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a v a i l a b l e a t w w w. s c i e n c e d i r e c t . c o m

w w w. e l s e v i e r. c o m / l o c a t e / b r a i n r e s r e v

Review

Cortical mechanisms involved in visuomotor coordination during precision walking

Trevor Drew, Jacques-Etienne Andujar, Kim Lajoie, Sergiy Yakovenko
Dpartment Physiologie, Universit de Montral, C.P. 6128, Succ. Centre-ville Montral, Qubec, Canada H3C 3J7

A R T I C LE I N FO Article history: Accepted 3 July 2007 Available online 22 August 2007 Keywords: Motor control Visuomotor Motor cortex Posterior parietal cortex

AB S T R A C T Goal-directed locomotion, in particular in situations where there is a need to step over or around obstacles, is largely guided by visual information. To negotiate an obstacle successfully, subjects must first plan how to perform the movement and then must execute that plan. In cats, this information must also be stored and used to guide the hindlimbs, which are moved in the absence of direct visual input. Experiments in cats have shown that the motor cortex makes an important contribution to the execution of gait modifications and is involved both in specifying limb trajectory and, when necessary, where the paw will be placed. We suggest that, in both situations, subpopulations of pyramidal tract neurons in the motor cortex act to regulate the duration, level and timing of small groups of synergistic muscles, active at different times during the gait modification. However, the available evidence suggests that the motor cortex plays little role in the planning of these gait modifications. Instead, recent work suggests that the posterior parietal cortex (PPC) may contribute to this function. In agreement with this proposal, we have found that lesions to this structure lead to errors in forelimb placement in front of an advancing obstacle and may produce deficits in forelimbhindlimb coordination. Single-unit recordings from neurons in the PPC support a role for the PPC in these two aspects of visually guided locomotion and further show that the signal in this structure might be limb-independent. 2007 Elsevier B.V. All rights reserved.

Contents
1. 2. 3. Introduction . . . . . . . . . . . Visual regulation of locomotion. Neural control of locomotion . . 3.1. Motor cortex. . . . . . . . 3.2. Parietal cortex . . . . . . . 4. Concluding remarks . . . . . . . Acknowledgments. . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200 200 200 201 204 209 210 210

Corresponding author. Fax: +1 514 343 6113. E-mail address: Trevor.Drew@umontreal.ca (T. Drew). 0165-0173/$ see front matter 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.brainresrev.2007.07.017

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1.

Introduction

Vision is critical for locomotion. Even during locomotion over level terrain, there is a constant need to survey the ground in front of the path of advance for potential obstacles and to scan the surrounding area for potential threats or, in the case of a carnivore, potential prey. Depending on the visual information that is received, the subject will need to make anticipatory modifications of gait. These might include altering direction to avoid a threat or making modifications of step length, limb trajectory and paw placement to avoid an obstacle or to place the paw precisely in a secure position if walking over uneven terrain. The question of how these latter gait modifications are controlled by cortical areas is the subject of this review.

2.

Visual regulation of locomotion

The role that vision plays in the control of goal-directed locomotion has been the subject of much research, especially in the field of behavioural studies. From a wide range of experiments, two fundamental ideas have arisen. One is that, in most circumstances, intermittent visual information about the environment is sufficient to guide locomotion while the other is that the predicted time to contact () with an object may be used to guide locomotion. The first idea comes from experiments showing that neither humans (Assaiante et al., 1989; Laurent and Thomson, 1988; Patla et al., 1996; Patla, 1991; Thomson, 1980, 1983), nor cats (Sherk and Fowler, 2000; Wilkinson and Sherk, 2005) need to look continually at a target or location in space in order to be able to navigate around it. In experiments designed to determine how frequently subjects needed to obtain visual information, Patla et al. (1996) fitted human subjects with glasses containing LED lenses that the subjects could make transparent or opaque by pressing a switch. They found that in undemanding circumstances subjects sampled the environment infrequently. However, when obstacles were introduced into the walking path, the subjects increased the sampling frequency and duration. In a complementary series of experiments, Patla and Vickers (1997) used a head-mounted camera and eye tracking device to determine how gaze is normally directed during locomotion in an obstructed environment. They found that visual sampling was divided between two principal modes. For periods of time subjects would direct their gaze at the ground a fixed distance in front of them so that the visual field moved along with the subject. They referred to this as travelling fixation and the visual information obtained during this time presumably provides optic flow fields (see following paragraph) with information about heading and velocity. Interspersed with these periods of travelling fixation, the subjects saccade to the obstacle placed in their path; this information is presumably used to integrate the location of the object with the proprioceptive and visual information concerning the subject's locomotion. In extremely difficult situations, such as stepping from one stone to another, subjects may fixate the location of their next footfall in every step (Hollands and Marple-Horvat, 1996; 2001; Hollands et al., 1995).

One view that has come to dominate the field is that optic flow plays a critical role in determining the direction and the velocity of movement through the environment. In large part, this view is based on the ground-breaking ideas of Gibson (1958, 1968) who proposed that an organism uses the flow field produced by the reflections of light from the various objects in the field of vision and that changes in these flow fields, particularly the radial changes produced by movement towards an object, provide the relevant information necessary to guide locomotion. Despite some challenges to this view (Rushton et al., 1998), the basic ideas proposed by Gibson have received general support (Lee, 1976, 1980, 1998; Nomura et al., 2005; Sherk and Fowler, 2000; Turano et al., 2005; Warren et al., 1986, 2001). One way in which this information may be used to control locomotion was proposed by Lee (1976) who examined the visual cues that were used by drivers to initiate and control braking. He found that the controlled variable was not the distance of one car from another but rather the calculated time that it would take for one car to hit the other, i.e. the time to contact (). He presented an analysis to show that this information can be calculated from the optic flow. Further experiments have suggested that time to contact may be the controlled variable in athletes adjusting their run-up in the long jump (Lee et al., 1977). Moreover, Sun et al. (1992) showed that running gerbils used to adjust their speed when confronted with an obstacle. Similarly, Warren et al. (1986) suggested that human subjects running on a treadmill used to ensure their feet were accurately placed on marks painted onto the belt. Indeed, it is possible that might be used as a basis for controlling locomotion under a wide range of circumstances and in a number of different species (Egelhaaf and Borst, 1993; Goodale et al., 1990; Rind and Simmons, 1999; Srinivasan, 1992), although some more recent experiments suggest that information concerning alone is not sufficient to produce precise visuomotor control in all conditions (Fajen and Warren, 2004).

3.

Neural control of locomotion

Studies directed specifically at examining the role of different parts of the brain in the execution of visually guided locomotion have been performed on primarily two structures: the cerebellum and the motor cortex. Both of these structures play an important role in the control of locomotion as summarized in several reviews (Armstrong, 1986; Armstrong and Marple-Horvat, 1996; Drew, 1993; Drew et al., 1996; Rossignol, 1996) and both probably contribute to the modifications of the base locomotor activity required to control paw placement and limb trajectory in situations requiring visual regulation of the base rhythm. However, there is little evidence that the motor cortex contributes to the planning of locomotion. Instead, recent work suggests that the posterior parietal cortex (PPC) may make a large contribution to this aspect of visually guided locomotion. The following sections first review the work showing the contribution of the motor cortex to the control of locomotion in situations requiring visual input and then summarize some recent work on the PPC.

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3.1.

Motor cortex

Damage to the motor cortex, the pyramidal tract or the corticospinal tract leads to characteristic deficits in locomotion, especially in situations in which there is a requirement for precision. These deficits include a dragging of the paw along the ground and changes in limb trajectory, probably subsequent to modifications of intralimb control, as well as problems in precise placement of the paw (Adkins et al., 1971; Chambers and Liu, 1957; Courtine et al., 2005; Eidelberg and Yu, 1981; Gorska et al., 1993; Jiang and Drew, 1996; Laursen and Wiesendanger, 1966; Marshall, 1936). An inability to place the limb precisely was first detailed in the studies of Liddell and Phillips (1944) who showed that bilateral section of the pyramidal tract in cats led to an inability to step from rung to rung of an horizontal ladder. Instead the cats placed the limb too far and the limb then protruded helplessly downward. A similar deficit was reported by Beloozerova and Sirota (1988) following motor cortex ablation or injection of TTX and was also seen after injection of muscimol into the motor cortex (our unpublished observations). Recently, Friel et al. (2007) have reported that inactivation of the motor cortex by a continual infusion of muscimol during a critical developmental period in the kitten leads to a long-term inability to place the paw accurately on the rungs of a horizontal ladder. As in the studies of Liddell and Phillips (1944), there was hypermetria of the limb so that it was placed too far forward on the rungs and slipped off. Deficits in limb trajectory or in intralimb coordination have been less well defined but are undoubtedly reflected in the paw drag that is such a consistent feature of any lesion that damages the motor cortex or the corticospinal system. In those studies that have specifically examined changes in intralimb coordination, changes in the coupling of EMG activity, especially around the hip and the knee, have been reported in both cats (Drew et al., 2002; Jiang and Drew, 1996) and primates (Courtine et al., 2005). These changes in limb coupling also lead to an inability to step over obstacles; a similar finding is made after injection of muscimol into the forelimb representation of the motor cortex (Drew et al., 1996). Changes in the timing of muscle activity have also been reported in hemiplegic patients (Knutsson and Richards, 1979). In most of the above experiments, motor cortical impairment has either implicitly or explicitly been assumed to affect changes in both limb trajectory and paw placement, collectively leading to a loss in precision. However, the recent study of Friel et al. (2007) showed that although the kittens with the inactivated motor cortex showed errors in placing the limb on the rungs of a horizontal ladder, even several weeks after muscimol application was stopped, they successfully stepped over obstacles attached to a moving belt. Moreover, analysis of limb trajectory, including the height of the paw as it cleared the obstacle, showed no differences in the limb contralateral to the inactivated cortex and the unaffected, ipsilateral limb. These experiments raise the possibility that end-point control (paw placement) and trajectory may be controlled, to some extent, independently, (although see below) even if both are required for precision. Moreover, the fact that these deficits were observed even after the muscimol infusion was stopped

suggests that activity-dependent processes during development are essential for the appropriate calibration of the visuomotor transformations that ensure accurate paw placement. Moreover, they suggest that different neuronal populations in the motor cortex contribute to the adjustments needed to place the paw precisely and those required to regulate limb trajectory. A contribution from the motor cortex to the control of paw placement, or end-point control, is supported by single-unit recording studies from several laboratories. For example, both Armstrong (Armstrong, 1986; Armstrong and Marple-Horvat, 1996) and Beloozerova and Sirota (1993) have described substantial increases in the discharge frequency of neurones in the motor cortex when cats walk on an horizontal ladder as compared to a flat surface. Beloozerova and Sirota (1993) have also described a similar increase in cell discharge as cats stepped over barriers that were placed closer and closer together. Moreover, it is interesting to note that in both studies the major increase in discharge activity in many cells occurred in the latter part of the swing phase, just prior to paw

Fig. 1 Average activity of 7 representative forelimb muscles during steps over a cylindrical obstacle with a cross section of 10 cm. The traces are aligned to the onset of the shoulder protractor, the cleidobrachialis (ClB) and display electromyographic (EMG) activity in the step before, during and after the step over the obstacle. The thinner traces show activity when no obstacle is attached to the treadmill belt and the thicker lines during the step over the obstacle. Abbreviations: Bic, biceps brachii; Br, brachialis; ECR, extensor carpi radialis; EDC, extensor digitorum communis; TrM, teres major; TriL, triceps brachii, lateral head. The 1st vertical dotted line, aligned on the onset of the second period of activity in the EDC, makes an approximate separation between the flexion (F) phase of locomotion and the subsequent extension (E1) as the limb is placed on the support surface. The 2nd dotted line indicates the approximate end of the swing phase of locomotion. Adapted from Drew (1993).

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contact. This suggests that the major requirement in the control of accuracy or end-point control is the regulation of muscles active just before the paw is placed on the contact surface. In the experiments from our laboratory, we have used a task in which cats are trained to step over obstacles attached to a moving treadmill belt. In this task, the major challenge for the cat is to determine the size and shape of the advancing obstacle, as well as its relative speed, and then to modify the gait pattern to step over that obstacle, smoothly, and without undue interruption of the gait pattern. The main constraint in this task is, therefore, to adapt the limb trajectory to the form and shape of the obstacle to ensure that it passes smoothly over the top without interrupting the gait cycle. The position in which the paw is placed on the other side of the obstacle is not a major consideration. As we have detailed previously (Drew, 1988, 1993; Drew et al., 1996), although the change in limb trajectory is seamlessly superimposed upon the normal gait pattern, the production of this limb trajectory requires complex changes in the duration, magnitude and timing of multiple muscles acting across all joints of the forelimb. This is illustrated for a number of representative muscles recorded from the forelimb in Fig. 1. In some cases, such as for the shoulder protractor, the cleidobrachialis (ClB), the major change is one

of duration as the leg is transported over the obstacle. In others, such as the shoulder retractor, the teres major (TrM), and the elbow flexor, the brachialis (Br), the major change is one of magnitude as the paw is lifted from the ground and the forearm raised above the obstacle. In yet others, such as the wrist and digit dorsiflexor, the EDC, the major change is one of timing in which the single burst observed during control locomotion is modified into two periods of activity, one early in the swing phase at the same time as the period of activity in the wrist dorsiflexor, the extensor carpi radialis (ECR) and the other at the end of the prolonged swing phase. Moreover, inspection of Fig. 1 shows that the major changes in EMG activity occur sequentially. This is better illustrated in Fig. 2A for a subset of these muscles. In this illustration, it can be clearly seen that the successful completion of the gait modification requires that the cat first modify the activity in the TrM, then that of the Br, the ECR, and finally the EDC. The data in Figs. 1 and 2 therefore emphasise that in order to step over an obstacle the central nervous system has to produce sequential changes in the duration, the magnitude and the timing of activity in a large number of muscles acting around multiple joints. The data from our unit recording studies suggest that both the motor cortex and the red nucleus (Lavoie and Drew, 2002) contribute to the production of these changes in EMG activity.

Fig. 2 Muscles and pyramidal tract neurones (PTNs) are activated sequentially during the swing phase of the gait cycle. Each pair of traces shows the averaged activity of a given muscle (A) and of the PTN recorded simultaneously with that muscle (B). Data are synchronized to the onset of activity in the ClB. Numerical values to the right of each trace indicate the time of peak activity with respect to the onset of the ClB. (C) Illustrations to show that each of the muscles shown in panel A is activated during different behavioural epochs during the swing phase of the modified cycle. These muscles are representative of small groups of synergistic muscles that are activated simultaneously (Krouchev et al., 2006). Abbreviation: LtD, latissimus dorsi. Panels A and B adapted from Lavoie and Drew (2002).

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Our initial recordings from pyramidal tract neurones (PTNs) in the motor cortex of cats performing this task showed that a large proportion of the neurones (86% in Drew, 1993) showed changes in activity during the cycle in which the cat stepped over the obstacle, with most of these showing increases in activity. The increases in discharge activity were normally discrete, involving brief phasic changes in activity during a restricted portion of the swing phase. Different populations of neurones were recorded that showed increases in activity at different times during the swing phase of locomotion (Drew, 1993; Lavoie and Drew, 2002). We have suggested that these populations of neurones are involved in controlling the changes in activity of small groups of muscles active at different times of the step cycle. This concept is illustrated in Fig. 2B, which illustrates representative neuronal activity recorded from 4 different PTNs. Each of these neurones was recorded simultaneously with the EMG trace shown to the left in Fig. 2A and each PTN was best temporally correlated with that muscle. It is not too surprising then that these PTNs are activated sequentially in the same manner as the EMGs. Our interpretation of these data is that these PTNs are representative of subpopulations of motor cortical neurones each of which modulates the activity of small groups of muscles active at different times during the step over the obstacle. In the same manner, we suggest that the muscles illustrated in Fig. 2A are equally representative of the groups of synergists controlled by these PTNs. This idea receives support from our recent study on the synergistic organisation of muscles during unobstructed locomotion using a novel cluster analysis (Krouchev et al., 2006). This analysis shows that the TrM, for example, is representative of a group of simultaneously activated synergistic muscles that contribute to raising the paw from the support surface (Fig. 2C). Similarly, the late burst of activity in the EDC muscle is representative of

another group of muscles that act together to control where the paw is positioned on the support surface as well as to stabilize the wrist and digits. We suggest that this organisation, whereby subpopulations of P regulate the activity of small groups of synergistic muscles, provides a flexible substrate by which limb trajectory can be readily modified to take into account the specific size and shape of a given obstacle. For example, in the lead condition, stepping over a wide obstacle requires a prolonged protraction of the shoulder. The increased duration of the discharge of the subpopulation projecting to synergists involved in limb transport would, therefore, increase the duration of muscles such as the ClB. Similarly, in the trail condition, the subpopulation of neurones active early in swing would modify the phase of activation and the magnitude of the discharge in those synergies responsible for lifting the paw from the support surface. Appropriate modulation of the phase, duration and relative timing of the signal to different groups of synergists would allow the limb trajectory to be readily adapted to any shape of obstacle. This type of flexible organisation might also be used to exert a precise control over the location in which the paw is placed in the tasks used in the studies of Armstrong (Armstrong, 1986; Armstrong and Marple-Horvat, 1996) and Beloozerova and Sirota (1993). In both of these tasks, the finding that many of the cells increased their discharge at the end of swing suggests that the motor cortex may be primarily controlling a muscle synergy active just prior to contact of the paw with the support surface (Fig. 2C; see Krouchev et al., 2006). This suggestion is supported by the results from our own studies in which we recorded activity from PTNs in a task in which cats were required to control the accuracy of their gait modification by stepping between two obstacles. In this condition, we found some cells that discharged more intensely in this condition

Fig. 3 Example of a PTN that showed its greatest discharge activity when there was a need to precisely control the location in which the paw was placed. Post event histograms and rasters of cell activity are synchronized to the onset of EDC activity (vertical line) during four different conditions. Adapted from Drew (1991).

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than when the cat stepped over larger obstacles. One such example is illustrated in Fig. 3 which shows a cell whose activity was temporally correlated with the period of activity in the EDC. The discharge frequency of the PTN was greater in the situation in which the cat was required to place its paw between two obstacles than when it stepped over 2 larger obstacles. This suggests that control of paw placement might rely largely on precisely regulating that small group of muscles responsible for controlling the limb trajectory at the end of the swing phase. These data show that the motor cortex makes an important contribution to the control of precision during visually guided locomotion. However, it is important to note that in the experiments from our laboratory, in which gait modifications were interspersed with periods of unobstructed locomotion, changes in cell activity were primarily observed in the step cycle in which the cat stepped over the obstacle. In the PTN illustrated in Fig. 4, for example, the cell showed a strong increase in its discharge activity when the cat stepped over the obstacle but no substantial change in activity in the steps preceding that over the obstacle. Indeed, in only a few cases did we observe any change in activity in the step preceding that over the obstacle and when we did, it was normally correlated with the activity of muscles likewise increasing their discharge activity just prior to the onset of swing. As such, the results from these studies suggest that during these visually guided gait modifications, the motor cortex contributes more to the execution of the movement than to its planning.

3.2.

Parietal cortex

The question then arises as to which structures are involved in planning a gait modification during visually guided

Fig. 4 Example of a PTN illustrating a strong increase in discharge frequency during the step over the obstacle but little, if any, change in activity in the preceding steps. We display both the raw recording of PTN activity and the instantaneous frequency of the discharge activity.

locomotion. Clearly, it is unlikely that there is any single structure that is responsible for this function and the results from studies in primates suggest that many cortical regions and subcortical structures, including the basal ganglia and the cerebellum, contribute to movement planning. However, in this review, we will concentrate on a structure that has been the subject of recent studies in this laboratory directed at understanding the control of visually guided locomotion, namely the posterior parietal cortex (PPC). The PPC, located primarily within and caudal to the ansate suclus projects strongly to all regions of the motor cortex (Andujar and Drew, 2007; Babb et al., 1984; Ghosh, 1997; Yumiya and Ghez, 1984) as illustrated in Figs. 5A, B. Moreover, we have recently shown that this pathway is organised topographically, albeit with a large degree of convergence and divergence in the projections (Andujar and Drew, 2007). This projection provides a substrate by which the PPC could directly modulate motor activity. As illustrated schematically in Fig. 5C, the PPC also has strong projections to the pontine grey nuclei which, in turn, project to the lateral cerebellum (Stein and Glickstein, 1992). As such, the PPC could also contribute to the control of visually guided movements via the lateral cerebellum which has been shown to contain neurones that discharge in response to visual stimuli during locomotion (Cerminara et al., 2005; Marple-Horvat et al., 1998; Marple-Horvat and Criado, 1999). A contribution of the PPC to the control of visually guided reaching movements in primates has been shown by a wide range of experiments. Particularly relevant are those studies that show increased discharge activity in the PPC during instructed delay tasks, prior to the onset of movement (Kalaska, 1996) and those that have specifically designed experiments to demonstrate that this increased activity is truly related to the intention to move and not to any attentional confounds (Andersen, 1995; Quiroga et al., 2006; Snyder et al., 1997, 2000). Together, these studies demonstrate a role for the PPC in the planning of arm movements to a specific target. The little information that is available on the function of the PPC in cats suggests that it makes a similar contribution to visually guided behaviour in this species. For example, a lesion study by Fabre and Buser (1981) that damaged the lateral and posterior regions of the PPC showed that cats subsequently had great difficulty in making a reaching movement to a moving target, although they could reach normally to a stationary one. A specific contribution to the control of locomotion is shown by the recent study of Beloozerova and Sirota (2003) who recorded from neurones in the PPC during their locomotor task in which cats had to step over barriers, walk along a narrow pathway, or step from rung to rung of an horizontal ladder. Cell discharge activity was rhythmically modulated during walking and was increased during the two tasks. This clearly shows that the PPC can contribute to locomotor control. The nature of that control, however, remains unclear. We have, therefore, designed a series of studies to better examine the contribution of the PPC to locomotor control in a situation in which visual input is critical to the successful completion of the locomotor task. In brief, we have modified our standard locomotor task in which cats are required to step over a

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Fig. 5 (A, B) Injections of dextran amines into the motor cortex leads to dense labelling of neurones in areas 5 and 7 around the ansate sulcus of the cat. Texas Red was injected in to the more proximal region of the motor cortex (injection site indicated as filled region in panel A) and Fluorescein was injected into more lateral regions (hatched region in panel B). The laterality of the sagittal sections in panels A and B are indicated in the inset of the dorsal view of the hemisphere. Red and green circles indicate cells retrogradely labelled Aby Texas Red and Fluorescein, respectively; yellow circles indicate double-labelled neurones. (C) Indication of selected connections of the posterior parietal cortex (PPC). Note that the projections to the motor cortex are from layer III while those to the pontine nuclei are from layer V (modified from Andujar and Drew, 2007).

moving obstacle, by permitting the speed of the obstacle to be varied independently of the speed at which the cat walks. In this situation, visual information from the moving obstacle is uncoupled from the visual and proprioceptive information generated by the walking cat. We, therefore, refer to this as a visual dissociation task. In this condition, visual information from the advancing obstacle becomes critical to the cat as it is the only source of information that allows gait to be modified in preparation for the step over the obstacle (Lajoie and Drew, 2005, 2007). Our studies of the behavioural effects of modifying the speed of the obstacle show that the cats make three important modifications to their gait in this condition. First, because the cats are walking at a different speed from the advancing obstacle they modify the step length in the 23 steps leading up to the step over the obstacle. Second, because changing the speed of the obstacle alters the time taken for the obstacle to

pass under the body, they must also modify the coupling of the fore- and the hindlimbs. Third, when the obstacle speed is slowed to a critical level ( 0.7 of the treadmill speed), the cats are no longer able to adapt simply by modifying the forelimb hindlimb coupling but must now make a major change in strategy (Lajoie and Drew, 2007). In the normal situation, when the obstacle and the treadmill were at the same speed, the first hindlimb to step over the obstacle was always on the same side of the body as the lead forelimb (Widajewicz et al., 1994). We refer to this as the standard strategy (Fig. 6A). When the speed of the obstacle was slowed to 0.35 m s 1, the cats were forced to take a supplementary step with the hindlimb ipsilateral to the leading forelimb. As a result, the first limb to pass over the obstacle was now the one contralateral to the leading forelimb. We refer to this as the double-step strategy (Fig. 6B). Conversely, if the speed of the obstacle was increased with respect to the speed of the treadmill, the obstacle now

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Fig. 6 When the speed of the obstacles was equal to that of the treadmill (0.5 m s 1), the first hindlimb to step over the obstacle was always on the same side as the first (lead) forelimb; we refer to this as the standard strategy (A). When the speed of the obstacles was reduced to 0.35 m s 1, cats frequently used a double-step strategy with the hindlimbs (B). In this situation, the hindlimb on the same side as the lead forelimb did not step over the obstacle but was placed in front of it (3rd trace). The cat, therefore, had to take an extra step and the first hindlimb to step over the obstacle was contralateral to the lead hindlimb (4th trace). The homolateral hindlimb, therefore, made two steps before passing over the obstacle, instead of the one required in the standard strategy. When the speed of the obstacle was increased to 0.6 m s 1, cat used a different strategy, the quick-step strategy, in which the forelimb and the hindlimb contralateral to the lead forelimb passed over the obstacle together (C). The numbers indicate the sequence in which each limb is moved. Modified from Lajoie and Drew (2007).

took less time to pass under the body and the cat was again constrained to modify its strategy. In this situation, the contralateral hindlimb passed over the obstacle at the same time as the trailing forelimb. We refer to this as the quick-step strategy (Fig. 6C). In our initial studies of the contribution of the PPC to these visually guided movements, we have studied the effects of lesions to the PPC on the ability of the cats to perform on our standard task as well as during the more challenging situation when the speed of the obstacle was slowed (Lajoie and Drew, 2005, 2007). The results showed that following lesions of the PPC, the performance of the cats was deficient, particularly in the visual dissociation condition. In particular, they were unable to step smoothly over the obstacle without hitting it as they did prior to the lesion. In some steps, they hit the obstacle on the front of the advancing obstacle, and on others on the back of the obstacle as the cat tried to replace the paw on the treadmill. In some cases, the cats were unable to negotiate the obstacle without jumping. Indeed, if considering all errors

together, irrespective of their nature (see below), the two cats with the biggest lesions performed at less than 40% success rate in the days following the lesion and recovery was slow, although progressive. In the two cats in which the lesion extended to the more medial aspects of the ansate sulcus, there were also errors in the forelimbhindlimb coupling. Deficits were much more frequent in the visual dissociation task, in which the speed of the obstacle was slowed with respect to the speed of the treadmill. To determine why the cats hit the obstacle, we made a detailed examination of the position in which the paws were placed with respect to the position of the advancing obstacle in the step prior to the gait modification. For this analysis, we measured the position of the lead paw with respect to the front of the obstacle. In steps in which the cats stepped over the obstacle without hitting it, this distance was not significantly different from that observed in the pre-lesion controls. However, when the cat hit the obstacle, there was frequently a significant difference in the position in which the paw was

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Fig. 7 Lesion of the PPC leads to errors in paw placement prior to the step over the obstacle. (A) Top: the position of the contralateral, lead, forelimb (right side) was measured with respect to the front edge of the obstacle in the step before that over the obstacle. In the example illustrated, the cat subsequently hit the front of the obstacle. (B) A similar situation when the contralateral limb was the trail limb. In this situation, paw position was measured with respect to the ipsilateral (left) limb. (C, D) Quantitative analysis of the position of the lead forelimb when the cat hit the front or the back of the obstacle with the contralateral limb (as either the lead or trail limb). Data are shown the situation when the obstacle was at the same speed as the treadmill (0.5 m s 1, C) and when the obstacle was slowed to 0.35 m s 1 (D, visual dissociation task). In both Panels C and D, we show the situation when the contralateral limb led and when it trailed. Black bars show the position of the paw in steps in which the cat did not hit the obstacle (1042 steps); grey bars show the position of the forelimb in the indicated condition. Asterisks indicate significant differences in paw position (p < 0.05). Modified from Lajoie and Drew (2007).

placed. This is illustrated in Fig. 7 for the position of the right forelimb which was contralateral to the site of the lesion in the illustrated cat. Fig. 7A shows the relative positions of the limbs when the contralateral limb was the first (lead) limb to step over the obstacle and Fig. 7B shows the situation when it was the second (trail) limb. In both situations, we measured the distance of the lead limb from the front of the obstacle (Figs. 7A, B). A comparison of the paw position when the contralateral limb led showed that both when the treadmill speed and the obstacle speed were the same (Fig. 7C), as well as in the visual dissociation condition (Fig. 7D), the paw was placed closer to the obstacle when the cat hit the front of the obstacle and further away when it hit the back. This difference, with respect

to the steps when the cat successfully negotiated the obstacle, was significant in 3 of 4 of these conditions. When the contralateral limb trailed, the change in paw position was less consistent than when it led. However, in most conditions, the changes were consistent with those observed when the contralateral limb led. In neither situation was there any change in the limb trajectory as determined from measures of the height of the paw above the obstacle in steps in which the limb did not hit the obstacle. Together, these results suggest that an important function of the PPC may be to control the precise position of the limbs prior to the gait modification, thus assuring that the gait modification is initiated at the appropriate time and in the appropriate place to clear the advancing obstacle.

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It is important to note that we consider the deficit produced by lesion of the PPC to be one of inappropriate integration of the visual signal with the motor plan rather than one of perception. This position is supported by the fact that the cats adopted the double-step strategy as frequently following the lesion as they did in the control situation (although they frequently hit the obstacle post-lesion). This result suggests that the cats perceive the obstacle appropriately and are able to determine that the speed of advance of the obstacle requires a change of strategy. However, they are unable to produce the appropriate motor pattern to implement the strategy. This resembles the syndrome of optic ataxia that is observed following damage to the parietal lobe in humans and non-human primates (Jakobson and Goodale, 1989; Rizzolatti and Matelli, 2003) and suggests some homology in the functions of the PPC in cats and primates. To determine the neuronal mechanisms underlying these deficits, we have recently begun to record neuronal activity

from these same regions of the PPC in the conditions of our task. These experiments have shown the presence of a large number of neurones that discharge during locomotion and which modify their activity as the cat steps over the obstacle (Andujar and Drew, 2006; Lajoie and Drew, 2006). One example of such a cell is illustrated in Fig. 8. This cell was weakly modulated in the steps prior to the obstacle and then showed an increase in its discharge activity during the step over the obstacle with the contralateral limb (Fig. 8A). In this respect, the pattern of discharge activity resembles that observed in the motor cortex. However, two aspects of the characteristics of this cell differentiate it from most motor cortical neurones that we have recorded. The first feature is that the increase in cell discharge began at the beginning of the step preceding that over the obstacle. Such an early increase in discharge was rarely observed in motor cortical neurones but was common among the population of neurones that we have recorded in the PPC. Indeed, in

Fig. 8 Neurone recorded from the PPC during gait modifications and related to forelimb activity. (A) Discharge activity of the cell when the contralateral limb was the first to pass over the obstacle. (B) The discharge of the same cell when the ipsilateral limb led. In both panels A and B, the shaded bar indicates the swing phase of the contralateral limb as the leg goes over the obstacle. We illustrate the step over the obstacle, the 4 cycles preceding that step and the 2 steps after; vertical dashed lines delimit step cycles. (C) The two traces are superimposed, synchronized to the onset of the coClB in the step of the contralateral limb over the obstacle.

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some cells, this increase in activity began even earlier, in the 2 3 steps leading up to the one over the obstacle (not illustrated). It is possible that this increased discharge prior to the step over the obstacle might contribute to assuring the precise placement of the paw in front of the advancing obstacle. This would be compatible with the results from our lesion study. The second feature that differentiates neurones in the PPC from motor cortical neurones is that many of these neurones also show a substantial increase in activity related to the passage of the ipsilateral limb over the obstacle (Fig. 8B). In the illustrated example, the discharge activity as the ipsilateral limb stepped over the obstacle was as large as that observed during the passage of the contralateral limb. Moreover, this discharge did not maintain the same relationship to the contralateral limb as it did when this limb led (Fig. 8A) but instead now showed a similar relationship to the ipsilateral limb (Fig. 8B). In other words, the cell discharged with respect to the first (lead) limb to pass over the obstacle, regardless of whether that limb was contralateral or ipsilateral to the recording site. In both cases, cell discharge ceased just after the gait initiation in the lead limb was initiated. The difference in the phase of activity of this PPC cells is illustrated in Fig. 8C which superimposes the two traces synchronized to the onset of activity in the coClB. This clearly shows that the discharge activity when the ipsilateral limb was the first to pass over the obstacle (blue trace) preceded that observed when the contralateral limb led. In contrast, in the motor cortex, cells always discharge with respect to the contralateral limb in both the lead and the trail condition (Drew, 1993).

One of the deficits observed in the lesion study was a lack of forelimbhindlimb coordination as reflected in the fact that in some cases the hindlimbs frequently hit the obstacles even in steps in which the forelimbs passed over the obstacle without touching it. A role for the PPC in forelimbhindlimb coordination is also suggested by our single-unit studies. An example of one neurone whose discharge is compatible with such a function is illustrated in Fig. 9. This cell showed a strong increase in its discharge frequency that began just after the onset of the activity in the contralateral forelimb and continued until the passage of the contralateral hindlimb over the obstacle. Cells showing this pattern of activity also frequently discharged between the passage of the ipsilateral fore- and hindlimb in steps over the obstacle in which the ipsilateral limb led (not illustrated). This suggests that cells in the PPC might have a preferential role in coordinating the foreand hindlimbs irrespective of whether the limb ipsilateral or contralateral was the first to pass over the obstacle.

4.

Concluding remarks

Fig. 9 Neurones discharging between the passage of the forelimb and the hindlimb over the obstacle. The shaded bar indicates the period between the onset of the coClB and the end of the period of activity in the anterior head of the contralateral sartorius (coSrt).

Despite the ease with which we are able to modify our gait to step over obstacles in our path, this review emphasises the complexity of the planning and execution that is required to perform such an easy task. Behavioural experiments in cats and humans have demonstrated that while visual information is clearly essential to negotiate any obstacle in one's path, there is no need to fixate that object. Intermittent visual information is sufficient, although more prolonged visual examination is required as the difficulty of the locomotor task increases. Moreover, there is now abundant information suggesting that optic flow information from objects in the locomotor path is used for navigation and adjusting gait. With respect to the mechanisms involved in the control of visually guided gait modifications, it is clear that studies in intact cats, in situations that challenge the cat to modify its gait on the basis of visual information, are providing important insights into how goal-directed locomotion is produced and regulated. We now have a large body of information detailing how the motor cortex contributes to the detailed modifications in EMG activity that are required to precisely control gait both with respect to determining limb trajectory and guiding the paw to a secure location. Moreover, recent studies are beginning to show how such movements are planned and to reveal the contribution of structures such as the PPC to these planning processes. However, it is clear that our understanding of how locomotor modifications are planned lags our understanding of how they are executed. A major challenge for the future will be to determine the relative contribution to locomotion planning of the multiple structures suggested to be involved in sensorimotor transformation. Equally important will be to determine the anatomical and functional connections between these areas involved more in the planning of the gait modifications and those involved more in their execution. Lastly, while the planning and execution of gait modifications in cats undoubtedly share many features with similar studies on the control of reaching movements and saccades in primates, locomotion in the unrestrained cat provides a unique platform for examining

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visuomotor integration during a natural behaviour that may provide insights not available in the primate model.

Acknowledgments
We would like to acknowledge the technical assistance of J. Brichon, S. Bos, M. Bourdeau, N. de Sylva, P. Drapeau, J. Lavoie, F. Lebel and G. Richard in different aspects of these studies. We thank. E. Chapman and S. Rossignol for their comments on the manuscript and C. Gauthier for illustrations. Supported by grants MT 9578 and FRN 53339 from the Canadian Institutes of Health Research (CIHR).

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