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

Caracterização comportamental e distribuição de neurônios inibitórios em um modelo animal de autismo induzido por ácido valpróico

Autism comprises a heterogeneous group of neurodevelopmental disorders that affects the brain maturation and produces sensorial, motor, language and social interaction deficits in early childhood. Several studies have shown a major involvement of genetic factors leading to a predisposition to autism, which are possibly affected by environmental modulators during embryonic and post-natal life. Recent studies in animal models indicate that alterations in epigenetic control during development can generate neuronal maturation disturbances and produce a hyper-excitable circuit, resulting in typical symptoms of autism. In the animal model of autism induced by valproic acid (VPA) during rat pregnancy, behavioral, electrophysiological and cellular alterations have been reported which can also be observed in patients with autism. However, only a few studies have correlated behavioral alterations with the supposed neuronal hyper-excitability in this model. The aim of this project was to generate an animal model of autism by pre-natal exposure to VPA and evaluate the early post-natal development and pre-puberal (PND30) behavior in the offspring. Furthermore, we quantified the parvalbumin-positive neuronal distribution in the medial prefrontal cortex and Purkinje cells in the cerebellum of VPA animals. Our results show that VPA treatment induced developmental alterations, which were observed in behavioral changes as compared to vehicle-treated controls. VPA animals showed clear behavioral abnormalities such as hyperlocomotion, prolonged stereotipies and reduced social interaction with an unfamiliar mate. Cellular quantification revealed a decrease in the number of parvalbumin-positive interneurons in the anterior cingulate cortex and in the prelimbic cortex of the mPFC, suggesting an excitatory/inhibitory unbalance in this animal model of autism. Moreover, we also observed that the neuronal reduction occurred mainly in the cortical layers II/III and V/VI. We did not detect any change in the density of Purkinje neurons in the Crus I region of the cerebellar cortex. Together, our results strengthens the face validity of the VPA model in rats and shed light on specific changes in the inhibitory circuitry of the prefrontal cortex in this autism model. Further studies should address the challenges to clarify particular electrophysiological correlates of the cellular alterations in order to better understand the behavioral dysfunctions

Expressão de genes imediatos induzidos por vocalizações em sagüis-comuns (Callithrix jacchus)

Immediate-early genes (IEGs) expression has been widely used as a valuable tool to investigate brain areas activated by specific stimuli. Studies of natural vocalizations, specially in songbirds, have largely benefited from this tool. Here we used IEGs expression to investigate brain areas activated by the hearing of conspecific common marmoset (Callithrix jacchus) vocalizations and/or utterance of antiphonal vocalizations. Nine adult male common marmosets were housed in sound-attenuating cages. Six animals were stimulated with playbacks of freely recorded natural long distance vocalizations (phee calls and twitters; 45 min. total duration). Three of them vocalized in response (O/V group) and three did not (O/n group). The control group (C) was composed by the remaining animals, which neither heard the playbacks nor spontaneously vocalized. After one hour of the stimulation onset (or no stimulation, in the case of the C group), animals were perfused with 0,9% phosphate-saline buffer and 4% paraformaldehyde. The tissue was coronally sectioned at 20 micro meter in a cryostat and submitted to immunohistochemistry for the IEGs egr-1 and c-fos. Marked immunoreactivity was observed in the auditory cortex of O/V and O/n subjects and in the anterior cingulate cortex, the dorsomedial prefrontal cortex and the ventrolateral prefrontal cortex of O/V subjects. In this study, brain areas activated by vocalizations of common marmosets were investigated using IEGs expression for the first time. Our results with the egr-1 gene indicate that potential plastic phenomena occur in areas related to hearing and uttering conspecific vocalizations.

Efeito agudo da respiração abdominal lenta sobre a atividade cerebral, respostas emocionais e cardiovasculares

Introduction: Slow abdominal breathing (SAB) stimulates baroreflex and generates respiratory sinus arrhythmia, changing cardiovascular, emotional and cerebral systems acute and chronically. However, although meditative practices have been receiving increasingly attention in the last years, there is no agreement on the neurophysiological changes underlying them, mainly because of the lack of topographical pieces of information. Purpose: We aimed to analyze the acute effect of SAB on brain activity, emotional and cardiovascular responses in untrained subjects in meditative techniques. Methods: Seventeen healthy adults’ men were assessed into two different sessions in a random and crossed order. Into experimental session, they breathed in 6 cycles/minute and in control session they kept breathing in normal rate, both for 20 minutes. xi Before, during, and after each session we assessed brain activity using electroencephalography (EEG), anxiety, mood, heart rate variability (HRV) and blood pressure. The sLORETA software was used to analyze EEG data for source localization of brain areas in which activity was changed. Results: The sLORETA showed that beta band frequency was reduced in frontal gyrus (P<0.01) and anterior cingulate cortex (P<0.05) both during and after SAB (P<0.05) compared to the moment before it. There was no change in brain activity in control session. Additionally, a two-way repeated measures ANOVA showed that there was no effect on anxiety (P>0.8) and mood (P>0.08). There were improvements in HRV (P<0.03), with increased RR interval and decreased HR after SAB, as well as increased SDNN, RMSSD, pNN50, low frequency, LF/HF ratio, and total power during it, with no changes in SBP and DBP. Conclusions: We conclude that SAB is able to change brain activity in areas responsible for emotional processing, even without behavioral changes. Furthermore, SAB improves HRV and does not change blood pressure in normotensive.

Prevalence of biomicroscopic findings in the anterior segment and ocular adnexa among schoolchildren in Natal/Brazil

Objective: To determine the prevalence of ocular findings of the external structures and anterior segment of the eye, detected by biomicroscopic examination in schoolchildren in Natal (RN) - Brazil. Methods: After previous random selection, 1,024 pupils from elementary and secondary public and private schools in the city of Natal were evaluated from March to June 2001. All were submitted to preestablished standard research norms, consisting of identification, demographic information, ophthalmologic biomicroscopic examination, with slit lamp, performed by ophthalmologists from the “Onofre Lopes” University Hospital. Results: Alterations of the conjunctival and palpebral conditions were the most prevalent (10.4% and 6.2% respectively). Follicles (4.2%) and papillae (3.0%) were the frequent conjunctival lesions, while blepharitis (3.5%) and meibomitis (1.1%) were the most detected abnormalities in the eyelids. Upon examining the cornea, iris, lens and anterior vitreous, the most encountered findings were nubecula (0.5%), papillary membrane reliquiae (0.5%), posterior capsula opacity (0.8%) and hyaloid arteria reliquiae (2.0%). Conclusion: The most prevalent findings affecting the external structures of the eye such as eyelids and conjunctiva, consisted of blepharitis followed by follicular reaction of the conjunctiva. The most prevalent abnormalities in the cornea, iris, lens and anterior vitreous were nubecula, papillary membrane reliquiae, posterior capsular opacity and hyaloid arteria reliquiae, in that order

Sonic hedgehog signaling regulates mode of cell division of early cerebral cortex progenitors and increases

The morphogen Sonic Hedgehog (SHH) plays a critical role in the development of different tissues. In the central nervous system, SHH is well known to contribute to the patterning of the spinal cord and separation of the brain hemispheres. In addition, it has recently been shown that SHH signaling also contributes to the patterning of the telencephalon and establishment of adult neurogenic niches. In this work, we investigated whether SHH signaling influences the behavior of neural progenitors isolated from the dorsal telencephalon, which generate excitatory neurons and macroglial cells in vitro. We observed that SHH increases proliferation of cortical progenitors and generation of astrocytes, whereas blocking SHH signaling with cyclopamine has opposite effects. In both cases, generation of neurons did not seem to be affected. However, cell survival was broadly affected by blockade of SHH signaling. SHH effects were related to three different cell phenomena: mode of cell division, cell cycle length and cell growth. Together, our data in vitro demonstrate that SHH signaling controls cell behaviors that are important for proliferation of cerebral cortex progenitors, as well as differentiation and survival of neurons and astroglial cells.

Local Field Potentials in the Gustatory Cortex Carry Taste Information

It has been recently shownthat localfield potentials (LFPs)fromthe auditory and visual cortices carry information about sensory stimuli, but whether this is a universal property of sensory cortices remains to be determined. Moreover, little is known about the temporal dynamics of sensory information contained in LFPs following stimulus onset. Here we investigated the time course of the amount of stimulus information in LFPs and spikes from the gustatory cortex of awake rats subjected to tastants and water delivery on the tongue. We found that the phase and amplitude of multiple LFP frequencies carry information about stimuli, which have specific time courses after stimulus delivery. The information carried by LFP phase and amplitude was independent within frequency bands, since the joint information exhibited neither synergy nor redundancy. Tastant information in LFPs was also independent and had a different time course from the information carried by spikes. These findings support the hypothesis that the brain uses different frequency channels to dynamically code for multiple features of a stimulus.

Proliferative Defects and Formation of a Double Cortex in Mice Lacking Mltt4 and Cdh2 in the Dorsal Telencephalon

Radial glial cells (RGCs) in the ventricular neuroepithelium of the dorsal telencephalon are the progenitor cells for neocortical projection neurons and astrocytes. Here we showthatthe adherens junction proteins afadin and CDH2 are criticalforthe control of cell proliferation in the dorsal telencephalon and for the formation of its normal laminar structure. Inactivation of afadin or CDH2 in the dorsal telenceph-alon leads to a phenotype resembling subcortical band heterotopia, also known as “double cortex,” a brain malformation in which heterotopic gray matter is interposed between zones of white matter. Adherens junctions between RGCs are disrupted in the mutants, progenitor cells are widely dispersed throughout the developing neocortex, and their proliferation is dramatically increased. Major subtypes of neocortical projection neurons are generated, but their integration into cell layers is disrupted. Our findings suggest that defects in adherens junctions components in mice massively affects progenitor cell proliferation and leads to a double cortex-like phenotype.

Influência da fadiga no comportamento neuromuscular do quadríceps femoral, após reconstrução do ligamento cruzado anterior

Muscle fatigue is a phenomenon that promotes physiological and biomechanical disorders and their changes in healthy subjects have been widely studied and have significant importance for care in preventing injuries, but we do not have many information about its effects in patients after ACL reconstruction. Thus, this study is to analyze the effects of fatigue on neuromuscular behavior of quadriceps after ACL reconstruction. To reach this objective, participants were forty men, twenty healthy (26,90 ± 6,29 years) and twenty after ACL reconstruction (29,75 ± 7,01 years) with a graft of semitendinosus and gracilis tendons, between four to six months after surgery. At first, there was an assessment of joint position sense (JPS) at the isokinetic dynamometer at a speed of 5°/s and target angle of 45° to analyze the absolute error of JPS. Next, we applied the a muscle fatigue protocol, running 100 repetitions of isokinetic knee flexion-extension at 90°/s. Concurrently with this protocol, there was the assessment of muscle performance, as the peak torque (PT) and fatigue index, and electromyographic activity (RMS and median frequency). Finally, we repeated the assessment of JPS. The statistical analysis showed that patients after ACL reconstruction have, even under normal conditions, the amended JPS compared with healthy subjects and that after fatigue, both have disturbances in the JPS, but this alteration is significantly exacerbated in patients after ACL reconstruction. About muscle performance, we could notice that these patients have a lower PT, although there are no differences between the dynamometric and EMG fatigue index. These findings show the necessity about the cares of pacients with ACL reconstruction in respect of the risks of articulate instability and overload in ligamentar graft

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

Avaliação mecânica in vitro utilizando miniplacas quadradas e retangulares do sistema 2.0 mm em fraturas da região anterior de mandíbula

The aim of this study was to comparatively evaluate the mechanical strength of squared and rectangular 2.0 mm system miniplates comparing them to the standard configuration with 2 straight miniplates in stabilizing fractures in the anterior mandible. Ninety synthetic polyurethane mandible replicas were used in mechanical test. The samples were divided into six groups of three different methods for fixation. Groups 1, 2 and 3 showed complete fractures in symphysis, characterized by a linear separation between the medial incisor, and groups 4, 5 and 6 showed complete fractures in parasymphysis with oblique design. Groups 1 and 4 were represented by the standard technique with two straight miniplates parallel to each other. Groups 2 and 5 were stabilized by squared miniplates and groups 3 and 6 were fixed by rectangular design. Each group was subjected to a mechanical test at a displacement speed of 10 mm/min on a universal testing machine, receiving linear vertical load on the region of the left first molar. The values of the maximum load and when displacements reached 5 mm were obtained and statistically analyzed by calculating the confidence interval of 95%. Fixation systems using squared (G2) and rectangular (G3) miniplates obtained similar results. No statistically significant differences with respect to the maximum load and the load at 5 mm displacement were found when compared to standard method in symphyseal fractures (G1). In parasymphysis the fixation method using squared miniplates (G5) obtained results without significant differences regarding the maximum load and the load at 5 mm when compared to the standard configuration (G4). The fixation method using rectangular miniplates (G6) showed inferior results which were statistically significant when compared to the standard configuration (G4) for parasymphysis fractures. The mechanical behavior of the fixation methods was similar, except when rectangular miniplates were used. The fixation methods showed better results with statistical significance in symphyseal fractures