Journal of Vestibular Research. Vol. 8. No.1. pp. 7-16.1998 Copyright © 1998 Elsevier Science Inc. Printed in the USA. All rights reserved

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NEUROANATOMIC SUBSTRATES FOR VESTIBULO-AUTONOMIC INTERACTIONS

Carey D. 8alaban* and Jennifer D. Portert

*Departments of Otolaryngology and Neurobiology, University of Pittsburgh School of Medicine; tDepartment of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Reprint address: Carey D. Balaban, Ph.D., Department of Otolaryngology, University of Pittsburgh, Eye & Ear Institute, 203 Lothrop Street, Pittsburgh, PA 15213

o Abstract-Recent anatomical studies have identified a network of central neural circuits that appear to integrate vestibular and autonomic in­formation. Like vestibulo-ocular and vestibulospi­nal circuits, these pathways appear to be under in­hibitory modulation by distinct regions in the medial aspect of the cerebellar cortex. These cen­tral circuits have the potential to explain the known influence of vestibular stimulation on auto­nomic motor responses through descending effects on brain stem autonomic regions. In a more global context, the extensive convergence of vestibular and autonomic information in both vestibular and autonomic brain regions is consistent with the concept that vestibular and visceral information (for example, blood pooling and visceral proprio­ception) are used to form a central representation of gravitoinertial parameters during movements. Thb representation can influence neural circuitr~ invoh e(: in postural control. cardiovascular con­trol. perception o~' the spatiai vl"rticai and emo­tional or aff'e cti "t' responsc!>. © 1991) Elst'\'ic:­~cicnct Inc.

:J hey" ords - anatomy: vcstibular llu::Je:: cerehellum; autonomic nervous system.

Introduction

The clinical observation that vertigo is accom­panied by gastrointestinal discomfort, nausea, and vomiting has long been the basis for specu­lations regarding mechanistic links between ves-

7

tibular and visceral function. Prior to the 19th century, this observation was evident in the de­scriptions of the etiology of vertigo in the medi­cal literature. which often recommended vertigo therapies directed at both the stomach (or other viscera) and brain. For example, a mid-17th century English translation of Paracelsus' Of the Mysteries of the Signes of the Zodiack con­tained the following discussion of vertigo:

Many who labour with this disease, the Heaven and Earth seems to them to tum like a wheel, and all things to run around ... For there is such a Convulsion of the Brain, that the Spirits of the Sight and the Brain, are im­pedited by a certain gross thick vapour ascend­ing from the Stomach to the head. through the optick nerves. (1)

Thi. them, wa', al-.o eviclen; in n 17th centur:- En­glish edition (I " Amhrose Pare ' ~ worl:~ which ree­(I~lllzecl a rob: oj optic f1 0 \ \ stimulation ("wheeL­ru nnln~ round. 0'" wn irl p It~ iI' water.,·· i. visual d ill efrect~ and tinn Itu~ ("noyse in the ear~") U5

factors gel111ane to the etiology of vertigo:

The \ferngo i ~ a sudden darkening of the eye~ and sighl by a vaporous & hot spiri t which a&­cendeth to the head by the sleepy arteryes [ca­rotid arteries]. and fils the braine, disturbing the humours and spirits which are cantey ned there, & tossing them unequally, as if one ran round, or had drunk too much wine. This hot spirit oft-times riseth from the heart upwards

8

by the internall sleepy arteries to the Rete mirabile, or wonderfull net; otherwhiles it is generated in the brain, its selfe being more hot than is fitting; also it oft-times ariseth from the stomack, spleen, liver and other entrals being too hot. The signe of this disease is the sudden darkening of the sight, and the closing up as it were of the eyes, the body being lightly turned about. or by looking upon wheels running round. or whirle pits in waters. or by looking dmvn allY deep '> 1' qeep place~ . If The ()riglnall t 1(' the disease '1 rnceed from the braille. I he na­

: lL' ntS .Ire [!'IlubieJ ·.\'lIh the ht.:aLi- Iche. ;1 e ~ ~' 1-

tles:.:e of ihe heau. the !1ny,e in il1(:: ~ars Clnu Ilft­tllnes lhey lose their smell. .. , :2)

Based upon these etiologic schemata, treatments included a combination of measures directed at the stomach and central nervous system:

Fyrst let ye paciem beware of drynkyng of wine or strong drynkes, they must beware of eatyng of chibolles, garlyke, and onyons, and all vaporous meates & drynkes, and let them use pilles of cochie to purge the stomake and the hed, and gargariees be good for this matter, and yerapigra, and sue he men havynge this passion let them beware of clymnge or goynge up upon highe hyUes or rounde stayres. (3)

This communication reviews recent advances in our understanding of pathways in the central nervous system that receive vestibular and vis­ceral information. These pathways appear to be neural substrates for vestibular influences on

C. D. Balaban and J . D. Porter

direct projections from cerebellar Purkinje cells, which form a second major component of these circuits. Different brain stem pathways receive projections from different cerebellar regions. For example, vestibulo-ocular reflex pathways are af­fected by the flocculo-nodular lobe, while vestib­ulospinal pathways are intluenced by the anterior lobe. We will develop an initial working hypothe­sis that vestibulo-autonomic pathways follow rhese ~ame ba!-.lc principles' ,)f organization.

Detailed .;(uuies nf rhe relationship between rhe fl()c..:~I1(j- ;l uLiuiar :()iJe anti ve~[ibLllo-oclllar

.;·erlex relay neurons ha .. e generated the hypoth­esis that cer~bellar ..:: ircuits can be divided into discrete modular units that modulate activity in highly specific vestibulo-ocular reflex pathways (for example, 4-15). These data gave rise to the microcomplex hypothesis (4), which stated that the cerebellum is organized into basic units, termed microcomplexes (Figure 1, panels B and C). Microcomplexes are defined anatomically by a network of specific interconnections be­tween groups of cells in the inferior olive, sagit­tal groups of cerebellar Purkinje cells (micro­zones) and pools of cells in the cerebellar nuclei and/or the vestibular nuclei. The inferior olivary component is defined by crossed projections of their axons (climbing fibers) to both a pool of Purkinje cells in cerebellar cortex and the target neurons of the same Purkinje cells in the cere­bellar or vestibular nuclei. The cerebellar com­ponent, or microzone is defined both by efferent projections of Purkinje cells to specitlc pools of cerebellar or vestibular nuclear neurons and by

re­motion sickness and the perception of one's re- flexes. distinct cerebellar microcomplexes ap­lationship to gravitointertial forces . pear to be responsible for control of vestibulo-

--------oIP~roee.,'"ie"'alt!"~!lS48!!1t!lt!Ie~ie!'J!!!I ... (Etf'iee"'r'f!ft~rf'Ee"".o!.ie~'fI"'~, ~!leele~iee1'~e~iee'li!lte~e~ ... e~e~dril!llltil'"2!ltimld~o~prttoO'lki~·mhreetiti-c.-c reflex eye movements in 4) indicate that there are several basic principles the planes of the horizontal, posterior, and supe­of organization of vestibular nuclear pathways rior semicircular canals (4,13). For example, a that mediate vestibulo-ocular and vestibulospi- microcomplex related to horizontal vestibulo­nal responses (Figure 1, panel A). At the core of ocular reflex control consists of climbing tiber each pathway is a pool of neurons in the vestib- projections from the caudal dorsal cap that re­ular nuclei, which receives inputs from specific spond to retinal slip (global movement of the vi­combinations of afferents from vestibular end- sual world) in the plane of the horizontal semi­organs and projects to either motoneurons or in- circular canal (16), a band of Purkinje cells in temeurons that mediate the motor responses the central flocculus termed zone II or "H-zone", (for example, see references 4,7). These pools and a pool of neurons in a region termed "pars of vestibular nucleus cells are also modulated by beta" of the lateral vestibular nucleus or the

Vestibulo-Autonomic Pathways 9

A Cerebellar Purkinje

Cells

Vestibular Vestibular Motoneuronsl Nerve

B

I

I

Nuclei

Cerebellar Microzone

I

I

I

I

'midline I

I ~r.~ Nucleo-ollvary V

fibers Inferior Olive

Premotor Circuits

cr--___ ~

Nucleo-ollvary

flbers@,--:-/'--__ --

Inferior Olive

. ,

I mldllna I

Figure 1. Schematic diagram of the organization of cerebellar microcomplexes involved in vestibular informa­tion processing. (A) Block diagram of the basic organization of these pathways. (B) Basic form of the micro­complex hypothesis (4). Microcompiexes are modular circuits defined by a specific pattern of connections be­tween a pool of inferior olivary cells, a sagittal group of cerebellar Purkinje cells, and a pool of neurons in the vestibular (or, in the general case, cerebellar) nuclei. (e) Modified form of the microcomplex hypothesis based on more recent data. Two additional features are incorporatec. First. ipsilateral nucleo-olivarl' connections may provide <. substrate for bilaterai coordination 0 " activity in microzones. Second. collateralized projection~ of Climbing fibers to multiple cerebeller mlcrozones may oe a substrate for coordinatior 0; activity ir paralle mo­tor pathways.

magnocellular medial vestibular nucl~ui> (re-viewed in reference 4). .

The result~ of recent neuroanatomical stud­ies are consistent with the hypothesis that vesti­bulo-ocular and vestibulo-autonomic pathways in the brain stem and cerebellum show similar principles of organization. Following the exam­ple of studies of vestibulo-ocular circuits, these studies have proceeded in two logical steps: (a) identification of the topographic organization of cells in the vestibular nuclei that project to cen-

tral autonomic pathway~ and (b) identification of connectiom between "autonomic" sites it: the cerebellar conex and vestibular nuclear region~ that influence brain stem autonomic regions. These studies have provided the first anatomical characterization of direct vestibular nucleus pro­jections to brain stem autonomic pathways (17-22) and have identified connections between these vestibulo-autonomic regions and several regions of the cerebellum. These findings are consistent with the basic organizational features

, \ " ,

I "

10

of vestibulo-ocular pathways and provide a ba­sis for identifying features of cerebellar micro­complexes that influence the activity of striated muscle (somatic motor system) versus smooth muscle (autonomic nervous system). These find­ings also may provide insights into neural mech­anisms that coordinate somatic and autonomic motor activity during gravito-inertial challenges imposed by changes in posture. by aircraft ma­neuvers, by travel on ~hips. or by space travel.

Vestibuiar :"iuciei :mo Vestibuio-Autonomic Pathways

A major result from recent studies has been the characterization of a network of vestibulo­autonomic projections in the brain stem of rab­bits, rats, and cats (17-22). The results are sum­marized schematically in Figure 2, which di­vides brain stem vestibulo-autonomic circuits into three components: (a) a vestibulo-autonomic region in the vestibular nuclei, (b) a direct de-

C. D B:!8hnn and J. O. Porter

scending pathway to brain stem circuitry for vestibulo-autonomic "reflexes", and (c) an as­cending pathway to the parabrachial nucleus. This latter pathway can int1uence both the med­ullary autonomic regions (telmed the indirect de­scending vestibulo-autonomic pathway) and more rostral regions of the hypothalamus, amygdala and neocortex. which are likely to mediate neu­roendocrine and affccti ve responses' to vestibu­lar and autonomic ~til11ulati()n (see rel"erence :20 fOI' further discussion l.

·-\na[(1l11lcal uala lI1uic:lle Lilal ··.'esribulo-.lu[O­nomic :J<lrhways Ilnginat-: from a region tilat in­cl uJe~ the dorsal aspect of [he superior vestibu­lar nucleus (SVNl. 'pars alpha (or cauJovenrral aspect) of the lateral vestibular nucleus (La),

the caudal half of the medial vestibular nucleus and the inferior vestibular nucleus (17-22). Two subdivisions of this vestibular nuclear region can be distinguished on the basis of efferent connectivity. A caudal region (caudal medial vestibular nucleus and the inferior vestibular nu­cleus) contributes both (a) light descending pro-

Vestibulo-autonomic "relay" Affective and Neuroendocrine effects

Direct Descending Pathway

Vestibula-autonomic "reflexes"

Visceral Afferents

Nucleus Tractus Solitarius

Ascending Pathway

1--____ ....1 •••

Infralimbic & Insular Cortex

, , , . (----...

\ ................ . ............ ~ .......

Central Amygdaloid Nucleus

.. -+/~ Indirect Descending Pathway

OM Vagus VLM L Tegmentum Amb/PAmb

Autonomic Pathways

Figure 2. Diagram of central vestibulo-autonomlc pathways. Abbreviations: Amb/PAmb-nucleus ambiguusl nucleus paramblguus complex, OM Vagus-dorsal motor nucleus of the vagus nerve, L Tegmentum-lateral tegmental field of the medullary reticular formation, VLM-rostral ventrolateral medulla.

Vestibulo-Autonomic Pathways

jections to the nucleus of the solitary tract, the dorsal motor vagal nucleus, the nucleus ambig­uus, the ventrolateral medullary reticular forma­tion (rVLM), the nucleus raphe magnus, and the lateral medullary tegmentum and (b) ascending projections to the parabrachial nucleus. A ro<,­tral region (the superior vestibular nucleu!> and the rostral pole of the medial vestibular nucleus), though, contributes only ascending projections

The two vestibular

ciprocal connections. However. there is evi­dence that they differ in the relative density of

(23), rabbits. and monkeys (24). density noradrenergic innervation is substantially greater in the rostral region (superior vestibular nucleus) than caudally. By contrast, the limited evidence to date suggests that the caudal region receives a denser serotonergic innervation (25,26).

The connection diagram in Figure 2 presents the hypothesis that descending vestibulo-auto­nomic projections represent a final common output of the "vestibular nucleus relay" to brain stem autonomic output circuits. A corollary is that these pathways mediate the so-called "ves­tibulo-sympathetic reflex" (27,28). This hypoth­esis is consistent with the replicated observation that lesions of the caudal medial vestibular nu­cleus abolish vestibular-evoked autonomic re­sponses (28-30). It also appears that interspecies differences in the organization of descending vestibulo-autonomic projections are associated with different autonomic responses during ve~­tibular dysfunction and l11otiol~ sickne!>~ . For example. the projection 1(' nu:ku.' tractw-. ~oh ­

tarius shows a common patlern in rat~ and rah­bit~. with reiativei) heu\') innej'\ aLIUI , IC ilk

ventrolateral subnucleus (dorsal respiratory group) and to the ventral and intermediate ~L1b­nuclei. By contrast. there are negligible vestibu­lar nuclear projections to the medial subnucleu!.. a region that receives gastrointestinal inputs (31-33). It is interesting that the projections to the dorsal respiratory group and a lack of input to the medial solitary subnucleus are present in species with extremely prominent respiratory responses to vestibular stimulation (35-36), but no emetic responses. Cats show the opposite pattern of organization of vestibulosolitary pro-

11

jections: the medial SUbnucleus receives the densest vestibular nucleus inputs, with few ter­minations in the ventrolateral subnucleus. These differences are consistent with reported behav­ior during vestibular dysfunction in these spe­cies. These findings are consistent with the fail­ure of dorsal respiratory group lesions to alter vestibulorespiratory responses in cats (38). In addition, the prominent projections to the me-dial subnucleus contribute to

tibular dysfunction in cats (37). An hypothesis implicit in Figure 2 is the ex-

on 10 portIOns of classically defined vestibular and autonomic pathways, such that both acceleration of the head and visceral consequences of changes in body orientation are integrated in these path­ways to control somatic and visceral responses. Both anatomic and physiologic evidence indi­cate a direct convergence of vestibular and vis­ceral information on neurons in sites such as the nucleus of the solitary tract (17,18,21) and the rostral ventrolateral medullary reticular forma­tion (21,37), which may be a factor in the well­noted similarities between motion sickness and responses to ingestion of toxins (38). Anatomi­cal data predict a similar convergence within the parabrachial nuclear complex (20,21). Fi­nally, recent data suggest a direct convergence of vestibular and autonomic information with the vestibular nuclei via parabrachiovestibular connections (39). The potential convergence of vestibular and milonomic info:-mation in vestib­ular l1ucle~i;' cirC'Llil~ is anaiog(lu~ tll the conver­gence of ocuiar milto]" i e~/e po;..itiol1 and e~' c ve-

cells mediating vestibulo-ocular reflexe~ (40. 41 ). These interactions prcl\"ide a potentia; ana­tomical basis for Mittelstaedt's experimental evidence that psychophysical determinations of the spatial vertical reflect an interaction between vestibular and visceral signals (42). However, in a broader sense, these data are consistent with the hypothesis that vestibular and auto­nomic pathways use both vestibular (semicircu­lar canal and otolith) and visceral (for example, blood pooling and visceral proprioception) to construct central rcprC:S i ' icltions of the gr, ito-

12

Inertial forces. These central repl"""ntations then influence vestibular and autonomic function.

The ascending projections to the parabra­chial nucleus appear to represent an integrated vestibular and autonomic influence on ascend­ing limbic, prefrontaL and hypothalamic path­ways. These pathways may form a neural sub­strate for affective. cognitive, and neuroendocline manifestations of vestibular dysfunction. mo­tion 'ickness. and responses to altered gravita­.t ional enVironments (~O.21) . [11 parricu lar. cir­I:uitry linking rhe vestibular and parabrach ial ;WCle! :n;l ) pro ' 'ue ~ l le llr~il ,uo-,tralc ,'O f :. 11.: :11 -

leracti PIlS be[ween rrcti i "jJ') ~ing cognitive .IIlU affect! Ve fac tors in the de\ c lopment \)f both mo­tion sickness ,lIld ps ychiatric disorders (for i~X­

ample. panic disorder with agoraphobia and height phobia) that are chmacterized by space and motion discomfort (43,44).

Cerebellar Modulation of Vestibulo-autonomic Circuits

It is well-known that the effects of vestibular nucleus circuits on somatic motor function are under cerebellar modulation (see reference 4 for a review). An extensive literature has character­ized discrete regions of the cerebellar cortex that contribute direct projections to vestibulo­ocular and vestibulospinal reflex circuitry in the vestibular nuclei (reviewed in reference 4). For example, different parasagittal groups of Purkinje cells in the cerebellar flocculus are connected with pools of vestibular nucleus neurons that

C. D. Balaban and J. D. Porter

dlJ lJh.:rcase in the gain of the vestibulo-ocular reflex (due to disinhibition) and an attenuation of adaptive changes in reflex performance. For example, microinjections of GABA agonists in the flocculus depress the gain of both vestibulo­ocular and optokinetic responses (46), and le­sions impair the adaptive modification of vesti­bulo-ocular retlexes (reviewed in reference 4).

Previous studies have identified foul' regions of the medial aspect of cerebellar cortex that af­fect :lUtonomic function (Figure 3): I) an inter­meuinlateral site on the border of lobule IX and che H)UlIiu':. 2) a calldai /osterim lohe region in .w ne -\ of lobule IX . .3) a "oslral posterior lobe region in zone .-\ of lobules VlIa Through VUla. ;lno .1) ;ln ~lnterior lobe region within lOne A of lobules I through III (reviewed in reference -\,7). Elecuical stimulation of different sites in these regions produces either pressor of depressor re­sponses, probably through inhibition of brain stem autonomic circuits that influence tonic adrenergic (sympathetic) outflow to the periph­ery. The data also suggest that both the anterior lobe and caudal posterior lobe regions can alter the gain (sensitivity) of brain stem cardiovascu­lar reflexes. These medial cerebellar regions, par­ticularly the anterior lobe and the uvula-nodulus, also subserve a role in control of posture and lo­comotion (reviewed in reference 4). Since the cerebellar cortex plays an important role in the coordination of somatic movements, it is possi­ble that these regions contribute differentially to the coordination of somatic and autonomic mo­tor activity (reviewed in reference 47). The ex­isting evidence suggests that the rostral poste-

Two properties of these circuits are useful as criteria for triggering orienting responses and general criteria for identification of cerebellar assists in coordination of the visceral and so-

_______ J;egiQn~that-dir_eetly_influe8ee--vestibttlar-ntF--matiC-1IlOtor compolieIlts of OIiellring"' responseS' - == * ll<U

clear circuits. First, stimulation of the cerebellar (reviewed in reference 47). However, the pub-region produces effects consistent with inhibi- lished evidence suggests that the intermediolat-tion of the post-synaptic vestibular nucleus cir- eral nodulus-uvula, caudal posterior lobe. and cuit. In the case of the tlocculus, microstimula- anterior lobe areas are strong candidates for cer-tion of sites in different zones both inhibits ebellar regions that directly inhibit the sites of discrete canal-ocular reflexes (4,6,7) and pro- origin of vestibulo-autonomic pathways. duces slow eye movements (for example, 45), Three convergent lines of evidence suggest presumably by inhibiting the tonic discharge that a zone in the intermediolateral aspect of the rates of cells that mediate plane-specific reflexes. nodulus and ventral uvula is the cerebellar com­Secondly, inactivation or ablation produces both ponent of circuitry mediating vestibulo-auto-

Vestibulo-Autonomic Pathways

Anterior Lobe

Posterolateral

Lobule I

Fissure -_~

Flocculonodular Lobe

Vestibular nuclei ~..,----~ Fastigial nucleus

Parabrachial nucleus

Superior ~ ___ • Vestibular

Nucleus

13

Figure 3. Diagram of cerebellar regions related to autonomic function. Four medial cerebellar regions (shaded) appear to influence autonomic function: 1) an intermediolateral site on the border of lobule IX and the nodulus (Lateral Nodulus-Uvula Region), 2) a caudal posterior lobe region in zone A of lobule IX (Medial Uvula Region), 3) a rostral posterior lobe region in zone A of lobules Vila through Villa (Rostral Posterior Lobe Region), and 4) an anterior lobe region within zone A of lobules I through III (reviewed in reference 47). A region in lobules IV and V that Influences respiratory movements is also Indicated. Arrows schematically Indicate the efferent con­nectivity of three regions that are likely to affect regions of the vestibular nuclei that contribute ascending and descending vestibulo-autonomic connections.

nomic responses. First, anatomical evidence from rabbits indicates that the dorsal aspect of the su­perior vestibular nucleus receives projections from a sagittal group of Purkinje cells centered approximatel) :; mm lateral to the midline (48-50 and unpubl ished observations). Second. the intermediolateral aspec: of the n(ldulu~-L1vLlI'1

border U1:ea ha" been termeci the "n(\dulu~-lI\'ul,: depre\sor site" in rabbit~ beCUL!<,t •. ::·'!:):":·~il '

dror in blood pressure: is evokec b) electrical. microstimulation (49.5 i .52). Tim site is cen­tered approximately 3 mm lateral to the mid­line. Third, the depressor response elicited trom this region is blocked by microinjections of bicuculline into the dorsal aspect of the superior vestibular nucleus (49). Finally, the climbing fi­ber innervation of this zone apparently reflects retinal slip signals in the plane of the vertical semicircular canals (53) (with possibly a small intercalated area in thr dorsal nodulus reflecting

an otolithic (utricular) signal (15,54)). These di­rectional tuning signs of the physiologic re­sponse properties of the climbing fiber input are consistent with the tuning of vestibulosympa­. thetic responses near the pitch plane (55).

The l1lediai a"peci of thl:' uvula (lobule IX) is another candiclat~· for a cerehella;' cOl1lpOnelll of' veslibui0-:Iutf"1. '!'1ic ::irC'uit~. Slil11uiatioi' If thi~

p:gior f'··(lCi~~:. ~. \,. -;\:1'.~"'~'1' :· ~\I:..n~):"\ ' .. ~ t') .. · ".,, · .... ~!l·­

cii<!. decreased rena ; nerVe" aCli\'i[y and hindlimb vasodilatation in anesthetized preparatiom and pressor response~. tachycardia. increa~ed renal nerve activity, and both renal and hindlimb vas­oconstriction in decrebrate animals (56-58). Le­sion studies suggest that the depressorlbrady­cardic responses in anesthetized animals are mediated via ascending Purkinje cell projections (through the superior cerebellar peduncle or the uncinate fasciculus) to the region of lateral parabrachial nucleus, but that pressorltachy-

14

ccu'die responses are mediated via projections through the inferior cerebellar peduncle to ei­ther the medial parabrachial nucleus (59) or the superior, rostral medial and inferior vestibular nuclei (for example, 10,59,60). Although Paton and colleagues (59) presented autoradiographic evidence that tritiated amino acid injections into lobule IXb produce anterograde labeling in the caudal aspect of the lateral and medial parabra­chi.1! nucleus. it is unclear whether this repre­sents axon . termi nal or uvula-vestibular fiber!> of pas\age in rhe ::tncinate fascicuillS (50). TI1Ll~. ' ne ":\I ~ tll1g data ar .: _·() I1S j ~. iI:::1t ' vq h 'he: .1yo" [I~e­

.~I;' Ihat ;~ones i )f uVlli a ? urkinje : ..!!l, nay be ':0111-

pnnenrs of central vestibulo-autonomic circuits. The medial aspect of the anterior lobe is a

third potential cerebell:.u· component of vestib­ulo-autonomic circuits. Beginning with pioneer­ing studies by Moruzzi (61-63) and Wiggers (64), both depressor responses and pressor re­sponses have been elicited from sites within the medial aspect of lobules I through III (57,65,66). These blood pressure changes are not accompa­nied by heart rate responses (61,62), which sug­gests that activation of these regions may also de­press baroreceptor reflexes. Two other lines of evidence suggest that the anterior lobe may con­tribute to control of blood pressure lability. First, anterior lobe stimulation suppresses both sponta­neous Meyer waves (fluctuations in mean blood pressure with a period of 10 s) and carotid sinus ret1exes (61-64). Second, these effects of cere­beller stimulation on cardiovascular lability are selective because Meyer waves are enhanced by anterior lobe ablation (67) without a concomitant effect on Heling-Traube waves (spontaneous blood pressure variations at respiratory fre­quency). Nisimaru and colleagues (66) reported that stimulation sites that produce cardiovascular effects are located.predorninantly in zone A, a re­gion that reportedly projects to the rostral fasti-

C D. Balaban and J . D. Porte r

gial nucleus (for example, 4,68), rostral medial vestibular nucleus (10) and parabrachial region (69). However, more detailed studies are needed to determine whether anterior lobe Purkinje cells influence vestibulo-autonomic pathways.

Conclusion

In conclusion. recent stl1die~ have identified ~oth vestibular nuckar and <.:~rebellar regions ,hal .tppe:t!' '0 :ntegrale vestibular and auto­Jomic :n(ll1'1l1ulion . The!>e central circuits have the pUlenrial [0 explain the strong association hetween vestibular stimulation and autonomic Illotor responses through descending effects on brain stem autonomic regions. In addition to providing substrates for autonomic manifesta­tions of vestibular dysfunction (70) and motion sickness (71) , these pathways provide potential substrates for documented effects of vestibular stimulation on cardiovascular (72,73) and respi­ratory responses (74). Similarly, convergence of vestibular and autonomic information in these pathways is consistent with the concept that perception of the spatial vertical is determined as a function of both vestibular and visceral in­puts (42). Even more intriguing is the emerging recognition that vestibular dysfunction can have major affective consequences, contributing to the symptomatology of several anxiety disor­ders, such as panic disorder with agoraphobia, agoraphobia without panic, and height phobias (-1.3.44). Further studies of the ascending vestib-ulo-autonomic path ways ha v~e-,t~h~e_p~o~t~e!!ntl!"!' al~~to:....-__ ..... ___ • provide important insights into the neurobio~ logic bases for these disorders.

Acknowledgment-Supported by PHS grant ROl DC00739 from the NIDCD.

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Vestibulo-Autonomic Pathways

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