- Email: [email protected]
Mechanisms of voluntary movements
Parkinsonism and Related Disorders 9 (2002) 55–59 www.elsevier.com/locate/parkreldis
Review
Mechanisms of voluntary movements Hans-Joachim Freund* Department of Neurology, Heinrich-Heine-University Du¨sseldorf, Moorenstrasse 5, 40225 Du¨sseldorf, Germany
Abstract Voluntary movements constitute a mixture of drive related, motivational deep brain mechanisms and cortical goal representations. Some recent studies led to a better understanding of these aspects of voluntary motor behaviour. These data are discussed with reference to the pathophysiology of Parkinson’s disease. q 2002 Published by Elsevier Science Ltd. Keywords: Voluntary movements; Neurones; Parkinson’s Disease
Contents 1. The voluntary – automatic dichotomy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. The action – observation matching system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. The role of the medial wall motor areas for self-generated movement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. Repetitive movements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
In the context of this book I will first consider a few general aspects of voluntary movements and the cerebral mechanisms underlying their generation. Thereafter those aspects that are of particular relevance for a better understanding of the pathophysiology of Parkinson’s disease will be discussed. Voluntary movements are self-generated, willed actions. Jackson coined the term ‘least automatic’ movements in order to emphasise the wide range between the least automatic and the automatic, reflexive movements. Voluntary actions are usually regarded as single voluntary motor acts generated by internal drive forces, the ‘urge to move’. The dopaminergic system plays a prominent role for these internally generated movements. Dopamine neurones are an important component of the principle reward systems of the brain and respond to rewards in a manner compatible with the coding of prediction errors. Waelti et al. [1] have recently demonstrated that both behavioural and neuronal learning occurred when dopamine neurones registered a reward prediction error at the time of the reward. It is further known that stimulation of the ventral tegmental area dopamine neurones when paired with an auditory stimulus of a particular tone increased the cortical area and selectivity of the neuronal response in auditory cortex [2]. Stimulation of dopaminergic neurones thus can induce long * Tel.: þ49-211-811-7880; fax: þ49-211-811-8649. E-mail address: [email protected] (H.J. Freund). 1353-8020/02/$ - see front matter q 2002 Published by Elsevier Science Ltd. PII: S 1 3 5 3 - 8 0 2 0 ( 0 2 ) 0 0 0 4 4 - 5
55 56 56 58 58
range cross-area synchronisation of neuronal activity thereby mediating the learning-based grouping of cortical neurones into distributed functional neuronal assemblies. Consequently, the cerebral cortex undergoes remodelling according to the behavioural significance of the sensory input.
1. The voluntary – automatic dichotomy The internal drive forces along with reward and goal directed behaviour are of prime importance for selfgenerated movements. This raises the question about the relation between the neural midbrain mechanisms and the cortical processes associated with conscious awareness. One approach to tackle this problem is the investigation of the temporal relationship between the subjective awareness of the decision to move and the occurrence of the actual physical event. In a classical experiment Libet [3] asked subjects to generate self-paced movements deliberately and to demarcate the moment when they decided to do so. Surprisingly, they assigned this to a time epoch around 250 ms prior to movement onset, whereas the simultaneously recorded Bereitschaftspotential preceded movement onset by 1– 2 s, indicating that the cerebral processes associated with movement preparation were operating well before subjective awareness of the wish to move.
56
H.-J. Freund / Parkinsonism and Related Disorders 9 (2002) 55–59
These experiments already pointed towards a functional dichotomy of the processes underlying self-generated movements with respect to conscious awareness. For visual information processing such a dichotomy is well established. The ventral stream funnels into the temporal lobe structures and is involved in the cognitive processing of visual information. The dorsal stream is action-related. These dorsal route processes remain subconscious whereas the ventral stream underlies our perceptual awareness of what we see. On the basis of this functional dichotomy the question arises how we become aware of our own actions. There is now ample evidence (for survey see [4]) that there is no privileged access to first person knowledge of the mental preparation of the upcoming motor act since we perceive our actions like any other physical event, i.e. after the act. When we steer a car our movements are targeted to adjust its path properly through the ongoing traffic. The way how this is done in terms of motor commands remains totally subconscious: the ongoing executional processes— the movement kinematics and dynamics are automatically adjusted. Voluntary actions are thus represented in terms of their behavioural goals and the percepts they generate. We are aware of the effects of our actions in the environment, but not of the processes determining the biomechanics. This voluntary –automatic dichotomy is further reflected in the different systems of declarative and procedural memory. Since both systems are anatomically distinct, lesions can selectively interfere with either function. The basal ganglia are a major component of the automatic, procedural system. It follows that the cognitive and declarative aspects of motor behaviour that determine our conscious interaction with the environment are processed in parallel to the automatic processing stream that is so severely hampered in basal ganglia disease. In contrast, ventral route functions remain intact so that the recognition of the symbolic content of the observed motor behaviour is preserved. The parietal lobe is a major cortical component of the procedural system. Parietal lesions interfere with the patients’ ability how to organize movements [5]. A recent study on the recognition and imitation of pantomimed motor acts after unilateral parietal and premotor lesions has demonstrated that the comprehension of the symbolic and representational content of motor acts is either only slightly or not disturbed in apraxic patients with parietal lobe lesions [6]. The dissociation between the most pronounced disturbances in the production of movements and relatively preserved comprehension of its symbolic meaning did not favour the hypothesis that apraxic disturbances are routed in a common deficit of the representation of the form or the meaning of a particular action. Rather, the apraxic disturbance in the parietal patient group appeared primarily as a motor production disorder, thus supporting a dissociation between conceptual and production components.
2. The action– observation matching system Voluntary motor behaviour underlies our active interaction with the environment. It also relies on the interaction with other people. For this capacity it is necessary to understand other people’s behaviour and to attribute it to intention or believes to others. Neuroimaging data have shown that this ability is routed in an observation execution matching system that exhibits a functional equivalence between imagining, performing and observing an action [7]. In this context the mirror neurone concept of Rizzolatti et al. [8] has provided new experimental evidence for such an observation execution matching system. Their novel observation was that neurones in ventral premotor cortex (area F5) were activated not only when the monkey performed a particular movement but also when he observed the experimenter or another monkey doing it. This activation was only evoked by the very same movement and not by any others. The mirror neurone concept has recently been extended by experiments on movement observation on humans [9]. These experiments demonstrated that during action observation the same neural structures were recruited which would normally be involved in the execution of the observed action. Consequently, when individuals observe an action they code it in terms of the related voluntary movement. The observed actions were mapped onto the corresponding motor representations of premotor cortex in a somatotopic manner. This activation was not confined to ventral premotor cortex but extended from ventral to dorsolateral premotor cortex in a somatotopic manner. Whenever the movement was object-related a strong parietal activation was seen in addition to the premotor activations. The results support the concept that the parietal lobe is implemented in action related object description even when watching such actions passively. Observing and imitating other people is a powerful way to learn new skills. At variance with a widely held view there is mounting evidence that voluntary movements are organized by means of the representation of the perceptual goals, whereas the motoric processes—even in the case of highly complex movements—are tuned in subconsciously [10].
3. The role of the medial wall motor areas for selfgenerated movement The prominent role of the medial wall motor area, supplementary (SMA) and cingulate motor areas (CMA) for movement initiation has already been known from lesion studies indicating that damage of the medial frontal lobe interferes with the capacity to produce self-generated movements. Unilateral damage usually causes a mild hemiakinesia associated with poverty of speech that resolves within a few weeks. In contrast, bilateral damage causes permanent akinetic mutism resembling severe
H.-J. Freund / Parkinsonism and Related Disorders 9 (2002) 55–59
57
Fig. 1. Distribution of the frequencies at which finger movements are performed during four tactile exploratory tasks (left), and of hand movements during the execution of three manual skills (right). From Kunesch et al., 1998.
akinetic parkinsonism without tremor [11]. In basal ganglia disease akinetic mutistic states are not only seen after dopamine depletion but also in cases with bilateral damage of the pallidum, where ‘loss of the volitional processes’ and a total ‘psychomotor akinesia’ have been described [12,13]. Readiness potential recordings provided further evidence for the significance of the medial wall areas for selfgenerated movements. They demonstrated that the sources of their early components preceded self-generated movements by more than a second [14,15]. The spatial extent of the medial wall areas activated has been demonstrated by functional activation studies mapping cerebral activations during self-generated movements by positron emission tomography and functional MRI [16]. Both motor areas— SMA and CMA—that have strong direct corticospinal
connections were activated during many types of voluntary movements including repetitive alternating movements, bimanual and bipedal movements but also by unilateral limb movements in particular if they were complex. Electrical stimulation has further pinpointed the role of these midline structures for movement initiation. Stimulation of these areas during epilepsy surgery elicited synergistic movements of the limbs and also of the trunk. In addition to these positive motor responses electrical stimulation in particular of the rostral parts also elicited negative motor responses associated with movement or speech arrest [17]. The functional role of these negative motor areas is still elusive. Illustrative cases with alien limb syndromes as they are seen after midline lesions demonstrate how chaotic motor behaviour can be when not
58
H.-J. Freund / Parkinsonism and Related Disorders 9 (2002) 55–59
properly shaped by the interplay between excitation and inhibition.
4. Repetitive movements Much of our motor repertoire consists of serial repetitive highly automized movements. An analysis of these movements has shown that they can be grouped in two types [18]. Although the cyclical performance represented one single common feature of the eight natural manual motor behaviours tested, the consistent difference was in the time domain. Type I movements (Fig. 1) consist of slow alternating finger movements as they are usually employed during object exploration. The four exploratory tasks (tactile recognition of the four objects listed in the figure) scatter in the low frequency domain around 1 Hz whereas type II movements such as tapping, pencil shading and handwriting lie in the range between 4 and 7 Hz. Instead of a broad scatter of frequencies the two types of manual activities showed a surprisingly clear bimodal distribution without any overlap. The grouping into two frequency classes reflects different behavioural goals. The low frequency type I group represents exploratory digital movements performed to collect sensory information. The type II movements are movements of the hand or a prehended object as a whole, as they are also employed during tool-use like hammering or writing. The different performance rates reflect not only differences in the behaviour goals but also of their associated sensory processes. Type I movements are used for collecting focal sensory input from the fingertips during active touch. Type II movements require only preattentive sensory control during highly overlearned fast movements of the whole hand. Obviously, intrinsic oscillators play an important role for the generation of these repetitive rhythmic movements that are also predominant for many basic rhythms such as swimming, flying, walking, hopping, dancing, chewing and the like. These rhythms are known to be generated by central pattern generators in the brain stem. Parkinson’s disease is not only a severe disturbance of movement initiation but also of the performance of these repetitive serial movements. The type II movements lie just below the range of physiological tremor. Since tremor is slowed in basal ganglia and cerebellar disease, the type II movements are slowed along with tremor and therefore are performed below their normal working range. Obviously, this departure from their preferred rate represents a basic pathophysiological mechanism since most repetitive motor behaviour is grossly disturbed. In contrast, the type I movements remain better preserved. Intraoperative recordings in patients with Parkinson’s disease by means of microelectrodes recordings in MPTP monkeys have shown that the normal activity in the internal pallidum (GPI) and subthalamic nucleus (STN) undergoes two typical changes: enhanced synchronisation and an increase in spontaneous activity. The increase in excitatory
glutamatergic STN output to the next processing stages in the GPI drives the inhibitory gabaergic GPI neurones thus arresting the thalamic throughput to motor cortex. The second major abnormality, increased synchronisation, is not only changing the ongoing tonic neuronal activity into burst-like patterns but is slaving other neurones into synchrony. This oversynchronised rhythmic burst activity shows similar rates as tremor. Deep brain stimulation is thought to desynchronise this pathological synchronisation and to decrease the abnormally high spontaneous activity. This modulation of the abnormal neuronal discharge characteristics is a powerful demonstration of the effectiveness of therapeutic neurophysiology.
References [1] Waelti P, Dickinson A, Schultz W. Dopamine-responses comply with basic assumptions of formal learning theory. Nature 2001;412:43–8. [2] Bao S, Chan VT, Merzenich MM. Cortical remodelling induced by activity of ventral tegmental dopamine neurons. Nature 2001;412: 79– 83. [3] Libet B. Conscious vs. neural time. Nature 1991;352:27– 8. [4] Prinz W. How do we know about our own actions? In: Maasen S, Prinz W, Roth G, editors. Voluntary action: an issue at the interface of nature and culture. 2001: in press. [5] Freund H-J. Abnormalities of motor behaviour after cortical lesions in humans. In: Plum F, editor. Handbook of Physiology. Section 1. The Nervous System. Vol. V. Higher Functions of the Brain. Part 2, Bethesda: American Physiology Society; 1987. p. 763–810. [6] Halsband U, Schmitt J, Weyers M, Binkofski F, Gru¨tzner G, Freund HJ. Recognition and imitation of pantomimed motor acts after unilateral parietal and premotor lesions: a perspective on apraxia. Neuropsychologia 2001;39:200 –16. [7] Grezes J, Decety J. Functional anatomy of execution, mental simulation, observation, and verb generation of actions: a metaanalysis. Hum Brain Mapp 2001;12:1–19. [8] Rizzolatti G, Fadiga L, Gallese V, Fogassi L. Premotor cortex and the recognition of motor actions. Cogn Brain Res 1996;3:131–41. [9] Buccino G, Binkofski F, Fink GR, Fadiga L, Fogassi L, Gallese V, Seitz RJ, Zilles K, Rizzolatti G, Freund H-J. Action observation activates premotor and parietal areas in a somatotopic manner: an fMRI study. Eur J Neurosci 2001;13:400–4. [10] Mechsner F, Kerzel D, Knoblich G, Prinz W. Perceptual basis of bimanual coordination. Nature 2001;414:69– 73. [11] Laplane D, Talairach J, Meininger V, Bancaud J, Orgogozo JM. Clinical consequences of corticectomies involving the supplementary motor area in man. J Neurol Sci 1977;34:301 –14. [12] Cairns H. Disturbances of consciousness with lesions of the brainstem and diencephalons. Brain 1952;75:109– 45. [13] Hassler R. Brain mechanisms of intention and attention with introductory remarks on other volitional processes. In: Kornhuber HH, Deecke L, editors. Motivation, Motor and Sensory Processes of the Brain. Progress in Brain Research, vol. 54. Amsterdam: Elsevier Biomedical Press; 1980. p. 585–614. [14] Kornhuber D, Deecke L. Hirnpotentiala¨nderungen bei Willku¨rbewegungen und passiven Bewegungen des Menschen: Bereitschaftspotential und reafferente Potentiale. Pfluegers Arch Gesamte Physiol Menschen Tiere 1965;284:1–17. [15] Ikeda A, Lu¨ders HO, Burgess RC, Shibasaki H. Movement-related potentials recorded from supplementary motor area and primary motor area: role of supplementary motor area in voluntary movements. Brain 1992;115:1017–43.
H.-J. Freund / Parkinsonism and Related Disorders 9 (2002) 55–59 [16] Stephan KM, Binkofski F, Halsband U, Dohle C, Wunderlich G, Schnitzler A, Tass P, Posse S, Herzog H, Sturm V, Zilles K, Seitz RJ, Freund H-J. The role of ventral medial wall motor areas in bimanual co-ordination. A combined lesion and activation study. Brain 1999; 122:351–68. [17] Lu¨ders H, Lesser RP, Morris HH, Dinner DS, Hahn J. Negative motor
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responses elicited by stimulation of the human cortex. Adv Epileptol 1987;16:229 –31. [18] Kunesch E, Binkofski F, Freund H-J. Invariant temporal characteristics of manipulative hand movements. Exp Brain Res 1989;78: 539–46.
Review
Mechanisms of voluntary movements Hans-Joachim Freund* Department of Neurology, Heinrich-Heine-University Du¨sseldorf, Moorenstrasse 5, 40225 Du¨sseldorf, Germany
Abstract Voluntary movements constitute a mixture of drive related, motivational deep brain mechanisms and cortical goal representations. Some recent studies led to a better understanding of these aspects of voluntary motor behaviour. These data are discussed with reference to the pathophysiology of Parkinson’s disease. q 2002 Published by Elsevier Science Ltd. Keywords: Voluntary movements; Neurones; Parkinson’s Disease
Contents 1. The voluntary – automatic dichotomy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. The action – observation matching system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. The role of the medial wall motor areas for self-generated movement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. Repetitive movements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
In the context of this book I will first consider a few general aspects of voluntary movements and the cerebral mechanisms underlying their generation. Thereafter those aspects that are of particular relevance for a better understanding of the pathophysiology of Parkinson’s disease will be discussed. Voluntary movements are self-generated, willed actions. Jackson coined the term ‘least automatic’ movements in order to emphasise the wide range between the least automatic and the automatic, reflexive movements. Voluntary actions are usually regarded as single voluntary motor acts generated by internal drive forces, the ‘urge to move’. The dopaminergic system plays a prominent role for these internally generated movements. Dopamine neurones are an important component of the principle reward systems of the brain and respond to rewards in a manner compatible with the coding of prediction errors. Waelti et al. [1] have recently demonstrated that both behavioural and neuronal learning occurred when dopamine neurones registered a reward prediction error at the time of the reward. It is further known that stimulation of the ventral tegmental area dopamine neurones when paired with an auditory stimulus of a particular tone increased the cortical area and selectivity of the neuronal response in auditory cortex [2]. Stimulation of dopaminergic neurones thus can induce long * Tel.: þ49-211-811-7880; fax: þ49-211-811-8649. E-mail address: [email protected] (H.J. Freund). 1353-8020/02/$ - see front matter q 2002 Published by Elsevier Science Ltd. PII: S 1 3 5 3 - 8 0 2 0 ( 0 2 ) 0 0 0 4 4 - 5
55 56 56 58 58
range cross-area synchronisation of neuronal activity thereby mediating the learning-based grouping of cortical neurones into distributed functional neuronal assemblies. Consequently, the cerebral cortex undergoes remodelling according to the behavioural significance of the sensory input.
1. The voluntary – automatic dichotomy The internal drive forces along with reward and goal directed behaviour are of prime importance for selfgenerated movements. This raises the question about the relation between the neural midbrain mechanisms and the cortical processes associated with conscious awareness. One approach to tackle this problem is the investigation of the temporal relationship between the subjective awareness of the decision to move and the occurrence of the actual physical event. In a classical experiment Libet [3] asked subjects to generate self-paced movements deliberately and to demarcate the moment when they decided to do so. Surprisingly, they assigned this to a time epoch around 250 ms prior to movement onset, whereas the simultaneously recorded Bereitschaftspotential preceded movement onset by 1– 2 s, indicating that the cerebral processes associated with movement preparation were operating well before subjective awareness of the wish to move.
56
H.-J. Freund / Parkinsonism and Related Disorders 9 (2002) 55–59
These experiments already pointed towards a functional dichotomy of the processes underlying self-generated movements with respect to conscious awareness. For visual information processing such a dichotomy is well established. The ventral stream funnels into the temporal lobe structures and is involved in the cognitive processing of visual information. The dorsal stream is action-related. These dorsal route processes remain subconscious whereas the ventral stream underlies our perceptual awareness of what we see. On the basis of this functional dichotomy the question arises how we become aware of our own actions. There is now ample evidence (for survey see [4]) that there is no privileged access to first person knowledge of the mental preparation of the upcoming motor act since we perceive our actions like any other physical event, i.e. after the act. When we steer a car our movements are targeted to adjust its path properly through the ongoing traffic. The way how this is done in terms of motor commands remains totally subconscious: the ongoing executional processes— the movement kinematics and dynamics are automatically adjusted. Voluntary actions are thus represented in terms of their behavioural goals and the percepts they generate. We are aware of the effects of our actions in the environment, but not of the processes determining the biomechanics. This voluntary –automatic dichotomy is further reflected in the different systems of declarative and procedural memory. Since both systems are anatomically distinct, lesions can selectively interfere with either function. The basal ganglia are a major component of the automatic, procedural system. It follows that the cognitive and declarative aspects of motor behaviour that determine our conscious interaction with the environment are processed in parallel to the automatic processing stream that is so severely hampered in basal ganglia disease. In contrast, ventral route functions remain intact so that the recognition of the symbolic content of the observed motor behaviour is preserved. The parietal lobe is a major cortical component of the procedural system. Parietal lesions interfere with the patients’ ability how to organize movements [5]. A recent study on the recognition and imitation of pantomimed motor acts after unilateral parietal and premotor lesions has demonstrated that the comprehension of the symbolic and representational content of motor acts is either only slightly or not disturbed in apraxic patients with parietal lobe lesions [6]. The dissociation between the most pronounced disturbances in the production of movements and relatively preserved comprehension of its symbolic meaning did not favour the hypothesis that apraxic disturbances are routed in a common deficit of the representation of the form or the meaning of a particular action. Rather, the apraxic disturbance in the parietal patient group appeared primarily as a motor production disorder, thus supporting a dissociation between conceptual and production components.
2. The action– observation matching system Voluntary motor behaviour underlies our active interaction with the environment. It also relies on the interaction with other people. For this capacity it is necessary to understand other people’s behaviour and to attribute it to intention or believes to others. Neuroimaging data have shown that this ability is routed in an observation execution matching system that exhibits a functional equivalence between imagining, performing and observing an action [7]. In this context the mirror neurone concept of Rizzolatti et al. [8] has provided new experimental evidence for such an observation execution matching system. Their novel observation was that neurones in ventral premotor cortex (area F5) were activated not only when the monkey performed a particular movement but also when he observed the experimenter or another monkey doing it. This activation was only evoked by the very same movement and not by any others. The mirror neurone concept has recently been extended by experiments on movement observation on humans [9]. These experiments demonstrated that during action observation the same neural structures were recruited which would normally be involved in the execution of the observed action. Consequently, when individuals observe an action they code it in terms of the related voluntary movement. The observed actions were mapped onto the corresponding motor representations of premotor cortex in a somatotopic manner. This activation was not confined to ventral premotor cortex but extended from ventral to dorsolateral premotor cortex in a somatotopic manner. Whenever the movement was object-related a strong parietal activation was seen in addition to the premotor activations. The results support the concept that the parietal lobe is implemented in action related object description even when watching such actions passively. Observing and imitating other people is a powerful way to learn new skills. At variance with a widely held view there is mounting evidence that voluntary movements are organized by means of the representation of the perceptual goals, whereas the motoric processes—even in the case of highly complex movements—are tuned in subconsciously [10].
3. The role of the medial wall motor areas for selfgenerated movement The prominent role of the medial wall motor area, supplementary (SMA) and cingulate motor areas (CMA) for movement initiation has already been known from lesion studies indicating that damage of the medial frontal lobe interferes with the capacity to produce self-generated movements. Unilateral damage usually causes a mild hemiakinesia associated with poverty of speech that resolves within a few weeks. In contrast, bilateral damage causes permanent akinetic mutism resembling severe
H.-J. Freund / Parkinsonism and Related Disorders 9 (2002) 55–59
57
Fig. 1. Distribution of the frequencies at which finger movements are performed during four tactile exploratory tasks (left), and of hand movements during the execution of three manual skills (right). From Kunesch et al., 1998.
akinetic parkinsonism without tremor [11]. In basal ganglia disease akinetic mutistic states are not only seen after dopamine depletion but also in cases with bilateral damage of the pallidum, where ‘loss of the volitional processes’ and a total ‘psychomotor akinesia’ have been described [12,13]. Readiness potential recordings provided further evidence for the significance of the medial wall areas for selfgenerated movements. They demonstrated that the sources of their early components preceded self-generated movements by more than a second [14,15]. The spatial extent of the medial wall areas activated has been demonstrated by functional activation studies mapping cerebral activations during self-generated movements by positron emission tomography and functional MRI [16]. Both motor areas— SMA and CMA—that have strong direct corticospinal
connections were activated during many types of voluntary movements including repetitive alternating movements, bimanual and bipedal movements but also by unilateral limb movements in particular if they were complex. Electrical stimulation has further pinpointed the role of these midline structures for movement initiation. Stimulation of these areas during epilepsy surgery elicited synergistic movements of the limbs and also of the trunk. In addition to these positive motor responses electrical stimulation in particular of the rostral parts also elicited negative motor responses associated with movement or speech arrest [17]. The functional role of these negative motor areas is still elusive. Illustrative cases with alien limb syndromes as they are seen after midline lesions demonstrate how chaotic motor behaviour can be when not
58
H.-J. Freund / Parkinsonism and Related Disorders 9 (2002) 55–59
properly shaped by the interplay between excitation and inhibition.
4. Repetitive movements Much of our motor repertoire consists of serial repetitive highly automized movements. An analysis of these movements has shown that they can be grouped in two types [18]. Although the cyclical performance represented one single common feature of the eight natural manual motor behaviours tested, the consistent difference was in the time domain. Type I movements (Fig. 1) consist of slow alternating finger movements as they are usually employed during object exploration. The four exploratory tasks (tactile recognition of the four objects listed in the figure) scatter in the low frequency domain around 1 Hz whereas type II movements such as tapping, pencil shading and handwriting lie in the range between 4 and 7 Hz. Instead of a broad scatter of frequencies the two types of manual activities showed a surprisingly clear bimodal distribution without any overlap. The grouping into two frequency classes reflects different behavioural goals. The low frequency type I group represents exploratory digital movements performed to collect sensory information. The type II movements are movements of the hand or a prehended object as a whole, as they are also employed during tool-use like hammering or writing. The different performance rates reflect not only differences in the behaviour goals but also of their associated sensory processes. Type I movements are used for collecting focal sensory input from the fingertips during active touch. Type II movements require only preattentive sensory control during highly overlearned fast movements of the whole hand. Obviously, intrinsic oscillators play an important role for the generation of these repetitive rhythmic movements that are also predominant for many basic rhythms such as swimming, flying, walking, hopping, dancing, chewing and the like. These rhythms are known to be generated by central pattern generators in the brain stem. Parkinson’s disease is not only a severe disturbance of movement initiation but also of the performance of these repetitive serial movements. The type II movements lie just below the range of physiological tremor. Since tremor is slowed in basal ganglia and cerebellar disease, the type II movements are slowed along with tremor and therefore are performed below their normal working range. Obviously, this departure from their preferred rate represents a basic pathophysiological mechanism since most repetitive motor behaviour is grossly disturbed. In contrast, the type I movements remain better preserved. Intraoperative recordings in patients with Parkinson’s disease by means of microelectrodes recordings in MPTP monkeys have shown that the normal activity in the internal pallidum (GPI) and subthalamic nucleus (STN) undergoes two typical changes: enhanced synchronisation and an increase in spontaneous activity. The increase in excitatory
glutamatergic STN output to the next processing stages in the GPI drives the inhibitory gabaergic GPI neurones thus arresting the thalamic throughput to motor cortex. The second major abnormality, increased synchronisation, is not only changing the ongoing tonic neuronal activity into burst-like patterns but is slaving other neurones into synchrony. This oversynchronised rhythmic burst activity shows similar rates as tremor. Deep brain stimulation is thought to desynchronise this pathological synchronisation and to decrease the abnormally high spontaneous activity. This modulation of the abnormal neuronal discharge characteristics is a powerful demonstration of the effectiveness of therapeutic neurophysiology.
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