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Tremor of Parkinsonism and Stereotactic Thalamotomy
Editorial Tremor of Parkinsonism and Stereotactic Thalamotomy The issue of Parkinson's disease, stereotactic sur gical procedures, and the involved technology is timely (see the article by Kelly and associates in this issue of the Proceedings, pages 655 to 664). Parkinson's disease is a common condition, with a prevalence rate in Western societies as high as 179.8 per 100,000 population. As many as 700 to 1,000 persons per 100,000 population older than 80 years of age apparently suffer from the dis ease. 1 Moreover, it has not shown signs of de clining despite the virtual disappearance of the postencephalitic form of the disease. Levodopa.—Even with our best endeavors, Parkinson's disease remains incurable, progres sively disabling victims despite optimal therapy. Although cure or arrest of the disease has thus far been elusive, the quality of life has been infinitely better for those with parkinsonism since the pioneering work of Birkmayer and Hornykiewicz, 2 Barbeau and colleagues, 3 and others, which has led to contemporary therapy with levodopa. Underlying Mechanisms for Tremor.—The remarkable effectiveness of levodopa should not obscure an important fact. For a long time, in vestigators have recognized that the pathophys iologic mechanisms of parkinsonian tremor and of the akinesia to which levodopa and the nigrostriatal pathway relate differ, no more clearly demonstrated than in the correlative studies of pathologic and neurochemical changes con ducted in simian models of the disease by Poirier and associates. 4 MPTP (l-methyl-4-phenyl1,2,3,6-tetrahydropyridine), the specific neurotoxin for dopamine cells, induces a devastating parkinsonian syndrome in which tremor does not predominate. In fact, the pathophysiologic mech anism of parkinsonian tremor remains obscure, and we lack a specific drug for the tremor.
Address reprint requests to Dr. R. R. Tasker, Division of Neurosurgery, Toronto General Hospital, Toronto, Ontario, Canada M5G 2C4. Mayo Clin Proc 62:736-739, 1987
Thalamotomy.—An alternative treatment for truly disabling parkinsonian tremor is available in the form of thalamotomy, which, when used in appropriately selected patients and with con temporary technology, exposes them to at least no more morbidity and inconvenience than pro longed multiple drug trials. Even though the ultimate goal is to replace surgical intervention with noninvasive therapy, one ought not ignore operative treatment when a good technique is available and no medical substitute exists. It is perhaps unfortunate that in the fervor of the early 1960s before the advent of modern drug therapy, many suboptimal candidates underwent stereotactic procedures simply because physi cians wanted to help and no better treatment modality was available. Those early experiences sullied the reputation of stereotactic surgical procedures and, understandably, stimulated a counterreaction to them that persists to this day. Not only is stereotactic thalamotomy effective for treating tremor but also the results are usually permanent. Moreover, reduction in tremor is ac companied by substantial relief of rigidity and protection against levodopa-induced dyskinesia, all on the side of the body opposite the thalamic lesion. One important matter still needs further attention. Matsumoto and colleagues 5 in Tokushima, Japan, reactivated an old issue by noting, in a 10-year or longer follow-up, that 31 of 64 patients operated on unilaterally and 14 of 22 patients operated on bilaterally seemed protected from progress of their disease postoperatively. This important issue certainly needs immediate attention from other groups. Technologic Advances.—Today, extraordi nary advances in technology have brought within the reach of every neuroscience center the potential for intraoperative computer graphics displays to assist in visualizing the advance of the probe through the anatomic framework of the brain, a potential developed by the pioneering efforts in the field.6,7 Relatively early in the de velopment of this technique, it became possible to add to that display the wealth of physiologic data collected to guide the surgeon, as was done in a modest way by our own group. 8 Currently, stereotactic coordination of such computer dis-
736
Mayo Clin Proc, August 1987, Vol 62
plays with data collected from various imaging techniques, including angiography, is possible; thus, the surgeon can, on the one hand, instantly select the stereotactic coordinates of any desired structure and, on the other, review any phase of the penetration of the probe, appreciating its impingement and that of the lesion he intends to make on nearby sensitive brain structures that have been identified by both imaging and phys iologic methods. Nowhere have such techniques been better developed than in the stereotactic operating rooms of the Mayo Clinic. Another important technologic aspect is that of physiologic localization. Stereotactic surgical procedures in humans are dependent on five things. First, the stereotactic principle itself had to be developed; in laboratories, it has been ap plied successfully with use of external skull land marks since the turn of the century. Second, a stereotactic atlas was necessary. A method of intracerebral radiologic localization had to be added by Spiegel and associates 9 before stereo tactic procedures became practical in humans; external skull landmarks alone were not enough. The evolution of computer-assisted stereotactic operations has been mentioned. Finally, from the very start, it became apparent that physiologic identification of target sites was essential be cause of the astonishing variability of location of functional structures representing each part of the body within the structural fabric of the brain. Cerebral cortical mapping had shown how great the variability could be, 10 and deep brain struc tures were no exception. Initially, macrostimulation or the recording of evoked potentials was used to confirm that the surgeon's probe rested in the intended structure, but the large electrodes used introduced, through spread of the current, a certain element of inaccuracy. This difficulty was overcome early in the history of human stereotactic surgical techniques when Guiot and Albe-Fessard and their group 11,12 introduced the use of microelectrodes. At once, this microelectrode technique over came two problems. Because it allowed the recog nition of brain structures by the spontaneously evoked activity of the neurons they contained, it provided an objective method of localization not dependent on patient cooperation. Furthermore, because of the recording technique and the small electrode tip, the problem created by spread of current was largely overcome. Although adopted
EDITORIAL
737
profitably by Narabayashi in Tokyo, Ohye in Maebashi, and G. Bertrand at the Montreal Neurological Institute and continued by J. Hardy, C. Bertrand, and Martinez at the Univer sity of Montreal, the microelectrode technique did not achieve wide acceptance until relatively re cently. In fact, the first meeting of the Study Group on the Use of Microphysiological Record ings During Stereotactic Surgery will be held on September 4 through 6, 1987, at Evian les Bains, France. Application of Microelectrode Techniques in Patients With Parkinsonism.—With a microelectrode, single human neurons can be identified and discriminated on-line during stereotactic operations, and the findings can be used for objective and accurate localization of the lesion to stop parkinsonian tremor. Practi cally, the tactile neurons in the ventrocaudal nucleus for the contralateral manual digits or lips are located by identifying neurons that respond to tactile stimuli applied to an area as small as a few square millimeters on a digit. Confirmation can be achieved by microstimulation with the same microelectrode at the same site, producing paresthesias usually in the same area as the receptive field with current as low as 3 μΑ. In addition, evoked potentials from stimulation of the median or other nerves or the skin of the face can be recorded with the same microelectrode for correlation. 13 A spin-off of this technique is the ability to record the data on magnetic tape for off-line analysis in the laboratory, which has confirmed that the human tactile nucleus is organized sim ilarly to that of the subhuman primate. 14 The im portant finding with respect to Parkinson's disease is that rostral to these tactile cells lie neurons that respond to contralateral muscle squeezing or joint stretching—so-called kinesthetic cells—and rostral to them again are cells with or without receptive fields that fire in ad vance of a given contralateral voluntary move ment. 15 All these types of cell can behave as tremor cells (originally reported by Guiot and Albe-Fessard and their group 11 ), firing statisti cally significantly synchronously with the con tralateral peripheral tremor (Fig. I). 16 The tremor activity of these kinesthetic cells is evoked, of course, but the "voluntary" cells may fire in advance of the peripheral tremor. Microstimula tion at the site of kinesthetic cells induces either
738
EDITORIAL
Mayo Clin Proc, August 1987, Vol 62
a sense of movement when none occurs or paresthesias, both in the same general area as the receptive field. Microstimulation at sites where voluntary cells are recorded induces either a mo tor contraction in the same muscles as are in-
A
Call 1
-0.9
-2.1
8NR 3 4
5.5
-3.9 1.2
_Lz_=
0
_ Frequency
25Hz
0.8-
Γ "
0.4·
02J -4.0
-3.0
-2.0
-1.0
0
Log 1 0 Spike Autopower
Fig. 1. Spectral cross-correlation analysis of human parkinsonian tremor cells. A, Upper trace depicts thalamic tremor cell spike train; lower trace shows contralateral upper limb electromyogram. B, Autopower (above) and coherence (below) spectra, calculated for the cell in A and two others. Numbers above autopower spectra are tremor frequency values for log of autopower (upper) and signal-to-noise ratio (SNR) (lower). Numbers above coherence spectra represent the coherence at tremor frequency. Circles mark tremor frequency measured from electromyographic spectra. C, Coherence plotted against log of autopower for 59 tremor cells. (From Lenz FA, Tasker RR, Kwan HC, Schnider S, Kwong R, Murphy JT: Crosscorrelation analysis of thalamic neurons and EMG activity in parkinsonian tremor. Appl Neurophysiol 48:305-308, 1985. By permission of S. Karger AG, Basel, Switzerland.)
volved in the voluntary movement, occurring at the onset of the stimulation train, or else a sense of movement. Stimulation at both sites sup presses tremor or occasionally drives it. These findings raise the question about whether kinesthetic cells may consist of lemniscal cells on the one hand and spindle afferents on the other; voluntary cells lie in the dentatothalamocortical pathway. The site at which these tremor cells are identified marks the position for the optimal lesion for the control of parkinsonian tremor—a precise, objective exercise that allows a very small (3- to 5-mm-diameter) lesion to con trol the tremor. The effect, however, is diluted by the presence of other more widespread "tremor cells" that fire synchronously with the tremor but have no recognizable characteristics. Other cells fire rhythmically at rates near, but not synchro nous with, that of the tremor. Although the voluntary tremor cells are cap able, by virtue of connectivity, latency, and physiologic analysis, of acting as "tremor pace makers," systems analysis suggests that the re lationship of the identified tremor cells to tremorogenesis is one of a long loop feedback reflex.17 Much more must be learned about the mechanism of parkinsonian tremor and that of other types of phasic movement disorders. With use of such techniques in properly selected patients with Parkinson's disease, in whom tremor is the major cause of disability, current neurosurgical practice is improving on the results of stereotactic surgical procedures performed with more conventional technology, which, with less than 0.5% mortality and 8% significant mor bidity, was capable of abolishing manual tremor after a 2-year follow-up in 82% of patients. 18 Future Possibilities.—Finally, the report in this issue of the Proceedings by Kelly and asso ciates about their ongoing stereotactic program provides a glimpse of the future. Stereotactic procedures are currently limited by the few de grees of freedom they can exploit—creation of lesions, biopsy, excision of lesions, or insertion of a stimulating electrode for the treatment of a small group of functional disorders such as pain, dyskinesia, and epilepsy. With a better under standing of the neurophysiologic and neurochemical aspects of a wider range of illnesses, coupled with the development of chemical agents that are capable of destroying or augmenting specific neuronal circuits, the scope of stereotaxis will be
Mayo Clin Proc, August 1987, Vol 62
considerably greater. To this spectrum will be added the possibility of stereotactic functional tissue implants. To exploit these applications, however, the stereotactic surgeon of the future will need to have mastered the fields of neurochemistry, neurophysiology, and computer tech niques as well as conventional neurology and neurosurgery. The work in progress in stereotac tic surgical procedures at the Mayo Clinic assures us that the technology is available and waiting. Ronald R. Tasker, M.D. Division of Neurosurgery Toronto General Hospital Toronto, Ontario, Canada
REFERENCES 1. Schoenberg BS: Descriptive epidemiology of Parkinson's disease: disease distribution and hypothesis formula tion. Adv Neurol 45:277-283,1987 2. Birkmayer W, Hornykiewicz O: Der L·Dioxyphenylalanin (=L-DOPA)-Effekt beim Parkinson-Syndrom des Men schen: zur Pathogenese und Behandlung der ParkinsonAkinese. Arch Psychiatr Nervenkr 203:560-574,1962 3. Barbeau A, Sourkes TL, Murphy GF: Les catecholamines dans le maladie de Parkinson. In Monoamines et Systeme Nerveux Central. Edited by J de Ajuriaguerra. Geneve, Georg, 1962, pp 247-262 4. Poirier LJ, Sourkes TL, Bouvier G, Boucher R, Carabin S: Striatal amines, experimental tremor and the effect of harmaline in the monkey. Brain 89:37-52,1966 5. Matsumoto K, Shichijo F, Fukami T: Long-term followup review of cases of Parkinson's disease after unilateral or bilateral thalamotomy. J Neurosurg 60:1033-1044, 1984
EDITORIAL
739
6. Peluso F, Gybels J: Computer calculation of the position of the side-protruding electrode tip during penetration in human brain. Confin Neurol 34:94-100,1972 7. Bertrand G, Thompson C: Computer program to aid the neurosurgeon to locate probes used during stereotaxic surgery. Comput Programs Biomed 2:265-276, 1972 8. Hawrylyshyn P, Rowe IH, Tasker RR, Organ LW: A computer system for stereotaxic neurosurgery. Comput Biol Med 6:87-97,1976 9. Spiegel EA, Wycis HT, Marks M, Lee AJ: Stereotaxic apparatus for operations on the human brain. Science 106:349-350, 1947 10. Penfield W, Boldrey E: Somatic motor and sensory rep resentation in the cerebral cortex of man as studied by electrical stimulation. Brain 60:389-443,1937 11. Guiot G, Hardy J, Albe-Fessard D: Delimitation precise des structures sous-corticales et identification de noyaux thalamiques chez l'homme par l'electrophysiologie st§r£otaxique. Neurochirurgie 5:1-18, 1962 12. Albe-Fessard D, Ariel G, Guiot G: Activitos electriques caracteristiques de quelques structures corobrales chez l'homme. Ann Chir 17:1185-1214,1963 13. Tasker R: Effets sensitifs et moteurs de la stimulation thalamique chez l'homme: applications cliniques. Rev Neurol (Paris) 142:316-326,1986 14. Lenz FA, Tasker RR, Dostrovsky JO, Kwan HC, Murphy JT: Single unit analysis of the ventral nuclear group of human thalamus: somatosensory responses. J Neurophysiol (in press) 15. Lenz FA, Tasker RR, Kwan HC, Dostrovsky JO, Murphy JT: Single unit analysis of the human ventral thalamic nuclear group: activity correlated with active movement. J Neurophysiol (in press) 16. Lenz FA, Tasker RR, Kwan HC, Schnider S, Kwong R, Muriyama Y, Dostrovsky JO, Murphy JT: Single unit analysis of the human ventral thalamic nuclear group: correlation of thalamic tremor cells with the 3-6 Hz component of parkinsonian tremor. J Neuroscience (in press) 17. Schnider SM: Detection of feedback in the central ner vous system of parkinsonian patients using system iden tification techniques. Thesis, University of Toronto, To ronto, 1985 18. Tasker RR, Siqueira J, Hawrylyshyn P, Organ LW: What happened to VIM thalamotomy for Parkinson's disease? Appl Neurophysiol 46:68-83, 1983
Address reprint requests to Dr. R. R. Tasker, Division of Neurosurgery, Toronto General Hospital, Toronto, Ontario, Canada M5G 2C4. Mayo Clin Proc 62:736-739, 1987
Thalamotomy.—An alternative treatment for truly disabling parkinsonian tremor is available in the form of thalamotomy, which, when used in appropriately selected patients and with con temporary technology, exposes them to at least no more morbidity and inconvenience than pro longed multiple drug trials. Even though the ultimate goal is to replace surgical intervention with noninvasive therapy, one ought not ignore operative treatment when a good technique is available and no medical substitute exists. It is perhaps unfortunate that in the fervor of the early 1960s before the advent of modern drug therapy, many suboptimal candidates underwent stereotactic procedures simply because physi cians wanted to help and no better treatment modality was available. Those early experiences sullied the reputation of stereotactic surgical procedures and, understandably, stimulated a counterreaction to them that persists to this day. Not only is stereotactic thalamotomy effective for treating tremor but also the results are usually permanent. Moreover, reduction in tremor is ac companied by substantial relief of rigidity and protection against levodopa-induced dyskinesia, all on the side of the body opposite the thalamic lesion. One important matter still needs further attention. Matsumoto and colleagues 5 in Tokushima, Japan, reactivated an old issue by noting, in a 10-year or longer follow-up, that 31 of 64 patients operated on unilaterally and 14 of 22 patients operated on bilaterally seemed protected from progress of their disease postoperatively. This important issue certainly needs immediate attention from other groups. Technologic Advances.—Today, extraordi nary advances in technology have brought within the reach of every neuroscience center the potential for intraoperative computer graphics displays to assist in visualizing the advance of the probe through the anatomic framework of the brain, a potential developed by the pioneering efforts in the field.6,7 Relatively early in the de velopment of this technique, it became possible to add to that display the wealth of physiologic data collected to guide the surgeon, as was done in a modest way by our own group. 8 Currently, stereotactic coordination of such computer dis-
736
Mayo Clin Proc, August 1987, Vol 62
plays with data collected from various imaging techniques, including angiography, is possible; thus, the surgeon can, on the one hand, instantly select the stereotactic coordinates of any desired structure and, on the other, review any phase of the penetration of the probe, appreciating its impingement and that of the lesion he intends to make on nearby sensitive brain structures that have been identified by both imaging and phys iologic methods. Nowhere have such techniques been better developed than in the stereotactic operating rooms of the Mayo Clinic. Another important technologic aspect is that of physiologic localization. Stereotactic surgical procedures in humans are dependent on five things. First, the stereotactic principle itself had to be developed; in laboratories, it has been ap plied successfully with use of external skull land marks since the turn of the century. Second, a stereotactic atlas was necessary. A method of intracerebral radiologic localization had to be added by Spiegel and associates 9 before stereo tactic procedures became practical in humans; external skull landmarks alone were not enough. The evolution of computer-assisted stereotactic operations has been mentioned. Finally, from the very start, it became apparent that physiologic identification of target sites was essential be cause of the astonishing variability of location of functional structures representing each part of the body within the structural fabric of the brain. Cerebral cortical mapping had shown how great the variability could be, 10 and deep brain struc tures were no exception. Initially, macrostimulation or the recording of evoked potentials was used to confirm that the surgeon's probe rested in the intended structure, but the large electrodes used introduced, through spread of the current, a certain element of inaccuracy. This difficulty was overcome early in the history of human stereotactic surgical techniques when Guiot and Albe-Fessard and their group 11,12 introduced the use of microelectrodes. At once, this microelectrode technique over came two problems. Because it allowed the recog nition of brain structures by the spontaneously evoked activity of the neurons they contained, it provided an objective method of localization not dependent on patient cooperation. Furthermore, because of the recording technique and the small electrode tip, the problem created by spread of current was largely overcome. Although adopted
EDITORIAL
737
profitably by Narabayashi in Tokyo, Ohye in Maebashi, and G. Bertrand at the Montreal Neurological Institute and continued by J. Hardy, C. Bertrand, and Martinez at the Univer sity of Montreal, the microelectrode technique did not achieve wide acceptance until relatively re cently. In fact, the first meeting of the Study Group on the Use of Microphysiological Record ings During Stereotactic Surgery will be held on September 4 through 6, 1987, at Evian les Bains, France. Application of Microelectrode Techniques in Patients With Parkinsonism.—With a microelectrode, single human neurons can be identified and discriminated on-line during stereotactic operations, and the findings can be used for objective and accurate localization of the lesion to stop parkinsonian tremor. Practi cally, the tactile neurons in the ventrocaudal nucleus for the contralateral manual digits or lips are located by identifying neurons that respond to tactile stimuli applied to an area as small as a few square millimeters on a digit. Confirmation can be achieved by microstimulation with the same microelectrode at the same site, producing paresthesias usually in the same area as the receptive field with current as low as 3 μΑ. In addition, evoked potentials from stimulation of the median or other nerves or the skin of the face can be recorded with the same microelectrode for correlation. 13 A spin-off of this technique is the ability to record the data on magnetic tape for off-line analysis in the laboratory, which has confirmed that the human tactile nucleus is organized sim ilarly to that of the subhuman primate. 14 The im portant finding with respect to Parkinson's disease is that rostral to these tactile cells lie neurons that respond to contralateral muscle squeezing or joint stretching—so-called kinesthetic cells—and rostral to them again are cells with or without receptive fields that fire in ad vance of a given contralateral voluntary move ment. 15 All these types of cell can behave as tremor cells (originally reported by Guiot and Albe-Fessard and their group 11 ), firing statisti cally significantly synchronously with the con tralateral peripheral tremor (Fig. I). 16 The tremor activity of these kinesthetic cells is evoked, of course, but the "voluntary" cells may fire in advance of the peripheral tremor. Microstimula tion at the site of kinesthetic cells induces either
738
EDITORIAL
Mayo Clin Proc, August 1987, Vol 62
a sense of movement when none occurs or paresthesias, both in the same general area as the receptive field. Microstimulation at sites where voluntary cells are recorded induces either a mo tor contraction in the same muscles as are in-
A
Call 1
-0.9
-2.1
8NR 3 4
5.5
-3.9 1.2
_Lz_=
0
_ Frequency
25Hz
0.8-
Γ "
0.4·
02J -4.0
-3.0
-2.0
-1.0
0
Log 1 0 Spike Autopower
Fig. 1. Spectral cross-correlation analysis of human parkinsonian tremor cells. A, Upper trace depicts thalamic tremor cell spike train; lower trace shows contralateral upper limb electromyogram. B, Autopower (above) and coherence (below) spectra, calculated for the cell in A and two others. Numbers above autopower spectra are tremor frequency values for log of autopower (upper) and signal-to-noise ratio (SNR) (lower). Numbers above coherence spectra represent the coherence at tremor frequency. Circles mark tremor frequency measured from electromyographic spectra. C, Coherence plotted against log of autopower for 59 tremor cells. (From Lenz FA, Tasker RR, Kwan HC, Schnider S, Kwong R, Murphy JT: Crosscorrelation analysis of thalamic neurons and EMG activity in parkinsonian tremor. Appl Neurophysiol 48:305-308, 1985. By permission of S. Karger AG, Basel, Switzerland.)
volved in the voluntary movement, occurring at the onset of the stimulation train, or else a sense of movement. Stimulation at both sites sup presses tremor or occasionally drives it. These findings raise the question about whether kinesthetic cells may consist of lemniscal cells on the one hand and spindle afferents on the other; voluntary cells lie in the dentatothalamocortical pathway. The site at which these tremor cells are identified marks the position for the optimal lesion for the control of parkinsonian tremor—a precise, objective exercise that allows a very small (3- to 5-mm-diameter) lesion to con trol the tremor. The effect, however, is diluted by the presence of other more widespread "tremor cells" that fire synchronously with the tremor but have no recognizable characteristics. Other cells fire rhythmically at rates near, but not synchro nous with, that of the tremor. Although the voluntary tremor cells are cap able, by virtue of connectivity, latency, and physiologic analysis, of acting as "tremor pace makers," systems analysis suggests that the re lationship of the identified tremor cells to tremorogenesis is one of a long loop feedback reflex.17 Much more must be learned about the mechanism of parkinsonian tremor and that of other types of phasic movement disorders. With use of such techniques in properly selected patients with Parkinson's disease, in whom tremor is the major cause of disability, current neurosurgical practice is improving on the results of stereotactic surgical procedures performed with more conventional technology, which, with less than 0.5% mortality and 8% significant mor bidity, was capable of abolishing manual tremor after a 2-year follow-up in 82% of patients. 18 Future Possibilities.—Finally, the report in this issue of the Proceedings by Kelly and asso ciates about their ongoing stereotactic program provides a glimpse of the future. Stereotactic procedures are currently limited by the few de grees of freedom they can exploit—creation of lesions, biopsy, excision of lesions, or insertion of a stimulating electrode for the treatment of a small group of functional disorders such as pain, dyskinesia, and epilepsy. With a better under standing of the neurophysiologic and neurochemical aspects of a wider range of illnesses, coupled with the development of chemical agents that are capable of destroying or augmenting specific neuronal circuits, the scope of stereotaxis will be
Mayo Clin Proc, August 1987, Vol 62
considerably greater. To this spectrum will be added the possibility of stereotactic functional tissue implants. To exploit these applications, however, the stereotactic surgeon of the future will need to have mastered the fields of neurochemistry, neurophysiology, and computer tech niques as well as conventional neurology and neurosurgery. The work in progress in stereotac tic surgical procedures at the Mayo Clinic assures us that the technology is available and waiting. Ronald R. Tasker, M.D. Division of Neurosurgery Toronto General Hospital Toronto, Ontario, Canada
REFERENCES 1. Schoenberg BS: Descriptive epidemiology of Parkinson's disease: disease distribution and hypothesis formula tion. Adv Neurol 45:277-283,1987 2. Birkmayer W, Hornykiewicz O: Der L·Dioxyphenylalanin (=L-DOPA)-Effekt beim Parkinson-Syndrom des Men schen: zur Pathogenese und Behandlung der ParkinsonAkinese. Arch Psychiatr Nervenkr 203:560-574,1962 3. Barbeau A, Sourkes TL, Murphy GF: Les catecholamines dans le maladie de Parkinson. In Monoamines et Systeme Nerveux Central. Edited by J de Ajuriaguerra. Geneve, Georg, 1962, pp 247-262 4. Poirier LJ, Sourkes TL, Bouvier G, Boucher R, Carabin S: Striatal amines, experimental tremor and the effect of harmaline in the monkey. Brain 89:37-52,1966 5. Matsumoto K, Shichijo F, Fukami T: Long-term followup review of cases of Parkinson's disease after unilateral or bilateral thalamotomy. J Neurosurg 60:1033-1044, 1984
EDITORIAL
739
6. Peluso F, Gybels J: Computer calculation of the position of the side-protruding electrode tip during penetration in human brain. Confin Neurol 34:94-100,1972 7. Bertrand G, Thompson C: Computer program to aid the neurosurgeon to locate probes used during stereotaxic surgery. Comput Programs Biomed 2:265-276, 1972 8. Hawrylyshyn P, Rowe IH, Tasker RR, Organ LW: A computer system for stereotaxic neurosurgery. Comput Biol Med 6:87-97,1976 9. Spiegel EA, Wycis HT, Marks M, Lee AJ: Stereotaxic apparatus for operations on the human brain. Science 106:349-350, 1947 10. Penfield W, Boldrey E: Somatic motor and sensory rep resentation in the cerebral cortex of man as studied by electrical stimulation. Brain 60:389-443,1937 11. Guiot G, Hardy J, Albe-Fessard D: Delimitation precise des structures sous-corticales et identification de noyaux thalamiques chez l'homme par l'electrophysiologie st§r£otaxique. Neurochirurgie 5:1-18, 1962 12. Albe-Fessard D, Ariel G, Guiot G: Activitos electriques caracteristiques de quelques structures corobrales chez l'homme. Ann Chir 17:1185-1214,1963 13. Tasker R: Effets sensitifs et moteurs de la stimulation thalamique chez l'homme: applications cliniques. Rev Neurol (Paris) 142:316-326,1986 14. Lenz FA, Tasker RR, Dostrovsky JO, Kwan HC, Murphy JT: Single unit analysis of the ventral nuclear group of human thalamus: somatosensory responses. J Neurophysiol (in press) 15. Lenz FA, Tasker RR, Kwan HC, Dostrovsky JO, Murphy JT: Single unit analysis of the human ventral thalamic nuclear group: activity correlated with active movement. J Neurophysiol (in press) 16. Lenz FA, Tasker RR, Kwan HC, Schnider S, Kwong R, Muriyama Y, Dostrovsky JO, Murphy JT: Single unit analysis of the human ventral thalamic nuclear group: correlation of thalamic tremor cells with the 3-6 Hz component of parkinsonian tremor. J Neuroscience (in press) 17. Schnider SM: Detection of feedback in the central ner vous system of parkinsonian patients using system iden tification techniques. Thesis, University of Toronto, To ronto, 1985 18. Tasker RR, Siqueira J, Hawrylyshyn P, Organ LW: What happened to VIM thalamotomy for Parkinson's disease? Appl Neurophysiol 46:68-83, 1983