Instituto do Cérebro

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3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for victims of sexual abuse with severe post-traumatic stress disorder: an open label pilot study in Brazil
(2020-07-03) Jardim, Alvaro V.; Jardim, Dora V.; Chaves, Bruno Rasmussen; Steglich, Matheus; Ot’alora G., Marcela; Mithoefer, Michael C.; Silveira, Dartiu X. da; Tófoli, Luís F.; Ribeiro, Sidarta Tollendal Gomes; Matthews, Rebecca; Doblin, Rick; Schenberg, Eduardo E.
Objective: To conduct Brazil’s first clinical trial employing 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder (PTSD), given its high prevalence resulting from epidemic violence. Methods: Of 60 volunteers, four matched the inclusion & exclusion criteria. Three patients with PTSD secondary to sexual abuse (diagnosed by the Structured Clinical Interview for DSM-IV and the Clinician Administered PTSD Scale for DSMV-4 [CAPS 4]) completed enrollment and treatment, following a standardized Multidisciplinary Association for Psychedelic Studies protocol consisting of 15 weekly therapy sessions: three with orally administered MDMA with concurrent psychotherapy and music, spaced approximately 1 month apart. CAPS-4 scores two months after the final MDMA session were the primary outcome. Results: No serious adverse events occurred. The most frequent adverse events were somatic pains and anguish. CAPS-4 reductions were always greater than 25 points. The final scores were 61, 27, and 8, down from baseline scores of 90, 78, and 72, respectively. All reductions were greater than 30%, which is indicative of clinically significant improvement. Secondary outcomes included lower Beck Depressive Inventory scores and higher Post-Traumatic Growth Inventory and Global Assessment of Functioning scores. Conclusions: Considering the current limitations in safe and efficacious treatments for PTSD and recent studies abroad with larger patient samples, MDMA-assisted psychotherapy could become a viable treatment in Brazil.
5-MeO-DMT induces sleep-like LFP spectral signatures in the hippocampus and prefrontal cortex of awake rats
(Springer Science and Business Media LLC, 2024-05) Souza, Annie da Costa; Souza, Bryan da Costa; França, Arthur Sergio Cavalcanti de; Moradi, Marzieh; Souza, Nicholy C.; Leão, Emelie Katarina Svahn; Tort, Adriano Bretanha Lopes; Leao, Richardson Naves; Santos, Vítor Lopes dos; Ribeiro, Sidarta Tollendal Gomes
5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a potent classical psychedelic known to induce changes in locomotion, behaviour, and sleep in rodents. However, there is limited knowledge regarding its acute neurophysiological effects. Local field potentials (LFPs) are commonly used as a proxy for neural activity, but previous studies investigating psychedelics have been hindered by confounding effects of behavioural changes and anaesthesia, which alter these signals. To address this gap, we investigated acute LFP changes in the hippocampus (HP) and medial prefrontal cortex (mPFC) of freely behaving rats, following 5-MeO-DMT administration. 5-MeO-DMT led to an increase of delta power and a decrease of theta power in the HP LFPs, which could not be accounted for by changes in locomotion. Furthermore, we observed a dose-dependent reduction in slow (20–50 Hz) and mid (50–100 Hz) gamma power, as well as in theta phase modulation, even after controlling for the effects of speed and theta power. State map analysis of the spectral profile of waking behaviour induced by 5-MeO-DMT revealed similarities to electrophysiological states observed during slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. Our findings suggest that the psychoactive effects of classical psychedelics are associated with the integration of waking behaviours with sleep-like spectral patterns in LFPs
Ablation of sensory nerves favours melanoma progression
(Wiley, 2020-07-20) Prazeres, Pedro H. D. M.; Leonel, Caroline; Silva, Walison N.; Rocha, Beatriz G. S.; Santos, Gabryella S. P.; Costa, Alinne C.; Picoli, Caroline C.; Sena, Isadora F. G.; Gonçalves, William A.; Vieira, Mariana S.; Costa, Pedro A. C.; Campos, Leda M. C. C.; Lopes, Miriam T. P.; Costa, Marcos Romualdo; Resende, Rodrigo R.; Cunha, Thiago M.; Mintz, Akiva; Birbrair, Alexander
The tumour mass is composed not only of heterogeneous neoplastic cells, but also a variety of other components that may affect cancer cells behaviour. The lack of detailed knowledge about all the constituents of the tumour microenvironment restricts the design of effective treatments. Nerves have been reported to contribute to the growth and maintenance of numerous tissues. The effects of sensory innervations on tumour growth remain unclear. Here, by using state‐of‐the‐art techniques, including Cre/loxP technologies, confocal microscopy, in vivo‐tracing and chemical denervation, we revealed the presence of sensory nerves infiltrating within the melanoma microenvironment, and affecting cancer progression. Strikingly, melanoma growth in vivo was accelerated following genetic ablation or chemical denervation of sensory nerves. In humans, a retrospective analysis of melanoma patients revealed that increased expression of genes related to sensory nerves in tumours was associated with better clinical outcomes. These findings suggest that sensory innervations counteract melanoma progression. The emerging knowledge from this research provides a novel target in the tumour microenvironment for therapeutic benefit in cancer patients.
Uma abordagem da prova testemunhal a partir da neurolaw
(2020-06-29) Pereira, Carlos André Maciel Pinheiro; Bevilaqua, Lia Rejane Müller; Bezerra, Bruno Tavares Padilha
Neste trabalho analisa-se a prova testemunhal no contexto do direito processual civil sob o enfoque da neurolaw. O estudo faz uma breve revisão sobre as características e natureza jurídica da referida prova, focando no testemunho de terceiros que aportam, sob compromisso de dizer a verdade, conhecimento subjetivo pertinente à lide. Utiliza o método indutivo, através de pesquisa qualitativa com suporte em fontes científicas, doutrinárias e legais com o intuito de melhor compreender metodologias que propõe a localização de circuitarias cerebrais relacionadas com o armazenamento de informações específicas e sua relação com a compreensão da prova testemunhal pelos atores do direito. As memórias não são perfeitas e a prova testemunhal é indissociável do processo de evocação da informação adquirida. Debate-se aqui as particularidades e características das memórias para que, quando transmitidas por um testemunho, possam ser devidamente escrutinizadas pelo julgador. Assim a eficácia da decisão judicial será maximizada ao alcançar a verdade material por trás do processo, ao mesmo tempo que salvaguarda a segurança jurídica
Acesso lexical: uma rota dupla para o português brasileiro
(2014) Medeiros, Joyse; Weissheimer, Janaina; França, Aniela Improta; Ribeiro, Sidarta Tollendal Gomes
O presente estudo avalia se o modo como acessamos as palavras é influenciado pela estrutura do léxico; mais especificamente, se há diferenças na forma como reconhecemos palavras simples e compostas do Português Brasileiro (PB). Para isto, aplicamos dois testes de acesso lexical a 80 participantes para determinar (i) se há diferenças nos tempos de reação e acurácia de resposta entre palavras simples e compostas, e (ii) se essas diferenças se correlacionam com a frequência de uso dessas palavras. Os resultados do experimento 1 fornecem evidências para ocorrências de decomposição no reconhecimento de palavras compostas do PB. No entanto, as latências de resposta das palavras de altas frequências dos experimentos 1 e 2 confirmam as predições de modelos de listagem plena. Para explicar esses resultados sugerimos um mecanismo de acesso lexical em rota dupla, em que cada tipo de palavra é acessado mais rapidamente dependendo da sua frequência e de propriedades morfológicas.
Active neural coordination of motor behaviors with internal states
(Proceedings of the National Academy of Sciences, 2022-09) Zhang, Yisi S; Takahashi, Daniel Yasumasa; Hady, Ahmed El; Liao, Diana A; Ghazanfar, Asif A
The brain continuously coordinates skeletomuscular movements with internal physiological states like arousal, but how is this coordination achieved? One possibility is that the brain simply reacts to changes in external and/or internal signals. Another possibility is that it is actively coordinating both external and internal activities. We used functional ultrasound imaging to capture a large medial section of the brain, including multiple cortical and subcortical areas, in marmoset monkeys while monitoring their spontaneous movements and cardiac activity. By analyzing the causal ordering of these different time series, we found that information flowing from the brain to movements and heart-rate fluctuations were significantly greater than in the opposite direction. The brain areas involved in this external versus internal coordination were spatially distinct, but also extensively interconnected. Temporally, the brain alternated between network states for this regulation. These findings suggest that the brain's dynamics actively and efficiently coordinate motor behavior with internal physiology
Active sampling as an information seeking strategy in primate vocal interactions
(Springer Science and Business Media LLC, 2024-09) Varella, Thiago T.; Takahashi, Daniel Yasumasa; Ghazanfar, Asif A.
Active sensing is a behavioral strategy for exploring the environment. In this study, we show that contact vocal behaviors can be an active sensing mechanism that uses sampling to gain information about the social environment, in particular, the vocal behavior of others. With a focus on the real-time vocal interactions of marmoset monkeys, we contrast active sampling to a vocal accommodation framework in which vocalizations are adjusted simply to maximize responses. We conduct simulations of a vocal accommodation and an active sampling policy and compare them with actual vocal interaction data. Our findings support active sampling as the best model for real-time marmoset monkey vocal exchanges. In some cases, the active sampling model was even able to partially predict the distribution of vocal durations for individuals to approximate the optimal call duration. These results suggest a non-traditional function for primate vocal interactions in which they are used by animals to seek information about their social environments
Activity-Independent Effects of CREB on Neuronal Survival and Differentiation during Mouse Cerebral Cortex Development
(2016-12) Landeira, Bruna Soares; Santana, Themis Taynah da Silva; Araújo, Jéssica Alves de Medeiros; Tabet, Elie I.; Tannous, Bakhos A.; Schroeder, Timm; Costa, Marcos Romualdo
Neuronal survival and morphological maturation depends on the action of the transcription factor calcium responsive element binding protein (CREB), which regulates expression of several target genes in an activity-dependent manner. However, it remains largely unknown whether CREB-mediated transcription could play a role at early stages of neuronal differentiation, prior to the establishment of functional synaptic contacts. Here, we show that CREB is phosphorylated at very early stages of neuronal differentiation in vivo and in vitro, even in the absence of depolarizing agents. Using genetic tools, we also show that inhibition of CREB-signaling affects neuronal growth and survival in vitro without affecting cell proliferation and neurogenesis. Expression of A-CREB or M-CREB, 2 dominant-negative inhibitors of CREB, decreases cell survival and the complexity of neuronal arborization. Similar changes are observed in neurons treated with protein kinase A (PKA) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitors, which also show decreased levels of pCREBSer133. Notably, expression of CREB-FY, a Tyr134Phe CREB mutant with a lower Km for phosphorylation, partly rescues the effects of PKA and CaMKII inhibition. Our data indicate that CREB-mediated signaling play important roles at early stages of cortical neuron differentiation, prior to the establishment of fully functional synaptic contacts.
Acute effects of ayahuasca in a juvenile non-human primate model of depression
(2018-11-08) Silva, Flávia S. da; Silva, Erick A. S.; Sousa Jr., Geovan M. de; Maia-de-Oliveira, João P.; Soares-Rachetti, Vanessa de Paula; Araújo, Dráulio Barros de; Sousa, Maria Bernardete Cordeiro de; Lobão-Soares, Bruno; Hallak, Jaime; Galvão-Coelho, Nicole L.
Objective: The incidence rate of major depression in adolescents reaches approximately 14%. This disorder is usually recurrent, without remission of symptoms even after pharmacological treatment, and persists throughout adult life. Since the effects of antidepressants take approximately 2 weeks to begin, new pharmacological therapies are under continuous exploration. Recent evidence suggests that psychedelics could produce rapid antidepressant effects. In this study, we evaluated the potential antidepressant effects of ayahuasca in a juvenile non-human primate model of depression. Methods: While living with their families, juvenile marmosets (8 males; 7 females) were observed on alternate days for four weeks during a baseline phase. This was followed by 8 weeks of an induced depressive state protocol, the social isolated context (IC), in which the animals were monitored in the first and last weeks. Subsequently, five males and four females were randomly selected for treatment, first with a single administration of saline vehicle (1.67 mL/300 g of body weight, via gavage), followed by a single dose of ayahuasca (1.67 mL/300 g of body weight, via gavage). Both phases lasted 1 week and the animals were monitored daily. A third week of sampling was called the tardive-pharmacological effects phase. In all phases the marmosets were assessed for behavior, fecal cortisol levels, and body weight. Results: After IC, the animals presented typical hypocortisolemia, but cortisol recovered to baseline levels 24 h after an acute dose of ayahuasca; this recovery was not observed in vehicle-treated animals. Additionally, in males, ayahuasca, but not the vehicle, reduced scratching, a stereotypic behavior, and increased feeding. Ayahuasca treatment also improved body weight to baseline levels in both sexes. The ayahuasca-induced behavioral response had long-term effects (14 days). Thus, in this translational juvenile animal model of depression, ayahuasca presented beneficial effects. Conclusions: These results can contribute to the validation of ayahuasca as an antidepressant drug and encourage new studies on psychedelic drugs as a tool for treating mood disorders, including for adolescents with early-onset depression.
Adult neural stem cells: plastic or restricted neuronal fates?
(2013) Sequerra, Eduardo Bouth; Costa, Marcos Romualdo; Menezes, João R. L.; Hedin-Pereira, Cecilia
During embryonic development, the telencephalon is specified along its axis through morphogenetic gradients, leading to the positional-dependent generation of multiple neuronal types. After embryogenesis, however, the fate of neuronal progenitors becomes more restricted, and they generate only a subset of neurons. Here, we review studies of postnatal and adult neurogenesis, challenging the notion that fixed genetic programs restrict neuronal fate. We hypothesize that the adult brain maintains plastic neural stem cells that are capable of responding to changes in environmental cues and generating diverse neuronal types. Thus, the limited diversity of neurons generated under normal conditions must be actively maintained by the adult milieu.
AMPA receptors mediate passive avoidance deficits induced by sleep deprivation
(2013) Dubiela, Francisco Paulino; Queiroz, Claudio Marcos Teixeira de; Moreira, Karin Di Monteiro; Nobrega, Jose N.; Sita, Luciane Valéria; Tufik, Sergio; Hipolide, Debora Cristina
The present study addressed the effects of sleep deprivation (SD) on AMPA receptor (AMPAR) binding in brain regions associated with learning and memory, and investigated whether treatment with drugs acting on AMPAR could prevent passive avoidance deficits in sleep deprived animals. [(3)H]AMPA binding and GluR1 in situ hybridization signals were quantified in different brain regions of male Wistar rats either immediately after 96 h of sleep deprivation or after 24h of sleep recovery following 96 h of sleep deprivation. Another group of animals were sleep deprived and then treated with either the AMPAR potentiator, aniracetam (25, 50 and 100mg/kg, acute administration) or the AMPAR antagonist GYKI-52466 (5 and 10mg/kg, acute and chronic administration) before passive avoidance training. Task performance was evaluated 2h and 24h after training. A significant reduction in [(3)H]AMPA binding was found in the hippocampal formation of SD animals, while no alterations were observed in GluR1 mRNA levels. The highest dose of aniracetam (100mg/kg) reverted SD-induced impairment of passive avoidance performance in both retention tests, whereas GYKI-52466 treatment had no effect. Pharmacological enhancement of AMPAR function may revert hippocampal-dependent learning impairments produced after SD. We argue that such effects might be associated with reduced AMPAR binding in the hippocampus of sleep deprived animals.
Amygdala responses to unpleasant pictures are influenced by task demands and positive affect trait
(2015-03-04) Sanchez, Tiago A.; Mocaiber, Izabela; Erthal, Fatima S.; Joffily, Mateus; Volchan, Eliane; Pereira, Mirtes G.; Araújo, Dráulio Barros de; Oliveira, Leticia
The role of attention in emotional processing is still the subject of debate. Recent studies have found that high positive affect in approach motivation narrows attention. Furthermore, the positive affect trait has been suggested as an important component for determining human variability in threat reactivity. We employed functional magnetic resonance imaging to investigate whether different states of attention control would modulate amygdala responses to highly unpleasant pictures relative to neutral and whether this modulation would be influenced by the positive affect trait. Participants (n = 22, 12 male) were scanned while viewing neutral (people) or unpleasant pictures (mutilated bodies) flanked by two peripheral bars. They were instructed to (a) judge the picture content as unpleasant or neutral or (b) to judge the difference in orientation between the bars in an easy condition (0 or 90∘ orientation difference) or (c) in a hard condition (0 or 6∘ orientation difference). Whole brain analysis revealed a task main effect of brain areas related to the experimental manipulation of attentional control, including the amygdala, dorsolateral prefrontal cortex, and posterior parietal cortex. Region of interest analysis showed an inverse correlation (r = -0.51, p < 0.01) between left amygdala activation and positive affect level when participants viewed unpleasant stimuli and judged bar orientation in the easy condition. This result suggests that subjects with high positive affect exhibit lower amygdala reactivity to distracting unpleasant pictures. In conclusion, the current study suggests that positive affect modulates attention effect on unpleasant pictures, therefore attenuating emotional responses.
An integrated approach to identify bimodal genes associated with prognosis in cancer
(FapUNIFESP (SciELO), 2021-07-08) Justino, Josivan Ribeiro; Reis, Clovis Ferreira dos; Fonseca, André Luiz; Souza, Sandro José de; Stransky, Beatriz
Bimodal gene expression (where a gene expression distribution has two maxima) is associated with phenotypic diversity in different biological systems. A critical issue, thus, is the integration of expression and phenotype data to identify genuine associations. Here, we developed tools that allow both: i) the identification of genes with bimodal gene expression and ii) their association with prognosis in cancer patients from The Cancer Genome Atlas (TCGA). Bimodality was observed for 554 genes in expression data from 25 tumor types. Furthermore, 96 of these genes presented different prognosis when patients belonging to the two expression peaks were compared. The software to execute the method and the corresponding documentation are available at the Data access section
An investigation of Hebbian phase sequences as assembly graphs
(2014-04) Almeida-Filho, Daniel G.; Lopes-dos-Santos, Vitor; Vasconcelos, Nivaldo A. P.; Miranda, José G.; Tort, Adriano Bretanha Lopes; Ribeiro, Sidarta Tollendal Gomes
An Updated Midline Rule: Visual Callosal Connections Anticipate Shape and Motion in Ongoing Activity across the Hemispheres
(2013) Peiker, Christiane; Wunderle, Thomas; Eriksson, David; Schmidt, Anne; Schmidt, Kerstin Erika
It is generally thought that callosal connections (CCs) in primary visual cortices serve to unify the visual scenery parted in two at the vertical midline (VM). Here, we present evidence that this applies also to visual features that do not cross yet but might cross the VM in the future. During reversible deactivation of the contralateral visual cortex in cats, we observed that ipsilaterally recorded neurons close to the border between areas 17 and 18 receive selective excitatory callosal input on both ongoing and evoked activity. In detail, neurons responding well to a vertical Gabor patch moving away from the deactivated hemifield decreased prestimulus and stimulus-driven activity much more than those preferring motion toward the cooled hemifield. Further, activity of neurons responding to horizontal lines decreased more than the response to vertical lines. Embedding a single Gabor into a collinear line context selectively stabilized responses, especially when the context was limited to the intact hemifield. These findings indicate that CCs interconnect not only neurons coding for similar orientations but also for similar directions of motion. We conclude that CCs anticipate stimulus features that are potentially relevant for both hemifields (i.e., coherent motion but also collinear shape) because already prestimulus activity and activity to stimuli not crossing the VM revealed feature specificity. Finally, we hypothesize that intrinsic and callosal networks processing different orientations and directions are anisotropic close to the VM facilitating perceptual grouping along likely future motion or (shape) trajectories before the visual stimulus arrives.
Analysis of modular gene co-expression networks reveals molecular pathways underlying Alzheimer’s disease and progressive supranuclear palsy
(Public Library of Science (PLoS), 2022-04-14) Iohan, Lukas da Cruz Carvalho; Lambert, Jean-Charles; Costa, Marcos Romualdo; 0000-0002-4928-2163
A comprehensive understanding of the pathological mechanisms involved at different stages of neurodegenerative diseases is key for the advance of preventive and disease-modifying treatments. Gene expression alterations in the diseased brain is a potential source of information about biological processes affected by pathology. In this work, we performed a systematic comparison of gene expression alterations in the brains of human patients diagnosed with Alzheimer’s disease (AD) or Progressive Supranuclear Palsy (PSP) and animal models of amyloidopathy and tauopathy. Using a systems biology approach to uncover biological processes associated with gene expression alterations, we could pinpoint processes more strongly associated with tauopathy/PSP and amyloidopathy/AD. We show that gene expression alterations related to immune-inflammatory responses preponderate in younger, whereas those associated to synaptic transmission are mainly observed in older AD patients. In PSP, however, changes associated with immune-inflammatory responses and synaptic transmission overlap. These two different patterns observed in AD and PSP brains are fairly recapitulated in animal models of amyloidopathy and tauopathy, respectively. Moreover, in AD, but not PSP or animal models, gene expression alterations related to RNA splicing are highly prevalent, whereas those associated with myelination are enriched both in AD and PSP, but not in animal models. Finally, we identify 12 AD and 4 PSP genetic risk factors in cell-type specific co-expression modules, thus contributing to unveil the possible role of these genes to pathogenesis. Altogether, this work contributes to unravel the potential biological processes affected by amyloid versus tau pathology and how they could contribute to the pathogenesis of AD and PSP
Analysis of the microarray gene expression for breast cancer progression after the application modified logistic regression
(2019-11-21) Morais-Rodrigues, Francielly; Silv́erio-Machado, Rita; Kato, Rodrigo Bentes; Rodrigues, Diego Lucas Neres; Valdez-Baez, Juan; Fonseca, Vagner; San, Emmanuel James; Gomes, Lucas Gabriel Rodrigues; Santos, Roselane Gonçalves dos; Viana, Marcus Vinicius Canário; Dutra, Joyceda Cruz Ferraz; Parise, Mariana Teixeira Dornelles; Parise, Doglas; Campos, Frederico F.; Souza, Sandro José de; Ortega, José Miguel; Barh, Debmalya; Ghosh, Preetam; Azevedo, Vasco A. C.; Santos, Marcos A. dos
Methods based around statistics and linear algebra have been increasingly used in attempts to address emerging questions in microarray literature. Microarray technology is a long-used tool in the global analysis of gene expression, allowing for the simultaneous investigation of hundreds or thousands of genes in a sample. It is characterized by a low sample size and a large feature number created a non-square matrix, and by the incomplete rank, that can generate countless more solution in classifiers. To avoid the problem of the ‘curse of dimensionality’ many authors have performed feature selection or reduced the size of data matrix. In this work, we introduce a new logistic regression-based model to classify breast cancer tumor samples based on microarray expression data, including all features of gene expression and without reducing the microarray data matrix. If the user still deems it necessary to perform feature reduction, it can be done after the application of the methodology, still maintaining a good classification. This methodology allowed the correct classification of breast cancer sample data sets from Gene Expression Omnibus (GEO) data series GSE65194, GSE20711, and GSE25055, which contain the microarray data of said breast cancer samples. Classification had a minimum performance of 80% (sensitivity and specificity), and explored all possible data combinations, including breast cancer subtypes. This methodology highlighted genes not yet studied in breast cancer, some of which have been observed in Gene Regulatory Networks (GRNs). In this work we examine the patterns and features of a GRN composed of transcription factors (TFs) in MCF-7 breast cancer cell lines, providing valuable information regarding breast cancer. In particular, some genes whose αi ∗ associated parameter values revealed extreme positive and negative values, and, as such, can be identified as breast cancer prediction genes. We indicate that the PKN2, MKL1, MED23, CUL5 and GLI genes demonstrate a tumor suppressor profile, and that the MTR, ITGA2B, TELO2, MRPL9, MTTL1, WIPI1, KLHL20, PI4KB, FOLR1 and SHC1 genes demonstrate an oncogenic profile. We propose that these may serve as potential breast cancer prediction genes, and should be prioritized for further clinical studies on breast cancer. This new model allows for the assignment of values to the αi ∗ parameters associated with gene expression. It was noted that some αi ∗ parameters are associated with genes previously described as breast cancer biomarkers, as well as other genes not yet studied in relation to this disease.
Anatomical and functional MRI changes after one year of auditory rehabilitation with hearing aids
(2018-09-10) Pereira-Jorge, M. R.; Andrade, K. C.; Palhano-Fontes, F. X.; Diniz, P. R. B.; Sturzbecher, M.; Santos, A. C.; Araújo, Dráulio Barros de
Hearing aids (HAs) are an effective strategy for auditory rehabilitation in patients with peripheral hearing deficits. Yet, the neurophysiological mechanisms behind HA use are still unclear. Thus far, most studies have focused on changes in the auditory system, although it is expected that hearing deficits affect a number of cognitive systems, notably speech. In the present study, we used audiometric evaluations in 14 patients with bilateral hearing loss before and after one year of continuous HA use and functional magnetic resonance imaging (fMRI) and cortical thickness analysis in 12 and 10 of them compared with a normal hearing control group. Prior to HA fitting, fMRI activity was found reduced in the auditory and language systems and increased in visual and frontal areas, expanding to multimodal integration cortices, such as the superior temporal gyrus, intraparietal sulcus, and insula. One year after rehabilitation with HA, significant audiometric improvement was observed, especially in free-field Speech Reception Threshold (SRT) test and functional gain, a measure of HA efficiency. HA use increased fMRI activity in the auditory and language cortices and multimodal integration areas. Individual fMRI signal changes from all these areas were positively correlated with individual SRT changes. Before rehabilitation, cortical thickness was increased in parts of the prefrontal cortex, precuneus, fusiform gyrus, and middle temporal gyrus. It was reduced in the insula, supramarginal gyrus, medial temporal gyrus, occipital cortex, posterior cingulate cortex, and claustrum. After HA use, increased cortical thickness was observed in multimodal integration regions, particularly the very caudal end of the superior temporal sulcus, the angular gyrus, and the inferior parietal gyrus/superior temporal gyrus/insula. Our data provide the first evidence that one year of HA use is related to functional and anatomical brain changes, notably in auditory and language systems, extending to multimodal cortices.
Antecedent descriptions change brain reactivity to emotional stimuli: a Functional Magnetic Resonance imaging study of an extrinsic and incidental reappraisal strategy
(2011) MOCAIBER, I.; SANCHEZ, T. A.; PEREIRA, M. G.; ERTHAL, F. S.; JOFFILY, M.; Araújo, Dráulio Barros de; VOLCHAN, E.; OLIVEIRA, L. DE
In the present study we investigated whether individuals would take advantage of an extrinsic and incidental reappraisal strategy by giving them precedent descriptions to attenuate the emotional impact of unpleasant pictures. In fact, precedent descriptions have successfully promoted down-regulation of electrocortical activity and physiological responses to unpleasant pictures. However, the neuronal substrate underlying this effect remains unclear. Particularly, we investigated whether amygdala and insula responses, brain regions consistently implicated in emotional processing, would be modulated by this strategy. To achieve this, highly unpleasant pictures were shown in two contexts in which a prior description presented them as taken from movie scenes (fictitious) or real scenes. Results showed that the fictitious condition was characterized by down-regulation of amygdala and insula responses. Thus, the present study provides new evidence on reappraisal strategies to downregulate emotional reactions and suggest that amygdala and insula responses to emotional stimuli are adaptive and highly flexible.
Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report
(2015) Osório, Flávia de L.; Sanches, Rafael F.; Macedo, Ligia R.; Santos, Rafael G. dos; Maia-de-Oliveira, João P.; Wichert-Ana, Lauro; Araújo, Dráulio Barros de; Riba, Jordi; Crippa, José A.; Hallak, Jaime E.
Objectives: Ayahuasca (AYA), a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT) and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode. Methods: Open-label trial conducted in an inpatient psychiatric unit. Results: Statistically significant reductions of up to 82% in depressive scores were observed between baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS). AYA administration resulted in nonsignificant changes in Young Mania Rating Scale (YMRS) scores and in the thinking disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or hypomania in patients with mood disorders and that modifications in thought content, which could indicate psychedelic effects, are not essential for mood improvement. Conclusions: These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder.

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