Movement Disorders Vol. 5 , No. 1, 1990, pp. 71-77 0 1990 Movement Disorder Society
Uniform Frequency of Parkinsonian Resting Tremor in the Lips, Jaw, Tongue, and Index Finger *?Chauncey J. Hunker and *?$James H. Abbs *Speech and Motor Control Laboratories, Waisman Center, TDepartment of Neurology, and $Department of Neurophysiology, University of Wisconsin, Madison, Wisconsin, U.S.A.
Summary: Parkinsonian resting tremor was examined in the lips, jaw, tongue, and index finger using electromyography (EMG) and displacement transduction. Long-term spectral averaging of tremor movement and EMG signals revealed that resting tremor frequencies were remarkably uniform across these orofacial and hand structures within the same parkinsonian subjects. However, marked variability in tremor spectral amplitude across structures and subtle moment-to-moment variations in tremor period, amplitude, and waveform shape were also observed. Although these observations argue for a central source of tremor, it appears that interactive central a n d o r peripheral neural circuitry may yield variations in tremor characteristics. Key Words: Parkinson’s disease-Resting tremor-Face-Hand.
to project autogenically to hypoglossal motor neurons within the lower brainstem (7). Inasmuch as the orofacial motor systems (i.e., lips, tongue, jaw) are differentially endowed with muscle spindles, respective lower motor neuron pools seemingly are not influenced uniformly by conventional muscle spindle actions (e.g., long-term synchronization of motor units) (8). Moreover, in motor systems subserved by spindle mediated stretch reflex arcs, feedback pathways of varying lengths would yield corresponding pathway latencies. As such, if spindle afferents are involved in parkinsonian tremor, then by virtue of these neurophysiological variants across these cranial and spinal motor systems, the frequency of respective tremors would be similarly different (9-14). Furthermore, although segmental patterns of recurrent and reciprocal inhibition are manifest for the limbs via lower motor neuron interactions with collaterals to inhibitory interneurons, parallel processes do not appear to be operating for the cranial nerves; rather, these patterns are regulated more centrally (15-18). Hence, if segmental interneuronal mechanisms are potential sources of parkinsonian tremor, then the differ-
The characteristics of parkinsonian resting tremor (e.g., frequency, amplitude, waveform shape, mode of activation) have had considerable influence on the development of theories explaining the neural substrates of tremor. However, most observations of tremor have been limited to the upper limbs with resultant hypotheses based primarily on spinal-specific physiology (1). Parkinsonian resting tremor has not been systematically examined throughout the cranial motor system (2). Musculature innervated by the spinal and cranial nerves vary in a number of significant biomechanical, neuroanatomical, and neurophysiological dimensions (3,4). The cranial motor systems are different from the upper limbs with regard to the presence and operation of muscle receptors and inhibitory networks as well as in relation to their inherent biomechanical properties. For example, muscle spindles have not been found in the lip muscles (5,6) and tongue muscle spindles do not appear Address correspondence and reprint requests to Dr. C. J. Hunker at Waisman Center, 1500 Highland Avenue, Madison, WI 53705-2280, U.S.A.
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c. .I. HUNKER AND J . H . ABBS
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ences between the cranial and spinal motor systems with respect to these mechanisms should be reflected in the oscillatory characteristics. By exploiting these known differences, it is possible to test neurophysiological and biomechanical hypotheses regarding parkinsonian tremor directly. If the primary mechanism underlying parkinsonian resting tremor is central, either as a neuronal pacemaker or an oscillatory network dominating peripheral influences (1 1,14,19,20), then the tremor would be manifest uniformly across the diverse orofacial and limb motor systems. Alternatively, if lower motor neuron mechanisms are dominant or interact with the central supranuclear activity (912,21-23), the frequency characteristics of the resting tremor would vary between the two sets of motor systems. METHODS Subjects To avoid the difficulties inherent in many previous studies of this kind, the selected parkinsonian subjects had to meet very specific inclusionary criteria. All subjects were examined by a consulting neurologist to ensure that they were free from secondary signs not typically associated with idiopathic Parkinson’s disease. Furthermore, the subjects’ medications were carefully matched to their respective symptom profiles and were stabilized for at least 6 months. Finally, to study the uniformity of parkinsonian resting tremor without the complicating influence of muscle rigidity, patients were selected who manifested only resting tremor in the orofacial system and in the distal part of the upper limbs. Although only three subjects were selected, these individuals were intensively studied to address the issues that motivated this work. These male subjects (T1-T3) ranged in age from 60.4 to 73.3 years (mean age: 66.0 years) and in severity from stage I1 to stage IV (24). Pharmacological therapy for these subjects consisted of levodopa/ carbidopa in combination with either trihexyphenidyl or benztropine. Three age-matched male adults (Nl-N3) free of neurological impairments as documented by the consulting neurologist served as controls (age range: 56.1 to 74.1 years; mean age: 63.7 years). Neurological examinations and experimental data acquisition sessions were completed only at the end of the parkinsonian subjects’ respective dosage cycles when the medication effect on the symptom profile was minimal.
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Apparatus Parkinsonian resting tremor of the lips, tongue, jaw, and index finger was recorded using cantilever strain-gauge transduction devices (25-27). The bandwidth of each device (at least 20.0 Hz) exceeded known pathological tremor frequencies (28). Using hooked-wire intramuscular electrodes (29), electromyographic (EMG) activity was observed from the following lip, tongue, jaw, and hand muscles: orbicularis oris superior and inferior, superior longitudinal, anterior digastric, and extensor digitorum superficialis. Electrode placement sites were based on cadaveric studies (30) and were confirmed in each subject through (a) location of anatomical landmarks, (b) surface palpation, and (c) performance of a variety of independent gestures (3 1,32). All signals were recorded on FM tape with a bandwidth of DC-2,500 Hz for each channel. Procedures Specific procedures were developed to optimally monitor resting tremor from each body part. A 9.0mm intermolar biteblock was custom made of dental impression compound to configure the lips at rest in an open-mouth position, permitting the transduction of labial resting tremor without potential distortions imparted by the opposing lip and the influence of jaw oscillations. For the jaw, the subjects assumed a facial resting position with the lips slightly touching. Lingual tremor was recorded while the subjects relaxed the tongue on the floor of the mouth. For finger-tremor recording, the left forearm was placed on the horizontal arm of a dental chair with the fingers resting vertically over the edge. Muscle activity was monitored to ensure the absence of voluntary activation. Ten 10-s rest trials were obtained separately for each body part. The subjects were required to move the body part between rest trials. To minimize performance fluctuations due to fatigue and drug influences, data collection was completed in two experimental sessions consisting of the lip-jaw procedures and t h e tongue-finger procedures, respectively. The order of the sessions was counterbalanced across subjects. Data Analyses To eliminate voluntary movement fluctuations and improve the resolution of the tremor, the movement signals from each transducer were bandpass filtered (serially connected fourth-order filters; -3.0 dB high-pass at 2.4 Hz and low-pass 19.8 Hz)
UNIFORM FREQUENCY OF PARKINSONIAN REST TREMOR
(33,34). The EMG signals were full-wave rectified and smoothed with a fourth-order low-pass filter with a 19.8 Hz cutoff frequency. The frequency domain analyses of the conditioned tremor movement and EMG signals were analyzed using a HewlettPackard (Palo Alto, CA) 3582-A real-time spectrum analyzer (frequency resolution 0.20 Hz). For each spectrum, 5-s segments of the conditioned tremor movement and EMG signals from the center of the ten 10-s resting epochs were averaged in the frequency domain. This process yielded five spectra for tremor movement and five spectra for EMG (upper lip, lower lip, jaw, tongue, and finger) from each subject. The frequency and amplitude at the peak frequency for each spectra were visually identified and measured. RESULTS Figure 1 illustrates typical resting tremor waveforms obtained from the upper lip, lower lip, jaw, tongue, and index finger along with associated muscle activity from the tremorous parkinsonian subjects. The oscillatory patterns obtained from each tremorous structure were strikingly periodic. However, subtle variations in tremor period, amplitude, and waveform shape occurred on a cycle-to-cycle basis as well as from epoch to epoch for each structure. In some instances, tremor waveforms were essentially sinusoidal with fairly constant amplitude (e.g., tongue in Fig. 1). A relatively uniform amplitude modulation was sometimes encountered (e.g., finger and upper lip in Fig. 1) and in some cases waveforms were erratic (e.g., lower lip and jaw in Fig. 1). These characteristics of resting tremor observed from orofacial and limb sites in the present study have been described previously in the limbs (35). For the most part, the variations in the period, amplitude, and waveform shape of the involuntary movements appeared to occur irrespective of exogenous factors. During the jaw procedure, the configuration of the lipjaw transducers permitted simultaneous observations of lip and jaw resting tremor. Although tremor amplitudes across both channels did increase temporarily if the subjects were startled or if mental concentration was increased, the variations in period, amplitude, and waveform shape observed from trial to trial across these structures were quite different from one another. Although not examined empirically, the waveform characteristics were structure-specific and apparently endogenously generated. When the
I
73
I
00s
Lower tip
001
Jaw ABD
I
I I
I
I
Tongue
I
aLs
Finser ED
1000 rns
I1
FIG. 1. Representative computer-generated oscillographic records of resting tremor in the upper lip and orbicularis oris superior muscle ( 0 0 s ) ; lower lip and orbicularis oris inferior jaw and anterior digastric muscle (ABD); tongue muscle (001); and superior longitudinal muscle (SL); and index finger and extensor digitorum superficialis muscle (ED).
normal subjects assumed the same resting positions, the regular rhythmical oscillations seen in the tremorous parkinsonian subjects. were not discernible (2). These instrumental observations confirmed the findings of the clinical neurologist. EMG activity from the tremor-generating muscles showed discrete excitatorylinhibitory periods in synchrony with the involuntary movement oscillations. These observations concur with most descriptions of tremorous EMG activity in the limbs (36-40). By comparison, EMG signals from the normal subjects were quiescent during these rest periods. Representative long-term spectral averages from the tremor movement (thick lines) and EMG (thin lines) signals from a normal subject and a parkinso-
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C. J . HUNKER AND J . H . ABBS
nian subject are illustrated in Fig. 2. Parkinsonian resting tremor movement and EMG spectral averages (Fig. 2b) were characterized by single narrow peaks showing identical concentrations of energy. These spectral observations obtained from orofacial and index finger sites are consonant with the marked periodicity observed in oscillographic representations of the tremor waveforms (Fig. 1) and in agreement with other oscillographic and spectral analyses of pathological tremor of the limbs (20,28,41). However, these data are in contrast with reports of jaw resting-tremor spectra characterized by broadly based peaks with a 1.k7.0-Hz bandwidth (42,43), possibly reflecting large momentto-moment fluctuations in the tremor waveform due either to recording techniques or to idiosyncratic manifestations in these particular subjects. The peak frequencies from the spectral averages of the tremor movement and EMG activity were
correlated for each parkinsonian subject. The correlations were very high, ranging from 0.956 to 1 .OO. This isotropy in frequency composition confirms the hypothesis that parkinsonian resting tremor is a forced oscillation driven by motor-unit activity. Likewise, Homberg et al. (20) reported that the prominent resting-tremor peaks in accelerometer and EMG spectra always occurred at the same frequency in the hands, even when the mechanical state of the limbs was altered by adding various loads, reflecting strong motor-unit synchronization for parkinsonian resting tremor. Figure 2a illustrates the effect of spectral averaging the resting epochs from the orofacial structures and from the index finger of a normal subject. These exemplary tremor movement spectra decreased monotonically through the frequency range of interest with no salient peaks. The EMG spectra had a nearly flat slope resembling “white noise” indicatNORMAL Jaw
Lower Lip
Upper Lip
1
Flnger
Tongue
6 . 2 5 m m rma
1.3mm rm8
a -80
a -100
0
5
10
PARKINSON
d 5.9mm r m s
-10
0
5
Frequency
10
(Hz)
I 4.2mrn rms
b
FIG. 2. Representative spectral plots of the upper lip, lower lip, jaw, tongue, and index finger tremor movement (thick line) and electromyogram (EMG) from respective muscles (thin line) from normal subjects (a) and parkinsonian subjects (b) while at rest. For comparison, the tremor movement and EMG spectra were reproduced on the same axes.
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UNIFORM FREQUENCY OF PARKINSONIAN REST TREMOR ing that the myoelectric signals contained energy distributed across the frequency range. Similar spectral averages were obtained from each of the other normal subjects. By comparing the peak frequency values obtained from the tremor movement and EMG spectra (Table l), it is obvious that the dominant tremor frequencies from the upper lip, lower lip, jaw, tongue, and index finger were remarkably consistent. The range of tremor frequencies across the various structures for each subject is quite narrow, with a maximum of 8% variation for subject T3. Statistically as well, these peak tremor frequencies were not significantly different across the symptomatic structures in any parkinsonian subject (Tl: F = 1.20; T2: F = 1.75; T3: F = 3.0; 4, 5 ; p > 0.05). This result is somewhat surprising given the diverse neuroanatomical, neurophysiological, and biomechanical nature of the involved motor systems. When comparing the amplitude of the spectral peaks, each tremorous subject presented a different profile across the structures examined. There were no systematic trends in spectral amplitude as a function of structure (Table 1). For example, the finger of TI displayed the largest average restingtremor amplitude among the other symptomatic structures, whereas the tongue of subject T2 had the largest average oscillations. Hence, it appears that as the disease progresses (i.e., nerve cell degeneration in the somatotopically organized substantia nigra increases), the amplitude of the resting tremor in the symptomatic structures is not specifically increased; rather, previously asymptomatic muscle groups become affected. Tremor amplitude, in theory, may reflect the depth of central modulation of motor neuron activity on which peripheral neural input is imposed. In this regard, Scholz et al. (41) reported that the average hand-tremor ampli-
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tude remained constant for three 24-h periods. Furthermore, as observed in the present study, the intensity of the tremor in various body parts, although simultaneously increased across different structures by such factors as level of alertness or emotion, appears to be independently determined by factors specific to the symptomatic structures. For example, increasing mass may not affect tremor frequency (20,23) but it may affect tremor spectral amplitude. Likewise, changes in the position of a structure and rigidity may account for variations in tremor amplitude. These factors have not been investigated systematically in Parkinson's disease. CONCLUSIONS Despite a number of clinical and basic studies, the neural substrate of parkinsonian resting tremor remains unclear. From neurosurgical intervention and central unit recording studies in both humans and monkeys, it appears that parkinsonian resting tremor is due to (a) rhythmic activity in groups of neurons within portions of the cortex or within the ventrolateral region of the thalamus functioning as central pacemakers (44)or (b) an oscillatory neural network between the thalamus and the cortex (4547). In contrast, inappropriate or delayed feedback in segmental reflex loops (i.e., spindle afferent pathways, recurrent or reciprocal inhibitory loops) also have been postulated as the mechanism responsible for parkinsonian tremors (11,12,15,23,39). An alternative explanation implicates an interactive network involving both central (cortex, thalamic, basal ganglia) and peripheral circuitry (21-23,48-50). In this study, resting-tremor frequencies were found to be remarkably uniform for all orofacial and upper limb sites. The coincidence of the peak frequencies in cranial and spinal motor systems seriously challenges some explanations of resting
TABLE 1. Summary of peak frequencies and amplitudes from each parkinsonian subject ~~
T1
Upper lip Lower lip Jaw Tongue Finger
F
Movement Amp
4.4 4.4 4.5 4.5 4.5
0.230 0.340 0.124 0.500 2.655
T2
EMG F
F
Movement Amp
4.4 4.4 4.5 4.5 4.5
4.3 4.2 4.4 4.4 4.3
0.340 1.270 0.536 1.940 0.163
4.46 .096
4.32 .lo3
T3
EMG F
F
Movement Amp
4.3 4.2 4.4 4.4 4.4
4.8 4.8 4.4 5.0 4.8
0.079 0.780 1.140 0.158 0.280
4.34 .096
4.82 .114
EMG F 4.8 4.8 4.4 5 .O 4.8 4.82 .114
Peak frequencies (F) in hertz and amplitudes (Amp) in millimeters (mm rms) obtained from the tremor movement and electromyographic (EMG) spectra from each of the parkinsonian subjects (F, mean frequency).
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tremor based solely on peripheral spinal physiology. If resting tremor resulted exclusively from focal oscillations in stretch reflex pathways or in spinal recurrent or reciprocal inhibitory networks, then tremor would be manifest differentially across these motor systems because stretch reflexes are not present in the lips and tongue, and recurrent or reciprocal inhibitory networks as they are posited in the spinal motor systems are not present in the cranial motor system. The data from this study thus argue strongly for a dominant central generatoreither neuronal pacemakers or oscillatory networks-influencing the cranial and spinal motor neurons in a uniform manner. On the other hand, the spectral average amplitudes were found to differ significantly across symptomatic structures. Because of this observation as well as the subtle cycle-to-cycle waveform variations reported here and in other studies (28, 35), segmental influences cannot be completely discounted. However, the extent to which afferent inputs interact or are coupled with the central oscillator remains a question. In a reflex study, Lee and Stein (19) using sudden torque perturbations of ongoing tremor showed that parkinsonian tremor could not be reset. Likewise, Homberg et al. (20) demonstrated that altering the mechanical state of the hand by adding various loads did not affect the frequency of parkinsonian tremor. These studies indicate that peripheral mechanisms did not significantly influence the frequency generator of parkinsonian tremor. In contrast, the amplitude of rest tremor has been found to be modulated by many factors; complete relaxation and removal of sensory stimulation diminishes the amplitude of resting tremor, whereas emotions and ambient noise as well as intellectual concentration on a problem increase the amplitude of the tremor. Rondot and Bathien (17) found that ischemia, tonic vibration, and partial nerve block modified the amplitude of parkinsonian resting tremor. Most recently, Rack and Ross (23) observed wrist-tremor frequency shifts in some parkinsonian subjects with changes in inertial loads and, furthermore, that the tremor was entrained by 3-5-H~ tremor movements of the wrist. They proposed a “double-loop model” in which a central oscillatory mechanism interacts with a reflex pathway and that, depending on loop gains or level of nervous system dominance, imposed movements or changes in mechanical load may affect the course of the tremor (see Fig. 14 in ref. 23). Supporting this hy-
Movement Disorders, Vol. 5 , No. I , 1990
pothesis, Hagbarth et al. (11) recorded spindle discharges after the EMG burst in parkinsonian resting tremor and concluded that although segmental spindle feedback loops are not involved in the initiation of individual tremor bursts, they may function as “servo-assist’’ mechanisms facilitating a more central source. Hence, peripheral afferent mechanisms may play a supplementary role potentially contributing to increased motor neuron synchronization in tremorous muscles. Parkinsonian resting tremor, therefore, may be the product of variable central sources or of an interactive network dominated by central oscillators that, under certain circumstances, are influenced by local afferent mechanisms and peripheral biomechanics. Acknowledgment:This work was supported by the National Institutes of Health grants NS-20747, NS-16373, NS-13274, and HD-03352. The authors are grateful to Kirk Hogan, M.D., Department of Neurology, University of Wisconsin Clinical Science Center, for his assistance. The very efficient secretarial and editorial assistance of Geri Torti is greatly appreciated.
REFERENCES 1 . Desmedt JE, ed. Physiological tremor, pathological tremor, and clonus. Basel: Karger, 1978. 2. Hunker CJ, Abbs JH. Physiological analyses of parkinsonian tremor in the orofacial system. In: McNeil MR, Rosenbek JC, Aronson A , eds. The dysarthrias: physiology, acoustics, perception, management. San Diego: College-Hill Press, 1984:69-100. 3. Abbs JH, Hunker CJ, Barlow, SM. Differential speech motor subsystem impairments in subjects with suprabulbar lesions: neurophysiological framework and supporting data. In: Berry W, ed. Clinical Dysarthria. San Diego: CollegeHill Press, 1983:21-56. 4. Dubner R, Sessle BJ, Storey AT. The neural basis of oral and facial function. New York: Plenum, 1978. 5. Folkins JW, Larson CR. In search of a tonic vibration reflex in the human lip. Brain Res 1978;151:409-12. 6. Lovell M, Sutton D, Lindeman R. Muscle spindles in the non-human primate extrinsic auricular muscles. Anat Rev 1977;189519-24. 7. Bratzlavsky M, Vander Eecken H. Afferent influences on human genioglossus muscle. J Neurol 1974;207:19-25. 8. Allum JHJ. Segmental reflex, muscle mechanical and central mechanisms underlying human physiological tremor. In: Findley LJ, Capildeo R, eds. Movement disorders: tremor. London: Macmillan, 1984: 135-56. 9. Hammong PH, Merton PA, Sutton GC. Nervous gradation of muscular contraction. Br Med Bull 1956;12:214-8. 10. Lippold OCJ, Redfearn JWT, Vuco J. The rhythmical activity of groups of motor units in the voluntary contraction of muscle. J Pbysiol (Lon4 1957;137:473-87. 1 1 . Hagbarth K-E, Wallin G, Lofstedt L , Aquilonius SM. Muscle spindle activity in alternatingtremor of parkinsonism and in clonus. J Neurol Neurosurg Psychiatry 1975;38:636-41. 12. Stiles RN, Pozos RS. A mechanical-reflex oscillator hypothesis for parkinsonian hand tremor. J Appl Physiol 1976; 40:990-8. 13. Oguztoreli MN, Stein RB. The effects of multiple reflex
UNIFORM FREQUENCY OF PARKINSONIAN REST TREMOR pathways on the oscillations in neuro-muscular systems. J Math Biol 1976;3:87-101. 14. Wallin G, Hagbarth K-E. Muscle spindle activity in man during voluntary alternating movements, parkinsonian tremor and clonus. Progr Clin Neurophysiol 1978;5:150-9. 15. Lance JW, Schwab RS, Peterson EA. Action tremor and the cogwheel phenomena in Parkinson’s disease. Brain 1963; 86:95-110. 16. Penders CA, Delwaide PJ. Physiological approach to the human eye blink reflex. In: Desmedt JE, ed. New developments in electromyography and clinical neurophysiology. Basel: Karger, 1973:64%57. 17. Rondot P, Bathien N. Peripheral factors modulating parkinsonian tremors. In: Birkmeyer W, Hornykiewicx G, eds. Advances in parkinsonism. Basel: Roche, 1976:269-87. 18. Shahani BT, Young RR. Blink reflexes in orbicularis oris. In: Desmedt JE, ed. New developments in electromyography and clinical neurophysiology. Basel: Karger, 197354184. 19. Lee RG, Stein RB. Resetting of tremor by mechanical perturbations: a comparison of essential tremor and parkinsonian tremor. Ann Neurol 1981;10:523-31. 20. Homberg V, Hefter H, Reiners K, Freund H-J. Differential effects of changes in mechanical limb properties on physiological and pathological tremor. J Neurol Neurosurg Psychiatry 1987;50:568-79. 21. Dietz V, Hillesheimer W, Freund H-J. Correlation between tremor, voluntary contraction, and firing pattern of motor units in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1974;37:927-37. 22. Teravainen H, Calne DB. Developments in understanding the physiology and pharmacology of parkinsonism. Acta Neurol Scand 1979;60:1-1 1 . 23. Rack PMH, Ross HF. The role of reflexes in the resting tremor of Parkinson’s disease. Brain 1986;109:11541. 24. Hoehn MM, Yahr MD. Parkinsonism: onset, progression, and mortality. Neurology 1967;17:427-42. 25. Barlow SM, Cole KJ, Abbs JH. A new headmounted lip-jaw movement transduction system for the study of motor speech disorders. J Speech Hear Res 1983;26:283-8. 26. Barlow SM. Fine force and position control of select limb and orofacial structures in the upper motor neuronsyndrome [Doctoral dissertation, University of Wisconsin]. Dissertation Abstr Int 1984;45. 27. Miiller EM, Abbs JH. Strain gauge transduction of lip and jaw motion in the midsaggital plane: refinement of a prototype. J Acoust SOCAm 1979;65:481-6. 28. Findley LG, Gresty MA, Halmagyi GM. Tremor, the cogwheel phenomenon and clonus in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1981 ;44:53446. 29. Konopacki RA, Cole KJ. Evaluation of electrodes for speech muscle electromyography [Abstract]. J Acoust SOC Am 1982;71(suppl 1):S33. 30. Kennedy JG, Abbs JH. Anatomic studies of the penoral motor system: foundations for studies in speech physiology. In: Lass NJ, ed. Speech and language, vol. 1 . New York: Academic Press, 1979:21242. 31. Kendall HO, Kendall FP, Wadsworth GE. Muscles: testing and function. Baltimore: Williams and Wilkins, 197 1. 32. O’Dwyer NJ, Quinn FT,Guitar BE, Andrews G, Neilson, PD. Procedures for verification of electrode placement in
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EMG studies of orofacial and mandibular muscles. J Speech Hearing Res 1981;24:273-88. Elble RJ, Randall JE. Motor-unit activity responsible for 8to 12-Hz component of human physiologicalfinger tremor. J Neurophysiol 1976;39:370-83. Freund HJ, Dietz V. The relationship between physiological and pathological tremor. In: Desmedt JE, ed. Physiological tremor, pathological tremor and clonus. Basel: Karger, 1978:66-89. Wachs EG, Boshes B. Tremor studies in normals and in parkinsonism. Arch Neurol 1961 ;4:6642. Calne D. Parkinsonism: physiology, pharmacology and treatment. London: Edward Arnold, 1970. Calne DB, Lader MH. Electromyographic studies of tremor using an averaging computer. Electroencephalogr Clin Neurophysiot 1969;26:8&92. Hoefer PF, Putnam TJ. Action potentials of muscles in rigidity and tremor. Acta Neurol Scand 1940;54:431-44. Rondot P, Bathien N. Pathophysiology of parkinsonian tremor: a study of the patterns of motor unit discharges. In: Desmedt JE, ed. Physiological tremor, pathological tremor, and clonus. Basel: Karger, 1978:138-49. Schwab RS, Cobb S. Simultaneous electromyograms and electroencephalograms in paralysis agitans. J Neurophysiol 1939;2:3641. Scholz E, Bacher M, Diener HC, Dichgans J. Twentyfour-hour tremor recordings in the evaluation of the treatment of Parkinson’s disease. J Neurol 1988;233:473-84. Palla S, Ash MM. Frequency analysis of human jaw tremor at rest. Arch Oral Biol 1979;24:709-18. van Steenberghe D, De Vries JH. The effect of the suppression of the periodontal neural input on mandibular tremor in man. Arch Oral Biol 1980;25:471-6. Marsden CD. The mechanisms of physiological tremor and their significance for pathological tremors. In: Desmedt JE, ed. Physiological tremor, pathological tremor, and clonus. Basel: Karger, 1978:1-16. Growdon JH, Young HH, Shahani BT. The differential diagnosis of tremor in Parkinson’s disease. Trans A m Neurol Assoc 1975;100:197-9. Lamarre Y, Joffroy AJ, Dumont M, De Montigny C, Grou F, Lund JP. Central mechanisms of tremor in some feline and primate models. J Can Sci Neurologiques 1975;2:227-33. Lamarre Y, Joffroy AJ. Experimental tremor in monkey: activity of thalamus and precentral cortical neurons in the absence of peripheral feedback. In: Poirier LJ, Sourkes TL, Bedard PJ, eds. The extrapyramidal system and its disorders: VIth international conference on Parkinson’s disease. New York: Raven Press, 1979:10!9-22. Evarts EV, Teravainen HT, Beuchert DE, Calne DB. Pathophysiology of motor performance in Parkinson’s disease. In: Calne D, Fuxe K, eds. Dopaminergic ergot derivatives and motor functions. Oxford: Pergamon, 1979:45-59. Teravainen H, Calne DB. Action tremor in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1980;43:257-63. Llinas RR. Rebound excitation as the physiological basis for tremor: a biophysical study of oscillatory properties of mammalian central neurones in vitro. In: Findley LJ, Capildeo R, eds. Movement disorders: tremor. London: Macmillan, 1984:165-82.
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Uniform Frequency of Parkinsonian Resting Tremor in the Lips, Jaw, Tongue, and Index Finger *?Chauncey J. Hunker and *?$James H. Abbs *Speech and Motor Control Laboratories, Waisman Center, TDepartment of Neurology, and $Department of Neurophysiology, University of Wisconsin, Madison, Wisconsin, U.S.A.
Summary: Parkinsonian resting tremor was examined in the lips, jaw, tongue, and index finger using electromyography (EMG) and displacement transduction. Long-term spectral averaging of tremor movement and EMG signals revealed that resting tremor frequencies were remarkably uniform across these orofacial and hand structures within the same parkinsonian subjects. However, marked variability in tremor spectral amplitude across structures and subtle moment-to-moment variations in tremor period, amplitude, and waveform shape were also observed. Although these observations argue for a central source of tremor, it appears that interactive central a n d o r peripheral neural circuitry may yield variations in tremor characteristics. Key Words: Parkinson’s disease-Resting tremor-Face-Hand.
to project autogenically to hypoglossal motor neurons within the lower brainstem (7). Inasmuch as the orofacial motor systems (i.e., lips, tongue, jaw) are differentially endowed with muscle spindles, respective lower motor neuron pools seemingly are not influenced uniformly by conventional muscle spindle actions (e.g., long-term synchronization of motor units) (8). Moreover, in motor systems subserved by spindle mediated stretch reflex arcs, feedback pathways of varying lengths would yield corresponding pathway latencies. As such, if spindle afferents are involved in parkinsonian tremor, then by virtue of these neurophysiological variants across these cranial and spinal motor systems, the frequency of respective tremors would be similarly different (9-14). Furthermore, although segmental patterns of recurrent and reciprocal inhibition are manifest for the limbs via lower motor neuron interactions with collaterals to inhibitory interneurons, parallel processes do not appear to be operating for the cranial nerves; rather, these patterns are regulated more centrally (15-18). Hence, if segmental interneuronal mechanisms are potential sources of parkinsonian tremor, then the differ-
The characteristics of parkinsonian resting tremor (e.g., frequency, amplitude, waveform shape, mode of activation) have had considerable influence on the development of theories explaining the neural substrates of tremor. However, most observations of tremor have been limited to the upper limbs with resultant hypotheses based primarily on spinal-specific physiology (1). Parkinsonian resting tremor has not been systematically examined throughout the cranial motor system (2). Musculature innervated by the spinal and cranial nerves vary in a number of significant biomechanical, neuroanatomical, and neurophysiological dimensions (3,4). The cranial motor systems are different from the upper limbs with regard to the presence and operation of muscle receptors and inhibitory networks as well as in relation to their inherent biomechanical properties. For example, muscle spindles have not been found in the lip muscles (5,6) and tongue muscle spindles do not appear Address correspondence and reprint requests to Dr. C. J. Hunker at Waisman Center, 1500 Highland Avenue, Madison, WI 53705-2280, U.S.A.
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c. .I. HUNKER AND J . H . ABBS
72
ences between the cranial and spinal motor systems with respect to these mechanisms should be reflected in the oscillatory characteristics. By exploiting these known differences, it is possible to test neurophysiological and biomechanical hypotheses regarding parkinsonian tremor directly. If the primary mechanism underlying parkinsonian resting tremor is central, either as a neuronal pacemaker or an oscillatory network dominating peripheral influences (1 1,14,19,20), then the tremor would be manifest uniformly across the diverse orofacial and limb motor systems. Alternatively, if lower motor neuron mechanisms are dominant or interact with the central supranuclear activity (912,21-23), the frequency characteristics of the resting tremor would vary between the two sets of motor systems. METHODS Subjects To avoid the difficulties inherent in many previous studies of this kind, the selected parkinsonian subjects had to meet very specific inclusionary criteria. All subjects were examined by a consulting neurologist to ensure that they were free from secondary signs not typically associated with idiopathic Parkinson’s disease. Furthermore, the subjects’ medications were carefully matched to their respective symptom profiles and were stabilized for at least 6 months. Finally, to study the uniformity of parkinsonian resting tremor without the complicating influence of muscle rigidity, patients were selected who manifested only resting tremor in the orofacial system and in the distal part of the upper limbs. Although only three subjects were selected, these individuals were intensively studied to address the issues that motivated this work. These male subjects (T1-T3) ranged in age from 60.4 to 73.3 years (mean age: 66.0 years) and in severity from stage I1 to stage IV (24). Pharmacological therapy for these subjects consisted of levodopa/ carbidopa in combination with either trihexyphenidyl or benztropine. Three age-matched male adults (Nl-N3) free of neurological impairments as documented by the consulting neurologist served as controls (age range: 56.1 to 74.1 years; mean age: 63.7 years). Neurological examinations and experimental data acquisition sessions were completed only at the end of the parkinsonian subjects’ respective dosage cycles when the medication effect on the symptom profile was minimal.
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Apparatus Parkinsonian resting tremor of the lips, tongue, jaw, and index finger was recorded using cantilever strain-gauge transduction devices (25-27). The bandwidth of each device (at least 20.0 Hz) exceeded known pathological tremor frequencies (28). Using hooked-wire intramuscular electrodes (29), electromyographic (EMG) activity was observed from the following lip, tongue, jaw, and hand muscles: orbicularis oris superior and inferior, superior longitudinal, anterior digastric, and extensor digitorum superficialis. Electrode placement sites were based on cadaveric studies (30) and were confirmed in each subject through (a) location of anatomical landmarks, (b) surface palpation, and (c) performance of a variety of independent gestures (3 1,32). All signals were recorded on FM tape with a bandwidth of DC-2,500 Hz for each channel. Procedures Specific procedures were developed to optimally monitor resting tremor from each body part. A 9.0mm intermolar biteblock was custom made of dental impression compound to configure the lips at rest in an open-mouth position, permitting the transduction of labial resting tremor without potential distortions imparted by the opposing lip and the influence of jaw oscillations. For the jaw, the subjects assumed a facial resting position with the lips slightly touching. Lingual tremor was recorded while the subjects relaxed the tongue on the floor of the mouth. For finger-tremor recording, the left forearm was placed on the horizontal arm of a dental chair with the fingers resting vertically over the edge. Muscle activity was monitored to ensure the absence of voluntary activation. Ten 10-s rest trials were obtained separately for each body part. The subjects were required to move the body part between rest trials. To minimize performance fluctuations due to fatigue and drug influences, data collection was completed in two experimental sessions consisting of the lip-jaw procedures and t h e tongue-finger procedures, respectively. The order of the sessions was counterbalanced across subjects. Data Analyses To eliminate voluntary movement fluctuations and improve the resolution of the tremor, the movement signals from each transducer were bandpass filtered (serially connected fourth-order filters; -3.0 dB high-pass at 2.4 Hz and low-pass 19.8 Hz)
UNIFORM FREQUENCY OF PARKINSONIAN REST TREMOR
(33,34). The EMG signals were full-wave rectified and smoothed with a fourth-order low-pass filter with a 19.8 Hz cutoff frequency. The frequency domain analyses of the conditioned tremor movement and EMG signals were analyzed using a HewlettPackard (Palo Alto, CA) 3582-A real-time spectrum analyzer (frequency resolution 0.20 Hz). For each spectrum, 5-s segments of the conditioned tremor movement and EMG signals from the center of the ten 10-s resting epochs were averaged in the frequency domain. This process yielded five spectra for tremor movement and five spectra for EMG (upper lip, lower lip, jaw, tongue, and finger) from each subject. The frequency and amplitude at the peak frequency for each spectra were visually identified and measured. RESULTS Figure 1 illustrates typical resting tremor waveforms obtained from the upper lip, lower lip, jaw, tongue, and index finger along with associated muscle activity from the tremorous parkinsonian subjects. The oscillatory patterns obtained from each tremorous structure were strikingly periodic. However, subtle variations in tremor period, amplitude, and waveform shape occurred on a cycle-to-cycle basis as well as from epoch to epoch for each structure. In some instances, tremor waveforms were essentially sinusoidal with fairly constant amplitude (e.g., tongue in Fig. 1). A relatively uniform amplitude modulation was sometimes encountered (e.g., finger and upper lip in Fig. 1) and in some cases waveforms were erratic (e.g., lower lip and jaw in Fig. 1). These characteristics of resting tremor observed from orofacial and limb sites in the present study have been described previously in the limbs (35). For the most part, the variations in the period, amplitude, and waveform shape of the involuntary movements appeared to occur irrespective of exogenous factors. During the jaw procedure, the configuration of the lipjaw transducers permitted simultaneous observations of lip and jaw resting tremor. Although tremor amplitudes across both channels did increase temporarily if the subjects were startled or if mental concentration was increased, the variations in period, amplitude, and waveform shape observed from trial to trial across these structures were quite different from one another. Although not examined empirically, the waveform characteristics were structure-specific and apparently endogenously generated. When the
I
73
I
00s
Lower tip
001
Jaw ABD
I
I I
I
I
Tongue
I
aLs
Finser ED
1000 rns
I1
FIG. 1. Representative computer-generated oscillographic records of resting tremor in the upper lip and orbicularis oris superior muscle ( 0 0 s ) ; lower lip and orbicularis oris inferior jaw and anterior digastric muscle (ABD); tongue muscle (001); and superior longitudinal muscle (SL); and index finger and extensor digitorum superficialis muscle (ED).
normal subjects assumed the same resting positions, the regular rhythmical oscillations seen in the tremorous parkinsonian subjects. were not discernible (2). These instrumental observations confirmed the findings of the clinical neurologist. EMG activity from the tremor-generating muscles showed discrete excitatorylinhibitory periods in synchrony with the involuntary movement oscillations. These observations concur with most descriptions of tremorous EMG activity in the limbs (36-40). By comparison, EMG signals from the normal subjects were quiescent during these rest periods. Representative long-term spectral averages from the tremor movement (thick lines) and EMG (thin lines) signals from a normal subject and a parkinso-
Movement Disorders, Vol. 5 . N o . 1 , 1990
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C. J . HUNKER AND J . H . ABBS
nian subject are illustrated in Fig. 2. Parkinsonian resting tremor movement and EMG spectral averages (Fig. 2b) were characterized by single narrow peaks showing identical concentrations of energy. These spectral observations obtained from orofacial and index finger sites are consonant with the marked periodicity observed in oscillographic representations of the tremor waveforms (Fig. 1) and in agreement with other oscillographic and spectral analyses of pathological tremor of the limbs (20,28,41). However, these data are in contrast with reports of jaw resting-tremor spectra characterized by broadly based peaks with a 1.k7.0-Hz bandwidth (42,43), possibly reflecting large momentto-moment fluctuations in the tremor waveform due either to recording techniques or to idiosyncratic manifestations in these particular subjects. The peak frequencies from the spectral averages of the tremor movement and EMG activity were
correlated for each parkinsonian subject. The correlations were very high, ranging from 0.956 to 1 .OO. This isotropy in frequency composition confirms the hypothesis that parkinsonian resting tremor is a forced oscillation driven by motor-unit activity. Likewise, Homberg et al. (20) reported that the prominent resting-tremor peaks in accelerometer and EMG spectra always occurred at the same frequency in the hands, even when the mechanical state of the limbs was altered by adding various loads, reflecting strong motor-unit synchronization for parkinsonian resting tremor. Figure 2a illustrates the effect of spectral averaging the resting epochs from the orofacial structures and from the index finger of a normal subject. These exemplary tremor movement spectra decreased monotonically through the frequency range of interest with no salient peaks. The EMG spectra had a nearly flat slope resembling “white noise” indicatNORMAL Jaw
Lower Lip
Upper Lip
1
Flnger
Tongue
6 . 2 5 m m rma
1.3mm rm8
a -80
a -100
0
5
10
PARKINSON
d 5.9mm r m s
-10
0
5
Frequency
10
(Hz)
I 4.2mrn rms
b
FIG. 2. Representative spectral plots of the upper lip, lower lip, jaw, tongue, and index finger tremor movement (thick line) and electromyogram (EMG) from respective muscles (thin line) from normal subjects (a) and parkinsonian subjects (b) while at rest. For comparison, the tremor movement and EMG spectra were reproduced on the same axes.
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UNIFORM FREQUENCY OF PARKINSONIAN REST TREMOR ing that the myoelectric signals contained energy distributed across the frequency range. Similar spectral averages were obtained from each of the other normal subjects. By comparing the peak frequency values obtained from the tremor movement and EMG spectra (Table l), it is obvious that the dominant tremor frequencies from the upper lip, lower lip, jaw, tongue, and index finger were remarkably consistent. The range of tremor frequencies across the various structures for each subject is quite narrow, with a maximum of 8% variation for subject T3. Statistically as well, these peak tremor frequencies were not significantly different across the symptomatic structures in any parkinsonian subject (Tl: F = 1.20; T2: F = 1.75; T3: F = 3.0; 4, 5 ; p > 0.05). This result is somewhat surprising given the diverse neuroanatomical, neurophysiological, and biomechanical nature of the involved motor systems. When comparing the amplitude of the spectral peaks, each tremorous subject presented a different profile across the structures examined. There were no systematic trends in spectral amplitude as a function of structure (Table 1). For example, the finger of TI displayed the largest average restingtremor amplitude among the other symptomatic structures, whereas the tongue of subject T2 had the largest average oscillations. Hence, it appears that as the disease progresses (i.e., nerve cell degeneration in the somatotopically organized substantia nigra increases), the amplitude of the resting tremor in the symptomatic structures is not specifically increased; rather, previously asymptomatic muscle groups become affected. Tremor amplitude, in theory, may reflect the depth of central modulation of motor neuron activity on which peripheral neural input is imposed. In this regard, Scholz et al. (41) reported that the average hand-tremor ampli-
75
tude remained constant for three 24-h periods. Furthermore, as observed in the present study, the intensity of the tremor in various body parts, although simultaneously increased across different structures by such factors as level of alertness or emotion, appears to be independently determined by factors specific to the symptomatic structures. For example, increasing mass may not affect tremor frequency (20,23) but it may affect tremor spectral amplitude. Likewise, changes in the position of a structure and rigidity may account for variations in tremor amplitude. These factors have not been investigated systematically in Parkinson's disease. CONCLUSIONS Despite a number of clinical and basic studies, the neural substrate of parkinsonian resting tremor remains unclear. From neurosurgical intervention and central unit recording studies in both humans and monkeys, it appears that parkinsonian resting tremor is due to (a) rhythmic activity in groups of neurons within portions of the cortex or within the ventrolateral region of the thalamus functioning as central pacemakers (44)or (b) an oscillatory neural network between the thalamus and the cortex (4547). In contrast, inappropriate or delayed feedback in segmental reflex loops (i.e., spindle afferent pathways, recurrent or reciprocal inhibitory loops) also have been postulated as the mechanism responsible for parkinsonian tremors (11,12,15,23,39). An alternative explanation implicates an interactive network involving both central (cortex, thalamic, basal ganglia) and peripheral circuitry (21-23,48-50). In this study, resting-tremor frequencies were found to be remarkably uniform for all orofacial and upper limb sites. The coincidence of the peak frequencies in cranial and spinal motor systems seriously challenges some explanations of resting
TABLE 1. Summary of peak frequencies and amplitudes from each parkinsonian subject ~~
T1
Upper lip Lower lip Jaw Tongue Finger
F
Movement Amp
4.4 4.4 4.5 4.5 4.5
0.230 0.340 0.124 0.500 2.655
T2
EMG F
F
Movement Amp
4.4 4.4 4.5 4.5 4.5
4.3 4.2 4.4 4.4 4.3
0.340 1.270 0.536 1.940 0.163
4.46 .096
4.32 .lo3
T3
EMG F
F
Movement Amp
4.3 4.2 4.4 4.4 4.4
4.8 4.8 4.4 5.0 4.8
0.079 0.780 1.140 0.158 0.280
4.34 .096
4.82 .114
EMG F 4.8 4.8 4.4 5 .O 4.8 4.82 .114
Peak frequencies (F) in hertz and amplitudes (Amp) in millimeters (mm rms) obtained from the tremor movement and electromyographic (EMG) spectra from each of the parkinsonian subjects (F, mean frequency).
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C. J . HUNKER AND J . H . ABBS
tremor based solely on peripheral spinal physiology. If resting tremor resulted exclusively from focal oscillations in stretch reflex pathways or in spinal recurrent or reciprocal inhibitory networks, then tremor would be manifest differentially across these motor systems because stretch reflexes are not present in the lips and tongue, and recurrent or reciprocal inhibitory networks as they are posited in the spinal motor systems are not present in the cranial motor system. The data from this study thus argue strongly for a dominant central generatoreither neuronal pacemakers or oscillatory networks-influencing the cranial and spinal motor neurons in a uniform manner. On the other hand, the spectral average amplitudes were found to differ significantly across symptomatic structures. Because of this observation as well as the subtle cycle-to-cycle waveform variations reported here and in other studies (28, 35), segmental influences cannot be completely discounted. However, the extent to which afferent inputs interact or are coupled with the central oscillator remains a question. In a reflex study, Lee and Stein (19) using sudden torque perturbations of ongoing tremor showed that parkinsonian tremor could not be reset. Likewise, Homberg et al. (20) demonstrated that altering the mechanical state of the hand by adding various loads did not affect the frequency of parkinsonian tremor. These studies indicate that peripheral mechanisms did not significantly influence the frequency generator of parkinsonian tremor. In contrast, the amplitude of rest tremor has been found to be modulated by many factors; complete relaxation and removal of sensory stimulation diminishes the amplitude of resting tremor, whereas emotions and ambient noise as well as intellectual concentration on a problem increase the amplitude of the tremor. Rondot and Bathien (17) found that ischemia, tonic vibration, and partial nerve block modified the amplitude of parkinsonian resting tremor. Most recently, Rack and Ross (23) observed wrist-tremor frequency shifts in some parkinsonian subjects with changes in inertial loads and, furthermore, that the tremor was entrained by 3-5-H~ tremor movements of the wrist. They proposed a “double-loop model” in which a central oscillatory mechanism interacts with a reflex pathway and that, depending on loop gains or level of nervous system dominance, imposed movements or changes in mechanical load may affect the course of the tremor (see Fig. 14 in ref. 23). Supporting this hy-
Movement Disorders, Vol. 5 , No. I , 1990
pothesis, Hagbarth et al. (11) recorded spindle discharges after the EMG burst in parkinsonian resting tremor and concluded that although segmental spindle feedback loops are not involved in the initiation of individual tremor bursts, they may function as “servo-assist’’ mechanisms facilitating a more central source. Hence, peripheral afferent mechanisms may play a supplementary role potentially contributing to increased motor neuron synchronization in tremorous muscles. Parkinsonian resting tremor, therefore, may be the product of variable central sources or of an interactive network dominated by central oscillators that, under certain circumstances, are influenced by local afferent mechanisms and peripheral biomechanics. Acknowledgment:This work was supported by the National Institutes of Health grants NS-20747, NS-16373, NS-13274, and HD-03352. The authors are grateful to Kirk Hogan, M.D., Department of Neurology, University of Wisconsin Clinical Science Center, for his assistance. The very efficient secretarial and editorial assistance of Geri Torti is greatly appreciated.
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