation of the largest motor units. Our findings indicate that the patterned modulation of excitability in motor pathways that occurs during rhythmic movements of the opposite limb is mediated primarily by interhemispheric interactions between cortical motor areas.

Factores neuro-músculo-esqueléticos en la coordinación de movimientos de pronosupinacion / Neuromuscular-skeletal constraints in the coordination of prono-supination

Objetivo: valorar la influencia de los cambios de posición del eje de rotación del antebrazo sobre la estabilidad de la coordinación de movimientos de pronosupinación y sobre los patrones de activación de algunos de los músculos implicados. Participantes: 15 sujetos voluntarios realizaron ciclos completos de pronosupinación del antebrazo a distintas frecuencias de movimiento controladas por un metrónomo (desde 1.75Hz hasta 3.5Hz).Métodos: se registró el desplazamiento angular (grados de movimiento) durante la realización de cielos completos de pronación-supinación del antebrazo con el eje de rotación: por encima, en línea o por debajo del eje longitudinal del antebrazo; y bajo 2 modos de coordinación: p) haciendo coincidir la señal auditiva con la posición de pronación máxima y s) haciendo coincidir la señal auditiva con la posición de supinación máxima. Los tiempos en los que se produjeron las transiciones a un modo de coordinación distinto al solicitado fueron determinados para valorar la estabilidad de cada modo de coordinación. La actividad electromiográfica de los músculos pronador redondo, bíceps braquial, palmar mayor y primer radial fue registrada en 4 sujetos. Resultados: la estabilidad del modo de coordinación pronación en la señal fue mayor cuando el eje de rotación se situó por debajo del eje longitudinal del antebrazo. Por el contrario, la estabilidad del modo de coordinación supinación en la señal fue mayor cuando el eje de rotación se situó por encima. La dominancia relativa de las fases de pronación y supinación durante la rotación del antebrazo dependió mayormente del grado de participación de los músculos palmar mayor y primer radial. Conclusión: la estabilidad de los modos de coordinación estuvo supeditada al contexto mecánico. Los cambios en el contexto mecánico alteraron los patrones de activación de los músculos que contribuyen a la pronación y supinación del antebrazo, particularmente el palmar mayor (AU)

A method to monitor corticomotor excitability during passive rhythmic movement of the upper limb.

A procedure is outlined in which the excitability of the corticomotor pathway is examined during rhythmic, passive upper limb movement. Using a custom built apparatus and software, wrist flexion-extension movements of a programmable frequency, amplitude and duration are induced while transcranial magnetic stimuli are delivered to the contralateral cortex over the area representing the flexor carpi radialis muscle. Stimuli are timed to occur during different phases of the movement cycle in order to examine the influence of ascending sensory input on the excitability of the corticospinal pathway. The protocol enables modulations in evoked responses to be analysed during movement of different frequencies and amplitudes, and permits alterations in cortical excitability to be examined by using paired pulse paradigms. The technique may also be utilised to examine hemispheric and segmental transfer if a stationary target limb is probed while the contralateral limb is passively moved. The protocol has potential use in examining corticomotor excitability in subjects with deficits in sensory and/or motor function, such as patients with Parkinson's disease or individuals recovering from stroke.

Symmetric facilitation between motor cortices during contraction of ipsilateral hand muscles.

Using transcranial magnetic stimulation (TMS) over the contralateral motor cortex, motor evoked potentials (MEPs) were recorded from resting abductor pollicis brevis (APB) and first dorsal interosseous (FDI) muscles of eight subjects while they either rested or produced one of six levels of force with the APB ipsilateral to the TMS. F-waves were recorded from each APB at rest in response to median nerve stimulation while subjects either rested or produced one of two levels of force with their contralateral APB. Contraction of the APB ipsilateral to TMS produced facilitation of the MEPs recorded from resting APB and FDI muscles contralateral to TMS but did not modulate F-wave amplitude. Negligible asymmetries in MEP facilitation were observed between dominant and subdominant hands. These results suggest that facilitation arising from isometric contraction of ipsilateral hand muscles occurs primarily at supraspinal levels, and this occurs symmetrically between dominant and subdominant hemispheres.

Phasic modulation of corticomotor excitability during passive movement of the upper limb: effects of movement frequency and muscle specificity.

Modulations in the excitability of spinal reflex pathways during passive rhythmic movements of the lower limb have been demonstrated by a number of previous studies [4]. Less emphasis has been placed on the role of supraspinal pathways during passive movement, and on tasks involving the upper limb. In the present study, transcranial magnetic stimulation (TMS) was delivered to subjects while undergoing passive flexion-extension movements of the contralateral wrist. Motor evoked potentials (MEPs) of flexor carpi radialis (FCR) and abductor pollicus brevis (APB) muscles were recorded. Stimuli were delivered in eight phases of the movement cycle during three different frequencies of movement. Evidence of marked modulations in pathway excitability was found in the MEP amplitudes of the FCR muscle, with responses inhibited and facilitated from static values in the extension and flexion phases, respectively. The results indicated that at higher frequencies of movement there was greater modulation in pathway excitability. Paired-pulse TMS (sub-threshold conditioning) at short interstimulus intervals revealed modulations in the extent of inhibition in MEP amplitude at high movement frequencies. In the APB muscle, there was some evidence of phasic modulations of response amplitude, although the effects were less marked than those observed in FCR. It is speculated that these modulatory effects are mediated via Ia afferent pathways and arise as a consequence of the induced forearm muscle shortening and lengthening. Although the level at which this input influences the corticomotoneuronal pathway is difficult to discern, a contribution from cortical regions is suggested.

Phase transitions and postural deviations during bimanual kinesthetic tracking.

Upper limb coordination was studied by examining pattern stability of between-hand rhythmical coordination. In the first of two experiments, relative phase of rhythmical wrist flexion-extension was examined within a kinesthetic tracking paradigm. Eight right-handed subjects actively tracked a driven hand being flexed and extended by a computer-controlled AC servo-motor. Hand movements were constrained in flexion or extension. The simultaneous contraction of wrist flexors and extensors was defined as inphase (IP) and the alternating contraction of wrist flexors and extensors as antiphase (AP). Phase transitions (from AP to IP) were observed in 16% of trials prepared in AP. Fewer phase transitions occurred when the right wrist was constrained in flexion, and also when the left wrist was constrained in extension. IP patterns were performed with greater stability than AP patterns. These effects were explored further in a second experiment with the addition of a secondary probe reaction time task to assess demands on central capacity, and the analysis of wrist flexor and extensor electromyographic activity. Subjects returned longer reaction times for AP than IP movement, suggesting the AP movement pattern placed a greater demand on central capacity than the IP movement pattern. During this kinesthetic tracking task, similar dynamic principles emerged as those observed during bilaterally active bimanual rhythmical coordination. The greater stability of the hand-posture combination where the driven left hand was constrained in extension and the active right hand was constrained in flexion may be a demonstration of unique central control of coupled activity.

Stride length regulation in Parkinson's disease: the use of extrinsic, visual cues.

It has been well documented that marked improvements in the hypokinetic gait pattern of Parkinson's disease patients are possible with the use of appropriate visual cues. This project served to evaluate Parkinson's disease gait performance as well as residual processing capacity while using fixed or gait-regulated visual cues. Three-dimensional kinematic, kinetic and electromyographic gait analysis was carried out on 14 patients and 14 matched controls in baseline conditions and with two types of visual cues: taped step length (SL) markers and an individualized subject-mounted light device (SMLD). A probe reaction time paradigm was invoked to assess residual processing capacity. Ratings of perceived task load were also made using the NASA-Task Load Index. Stride length and gait velocity were reduced in patients in baseline conditions. Both of these parameters increased to control levels with the use of visual cues. These alterations were generally accompanied by modifications of lower limb kinematics and kinetics towards control subjects. Perceived task load was higher in all conditions and was further elevated by the use of the SMLD for both groups. Patients produced larger overall reaction times, although reaction time was not different between baseline and SL marker conditions. Reaction time was increased in both groups when using the SMLD. The overarching finding is that stride length can be regulated in Parkinson's disease using stationary visual cues without increased central processing capacity or perceived effort. This may occur via utilization of visual feedback, reducing the patients' reliance on kinaesthetic feedback for the regulation of movement amplitude.

The subdominant hand increases in the efficacy of voluntary alterations in bimanual coordination.

Subjects performed a bimanual circle-tracing task in time with an auditory metronome while restricted to moving with either proximal or distal musculature of the upper limb. Patterns were made in symmetric or asymmetric directions with respect to the midline. Symmetric patterns were more stable than asymmetric patterns. In response to a visual stimulus, subjects reversed the direction of one limb. Unwanted disruptions (momentary or lasting reversals) in the limb contralateral to the reversing limb were observed in 48% of trials. Incidence of disruption was equivalent between postures, but occurred more frequently when the dominant hand reversed direction. This result is consistent with anisotropy in coupling between hands and reveals a unifying constraint between spontaneous and intentional dynamics in bimanual coordination.

Neuromuscular-skeletal constraints upon the dynamics of unimanual and bimanual coordination.

In the first of three experiments, 11 participants generated pronation and supination movements of the forearm. in time with an auditory metronome. The metronome frequency was increased in eight steps (0.25 Hz) from a base frequency of 1.75 Hz. On alternating trials, participants were required to coordinate either maximum pronation or maximum supination with each beat of the metronome. In each block of trials, the axis of rotation was either coincident with the long axis of the forearm, above this axis, or below this axis. The stability of the pronate-on-the-beat pattern, as indexed by the number of pattern changes, and the time of onset of pattern change, was greatest when the axis of rotation of the movement was below the long axis of the forearm. In contrast, the stability of the supinate-on-the-beat pattern was greatest when the axis of rotation of the movement was above the long axis of the forearm. In a second experiment, we examined how changes in the position of the axis of rotation alter the activation patterns of muscles that contribute to pronation and supination of the forearm. Variations in the relative dominance of the pronation and supination phases of the movement cycle across conditions were accounted for primarily by changes in the activation profile of flexor carpi radialis (FCR) and extensor carpi radialis longus (ECR). In the final experiment we examined how these constraints impact upon the stability of bimanual coordination. Thirty-two participants were assigned at random to one of four conditions, each of which combined an axis of rotation configuration (bottom or top) for each limb. The participants generated both inphase (both limbs pronating simultaneously, and supinating simultaneously) and antiphase (left limb pronating and right limb supinating simultaneously, and vice versa) patterns of coordination. When the position of the axis of rotation was equivalent for the left and the right limb, transitions from antiphase to inphase patterns of coordination were frequently observed. In marked contrast, when the position of the axis of rotation for the left and right limb was contradistinct, transitions from inphase to antiphase patterns of coordination occurred. The results demonstrated that when movements are performed in an appropriate mechanical context, inphase patterns of coordination are less stable than antiphase patterns.

Spontaneous and intentional pattern switching in a multisegmental bimanual coordination task.

Two experiments required right-handed subjects to trace circular trajectories while complying with either a symmetric or asymmetric pattern. In symmetric patterns, circles were traced in a mirror image either inward or outward. In asymmetric patterns, circles were traced in the same direction either clockwise or counterclockwise. Subjects were instructed to trace with spatial accuracy while maintaining a strict temporal relationship to a metronome that scaled movement rates from 1.25 to 3 Hz. The symmetric patterns were more stable than asymmetric patterns; the circularity of trajectories was greater for the dominant side; and there were spontaneous reversals in the direction of circling in the nondominant limb when performing asymmetric patterns. The second experiment examined the same subjects under the instruction of intentionally changing the pattern by reversing the left or right limb circling direction when cued to do so. The degree of interlimb interference was highly asymmetric and contingent on the direction of pattern change. Intentional direction reversals were more expedient and with less disruption to the contralateral limb when asymmetric to symmetric pattern changes were effected through a reversal in the direction of nondominant side. The results are interpreted with reference to evidence that the supplementary motor area mediates descending input to the upper limbs during disparate bimanual actions, but not during symmetric actions.

Changes in posture alter the attentional demands of voluntary movement.

Two simple experiments reveal that the ease with which an action is performed by the neuromuscular-skeletal system determines the attentional resources devoted to the movement. Participants were required to perform a primary task, consisting of rhythmic flexion and extension movements of the index finger, while being paced by an auditory metronome, in one of two modes of coordination: flex on the beat or extend on the beat. Using a classical dual-task methodology, we demonstrated that the time taken to react to an unpredictable visual probe stimulus (the secondary task) by means of a pedal response was greater when the extension phase of the finger movement sequence was made on the beat of the metronome than when the flexion phase was coordinated with the beat. In a second experiment, the posture of the wrist was manipulated in order to alter the operating lengths of muscles that flex and extend the index finger. The attentional demands of maintaining the extend-on-the-beat pattern of coordination were altered in a systematic fashion by changes in wrist posture, even though the effector used to respond to the visual probe stimulus was unaffected.

Bimanual circle drawing during secondary task loading.

Seven right-handed participants performed bimanual circling movements in either a symmetrical or an asymmetrical coordination mode. Movements were paced with an auditory metronome at predetermined frequencies corresponding to transition frequency, where asymmetrical patterns became unstable, or at two-thirds transition frequency where both symmetrical and asymmetrical patterns were stable. The pacing tones were presented in either a high (1000 Hz) or low (500 Hz) pitch, and the percentage of high-pitched tones during a 20 s trial varied between 0% and 70%. Participants were instructed to count the number of high-pitched pacing tones that occurred during a trial of bimanual circling. Overall, the symmetrical pattern was more stable than the asymmetrical pattern at both frequencies. Errors on the tone-counting task were significantly higher during asymmetrical circling than symmetrical circling but only at the transition movement frequency. The results suggest that cognitive processes play a role in maintaining coordination patterns within regions of instability.

The preparation of aiming movements.

Three experiments are reported in which subjects made rapid aiming movements to visual targets with their left and right hands. In Experiments 1 and 3, a precue protocol was employed. In the "simple" reaction time condition, subjects were precued with complete information concerning the target position. In the four-choice condition, subjects were precued with partial information, indicating a subset of four possible target positions. In the eight-choice condition, advance information regarding the target position was entirely ambiguous. Results indicated that when subjects were provided with unspecific advance information concerning the position of the target, and thus were unable to partially prepare movements prior to the imperative stimulus, a left hand advantage for speed of initiation was obtained. When complete advance information was available, reaction times for the left and right hands were equivalent. The left hand advantage in choice conditions was eliminated when the accuracy of response execution was emphasized and subjects were afforded the opportunity for "on-line" preparation (Experiment 3). These data are discussed in relation to the role of the right hemisphere in the preparation of movement.

Asymmetries in Coupling Dynamics of Perception and Action.

The influence of information-based dynamics on coordination dynamics of rhythmic movement was examined with special reference to the expression of asymmetries. In Experiment 1, right-handed subjects performed unimanual, rhythmical movements in coordination with either a discrete or continuous visual display. The right hand-visual display system defined a more stable perception-action collective than the left, particularly when continuous visual information was available. In Experiment 2, the same subjects performed rhythmic bimanual movements in coordination with a continuous visual display. The action collective was inherently more stable than the perception-action collective, although similar patterns were observed at both levels. Importantly, the dynamics of the perception-action collective impinged upon the dynamics of the action collective in terms of stability. Asymmetries remained evident between limbs in the bimanual preparations, with the left hand exhibiting greater limit-cycle variability and also a tendency to more often effect transitions at the action couple. Features of dynamical models that capture characteristics of manual asymmetries are discussed.

Order effects and the weighting process in workload assessment.

Operators controlling a power grid were subjects in a mental workload experiment in which they performed their normal tasks under simulated quiet and busy conditions. Workload was assessed using the NASA Task-Load Index (TLX). It was found that there were significant differences between the two conditions, but there were no order effects. The value of the weighting procedure was assessed by correlating unweighted and weighted workload ratings. Although the correlations were high, they were not perfect, indicating some value for weighting the dimensions of the TLX. Large individual differences were observed in perceived workload.

Effects of redundancy in the comparison of speech and pictorial displays in the cockpit environment.

Synthesised speech and pictorial displays were compared in a spatially compatible simulated cockpit environment. Messages of high or low levels of redundancy were presented to subjects in both modality conditions. Subjects responded to warnings presented in a warning-only condition and in a dual-task condition, in which a simulated flight task was performed with visual and manual input/output modalities. Because the amount of information presented in most real-world applications and experimental paradigms is quantifiably large with respect to present guidelines for the use of synthesised speech warnings, the low-redundancy condition was hypothesised to allow for better performance. Results showed that subjects respond quicker to messages of low redundancy in both modalities. It is suggested that speech messages with low-redundancy levels were effective in minimising message length and ensuring that messages did not overload the short-term memory required to process and maintain speech in memory. Manipulation of phrase structure was used to optimise message redundancy and enhance the conceptual compatibility of the message without increasing message length or imposing a perceptual cost or memory overload. The results also suggest that system response times were quicker when synthesised speech warnings were used. This result is consistent with predictions from multiple resource theory which states that the resources required for the perception of verbal warnings are different from those for the flight task. It is also suggested that the perception of a pictorial display requires the same resources used for the perception of the primary flight task. An alternative explanation is that pictorial displays impose a visual scanning cost which is responsible for decreased performance. Based on the findings reported here, it is suggested that speech displays be incorporated in a spatially compatible cockpit environment because they allow equal or better performance when compared with pictorial displays. More importantly, the amount of time that the operator must direct his vision away from information vital to the flight task is decreased.