Acute effects of ayahuasca in a juvenile non-human primate model of depression

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.

Performance quantification of clustering algorithms for false positive removal in fMRI by ROC curves

Abstract Introduction Functional magnetic resonance imaging (fMRI) is a non-invasive technique that allows the detection of specific cerebral functions in humans based on hemodynamic changes. The contrast changes are about 5%, making visual inspection impossible. Thus, statistic strategies are applied to infer which brain region is engaged in a task. However, the traditional methods like general linear model and cross-correlation utilize voxel-wise calculation, introducing a lot of false-positive data. So, in this work we tested post-processing cluster algorithms to diminish the false-positives. Methods In this study, three clustering algorithms (the hierarchical cluster, k-means and self-organizing maps) were tested and compared for false-positive removal in the post-processing of cross-correlation analyses. Results Our results showed that the hierarchical cluster presented the best performance to remove the false positives in fMRI, being 2.3 times more accurate than k-means, and 1.9 times more accurate than self-organizing maps. Conclusion The hierarchical cluster presented the best performance in false-positive removal because it uses the inconsistency coefficient threshold, while k-means and self-organizing maps utilize a priori cluster number (centroids and neurons number); thus, the hierarchical cluster avoids clustering scattered voxels, as the inconsistency coefficient threshold allows only the voxels to be clustered that are at a minimum distance to some cluster.

Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report

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. .

Galvanic vestibular stimulator for fMRI studies

INTRODUCTION: Areas of the brain that are associated with the vestibular system can be activated using galvanic vestibular stimulation. These areas can be studied through a combination of galvanic vestibular stimulation with functional magnetic resonance imaging (fMRI). In order to provide an appropriate sequence of galvanic stimulation synchronous with the MRI pulse sequence, a specific electronic device that was built and assessed is presented. METHODS: The electronic project of the GVS is divided in analog and digital circuits. The analog circuits are mounted in an aluminum case, supplied by sealed batteries, and goes inside the MRI room near to the feet of the subject. The digital circuits are placed in the MRI control room. Those circuits communicate through each other by an optical fiber. Tests to verify the GVS-MRI compatibility were conducted. Silicone (in-house) and Ag/AgCl (commercial) electrodes were evaluated for maximum balance and minimal pain sensations. fMRI experiments were conducted in eight human volunteers. RESULTS: GVS-MRI compatibility experiments demonstrate that the GVS did not interfere with the MRI scanner functionality and vice versa. The circular silicone electrode was considered the most suitable to apply the galvanic vestibular stimulation. The 1 Hz stimulation sinusoid frequency produced the biggest balance and the less pain sensations when compared to 2 Hz. The GVS was capable of eliciting activation in the precentral and postcentral gyri, in the central sulcus, in the supplementary motor area, in the middle and inferior frontal gyri, in the inferior parietal lobule, in the insula, in the superior temporal gyrus, in the middle cingulate cortex, and in the cerebellum. CONCLUSION: This study shows the development and description of a neurovestibular stimulator that can be safely used inside the MRI scanner room without interfering on its operation and vice versa. The developed GVS could successfully activate the major areas involved with multimodal functions of the vestibular system, demonstrating its validity as a stimulator for neurovestibular research. To the best of our knowledge, this is the first work that shows the development and the construction of a galvanic vestibular stimulator that could be safely used inside the MRI room.

Supine sleep and positional sleep apnea after acute ischemic stroke and intracerebral hemorrhage

OBJECTIVE: Obstructive sleep apnea is frequent during the acute phase of stroke, and it is associated with poorer outcomes. A well-established relationship between supine sleep and obstructive sleep apnea severity exists in non-stroke patients. This study investigated the frequency of supine sleep and positional obstructive sleep apnea in patients with ischemic or hemorrhagic stroke. METHODS: Patients who suffered their first acute stroke, either ischemic or hemorrhagic, were subjected to a full polysomnography, including the continuous monitoring of sleep positions, during the first night after symptom onset. Obstructive sleep apnea severity was measured using the apnea-hypopnea index, and the NIHSS measured stroke severity. RESULTS: We prospectively studied 66 stroke patients. The mean age was 57.6±11.5 years, and the mean body mass index was 26.5±4.9. Obstructive sleep apnea (apnea-hypopnea index >5) was present in 78.8% of patients, and the mean apnea-hypopnea index was 29.7±26.6. The majority of subjects (66.7%) spent the entire sleep time in a supine position, and positional obstructive sleep apnea was clearly present in the other 23.1% of cases. A positive correlation was observed between the NIHSS and sleep time in the supine position (r s = 0.5; p<0.001). CONCLUSIONS: Prolonged supine positioning during sleep was highly frequent after stroke, and it was related to stroke severity. Positional sleep apnea was observed in one quarter of stroke patients, which was likely underestimated during the acute phase of stroke. The adequate positioning of patients during sleep during the acute phase of stroke may decrease obstructive respiratory events, regardless of the stroke subtype.

Neuroimaging in stroke and non-stroke pusher patients / Análise de neuroimagens de pacientes com síndrome do empurrador decorrente de AVC e outras etiologias

Pusher behavior (PB) is a disorder of postural control affecting patients with encephalic lesions. This study has aimed to identify the brain substrates that are critical for the occurrence of PB, to analyze the influence of the midline shift (MS) and hemorrhagic stroke volume (HSV) on the severity and prognosis of the PB. We identified 31 pusher patients of a neurological unit, mean age 67.4±11.89, 61.3 percent male. Additional neurological and functional examinations were assessed. Neuroimaging workup included measurement of the MS, the HSV in patients with hemorrhagic stroke, the analysis of the vascular territory, etiology and side of the lesion. Lesions in the parietal region (p=0.041) and thalamus (p=0.001) were significantly more frequent in PB patients. Neither the MS nor the HSV were correlated with the PB severity or recovery time.

A síndrome do empurrador (SE) é um distúrbio de controle postural que acomete indivíduos com lesões encefálicas. Os objetivos deste estudo foram identificar as estruturas encefálicas envolvidas na SE, analisar a influência dos desvios de linha média (DLM) e volume do hematoma (VH) na gravidade e duração da SE. Dentre os pacientes internados na enfermaria de neurologia, foram identificados 31 pacientes com SE, idade média 67,4±11,89, 61,3 por cento homens. Foram realizados exames neurológico e funcional. As análises das neuroimagens incluíram medidas de VH em pacientes com doença cerebrovascular (DC) hemorrágica, DLM, análise do território vascular, etiologia e lado da lesão. Lesão nas regiões parietal (p=0,041) e talâmica (p=0,001) foram significativamente mais frequentes nos pacientes com SE. Não foi observada correlação dos DLM e volume do hematoma com a gravidade e duração da SE.

Variable fMRI activation during two different language tasks in a patient with cognitive delay

Functional MRI produces a more accurate localization of the language areas for epilepsy surgery purpose, but requires the patient cooperation. We report a 34 years-old woman with mental retardation who underwent two different verbal fluency tasks, category and word naming. We found a strong activation of the Broca’s area in the most difficult task. We suggest that a multi-task fMRI study could be successful in patients with cognitive delay.

A ressonância magnética funcional permite uma localização acurada da área da linguagem para fins de cirurgia de epilepsia, mas requer a colaboração do paciente na execução da tarefa proposta, o que pode limitar a sua utilização em pacientes com retardo mental. Nós apresentamos o caso de uma mulher com 34 anos de idade, com retardo mental, que foi submetida a duas tarefas distintas de geração silenciosa de palavras, por categoria e letras. Encontramos forte ativação da área de Broca na tarefa mais complexa. Sugerimos que um estudo com múltiplas tarefas pode ser útil em pacientes com retardo mental.

Pushing behavior and hemiparesis: which is critical for functional recovery in pusher patients?: case report

We report a sequential neuroimaging study in a 48-years-old man with a history of chronic hypertension and lacunar strokes involving the ventral lateral posterior nucleus of the thalamus. The patient developed mild hemiparesis and severe contraversive pushing behavior after an acute hemorrhage affecting the right thalamus. Following standard motor physiotherapy, the pusher behavior completely resolved 3 months after the onset and, at that time, he had a Barthel Index of 85, although mild left hemiparesis was still present. This case report illustrates that pushing behavior itself may be severely incapacitating, may occur with only mild hemiparesis and affected patients may have dramatic functional improvement (Barthel Index 0 to 85) after resolution pushing behavior without recovery of hemiparesis.

Relatamos o estudo de neuroimagem seqüencial de um homem de 48 anos com história de hipertensão arterial crônica e acidentes vasculares cerebrais (AVCs) lacunares nos núcleos ventral lateral posterior do tálamo. O paciente desenvolveu hemiparesia leve e síndrome do empurrador (SE) grave após AVC hemorrágico no tálamo direito, sendo tratado com fisioterapia motora convencional. Três meses após o ictus, os sinais da síndrome haviam desaparecido e o paciente apresentava índice de Barthel 85, apesar da permanência da hemiparesia leve. Este caso demonstra que a síndrome do empurrador isolada pode ser gravemente incapacitante, pode ocorrer associada a hemiparesia leve e que os pacientes com esta síndrome podem apresentar recuperação funcional importante (índice de Barthel inicial 0 e final 85) após a resolução da SP sem alteração do grau de hemiparesia.

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.

Controle postural na síndrome de Pusher: influência dos canais semicirculares laterais / Posture control in Pusher syndrome: influence of lateral semicircular canals

A síndrome de Pusher caracteriza-se por uma alteração do equilíbrio na qual pacientes com lesões encefálicas empurram-se em direção ao lado parético utilizando o membro não-afetado. O papel do sistema vestibular na alteração postural da síndrome de Pusher ainda não foi devidamente elucidado. OBJETIVO: Neste estudo objetivamos avaliar o papel dos canais semicirculares horizontais na expressão clínica da síndrome de Pusher, através da aplicação das provas calórica e rotatória. FORMA DE ESTUDO: Observacional, clínico e prospectivo. MATERIAL E MÉTODO: Avaliamos 9 pacientes com AVC e síndrome de Pusher internados na Enfermaria de Neurologia do HCFMRP-USP. Os pacientes foram submetidos à avaliação neurológica clínica e neuropsicológica, NIHSS, Scale for Contraversive Pushing - SCP, teste calórico e teste rotatório. RESULTADOS: Foram estudados 9 pacientes (5 homens) com idade média de 71,8 ± 5,9 anos e com NIHSS médio de 18.33. Três pacientes apresentaram preponderância direcional contralateral à lesão encefálica na prova calórica. Na prova rotatória, foram observados quatro pacientes com preponderância direcional na análise de velocidade da componente lenta. CONCLUSÃO: Os resultados do presente estudo indicam que a disfunção dos canais semicirculares não parece ser fundamental para a expressão da síndrome de Pusher.

SPECT and PET Imaging in epilepsy: principles and clinical applications

Functional neuroimaging with single photon emission computed tomography (SPECT) and positron emission tomography (PET) has documented several perfusion, metabolic and neurochemical dysfunctions in a variety of neurological conditions. In the presurgical workup of medically intractable epilepsies, a group of investigations is included to ascertain the lacalization of the epileptogenic zone. The aim of the present study is to review the principles and revelant investigations about the application of SPECT and PET to the epilepsies. We reviewed the physiological aspects of cerebral blood flow during seizures, pharmacological characteriristics of radiopharmaceuticals, and clinical applications of SPECT in the investigation of epileptic seizures, and provided a review of the main clinical contributions of PET in epilepsy. SPECT and PET have an important and complementary role in the presurgical evaluation as well as in pathophysiological researchs about epilepsy. Both may evaluate the ictal and interictal states of cerebral functions, playing a particular role in those patients who present with inconclusive studies of both Magnetic Resonance Imaging and the Video - EEG monitoring. Additionally, they may avoid or guide invasive neurophysiological studies, and help suggest the localization of the epileptogenic zone in those cases with extensive or multiple lesions

fMRI in epilepsy and recent advances in spatial memory mapping

A localização precisa das áreas corticais eloquentes é de fundamental importância no planejamento neurocirúrgico, especialmente num contexto em que lesões expansivas, destrutivas ou anomalias do desenvolvimento cortical podem distorcer a anatomia cerebral normal. Recentemente tem sido demonstrado que a ressonãncia magnética funcional mesmo na presença destas distorções é útil na localização das principais ´´areas eloquentes, facilitando o planejamento cirúrgico. Este artigo analisa os principais aspectos relativos ao uso da ressonância funcional em cirurgia de epilepsia, incluindo suas limitações. Adicionalmente avalia o uso potencial de um paradigma específico para análise da memória espacial. Apresentamos os resultados da experiência recente do Centro de Cirurgia de Epilepsia (CIREP) da Faculdade de Medicina de Ribeirão Preto, envolvendo estudos funcionais em 40 pacientes candidatos à ressecções de zonas epileptogências localizadas em áreas eloquentes ou nas suas proximidades, e ainda 17 voluntários normais em um paradigma de navegação. Nossos resultados confirmam que a ressonância funcional em conjunção com outros métodos é inequivocamente útil na redução do tempo cirúrgico, na otimização da ressecção cirúrgica e na prevenção de potenciais déficits funcionais