Biological markers in noninvasive brain stimulation trials in major depressive disorder: a systematic review

Objectives: The therapeutic effects of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation in patients with major depression have shown promising results; however, there is a lack of mechanistic studies using biological markers (BMs) as an outcome. Therefore, our aim was to review noninvasive brain stimulation trials in depression using BMs. Methods: The following databases were used for our systematic review: MEDLINE, Web of Science, Cochrane, and SCIELO. We examined articles published before November 2012 that used TMS and transcranial direct current stimulation as an intervention for depression and had BM as an outcome measure. The search was limited to human studies written in English. Results: Of 1234 potential articles, 52 articles were included. Only studies using TMS were found. Biological markers included immune and endocrine serum markers, neuroimaging techniques, and electrophysiological outcomes. In 12 articles (21.4%), end point BM measurements were not significantly associated with clinical outcomes. All studies reached significant results in the main clinical rating scales. Biological marker outcomes were used as predictors of response, to understand mechanisms of TMS, and as a surrogate of safety. Conclusions: Functional magnetic resonance imaging, single-photon emission computed tomography, positron emission tomography, magnetic resonance spectroscopy, cortical excitability, and brain-derived neurotrophic factor consistently showed positive results. Brain-derived neurotrophic factor was the best predictor of patients’ likeliness to respond. These initial results are promising; however, all studies investigating BMs are small, used heterogeneous samples, and did not take into account confounders such as age, sex, or family history. Based on our findings, we recommend further studies to validate BMs in noninvasive brain stimulation trials in MDD.

Diversity of sand flies in domiciliary environment of Santarém, state of Pará, Brazil: species composition and abundance patterns in rural and urban areas

This paper aimed to evaluate the richness, abundance and frequency of sand fly occurrence in rural and urban areas American visceral Leishmaniasis -AVL is endemic in the study area of Santarém municipality, Pará state. Sand flies were collected during 1995-2000, using CDC light traps placed in neighborhoods and rural areas of the municipality. A total of 53.454 individuals and 26 species of sand flies were collected. The most abundant species in both urban and rural environments was Lutzomyia longipalpis, vector of AVL in the area. The highest species richness by capture was in rural area. In all years sampled, the largest number of species of sand fly collected was always in rural areas. The species of sand flies in urban and rural area were similar in 11 species. In the rural area other 11 species were found, a total of 22 species. Shannon-Wiener index ranged from 0.12 to 0.84 at rural areas and 0.08 to 0.34 at urban ones. In general, rural localities showed higher diversity (H') of phlebotomines than urban ones. Individual-based rarefaction curves for each area demonstrated that urban localities had the lowest expected number of phlebotomine species and the richest rural ones reach higher expected values with lower amount of individuals than urban sites. The most frequent species were Lutzomyia longipalpis, Evandromyia carmelinoi and Bichromomyia flaviscutellata.

[Letter to the editor] Sustained effects of a neural-based intervention in a refractory case of Tourette syndrome

There are only a few treatments available for Tourette syndrome (TS). These treatments frequently do notwork in patients with moderate to severe TS [1]. Neuroimaging studies show a correlation between tics severity and increased activation over motor pathways, along with reduced activation over the control areas of the cortico-striato-thalamo-cortical circuits [2]. Moreover, the temporal pattern of tic generation suggests that cortical activation especially in the SMA precedes subcortical activation [3]. Following this assumption, here we explored the brain effects of 10-daily sessions of cathodal transcranial Direct Current Stimulation (tDCS) delivered over the pre-SMA in a patient with refractory and severe TS and also assessed whether those changes were long lasting (up to 6 months).

Differential activation of the default mode network in jet lagged individuals

Long-term exposure to transmeridian flights has been shown to impact cognitive functioning. Nevertheless, the immediate effects of jet lag in the activation of specific brain networks have not been investigated. We analyzed the impact of short-term jet lag on the activation of the default mode network (DMN). A group of individuals who were on a transmeridian flight and a control group went through a functional magnetic resonance imaging acquisition. Statistical analysis was performed to test for differences in the DMN activation between groups. Participants from the jet lag group presented decreased activation in the anterior nodes of the DMN, specifically in bilateral medial prefrontal and anterior cingulate cortex. No areas of increased activation were observed for the jet lag group. These results may be suggestive of a negative impact of jet lag on important cognitive functions such as introspection, emotional regulation and decision making in a few days after individuals arrive at their destination.

Assessment of distinctive road runoff quality in coastal areas, based on a monitoring case study

High levels of marine salt deposition present in coastal areas have a relevant effect on road runoff characteristics. This study assesses this effect with the purpose of identifying the relationships between monitored water quality parameters and intrinsic site variables. To achieve this objective, an extensive monitoring program was conducted on a Portuguese coastal highway. The study included 30 rainfall events, in different weather, traffic, and salt deposition conditions. The evaluations of various water quality parameters were carried out in over 200 samples. In addition, the meteorological, hydrological, and traffic parameters were continuously measured. The salt deposition rates were determined by means of a wet candle device, which is an innovative feature of the monitoring program. The relation between road runoff pollutants and independent variables associated with weather, traffic, and salt deposition conditions was assessed. Significant correlations among pollutants were observed. A high salinity concentration and its influence on the road runoff were confirmed. Furthermore, the concentrations of the most relevant pollutants seemed to be very dependent on some meteorological variables, particularly the duration of the antecedent dry period prior to each rainfall event and the average wind speed.

Tocopherol profile of Brazil nut oil from different geographic areas of the Amazon region

The tocopherol content of Brazil nut oil from different Amazon regions (Manicoré-AM, Rio Preto da Eva-AM, São João da Baliza-RR, Caroebe-RR, Belém-PA, and Xapurí-AC) was investigated by normal-phase high-performance liquid chromatography. For all authentic oils, two isomers: α- and γ-tocopherols were observed (37.92-74.48 µg g-1, 106.88-171.80 µg g-1, respectively), and their levels were relatively constant among the oils having these geographic origins, which would enable to distinguish Brazil nut oil from other plant oils for authentication purposes. Commercial Brazil nut oils were also evaluated, and some of these oils demonstrated a tocopherol content that was very different from that of the authentic oils. Therefore, we suggest that the tocopherol profile of Brazil nut oil can be useful chemical marker for quality control and authentication.

Multi-temporal analysis of radiometric changes in satellite images of forest edges to infer selective-logging areas in the Amazon forest

Radiometric changes observed in multi-temporal optical satellite images have an important role in efforts to characterize selective-logging areas. The aim of this study was to analyze the multi-temporal behavior of spectral-mixture responses in satellite images in simulated selective-logging areas in the Amazon forest, considering red/near-infrared spectral relationships. Forest edges were used to infer the selective-logging infrastructure using differently oriented edges in the transition between forest and deforested areas in satellite images. TM/Landsat-5 images acquired at three dates with different solar-illumination geometries were used in this analysis. The method assumed that the radiometric responses between forest with selective-logging effects and forest edges in contact with recent clear-cuts are related. The spatial frequency attributes of red/near infrared bands for edge areas were analyzed. Analysis of dispersion diagrams showed two groups of pixels that represent selective-logging areas. The attributes for size and radiometric distance representing these two groups were related to solar-elevation angle. The results suggest that detection of timber exploitation areas is limited because of the complexity of the selective-logging radiometric response. Thus, the accuracy of detecting selective logging can be influenced by the solar-elevation angle at the time of image acquisition. We conclude that images with lower solar-elevation angles are less reliable for delineation of selecting logging.

High-aspect-ratio tridimensional electrode arrays for neural applications

Tese de Doutoramento em Engenharia Biomédica.

Cognitive functioning and efficacy of cognitive intervention in Multiple Sclerosis

Tese de Doutoramento em Psicologia Clínica / Psicologia

A network approach to brain aging through multimodal neuroimaging

Tese de Doutoramento em Ciências da Saúde.

Female hippocampus vulnerability to environmental stress, a precipitating factor in tau aggregation pathology

Tau-mediated neurodegeneration is a central event in Alzheimer's disease (AD) and other tauopathies. Consistent with suggestions that lifetime stress may be a clinically-relevant precipitant of AD pathology, we previously showed that stress triggers tau hyperphosphorylation and accumulation; however, little is known about the etiopathogenic interaction of chronic stress with other AD risk factors, such as sex and aging. This study focused on how these various factors converge on the cellular mechanisms underlying tau aggregation in the hippocampus of chronically stressed male and female (middle-aged and old) mice expressing the most commonly found disease-associated Tau mutation in humans, P301L-Tau. We report that environmental stress triggers memory impairments in female, but not male, P301L-Tau transgenic mice. Furthermore, stress elevates levels of caspase-3-truncated tau and insoluble tau aggregates exclusively in the female hippocampus while it also alters the expression of the molecular chaperones Hsp90, Hsp70, and Hsp105, thus favoring accumulation of tau aggregates. Our findings provide new insights into the molecular mechanisms through which clinically-relevant precipitating factors contribute to the pathophysiology of AD. Our data point to the exquisite sensitivity of the female hippocampus to stress-triggered tau pathology.

The bounds of education in the human brain connectome

Inter-individual heterogeneity is evident in aging; education level is known to contribute for this heterogeneity. Using a cross-sectional study design and network inference applied to resting-state fMRI data, we show that aging was associated with decreased functional connectivity in a large cortical network. On the other hand, education level, as measured by years of formal education, produced an opposite effect on the long-term. These results demonstrate the increased brain efficiency in individuals with higher education level that may mitigate the impact of age on brain functional connectivity.

The role of IFNγ in higher brain function: in health and under chronic stress

Tese de Doutoramento em Ciências da Saúde

Synthesis and biological evaluation of mono and bis-naphthalimide derivatives against SH-SY5Y, human brain cancer cells

Dissertação de mestrado em Medicinal Chemistry