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Electroencephalography and Clinical Neurophysiology, 1981, 52:400--404
Elsevier/North-Holland Scientific Publishers, Ltd.
F R E Q U E N C Y - F O L L O W I N G POTENTIALS IN MAN BY LOCK-IN TECHNIQUE MANFRED EULER and JURGEN KIESSLING Fb. 10, Physik-Technologie, Universita't Duisburg, D-4100 Duisburg, and University ENT-Clinic, D-6300 Giessen (G.F.R.)
(Accepted for publication: June 25, 1981)
The early human auditory responses to low frequency tones in the speech range are of considerable interest for objective audiometry, because they probably test the integrity of the low frequency auditory channels. These responses are phase locked to the stimulus and follow the stimulus wave form (frequency-following response ( F F R ) , Marsh and Worden 1968). It is possible to detect F F R by scalp electrodes (Moushegian et a l . 1973). Several workers have suggested the inferior colliculus (IC) as a possible source of the scalp-recorded response, mainly because F F R latency (6 msec) equals the click stimulation latency of the IC (Glaser et al. 1976). Further evidence for the IC origin is based on depth electrode measurements (Smith et al. 1975) and on data from subjects with brain stem lesions (Sohmer and Pratt 1977). Ablation experiments, however, tend to question the role of IC in F F R generation (Gardi et al. 1979). Additionally, the question of h o w far F F R is related to the apical turn of the cochlea needs further clarification. Up to now this problem could only be tackled by high-pass masking noise (e.g., De Boer et al. 1977). By using continuous tone stimulation and sensitive frequency selective analysis techniques the present investigation allows definite conclusions on these issues. Conventional F F R investigations are based on transient stimulation and c o m p u t e r averaging procedures. Response latencies are somewhat arbitrarily estimated from the F F R onset. Instead of time domain averaging fre-
quency selective analysis methods appear to be more appropriate because of the welldefined response frequency. An off-line spectrum analysis of the averaged F F R has considerably improved sensitivity (De Boer et al. 1977). This procedure does not preserve time information. As an alternative approach we use lock-in amplification to obtain a rapid and sensitive on-line F F R analysis. The lock-in amplifier can be regarded as a very narrow tunable filter designed to extract the amplitude of harmonic signals from statistical background noise. The analysis is phase sensitive, which is an important feature, as the F F R phase contains time delay information.
Method Fig. 1 shows the experimental design. The stimulus section consists of a voltage-controlled oscillator (VCO) driving a high impedance headphone (Sennheiser HD 415 X). To avoid magnetic pick up the phone is shielded by a /a-metal case and, additionally, the distance between acoustic stimulus generator and recording site has been increased by a plastic tube acting as an acoustic delay line (70 cm minimum length). With these precautions, tests with an equivalent circuit (10 kg2 wire loop) prove that the induced voltage is at least 40 dB below the F F R voltage. Further evidence, that no stimulus artefacts were measured, could be established by clamping the plastic tube; thus the sound is prevented from
0013-4649/81/0000--0000/$02.50 © 1981 Elsevier/North-Holland Scientific Publishers, Ltd.
FREQUENCY-FOLLOWING POTENTIALS BY LOCK-IN TECHNIQUE
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X Y recorder
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IO0 nV VoH'oge 5O
dela y t r~e beac~ phorqe I voitage c or~ t r o t t e d oscillator ,HJ - r'r'e t a t
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Fig. 1. Experimental arrangement for continuous tone F F R measurements by lock-in technique.
reaching the subject's ear and the F F R vanishes. A ramp generator provides the voltage to sweep the VCO frequency and to drive the X-axis of the XY-recorder. We use bipolar recording (Beckman mini disc electrodes) between forehead and mastoid with the opposite mastoid as ground. After amplification (g = 2 X 104) the lock-in analysis yields two vector components (A" cos ~ and A • sin ~) which are recorded simultaneously as a function of frequency. From these two plots F F R amplitude A and phase angle ~ in relation to the stimultis can be calculated. Usually sweep rates are in the order of 2 Hz/sec with analyser time constants of 4 sec (equivalent filter bandwidth 0.03 Hz). So it takes about 4 min to obtain F F R records in the frequency range from 100 to 600 Hz. Ten normally hearing adults served as subjects in the study. During the recording procedure that t o o k place in a silent room they were seated in a comfortable chair. As subjects were cooperative elimination of movem e n t artifacts turned out to be unnecessary.
Results To check the reliability of the m e t h o d and to identify the measured F F R components different acoustic delay lines and different electrode configurations were used. Represen-
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C
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600 Hz 800
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Fig. 2. F F R records to continuous tone stimulation as a function of stimulus frequency. The records show A • sin ~ output of the lock-in amplifier. A: ipsilateral recording (approximately 60 dB HL), length of delay tube 70 cm. B: ipsilateral recording (approximately 50 dB HL), length of delay tube 200 cm. C: contralateral recording (approximately 50 dB HL), length of delay tube 70 cm.
tative results for one person are given in Fig. 2. Traces A and B show the A • sin ~ F F R c o m p o n e n t from ipsilateral electrodes (differential amplification between forehead and mastoid of the stimulated ear) using two different delay lines. The response extended up to several kHz and exhibited a rather regular variation of phase versus frequency with constant spacings between maxima and minima, depending on delay line length. Additional white noise did n o t affect the response appreciably. Contralateral recording showed quite dif-
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ferent A • sin ~ patterns, with response maxima below 500 Hz (Fig. 2C). These potentials could be masked completely b y white noise at intensities equal to those producing subjective masking. The most remarkable feature of the contralateral c o m p o n e n t is its frequencydependent phase change, indicated b y the distance between maxima and minima increasing with frequency. By computing the derivative of phase versus circular frequency ( d ~ / d ~ ) F F R group delays could be obtained (i.e., the time delay of a wave package composed of a group of neighbouring frequencies). The ipsilateral response phase was obviously a linear function of frequency. Its group delay, therefore, was constant and turned o u t to be only 0.5 msec longer than the acoustic time delay of the respective delay line. In contralateral recording a dispersion p h e n o m e n o n occurred, till n o w undiscovered in F F R measurements. The group delay was frequency dependent and increased for lower frequencies. After subtraction of 2.78 msec acoustic delay (70 cm tube), the delay of the contralateral c o m p o n e n t amounted to 5.2 msec at 500 Hz and increased to 12 msec at 200 Hz.
Discussion
The results allow unequivocal conclusions a b o u t the origins of the main scalp recorded F F R components. In ipsilateral measurements a cochlear microphonic c o m p o n e n t (CM) prevails and supersedes neural components. The latter can be isolated b y contralateral recording. Such a view of CM components is generally accepted in far-field electrocochleography (Terkildsen et al. 1973). The far-field CM must originate in the basal cochlear turn in consequence of its extremely short latency of 0.5 msec in normal ears. This conclusion agrees with findings b y conventional recording technique (Sohmer and Pratt 1977). The absence of dispersion in the present frequency-specific measurements gives
M. EULER, J. KIESSLING
additional evidence for a basal origin, as responses from the best frequency region would exhibit dispersion according to a travelling wave phenomenon. Obviously, the CM c o m p o n e n t is an indicator of the integrity of the high frequency sensitive basal cochlear turn. We expect the amplitude-phase characteristics in ipsilateral records to shift considerably towards longer time delays in recruiting ears. The dispersion p h e n o m e n o n in contralateral F F R c o m p o n e n t s is a definite p r o o f of its apical specificity and demonstrates the cochlear frequency dispersion mechanism. The total group delay of this c o m p o n e n t consists of the acoustic delay, the travelling wave delay in the cochlea and neural delays. A more sophisticated view may additionally refer to the group delay due to the 'second filter,' but, for simplicity, we shall include this term in the total travelling wave delay. Among these different delay mechanisms only the travelling wave delay is frequency dependent. After subtracting 1 msec corresponding to the supposed neural delay from the above calculated group delays at 200 and 500 Hz, the resulting delay times agree well with travelling wave delays to the best frequency basilar membrane region obtained in single nerve studies (Anderson et al. 1971) and in derived narrow band action potentials (Eggermont 1976). The data of Anderson et al. on squirrel monkeys range from 3 msec delay at 500 Hz to 6--7 msec at 200 Hz. The human-derived action potential data come quite close to our results (5 msec delay at 500 Hz, approximately 12 msec at 200 Hz as can be found by extrapolating Fig. 5 of Eggermont 1976). The present dispersion p h e n o m e n o n is consistent with the assumption that, at moderate intensities, F F R originate in neurones tuned to respective frequency. As a consequence, the 6 msec argument for brain stem origin appears questionable, as at 500 Hz the travelling wave delay alone, already amounts to 4 msec at least, and it increases considerably for lower frequencies. The obvious contradiction to the
FREQUENCY-FOLLOWING POTENTIALS BY LOCK-IN TECHNIQUE
results of depth electrode measurements (Smith et al. 1975) may arise from the different latency determination procedures and stimulus conditions. One possible explanation is that transient stimulation involves neural structures completely different from those activated in the steady state, which are probed b y the present method. The continuous tone F F R is likely to reflect neural activity from a more peripheral origin, probably related to N1 or N2 activity known from electrocochleography. The study demonstrates the feasibility of continuous tone lock-in F F R analysis and shows the inherent advantages over conventional techniques, owing to the continuous frequency-specific information. Apical audiometry (cf., Davis 1976) appears to be practicable with the present detection method, which may become a valuable tool of electric response audiometry.
Summary Frequency-following responses ( F F R ) from continuous tone stimulation were investigated b y lock-in analysis. The technique is superior to conventional tone-burst stimulation, because it allows continuous registration of the response parameters with sweeping frequency. The scalp recorded F F R consists of at least t w o components separable from each other by their phase/frequency relationship. The microphonic c o m p o n e n t that dominates in ipsilateral records shows latencies of a b o u t 0.5 msec with negligible dispersion and must therefore originate in the basal cochlear turn. The neural c o m p o n e n t exhibits considerable dispersion, reflecting the travelling wave delay up to the region of best frequency. These long cochlear time delays are consistent with an apical F F R origin, and brain stem sources of the continuous tone response appear to be questionable. The present F F R analysis technique opens up a very direct and comprehensive way to assess the integrity of the entire inner ear for high frequency basal and low frequency apical cochlear regions as well.
403
R~sumd Potentiels accord~s d la fr~quence ~tudi~s chez l'homme par une m~thode 'lock-in'
La rdponse accordde ~ la frdquence ( F F R ) pour une stimulation sonore continue est analys~e par 'lock-in'. Cette technique se montre supdrieure ~ la stimulation conventionnelle par bouffdes tonales, du fait que les caract~ristiques de la F F R sont enregistr~es de fa~on continue avec la fr~quence. La F F R mesur~e par les dlectrodes de scalp est composde de deux ~ldments principaux au moins d'origine microphonique et neuronale, que l'on peut distinguer par leur relation entre phase et frdquence. La composante microphonique, prddominante dans les enregistrements ipsilatdraux, est produite dans la spirale basale, vu sa courte latence (0,5 msec) et son absence de dispersion. La grande dispersion de la composante neuronale refl~te le d~lai de progression le long de la membrane basilaire jusqu'~ la rdgion de frdquence optimale. Ces longs ddlais cochl~aires sont en accord avec une origine apicale de la F F R , et jettent un doute sur l'hypoth~se de leur origine dans le tronc c~rdbral. La prdsente mdthode d'analyse de la F F R permet de vdrifier de faqon directe et complete l'intdgrit~ de l'oreille interne tout enti~re, aussi bien pour les rdgions cochldaires basales (des hautes fr~quences) qu'apicales (des basses frdquences).
References Anderson, D.J., Rose, J.E., Hind, J.E. and Brugge, J.F. Temporal position of discharge in single nerve fibers within the cycle of a sine-wave stimulus: frequency and intensity effects. J. acoust. Soc. Amer., 1971, 49: 1131--1139. Davis, H. Brain stem and other responses in electric response audiometry. Ann. Otol. (St. Louis), 1976, 85: 3--14. De Boer, E., Machiels, M.B. and Kruidenier, C. Lowlevel frequency-following response. Audiology, 1977, 16: 229--240.
404 Eggermont, J.J. Analysis of compound action potential responses to tone bursts in the human and guinea pig cochlea. J. acoust. Soc. Amer., 1976, 60: 1132--1139. Gardi, J., Merzenich, M. and McKean, C. Origins of the scalp-recorded frequency-following response in the cat. Audiology, 1979, 18: 353--381. Glaser, E.M., Suter, C.M., Dasheiff, R. and Goldberg, A. The human frequency following response: its behavior during continuous tone and tone burst stimulation. Electroenceph. clin. Neurophysiol., 1976, 40: 25--32. Marsh, J.T. and Worden, F.G. Sound evoked frequency-following responses in the central auditory pathway. Laryngoscope (St. Louis), 1968, 78: 1149--1163.
M. EULER, J. KIESSLING Moushegian, G., Rupert, A.L. and Stillman, R.D. Scalp-recorded early responses in man to frequencies in the speech range. Electroenceph. clin. Neurophysiol., 1973, 35: 665--667. Smith, J.C., Marsh, J.T. and Brown, W.S. Far-field recorded frequency-following responses: evidence for the locus of brain stem sources. Electroenceph. clin. Neurophysiol., 1975, 39: 465--472. Sohmer, H. and Pratt, H. Identification and separation of acoustic frequency following responses ( F F R s ) in man. Electroenceph. clin. Neurophysiol., 1977, 42: 493--500. Terkildsen, K., Osterhammel, P. and Huis in 't Veld, F. Electrocochleography with a far field technique. Scand. Audiol., 1973, 2" 141--148.