- Email: [email protected]
Co-ordination between posture and movement
199
TINS - A u g u s t 1 981 dopaminergic properties of neuroleptics, the implication was that an asymmetry in basal ganglia dopamine, similar to that observed in rats, would be identified in humans. Supporting this and other inferences, direct evidence of neurochemical asymmetries in post-mortem human brain has now been obtained (Glick, Ross and Hough, unpublished). Asymmetries in gamma-aminobutyric acid and choline acetyltransferase were observed in both cortical and subcortical structures. Of special interest was that dopamine was found to be significantly higher in the left than in the right globus pallidus with the average asymmetry in basal ganglia dopamine levels approximately twice that observed in the rat. Pallidal dopamine levels in humans were higher on the side contralateral to hand preferences just as striatal dopamine levels are higher on the side contralateral to side preferences in rats. Another commonality between species was reported by Oke and colleagues, who demonstrated left-right asymmetries in norepinephrine content in both rat and human thalamus. Using the labeled deoxyglucose technique in rats, we discovered, as noted above, a relationship between activity of a structure and its left-right bias, with fight bias being associated with higher activity and vice-versa. Similarly, a relationship between dopamine levels and left-right dopamine asymmetries was evident in human basal ganglia, with greater dopamine being associated with a right bias and less dopamine with a left bias. These kinds of relationships suggest that brain asymmetry is a dynamic process, depending, in part, on the activity of a particular system as a whole. Treatments which specifically increase or decrease activity of a system should then have predictable effects on the left-right asymmetry of the same system. More importantly, it is now clear that the same predictions apply equally to both rats and humans and that studies in the rat may reveal mechanisms and functions of brain asymmetry that are relevant to humans. A similar view was espoused almost a century ago: 'The idea that the distinction between right and left depends upon an asymmetry, and possibly in the last resort upon a chemical difference, is one which has been present to me from my earliest years . . . Human beings and animals that have lost their direction move, almost without exception, nearly in circle.., we have here a teleological device to help parents to find their hungry young again when they have been lost.' (From Ernst Mach (1885) The Analysis of Sensations. )
Acknowledgements This work was supported by Grants NS 14812 and DA 01044 and by Research Scientist Development Award DA 70082 to S.D.G.
Reading list 1 Anden, N. E., Dahlstrom,A., Faxe, K. and Larsson, K. (1966) Acta Pharmacol. Toxicol. 24, 263-274 2 Denenberg, V. H., Garbanati, J., Sherman, G., Yutzey, D. A. and Kaplan, R. (1978)Science 201, 1150-1152 3 Diamond, M. C., Johnson, R. E. and Ingham, C. A. (1975) Behav Biol. 14, 163-174 4 Flor-Henry,P. (1976)Ann. N.Y. Acad. Sci. 280, 777-795 5 Gainotti,G. (1972) Cortex 8, 41-55 6 Galaburda,A. M., LeMay,M., Kemper,T. L. and Geschwind,N. (1978) Science 199, 852-856 7 Glick, S. D. and Cox, R.D. (1976)J. Comp. Physiol. Psychol. 90, 528-535 8 Glick, S. D. and Cox, R. D. (1978) Brain Res. 150, 149-161 9 Glick, S. D., Jerussi, T. P. and Zimmerberg, B. (1977) in Lateralization in the Nervous System (Harnad, S., Doty,R. W., Goldstein, L., Jaynes,J. and Krauthamer, G., eds.), pp. 213-249, Academic Press,New York 10 Glick, S. D., Meibach, R.C., Cox, R.D. and Maayani, S. (1979) Life Sci. 25,395-400 11 Glick, S. D. and Ross, D. A. (1981)Brain Res. 205,222-225 12 Glick, S. D., Schonfeld, A. R. and Strumpf,A. J. (1980) Behav. Brain Sci. 3,236 13 Glick, S. D., Weaver, L. M. and Meibach, R. C. (1980)Science 207, 1093-1095 14 Glick, S. D., Weaver, L. M. and Meibach, R. C. Psychopharmacology (in press)
15 Gruzelier, J. H. and Flor-Henry, P. (1979) Hemisphere Asymmetries and Psychopathology, Elsevier, Amsterdam 16 Gur, R. E. (1978) J. Abnorm. Psychol. 87, 226-238 17 Jerussi, T. P., Glick, S.D. and Johnson, C. L. (1977) Brain Res. 129, 385-388 18 Levy, J. (1977) Ann. N.Y. Acad. Sci. 299. 264-272 19 Ross, D. A. and Glick, S. D. (1981) Brain Res. 210, 379-382 20 Ross, D. A., Glick, S. D. and Meibach, R. C. (1981) Proc. Natl Acad. Sci. U.S.A. 78, 1958-1961 21 Ross, D. A., Glick, S. D. and Meibach, R. C. (1981) Fed. Proc. Fed. Am. Soc. Exp. Biol. 40, 251 22 Rothman, A. R. and Glick, S. D. (1976) Brain Res. 188, 361-369 23 Sokoloff, L., Reivich, M., Kennedy, C., Des Rosiers, M. H., Patlak, C. S., Penigrew, K. D., Sakurada, O. and Shinohara. M. (1977) J. Neurochem. 28, 897-916 24 Ungerstedt,U. (1971)Acta Physiol. Scand. SuppL 367, 49-93 25 Warren, J. M. (1981)) Physiol. Psychol. 8, 351-359 26 Waziri, R. (I980) Psychopharmacology 68. 51-53 27 Wexler, B. F. and Heninger, G. R. (1979)Arch. Gen. Psychiatry 36, 278-284 28 Wilson,S. A. K. (1914) Brain 36, 425-492 29 Witelson,S. F. (1976) Science 193,425-427 30 Zimmerberg,B., Strumpf,A. J. and Glick, S. D. (1978) Brain Res. 140, 194-196 S. T. Glick and D. A. Ross are at the Department of Pharmacology, Mount Sinai School of Medicine, City University of New York, One Gustave L. Levy Place, New York, NY 10029.
Co-ordination between posture and movement Yves Gah~ry and Jean Massion Even a simple and small movement o f a part o f the body is a component o f a complex pattern o f muscular activity, which involves not only muscles directly producing the observed movement but also other muscles often remotely located from the moving part. This latter group is responsible for the postural component o f the motor act. In this article we will examine how these two components o f motor acts, i.e. movements and their associated postural adjustment are co-ordinated. At any given time body posture is a function of the position of the different joints. The muscles with their visco-elastic properties ensure the rigidity of the joints, and thus the skeleton. They must continuously oppose the gravity force to which the body is submitted. Movement of a body segment is itself the source of a perturbation of posture and equilibrium. The displacement of a segment usually results in a displacement of the center of gravity, and therefore disequilibrium, which must be prevented. For example, Fig. l shows how raising both arms is accompanied by a backward displacement of head and trunk,
which maintains in the horizontal plane the position of the center of gravity with regard to the basis of support. Besides these static aspects, the moving segment exerts dynamic forces against the rest of the body. In the example in Fig. 1, raising the arms forwards requires forces to be directed forwards and upwards. Consequently, forces of equal magnitude, but acting in the opposite direction, are exerted on the trunk and must be opposed by muscle contraction. Thus, a motor act is composed of two parts, which were called by Hess TM 'teleokinetic' for the directed moving phase and 'ereismatic' for the postural, or Elsevier/North-Holland Biomedical O 3 7 8 - 5 9 1 2 / 8 1 / 0 0 0 0 - lll)Ol}/$02.~l)
P r e s s 1981
200 supporting component which prevents the displacement of the center of gravity and resists the dynamic forces that arise as a consequence of the movement.
Properties of postural adjustment Several types of postural adjustment were observed in humans. Babinski 4 was one of the first people to describe the adjustment of posture during the performance of movement. When a normal subject is asked to bend backwards, the knees flex forwards simultaneously. These opposing displacements tend to keep the center of gravity in its original position. In contrast, patients with 'asynergia' bend the head and back but do not compensate by flexing the knees, and thus fall backwards. Postural adjustments have been described for standing subjects performing various movements, such as respiration TM or limb movements ~,5,6.~2,a'~,~4 and when resisting external perturbations2*.2L The description of these postural changes includes electromyographic (EMG) data, measurement of joint displacement and the recording of vertical and horizontal forces exerted by the subject standing upon force platforms. Postural adjustment also occurs in quadrupeds, and provides an interesting model for analysing postural changes associated with limb movement. Gray TM compared the quadruped to a four-legged table whose rigidity could be modified t "" " along the back and betwee the legs. Movement of changes the distribution of 1 on the remaining three li~ urements of the vertical fo each provide a reasonable i change in posture. Myog and their latencies prm information. When a rigid table, ba force platforms, suddenly supports, the weight is distr the remaining pair of diag~ legs, whilst the leg diagom ported one becomes unk Ioffe and Andreyev ~7were that this 'diagonal pattern' occurs in dogs lifting one '. this pattern is not merely rigid body conforming t mechanics as was the cas~ There is in addition feedt over the postural changes, changes involved often pr{ of the limb'. Moreover, in limbs, myographic activity preceoes me force changes.
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This diagonal pattern of support is most pronounced when a limb is unexpectedly unloaded, e.g. by dropping a supporting platform, or applying a horizontal force to the limb in a forward or backward direction. Electrical stimulation of certain regions of the brain, such as the motor cortex or red nucleus, also produces single limb flexion with a diagonal support 7'9. From a functional point of view, this pattern permits a limb to be displaced without changing the position of the center of gravity. Consequently, the main orientation of the body is unchanged. However, this pattern. being bipedal, is unstable. When an animal is trained to raise a limb, a different, non-diagonal pattern of postural adjustment is observed 7'2°(Fig. 2). Only two limbs participate in the adjustment, the unloaded limb and its contralateral counterpart to which the weight is transferred. The postural adjustment is thus restricted to the forelimbs in the case of a forelimb movement, or to the hindlimbs for a hindlimb movement. Concurrently, there is a displacement of the center of gravity towards the site opposite to the moving limb. This non-diagonal support, being distributed on three legs, is more stable than the diagonal one. Both in humans and quadrupeds several interesting features characterize the postural adjustment associated with movement.
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1981
As first shown by Belenkii et al. ~ postural adjustment is initiated shortly before the movement (Fig. 3), anticipating the disequilibrium that the movement would have provoked. EMG changes in the muscles of the supporting leg or arm precede those of the prime mover of the displacing segment by some 30-50 ms ~,~,2~,24"2~. Another characteristic of postural adjustment is its adaptability, clearly apparent from the observations of Gurfinkel et al.t2. They noted that for subjects confined to bed for a few weeks, postural adjustment disappeared but quickly returned when mobility was restored. The form postural adjustment takes depends on the way the body is supported initially. It mainly involves the legs when the subject is standing and is observed in the arms 2x,24 when they are supporting the body. In the cat, during limb flexion induced by motor cortex stimulation, postural adjustment is also influenced by the initial posture "~9
Hierarchical organization One of the purposes of postural adjustment is to maintain equilibrium during movement. The 'feedforward' postural command must take into account parameters such as velocity, direction and amplitude, in order to be efficient. Thus, areas of the brain which participate in the control of movement can also be expected to con-
kig. 1. Postural changes observed in man whih" raising both arrn,s. M)tice that the line passes in front o f the ear when the arms are raised (accordingto Martin~2).
TINS -August
DIAGONAL
201
1981
NON DIAGONAL
1
Fig. 2. Two patterns o f postural adjustment in the quadruped.
pyramidal and rubrospinal tracts converge. Once again, the buibospinal level qualifies as a good candidate for this site. Finally, data from animals with lesions to the motor cortex 16." also favor the hypothesis that postural adjustments are organized at a low level. Unilateral lesions to the motor cortex depress contralateral movement and the associated postural adjustment, even if the latter involves both contralateral and ipsilateral musculature. Is there any indication that a neuralnetwork controlling postural adjustment exists at the bulbospinal level? As described by Sherrington ~ besides the crossed extensor reflex, in the decerebrate animal, there is a co-activation of flexors of diagonally opposite limbs, and this could provide a basis for the diagonal pattern of postural adjustment seen in quadrupeds. Whilst the basic mechanisms of postural adjustment could be organized at this level their execution appears to be regulated by several loops passing through cerebellum, such as the cerebello-rubrospinal pathway or the cerebello-thalamo-cortical pathways~.2L In that respect, regulation of the postural adjustment would be organized in a manner comparable to locomotion itself". Let us now shift our attention to the regions of the brain involved in movement preparation and initiation (Fig. 4), since reports of human pathological cases favor their contribution to postural adjustment. Babinski4 mentioned that asynergy was associated with cerebellar lesions, although this assertion has since been questioned by other authors 2,". Involvement of the basal ganglia was proposed by Martin2L and more recently by Traub et al. ~ on the basis of an examination of the parkinsonian patients. Finally, Gurfinkel et aL ~ observed a deficiency in the postural changes associated with respiratory movements in patients with lesions to the
tribute to postural adjustment. According to the schema for central organization of movement proposed by Allen and Tsukahara 2, certain regions are responsible for movement preparation and initiation (association cortical areas, neocerebellum, basal ganglia) whilst others are concerned with movement execution (motor cortex and its descending pathways, rubrospinal and vestibulospinal tracts, older parts of cerebellum). Are postural adjustments executed by areas associated with movement execution, or are they controlled by areas involved in movement preparation and initiation? From experiments in humans and quadrupeds, it appears that postural adjustment is associated with the execution of movement at a low, possibly bulbospinal level~ (see Fig. 4). In humans, this relationship is suggested by latent EMG measurements made when resisting externally applied changes in arm position ",~. Here the latency of onset of EMG response makes improbable long reflex pathways extending above the spinal level. A similar relationship was observed for an adjustment provoked by single limb perturbation in quadrupeds. Here, EMG latencies were as short as 15 ms, which clearly excludes a long supraspinal route. Experiments involving direct stimulation of the motor cortex or red nucleus also favor a low level basis for the organization CENTRAL ] COMMAND of postur~/l adjustment. When a movement . _ is produced by directly stimulating the Feedforword motor cortex and the red nucleus, it is accompanied by a diagonal postural adjustment, which is, according to latency measurements, initiated in a feedforward manner. These results could be interpreted by supposing that each stimulated site incorporates neural networks which control the movement and the associated postural changes. Although a more likely interpretation is that the postural changes are organized somewhere along the descending pathways at a site where the Fig. 3. Feedforward and feedback postural adjustment.
,
i
1
I POSTOR,. I =TOR A E I
[
,
MOVEMENT / PREPARATION Anociotlorlar~.i [ Basal 9(mglio [I NeocerebellumI1
INITIATION ]
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MOVE~IENT EXEC,mON
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Fig. 4. Central control o f postural adjustment. As illustrated by the schema, movement and posture would be linked at a 'low hierarchical level', probably the bulbospinal level. One or most likely several patterns o f posmral ad]ustmem are organized there (Posture: pattern 1, 2, others). The selection ofthe appropriate postural pattern would take place during movement 'preparation' and 'initiation'.
frontal cortex. However, these data do not provide any indication of how these particular structures might contribute to postural adjustment. Experiments in quadrupeds suggest that the choice of an appropriate postural pattern occurs during movement preparation and initiation. Which pathways make this selection? The question is still open, though there is experimental evidence from Ioffe ts that the pyramidal tract may be involved. Conclusion
To conclude, the postural adjustment which during movement performance controls the center of gravity position and counteracts the dynamic forces exerted by the moving segment appears to be organized at two levels. At a low hierarchical level one or several circuits are available which automatically provide a postural adjustment when a movement is triggered by central or sensory inputs. In turn these circuits are under the control of higher level structures which adapt the postural adjustment to each intentional movement. The schema proposed for the central organization of the co-cordination between posture and movement is Still provisional, and one may wish that further experimentation will complete and improve the understanding of this problem.
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Reading list
1 Alexeiev,M. A. and Naidel, A. V. (1972) Zh. Physiol. U.S.S.R. 58, 1721-1730 2 Allen, G. I. and Tsukahara, N. (1974) Physiol. Rev. 54, 957-1006 3 Andr6-Thomas(1940) Equilibre et #quilibration, 567 pp., Masson,Paris
202
T I N S - A u g u s t 1981
4 Babinski,J. (1899) Rev. Neural. 7. 806-816 5 Belenkii, V. E., Gurfinkel, V. S. and Paltsev, E. 1. (196 7) Biophysics, 12,154-161 6 Bouisset, S. and Zanara, M. 11981) Neurosci. Lett. 22. 263-270 7 Oah~ry, Y,, loffe, M., Massion, J. and Polii, A, (1980) Acta Neurobiol. Exp, 40. 741-756 8 Gah6ry, Y. and Legallet, E. (1978) Neurosci. Lett. Suppl. 1, S 124 9 Gah6ry, Y, and Nieoullon, A. (1978) Brain Re,~. 149, 25-37 10 Gray, J. (1944) J. Exp. Biol. 21J, 88-116 11 Grillner, S. (1975) Physiol. Rev. 55,247-31t4 12 Gurfinkel, V. S., Kots, J. M., Pahsev. F. I. and Feldman, A. G. (1971 ) in Models o f the structural fimctional organization o f certain biological system.s (Gelfand, 1. M., Gurfinkel. V. S., Fomin. S. V, and Tsetlin. M. L., eds). pp. 382-395. MIT Press, Cambridge, Mass. 13 Hess, W. R. (1943) Helv. Physiol. Phurmacol.
Acta, 1, C62~C'63 14 Holmes, O. (1939) Brain, 62, 1-311 15 Ioffe. M. E. (1973 ) Physiol. Behav. 1 l, 145-153 16 Ioffe, M. E. (1975) Cortieospinal mechanisms o f imtrumental motor reactions (in Russian), Nauka, MOSCOW 17 Ioffe, M. E. and Andreyev, A. E. 11969) Zh. Vy~sll, Nervn. Deyat. ira. L P. Pnvlova, 19, 557-565 18 Jung. R. ( 1981 ) in Advances in Physiol. Sci. (Szentagothai, J., Hamori, J. and Palkovits. M., eds), Vnl. I, Pergamon Press, New York 19 Legallet. E. and Gah6ry, Y. (1980) Exp. Brain Res. 40, 35-44 20 I~acPherson, J. E., Dufoss6, M. and Massion, 3. (1980) Soc. Neurosci. A bstr. 6, 464 21 Marsden, C. D., Merton P. A. and Morton, H. B. ( 1978)J. Physiol. (London), 275, 47-48P 22 Mar6n, J. P. (196 7) The basal gangliu und posture. Pilman, London
Immunocyt mistry of second mes nger systems
23 Massion, J. 11979) in Integration in the nervous system (Asanuma. H. and Wilson, V. J . eds), pp. 239-2611, Igaku-Shoin, Tokyo-New York 24 Nashner, L. M, and Cordo, P. J. (1980) Soc. Neurosci. Abstr. 6, 394 25 Padel, Y. and Steinberg, R. 11978)J. Physiol. (Paris), 74,265-282 26 Sherrington, C. S. (1906) The Integrative Actmn o f the ,Nervous System, Constable. London 27 Smith, A. M., Masskm, J., Gahdry, Y. and Roumieu. J. (1978) Brain Res, 149. 329-346 28 Traub, M. M., Rothwell. J. C. and Marsden, C. D. (19811) Brain, 1113. 393-412
Yve~ GahOo, and Jean Massion are at the DOpartement de Neurophysiologie G#n~rale, C.N.R.S.-I.N.P.5, 31 chemin Joseph-Aiguier, 13274 ,'¢lurseille Cedex 2, France.
Antibodies prepared against the purified subunit proteins from bovine tissues demonstrate partial similarity to rat tissue antigens, allowing the immunocytochemical localization of t h e ~ molecules to be determined in the rat CNSL In the cerebellar cortex, the regulatory (RI and Rll) and catalytic (C) subunits are observed in neurones and gila, suggesting that the The physiological response o f a cell to a neurotransmitter is dependent upon a chain o f physiological effects of cAMP are not conintracellular biochemical events, involving the cyclic nucleotides and Ca 2+. These 'second fined to the Purkinje cell. Perhaps the messenger' systems may occur in a variety o f neuronal, glial, vascular or connective tissue immunocytochemical procedure for cell types in the brain. This" review examines the advantages and complexities o f localizing cAMP fails to detect the nuimmunocytochemical techniques used to identify the cellular and sub-cellular localization cleotide at sites other than the Purkinje cell o f cyclic nucleotides, their receptor proteins and calmodulin. and granule cell due to loss of material Neurotransmitters are known to exert a duced inhibition of Purkinje cell firing, from the tissue sections during processing. The sub-cellular localization of the subvariety of actions in the CNS including which was mimicked by the extracellular modification of membrane excitability, cel- iontophoresis of both noradrenaline and units of cAMP-dependent protein kinase lular metabolism and protein synthesisL cAMP. Drugs preventing the enzymatic has been distinguished using immunoThese actions are usually not a direct result breakdown of cAMP increased the dura- cytochemistry. In the Purkinje cell for of receptor interaction, but occur via tion of these effects. Biochemical studies example, R1 is associated with granules in intracellular messengers such as cyclic established that noradrenaline activated a the cytoplasm and nucleus, while staining nucleotides and Ca 2+. Individual cells may B-receptor-sensitive adenylate cyclase in for RII is more diffuse and is additionally contain several of these systems each local- the membrane leading to an increased found on the nuclear membrane. In conized within discrete compartments. The fol- intracellular level of cAMP. These experi- trast, the C subunit is only seen at intralowing discussion considers the application ments also showed that the cellular hyper- nuclear sites, as demonstrated in Fig. 1. The final phase of the cAMP secondof sensitive immunocytochemical pro- polarization induced by noradrenaline was cedures to visualize cyclic AMP, cyclic mediated by a receptor-linked cAMP sys- messenger sequence involves the phosGMP, cyclic nucleotide-dependent protein tem. Application of antibodies against phorylation of enzymes or structural procAMP to frozen sections tT, showed specific teins. Greengard and associates have kinases and calmodulin. staining within the Purkinje cells and in the shown that one of these proteins, desigThe cyclic AMP system nuclei of granule cell interneurones. Sub- nated protein I, is an important substrate Immunocytochemical techniques were sequent experiments employing topical for cAMP-dependent protein kinase in the first used for studying second messenger application of noradrenaline to the cerebel- CNS. Recent immunocytochemical studies systems in 1972, when cAMP was iden- lar cortex, or stimulation of locus at the electron microscope level t demontified in specific neurones of the cerebel- coereleus, selectively increased the strate that protein I is localized to synaptic lum, and staining in one cell type was number of Purkinje cells staining for vesicles and the post-synaptic membrane at certain synapses, indicative of a possible shown to be modified by neurotransmitter cAMP between five and seven fold TM. The actions of cyclic nucleotides are role in neurotransmission. Furthermore. action 16. Bloom and co-workers had previously established that the cerebellar Pur- mediated by specific receptor proteins or biochemical studies indicate that depolarizkinje cell received, in addition to the classi- kinases ~°. Greengard's group at Yale and ing agents, as well as convulsant and decally described climbing and parallel fibre other workers have shown that cAMP- pressant drugs, determine whether the proinnervation, a noradrenergic input from dependent protein kinase exists in two tein is in the phosphorylated or de-phosthe nucleus locus coereleus. Electrical forms with different regulatory subunits, phorylated form. The state of phosphorylastimulation of the locus coereleus pro- but similar catalytic subunits (see box). tion of this protein therefore offers a
RichardCumming
j) [ilse~ier/Ntlrth-Holland Biom,-dicalPress lt~Sl O378 qg12/SJ/OOOO-O[)OO[$O2.SO
TINS - A u g u s t 1 981 dopaminergic properties of neuroleptics, the implication was that an asymmetry in basal ganglia dopamine, similar to that observed in rats, would be identified in humans. Supporting this and other inferences, direct evidence of neurochemical asymmetries in post-mortem human brain has now been obtained (Glick, Ross and Hough, unpublished). Asymmetries in gamma-aminobutyric acid and choline acetyltransferase were observed in both cortical and subcortical structures. Of special interest was that dopamine was found to be significantly higher in the left than in the right globus pallidus with the average asymmetry in basal ganglia dopamine levels approximately twice that observed in the rat. Pallidal dopamine levels in humans were higher on the side contralateral to hand preferences just as striatal dopamine levels are higher on the side contralateral to side preferences in rats. Another commonality between species was reported by Oke and colleagues, who demonstrated left-right asymmetries in norepinephrine content in both rat and human thalamus. Using the labeled deoxyglucose technique in rats, we discovered, as noted above, a relationship between activity of a structure and its left-right bias, with fight bias being associated with higher activity and vice-versa. Similarly, a relationship between dopamine levels and left-right dopamine asymmetries was evident in human basal ganglia, with greater dopamine being associated with a right bias and less dopamine with a left bias. These kinds of relationships suggest that brain asymmetry is a dynamic process, depending, in part, on the activity of a particular system as a whole. Treatments which specifically increase or decrease activity of a system should then have predictable effects on the left-right asymmetry of the same system. More importantly, it is now clear that the same predictions apply equally to both rats and humans and that studies in the rat may reveal mechanisms and functions of brain asymmetry that are relevant to humans. A similar view was espoused almost a century ago: 'The idea that the distinction between right and left depends upon an asymmetry, and possibly in the last resort upon a chemical difference, is one which has been present to me from my earliest years . . . Human beings and animals that have lost their direction move, almost without exception, nearly in circle.., we have here a teleological device to help parents to find their hungry young again when they have been lost.' (From Ernst Mach (1885) The Analysis of Sensations. )
Acknowledgements This work was supported by Grants NS 14812 and DA 01044 and by Research Scientist Development Award DA 70082 to S.D.G.
Reading list 1 Anden, N. E., Dahlstrom,A., Faxe, K. and Larsson, K. (1966) Acta Pharmacol. Toxicol. 24, 263-274 2 Denenberg, V. H., Garbanati, J., Sherman, G., Yutzey, D. A. and Kaplan, R. (1978)Science 201, 1150-1152 3 Diamond, M. C., Johnson, R. E. and Ingham, C. A. (1975) Behav Biol. 14, 163-174 4 Flor-Henry,P. (1976)Ann. N.Y. Acad. Sci. 280, 777-795 5 Gainotti,G. (1972) Cortex 8, 41-55 6 Galaburda,A. M., LeMay,M., Kemper,T. L. and Geschwind,N. (1978) Science 199, 852-856 7 Glick, S. D. and Cox, R.D. (1976)J. Comp. Physiol. Psychol. 90, 528-535 8 Glick, S. D. and Cox, R. D. (1978) Brain Res. 150, 149-161 9 Glick, S. D., Jerussi, T. P. and Zimmerberg, B. (1977) in Lateralization in the Nervous System (Harnad, S., Doty,R. W., Goldstein, L., Jaynes,J. and Krauthamer, G., eds.), pp. 213-249, Academic Press,New York 10 Glick, S. D., Meibach, R.C., Cox, R.D. and Maayani, S. (1979) Life Sci. 25,395-400 11 Glick, S. D. and Ross, D. A. (1981)Brain Res. 205,222-225 12 Glick, S. D., Schonfeld, A. R. and Strumpf,A. J. (1980) Behav. Brain Sci. 3,236 13 Glick, S. D., Weaver, L. M. and Meibach, R. C. (1980)Science 207, 1093-1095 14 Glick, S. D., Weaver, L. M. and Meibach, R. C. Psychopharmacology (in press)
15 Gruzelier, J. H. and Flor-Henry, P. (1979) Hemisphere Asymmetries and Psychopathology, Elsevier, Amsterdam 16 Gur, R. E. (1978) J. Abnorm. Psychol. 87, 226-238 17 Jerussi, T. P., Glick, S.D. and Johnson, C. L. (1977) Brain Res. 129, 385-388 18 Levy, J. (1977) Ann. N.Y. Acad. Sci. 299. 264-272 19 Ross, D. A. and Glick, S. D. (1981) Brain Res. 210, 379-382 20 Ross, D. A., Glick, S. D. and Meibach, R. C. (1981) Proc. Natl Acad. Sci. U.S.A. 78, 1958-1961 21 Ross, D. A., Glick, S. D. and Meibach, R. C. (1981) Fed. Proc. Fed. Am. Soc. Exp. Biol. 40, 251 22 Rothman, A. R. and Glick, S. D. (1976) Brain Res. 188, 361-369 23 Sokoloff, L., Reivich, M., Kennedy, C., Des Rosiers, M. H., Patlak, C. S., Penigrew, K. D., Sakurada, O. and Shinohara. M. (1977) J. Neurochem. 28, 897-916 24 Ungerstedt,U. (1971)Acta Physiol. Scand. SuppL 367, 49-93 25 Warren, J. M. (1981)) Physiol. Psychol. 8, 351-359 26 Waziri, R. (I980) Psychopharmacology 68. 51-53 27 Wexler, B. F. and Heninger, G. R. (1979)Arch. Gen. Psychiatry 36, 278-284 28 Wilson,S. A. K. (1914) Brain 36, 425-492 29 Witelson,S. F. (1976) Science 193,425-427 30 Zimmerberg,B., Strumpf,A. J. and Glick, S. D. (1978) Brain Res. 140, 194-196 S. T. Glick and D. A. Ross are at the Department of Pharmacology, Mount Sinai School of Medicine, City University of New York, One Gustave L. Levy Place, New York, NY 10029.
Co-ordination between posture and movement Yves Gah~ry and Jean Massion Even a simple and small movement o f a part o f the body is a component o f a complex pattern o f muscular activity, which involves not only muscles directly producing the observed movement but also other muscles often remotely located from the moving part. This latter group is responsible for the postural component o f the motor act. In this article we will examine how these two components o f motor acts, i.e. movements and their associated postural adjustment are co-ordinated. At any given time body posture is a function of the position of the different joints. The muscles with their visco-elastic properties ensure the rigidity of the joints, and thus the skeleton. They must continuously oppose the gravity force to which the body is submitted. Movement of a body segment is itself the source of a perturbation of posture and equilibrium. The displacement of a segment usually results in a displacement of the center of gravity, and therefore disequilibrium, which must be prevented. For example, Fig. l shows how raising both arms is accompanied by a backward displacement of head and trunk,
which maintains in the horizontal plane the position of the center of gravity with regard to the basis of support. Besides these static aspects, the moving segment exerts dynamic forces against the rest of the body. In the example in Fig. 1, raising the arms forwards requires forces to be directed forwards and upwards. Consequently, forces of equal magnitude, but acting in the opposite direction, are exerted on the trunk and must be opposed by muscle contraction. Thus, a motor act is composed of two parts, which were called by Hess TM 'teleokinetic' for the directed moving phase and 'ereismatic' for the postural, or Elsevier/North-Holland Biomedical O 3 7 8 - 5 9 1 2 / 8 1 / 0 0 0 0 - lll)Ol}/$02.~l)
P r e s s 1981
200 supporting component which prevents the displacement of the center of gravity and resists the dynamic forces that arise as a consequence of the movement.
Properties of postural adjustment Several types of postural adjustment were observed in humans. Babinski 4 was one of the first people to describe the adjustment of posture during the performance of movement. When a normal subject is asked to bend backwards, the knees flex forwards simultaneously. These opposing displacements tend to keep the center of gravity in its original position. In contrast, patients with 'asynergia' bend the head and back but do not compensate by flexing the knees, and thus fall backwards. Postural adjustments have been described for standing subjects performing various movements, such as respiration TM or limb movements ~,5,6.~2,a'~,~4 and when resisting external perturbations2*.2L The description of these postural changes includes electromyographic (EMG) data, measurement of joint displacement and the recording of vertical and horizontal forces exerted by the subject standing upon force platforms. Postural adjustment also occurs in quadrupeds, and provides an interesting model for analysing postural changes associated with limb movement. Gray TM compared the quadruped to a four-legged table whose rigidity could be modified t "" " along the back and betwee the legs. Movement of changes the distribution of 1 on the remaining three li~ urements of the vertical fo each provide a reasonable i change in posture. Myog and their latencies prm information. When a rigid table, ba force platforms, suddenly supports, the weight is distr the remaining pair of diag~ legs, whilst the leg diagom ported one becomes unk Ioffe and Andreyev ~7were that this 'diagonal pattern' occurs in dogs lifting one '. this pattern is not merely rigid body conforming t mechanics as was the cas~ There is in addition feedt over the postural changes, changes involved often pr{ of the limb'. Moreover, in limbs, myographic activity preceoes me force changes.
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This diagonal pattern of support is most pronounced when a limb is unexpectedly unloaded, e.g. by dropping a supporting platform, or applying a horizontal force to the limb in a forward or backward direction. Electrical stimulation of certain regions of the brain, such as the motor cortex or red nucleus, also produces single limb flexion with a diagonal support 7'9. From a functional point of view, this pattern permits a limb to be displaced without changing the position of the center of gravity. Consequently, the main orientation of the body is unchanged. However, this pattern. being bipedal, is unstable. When an animal is trained to raise a limb, a different, non-diagonal pattern of postural adjustment is observed 7'2°(Fig. 2). Only two limbs participate in the adjustment, the unloaded limb and its contralateral counterpart to which the weight is transferred. The postural adjustment is thus restricted to the forelimbs in the case of a forelimb movement, or to the hindlimbs for a hindlimb movement. Concurrently, there is a displacement of the center of gravity towards the site opposite to the moving limb. This non-diagonal support, being distributed on three legs, is more stable than the diagonal one. Both in humans and quadrupeds several interesting features characterize the postural adjustment associated with movement.
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As first shown by Belenkii et al. ~ postural adjustment is initiated shortly before the movement (Fig. 3), anticipating the disequilibrium that the movement would have provoked. EMG changes in the muscles of the supporting leg or arm precede those of the prime mover of the displacing segment by some 30-50 ms ~,~,2~,24"2~. Another characteristic of postural adjustment is its adaptability, clearly apparent from the observations of Gurfinkel et al.t2. They noted that for subjects confined to bed for a few weeks, postural adjustment disappeared but quickly returned when mobility was restored. The form postural adjustment takes depends on the way the body is supported initially. It mainly involves the legs when the subject is standing and is observed in the arms 2x,24 when they are supporting the body. In the cat, during limb flexion induced by motor cortex stimulation, postural adjustment is also influenced by the initial posture "~9
Hierarchical organization One of the purposes of postural adjustment is to maintain equilibrium during movement. The 'feedforward' postural command must take into account parameters such as velocity, direction and amplitude, in order to be efficient. Thus, areas of the brain which participate in the control of movement can also be expected to con-
kig. 1. Postural changes observed in man whih" raising both arrn,s. M)tice that the line passes in front o f the ear when the arms are raised (accordingto Martin~2).
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NON DIAGONAL
1
Fig. 2. Two patterns o f postural adjustment in the quadruped.
pyramidal and rubrospinal tracts converge. Once again, the buibospinal level qualifies as a good candidate for this site. Finally, data from animals with lesions to the motor cortex 16." also favor the hypothesis that postural adjustments are organized at a low level. Unilateral lesions to the motor cortex depress contralateral movement and the associated postural adjustment, even if the latter involves both contralateral and ipsilateral musculature. Is there any indication that a neuralnetwork controlling postural adjustment exists at the bulbospinal level? As described by Sherrington ~ besides the crossed extensor reflex, in the decerebrate animal, there is a co-activation of flexors of diagonally opposite limbs, and this could provide a basis for the diagonal pattern of postural adjustment seen in quadrupeds. Whilst the basic mechanisms of postural adjustment could be organized at this level their execution appears to be regulated by several loops passing through cerebellum, such as the cerebello-rubrospinal pathway or the cerebello-thalamo-cortical pathways~.2L In that respect, regulation of the postural adjustment would be organized in a manner comparable to locomotion itself". Let us now shift our attention to the regions of the brain involved in movement preparation and initiation (Fig. 4), since reports of human pathological cases favor their contribution to postural adjustment. Babinski4 mentioned that asynergy was associated with cerebellar lesions, although this assertion has since been questioned by other authors 2,". Involvement of the basal ganglia was proposed by Martin2L and more recently by Traub et al. ~ on the basis of an examination of the parkinsonian patients. Finally, Gurfinkel et aL ~ observed a deficiency in the postural changes associated with respiratory movements in patients with lesions to the
tribute to postural adjustment. According to the schema for central organization of movement proposed by Allen and Tsukahara 2, certain regions are responsible for movement preparation and initiation (association cortical areas, neocerebellum, basal ganglia) whilst others are concerned with movement execution (motor cortex and its descending pathways, rubrospinal and vestibulospinal tracts, older parts of cerebellum). Are postural adjustments executed by areas associated with movement execution, or are they controlled by areas involved in movement preparation and initiation? From experiments in humans and quadrupeds, it appears that postural adjustment is associated with the execution of movement at a low, possibly bulbospinal level~ (see Fig. 4). In humans, this relationship is suggested by latent EMG measurements made when resisting externally applied changes in arm position ",~. Here the latency of onset of EMG response makes improbable long reflex pathways extending above the spinal level. A similar relationship was observed for an adjustment provoked by single limb perturbation in quadrupeds. Here, EMG latencies were as short as 15 ms, which clearly excludes a long supraspinal route. Experiments involving direct stimulation of the motor cortex or red nucleus also favor a low level basis for the organization CENTRAL ] COMMAND of postur~/l adjustment. When a movement . _ is produced by directly stimulating the Feedforword motor cortex and the red nucleus, it is accompanied by a diagonal postural adjustment, which is, according to latency measurements, initiated in a feedforward manner. These results could be interpreted by supposing that each stimulated site incorporates neural networks which control the movement and the associated postural changes. Although a more likely interpretation is that the postural changes are organized somewhere along the descending pathways at a site where the Fig. 3. Feedforward and feedback postural adjustment.
,
i
1
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,
MOVEMENT / PREPARATION Anociotlorlar~.i [ Basal 9(mglio [I NeocerebellumI1
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Fig. 4. Central control o f postural adjustment. As illustrated by the schema, movement and posture would be linked at a 'low hierarchical level', probably the bulbospinal level. One or most likely several patterns o f posmral ad]ustmem are organized there (Posture: pattern 1, 2, others). The selection ofthe appropriate postural pattern would take place during movement 'preparation' and 'initiation'.
frontal cortex. However, these data do not provide any indication of how these particular structures might contribute to postural adjustment. Experiments in quadrupeds suggest that the choice of an appropriate postural pattern occurs during movement preparation and initiation. Which pathways make this selection? The question is still open, though there is experimental evidence from Ioffe ts that the pyramidal tract may be involved. Conclusion
To conclude, the postural adjustment which during movement performance controls the center of gravity position and counteracts the dynamic forces exerted by the moving segment appears to be organized at two levels. At a low hierarchical level one or several circuits are available which automatically provide a postural adjustment when a movement is triggered by central or sensory inputs. In turn these circuits are under the control of higher level structures which adapt the postural adjustment to each intentional movement. The schema proposed for the central organization of the co-cordination between posture and movement is Still provisional, and one may wish that further experimentation will complete and improve the understanding of this problem.
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Reading list
1 Alexeiev,M. A. and Naidel, A. V. (1972) Zh. Physiol. U.S.S.R. 58, 1721-1730 2 Allen, G. I. and Tsukahara, N. (1974) Physiol. Rev. 54, 957-1006 3 Andr6-Thomas(1940) Equilibre et #quilibration, 567 pp., Masson,Paris
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4 Babinski,J. (1899) Rev. Neural. 7. 806-816 5 Belenkii, V. E., Gurfinkel, V. S. and Paltsev, E. 1. (196 7) Biophysics, 12,154-161 6 Bouisset, S. and Zanara, M. 11981) Neurosci. Lett. 22. 263-270 7 Oah~ry, Y,, loffe, M., Massion, J. and Polii, A, (1980) Acta Neurobiol. Exp, 40. 741-756 8 Gah6ry, Y. and Legallet, E. (1978) Neurosci. Lett. Suppl. 1, S 124 9 Gah6ry, Y, and Nieoullon, A. (1978) Brain Re,~. 149, 25-37 10 Gray, J. (1944) J. Exp. Biol. 21J, 88-116 11 Grillner, S. (1975) Physiol. Rev. 55,247-31t4 12 Gurfinkel, V. S., Kots, J. M., Pahsev. F. I. and Feldman, A. G. (1971 ) in Models o f the structural fimctional organization o f certain biological system.s (Gelfand, 1. M., Gurfinkel. V. S., Fomin. S. V, and Tsetlin. M. L., eds). pp. 382-395. MIT Press, Cambridge, Mass. 13 Hess, W. R. (1943) Helv. Physiol. Phurmacol.
Acta, 1, C62~C'63 14 Holmes, O. (1939) Brain, 62, 1-311 15 Ioffe. M. E. (1973 ) Physiol. Behav. 1 l, 145-153 16 Ioffe, M. E. (1975) Cortieospinal mechanisms o f imtrumental motor reactions (in Russian), Nauka, MOSCOW 17 Ioffe, M. E. and Andreyev, A. E. 11969) Zh. Vy~sll, Nervn. Deyat. ira. L P. Pnvlova, 19, 557-565 18 Jung. R. ( 1981 ) in Advances in Physiol. Sci. (Szentagothai, J., Hamori, J. and Palkovits. M., eds), Vnl. I, Pergamon Press, New York 19 Legallet. E. and Gah6ry, Y. (1980) Exp. Brain Res. 40, 35-44 20 I~acPherson, J. E., Dufoss6, M. and Massion, 3. (1980) Soc. Neurosci. A bstr. 6, 464 21 Marsden, C. D., Merton P. A. and Morton, H. B. ( 1978)J. Physiol. (London), 275, 47-48P 22 Mar6n, J. P. (196 7) The basal gangliu und posture. Pilman, London
Immunocyt mistry of second mes nger systems
23 Massion, J. 11979) in Integration in the nervous system (Asanuma. H. and Wilson, V. J . eds), pp. 239-2611, Igaku-Shoin, Tokyo-New York 24 Nashner, L. M, and Cordo, P. J. (1980) Soc. Neurosci. Abstr. 6, 394 25 Padel, Y. and Steinberg, R. 11978)J. Physiol. (Paris), 74,265-282 26 Sherrington, C. S. (1906) The Integrative Actmn o f the ,Nervous System, Constable. London 27 Smith, A. M., Masskm, J., Gahdry, Y. and Roumieu. J. (1978) Brain Res, 149. 329-346 28 Traub, M. M., Rothwell. J. C. and Marsden, C. D. (19811) Brain, 1113. 393-412
Yve~ GahOo, and Jean Massion are at the DOpartement de Neurophysiologie G#n~rale, C.N.R.S.-I.N.P.5, 31 chemin Joseph-Aiguier, 13274 ,'¢lurseille Cedex 2, France.
Antibodies prepared against the purified subunit proteins from bovine tissues demonstrate partial similarity to rat tissue antigens, allowing the immunocytochemical localization of t h e ~ molecules to be determined in the rat CNSL In the cerebellar cortex, the regulatory (RI and Rll) and catalytic (C) subunits are observed in neurones and gila, suggesting that the The physiological response o f a cell to a neurotransmitter is dependent upon a chain o f physiological effects of cAMP are not conintracellular biochemical events, involving the cyclic nucleotides and Ca 2+. These 'second fined to the Purkinje cell. Perhaps the messenger' systems may occur in a variety o f neuronal, glial, vascular or connective tissue immunocytochemical procedure for cell types in the brain. This" review examines the advantages and complexities o f localizing cAMP fails to detect the nuimmunocytochemical techniques used to identify the cellular and sub-cellular localization cleotide at sites other than the Purkinje cell o f cyclic nucleotides, their receptor proteins and calmodulin. and granule cell due to loss of material Neurotransmitters are known to exert a duced inhibition of Purkinje cell firing, from the tissue sections during processing. The sub-cellular localization of the subvariety of actions in the CNS including which was mimicked by the extracellular modification of membrane excitability, cel- iontophoresis of both noradrenaline and units of cAMP-dependent protein kinase lular metabolism and protein synthesisL cAMP. Drugs preventing the enzymatic has been distinguished using immunoThese actions are usually not a direct result breakdown of cAMP increased the dura- cytochemistry. In the Purkinje cell for of receptor interaction, but occur via tion of these effects. Biochemical studies example, R1 is associated with granules in intracellular messengers such as cyclic established that noradrenaline activated a the cytoplasm and nucleus, while staining nucleotides and Ca 2+. Individual cells may B-receptor-sensitive adenylate cyclase in for RII is more diffuse and is additionally contain several of these systems each local- the membrane leading to an increased found on the nuclear membrane. In conized within discrete compartments. The fol- intracellular level of cAMP. These experi- trast, the C subunit is only seen at intralowing discussion considers the application ments also showed that the cellular hyper- nuclear sites, as demonstrated in Fig. 1. The final phase of the cAMP secondof sensitive immunocytochemical pro- polarization induced by noradrenaline was cedures to visualize cyclic AMP, cyclic mediated by a receptor-linked cAMP sys- messenger sequence involves the phosGMP, cyclic nucleotide-dependent protein tem. Application of antibodies against phorylation of enzymes or structural procAMP to frozen sections tT, showed specific teins. Greengard and associates have kinases and calmodulin. staining within the Purkinje cells and in the shown that one of these proteins, desigThe cyclic AMP system nuclei of granule cell interneurones. Sub- nated protein I, is an important substrate Immunocytochemical techniques were sequent experiments employing topical for cAMP-dependent protein kinase in the first used for studying second messenger application of noradrenaline to the cerebel- CNS. Recent immunocytochemical studies systems in 1972, when cAMP was iden- lar cortex, or stimulation of locus at the electron microscope level t demontified in specific neurones of the cerebel- coereleus, selectively increased the strate that protein I is localized to synaptic lum, and staining in one cell type was number of Purkinje cells staining for vesicles and the post-synaptic membrane at certain synapses, indicative of a possible shown to be modified by neurotransmitter cAMP between five and seven fold TM. The actions of cyclic nucleotides are role in neurotransmission. Furthermore. action 16. Bloom and co-workers had previously established that the cerebellar Pur- mediated by specific receptor proteins or biochemical studies indicate that depolarizkinje cell received, in addition to the classi- kinases ~°. Greengard's group at Yale and ing agents, as well as convulsant and decally described climbing and parallel fibre other workers have shown that cAMP- pressant drugs, determine whether the proinnervation, a noradrenergic input from dependent protein kinase exists in two tein is in the phosphorylated or de-phosthe nucleus locus coereleus. Electrical forms with different regulatory subunits, phorylated form. The state of phosphorylastimulation of the locus coereleus pro- but similar catalytic subunits (see box). tion of this protein therefore offers a
RichardCumming
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