Memory Networks in Tinnitus: A Functional Brain Image Study

Tinnitus is characterized by the perception of sound in the absence of an external auditory stimulus. the network connectivity of auditory and non-auditory brain structures associated with emotion, memory and attention are functionally altered in debilitating tinnitus. Current studies suggest that tinnitus results from neuroplastic changes in the frontal and limbic temporal regions. the objective of this study was to use Single-Photon Emission Computed Tomography (SPECT) to evaluate changes in the cerebral blood flow in tinnitus patients with normal hearing compared with healthy controls. Methods: Twenty tinnitus patients with normal hearing and 17 healthy controls, matched for sex, age and years of education, were subjected to Single Photon Emission Computed Tomography using the radiotracer ethylenedicysteine diethyl ester, labeled with Technetium 99 m (99 mTc-ECD SPECT). the severity of tinnitus was assessed using the Tinnitus Handicap Inventory (THI). the images were processed and analyzed using Statistical Parametric Mapping (SPM8). Results: A significant increase in cerebral perfusion in the left parahippocampal gyrus (pFWE<0.05) was observed in patients with tinnitus compared with healthy controls. the average total THI score was 50.8+18.24, classified as moderate tinnitus. Conclusion: It was possible to identify significant changes in the limbic system of the brain perfusion in tinnitus patients with normal hearing, suggesting that central mechanisms, not specific to the auditory pathway, are involved in the pathophysiology of symptoms, even in the absence of clinically diagnosed peripheral changes.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Psiquiatria, LiNC, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Otorrinolaringol & Cirurgia Cabeca & Pescoco, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Radiol, Secao Med Nucl, São Paulo, BrazilHosp Israelita Albert Einstein, Inst Cerebro, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Fonoaudiol, São Paulo, BrazilUniv Western Australia, Med Res Ctr, Western Australian Ctr Hlth & Ageing, Perth, WA 6009, AustraliaUniversidade Federal de São Paulo, Dept Psiquiatria, LiNC, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Otorrinolaringol & Cirurgia Cabeca & Pescoco, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Radiol, Secao Med Nucl, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Fonoaudiol, São Paulo, BrazilFAPESP: FAPESP-2010/14804-6Web of Scienc

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A estimulação auditiva é capaz de interferir na plasticidade neuroquímica e estrutural do sistema nervoso por meio da ativação neuronal, modificando os níveis endógenos de fatores neurotróficos e de neurotransmissores. Neste estudo analisamos as alterações químicas na via auditiva aferente de animais estimulados acusticamente. Ratos Wistar de 60 dias de idade foram submetidos ou não a um estímulo sonoro definido durante 1 hora por um período de 1 ou de 7 dias seguidos. Após a estimulação auditiva, os animais foram sacrificados e seus encéfalos e cócleas processados para imunohistoquímica para a visualização da imunorreatividade da proteína FOS e do ácido glutâmico descarboxilase (GAD) nos núcleos cocleares e da imunorreatividade do glutamato, da neurotensina e do neuropeptídeo Y nos órgãos de Corti, nos neurônios dos gânglios espirais e também nos núcleos coc1eares. O estímulo sonoro consistiu de um tom puro intermitente, na freqüência de 8KHz e na intensidade de 80 dB NPS, apresentado em caixas acústicas posicionadas acima da gaiola de cada animal. A estimulação auditiva promoveu aumento significativo na área de imunorreatividade da proteína FOS e do glutamato na região rostral do núcleo coclear dorsal. Não houve diferenças estatísticas na imunomarcação do GAD no núcleo coclear. Na cóclea, mais especificamente nas células ciliadas internas, foi observado aumento da imunorreatividade do glutamato no giro basal e diminuição da neurotensina no giro apical diante do estímulo sonoro. A análise da intensidade da imunomarcação nos neurônios do gânglio espiral revelou maior número de neurônios tipo II com forte imunorreatividade ao neuropeptídeo Y exclusivamente no giro apical da cóclea dos animais estimulados. A via auditiva periférica e o núcleo coclear respondem de forma plástica a estímulos sonoros. A estimulação auditiva específica, não prejudicial, pode ser uma estratégia para maximizar o potencial plástico das vias neurais relacionadasAcoustic stimulation can modify the neurochesmistry and also the morphological and functional plasticity of the nervous system, changing the endogenous levels of neurotrophic factors and neurotransmitters. It was analysed by this study the chemical changes in auditory pathway of animals acoustically stimulated. Young male Wistar healthy rats (8 weeks) received or not a specific sound stimulation during 1 hour for a period of one or seven days running. After acoustic stimulation the rats were sacrificed and their brains and cochleas were processed for immunohistochemistry for visualization of: i) FOS protein and glutamic acid decarboxlase (GAD) on cochlear nucleus; ii) glutamate, neurotensin and neuropeptide Y on organ of the Corti, spiral ganglion and cochlear nucleus. The stimulus consisted of a pure 8 KHz tone burst (50 ms duration presented at a late of 2 per second) with intensity of 80 dB SPL. The rats received the stimulus from acoustic sound boxes, positioned above the cage of each animal. The acoustic stimulation promoted a significant increase in the areas of FOS protein and glutamate immunoreactivities in rostral region of the dorsal cochlear nucleus. There was no difference in the immunostaining of GAD on cochlear nucleus. In the inner hair cells of cochlea it was observed an increase of glutamate immunoreactivity in the basal rum and a decrease of neurotensin in the apical turn after the sound stimulus. The analysis of the immunostaining intensity on spiral ganglion neurons revealed a greater number of type II neurons with strong NPY immunoreaction especially in the apical turn of the cochlea in acoustically stimulated group. The peripheral auditory pathway and the cochlear nucleus react to sound stimuli in a plastic way. The specific and unlesioned acoustic stimulation may be one strategy to maximize the plastic potential of the related neural pathwa

Psychosis in Machado-Joseph Disease: Clinical Correlates, Pathophysiological Discussion, and Functional Brain Imaging. Expanding the Cerebellar Cognitive Affective Syndrome

Machado-Joseph disease (MJD) is the most common spinocerebellar ataxia worldwide with a broad range of clinical manifestations, but psychotic symptoms were not previously characterized. We investigated the psychiatric manifestations of a large cohort of Brazilian patients with MJD in an attempt to characterize the presence of psychotic symptoms. We evaluated 112 patients with clinical and molecular diagnosis of MJD from February 2008 to November 2013. Patients with psychotic symptoms were referred to psychiatric evaluation and brain perfusion single-photon emission computed tomography (SPECT) analysis. A specific scale-Positive and Negative Syndrome Scale (PANSS)-was used to characterize psychotic symptoms in MJD patients. We also performed an autopsy from one of the patients with MJD and psychotic symptoms. Five patients presented psychotic symptoms. Patients with psychotic symptoms were older and had a late onset of the disease (p<0.05). SPECT results showed that MJD patients had significant regional cerebral blood flow (rCBF) decrease in the cerebellum bilaterally and vermis compared with healthy subjects. No significant rCBF differences were found in patients without psychotic symptoms compared to patients with psychotic symptoms. The pathological description of a patient with MJD and psychotic symptoms revealed severe loss of neuron bodies in the dentate nucleus and substantia nigra. MJD patients with a late onset of the disease and older ones are at risk to develop psychotic symptoms during the disease progression. These clinical findings may be markers for an underlying cortical-cerebellar disconnection or degeneration of specific cortical and subcortical regions that may characterize the cerebellar cognitive affective syndrome.Univ Fed Sao Paulo, Dept Neurol & Neurosurg, Div Gen Neurol, 650 Pedro de Toledo St, BR-04039002 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Neurol & Neurosurg, Ataxia Unit, 650 Pedro de Toledo St, BR-04039002 Sao Paulo, SP, BrazilUniv Estadual Ceara, Ctr Hlth Sci, Fortaleza, Ceara, BrazilUniv Fed Sao Paulo, Dept Psychiat, Sao Paulo, BrazilUniv Western Australia, Med Res Ctr, Western Australian Ctr Hlth & Ageing, Crawley, WA, AustraliaUniv Fed Sao Paulo, Dept Neurol & Neurosurg, Div Gen Neurol, 650 Pedro de Toledo St, BR-04039002 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Neurol & Neurosurg, Ataxia Unit, 650 Pedro de Toledo St, BR-04039002 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Psychiat, Sao Paulo, BrazilWeb of Scienc

Demographic and clinical characteristics of the study participants.

<p>THI, Tinnitus Handicap Inventory; TI, Tinnitus.</p

Regional cerebral blood flow increase in tinnitus patients compared with control subjects.

<p>FWE, Family-wise error; KE, number of voxels per cluster;</p

rCBF increase (pFWE <0.05 after SVC) in the left parahippocampal gyrus in tinnitus patients compared with control subjects.

<p>rCBF increase (pFWE <0.05 after SVC) in the left parahippocampal gyrus in tinnitus patients compared with control subjects.</p