Effects of Yoga Respiratory Practice (Bhastrika pranayama) on Anxiety, Affect, and Brain Functional Connectivity and Activity: A Randomized Controlled Trial.

Pranayama refers to a set of yoga breathing exercises. Recent evidence suggests that the practice of pranayama has positive effects on measures of clinical stress and anxiety. This study explored the impact of a Bhastrika pranayama training program on emotion processing, anxiety, and affect. We used a randomized controlled trial design with thirty healthy young adults assessed at baseline and after 4 weeks of pranayama practices. Two functional magnetic resonance imaging (MRI) protocols were used both at baseline and post-intervention: an emotion task as well as a resting-state acquisition. Our results suggest that pranayama significantly decreased states of anxiety and negative affect. The practice of pranayama also modulated the activity of brain regions involved in emotional processing, particularly the amygdala, anterior cingulate, anterior insula, and prefrontal cortex. Resting-state functional MRI (fMRI) showed significantly reduced functional connectivity involving the anterior insula and lateral portions of the prefrontal cortex. Correlation analysis revealed that changes in connectivity between the ventrolateral prefrontal cortex and the right anterior insula were associated with changes in anxiety. Although it should be noted that these analyses were preliminary and exploratory, it provides the first evidence that 4 weeks of B. pranayama significantly reduce the levels of anxiety and negative affect, and that these changes are associated with the modulation of activity and connectivity in brain areas involved in emotion processing, attention, and awareness. The study was registered at https://www.ensaiosclinicos.gov.br/rg/RBR-2gv5c2/(RBR-2gv5c2).

Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial.

BACKGROUND: Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. METHODS: To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing. RESULTS: We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054). CONCLUSIONS: To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769).

Neurofunctional changes after a single mirror therapy intervention in chronic ischemic stroke.

BACKGROUND: Mirror therapy (MT) is becoming an alternative rehabilitation strategy for various conditions, including stroke. Although recent studies suggest the positive benefit of MT in chronic stroke motor recovery, little is known about its neural mechanisms. PURPOSE: To identify functional brain changes induced by a single MT intervention in ischemic stroke survivors, assessed by both transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI). MATERIALS AND METHODS: TMS and fMRI were used to investigate 15 stroke survivors immediately before and after a single 30-min MT session. RESULTS: We found statistically significant increase in post-MT motor evoked potential (MEP) amplitude (increased excitability) from the affected primary motor cortex (M1), when compared to pre-MT MEP. Post-MT fMRI maps were associated with a more organized and constrained pattern, with a more focal M1 activity within the affected hemisphere after MT, limited to the cortical area of hand representation. Furthermore, we find a change in the balance of M1 activity toward the affected hemisphere. In addition, significant correlation was found between decreased fMRI ß-values and increased MEP amplitude post-MT, in the affected hemisphere. CONCLUSION: Our study suggests that a single MT intervention in stroke survivors is related to increased MEP of the affected limb, and a more constrained activity of the affected M1, as if activity had become more constrained and limited to the affected hemisphere.

The psychedelic state induced by ayahuasca modulates the activity and connectivity of the default mode network.

The experiences induced by psychedelics share a wide variety of subjective features, related to the complex changes in perception and cognition induced by this class of drugs. A remarkable increase in introspection is at the core of these altered states of consciousness. Self-oriented mental activity has been consistently linked to the Default Mode Network (DMN), a set of brain regions more active during rest than during the execution of a goal-directed task. Here we used fMRI technique to inspect the DMN during the psychedelic state induced by Ayahuasca in ten experienced subjects. Ayahuasca is a potion traditionally used by Amazonian Amerindians composed by a mixture of compounds that increase monoaminergic transmission. In particular, we examined whether Ayahuasca changes the activity and connectivity of the DMN and the connection between the DMN and the task-positive network (TPN). Ayahuasca caused a significant decrease in activity through most parts of the DMN, including its most consistent hubs: the Posterior Cingulate Cortex (PCC)/Precuneus and the medial Prefrontal Cortex (mPFC). Functional connectivity within the PCC/Precuneus decreased after Ayahuasca intake. No significant change was observed in the DMN-TPN orthogonality. Altogether, our results support the notion that the altered state of consciousness induced by Ayahuasca, like those induced by psilocybin (another serotonergic psychedelic), meditation and sleep, is linked to the modulation of the activity and the connectivity of the DMN.

Brain complex network analysis by means of resting state fMRI and graph analysis: will it be helpful in clinical epilepsy?

Functional magnetic resonance imaging (fMRI) has just completed 20 years of existence. It currently serves as a research tool in a broad range of human brain studies in normal and pathological conditions, as is the case of epilepsy. To date, most fMRI studies aimed at characterizing brain activity in response to various active paradigms. More recently, a number of strategies have been used to characterize the low-frequency oscillations of the ongoing fMRI signals when individuals are at rest. These datasets have been largely analyzed in the context of functional connectivity, which inspects the covariance of fMRI signals from different areas of the brain. In addition, resting state fMRI is progressively being used to evaluate complex network features of the brain. These strategies have been applied to a number of different problems in neuroscience, which include diseases such as Alzheimer's, schizophrenia, and epilepsy. Hence, we herein aimed at introducing the subject of complex network and how to use it for the analysis of fMRI data. This appears to be a promising strategy to be used in clinical epilepsy. Therefore, we also review the recent literature that has applied these ideas to the analysis of fMRI data in patients with epilepsy.

Resting state functional MRI connectivity predicts hypothalamus-pituitary-axis status in healthy males.

Homeostasis of the human stress response system is critically maintained by a hierarchical system of neural and endocrine elements for which intact negative feedback is important to prevent maladaptation towards stress. Such feedback is efficiently probed by the established combined dexamethasone-suppression/corticotropin-releasing hormone stimulation (dex/CRH) test. Here we investigate which suprahypothalamic networks might modulate the response assessed by this neuroendocrine test. Combined resting state fMRI (rs-fMRI)/EEG was acquired in 20 healthy male volunteers along with dex/CRH profiles obtained on a different day outside the scanner. Seed-based network analysis and inter-seed cross correlation analysis for selected atlas-based limbic, paralimbic and medial prefrontal cortex seeds were correlated with stimulated cortisol and adrenocorticotropin hormone (ACTH) concentrations. Lower connectivity between a left hippocampus-based network and the right hippocampus significantly predicted stimulated cortisol concentration (R(2)=0.70, corrected pcluster=0.001). Six further significantly negative correlations were detected mainly in the left anterior cingulate cortex (ACC) and the medial prefrontal cortex (mPFC). The strongest positive correlation with stimulated hormone concentration was detected for the left subcallosal ACC (ACTH, R(2)=0.57, corrected pcluster=0.009). Inter-seed connectivity mainly pointed to hippocampal/amygdala interactions as correlates of the dex/CRH response. In conclusion, resting state functional connectivity patterns of limbic, particularly hippocampal, as well as cingulate and medial prefrontal areas can explain some of the variance of the dex/CRH test in healthy subjects. Functional connectivity analysis can be considered useful to study supra-hypothalamic control systems of the HPA axis.

Statistical evaluation of recurrence quantification analysis applied on single trial evoked potential studies.

OBJECTIVE: We evaluated the potential of recurrence quantification analysis (RQA) to improve the analysis of trial-by-trial-variability in event-related potentials (ERPs) experiments. METHODS: We use an acoustic oddball paradigm to compare the efficiency of RQA with a linear amplitude based analysis of single trial ERPs with regard to the power to distinguish responses to different tone types. We further probed the robustness of both analyses towards structured noise induced by parallel magnetic resonance imaging (MRI). RESULTS: RQA provided robust discrimination of responses to different tone types, even when EEG data were contaminated by structured noise. Yet, its power to discriminate responses to different tone types was not significantly superior to a linear amplitude analysis. RQA measures were only moderately correlated with EEG amplitudes, suggesting that RQA may extract additional information from single trial responses not detected by amplitude evaluation. CONCLUSIONS: RQA allows quantifying signal characteristics of single trial ERPs measured with and without noise induced by parallel MRI. RQA power to discriminate responses to different tone types was similar to linear amplitude based analysis. SIGNIFICANCE: RQA has the potential to detect differences of signal features in response to a standard oddball paradigm and provide additional trial-by-trial information compared to classical amplitude based analysis.

Effects of rapid eye movement sleep deprivation on fear extinction recall and prediction error signaling.

In a temporal difference learning approach of classical conditioning, a theoretical error signal shifts from outcome deliverance to the onset of the conditioned stimulus. Omission of an expected outcome results in a negative prediction error signal, which is the initial step towards successful extinction and may therefore be relevant for fear extinction recall. As studies in rodents have observed a bidirectional relationship between fear extinction and rapid eye movement (REM) sleep, we aimed to test the hypothesis that REM sleep deprivation impairs recall of fear extinction through prediction error signaling in humans. In a three-day design with polysomnographically controlled REM sleep deprivation, 18 young, healthy subjects performed a fear conditioning, extinction and recall of extinction task with visual stimuli, and mild electrical shocks during combined functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) measurements. Compared to the control group, the REM sleep deprivation group had increased SCR scores to a previously extinguished stimulus at early recall of extinction trials, which was associated with an altered fMRI time-course in the left middle temporal gyrus. Post-hoc contrasts corrected for measures of NREM sleep variability also revealed between-group differences primarily in the temporal lobe. Our results demonstrate altered prediction error signaling during recall of fear extinction after REM sleep deprivation, which may further our understanding of anxiety disorders in which disturbed sleep and impaired fear extinction learning coincide. Moreover, our findings are indicative of REM sleep related plasticity in regions that also show an increase in activity during REM sleep.

Sleep spindles and hippocampal functional connectivity in human NREM sleep.

We investigated human hippocampal functional connectivity in wakefulness and throughout non-rapid eye movement sleep. Young healthy subjects underwent simultaneous EEG and functional magnetic resonance imaging (fMRI) measurements at 1.5 T under resting conditions in the descent to deep sleep. Continuous 5 min epochs representing a unique sleep stage (i.e., wakefulness, sleep stages 1 and 2, or slow-wave sleep) were extracted. fMRI time series of subregions of the hippocampal formation (HF) (cornu ammonis, dentate gyrus, and subiculum) were extracted based on cytoarchitectonical probability maps. We observed sleep stage-dependent changes in HF functional coupling. The HF was integrated to variable strength in the default mode network (DMN) in wakefulness and light sleep stages but not in slow-wave sleep. The strongest functional connectivity between the HF and neocortex was observed in sleep stage 2 (compared with both slow-wave sleep and wakefulness). We observed a strong interaction of sleep spindle occurrence and HF functional connectivity in sleep stage 2, with increased HF/neocortical connectivity during spindles. Moreover, the cornu ammonis exhibited strongest functional connectivity with the DMN during wakefulness, while the subiculum dominated hippocampal functional connectivity to frontal brain regions during sleep stage 2. Increased connectivity between HF and neocortical regions in sleep stage 2 suggests an increased capacity for possible global information transfer, while connectivity in slow-wave sleep is reflecting a functional system optimal for segregated information reprocessing. Our data may be relevant to differentiating sleep stage-specific contributions to neural plasticity as proposed in sleep-dependent memory consolidation.

Development of a large-scale functional brain network during human non-rapid eye movement sleep.

Graph theoretical analysis of functional magnetic resonance imaging (fMRI) time series has revealed a small-world organization of slow-frequency blood oxygen level-dependent (BOLD) signal fluctuations during wakeful resting. In this study, we used graph theoretical measures to explore how physiological changes during sleep are reflected in functional connectivity and small-world network properties of a large-scale, low-frequency functional brain network. Twenty-five young and healthy participants fell asleep during a 26.7 min fMRI scan with simultaneous polysomnography. A maximum overlap discrete wavelet transformation was applied to fMRI time series extracted from 90 cortical and subcortical regions in normalized space after residualization of the raw signal against unspecific sources of signal fluctuations; functional connectivity analysis focused on the slow-frequency BOLD signal fluctuations between 0.03 and 0.06 Hz. We observed that in the transition from wakefulness to light sleep, thalamocortical connectivity was sharply reduced, whereas corticocortical connectivity increased; corticocortical connectivity subsequently broke down in slow-wave sleep. Local clustering values were closest to random values in light sleep, whereas slow-wave sleep was characterized by the highest clustering ratio (gamma). Our findings support the hypothesis that changes in consciousness in the descent to sleep are subserved by reduced thalamocortical connectivity at sleep onset and a breakdown of general connectivity in slow-wave sleep, with both processes limiting the capacity of the brain to integrate information across functional modules.

Desenvolvimento neuromotor e dentição de crianças atendidas em serviços públicos de saúde do Brasil, no primeiro ano de vida / Neuromotor development and teething of children assisted in public health services in Brazil, in the first year of life

Este artigo tem como objetivo identificar, através da percepção materna, o desenvolvimento de crianças atendidas no primeiro ano de vida em serviços públicos de saúde do Brasil. Em entrevista com as mães, foram levantados sinais de desenvolvimento: firmar a cabeça, sentar, engatinhar, andar com ajuda ou sozinha, falar e dentição de 5655 crianças. As respostas categóricas (sim/não) foram avaliadas segundo associação com: idade e escolaridade maternas, idade gestacional no parto, peso ao nascer, estado nutricional e anemia da criança, aleitamento materno e uso de chupeta. Os resultados revelaram que a maior proporção de crianças apresenta-se atrasada em relação aos padrões estabelecidos pelo Ministério da Saúde para o desenvolvimento neuromotor e dentição. A prematuridade foi o fator mais freqüentemente associado a sinais de desenvolvimento não atingidos e a dentição foi o sinal mais sensível às mesmas variáveis. Verificou-se que parte dos resultados negativos talvez sejam conseqüência da dificuldade materna em identificar os sinais subjetivos de desenvolvimento. Sugere-se que um levantamento dos sinais de desenvolvimento seja realizado por profissionais treinados permitindo verificar critérios e/ou intervenções adequadas para modificar a situação encontrada(AU)

This article aims to estimate, through maternal perception, the prevalence of development signs, and determine associated risk factors among infants receiving routine health care in public clinics. The cross-sectional study included 5655 infants in the first year of life. The information regarding the child was obtained from the mother/caregiver by means of an interview. The development signs studied were: sustaining the head, seating, crawling, walking with some help or by itself, speaking, and also teething. The categorical answers (yes/no) were evaluated according to: maternal age and schooling, gestational age at childbirth, birth weight, child's nutritional status and anemia, breast-feeding, and use of pacifier. Results showed that most of the children are delayed according to the standards of neuromotor development and teething established by the Ministry of Health. Prematurity was the factor most often associated with non-reached development signs, and teething was the sign most frequently associated with the selected variables. It was verified that part of the negative results may be a consequence of the maternal difficulty in identifying subjective development signs. It is suggested that a survey to identify development signs is conducted by trained professionals to check criteria and/or adequate interventions to change the observed results.(AU)

Desenvolvimento neuromotor e dentição de crianças atendidas em serviços públicos de saúde do Brasil, no primeiro ano de vida / Neuromotor development and teething of children assisted in public health services in Brazil, in the first year of life

Este artigo tem como objetivo identificar, através da percepção materna, o desenvolvimento de crianças atendidas no primeiro ano de vida em serviços públicos de saúde do Brasil. Em entrevista com as mães, foram levantados sinais de desenvolvimentos: firmar a cabeça, sentar, engatinhar, andar com ajuda ou sozinha, falar e dentição 5655 crianças. As respostas categóricas (sim/não) foram avaliadas segundo associação com: idade e escolaridades maternas, idade gestacional no parto, peso ao nascer, estado nutricional e anemia da criança, aleitamento materno e uso de chupeta. Os resultados revelaram que a maior proporção de crianças apresenta-se atrasada em relação aos padrões estabelecidos pelo Ministério da Saúde para o desenvolvimento neuromotor e dentição. A prematuridade foi o fator mais freqüentemente associado a sinais de desenvolvimentos não atingidos e a dentição foi o sinal mais sensível às mesmas variáveis. Verificou-se que parte dos resultados negativos talvez sejam conseqüência da dificuldade materna em identificar os sinais subjetivos de desenvolvimento. Sugere-se que um levantamento dos sinais de desenvolvimento seja realizado por profissionais treinados permitindo verificar critérios e/ou intervenções adequadas para modificar a situação encontrada.

This article aims to estimate, through maternal perception, the prevalence of development signs, and determine associated risk factors among infants receiving routine health care in public clinics. The cross-sectional study included 5655 infants in the first year of life. The information regarding the child was obtained from the mother/caregiver by means of an interview. The development signs studied were: sustaining the head, seating, crawling, walking with some help or by itself, speaking, and also teething. The categorical answers (yes/no) were evaluated according to: maternal age and schooling, gestational age at childbirth, birth weight, child's nutritional status and anemia, breast-feeding, and use of pacifier. Results showed that most of the children are delayed according to the standards of neuromotor development and teething established by the Ministry of Health. Prematurity was the factor most often associated with non-reached development signs, and teething was the sign most frequently associated with the selected variables. It was verified that part of the negative results may be a consequence of the maternal difficulty in identifying subjective development signs. It is suggested that a survey to identify development signs is conducted by trained professionals to check criteria and/or adequate interventions to change the observed results.

Quantitative aspects of brain perfusion dynamic induced by BOLD fMRI / Aspectos quantitativos da dinâmica perfusional do cérebro induzida pelo BOLD fMRI

The increase of relative cerebral blood flow (rCBF) may contribute for a change in blood oxygenation level dependent signal (BOLD). The main purpose of this study is to investigate some aspects of perfusional alterations in the human brain in response to a uniform stimulation: hypercapnia induced by breath holding. It was observed that the BOLD signal increased globally during hypercapnia and that it is correlated with the time of breath holding. This signal increase shows a clear distinction between gray and white matter, being greater in the grey matter.

O aumento relativo do fluxo cerebral sangüíneo (relative Cerebral Blood Flow - rCBF) pode contribuir para uma mudança no sinal dependente da oxigenação do sangue (Blood Oxygenation Level Dependent - BOLD). O objetivo principal deste trabalho foi estudar alguns aspectos da alteração perfusional no cérebro humano em resposta a um estímulo uniforme: hipercapnia, causada por um estado de apnéia induzida. Foi observado um aumento global no sinal BOLD durante a hipercapnia. Este aumento é correlacionado com a duração da apnéia e mostra uma clara distinção entre a substância branca e cinzenta, sendo maior na substância cinzenta.

Quantitative aspects of brain perfusion dynamic induced by BOLD fMRI.

The increase of relative cerebral blood flow (rCBF) may contribute for a change in blood oxygenation level dependent signal (BOLD). The main purpose of this study is to investigate some aspects of perfusional alterations in the human brain in response to a uniform stimulation: hypercapnia induced by breath holding. It was observed that the BOLD signal increased globally during hypercapnia and that it is correlated with the time of breath holding. This signal increase shows a clear distinction between gray and white matter, being greater in the grey matter.