Neuronal population activity in the olivocerebellum encodes the frequency of essential tremor in mice and patients.

Essential tremor (ET) is the most prevalent movement disorder, characterized primarily by action tremor, an involuntary rhythmic movement with a specific frequency. However, the neuronal mechanism underlying the coding of tremor frequency remains unexplored. Here, we used in vivo electrophysiology, optogenetics, and simultaneous motion tracking in the Grid2dupE3 mouse model to investigate whether and how neuronal activity in the olivocerebellum determines the frequency of essential tremor. We report that tremor frequency was encoded by the temporal coherence of population neuronal firing within the olivocerebellums of these mice, leading to frequency-dependent cerebellar oscillations and tremors. This mechanism was precise and generalizable, enabling us to use optogenetic stimulation of the deep cerebellar nuclei to induce frequency-specific tremors in wild-type mice or alter tremor frequencies in tremor mice. In patients with ET, we showed that deep brain stimulation of the thalamus suppressed tremor symptoms but did not eliminate cerebellar oscillations measured by electroencephalgraphy, indicating that tremor-related oscillations in the cerebellum do not require the reciprocal interactions with the thalamus. Frequency-disrupting transcranial alternating current stimulation of the cerebellum could suppress tremor amplitudes, confirming the frequency modulatory role of the cerebellum in patients with ET. These findings offer a neurodynamic basis for the frequency-dependent stimulation of the cerebellum to treat essential tremor.

Função do sistema olivococlear medial em crianças com desvio fonológico / Function of the medial olivocochlear system in children with phonological disorders

OBJETIVO: Verificar se crianças com desvio fonológico apresentam alterações do sistema olivococlear medial. MÉTODOS: Trata-se de estudo prospectivo e transversal. Foram avaliadas 19 crianças normo-ouvintes, de ambos os gêneros, com idades entre 4 e 7 anos, que foram divididas em dois grupos: 11 crianças sem desvio fonológico (grupo controle) e oito com desvio fonológico (grupo estudo). A condição auditiva foi verificada por meio da inspeção visual do meato acústico externo, audiometria tonal liminar e imitanciometria. Foram incluídas em ambos os grupos somente as crianças com limiares tonais iguais ou inferiores a 15 dB, timpanometria tipo A e reflexos acústicos presentes. Para avaliar a função do sistema olivococlear medial procedeu-se à avaliação das emissões otoacústicas evocadas transientes (EOAET) com e sem aplicação de ruído branco na intensidade de 60 dBNA contralateralmente. Os dados foram analisados estatisticamente. RESULTADOS: A ocorrência e a média dos valores de supressão das EOAET das orelhas direita e esquerda não apresentaram diferenças nas frequências de 1, 2, 3 e 4 kHz intragrupos estudo e controle. Na comparação da média e ocorrência do efeito supressor das emissões otoacústicas evocadas transientes entre grupo controle e grupo estudo, também não houve diferenças nas frequências analisadas. CONCLUSÃO: Crianças com desvio fonológico não apresentam alterações do sistema olivococlear medial, aspecto evidenciado pela ocorrência do efeito supressor das emissões otoacústicas evocadas transientes.

PURPOSE: To verify whether children with phonological disorders present alterations in the medial olivocochlear system. METHODS: This is a prospective cross-sectional study in which 19 normal hearing children of both genders, with ages between 4 and 7 years, were divided into two groups: 11 children without phonological disorders (control group) and eight with phonological disorders (study group). The auditory condition was verified by visual examination of the external ear canal, pure tone audiometry, and tympanometry. The study included only children with hearing thresholds below or equal to 15 dB, type A tympanometry, and presence of acoustic reflexes. To evaluate the function of the medial olivocochlear system, it was carried out the evaluation of transient evoked otoacoustic emissions (TEOAE) with and without contralateral white noise at 60 dBHL. Data were statistically analyzed. RESULTS: The occurrence and average values of TEOAE suppression in right and left ears did not present differences in the frequencies of 1, 2, 3 and 4 kHz within groups. In the comparison of the mean and the occurrence of the suppressive effect of TEOAE between control and study groups, there was also no difference in the frequencies analyzed. CONCLUSION: Children with phonological disorders do not present alterations in the medial olivocochlear system, as evidenced by the occurrence of the suppressive effect of transient evoked otoacoustic emissions.