Navegando por Autor "Palhano-Fontes, Fernanda"

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Brain complex network analysis by means of resting state fMRI and graph analysis: Will it be helpful in clinical epilepsy?
(2014) Onias, Heloisa; Viol, Aline; Palhano-Fontes, Fernanda; Andrade, Katia C.; Sturzbecher, Marcio; Viswanathan, Gandhimohan; Araújo, Dráulio Barros de
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.
Changes in cortisol but not in brain-derived neurotrophic factor modulate the association between sleep disturbances and major depression
(2020-04-28) Santiago, Giuliana Travassos Pires; Galvão, Ana Cecília de Menezes; Almeida, Raíssa Nóbrega de; Mota-Rolim, Sergio Arthuro; Palhano-Fontes, Fernanda; Maia-de-Oliveira, João Paulo; Araújo, Dráulio Barros de; Lobão-Soares, Bruno; Galvão-Coelho, Nicole Leite
Sleep disturbance is a symptom consistently found in major depression and is associated with a longer course of illness, reduced response to treatment, increased risk of relapse and recurrence. Chronic insomnia has been associated with changes in cortisol and serum brain-derived neurotrophic factor (BDNF) levels, which in turn are also changed in major depression. Here, we evaluated the relationship between sleep quality, salivary cortisol awakening response (CAR), and serum BDNF levels in patients with sleep disturbance and treatment-resistant major depression (n = 18), and in a control group of healthy subjects with good (n = 21) and poor (n = 18) sleep quality. We observed that the patients had the lowest CAR and sleep duration of all three groups and a higher latency to sleep than the healthy volunteers with a good sleep profile. Besides, low CAR was correlated with more severe depressive symptoms and worse sleep quality. There was no difference in serum BDNF levels between groups with distinct sleep quality. Taken together, our results showed a relationship between changes in CAR and in sleep quality in patients with treatment-resistant depression, which were correlated with the severity of disease, suggesting that cortisol could be a physiological link between sleep disturbance and major depression.
Characterizing complex networks using entropy-degree diagrams: unveiling changes in functional brain connectivity induced by ayahuasca
(2019-01-30) Viol, Aline; Palhano-Fontes, Fernanda; Onias, Heloisa; Araújo, Dráulio Barros de; Hövel, Philipp; Viswanathan, Gandhi M.
With the aim of further advancing the understanding of the human brain’s functional connectivity, we propose a network metric which we term the geodesic entropy. This metric quantifies the Shannon entropy of the distance distribution to a specific node from all other nodes. It allows to characterize the influence exerted on a specific node considering statistics of the overall network structure. The measurement and characterization of this structural information has the potential to greatly improve our understanding of sustained activity and other emergent behaviors in networks. We apply this method to study how the psychedelic infusion Ayahuasca affects the functional connectivity of the human brain in resting state. We show that the geodesic entropy is able to differentiate functional networks of the human brain associated with two different states of consciousness in the awaking resting state: (i) the ordinary state and (ii) a state altered by ingestion of the Ayahuasca. The functional brain networks from subjects in the altered state have, on average, a larger geodesic entropy compared to the ordinary state. Finally, we discuss why the geodesic entropy may bring even further valuable insights into the study of the human brain and other empirical networks.
Cortisol modulation by ayahuasca in patients with treatment resistant depression and healthy controls
(2018-05-08) Galvão, Ana C. de Menezes; Almeida, Raíssa N. de; Silva, Erick A. dos Santos; Freire, Fúlvio A. M.; Palhano-Fontes, Fernanda; Onias, Heloisa; Arcoverde, Emerson; Maia-de-Oliveira, João P.; Araújo, Dráulio Barros de; Lobão-Soares, Bruno; Galvão-Coelho, Nicole L.
Major depression is a highly prevalent mood disorder, affecting about 350 million people, and around 30% of the patients are resistant to currently available antidepressant medications. Recent evidence from a randomized controlled trial (RCT) supports the rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression. The aim of this study was to explore the effect of ayahuasca on plasma cortisol and awakening salivary cortisol response, in the same group of treatment-resistant patients (MD) and in healthy volunteers (C). Subjects received a single dose of ayahuasca or placebo (dosing session), and both plasma and awakening salivary cortisol response were measured at baseline (before dosing session) and 48 h after the dosing session. Baseline assessment (D0) showed blunted awakening salivary cortisol response and hypocortisolemia in patients, with respect to healthy controls. Salivary cortisol was also measured during dosing session, and we observed higher increases for both C and MD that ingested ayahuasca than placebo. After 48 h from the dosing session with ayahuasca, patients' awakening salivary cortisol response is similar to the ones detected in controls. No significant changes in plasma cortisol levels were observed 48 h after the sessions. Therefore, these findings point to new evidence on the modulation of salivary cortisol levels as a result of an ayahuasca session, both in healthy and depressive volunteers. Considering that cortisol acts in regulation of distinct physiological pathways, emotional and cognitive processes, it is assumed to be critically involved to the etiology of depression and its regulation seems to be important for the treatment and remission of major depression, ayahuasca use as antidepressant should be further investigated. Moreover, this study highlights the importance of psychedelics in the treatment of human mental disorders.
Effects of yoga respiratory practice (bhastrika pranayama) on anxiety, affect, and brain functional connectivity and activity: a randomized controlled trial
(2020-05-21) Novaes, Morgana M.; Palhano-Fontes, Fernanda; Onias, Heloisa; Andrade, Katia C.; Lobão-Soares, Bruno; Arruda-Sanchez, Tiago; Kozasa, Elisa H.; Santaella, Danilo F.; Araújo, Dráulio Barros de
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.
Long-term use of psychedelic drugs is associated with differences in brain structure and personality in humans
(2015) Bouso, José Carlos; Palhano-Fontes, Fernanda; Rodríguez-Fornells, Antoni; Ribeiro, Sidarta Tollendal Gomes; Sanches, Rafael; Crippa, José Alexandre S.; Hallak, Jaime E.C.; Araújo, Dráulio Barros de; Riba, Jordi
Psychedelic agents have a long history of use by humans for their capacity to induce profound modifications in perception, emotion and cognitive processes. Despite increasing knowledge of the neural mechanisms involved in the acute effects of these drugs, the impact of sustained psychedelic use on the human brain remains largely unknown. Molecular pharmacology studies have shown that psychedelic 5-hydroxytryptamine (5HT)2A agonists stimulate neurotrophic and transcription factors associated with synaptic plasticity. These data suggest that psychedelics could potentially induce structural changes in brain tissue. Here we looked for differences in cortical thickness (CT) in regular users of psychedelics. We obtained magnetic resonance imaging (MRI) images of the brains of 22 regular users of ayahuasca (a preparation whose active principle is the psychedelic 5HT2A agonist N,N-dimethyltryptamine (DMT)) and 22 controls matched for age, sex, years of education, verbal IQ and fluid IQ. Ayahuasca users showed significant CT differences in midline structures of the brain, with thinning in the posterior cingulate cortex (PCC), a key node of the default mode network. CT values in the PCC were inversely correlated with the intensity and duration of prior use of ayahuasca and with scores on self-transcendence, a personality trait measuring religiousness, transpersonal feelings and spirituality. Although direct causation cannot be established, these data suggest that regular use of psychedelic drugs could potentially lead to structural changes in brain areas supporting attentional processes, self-referential thought, and internal mentation. These changes could underlie the previously reported personality changes in long-term users and highlight the involvement of the PCC in the effects of psychedelics.
Modulation of serum brain-derived neurotrophic factor by a single dose of Ayahuasca: observation from a randomized controlled trial
(2019-06-04) Almeida, Raíssa Nóbrega de; Galvão, Ana Cecília de Menezes; Silva, Flávia Santos da; Silva, Erick Allan dos Santos; Palhano-Fontes, Fernanda; Maia-de-Oliveira, João Paulo; Araújo, Dráulio Barros de; Lobão-Soares, Bruno; Galvão-Coelho, Nicole Leite
Serotonergic psychedelics are emerging as potential antidepressant therapeutic tools, as suggested in a recent randomized controlled trial with ayahuasca for treatment-resistant depression. Preclinical and clinical studies have suggested that serum brain-derived neurotrophic factor (BDNF) levels increase after treatment with serotoninergic antidepressants, but the exact role of BDNF as a biomarker for diagnostic and treatment of major depression is still poorly understood. Here we investigated serum BDNF levels in healthy controls (N = 45) and patients with treatment-resistant depression (N = 28) before (baseline) and 48 h after (D2) a single dose of ayahuasca or placebo. In our sample, baseline serum BDNF levels did not predict major depression and the clinical characteristics of the patients did not predict their BDNF levels. However, at baseline, serum cortisol was a predictor of serum BDNF levels, where lower levels of serum BDNF were detected in a subgroup of subjects with hypocortisolemia. Moreover, at baseline we found a negative correlation between BDNF and serum cortisol in volunteers with eucortisolemia. After treatment (D2) we observed higher BDNF levels in both patients and controls that ingested ayahuasca (N = 35) when compared to placebo (N = 34). Furthermore, at D2 just patients treated with ayahuasca (N = 14), and not with placebo (N = 14), presented a significant negative correlation between serum BDNF levels and depressive symptoms. This is the first double-blind randomized placebo-controlled clinical trial that explored the modulation of BDNF in response to a psychedelic in patients with depression. The results suggest a potential link between the observed antidepressant effects of ayahuasca and changes in serum BDNF, which contributes to the emerging view of using psychedelics as an antidepressant. This trial is registered at http://clinicaltrials.gov (NCT02914769).
Neurofunctional changes after a single mirror therapy intervention in chronic ischemic stroke
(2018-03-20) Novaes, Morgana M.; Palhano-Fontes, Fernanda; Peres, Andre; Mazzetto-Betti, Kelley; Pelicioni, Maristela; Andrade, Kátia C.; Santos, Antonio Carlos dos; Pontes-Neto, Octavio; Araújo, Dráulio Barros de
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 β-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.
Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial
(2018-06-15) Palhano-Fontes, Fernanda; Barreto, Dayanna; Onias, Heloisa; Andrade, Katia C.; Novaes, Morgana M.; Pessoa, Jessica A.; Mota-Rolim, Sergio A.; Osório, Flávia L.; Sanches, Rafael; Santos, Rafael G. dos; Tófoli, Luís Fernando; Silveira, Gabriela de Oliveira; Yonamine, Mauricio; Riba, Jordi; Santos, Francisco R.; Silva-Junior, Antonio A.; Alchieri, João C.; Galvão-Coelho, Nicole L.; Lobão-Soares, Bruno; Hallak, Jaime E. C.; Arcoverde, Emerson; Maia-de-Oliveira, João P.; Araújo, Dráulio Barros de
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).
Shannon entropy of brain functional complex networks under the influence of the psychedelic Ayahuasca
(2016) Viol, A.; Palhano-Fontes, Fernanda; Onias, Heloisa; Araújo, Dráulio Barros de; Viswanathan, G. M.
The entropic brain hypothesis holds that the key facts concerning psychedelics are partially explained in terms of increased entropy of the brain’s functional connectivity. Ayahuasca is a psychedelic beverage of Amazonian indigenous origin with legal status in Brazil in religious and scientific settings. In this context, we use tools and concepts from the theory of complex networks to analyze resting state fMRI data of the brains of human subjects under two distinct conditions: (i) under ordinary waking state and (ii) in an altered state of consciousness induced by ingestion of Ayahuasca. We report an increase in the Shannon entropy of the degree distribution of the networks subsequent to Ayahuasca ingestion. We also find increased local and decreased global network integration. Our results are broadly consistent with the entropic brain hypothesis. Finally, we discuss our findings in the context of descriptions of \mind-expansion" frequently seen in self-reports of users of psychedelic drugs.
Shannon entropy of brain functional complex networks under the infuence of the psychedelic Ayahuasca
(2017-08-07) Viol, A.; Palhano-Fontes, Fernanda; Onias, Heloisa; Araújo, Dráulio Barros de; Viswanathan, G. M.
The entropic brain hypothesis holds that the key facts concerning psychedelics are partially explained in terms of increased entropy of the brain’s functional connectivity. Ayahuasca is a psychedelic beverage of Amazonian indigenous origin with legal status in Brazil in religious and scientific settings. In this context, we use tools and concepts from the theory of complex networks to analyze resting state fMRI data of the brains of human subjects under two distinct conditions: (i) under ordinary waking state and (ii) in an altered state of consciousness induced by ingestion of Ayahuasca. We report an increase in the Shannon entropy of the degree distribution of the networks subsequent to Ayahuasca ingestion. We also find increased local and decreased global network integration. Our results are broadly consistent with the entropic brain hypothesis. Finally, we discuss our findings in the context of descriptions of “mind-expansion” frequently seen in self-reports of users of psychedelic drugs.
Subacute effects of the psychedelic ayahuasca on the salience and default mode networks
(2020-04-07) Pasquini, Lorenzo; Palhano-Fontes, Fernanda; Araújo, Dráulio Barros de
Background: Neuroimaging studies have just begun to explore the acute effects of psychedelics on large-scale brain networks' functional organization. Even less is known about the neural correlates of subacute effects taking place days after the psychedelic experience. This study explores the subacute changes of primary sensory brain networks and networks supporting higher-order affective and self-referential functions 24 hours after a single session with the psychedelic ayahuasca. Methods: We leveraged task-free functional magnetic resonance imaging data 1 day before and 1 day after a randomized placebo-controlled trial exploring the effects of ayahuasca in naïve healthy participants (21 placebo/22 ayahuasca). We derived intra- and inter-network functional connectivity of the salience, default mode, visual, and sensorimotor networks, and assessed post-session connectivity changes between the ayahuasca and placebo groups. Connectivity changes were associated with Hallucinogen Rating Scale scores assessed during the acute effects. Results: Our findings revealed increased anterior cingulate cortex connectivity within the salience network, decreased posterior cingulate cortex connectivity within the default mode network, and increased connectivity between the salience and default mode networks 1 day after the session in the ayahuasca group compared to placebo. Connectivity of primary sensory networks did not differ between groups. Salience network connectivity increases correlated with altered somesthesia scores, decreased default mode network connectivity correlated with altered volition scores, and increased salience default mode network connectivity correlated with altered affect scores. Conclusion: These findings provide preliminary evidence for subacute functional changes induced by the psychedelic ayahuasca on higher-order cognitive brain networks that support interoceptive, affective, and self-referential functions.
The impact of ayahuasca on suicidality: results from a randomized controlled trial
(2019-11-19) Zeifman, Richard J.; Palhano-Fontes, Fernanda; Hallak, Jaime; Arcoverde, Emerson; Maia-Oliveira, João Paulo; Araújo, Dráulio Barros de
Suicide is a major public health problem. Given increasing suicide rates and limitations surrounding current interventions, there is an urgent need for innovative interventions for suicidality. Although ayahuasca has been shown to target mental health concerns associated with suicidality (i.e., depression and hopelessness), research has not yet explored the impact of ayahuasca on suicidality. Therefore, we conducted secondary analyses of a randomized placebo-controlled trial in which individuals with treatment-resistant depression were administered one dose of ayahuasca (n = 14) or placebo (n = 15). Suicidality was assessed by a trained psychiatrist at baseline, as well as 1 day, 2 days, and 7 days after the intervention. A fixed-effects linear mixed model, as well as between and within-groups Cohen's d effect sizes were used to examine changes in suicidality. Controlling for baseline suicidality, we found a significant effect for time (p < .05). The effect of the intervention (i.e., ayahuasca vs. placebo) trended toward significance (p = .088). At all time points, we found medium between-group effect sizes (i.e., ayahuasca vs. placebo; day 1 Cohen’s d = 0.58; day 2 d = 0.56; day 7 d = 0.67), as well as large within-group (ayahuasca; day 1 Cohen's d = 1.33; day 2 d = 1.42; day 7 d = 1.19) effect sizes, for decreases in suicidality. Conclusions: This research is the first to explore the impact of ayahuasca on suicidality. The findings suggest that ayahuasca may show potential as an intervention for suicidality. We highlight important limitations of the study, potential mechanisms, and future directions for research on ayahuasca as an intervention for suicidality.
The Psychedelic State Induced by Ayahuasca Modulates the Activity and Connectivity of the Default Mode Network
(Plos One, 2015-02-18) Palhano-Fontes, Fernanda; Andrade, Katia C.; Tofoli, Luis F.; Santos, Antonio C.; Crippa, Jose Alexandre S.; Hallak, Jaime E. C.; Ribeiro, Sidarta Tollendal Gomes; Araújo, Dráulio Barros de

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Navegando por Autor "Palhano-Fontes, Fernanda"