Exp Brain Res (1994) 99:247-258 9 Springer-Verlag 1994
M. Alamy - E. Trouche 9 A. Nieoullon 9 E. Legallet
Globus Pallidus and motor initiation:
the bilateral effects of unilateral quisqualic acid-induced lesion on reaction times in monkeys
Received: 21 July 1993 / Accepted: 2 December 1993
Abstract The results of many experimental studies have shown that the globus pallidus (GP) is involved in the control of motor activities, particularly during mo- tor execution. Whether or not the GP is involved in the initiation phase is still a matter of controversy, however.
This question was investigated in the present study in Papio papio monkeys after GP lesion using a simple reaction time (RT) task, focusing particularly on the ini- tiation phase. The monkeys were trained to perform this task, which consisted of raising their hand as quickly as possible in response to a visual signal. The RT and its premotor and motor components were measured. In ad- dition, the distribution of the RTs was analyzed in order to assess the number of long latency responses. After making unilateral GP cell lesions by locally injecting small amounts of the excitatory amino acid quisqualic acid, a bilateral increase was observed in RT. This lengthening involved both the premotor and the motor phases of the RT when the task was performed with the contralateral limb and only the premotor phase when it was performed with the ipsilateral one. A significant increase was observed in the percentage of long latency responses recorded in the contralateral limb after the GP lesion but not in the ipsilateral one. Increases in the RT and in the percentage of long latency responses are thought to constitute two indices of the akinesia ob- served in our task involving speed constraints, which suggests that the GP may participate in motor initia- tion. A complete recovery of the RT was observed with- in one month, whereas the increase in the percentage of long latency responses persisted. These two indices of akinesia seemed therefore to result from an impairment involving both motor and nonmotor processes. These data suggest that the GP may be involved in the control of postural adjustment, motivation, and/or the control of the initial isometric part of movements. The time course of the recovery from the deficits observed after
M. Alamy 9 E. Trouche ( ~ ) - A. Nieoullon 9 E. Legallet CNRS, L N C F , 31 chemin Joseph Aiguier, F-13402 Marseille C E D E X 20, France, F A X no: 33-91-775083
GP lesion shows the existence of mechanisms which seem to have been operative particularly in the case of impairments affecting motor processes.
Key words Globus pallidus 9 Reaction time
Premotor and motor phases 9 Long latency responses Quisqualic acid lesion 9 Monkey
Introduction
The globus pallidus (GP), together with the other struc- tures belonging to the basal ganglia (BG), forms a func- tional group which participates in the regulation of mo- tor activity. It has been established on the basis of both experimental (DeLong 1971) and clinical data (Martin 1967) that this nucleus is involved in movement control.
In primates, the GP consists of two segments, the external (GPe) and internal (GPi) segments, which are separated by the internal medullary lamella. The GP has been classified as one of the "motor" structures on the basis of anatomical data on its afferent and efferent projections: the GP receives striatal afferents, mainly arising from the putamen (Put), which is one of the targets of the corticostriatal fibers originating from the motor cortex (MI; K/inzle 1975), the premotor cortex (PM) and the supplementary motor area (SMA; Kiinzle 1978). On the other hand, the GP gives off pallidal effer- ents via the ventroanterior (VA) and ventrolateral (VL) thalamus (Devito and Anderson 1982; Parent and De- bellefeuille 1982, 1984) to the SMA (Percheron et al.
1986; Schell and Strick 1984; Tokonu et al. 1992) and to the MI (Nambu et al. 1988) from its internal segment, which is one of the main output points from the BG.
Experimental investigations have established that the GP plays a key role in the control of motor execu- tion. After GP lesion, an increase in the movement time has been reported to occur (Beaubaton et al. 1981; Ho- rak and Anderson 1984; Mink and Thach 1991c). Like- wise, electrophysiological recordings have shown that a change in the activity of GP cells occurs during move-.,
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ments: these changes have been correlated with changes in m o v e m e n t p a r a m e t e r s such as direction, amplitude, and velocity ( G e o r g o p o u l o s et al. 1983). In o t h e r stud- ies, after assessing pallidal activity in a variety of tasks, no consistent relationship was observed, however, be- tween pallidal activity a n d the physical p a r a m e t e r s of m o v e m e n t defined above (Brotchie et al. 1991; M i n k and T h a c h 1991b). These results suggested that these m o v e m e n t p a r a m e t e r s m a y not be u n d e r pallidal con- trol.
T h e G P also seems to play an i m p o r t a n t role in pos- tural control. Experimental G P lesions have been f o u n d to induce a flexed posture in the anterior contralateral limb ( B e a u b a t o n et al. 1981; D e L o n g and Coyle 1979;
H o r e a n d Vilis 1980; M i n k a n d T h a c h 1991c) and a contraversive head deviation in the m o n k e y ( D e L o n g a n d Coyle 1979). Electrophysiological recordings have shown, m o r e o v e r , that a sustained discharge occurs in m o s t G P cells ( D e L o n g 1971; Iansek and P o r t e r 1980).
One of the reasons for the c o n t i n u o u s n a t u r e of this discharge m a y be that the activity of these n e u r o n s was coupled to that of postural muscles serving to s u p p o r t the trunk, neck, a n d h e a d (Iansek and P o r t e r 1980).
In electrophysiological studies, c o n t e x t - d e p e n d e n t responses to sensory stimuli that triggered m o t o r re- sponses have been r e c o r d e d in n e u r o n s of the c a u d a t e (Rolls et al. 1983; Rolls and Williams 1987) and the p u t a m e n (Liles 1985; Rolls and Williams 1987). As the functional representation observed in the striatum is m a i n t a i n e d in the G P (Delong et al. 1985) t h r o u g h stria- topallidal c o n n e c t i o n s with a specific t o p o g r a p h i c a l or- ganization (Smith and P a r e n t 1986; H e d r e e n and De- long 1991), it seems likely that this c o n t e x t - d e p e n d e n t activity m a y be reflected in the GP.
The existence of strong afferent inputs to the G P from the striatum, which is involved in m o v e m e n t initia- tion (Schultz and R o m o 1988), suggests that the G P m a y be engaged in the neural processes underlying the initiation of m o v e m e n t . T h e experimental d a t a relating to this question are c o n t r a d i c t o r y , however. Some elec- trophysiological d a t a seem to s u p p o r t the idea that the G P is involved in m o t o r initiation: a change in the neu- ronal discharge was observed p r i o r to the onset of elec- t r o m y o g r a p h i c activity ( E M G ) in the cat (Neafsey et al.
1978) and m o n k e y ( N a m b u et al. 1990). T h e results of three o t h e r electrophysiological studies suggested that the G P c a n n o t initiate m o v e m e n t , since the activity of only a few G P units changed before the E M G and the bulk m u c h later (Mitchell et al. 1987; M i n k and T h a c h 1991b). O t h e r d a t a from studies involving experimental lesions in monkeys, showing that after pallidal lesion no change in the m o v e m e n t latency occurred in a reaching task ( H o r a k and A n d e r s o n 1984) or in a tracking task 9 .(Mink and T h a c h 1991c), are not c o m p a t i b l e with the i d e a that the G P m a y c o n t r i b u t e to m o t o r initiation.
In view of the a b o v e discrepancies a m o n g the d a t a on the putative role of the G P in m o v e m e n t initiation, the aim of the present study was to analyze in c o n d i t i o n e d m o n k e y s the effects of selective unilateral lesions of pal-
lidal n e u r o n s on the latency of a forelimb-raising move- ment using a reaction time task where the subjects had to trigger the m o v e m e n t as quickly as possible. This procedure, focusing particularly on the initiation phase of the movement, seemed to be a p p r o p r i a t e for analyz- ing m o r e specifically the c o n t r i b u t i o n of the G P to the initiation processes. Some o f the preliminary results of this study have previously been r e p o r t e d in abstract form (Alamy et al. 1990).
Materials and methods The behavioral task
Two Papio papio monkeys (subjects P and T) were trained to perform a simple reaction time (RT) task. Briefly, the task consist- ed of raising one forelimb in response to a visual signal. The subject was placed in a cage facing a panel fitted with a platform, which served as the starting point of the motor response. The monkey spontaneously placed its muzzle in a mask attached to the top of the cage bars. By looking through the two eye-holes in the mask, it was able to see the panel. The motor sequence was triggered when the animal spontaneously placed its hand on the platform. After a preparatory period (PP) of variable length (400, 600, 800, or 1000 ms), a luminous signal was then switched on in the center of the panel. The subject was required to perform a nonaimed movement as quickly as possible before the luminous signal was switched off (maximum signal duration 250-300 ms during the training period and 1000 ms when the performances became stable). During the preoperative period (PREOP), the maximum signal duration (SD) was increased to 1000 ms both before and after the lesions, as the subjects were so severely hand- icapped after GP lesion that a longer SD was necessary for any movement to be observed. This change did not make any differ- ence to the RT, as the regression analysis of the PREOP RT showed that there existed no significant trends in the RT values during the PREOP (with subject P, F=0.024 and F=1.363, df=lg, P>0.05 in the two limbs; with subject T, F=0.333 and
S t
/
~ t l ' " t 2 ~
, . . - - - P P , ' . . R T ,
Fig. 1 Experimental procedure: the subject placed its hand on a starting platform, thus triggering the onset of a luminous signal (St) after a variable preparatory period (PP). The reaction time (RT) was the time elapsing between the onset of the luminous signal and the platform release. The strain gauge measurements of the amplitude (/'} of any changes in the force exerted by the sub- ject's hand during the RT showed the existence of two phases: the premotor phase (ti), corresponding to the latency of the force change, and the motor phase (t2), corresponding to the duration of this force change
