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.     

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.     

Exchange equilibria on anion resins, 2. Effect of chemical structure of functional groups in macroporous polystyrene resins

Anion exchange equilibria were studied by the batch technique on macroporous polystyrene resins with the following functional groups: \documentclass{article}\pagestyle{empty}\begin{document}$ - \mathop {\rm N}\limits^ + {\rm H}_{\rm 2} {\rm CH}_{\rm 3} ({\rm M),} - \mathop {\rm N}\limits^ + {\rm H(CH}_{\rm 3} )_2 ({\rm DE),} - \mathop {\rm N}\limits^ + {\rm (CH}_{\rm 3} )_3 ({\rm TM),} - \mathop {\rm N}\limits^ + {\rm H}_{\rm 2} {\rm CH}_{\rm 2} {\rm CH}_{\rm 2} {\rm OH (E),} - \mathop {\rm N}\limits^ + {\rm H}_{\rm 2} {\rm (CH}_{\rm 2} {\rm CH}_{\rm 2} {\rm OH)}_{\rm 2} ({\rm DE),} - \mathop {\rm N}\limits^ + {\rm (CH}_{\rm 2} {\rm CH}_{\rm 2} {\rm OH)}_{\rm 3} ({\rm TE),} - \mathop {\rm N}\limits^ + {\rm CH}_{\rm 3} {\rm (CH}_{\rm 2} {\rm CH}_{\rm 2} {\rm OH)}_{\rm 2} ({\rm MDE), and} - \mathop {\rm N}\limits^ + {\rm (CH}_{\rm 3} {\rm )}_{\rm 2} {\rm CH}_{\rm 2} {\rm CH}_{\rm 2} {\rm OH (DME)}$\end{document}. The selectivity order for these groups in slightly acidic, dilute solutions for the following anion systems: Br^?/Cl^?, I^?/Cl^?, and ClO₄^?/Cl^? was found to be TM > DME > MDE > TE > DM > M > DE > E, but it was entirely reversed in the case of F^?/Cl^? system. These results are discussed in view of some known theories of ion exchange selectivity. It seems that the experimental data can be best explained in terms of the Chu-Diamond-Whitney theory which takes into consideration mainly changes of the water structure caused by counter-ions, co-ions, and functional groups of the ion exchanger.     

Electrophysiological cross section of the motor unit.

A new technique to investigate the motor unit organisation in man is described. By moving an EMG electrode through the motor unit a continuous scan or "electrophysiological cross section" is obtained. Computer processing methods are used for analysis and display. Examples are shown from healthy subjects and from patients with neuromuscular diseases.