Biophysical foundations underlying TMS: Setting the stage for an effective use of neurostimulation in the cognitive neurosciences

Transcranial Magnetic Stimulation (TMS) induces electrical currents in the brain to stimulate neural tissue. This article reviews our present understanding of TMS methodology, focusing on its biophysical foundations. We concentrate on how the laws of electromagnetic induction apply to TMS; addressing issues such as the location, area (i.e., focality), depth, and mechanism of TMS. We also present a review of the present limitations and future potential of the technique.     

Differential analysis of the frequency-dependent effects of class 1 antiarrhythmic drugs according to periodical ligand binding: implications for antiarrhythmic and proarrhythmic efficacy.

The frequency-dependent block of cardiac sodium channels by class 1 antiarrhythmic drugs can be described by a periodical ligand binding process between drug molecules and channel binding sites. This predicts a linear relation between onset-rate constant of frequency-dependent block and diastolic interval as well as saturation of block with high stimulation rates. From both relationships, the binding kinetics (time constant, tau on) and saturation level of block (bdinf) can be estimated. This is exemplified for the frequency-dependent block (reduction of the maximal upstroke velocity of action potentials) induced by prajmaline (10(-6) M). In the same way, the frequency-dependent effects of 11 other class 1 drugs reported in the literature were analyzed and compared with each other. When the drugs are ranked with respect to their binding kinetics (tau on), there is a close relationship to the subclasses (1a, 1b, 1c), with 1b drugs exhibiting the fastest and 1c drugs the slowest kinetics. However, differences also exist in the saturation behavior of frequency-dependent block even within the same subclasses (1a and 1c). Thus, the class 1 drugs can also be subdivided in three other groups exhibiting clearly separated bands of block-frequency relations, with half-maximal saturation occurring at different stimulation rates. Our findings may have differential implications for the antiarrhythmic and proarrhythmic efficacy of class 1 drugs.     

Population-based study of emergency department admissions and deaths from injuries in Barcelona,Spain: Incidence,causes and severity

The aim of this study was to estimate the incidence of morbidity and mortality due to injuries in the population over the age of 14 years in Barcelona, Spain. Injury distribution according to sex, age, external cause, place of occurrence of the injury and severity was also obtained. A one-year survey was conducted in the emergency departments of the six main hospitals in Barcelona, based on a multistage sampling. Information was collected prospectively in emergency services by specially trained non-staff interviewers. Mortality data were drawn from death certificates. The incidence rate was 74.7 injury cases per 1,000 person-years over 14 years of age, higher in males than in females. Injury rates were highest in the youngest age-group and progressively lower until people over 75 years of age. Main external causes of injury were falls, being struck or caught by objects, and traffic-related injuries. The leading specific causes of injury mortality were traffic injuries, suicides and poisonings. While the overall admission incidence was 3.34 cases per 1,000 inhabitants, the proportion of hospitalized cases was 45.0 per 1,000 injury cases admitted to emergency rooms, higher for females, for traffic injuries and in the elderly population. Ninety-six percent of injury cases had an ISS value of 8 or less, mean ISS being highest for traffic injuries and falls. Injury morbidity and mortality amongst residents of Barcelona follow sex, age and cause of injury patterns which are, overall, comparable to those observed in other industrialized countries, suggesting that similar etiologic factors might be operating in those areas. The results should enable the orientation of injury prevention policies in the urban environment targeted on the young and the elderly population.     

Raman spectroscopic study of glutaraldehyde-stabilized collagen and pericardium tissue

For the first time, Raman spectroscopy has been employed to investigate formation of cross-links in collagen and porcine pericardium tissue upon glutaraldehyde (GA) treatment. GA treatment causes a very high fluorescence background, which overlaps Raman bands. It has been found that short fixation time, i.e. 2 h, reduces background radiation significantly, providing new possibilities for studying changes in molecular structure of collagen upon GA modification. The observed changes in position and intensity of Raman bands allowed us to recognize different types of GA-collagen interactions. Strong spectral evidence has been found for the peptide contribution to the formation of the GA-collagen cross-links and for the formation of secondary amines via Schiff base intermediates, and pyridinium-type cross-links. The results also revealed that different hydration levels and a more complex structure of intact tissue in comparison to collagen preparation strongly influence the formation of a GA cross-linking network, e.g. ether-type bond is preferred to form in a less hydrated collagen preparation. Our results have shown that GA treatment causes an increase in water content of pericardium tissue and collagen.     

New evidence from magnetic resonance imaging of brain changes after climbs at extreme altitude

The aim of the present study was to look for anatomical changes in climbers' brains, using magnetic resonance imaging (MRI), after extremely high-altitude climbs and to relate them to possible associated risk factors. Clinical history, neurological examinations and MRI were carried out on a group of nine climbers before and after climbing to over 7500 m without the use of supplementary oxygen. None of the subjects showed any neurological dysfunctions. In five climbers MRI abnormalities (high signal areas, cortical atrophy) were observed before the expedition. After the descent, two of them showed new high intensity signal areas recorded by MRI. Both subjects suffered severe neurological symptoms during the climb. The present study suggested that the brain changes observed by MRI could be related to the severity of clinical events at high altitude. However, we do not know the exact meaning of such MRI findings or the reason for their location, predominantly in posterior regions of the brain. The new evidence that a high percentage of climbers show MRI brain abnormalities, and especially the appearance of changes after the ascent, reinforces the possibility of a potential neurological risk in high-altitude climbing.     

Decreased depression up to one year following CBSM+ intervention in depressed women with AIDS: the smart/EST women's project

This prospective multisite Phase III clinical trial (Miami, New York, New Jersey) investigated the long-term (one year) effects of a 10-week group cognitive-behavioral stress management/expressive supportive therapy (CBSM+) intervention on disadvantaged minority women living with AIDS. The CBSM+ intervention consisted of 10-weekly group session of stress management, cognitive-behavioral skill training, relaxation techniques and expressive-supportive therapeutic strategies. The primary study outcome was self-reported depression scores as measured by the BDI. The CBSM+ Group intervention significantly decreased depression scores on the BDI for women following the intervention and maintained the decreased level at one-year follow-up.     

Follicular cells of tonsils metabolise more deoxycytidine than other cell populations

Nine subpopulations of tonsillar lymphocytes and the unseparated cells were compared in their utilization of exogenous deoxycytidine ([5-3H]CdR) and thymidine ([3H]TdR). Uptake phosphorylation and incorporation of labeled precursors were determined in B and T lymphocytes, in low density (LD; enriched in S phase cells) and in high density (HD; enriched in G0/G1 phase cells) cell fractions as well as in LD and HD subfractions of B and T lymphocytes, and in cells isolated from follicles of tonsils. As expected, LD cells and B lymphocytes were more active in TdR incorporation than HD cells and T lymphocytes. However, the ratio of [5-3H]CdR to [3H]TdR in their total phosphorylation and incorporation into DNA was much lower than the expected value of 1: about 0.5 for total phosphorylation and about 0.3 for incorporation in all subpopulations, except for the follicular cells, where these ratios were 1.0 and 0.7, respectively. These results show that the relative utilization of the two pyrimidine deoxyribonucleoside precursors varies among different lymphocyte subpopulations. However, this variation is not due to the different rate of DNA synthesis; rather, it depends on the differentiation stage of lymphocytes occurring in the germinal center of the follicles.