Neural correlates of emotional responses to music: an EEG study

This paper presents an EEG study into the neural correlates of music-induced emotions. We presented participants with a large dataset containing musical pieces in different styles, and asked them to report on their induced emotional responses. We found neural correlates of music-induced emotion in a number of frequencies over the pre-frontal cortex. Additionally, we found a set of patterns of functional connectivity, defined by inter-channel coherence measures,to be significantly different between groups of music-induced emotional responses.

The effects of acute fluoxetine administration on temporal discounting in youth with ADHD

Background Serotonin is under-researched in attention deficit hyperactivity disorder (ADHD), despite accumulating evidence for its involvement in impulsiveness and the disorder. Serotonin further modulates temporal discounting (TD), which is typically abnormal in ADHD relative to healthy subjects, underpinned by reduced fronto-striato-limbic activation. This study tested whether a single acute dose of the selective serotonin reuptake inhibitor (SSRI) fluoxetine up-regulates and normalizes reduced fronto-striato-limbic neurofunctional activation in ADHD during TD. Method Twelve boys with ADHD were scanned twice in a placebo-controlled randomized design under either fluoxetine (between 8 and 15 mg, titrated to weight) or placebo while performing an individually adjusted functional magnetic resonance imaging TD task. Twenty healthy controls were scanned once. Brain activation was compared in patients under either drug condition and compared to controls to test for normalization effects. Results Repeated-measures whole-brain analysis in patients revealed significant up-regulation with fluoxetine in a large cluster comprising right inferior frontal cortex, insula, premotor cortex and basal ganglia, which further correlated trend-wise with TD performance, which was impaired relative to controls under placebo, but normalized under fluoxetine. Fluoxetine further down-regulated default mode areas of posterior cingulate and precuneus. Comparisons between controls and patients under either drug condition revealed normalization with fluoxetine in right premotor-insular-parietal activation, which was reduced in patients under placebo. Conclusions The findings show that a serotonin agonist up-regulates activation in typical ADHD dysfunctional areas in right inferior frontal cortex, insula and striatum as well as down-regulating default mode network regions in the context of impulsivity and TD.

Alterações da default mode network provocadas pela ingestão de Ayahuasca investigadas por Ressonância Magnética Funcional

Ayahuasca is psychotropic beverage that has been used for ages by indigenous populations in South America, notably in the Amazon region, for religious and medicinal purposes. The tea is obtained by the decoction of leaves from the Psychotria viridis with the bark and stalk of a shrub, the Banisteriopsis caapi. The first is rich in N-N-dimethyltryptamine (DMT), which has an important and well-known hallucinogenic effect due to its agonistic action in serotonin receptors, specifically 5-HT2A. On the other hand, β-carbolines present in B. caapi, particularly harmine and harmaline, are potent monoamine oxidase inhibitors (MAOi). In addition, the tetrahydroharmine (THH), also present in B. caapi, acts as mild selective serotonin reuptake inhibitor and a weak MAOi. This unique composition induces a number of affective, sensitive, perceptual and cognitive changes in individuals under the effect of Ayahuasca. On the other hand, there is growing interest in the Default Mode Network (DMN), which has been consistently observed in functional neuroimaging studies. The key components of this network include structures in the brain midline, as the anterior medial frontal cortex, ventral medial frontal cortex, posterior cingulate cortex, precuneus, and some regions within the inferior parietal lobe and middle temporal gyrus. It has been argued that DMN participate in tasks involving self-judgments, autobiographical memory retrieval, mental simulations, thinking in perspective, meditative states, and others. In general, these tasks require an internal focus of attention, hence the conclusion that the DMN is associated with introspective mental activity. Therefore, this study aimed to evaluate by functional magnetic resonance imaging (fMRI) changes in DMN caused via the ingestion of Ayahuasca by 10 healthy subjects while submitted to two fMRI protocols: a verbal fluency task and a resting state acquisition. In general, it was observed that Ayahuasca causes a reduction in the fMRI signal in central nodes of DMN, such as the anterior cingulate cortex, the medial prefrontal cortex, the posterior cingulate cortex, precuneus and inferior parietal lobe. Furthermore, changes in connectivity patterns of the DMN were observed, especially a decrease in the functional connectivity of the precuneus. Together, these findings indicate an association between the altered state of consciousness experienced by individuals under the effect of Ayahuasca, and changes in the stream of spontaneous thoughts leading to an increased introspective mental activity

Aspectos epidemiológicos, cognitivo-comportamentais e neurofisiológicos do sonho lúcido

Lucid dreaming (LD) is a mental state in which the subject is aware of being dreaming while dreaming. The prevalence of LD among Europeans, North Americans and Asians is quite variable (between 26 and 92%) (Stepansky et al., 1998; Schredl & Erlacher, 2011; Yu, 2008); in Latin Americans it is yet to be investigated. Furthermore, the neural bases of LD remain controversial. Different studies have observed that LD presents power increases in the alpha frequency band (Tyson et al., 1984), in beta oscillations recorded from the parietal cortex (Holzinger et al., 2006) and in gamma rhythm recorded from the frontal cortex (Voss et al., 2009), in comparison with non-lucid dreaming. In this thesis we report epidemiological and neurophysiological investigations of LD. To investigate the epidemiology of LD (Study 1), we developed an online questionnaire about dreams that was answered by 3,427 volunteers. In this sample, 56% were women, 24% were men and 20% did not inform their gender (the median age was 25 years). A total of 76.5% of the subjects reported recalling dreams at least once a week, and about two-thirds of them reported dreaming always in the first person, i.e. when the dreamer observes the dream from within itself, not as another dream character. Dream reports typically depicted actions (93.3%), known people (92.9%), sounds/voices (78.5%), and colored images (76.3%). The oneiric content was related to plans for upcoming days (37.8%), and memories of the previous day (13.8%). Nightmares were characterized by general anxiety/fear (65.5%), feeling of being chased (48.5%), and non-painful unpleasant sensations (47.6%). With regard to LD, 77.2% of the subjects reported having experienced LD at least once in their lifetime (44.9% reported up to 10 episodes ever). LD frequency was weakly correlated with dream recall frequency (r = 0.20, p <0.001) and was higher in men (χ2=10.2, p=0.001). The control of LD was rare (29.7%) and inversely correlated with LD duration (r=-0.38, p <0.001), which is usually short: to 48.5% of the subjects, LD takes less than 1 minute. LD occurrence is mainly associated with having sleep without a fixed time to wake up (38.3%), which increases the chance of having REM sleep (REMS). LD is also associated with stress (30.1%), which increases REMS transitions into wakefulness. Overall, the data suggest that dreams and nightmares can be evolutionarily understood as a simulation of the common situations that happen in life, and that are related to our social, psychological and biological integrity. The results also indicate that LD is a relatively common experience (but not recurrent), often elusive and difficult to control, suggesting that LD is an incomplete stationary stage (or phase transition) between REMS and wake state. Moreover, despite the variability of LD prevalence among North Americans, Europeans and Asians, our data from Latin Americans strengthens the notion that LD is a general phenomenon of the human species. To further investigate the neural bases of LD (Study 2), we performed sleep recordings of 32 non-frequent lucid dreamers (sample 1) and 6 frequent lucid dreamers (sample 2). In sample 1, we applied two cognitive-behavioral techniques to induce LD: presleep LD suggestion (n=8) and light pulses applied during REMS (n=8); in a control group we made no attempt to influence dreaming (n=16). The results indicate that it is quite difficult but still possible to induce LD, since we could induce LD in a single subject, using the suggestion technique. EEG signals from this one subject exhibited alpha (7-14 Hz) bursts prior to LD. These bursts were brief (about 3s), without significant change in muscle tone, and independent of the presence of rapid eye movements. No such bursts were observed in the remaining 31 subjects. In addition, LD exhibited significantly higher occipital alpha and right temporo-parietal gamma (30-50 Hz) power, in comparison with non-lucid REMS. In sample 2, LD presented increased frontal high-gamma (50-100 Hz) power on average, in comparison with non-lucid REMS; however, this was not consistent across all subjects, being a clear phenomenon in just one subject. We also observed that four of these volunteers showed an increase in alpha rhythm power over the occipital region, immediately before or during LD. Altogether, our preliminary results suggest that LD presents neurophysiological characteristics that make it different from both waking and the typical REMS. To the extent that the right temporo-parietal and frontal regions are related to the formation of selfconsciousness and body internal image, we suggest that an increased activity in these regions during sleep may be the neurobiological mechanism underlying LD. The alpha rhythm bursts, as well as the alpha power increase over the occipital region, may represent micro-arousals, which facilitate the contact of the brain during sleep with the external environment, favoring the occurrence of LD. This also strengthens the notion that LD is an intermediary state between sleep and wakefulness

Efeitos do tratamento com lítio na memória aversiva, comportamentos relacionados à ansiedade e depressão e na expressão de BDNF em ratos

Lithium (Li) is the first choice to treat bipolar disorder, a psychiatric illness characterized by mood oscillations between mania and depression. However, studies have demonstrated that this drug might influence mnemonic process due to its neuroprotector, antiapoptotic and neurogenic effects. The use of Li in the treatment of cognitive deficits caused by brain injury or neurodegenerative disorders have been widely studied, and this drug shows to be effective in preventing or even alleviating the memory impairment. The effects of Li on anxiety and depression are controversial and the relationship of the effects of lithium on memory, anxiety and depression remain unknown. In this context, this study aims to: evaluate the effects of acute and chronic administration of lithium carbonate in aversive memory and anxiety, simultaneously, using the plus maze discriminative avoidance task (PMDAT); test the antidepressant effect of the drug through the forced swimming test (FS) and analyze brainderived neurotrophic factor (BDNF) expression in structures related to memory and emotion. To evaluation of the acute effects, male Wistar rats were submitted to i.p. administration of lithium carbonate (50, 100 or 200 mg/kg) one hour before the training session (PMDAT) or lithium carbonate (50 or 100 mg/kg) one hour before the test session (FS). To evaluation of the chronic effects, the doses administered were 50 or 100 mg/kg or vehicle once a day for 21 days before the beginning of behavioral tasks (PMDAT and FS). Afterwards, the animals were euthanized and their brains removed and submitted to immunohistochemistry procedure to quantify BDNF. The animals that received acute treatment with 100 and 200 mg/kg of Li did not discriminated between the enclosed arms (aversive and non-aversive) in the training session of PMDAT, showing that these animal did not learned the task. This lack of discrimination was also observed in the test session, showing that the animals did not recall the aversive task. We also observed an increased exploration of the open arms of these same groups, indicating an anxiolytic effect. The same groups showed a reduction of locomotor activity, however, this effect does not seem to be related with the anxiolytic effect of the drug. Chronic treatment with Li did not promote alterations on learning or memory processes. Nevertheless, we observed a reduction of open arms exploration by animals treated with 50 mg/kg when compared to the other groups, showing an anxiogenic effect caused by this dose. This effect it is not related to locomotor alterations since there were no alterations in these parameters. Both acute and chronic treatment were ineffective in the FS. Chronic treatment with lithium was not able to modify BDNF expression in hippocampus, amygdala and pre-frontal cortex. These results suggest that acute administration of lithium promote impairments on learning in an aversive task, blocking the occurrence of memory consolidation and retrieval. The reduction of anxiety following acute treatment may have prevented the learning of the aversive task, as it has been found that optimum levels of anxiety are necessary for the occurrence of learning with emotional context. With continued, treatment the animals recover the ability to learn and recall the task. Indeed, they do not show differences in relation to control group, and the lack of alterations on BDNF expression corroborates this result. Possibly, the regimen of treatment used was not able to promote cognitive improvement. Li showed acute anxiolytic effect, however chronic administration 4 promoted the opposite effect. More studies are necessary to clarify the potential beneficial effect of Li on aversive memory

A novel in situ Polymerase chain reaction hybridisation assay for the direct detection of bovine herpesvirus type 5 in formalin-fixed, paraffin-embedded tissues

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Fungal pyogranulomatous encephalitis in a dog with leishmaniosis

É relatado um caso de encefalite piogranulomatosa em um cão fêmea de um ano de idade, da raça Fila Brasileiro. Ao exame macroscópico do cérebro, evidenciou-se área amolecida e hemorrágica no córtex frontal direito e na superfície de corte do hemisfério esquerdo, afetando a substância branca e áreas corticais profundas. O diagnóstico de encefalite piogranulomatosa micótica multifocal foi realizado através de exame histopatológico, que mostrou a presença de macrófagos, células gigantes, focos de hemorragia e hifas septadas de coloração marrom, com distribuição difusa e invadindo a luz de vasos. A identificação de formas amastigotas no imprint de linfonodo poplíteo confirmou o diagnóstico de leishmaniose. A infecção micótica no cérebro deste cão foi relacionada com a ocorrência concomitante de leishmaniose, uma doença imunossupressora.

Effect of electrolytic lesion of the median raphe nucleus on behavioral and physiological measures of stress.

The effect of electrolytic lesion of the median raphe nucleus was measured on behavioral and physiological parameters related to stress 24 h after the lesion. In of the elevated plus-maze the lesion decreased the percentage of open arm entries and tended to shorten the time spent on the open arms indicating an increase in anxiety. In contrast, the lesion markedly increased the time spent in the bright (aversive) compartment of the light-dark box and decrease in attempts to cross from the dark toward the bright compartment, an anxiolyic effect. With the exception of plasma prolactin level, which was lowered by the lesion, the physiological measures used in the present study indicate that the lesioned animals are under stress. Thus, death rate and weight loss after the surgery were higher in lesioned than in control animals. In addition, lesioned animals showed higher plasma corticosterone levels, a high incidence of gastric ulcers in the fundus and a depressed immune response to the mitogen concavaline A. These results highlight the importance of the median raphe nucleus in the regulation of stress and anxiety. They also show that behavioral and physiological measures of stress may be dissociated.

Efeitos comportamentais e neuroquímicos agudos da cafeína em ratos adolescentes e adultos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Análise do líquido cefalorraquidiano, tomografia computadorizada craniana e angiotomografia cerebral de Alouatta guariba - Geoffroy Saint-Hilaire, 1812 (Bugio ruivo)

Pós-graduação em Medicina Veterinária - FMVZ

Estudo da neuropatologia induzida pelo vírus Marabá em modelo murino

O vírus Marabá (Be AR 411459) é um Vesiculovírus (VSV), membro da família Rhabdoviridae, isolado em 1983, de um pool de flebotomíneos capturado em Marabá-PA pela Seção de Arbovírus do Instituto Evandro Chagas. Na literatura pouco se tem sobre neuropatologia experimental induzida pelo vírus Marabá, apesar dos 30 anos de isolamento. Um único estudo, porém, revelou que a infecção viral em camundongos recém-nascidos provoca necrose e picnose em neurônios em várias regiões do sistema nervoso central (SNC) O objetivo do presente trabalho foi investigar a distribuição do vírus Marabá no SNC, a ativação microglial e astrocitária, aspectos histopatológicos; e a expressão de citocinas e óxido nítrico (NO), na encefalite induzida pelo vírus Marabá em camundongo BALB/c adultos. Para tanto, foram realizados processamentos de amostras para análise histopatologica; immunohistoquímica para marcação de microglia, astrócitos e antígeno viral; testes de quantificação de citocinas e NO; e análises estatísticas. Os resultados demonstraram que os animais infectados (Ai) 3 dias após a inoculação (d.p.i.) apresentam discreta marcação do antígeno viral, bem como quanto a ativação de microglia e astrócitos no SNC. Por outro lado, nos Ai 6 d.p.i. a marcação do antígeno viral foi observada em quase todas regiões encefálicas, observando-se intensa ativação microglial nestes locais, embora a astrogliose tenha sido menor. Edema, necrose e apoptose de neurônios foram observados principalmente no bulbo olfatório, septo interventrícular e córtex frontal dos Ai 6 d.p.i. A quantificação dos níveis de IL-12p40, IL-10, IL-6, TNF- α, INF-ү, MCP-1 e de NO mostrou aumentos significativos nos Ai 6 d.p.i., quando comparados aos animais controles e Ai 3 d.p.i.. Por outro lado, os níveis de TGF-β, importante imunossupressor, não foi significativo em todos os grupos e tempos avaliados (3 e 6 d.p.i.). Estes resultados indicam que o vírus Marabá pode infectar diversas regiões do SNC de camundongo BALB/c adulto 6 d.p.i., produzindo alterações anátomo-patológicas e uma forte resposta imune inflamatória que pode ser letal para o animal.

Perinatal Periodontal Disease Reduces Social Behavior in Male Offspring

Objective: Our objective was to verify whether prenatal maternal periodontitis is a risk factor for the development of central nervous system disorders in rats. Methods: Periodontitis was induced by placing a ligature around the upper and lower first molars in 9 female Wistar rats (experimental group); 9 rats were left unligated (control group). The maternal general activity in an open field was observed on gestational day (GD) 0, GD 4, and GD 14, and the maternal performance was assessed on the second day after birth. The pups' play behavior was assessed on postnatal day 30. The relative level of reelin was measured in the frontal cortex by real-time PCR analysis. Results: The results showed that, compared with the control group, (1) the general activity in female rats with periodontitis was decreased, (2) the maternal performance of these rats was not modified by periodontitis, (3) the play behavior of pups from dams with periodontitis was decreased, and (4) there were no differences in the frontal cortex reelin levels of pups from dams with periodontitis. Conclusions: We conclude that pre- and postnatal periodontitis induces maternal sickness behavior and reduces the pups' play behavior without interference with frontal cortex reelin expression. Copyright (C) 2012 S. Karger AG, Basel

Immunohistochemical approach to the pathogenesis of clinical cases of bovine Herpesvirus type 5 infections

Meningoencephalitis by Herpesvirus type 5 (BoHV-5) in cattle has some features that are similar to those of herpetic encephalitis in humans and other animal species. Human Herpesvirus 3 (commonly known as Varicella-zoster virus 1), herpes simplex viruses (HSV), and equid Herpesvirus 1 (EHV-1) induce an intense inflammatory, vascular and cellular response. In spite of the many reports describing the histological lesions associated with natural and experimental infections, the immunopathological mechanisms for the development of neurological disorder have not been established. A total of twenty calf brains were selected from the Veterinary School, University of São Paulo State, Araçatuba, Brazil, after confirmation of BoHV-5 infection by virus isolation as well as by a molecular approach. The first part of the study characterized the microscopic lesions associated with the brain areas in the central nervous system (CNS) that tested positive in a viral US9 gene hybridization assay. The frontal cortex (Fc), parietal cortex (Pc), thalamus (T) and mesencephalon (M) were studied. Secondly, distinct pathogenesis mechanisms that take place in acute cases were investigated by an immunohistochemistry assay. This study found the frontal cortex to be the main region where intense oxidative stress phenomena (AOP-1) and synaptic protein expression (SNAP-25) were closely related to inflammatory cuffs, satellitosis and gliosis, which represent the most frequently observed neurological lesions. Moreover, MMP-9 expression was shown to be localized in the leptomeninges, in the parenchyma and around mononuclear infiltrates (p < 0.0001). These data open a new perspective in understanding the role of the AOP-1, MMP-9 and SNAP-25 proteins in mediating BoHV-5 pathogenesis and the strategies of host-virus interaction in order to invade the CNS.

Avaliação da teneurina-2 (Ten-2) nos astrócitos do córtex cerebral de ratos adultos após lesão mecânica. Estudo imuno-histoquímico e de expressão gênica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação da teneurina-2 (Ten-2) nos astrócitos do córtex cerebral de ratos adultos após lesão mecânica. Estudo imuno-histoquímico e de expressão gênica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)