Activity-dependent modulation of synaptic transmission in the intact human motor cortex revealed with transcranial magnetic stimulation

Activity-dependent modulation of cortical synaptic transmission is a fundamental mechanism involved in learning and memory storage. This modulation has been widely studied in in vitro brain slices and in vivo animal models. More recently, transcranial magnetic stimulation has allowed detection of activity-dependent excitability modulation occurring in the intact human primary motor cortex (MI) after execution of different kinds of motor tasks. Both increased and decreased MI excitability have been described after exercise. While increased MI excitability is generally considered direct expression of cortical synaptic plasticity, a controversy still exists as to whether decreased MI excitability reflects fatigue of central nervous system (CNS) structures or cortical neuronal reorganization taking place after exercise. Here, we extend previous findings in order to provide further support for the latter hypothesis. Abduction- adduction movements of the thumb performed for 1 min at 2 Hz frequency rate produce a 55% decrease in MI excitability of mean 30 min duration. Similar decrements in amplitude and duration of motor evoked potentials (MEPs) are not reached if the same task is performed once again during the maximal inhibition phase (10 min post-exercise) produced by a previous activation. Moreover, the same task performed at a lower (1 Hz) frequency rate produces no significant MEP changes but can transiently reverse activity-dependent depression obtained after previous 2 Hz movements. Repeated execution of the same task (2 Hz), each being performed after recovery from a previously induced MEP depression, ceases to produce an MEP decrement, suggesting adaptation in MI excitability modulation. This adaptation is long lasting and task-specific, since a different motor task (1 min circular movement of the thumb) restores activity-dependent modulation. Overall, these findings suggest that the dynamic modulation of MEPs occurring after execution of different kinds of simple motor skills reflects some form of activity-dependent, plastic neuronal reorganization instead of CNS fatigue. Possible anatomo-functional mechanisms involved in this activity-dependent modulation of MI excitability are discussed.     

Toward refinement of the colony-forming unit-granulocyte/macrophage clonogenic assay: inclusion of a metabolic system.

This work represents a first attempt to refine the colony-forming unit-granulocyte/macrophage (CFU-GM) clonogenic assay by incorporating liver microsomes and co-factors as a metabolic system into the in vitro test system in response to an ECVAM recommendation. From the comparison of results obtained with the CFU-GM clonogenic assay currently used and with the new experimental protocol, different toxicity on granulocyte/macrophage precursors was demonstrated, when drugs with a known metabolism in vivo were tested.     

Automated detection of auditory response: applying sequential detection strategies with constant significance level to magnitude-squared coherence

Objective: The detection of the auditory steady-state responses is usually performed by an appropriate objective response detector applied to stimulus-related epochs of the raw electroencephalogram (EEG). In order to improve the detection time, sequential detection strategies are usually used. These multiple tests strategies increase the probability of mistakenly detecting a response. The aim of this study was to develop strategies to determine the critical values for the sequential detection strategies based on constant significance level tests.

Design: Extensive Monte Carlo simulations were used to test these strategies for the magnitude-squared coherence (MSC) detector. The performances of these strategies were compared with previous works found in the literature.

Study sample: All strategies were applied to synthetic and real EEG datasets.

Results: The strategies ensure the desired significance level at the end of the sequential detection strategy. The simulated results are in accordance with the real data results.

Conclusions: For the MSC detector, where the critical value depends on the number of epochs, the proposed sequential detection strategies obtain better performance regarding test time and detection rate, but worse overall detection rate compared to applying a test only once.     

Avoiding spectral leakage in objective detection of auditory steady-state evoked responses in the inferior colliculus of rat using coherence

Local field potentials (LFP) are bioelectric signals recorded from the brain that reflect neural activity in a high temporal resolution. Separating background activity from that evoked by specific somato-sensory input is a matter of great clinical relevance in neurology. The coherence function is a spectral coefficient that can be used as a detector of periodic responses in noisy environments. Auditory steady-state responses to amplitude-modulated tones generate periodic responses in neural networks that may be accessed by means of coherence between the stimulation signal and the LFP recorded from the auditory pathway. Such signal processing methodology was applied in this work to evaluate in vivo, anaesthetized Wistar rats, activation of neural networks due to single carrier sound stimulation frequencies, as well as to evaluate the effect of different modulating tones in the evoked responses. Our results show that an inappropriate choice of sound stimuli modulating frequencies can compromise coherence analysis, e.g. misleading conclusions due to mathematical artefact of signal processing. Two modulating frequency correction protocols were used: nearest integer and nearest prime number. The nearest prime number correction was successful in avoiding spectral leakage in the coherence analysis of steady-state auditory response, as predicted by Monte Carlo simulations.     

Display color affects motion sickness symptoms in an optokinetic drum

BACKGROUND: Many stationary participants who view the patterned interior of a rotating cylinder (optokinetic drum) experience motion sickness (MS) symptoms. Most drum interiors have consisted of black and white patterns. An experiment was conducted to investigate the effects of chromaticity on MS onset and severity. METHODS: There were 12 individuals who participated in the experiment (4 men, 8 women, mean age = 25). Keeping rotation speed constant (5 RPM), the color of vertical stripes in an optokinetic drum was manipulated. There were three conditions used: 1) alternating black and white stripes; 2) gray stripes having different luminance values; and 3) chromatic stripes (white, red, yellow, black, green, and blue) that approximately matched the luminance values of the stripes in the gray condition. Every 2 min, eight motion sickness symptoms were assessed (for up to 16 min) using a subjective scale (0 = none, 1 = slight, 2 = moderate, 3 = severe). RESULTS: Overall, MS onset was fastest, and symptoms the most severe, in the chromatic condition. The two major MS symptoms that were significantly affected were headache and dizziness. CONCLUSIONS: Chromaticity may affect how much an observer's visual environment appears to be stationary, perhaps because chromaticity is such a common feature of the stationary environment in which our visual system evolved. In an optokinetic drum, the addition of chromaticity may increase the disparity between visual and vestibular inputs, a factor thought by many to contribute to MS onset and severity.     

How an undiscovered extensive peripheral pulmonary venous thrombosis destroyed a heart transplant: a case report

This report details a recent experience with a 56-year-old man affected by an incompetent mitral valve due to Barlow's disease. The patient underwent a mitral valve repair and extracorporeal membrane oxygenator (ECMO) assistance due to postcardiotomy cardiogenic shock. During the ECMO assistance he experienced a left atrial thrombosis. A few days later, being unaware of the pulmonary vein thrombosis, we transplanted the patient, who ultimately died due to multiorgan failure and coagulopathy. This article highlights both the vain experience with ECMO and the uselessness of heart transplant, to avoid in the future an irresponsible waste of donor organs, as occurred in the current case.     

Genetic aspects and microenvironment affect expression of CD18 and VLA-4 in experimental tuberculosis

Control of infection by Mycobacterium tuberculosis is dependent on macrophage activation and efficient migration of effector T-cell populations. Lymphocyte differentiation is associated with changes in cell surface phenotype and alterations in the migratory pattern of these cells. In this study, we investigated the expression of adhesion receptors involved in activation and migration process in experimental tuberculosis. We observed that susceptible BALB/c mice infected with virulent M. tuberculosis by intraperitoneal route presented downmodulation of very late antigen 4 (VLA-4) and unchanged levels of CD18 and CD44hi on peritoneal lymphocytes. On the other hand, lymphocytes from resistant C57BL/6 mice infected by the same route showed unchanged levels of VLA-4 and upregulation of CD18 and CD44hi. However, when BALB/c mice were infected by intratracheal route, lung lymphocytes presented a different pattern of CD18, CD44hi and VLA-4 expression from that observed on peritoneal cells, characterized by unchanged levels of VLA-4 and upregulation of CD18 and CD44hi- coincidentally the same phenotype found on peritoneal cells from C57BL/6. These results suggest that susceptibility and resistance to M. tuberculosis infection, depending on the experimental model, are related to the expression of CD18, CD44hi and VLA-4. Moreover, the microenvironment at the site of infection seems to differentially regulate the expression of these receptors. Thus, the up- or downmodulation of these adhesion receptors is probably associated with differential recruitment of T cells at the site of infection, which may or may not mediate protection in experimental tuberculosis.