vestibular nerve projection to the cerebral cortex of the rhesus monkey

Experimental Brain l~ese~rch 2, 318--327 (1966)

Vestibular Nerve Projection to the Cerebral Cortex of the Rhesus Monkey

J.M. I~REDIaICKSON *, U. FIGGE, P. SCIIEID** and H.H. KORNIIUBER

Neurologische Klinik mit Abteilung fiir Neurophysiologie, Universit~t Freiburg, Freiburg i. Br., Germany

Received June 2, 1966

Summary. 1. Cortical potentials evoked by electrical stimulation of the vestibular nerve in the Rhesus monkey indicate that the primary receiving area for the vestibular nerve is located in the posterior part of the postcentral gyrus at the base of the intraparietal sulcus between the first and second somatosensory fields, probably in Brodmann's area 2.

2. An origin of the evoked cortical potential from other cranial nerves was excluded by extirpation of the cochlear, facial and intermedius nerves and by vestibular stimulation before and after section of the V, IX, X and XI nerve roots at the brainstem. Only sectioning the vestibular nerve abolished the response.

3. This field partially overlaps the SI cortical region responsive to electrical stimulation of the contralateral median nerve. There is interaction between vestibular and median nerve afferents within the overlap zone.

4. I t is postulated that the primary cortical vestibular field contributes information for higher motor regulation and conscious spatial orientation.

Key Words: Vestibular projection area - - Cortex cerebri - - Rhesus monkey

Introduction

The purpose of this investigation was to determine the primary cortical receiving field of the vestibular nerve in the macaque monkey, and to examine the possibility of convergence of somatosensory and vestibular afferents in the cortex, as had been previously demonstrated in the cat [12]. A preliminary note of our results appeared in 1965 [10].

A cortical projection of the vestibular nerve has been previously demonstrated in the cat [18]. I t was found to lie in juxtaposition to the first and second somatic and the acoustic areas. I ts position could not be accurate]y estimated in the primate due to the phylogenetic development of a deep sylvian fissure. The vestibular field in man was thought to be located in the temporal lobe [13], or in area 3a of the central fissure [7].

Methods

The experiment, was carried out on 11 healthy Rhesus monkeys, weighing 2 . 5 4 kg. A long-acting penicillin (600,000 units) was given intramuscu]ar]y preceding each experiment. Pentobarbital sodium (Nembutal) was the anesthetic agent used. The initial dose of 30 mg/kg

* Visiting investigator, Department of Surgery (Otolaryngology), University of Chicago. ** Stipendiat der Stiftung Volkswagenwerk-Stipendium, Germany.

Vest ibular Nerve Pro jec t ion to the Cerebral Cortex 319

given in t raper i toneal ly , was supp lemen ted in t ravenous ly to main ta in a, s table level o f cortical ac t iv i ty . The rectal t e m p e r a t u r e was main tMned be tween 36 and 38 ~ C.

Fol lowing a tempora.1 er~niotomy, the t empora l lobe was gent ly e levated ex t radurMly exposing the pe t rous por t ion of t he t empora l bone. U n d e r microscopic control, t h a t por t ion of the pe t rous bone overlying the in ternal audi tory mea tus and genieulate ganglion was carefully r emoved wi th cut t ing and d i amond burrs. The dural shea th enveloping the seven th

' ~ lOOper sec '10 m s@c

Fig. 1. Ssmidiag~'am of Macacc~ mula~ta brain with a superimposed pattern of evoked responses following contralateral vestibular nerve stimulation. Striped zone represents the extent of cortical exploration. Responses are located in the parietal lobe at the ibot of the intr~parietal suteus. ~esponse amplitudes are arbitrariiy divided into: 600--900 t~u (dark shading), 300--600 ~V (medium shading) and 0--300 #V (light shading). Numbe~ show

approxim~ location of Brodmann's eytoarchitectonie areas Beneath, is a photograph of 10 superimposed primary vestibular evoked potentials (downward deflection is

positive). Marker at right is 600 zV, and time marker below is 100 cycles/see. Monkey 4

and e ighth cranial nerves was incised. The fl~cial nerve, running f rom the b ra ins t em to t he middle ear was excised en bloc wi th the genieulate ganglion and in te rmedius nerve, followed by excision o f t he cochlear divis ion of t he e igh th nerve.

A curved bipolar s t ~ l s t imula t ing electrode was placed benea th the ves t ibular nerve as i t lay in si tu such t h a t the nerve laid upon the electrodes ' concave surface. The electrode had a 2mm t ip separa t ion and was insula ted except for t h a t por t ion in contac t wi th the nerve. The nerve was s t imula ted wi th 0.4 msec square waves a t a vol tage (usually abou t 1 volt) sufficient to produce a m a x i m u m cortical response. The cortex was then exposed and k e p t covered wi th w a r m mineral oil (37 ~ C).

Conica l evoked potent ia ls were recorded wi~h a silver bail e lectrode a t 1 m m httervals, The cor tex was explored eontra.lat~rally in 7 monkeys and bi la teral ly in 4, The boundr ies of explora- t ion were: t he superior saggital sinus, below t h e media l t empora l fissure, a line I cm poster ior to the lunate sulcus, and anter ior ly to inc[ude B r o d m a n n ' s areas 6 and 8. In several exper iments t he cortex bur ied in t he d e p t h of the sy]vian and central fissures was also explored. Ten st imuli were del ivered per e lectrode posit ion. Responses were super imposed and photographed . Evoked responses were p lo t t ed on ~ p h o t o g r a p h of the bra in surface.

320 J . M . FREDRICKSON, U . FIGGE, P. SCHEID and H.H. KOR~HVBER:

The median nerve, chosen because of its hand afferents was exposed at the wrist. I t was stimulated with a 0.3 msec square wave pulse through a bipolar electrode.

Paired stimuli (conditioning and test, stimuli) were delivered to the vestibular and/or median nerves at intervals varying up to 500 msec in order to determine relative and absolute depression times (recovery cycles) of the resulting cortical evoked responses. A four second interval was allowed between stimulus pairs. The resulting evoked potentials of 200 successive pairs of stimuli were recorded on tape, averaged by a Mnemotron CAT computer and auto- matically plotted. Interaction indices were calculated as described by Berman (3).

Results

Responses to Vestibular Nerve Stimulation: The pr imary cortical projection field of the vest ibular nerve was found to lie in the posterior par t of the postcentral gyrns caudal to the lower end of the in t rapar ie ta l sulcus (Fig. 1). I n the

20 msec

Ips i lo te ra l vest ibu lar nerve s t imula t ion .

Fig. 2. The ipsilateral evoked response (top) was obtained by averaging potentials resulting from 500 successive single vestibular nerve stimuli delivered at 4 see intervals. The 5--6 msec latency is similar to the contralateral response, but the ipsilateral response amplitude was just 50 #V. The cortical recording point at the foot of the

intraparietal sulcus is indicated, l~Ionkey 5

major i ty of animals, the field began immedia te ly below this sulcus. At t imes i t began about 1 mm. more caudal. I t did not ex tend to the central sulcus under deeper anesthesia.

This region appears to belong to area 2, as mapped by C. and O. VOGT [16]. I t is located between the somatic sensory project ion areas I and I I of WooLsEY

Vestibular Nerve Projection to the Cerebral Cortex 321

[20]. I t is separated from the temporal lobe by the second somatic area, parietal operculum and insula.

The vestibular response was almost exclusively eontralateral, consisting of a short positive wave with a 5--6 msee latency and an average amplitude of 600--800/~V (Fig. 1). The ipsilateral evoked potential had a similar latency, but the amplitude averaged only 50/IV (Fig. 2).

The primary response was often followed by a train of 3--8 regularly spaced surface positive waves (Fig. 3). The first wave began approximately 70 msec following the stimulus, and the interval between them varied from 50--70 msee.

I 1(]OpV

0 m sec Int. 300 msec Int. 30 msec

Int, ]25msec

DoubLe stimuLation of the contraLoteroL vestibular nerve.

Fig. 3. Recovery cycle s tudy for the contralateral evoked responses resul t ing f rom pai red s t imula t ion of the vest i- bular nerve (see Methods). W h e n the s t imulus in terval (Int .) was less than 400 msec. (relat ive depression t ime) the second evoked potent ia l became smaller as the in terval be tween st imuli was shortened, unti l there was no second response a t 20 insec (absolute depressiml t ime). The la tency of the second evoked potential remained similar to tha t of the first. The rhy thmic posi t ive af terdischarge potentials are well developed in the upper left curve. The

point of cortical recording is indicated. Monkey 7

A second, smaller, inconsistent vestibular projection was found bilaterally in the motor cortex, anterior to the lower part of the central sulcus. The response latency was similar to that of the postcentral field, but the amplitude was smaller and responses were sometimes unobtainable. The response in this field appeared to be more dependent upon the depth of barbiturate anesthesia.

The recovery cycle for the contralateral vestibular projection field is illustrated in Figures 3 and 6. The amplitude diminution indicating a relative depression

322 J. 1V[. ~'REDRICKSON, U. FroGS, P. SCH:~ID and H.H. KORNHUBER:

period of the evoked potentials was approximately 400 msec. The absolute depression period was 20 mscc. The test response was augmented at 80 msec (Fig. 6), corresponding to the rising phase of the first and most prominent wave of the repetitive discharge.

Control Experiments : The cortical origin of the potentials was verified in two ways: (1) in 2 monkeys movement artifacts were eliminated by immobilization with Flaxedil under artificial respiration. (2) The pr imary positive evoked potential at the surface of the vestibular cortex reversed to a pr imary negative potential when a microelectrode was introduced into the cortex.

Other sensory sources of the cortical potentials from neighbouring crania] nerves were excluded in two experiments. After the cortical vestibular field was mapped in the usual manner, the previously exposed cranial nerves V, IX, X and

I lO0~IV

20 m s e c

<J Int. 300 msec

Int . 130msec

Int. LOmsec

Int. 30 msec

DoubLe s t imuto to t ion of the controLoteroL median nerve.

Fig, 4. Recovery cycle stt~dy for the contralatcral evoked responses resul t ing f rom pai red s t imula t ion of the median nerve (see Methods). Note that there is no second evoked potential a t a s t imulus in terval of 30 msec (absolute depression time), l~hythmic waves following both p r imary responses are well developed at the 130 msee interval ,

The cortical recording point is i l lustrated. Monkey 7

X I were sectioned. The fifth cranial nerve was readily exposed through the temporal eraniotomy, while IX, X and X I were reached via an occipital eraniotomy. This procedure did not alter the threshold voltage of the stimulus or the cortieal


distribution of the vestibular evoked response. Finally, the vestibular nerve was sectioned at the brainstem. Thereafter, the vestibular cortical evoked potential eould only be obtained when the stimulating voltage was increased 20 told.

Overlap and Interaction between Vestibular and Median Nerve AGerents: The projection of the median nerve in the first somatic (SI) area under barbiturates was found to be exclusively contralateral. This primary response consisted of a

Int. 20msec

fo~

6: 2:

2 6 I0 14 ;8 22 26

4

Int Omsec

mV"

L2-

0.9.

0.6.

0 3

V S V+S alg

Interval. stimulation of the contraLateraL vestibuLar and median nerves.

V+S l"neos.

Fig. 5. Evoked potentials resulting respectively tram eontralateral vestibular and median nerve stimulation delivered at short intervals and recorded from a cortical point within an overlap area where a response was obtained from both modNities. This vestibular-somatosensory overlap, which is Iocated in the periphery of the vest ibular field cephalad to its center, is i l lustrated as a shaded area of cortex (lower left). The recording point within this overlap is marked, the sulci labelled, and a m m scale provided. The relative depression time for this vest ibular-median nerve sequence was approximately 80 msec, however, there wa.s no absolute depression time (note tha t the median nerve response is still prominent at 20 msec.). The ampli tude of the evoked potential (upper right) was larger when both st imuli were presented simultaneously (meas.) than when either was delivered separately, but not as large as

the algebraic (alg.) sum of both (see Histogram, lower right), monkey 7

short positive wave with a 7--8 msec latency, and an average amplitude of approximately 800/~V (Fig. 4). Under the given depth of anesthesia, the recovery cycle (Figs. 4, 6) had a relative depression time of approximately 400 msee and an absolute depression time of 30 msec.

Overlap between median and vestibular nerve responses occurred in a portion of cortex approximately 5 mm long and 3 mm wide (Fig. 5). In three monkeys, a point on the cortex was chosen where the vestibular and median nerve responses

324 J.M. FREDRIOKSON, U. FIGGE, P. SOHEID and H.H. KOI~VBm~:

were of nearly equal amplitude. Interact ion was studied. Representative results from one animal are illustrated in Figure 5. The recovery cycles were similar regardless of which of the two stimuli was presented first (Fig. 6). The relative

-5 E

C~

2

g

l

~-~ ~k ibu la r- //o ~ ~ e / / % / " x 0t11 t~., C . / / .

I / % 11 / , / / x x

l // / I x �9 Somatic- ~omas , .~. . - - / ~ . . . . . . . . . . . . . .

�9 I - 0 - - - - - q

J ~st:ibular I o / ~ e ~ i Ves~i bular- Veski bular

~01 i . - - �9 .// ol / :

0 20 40 60 80 I(X:) 120 14"0 160 180 200

Z.terst:irnulus Znf.erval ( r e s e t . )

Fig. 6. Graph o] recovery cycles o] various cortical 2~ointe (see }figures 3, 4 and 5). The stimulus sequence is identified for each curve. Monkey 7

depression t ime for each modali ty was approximately 70 msec, but there was no absolute depression as a response to the second stimulus was always present.

Discussion

Contrary to opinions expressed in the psychologic literature [19], this s tudy suggests tha t there is a vestibular representation in the primate cerebral cortex. Despite what might be presumed on the basis of the vestibular end organ location with the eoch]ea, the electrophysiological evidence places the vestibular cortical location in the postcentral gyrus of the monkey, not in the temporal lobe as proposed [13].

The location of the monkey 's cortical vestibular field between the first and second somatic areas is the same as tha t in the cat. However, the juxtaposition of the vestibular to the auditory cortex in the cat does not exist in the monkey, due to the expansion of the temporal and parietal fields in primates and the development of a deep sylvian fissure.

Because of the juxtaposition of the vestibular field to the first and second somatic projections of the face and ear, the intermediate, facial and cochlear nerves were extirpated and control experiments were done with stimulation of the vestibular nerve before and after section of the trigeminal, glossopharyngeal, vagal, accessory and vestibular roots at the brainstem. The results show clearly tha t the cortical potential evoked by electrical stimulation of the vestibular nerve is vestibular in origin.


From a functional point of view, vestibular mechanisms belong to the pro- prioceptive somatosensory system rather than to the auditory. Neither the vestibular nuclei nor cortical area 2 appear to have auditory afferents, but both have a strong input from "deep" somatosensory afferents [6, 14]. In a single unit analysis, POWELL and MOU~TCASTLE [14] found that 90 % of the neurons studied in area 2 responded exclusively to "deep" sensory stimulation. Their findings agree with those for units in the vestibular nuclei of the cat which responded to joint movement but not to stimulation of the skin [6].

The cortical overlap and interaction of vestibular and somatosensory responses corresponds to previous reports of sensory convergence in the two cortical vestibular areas found in the eat [8, 9, 12].

The second vestibular receiving field in the primate motor cortex, albeit inconsistent under barbiturate anesthesia, agrees with results obtained in a mieroelectrode study on flaxelidized cats [8].

Functional Significance o/ Vestibular Representation in the Postcentral Region: Vestibular afferents in the posteentral gyrus (probably area 2) may aid in two functions : higher motor regulations (area 2 is known anatomically to have strong connections with the motor cortex), and conscious orientation within space.

Spatial orientation and disorientation [5] involve visual, somatosensory and vestibular cues. BE~ITOF~ [2] has demonstrated a vestibular component in spatial orientation in children and dogs. Clinically, spatial orientation has been found to be disturbed following parietal lesions [15].

Otoneurological Findings Associated with Cortical Lesions. The assumption that vestibular afferents were located in the temporal cortex, has, in the past, led some clinicians to seek vestibular system defects in persons with temporal lobe lesions. Carmichael et a]. [4] proposed that ipsilateral directional preponderance of caloric induced nystagmus is the result of a lesion involving the temporal cortex.

The primate temporal cortex, however, appears neither to be a vestibulo- sensory nor an oculomotor area [11, 17]. The fact tha t ipsilateral directional preponderance of caloric nystagmus occurs only during visual fixation and only in subcortical posterior forebrain lesions with unilateral diminution of optoldnetic nystagmus suggests tha t it is due to an interruption of oculomotor efferents passing through the white substance of the posterior forebrain region to the brainstem rather than vestibular afferents to the cortex (1).

Zusammenfassung

1. Corticale Reizantworten nach elektrischer Rcizung des Nervus vestibularis bei Rhesus-Affen ergaben mit 5 msee Latenzzeit als prim/~re cortieale Vestibularis- Projektion den unteren hinteren Tell der PostzentrMwindung am Ende der Fissura intraparietalis. Das vestibul~re Rindenfeld liegt zwischen dem ersten und zweiten somatischen Feld und entspricht der unteren Area 2 nach VOGT.

2. Ein I r r tum durch Mitreizung benachbarter Hirnnerven wurde durch Exstir- pation yon Cochlearis, Facialis und Intermedius sowie durch Vestibularisreizung vor und nach Wurzeldurchschneidungen von Trigeminns, Glossopharyngeus, Vagus, Accessorius und Vestibularis ausgcschlossen.

326 J.M. FREDRICKSON, U. FIGGE, P. SCHEID and H.H. KORNIIUBER:

3. Das vestibul/~rc Rindenfcld ist partiell fiberlagert vom somatoseasiblen Projektionsfeld S I, das auf contrala teralen Mcdianus-Reiz antwortet . Es besteht In t e rak t ion dcr evoked potentials zwischen Vestibularis- und Medianus-Reizung in diescr Ubergangszone.

4. Die MSglichkeit, dab die corticalc Vest ibular is-Projckt ion zu h6heren motorischen Regclungen und zur bewul3ten r/~umliehen Orientierung beitrs wird diskutiert .

Acknowledgement: We wish to thank Herrn H. KAPP for his technical assistance.

References

[1] BADER, W., u. H.H. KORNI4UBER: GroBhirnl~sionen und vestibul~rer Nystagmus. Ver- gleichende e!ektronystagmographische Untersuchungen bei geschlossenen Augen und mit visueller Fixation. Acta otolaryng. (Stockh.) 60, 197 (1965).

[2] BERITOFF, J. S. : Spatial orientation of man and animals. 22 Internat. Congr. Physiol. Sci. (Leiden), Exerpta Med. Internat. Congr. Ser. No. 47, I, 3 (1962).

[3] BE~MA~, A.L. : Interaction of cortical responses to somatic and auditory stimuli in anterior ectosylvian gyrus of cat. J. Neurophysiol. 24, 608 (1961).

[4] CARMICHAEL, E.A., M.R. DIx and C.S. HALLPIKE: Lesions of the cerebral hemispheres and their effects upon optokinetic and calorie nystagmus. Brain 77, 345 (1954).

[5] C~AMBE~S, R.M.: Isolation and Disorientation. In: Physiological Problems in Space Exploration (J.D. Hardy edit.). Springfield/Illinois: C.C. Thomas 1964.

[6] FREDRICt;SON, J.M., D. SCHWARZ and H.H. KORNHUBE~: Convergence and interaction of vestibular and deep somatic afferents upon neurons in the vestibular nuclei of the cat. Acta otolaryng. (Stoekh.) 61, 168 (1966).

[7] HASSL~g, R. : Forels Haubenfaszikel als vestibul~re Empfindungsbahn mit Bemerkungen fiber einige andere sekundi~re Bahnen des Vestibularis und Trigeminus. Arch. Psychiat. Nervenkr. 180, 23 (1948).

[8] KOR~UBEg, H.H., u. J.C. ASC~OFF: Somatisch-vestibul~ire Integration an Neuronen des motorischen Cortex. Naturwissenschaften 51, 62 (1964).

[9] -- , and J. S. da Fo~S~CA: Optovestibular integration in the cat's cortex: a study of sensory convergence on cortical neurons. In: The Oculomotor System (M.B. Bender edit.) New York: Hoeber 1964.

[10]--, J.~/[. ~REDRs U. U. FIGGE: Die corticale Projektion der vestibul~ren Afferenz beim Rhesus-Affen. Pfliigers Arch. ges. Physiol. 283, 1~ 20 (1965).

[11] LILLY, J. C. : Correlation between neurophysiological activity in the cortex and short-term behavior in the monkey. In: Biological and Biochemical Bases of Behavior (H. F. Harlow and C.N. Woolsey eds.). Madison: University of Wisconsin Press 1958.

[12] MICXLn, W.A., and H.W. ADES: A composite sensory projection area in the cerebral cortex of the eat. Amer. J. Physiol. 170, 682 (1952).

[13] PEI~-I~I~LD, W. : Vestibular sensation and the cerebral cortex. Ann. Otol. 66, 691 (1957). [/4] POW]~LL, T.P.S., and V.B. MOV~TCASTLE: Some aspects of the functional organization

of the cortex of the post central gyrus of the monkey: a correlation of findings obtained in ~ single unit analysis with cytoarchitecture. Bull. Johns Hopk. Hosp. 105, 133 (1959).

[15] SEMM]~S, J., S. W]~I~ST]~I~, L. G~:N~ and H.L. T~.v~:m~: Spatial orientation in man after cerebral injury: Analysis by locus of lesion. J. Psychol. 38, 161 (1955).

[16] VOOT, C., u. O. VOGT: Allgemeinere Ergebnisse unserer Hirnforschung. J. Psychol. Neuro]. (Lpz.) 25, 361 (1919).

[17] WAOMA:~, I.H. : Eye movements induced by electric stimulation of cerebrum in monkeys and their relationship to bodily movements. In: The Oculomotor System (M. B. Bender edit.). New York: Hoeber 1964.


[18] WALZL, E.M., and V.B. MOUNTCASTLE: Projection of the vestibular nerve to cerebral cortex of the cat. Amer. J. Physiol. 159, 595 (1949).

[19] WENDT, G.R. : Vestibular Functions. In: Handbook of Experimental Psychology (S. S. Stevens edit.). New York: John Wiley and Sons 1951.

[20] WooLseY, C.N. : Patterns of sensory representation in the cerebral cortex. Fed. Proc. 6, 437 (1947).

Dr. J. M. FREDRICKSON, Department of Surgery (Otolaryngology) Stanford University, Palo Alto, California, USA

Doz. Dr. H.H. KORNHUBER, Abteilung ffir klinische Neurophysiologie der UniversitEt 78 Freiburg i. Br., West-Germany

vestibular nerve projection to the cerebral cortex of the rhesus monkey

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