Aplicações dos potenciais evocados miogênicos vestibulares: revisão sistemática de literatura / Applications of vestibular-evoked myogenic potentials: a systematic literature review

RESUMO Objetivos Revisar a literatura científica sobre as principais técnicas usadas para gerar o potencial evocado miogênico vestibular (VEMP) e suas aplicações clínicas. Estratégia de pesquisa Os artigos que descrevem os métodos de registro e as aplicações do VEMP foram localizados nas bases de dados PubMed, Web of Science, MEDLINE, Scopus, LILACS e SciELO. O levantamento realizado limitou-se aos artigos publicados nos idiomas Inglês, Português e Espanhol, entre janeiro de 2012 e maio de 2018. Critérios de seleção Artigos sobre os aspectos técnicos para a realização do VEMP ocular, cervical ou do músculo sóleo, com estimulação auditiva ou galvânica e artigos sobre as aplicações clínicas do VEMP foram incluídos; artigos repetidos nas bases de dados, artigos de revisão de literatura, relato de casos, cartas e editoriais foram excluídos. Resultados A estratégia de busca resultou na seleção de 28 artigos. Os estudos evidenciaram três métodos de registro do VEMP: cervical, ocular e no músculo sóleo. As aplicações clínicas do VEMP incluíram doença de Ménière, neurite vestibular, síndrome da deiscência do canal semicircular superior, doença de Parkinson, lesões centrais isquêmicas e mielopatias motoras. Conclusão Independentemente da técnica de registro, o VEMP mostrou-se útil como ferramenta complementar para o diagnóstico de doenças vestibulares periféricas e centrais.

ABSTRACT Purpose To review the scientific literature on the main techniques used to generate vestibular-evoked myogenic potential (VEMP) and its clinical applications. Research strategy A search for articles describing VEMP recording methods and applications was conducted in the PubMed, Web of Science, MEDLINE, Scopus, LILACS and SciELO databases. The search was limited to articles published in English, Portuguese, and Spanish between January 2012 and May 2018. Selection criteria Articles addressing the technical aspects for performing ocular, cervical or soleus VEMP with auditory or galvanic stimulation and articles on the clinical applications of VEMP were included in this review, whereas articles repeated in the databases, literature reviews, case reports, letters, and editorials were excluded. Results The search strategy resulted in the selection of 28 articles. The studies evidenced three methods of VEMP recording: responses from the cervical, ocular and soleus muscle. Clinical applications of VEMP included Meniere's disease, vestibular neuritis, superior semicircular canal dehiscence syndrome, Parkinson's disease, central ischemic lesions, and motor myelopathies. Conclusion Regardless of the recording technique, VEMP has proved to be useful as a complementary tool for the diagnosis of peripheral and central vestibular diseases.

Head-shaking tilt suppression: a clinical test to discern central from peripheral causes of vertigo.

Tilt suppression refers to both tilting the head away from an Earth vertical axis and a reduction of an induced horizontal nystagmus. This phenomenon of reducing an induced horizontal nystagmus involves a circuitry of neurons within the vestibular nuclei and the cerebellum (collectively referred to as velocity storage) and signals from the otolith end organs. Lesions involving this circuitry can disrupt tilt suppression of induced horizontal nystagmus. We investigated the clinical value of combining the horizontal head-shaking nystagmus test with tilt suppression in 28 patients with unilateral peripheral vestibular hypofunction and 11 patients with lesions affecting the central nervous system. Each of the subjects with peripheral vestibular lesions generated an appropriately directed horizontal nystagmus after head shaking that then suppressed the induced angular slow phase velocity on average 52 ± 17.6% following tilt down of the head. In contrast, patients with central lesions had very little ability to suppress post-head-shaking nystagmus (mean 3.4 ± 56%). We recommend tilting the head after head shaking as a useful clinical test to assist in the differential diagnosis of vertiginous patients. In the case of unilateral peripheral vestibular hypofunction, head tilt suppresses the induced nystagmus via influence of the otolith organ. In the case of central pathology, the inability to suppress the nystagmus is from lesions impairing the otolith mediation on the velocity storage circuitry.

Molecular identity, ontogeny, and cAMP modulation of the hyperpolarization-activated current in vestibular ganglion neurons.

Properties, developmental regulation, and cAMP modulation of the hyperpolarization-activated current (I(h)) were investigated by the whole cell patch-clamp technique in vestibular ganglion neurons of the rat at two postnatal stages (P7-10 and P25-28). In addition, by RT-PCR and immunohistochemistry the identity and distribution of hyperpolarization-activated and cyclic nucleotide-gated channel (HCN) isoforms that generate I(h) were investigated. I(h) current density was larger in P25-28 than P7-10 rats, increasing 410% for small cells (<30 pF) and 200% for larger cells (>30 pF). The half-maximum activation voltage (V(1/2)) of I(h) was -102 mV in P7-10 rats and in P25-28 rats shifted 7 mV toward positive voltages. At both ages, intracellular cAMP increased I(h) current density, decreased its activation time constant (τ), and resulted in a rightward shift of V(1/2) by 9 mV. Perfusion of 8-BrcAMP increased I(h) amplitude and speed up its activation kinetics. I(h) was blocked by Cs(+), zatebradine, and ZD7288. As expected, these drugs also reduced the voltage sag caused with hyperpolarizing pulses and prevented the postpulse action potential generation without changes in the resting potential. RT-PCR analysis showed that HCN1 and HCN2 subunits were predominantly amplified in vestibular ganglia and end organs and HCN3 and HCN4 to a lesser extent. Immunohistochemistry showed that the four HCN subunits were differentially expressed (HCN1 > HCN2 > HCN3 ≥ HCN4) in ganglion slices and in cultured neurons at both P7-10 and P25-28 stages. Developmental changes shifted V(1/2) of I(h) closer to the resting membrane potential, increasing its functional role. Modulation of I(h) by cAMP-mediated signaling pathway constitutes a potentially relevant control mechanism for the modulation of afferent neuron discharge.

Asymmetries of vestibular dysfunction in major depression.

Depression is characterized by alterations in the circadian secretion of hormones, sleep and motor activity, all of which are regulated by suprachiasmatic nuclei (SCN). The vestibular system in the inner ear registers the amount of motor activity. To test the integrity of this motion sensitive system in depression, we studied the vestibulo-ocular reflex (VOR) in depressive patients who were not taking medication and healthy control subjects, which allowed us to investigate each ear and its corresponding nerve centers. Ocular reflex movement depends on vestibular nuclei activity, and we found that at 30 degrees C stimulation the right vestibular system in depressive patients has approximately half the activity of the left side. Significant asymmetry was not detected in control subjects. We also found a significant decrease in the slow phase (16.92+/-9.13 degrees/s) of the reflex in the depressed group as compared with the control group (43.77+/-16.04 degrees/s). The vestibular nuclei of the right and left sides are hypoactive. Specifically, the right vestibular nucleus is hypoactive in depressed people and can easily be measured using VOR. These results support the abnormal asymmetries hypothesis of depression and suggest that these asymmetries also exist at the level of the brain stem or neuronal centers that are afferents to right vestibular nuclei, like SCN or raphe nuclei.

The supragenual nucleus: a putative relay station for ascending vestibular signs to head direction cells.

Head direction (HD) cells located in several regions of the brain, including the postsubiculum, retrosplenial cortex, lateral dorsal thalamic nucleus, anterior dorsal thalamic nucleus, and lateral mammillary nucleus, provide a signal of the rat's momentary directional heading. Experimental evidence suggests that vestibular inputs are critical for the maintenance these cells' directional sensitivity. However, it is still unclear how vestibular information is conveyed to the HD cell-related circuitry. In a recent study, the supragenual nucleus (SG) was suggested as a putative relay of vestibular inputs to this circuitry. In the present study, using anterograde and retrograde tract-tracing methods, we first investigated whether the SG is in a position to convey vestibular inputs. Next, we examined the projections of the SG with the Phaseolus vulgaris leucoagglutinin method. Our results indicate that the SG receives direct inputs from the medial vestibular nucleus and projects to elements of the HD cell-related circuitry, providing a massive input to the contralateral dorsal tegmental nucleus and a moderately dense projection to the shell region of the lateral mammillary nucleus. Overall, the present findings serve to clarify how vestibular inputs reach the HD cell-related circuit and point out the SG as an important interface to this end.

Potencial evocado miogênico vestibular: novas perspectivas diagnósticas em esclerose múltipla / Vestibular evoked myogenic potential: new perspectives in multiple sclerosis

OBJETIVO: Avaliar o potencial evocado miogênico vestibular em pacientes com esclerose múltipla, como método de auxílio diagnóstico. FORMA DE ESTUDO: Caso-controle. MATERIAL E MÉTODO: Estudamos um grupo-controle (n=15) de indivíduos normais e um grupo experimental (n=15) que foi composto por pacientes com diagnóstico de esclerose múltipla. Ambos os grupos foram submetidos ao exame de potencial evocado miogênico vestibular. Em cada orelha foram aplicados 200 estímulos na forma de cliques e repetidos por 2 ciclos consecutivos com objetivo de avaliar a reprodutibilidade. Os eletrodos ativos de superfície foram colocados no Scsuperior do músculo esternocleidomastoideo e de referência na borda anterior da clavícula ipsilateral. Os indivíduos foram instruídos à rotacão lateral da cabeca em direcão contralateral à orelha estimulada. RESULTADOS: Obtivemos no potencial evocado miogênico vestibular respostas rápidas, reprodutíveis e bifásicas. A latência das ondas P1 e N2 e amplitude P1-N2 apresentaram um maior valor no grupo experimental quando comparada com o grupo-controle. Não observamos diferenca significativa nas respostas das ondas P1 e N2 e amplitude P1-N2 quando comparamos as orelhas. Verificamos que os indivíduos com esclerose múltipla apresentaram ausência de respostas em 30 por cento dos casos. Ao avaliarmos os indivíduos do grupo experimental com sintomas otoneurológicos e compararmos com os pacientes sem sintomas, observamos que a latência da onda P1, N2 e amplitude P1-N2 estiveram maiores nos casos sintomáticos. CONCLUSAO: O potencial evocado miogênico vestibular foi considerado um bom método de auxílio diagnóstico da via vestíbulo-espinal nos casos de esclerose múltipla.

Vestibular evoked myogenic potential: new perspectives in multiple sclerosis.

AIM: To evaluate vestibular evoked myogenic potentials in patients with multiple sclerosis as method of diagnostic support. STUDY DESIGN: Case-control. MATERIAL AND METHOD: We studied a group of normal individuals (n=15) and a Studied group (n=15) that comprised patients with diagnosis of multiple sclerosis. Both groups were submitted to vestibular evoked myogenic potential exam. In each ear it was applied 200 stimuli by clicks and repeated for 2 consecutive cycles with the purpose of evaluating reproducibility. The active electrode of surface was put on the superior S++ of sternocleidomastoid muscle and the reference electrode on the anterior border of the clavicle. The individuals were instructed to rotate theirs head to the opposite side to the stimulated ear. RESULTS: Vestibular evoked myogenic potential responses were prompt, reproducible and biphasic. The latency of wave P1 and N2 and P1-N2 amplitude showed a higher value in the studied group when compared with the normal group. There was no significant difference when the ears were compared in P1 and N2 amplitude. We noticed that individuals with multiple sclerosis showed no response in 30% of the cases. In evaluating the individuals of the Studied group with otoneurology symptoms and compared with individuals without symptoms, it was observed that P1 and N2 latencies and P1-N2 amplitude were higher in symptomatic cases. CONCLUSION: Vestibular evoked myogenic potential was considered a good method of diagnostic support of vestibulospinal tract in cases of multiple sclerosis.

[Vestibular nerves and nuclei throughout history]. / Los nervios y núcleos vestibulares en la historia.

Throughout the evolution of the concepts concerning the peripheral nerves, different ideas have dominated at different moments in history. The studies and demonstrations conducted in an attempt to further our knowledge of our own constitution and working at the same time enabled us to gain a better understanding of the make-up and specific functioning of the vestibular nerves, together with their central connecting elements in the brainstem: the vestibular nuclei. It may be that the first references to vestibular nerves are now lost in time, yet the Ancient Greeks already attempted to understand their functional nature by carrying out studies essentially focused on neuroanatomical aspects, but heavily influenced by philosophical concepts. It was not until the 18th century that researchers came to understand that there were differences between the vestibular nerve and the cochlear nerve --until then they were believed to be one single nerve. Another century went by before attempts were made to clarify the role it plays in balance and not in hearing. The differences between the distinct vestibular nuclei situated between the medulla oblongata and the pons were established in the 19th and 20th centuries when a number of authors, backed by previous microscopic studies, contributed to clarifying the fuzzy limits of cells separating the four classic nuclear groups and four others taken as being accessory.

[Antiphospholipid antibodies in patients with vestibular manifestations. A study of 16 cases]. / Anticuerpos antifosfolipídicos en pacientes con manifestaciones vestibulares. Un estudio de 16 casos.

INTRODUCTION: Antiphospholipid antibodies lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) play a role in promoting arterial and venous thrombosis in several vascular territories. Acute vestibular syndromes are a common complaint in general and neurology practice. Approximately 9% of cases are due to central nervous system vestibular areas lesions, often associated with vascular disorders. OBJECTIVE: Define the potential relationship between these antibodies and central or peripheral vestibular failure. PATIENTS AND METHODS: We report the presence of antiphospholipid antibodies in 16 patients with central vestibular symptoms. All patients were seen in the Neuro otology and Vascular Neurology clinics at the Institute for Neurological Research in Buenos Aires. Magnetic resonance imaging (MRI) and ancillary neuro otologic tests were used to determine the etiology of vestibular manifestations. Determinations of LA and aCL were done using standard criteria. RESULTS: We evaluated 16 patients (13 women and 3 men), aged 44 4 years (21 65). Thirteen patients did not have stroke risk factors. MRI lesions were found in 11 subjects (1 cerebellar infarct, 3 pontine ischemic changes, and 9 white matter abnormalities). All patients had signs consistent with dysfunction of vestibulo cerebellar structures or the vestibular nuclei. All patients had positive LA and 4 of them had also elevated aCL. CONCLUSION: Our findings suggest a potential association between the presence of a prothrombotic state and central vestibular dysfunction of vascular etiology. To the best of our knowledge, this is the first report of such an association in the absence of clinically evident autoimmune disease.

Alterações vestibulares em doenças degenerativas do sistema nervoso central / Vestibular disorders in degenerative diseases of the central nervous system structures

Tema: alterações vestibulares em doenças degenerativas do sistema nervoso central. Objetivo: verificar os sinais de comprometimento do sistema vestibular central detectados através da vectoeletronistagmografia (VENG). Material e Método: 17 pacientes (6 do sexo feminino e 11 do sexo masculino, faixa etária de 12 a 72 anos), com queixas vestibulococleares, agrupados de acordo com a etiologia das doenças degenerativas do sistema nervoso central, foram submetidos a VENG e apresentaram sinais de afecção do sistema vestibular central. Resultados: 3 casos de doenças cerebelares, 7 de esclerose múltipla, 6 de atrofia cerebral e um de síndrome de Friedreich. Conclusão: os sinais centrais foram muito variáveis de caso para caso. O nistagmo semi-espontâneo unidirecional, bidirecional e múltiplo foi o sinal central que apresentou maior ocorrência.

Cortical responses of vestibular reactions measured by topographic brain mapping and vestibular evoked potentials.

With the brain electrical activity mapping, we started to create typical patterns of potentials distributions on the scalp during various neurootological experiments. We are applying this technique for spatiotemporal analysis of cerebral evoked potentials due to vestibular stimulation. We obtain the vestibular evoked potentials (VbEP) using for the stimulation, the rotatory chair. We control it, with an external computer, that by means of an interactive program builds different sort of stimuli varying each one of the stimulus components. The electrodes are distributed on the scalp in agreement with the international system 10/20. We recognize with security, 4 positive-negative waves in a period among 70 to 490 ms. We designate the waves N1, N2, P2, N3 and N4. Vestibular evoked potentials is a newly developed tool, which we also can utilize for differentiating central and peripheral vestibular diseases.

Organization of vestibular nucleus projections to the caudal dorsal cap of kooy in rabbits.

This study used retrograde and anterograde tracing methods to characterize the origin and terminal distribution of vestibular nuclear projections to the caudal dorsal cap of the inferior olive in albino rabbits. Comparisons of the retrograde labeling patterns from Cholera toxin B fragment-horseradish peroxidase and Fluoro-Gold injection sites centred in either the caudal dorsal cap or the rostral dorsal cap plus ventrolateral outgrowth revealed that they receive projections from different vestibular nuclear regions. Tracer injections in the rostral dorsal cap and ventrolateral outgrowth produced a sparse bilateral distribution of labeled neurons in the superior vestibular nucleus and an almost exclusively ipsilateral pattern of labeled neurons in caudal pars alpha of the lateral vestibular nucleus. Injections in the caudal dorsal cap, though, labeled neurons bilaterally in the rostral medial vestibular nucleus, predominantly ipsilaterally in pars beta of the lateral vestibular nucleus and almost exclusively ipsilaterally in caudal pars alpha of the lateral vestibular nucleus and the rostral aspect of the inferior vestibular nucleus. Vestibular nucleus injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin indicated (1) that a predominantly ipsilateral projection to the caudal dorsal cap originates bilaterally from the pars beta of the lateral vestibular nucleus and the rostroventral aspect of the rostral medial vestibular nucleus, (2) that the medial half of the caudal medial vestibular nucleus is the source of a predominantly contralateral projection to dorsal cap, (3) that the caudal aspect of nucleus prepositus hypoglossi contributes a predominantly ipsilateral projection to the medial accessory olive and (4) that the rostral aspect of inferior vestibular nucleus and the dorsal and lateral aspects of the caudal medial vestibular nucleus project to nucleus beta of the medial accessory olive. In addition, axons containing anterogradely transported PHA-L were observed bilaterally in the oculomotor and abducens nuclei from injection sites involving pars beta of the lateral vestibular nucleus. It is hypothesized that bilateral vestibulo-caudal dorsal cap pathways coordinate activity in the left and right flocculus and nodulus during horizontal head movements to facilitate the performance of conjugate vestibulo-ocular and optokinetic reflexes.

Histopathology of the brain-stem nuclei of horses with "Mal seco", an equine dysautonomia.

"Mal seco" is a disease of unknown aetiology affecting horses in Argentina. It is similar to grass sickness, a primary dysautonomia of horses in Europe. A histopathological study of the brain stem nuclei of three horses with "mal seco" was performed. Changes were found that consisted of chromatolysis, cytoplasmic vacuoles, eosinophilic sphaeroids, and pyknotic and eccentric nuclei. These changes were most severe at the oculomotor, vestibular and abducent nuclei. The results provide further evidence to suggest that "mal seco" and grass sickness may be the same disease.

Immunohistochemical demonstration of regionally selective projections from locus coeruleus to the vestibular nuclei in rats.

This study describes a regionally selective projection of tyrosine hydroxylase and dopamine beta-hydroxylase-immunoreactive fibers from locus coeruleus (LC) and the A4 region of nucleus subcoeruleus to the vestibular nuclear complex in Long-Evans and Sprague-Dawley rats. These fibers travel in two distinct pathways. A lateral descending noradrenergic bundle provides input from LC to the superior vestibular nucleus (SVN), the cochlear nuclei, and the cerebellar cortex. A medial descending noradrenergic bundle provides input to the lateral vestibular nucleus (LVN), medial vestibular nucleus (MVN), and the inferior vestibular nucleus (IVN) before continuing on to the cochlear and cerebellar nuclei. The terminal plexus of these fibers varies markedly across these vestibular nuclear regions. Immunoreactive axons form a dense plexus around somata and proximal dendrites of Deiters' neurons in dorsal LVN. The axon plexus is less dense in SVN and ventral LVN, and relatively sparse in MVN and IVN. This regional selectivity of noradrenergic innervation suggests that central adrenergic systems may selectively modulate vestibulospinal reflexes at the level of the vestibular nuclear complex.

Single unit activity in the guinea-pig cochlear nucleus during sleep and wakefulness.

The effects of waking and sleep on the response properties of auditory units in the ventral cochlear nucleus (CN) were explored by using extracellular recordings in chronic guinea-pigs. Significant increases and decreases in firing rate were detected in two neuronal groups, a) the "sound-responding" and b) the "spontaneous" (units that do not show responses to any acoustic stimuli controlled by the experimenter). The "spontaneous" may be considered as belonging to the auditory system because the corresponding units showed a suppression of their discharge when the receptor was destroyed. The auditory CN units were characterized by their PSTH in response to tones at their characteristic frequency and also by the changes in firing rate and probability of discharge evaluated during periods of waking, slow wave and paradoxical sleep. The CNS performs functions dependent on sensory inputs during wakefulness and sleep phases. By studying the auditory input at the level of the ventral CN with constant sound stimuli, it was shown that, in addition to the firing rate shifts, some units presented changes in the temporal probability of discharge, implying central actions on the corresponding neurons. The mean latency of the responses, however, did not show significant changes throughout the sleep-waking cycle. The auditory efferent pathways are postulated to modulate the auditory input at CN level during different animal states. The probability of firing and the changes in the temporal pattern, as shown by the PSTH, are thus dependent on both the auditory input and the functional brain state related to the sleep-waking cycle.

Plastic properties of the vestibulo-ocular reflex in olivo-ponto-cerebellar atrophy.

Disorders in vestibulo-ocular functions were studied in 4 patients with olivo-ponto-cerebellar atrophy (OPCA). The phenomenon of habituation, considered as a plastic property of the vestibulo-ocular reflex (VOR), was explored with a behavioural paradigm in these patients. When subjected to the habituation paradigm all patients presented a modified response opposite to that observed in normal subjects. The role played by the cerebellum in relation to VOR plasticity--well known in different experimental models--is analyzed. The hypothesis of a modification of the cerebellum's inhibitory action on vestibular nuclei neurons is put forward to explain the inversion of the VOR habituation phenomenon in these patients.

Toxic effects of somatostatin in the cerebellum and vestibular nuclei: multiple sites of action.

This study demonstrates that somatostatin (SRIF), an endogenous peptide in vestibular nuclei and cerebellum, can produce both a dose-dependent death of Purkinje cells in distinct sagittal regions of cerebellar cortex and vascular infarcts centered selectively in the inferior vestibular nucleus. Alert, adult male rats were given a 5 microliters intracerebroventricular (i.c.v.) bolus of either SRIF alone (20 or 40 micrograms) or a combined dose of SRIF plus either arginine-vasopressin (AVP, 1 micrograms) or an AVP V1 antagonist, (1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)-tyrosine)-arginine 8-vasopressin (mcAVP, 1 micrograms), through an implanted cannula. After a 4-5 day survival, the brains were stained with the cupric-silver selective degeneration method. Two types of dose-dependent lesions were observed in the cerebellar and vestibular nuclei of these animals: degeneration of Purkinje cell responses in the cerebellar cortex and vascular infarcts in vestibular nuclei. These toxic responses were unaffected by application of AVP or mcAVP; hence, they can be attributed to actions of SRIF. The distribution of Purkinje cell degeneration varied with the SRIF dose in different cerebellar regions. Purkinje cell responses in lobules I-III were equivalent at both SRIF doses, and degeneration in the copula pyramis, paraflocculus and paramedian lobule emerged at the higher SRIF dose. Purkinje cells in the medial aspect of lobules IX-X had an intermediate sensitivity to SRIF intoxication. Degenerating Purkinje cells tended to be arranged in parasagittal bands in each region, suggesting parasagittal zonal variations in susceptibility to SRIF intoxication. By contrast, infarctions in the vestibular nuclei only appeared at the higher SRIF dose. These infarcts could be unilateral or bilateral and always involved the inferior vestibular nucleus at the level of the caudal margin of the acoustic tubercle; they often extended into the medial and lateral vestibular nuclei. The infarcts had a necrotic core that was infiltrated by non-neuronal elements. Thus, they appear to reflect a direct or neurally-mediated vascular response to the peptide.

[Paralysis of the conjugated lateral gaze of pontile origin: neuroanatomical discussion of the fasciculus longitudinalis medialis]. / Parálisis de la mirada conjugada lateral de origen pontino: discusión neuroanatómica del fascículo longitudinal medio.

The case of a patient with paralysis of the lateral gaze to the left, paresis of both eyes when he tried to look upwards and a disfunction of the cerebellum to the left, is reported. During the evolution the paresia of both eyes when the patient looked upwards and the disfunction of the cerebellum disappeared, but the paralysis of the lateral gaze to the left, remained. Later on the patient went a little confuse, did not understand what other persons spoke to him, and speak badly. The necropsy showed one old infarct in the medial longitudinal fasciculus in the left, the same type of lesion in the ventral part of the upper pons which was also to the left and demyelinization of the motor lemniscus of the same side. It was also seen a more recent infarct in the transverse gyrus of the left cerebral hemisphere and also the white matter below it. The study of the medial longitudinal fasciculus by means of the secondary degeneration showed that it was crossed above the 6 degrees nuclei, but was straight to the contrary of what is said about it. The authors also observe that the cells of the interstitial nucleus of Cajal were in chromatolysis. These findings justify the syndrome and the absence of the internuclear anterior ophthalmoplegia to the right.

Neurophysiology of Spastic, a behavior mutant of the mexican axoloti: altered vestibular projection to cerebellar auricle and area acoustico-lateralis.

The spastic mutant of Ambystoma mexicanum shows deficiencies in swimming coordination and equilibrium. Behavior "phenocopy" experiments done previously indicated that vestibular projections to cerebellum and hindbrain interneurons might be responsible for mutant behavior patterns. To test function in mutant vestibular projections, single unit recordings were carried out in the vestibulo-cerebellum (auricle) and hindbrain area acoustico-lateralis (AAY) of wild-type and mutant animals in response to natural vestibular stimulation. Vestibular unit types responding during longitudinal tilting or to sustained tilt were encountered in equal proportions in both animal types. However, mutants showed a significant increase in spontaneously active units in these areas indicating possible deficiencies in inhibitory circuitry. In addition, the topographic location of vestibular units changed under the influence of the spastic gene. In mutants, significant numbers of units were found "translocated" into a ventro-caudal auricular zone abutting the AAL. Anatomical studies detailed in the following paper have shown this same area to contain grossly "translocated" cerebellar cells and afferent fiber tracts in mutants. These data are drawn together in a model in which deficiencies in the (form and) inhibitory function of the vestibulo-cerebellum is postulated to underly the behavioral abnormalities of the spastic phenotype.