IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. BME-26, NO. 1, JANUARY 1979

The Nature and Etiology of Normal and AlcoholWithdrawal Tremor

DUANE H. ZILM, MEMBER, IEEE, EDWARD M. SELLERS, RICHARD C. FRECKER, MEMBER, IEEE,

AND HANS KUNOV, MEMBER, IEEE

Abstract-Alcohol withdrawal tremor is principally a postural-typetremor. That is, the tremor manifests itself most when the limbs arevoluntarily maintained in a stationary position. The tremor of alcoholwithdrawal is typically 5 to 20 times as large and approximately thesame frequency as normal postural tremor. The fact that withdrawaltremor is uncorrelated in both outstretched hands argues against theinvolvement of a central pacemaker in the genesis of the tremor. Bothwithdrawal and normal physiologic type hand tremors are associatedwith synchronous firing of extensor motor units in phase with tremorvelocity at the frequency of limb resonance. Both kinds of tremor arereduced by the p-adrenergic receptor blocking drug, propranolol. Thereduction in tremor is caused by a decrease in the synchrony of motorunits and not a decrease in the total number of units involved in main-taining limb posture. It is proposed that increased tremor during with-drawal is due to the entrainment by 1 A muscle spindle afferents ofasynchronously firing motoneurons. Tremor is also increased by en-trainment of motoneurons firing synchronously at 9 to 10 Hz due toan oscillation in the stretch reflex control system. Tremor reductionfollowing propranolol is due to a decrease in entrainment because ofdecreased 1 A afferent inflow to the spinal cord or because of reducedsensitivity of alpha motoneurons to 1 A spindle afferent discharges.

INTRODUCTIONINCREASED tremor is one of the most common clinical

signs associated with the alcohol withdrawal syndrome inman. Wolfe and Victor (1) have suggested that there are twooverlapping phases in the first 120 h following the cessation ofalcohol consumption when tremor can occur. The first phase,which occurs in the first 6 to 40 h, is the mild withdrawalsyndrome characterized by hallucinations, convulsions, sweat-ing, and tremor. The second phase is a more serious with-drawal syndrome ("delirium tremens") and is associated withprofound disorientation, hallucinations, sweating, and alsotremor. The severity of symptoms during delirium tremens isgreatest between 70 and 80 h.The nature and etiology of alcohol withdrawal tremor is

discussed in this paper. The tremor which was investigated,and which will be referred to, is that which occurs in the earlywithdrawal phase since a majority of chronic alcoholics suit-able for the studies described below were admitted within 24 hfollowing abstinence.

Manuscript received July 15, 1976; revised November 21, 1977 andFebruary 21, 1978.D. H. Zilm is with the Addiction Research Foundation, Clinical

Institute, Toronto, Ont., Canada.E. M. Sellers is with the Departments of Pharmacology and Medicine,

University of Toronto, Toronto, Ont., Canada, and the Toronto Wes-tern Hospital, Toronto, Ont., Canada.R. C. Frecker and H. Kunov are with the Institute of Biomedical

Engineering, University of Toronto, Toronto, Ont., Canada.

Much of the experimental data pertaining to the etiology ofnormal physiologic and alcohol withdrawal tremor was derivedfrom experiments which decreased tremor by parenteral ad-ministration of the drug propranolol. Propranolol belongs to aclass of drugs known as beta-adrenergic receptor blockingagents. The drug has been shown to prevent the tremor in-crease following infused sympathomimetics (such as epine-phrine and isoproterenol) by blockade of skeletal muscle ,Breceptors (2). It has also been shown to decrease familial,benign essential (3) thyrotoxic (4), alcohol withdrawal (5),and normal physiologic tremors (6). Recent evidence (7), (8)suggests that propranolol may have a site of action in thecranial and/or spinal portions of the nervous system.

EXPERIMENTAL METHODFourteen chronic alcoholics were studied. Subjects were

admitted to the investigation if they: 1) were in mild tomoderately severe withdrawal characterized by elevatedheart rates (exceeding 90 beats per minute), sweating, andovert tremulousness and 2) had no history of cardiovasculardisease or asthma. All subjects were informed of and con-sented to the experimental procedures prior to the investiga-tion. None was experiencing hallucinations or disturbances ofthe sensorium and all were considered to be lucid and fit toparticipate by the attending physician.Twelve subjects participated in a study in which six individ-

uals received a propranolol (0.5 mg in 2.5 ml normal saline)injection via the brachial artery and six received a placeboinjection of 3.0 ml sterile normal saline by the same route.The dose of propranol used has been shown to reduce tremor(5), but not to decrease heart rate considerably. The proto-cols for the above study and those described below werereviewed and approved by the Human Ethics Committee ofthe Addiction Research Foundation.Tremor was measured while each subject was seated com-

fortably. Both forearms were supported proximal to thewrist joint at the height of the xiphoid process. The thumbof each hand was taped to the underside of the index fingerand all fingers were taped together. A 33 g piezoelectricaccelerometer was securely affixed to the right index fingerat the end of thumb so that when the hand was held out-stretched in a horizontal plan for a tremor measurement,the most sensitive axis of the accelerometer was in the verti-cal plane and the axis of maximum transverse sensitivity wasparallel to the forearm [the axis of least motion (9)]. Foreach tremor measurement, the subject held his hands out-

0018-9294/79/0100-0003$00.75 O 1979 IEEE

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IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. BME-26, NO. 1, JANUARY 1979

stretched for a 26 s recording. The tremor signal was ampli-fied and band filtered prior to being recorded on an FM taperecorder (HP 3960).The amplitude and phase characteristics of the amplifier,

filters, and recorder were measured, while those of the acceler-ometer and its preamplifier were taken from the manufac-turer's specifications (for lack of a reference device for accel-eration calibration). From these data the transfer function ofthe system was derived. Within the bandwidth of interest(4 to 20 Hz) amplitude attenuation reached a maximum of5 dB at 4 Hz. Phase shift at 4 Hz was +300, while at 20 Hzit was -20°. Within these limits phase shift varied propor-tionately with frequency. A similar accelerometer was affixedto the left hand, and the signal proportional to accelerationwas similarly filtered and recorded.The surface electromyogram (EMG) from the extensor

digitorum communis of the right forearm was recorded simul-taneously with tremor. The extensor digitorum is a principalmuscle involved in counteracting the torque on the hand dueto gravity (10). The EMG was filtered 10-1000 Hz by an EEGamplifier (Gould model 13-4218-00 medical preamplifier andGould model 11-4307-02 EEG coupler) prior to tape record-ing. The EMG was also rectified and filtered at 0.5 Hz to givea signal proportional to muscle force [(1 1), (12)] which wasrecorded on a chart recorder together with the tremor signals.A lead II electrocardiogram was monitered and recorded

throughout the experiment.Intra-arterial propranolol and saline were injected over 45

s. Tremor, the electromyogram, and electrocardiogram wererecorded every minute thereafter for 5 min, once at 7 minand 10 min, and then every 5 min for a total measurementperiod of 45 min.To more completely document the time course of the drug

effect on tremor, a second study was conducted in which twoalcoholic subjects received propranolol intravenously throughan indwelling cannula inserted in a vein in the left forearm.Tremor was measured at the times above and right handtremor, extensor electromyogram, and electrocardiogram wererecorded.In a third study, four normal nonalcoholics also received

intravenous propranolol (6) and hand tremor, electromyo-gram, and the electrocardiogram were recorded at the timesdescribed above.A schematic of the experimental arrangement for the intra-

arterial studies is shown in Figure 1. The arrangement forintravenous studies was similar except only one accelerometerwas employed.

SIGNAL PROCESSING

Tremor and EMG signals were each sampled at 2500 Hz bythe analog to digital (A/D) converter of the lab peripheralsystem attached to a PDP 11/45 computer. Since the A/Dsoftware did not permit variable channel sampling rates, thehigh sampling rate was selected to avoid aliasing of the electro-myogram. Digitized data was stored on digital tape and sub-sequently processed by an IBM 370/165 computer.Each of the 4 to 6 twenty-six s tremor and EMG signals

collected prior to and following drug administration was

analyzed as follows. Each was divided into equal 6.14-s seg-ments, and subjected to power and cross spectral analysis.The 16 to 24 spectra so obtained were averaged as shown inequations (2) and (3). The sample size of tremor records wasreduced prior to spectral analysis by discarding 14 of every 15samples to give an effective real-time sampling rate of 166.7Hz. The EMG was demodulated by rectifying and filteringtwice with a zero phase recursive digital filter, the recurrencerelationship of which was:

y(n)=y(n - 1) - x(n - 16) +x(n + 15) (1)

where y(n) is the nth output sample and x(n) is the nth inputsample. The zero-phase shift digital filter was used to avoidphase distortion of the demodulated EMG in the passband.The passband attenuation was such that the height of the firstlobe was 26.9 dB down from the size of the main lobe of DCand the first zero of the filter (which defines the passbandedge) was at 80.6 Hz. Following digital filtering, every 14 outof 15 samples of the demodulated EMG were discarded toproduce a resultant signal sampled at an effective rate of 166.7Hz.Ten percent of the data points at each end of the tremor and

demodulated EMG samples were tapered by an extended co-sine bell window (13) prior to power and cross spectral analy-sis. Power spectra for tremor and demodulated EMG werecalculated by the direct method from the Fourier transformsof the records. Smoothed spectral estimates were obtained bycombined ensemble and spectral averaging (13):

1 m 4GT(fk) = E2 EGTi (fk+j);4m =1 j=1

I m 4GE(fk)= 4mE EGEZi (fj);

1m=i j=1

16 <m S 24

16 Sm < 24

(2)

(3)

where GTi and GE, are power spectra for each 6.14 s tremorand demodulated EMG segment selected from four to sixconsecutive tremor and EMG recordings and m is the numberof sample spectra averaged. The bandwidth of spectral esti-mates was 0.63 Hz.Cross spectral phase and coherence function estimates were

also computed. The coherence yTE, the value of which liesbetween 0 and 1, provides an estimate of the degree to whichthe tremor and demodulated EMG signals are linearly relatedas a function of frequency.

(GTE (fk))2TE (fk) GT(fk))GE (fk)

where GT(fk), GE(fk), and GTE are smoothed tremor spec-tra, smoothed demodulated EMG spectra, and smoothedcross spectra estimates, respectively.

GENERAL OBSERVATIONSThe tremor ofwithdrawing alcoholics is principally a postural-

type (14) tremor. That is, the tremor manifests itself in alimb which is held voluntarily in a stationary position. Handtremor is frequently accompanied by tremoring of the shoulderand chest muscles as well as shaking of the head and tongue.

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ZILM et al.: NORMAL AND ALCOHOL WITHDRAWAL TREMOR

LIFIER, F~LTER 1 A/D CONVERTER PDPII/45

ON LINE OFF Ll`

Q ECG MONITOR

Figure 1. Schematic diagram of experimental arrangement.

Withdrawal tremor can be 100 times the size of normalpostural tremor, but is typically 5 to 20 times as large. Tremorsize is measured as the variance of the tremor accelerationsignal (6). In severe withdrawal, the task of maintaining thehand in a horizontal plane for a tremor recording can precipi-tate a response leading to increased tremor and uncontrolledflapping of the limbs.Figure 2 shows results from a chronic alcoholic in with-

drawal and who was very tremulous. The figure illustrates anumber of important features pertaining to withdrawal tremor.Figure 2(a) shows the power spectrum of hand tremor. Asshown, power is concentrated in a relatively narrow band be-tween 6 to 7 Hz which was the typical range for withdrawaltremor measured by the technique described above. The fre-quency of the dominant tremor component was similar to thatof normal tremor but the frequency range of the peak wasoften narrower. Figure 2(b) shows the power spectrum of thedemodulated extensor EMG. Figure 2(c) is the cross spectralphase function which is the phase of the demodulated EMGrelative to tremor acceleration. The cross spectral phasefunction was modified using the computed phase function forthe measurement system to correct for the phase distortion.Increased tremor during withdrawal is accompanied by syn-chronous firing of extensor motor units which is coherentwith tremor (coherence, y'E > 0.85 at peak frequency) andwhich lags hand tremor acceleration by approximately 90°.This demonstrates that increased tremor during withdrawalcan be largely attributed to motor units firing synchronouslywith 1 A muscle spindle information to the spinal cord.A second feature which often emerged, especially when the

tremor was small was the appearance of a second peak in thedemodulated EMG power spectrum at 9 to 10 Hz. This isillustrated in Figure 3(b).Power spectra of simultaneous tremor recordings from both

outstretched hands of one subject in withdrawal are shown inFigure 4(a) and Figure 4(b). The dominant tremor compon-ent was often at the same frequency in both hands albeit the

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0O.S.

Il

(b)

0 410 8 0 1O IeoHERT Z

,90-0-

tio~~~~~~~80 16-0w

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-90-0

Figure 2. Results of analysis from a tremulous alcoholic in withdrawal.(a) Hand tremor power spectrum (G = acceleration due to gravity =981 cm/s2). (b) Demodulated exterior EMG power spectrum. (c)Cross spectral phase function. Dashed lines indicated 95% confidencelimits on estimates.

tremor sizes were often different. However, there was nosignificant increase in the coherence function at the dominanttremor frequency indicating that there is no significant correla-tion in tremor activity in both hands. A similar conclusionwas reached by Marsden et al. (15) regarding postural tremor

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IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. BME-26, NO. 1, JANUARY 1979

0

040 80 120 16-0HERTZ

24r

00

:2. 08 _ ;- 6

.

0 40 B0 12-0 16-0HERTZ

Figure 3. Results of analysis from an alcoholic in withdrawal. (a) Handtremor power spectrum. (b) Demodulated EMG power spectrum.

of normal nonalcoholics. Such an observation argues againsta pacemaker in the central nervous system underlying with-drawal tremor.Another characteristic feature of withdrawal tremor is illus-

trated in Figure 5. Results from three subjects are shown.One subject [Figure 5(a)] had a large hand tremor, another[Figure 5(b)] had a moderately sized hand tremor, while athird [Figure 5(c)] had a small hand tremor. As shown,larger hand tremors were associated with a narrowing of thedominant tremor peak or a concentration of power into anarrower bandwidth. Marsden et al. (16) made a similarobservation for the hand tremor of a patient who was surgi-cally deafferented on one side. They noted that the tremorpower spectrum of the deafferented hand was flatter than thatof the nondeafferented hand and attributed the observation tothe fact that muscle spindle afferents tend to group the firingof anterior horn cell discharges more closely around the peakfrequency.The dominant frequency of withdrawal hand tremor was the

same as that for tremor of the hand at rest and was the reso-nant frequency of the outstretched limb. Rest tremor wasmeasured when the hand was left to hang free of obstructionswith the forearm supported as described above. Rest tremorduring withdrawal is approximately twice as large as normalrest tremor since, in addition to a ballistocardiographic com-ponent (17), there is a baseline of asynchronous exterior mo-tor unit firing which results from the inability of the chronicalcoholic to relax the limb completely.

EXPERIMENTAL RESULTS

Intra-arterial propranolol produced an equal and bilateraldecrease in tremor after a delay of 8 to 12 min. No corre-sponding decrease was observed in hand tremor of the groupthat received the saline placebo. Figure 6 shows what hap-pened when tremor was decreased in one hand. Figure 6(a)shows results of analysis of tremor and EMG records ob-

0

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N

0I

ID

ccID0

0-0*

-90-0

(a)

HERTZ

(b)

(c )HERTZ

0 4.0 8-0 12-0 16-0

Figure 4. (a) Power spectrum of right hand tremor. (b) Power spec-trum of left hand tremor. (c) Cross spectral phase function. Dashedlines indicated 95% confidence limits on estimates.

tained in the first 6 min following the injection before tremordecreased. Figure 6(b) shows results following the tremordecrease. The reduction in tremor, 8 to 12 min followingintra-brachial propranolol, was not accompanied by a decreasein the rectified, filtered EMG demonstrating that the tremordecrease was not associated with a decrease in total muscleforce or the number of motor units involved in maintaininglimb posture. Rather, there was a large decrease in the num-ber of synchronous motor units [Figure 6(al), Figure 6(a2)]firing at 6 to 7 Hz. In addition, the tremor decrease wasfrequently accompanied by the emergence of a second peak at9 to 10 Hz in the demodulated EMG power spectrum [Figure7(al), Figure 7(a2)].Similar time delays were also observed before normal physio-

logic (7) and withdrawal tremor was reduced by intravenouspropranolol. Figure 8 shows results from a normal nonalco-holic whose tremor was decreased by intravenous propranolol.In this case, tremor reduction was also not accompanied by adecrease in the rectified, filtered EMG but was associated witha reduction in the number of motor units firing synchronouslywith tremor velocity at limb resonance.

DISCUSSIONTwo principal hypotheses conceming the mechanism of

normal physiologic tremor have been proposed which bear onthe interpretation of the results described above and which areimportant in understanding the etiology of tremor.

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ZILM et al.: NORMAL AND ALCOHOL WITHDRAWAL TREMOR

a_12 -

4 S 12 16H E R T Z

5-0-

t4x

o-4 S 12 16

H ERTZ

1*0

4 8 12 16

HERTZ

Figure 5. (a) Tremor power spectrum from a chronic alcoholic in withdrawal who had a large tremor. (b) Tremor powerspectrum from an alcoholic with a moderate tremor. (c) Tremor power spectra from an alcoholic with a small tremor.Note scale changes in panels (a) through (c).

Lippold (18), (19), proposed that 8 to 12 Hz tremor is dueto an oscillation in the stretch reflex control system as a resultof the large time delays present in the loop. Although such asituation could not occur if the control system were linear, anonlinear control system would be capable of sustaining sucha stable, spontaneous oscillation (20).

Stiles and Randall (21) proposed that tremor is due to therandom stimulation of a second-order underdamped mechan-ical system made up of the mass of the outstretched limbtogether with viscoelastic elements in the muscles, tendons,and connective tissues. Random stimulation is by asynchro-nous firing of motor units in maintaining limb posture, andtremor occurs as a result of limb motion at its resonant fre-quency which is determined by the mechanical componentsdescribed above.The hypothesis outlined below incorporates features from

both hypotheses discussed above. It is proposed that normalphysiologic and alcohol withdrawal tremor arise from threesources, two of which are illustrated in Figure 9. Tremor, be-fore increase, [Figure 9(a)] results from the random stimula-tion of a second-order underdamped mechanical system whichgives rise to the peak at 7 Hz as suggested by Stiles and Ran-dall (21). Tremor is also caused by the excitation of that samemechanical system by motor units firing synchronously at 9 to10 Hz [Figure 9(b)] as a result of an oscillation in the stretchreflex control system [Lippold, (19)].Increased tremor during withdrawal, or elevated in non-

alcoholics, is caused by the "entrainment" by 1 A musclespindle afferents, firing in response to motion of the limbat resonance (6 to 7 Hz), of asynchronously firing moto-neurons, and motoneurons firing at 9 to 10 Hz due to anoscillation of the stretch reflex control system. The configura-

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IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. BME-26, NO. 1, JANUARY 1979

a

@1

4.0

b

bi

HERTZ HERTZ

Figure 6. (a) Results of analysis before tremor was decreased by propranolol; (al) tremor power spectrum, (a2) demodu-lated EMG power spectrum. (b) Results of analysis after tremor was decreased. Data are from a chronic alcoholic inwithdrawal. Note ordinate scale change from (al) to (bI) and (a2) to (b2) demonstrating a marked decrease in values.

a

o0

0.4

16.HERTZ

z

o0

b

bi

4

b i

Figure 7. (a) Results of analysis before tremor was decreased by propranolol; (al) tremor power spectrum, (a2) demodu-lated EMG power spectrum. (b) Results after tremor was decreased. Data are from a chronic alcoholic in withdrawal.Note change of ordinate scale from (al) to (bl) and (a2) to (b2).

tion is illustrated diagrammatically in Figure 10. Under small

tremor conditions [Figure 10 (a)], there is a contributionfrom the asynchronous portion of the a-motoneuron pool andsmall contributions from synchronous neurons firing at limbresonance and at 9 Hz. Under elevated tremor conditions, thesize of the fo portion of the pool is increased as a result ofentrainment of motoneurons from the other two groups.Entrainment is possible because the stretch reflex control

system is a nonlinear one and as such displays the character-

istics of frequency selective entrainment described by Hynd-man (22) for nonlinear biologic control systems. Experimentalevidence of Roberts (23) indicates that the stretch reflexcontrol system has the necessary features described by Hynd-man to sustain bounded spontaneous oscillations; namely, a

threshold and an increased sensitivity for afferent acitivity justexceeding threshold and saturation for greater levels of affer-ent activity.Enhanced tremor during withdrawal is due to enhanced en-

0

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ZILM et al.: NORMAL AND ALCOHOL WITHDRAWAL TREMOR

aI

0es,

?

al

b

bi

HE RTZ

4-0 8:0 12 0 160 4;0 8-0 12;0HERTZ HERTZ

Figure 8. (a) Results of analysis before tremor was decreased by propranolol; (al) tremor power spectrum, (a2) demodu-lated EMG power spectra. (b) Results after tremor was decreased. Data are from a nonalcoholic subject. Note changeof ordinate scale from (al) to (bl) and (a2) to (b2).

HERTZ

ca motoneuron pool

b4 8 12 16

H ERTZ

Figure 9. (a) Tremor power spectra. (b) Demodulated EMG powerspectrum. Results from an alcoholic who had a small tremor.

trainment by 1 A spindle afferents caused by: 1) increasedafferent inflow to the spinal cord because of an increase ingamma efferent bias to muscle spindles and/or, 2) an increasein the sensitivity of motoneurons to 1 A afferents as a result ofa decrease in pre- or postsynaptic inhibition or a decrease incentral inhibition of 1 A afferent spinal cord colaterals.Propranolol decreases tremor (Figures 7, 8, and 9) by de-

creasing entrainment, either by reducing fusimotor outflow,by increasing pre- or postsynaptic inhibition, or by increasinginhibition of 1 A colaterals. The delay time observed beforepropranolol reduces tremor is not due to simple circulationof the drug since the negative chronotropic effect on the heartcan be observed within three min following arterial injectionand within 45 s following intravenous injection. The delay

n I + 2+n3 = n4+ n5+ n6

Figure 10. Diagrammatic representation of how tremor is proposed tooriginate and increase. (a) Configuration under small tremor condi-tions. (b) Configuration under large tremor conditions.

may be due to the time taken for sufficient drug to bind atsites of action in the central nervous system or could be causedby the delay in the formation of an active metabolite.The hypothesis pertaining to the etiology of tremor de-

scribed above accounts for the observation that tremor de-crease is caused by a decrease in synchrony of motor units

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IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. BME-26, NO. 1, JANUARY 1979

rather than a decrease in the rectified filtered EMG. The pro-posal also accounts for the observation that larger tremors areassociated with a narrowing of the dominant power spectrapeak since 1 A afferents tend to group the firing of anterialhorn cells in the frequency range of limb resonance. An im-portant implication clinically, however, is that the proposalpredicts that those drugs which effectively increase pre- orpostsynaptic inhibition or which centrally depress the excita-bility of alpha or gamma motoneurons by polysynaptic path-ways are those which should have a high probability of de-creasing the tremor of alcohol withdrawal.

ACKNOWLEDGMENTThe authors wish to thank the nursing staff of the Clinical

Investigation Unit of the Clinical Institute of the AddictionResearch Foundation for their valuable assistance in the clin-ical investigations and Ms. M. Stewart for editorial assistance.

REFERENCES

(1) S. Wolfe and M. Victor, "The physiological basis of the with-drawal syndrome," in Recent Advances in Studies ofAlcoholism:An Interdisciplinary International Symposium, edited by N. K.Mello and J. H. Mendelson, Washington, 1970, pp. 188-199.

(2) C. D. Marsden, T. H. Foley, D. A. Owens and R. G. McAllister,"Peripheral beta-adrenergic receptors concerned with tremor."Clin. Sci. 33: 53-65, 1967.

(3) G. F. Winkler and R. R. Young, "Efficacy of chronic propranololtherapy in action tremors of the familial, senile or essentialvarieties," N. Engl. J. Med. 290: 984-988, 1974.

(4) C. D. Marsden, T. M. D. Gimlette, P. G. McAllister, D. A. L.Owen and T. N. Miller, "Effects of B-adrenergic blockade on fin-ger tremor and achilles reflex time in anxious and thyrotoxicpatients." Acta. Endocr. 57: 353-362, 1968.

(5) D. H. Zilm, E. M. Sellers, S. M. MacLeod and N. Degani, "Pro-pranolol effect on tremor in alcoholic withdrawal." Ann. Int.Med. 83: 234-235,1975.

(6) D. H. Zilm and E. M. Sellers, "The effect of propranolol on nor-mal physiologic tremor." Electroenceph. Clin. Neurophysiol. 41:310-313.

(7) D. H. Zilm, E. M. Sellers and S. M. MacLeod, "Central tremorlyticaction of propranolol in alcoholic withdrawal tremor." Proceed-ings of the Canadian Federation of Biological Sciences, (Winni-peg). 18: 158, 1975.

(8) R. R. Young, J. H. Growdon and B. T. Shahani. "Beta-adrenergicmechanisms in action tremor." New Engl. J. Med. 293: 950-953,1975.

(9) M. Salzer, "Three dimensional tremor measurements of thehand." J. Biomed. 5: 217-221, 1972.

(10) W. T. Dempster and J. C. Finerty, "Relative activity of wristmoving muscle in static support of the wrist joint: an electro-myographic study." Am. J. Physiol. 150: 596: 606, 1947.

(11) 0. C. Lippold, "The relations between integrated action potentialsin a human muscle and its isometric tension," J. Physiol (London).117: 492499, 1952.

(12) M. Cheng and J. H. Milsum, "Dynamic relationship between iso-metric force and EMG of human muscles," in Third CanadianMedical and Biological Engineering Conf. Dig., p. 45, 1969.

(13) J. S. Bendat and A. G. Piersol, Random Data: Analysis andMeasurement Procedures, Wiley-Interscience, New York, 1971,323-325.

(14) W. J. Friedlander, "Characteristics of postural tremor in normaland in various abnormal states," Neurology. 6: 716-724, 1956.

(15) C. D. Marsden, J. C. Meadows, G. W. Lange and R. S. Watson,"The relation between physiological tremor of the two hands inhealthy subjects." Electroenceph. Clin. Neurophysiol. 27: 179-185, 1969.

(16) C. D. Marsden, J. C. Meadows and G. W. Lange, "Effect of deaf-ferentation on human physiologic tremor." Lancet. II: 700-702,1967.

(17) J. Brumlik and C. Yap, Normal Tremor: A Comparative Study,Illinois, Thomas, 1970, 23-26.

(18) 0. C. Lippold, "Oscillation in the stretch reflex arc and the originof rhythmical, 8-12 c/s component of physiological tremor."J. Physiol. (London), 206: 359-382,1970.

(19) 0. C. Lippold, "Physiological tremor." Sci. Am 224: 64-73,1971.

(20) J. E. Gibson, Nonlinear Automatic Control, New York: McGrawHill, 1965, 422424.

(21) R. N. Stiles and J. E. Randall, "Mechanical factors in humantremor frequency." J. Appl. Physiol. 23: 324-3 30, 1967.

(22) B. W. Hyndman, "The role of rhythms in homeostasis." Kyber-netic. 15: 227-236, 1974.

(23) T. D. M. Roberts, Neurophysiology of Postural Mechanisms,London: Butterworths, 1967, 93-103.

Duane H. Zilm (M'76), photograph and biography not available at thetime of publication.

Edward M. Sellers, photograph and biography not available at the timeof publication.

Richard C. Frecker (M'73), photograph and biography not available atthe time of publication.

Hans Kunov (A'61-M'63), photograph and biography not available at thetime of publication.

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