Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique able to induce long-lasting changes in cortical excitability that can benefit cognitive functioning and clinical treatment. In order to both better understand the mechanisms behind tDCS and possibly improve the technique, finite element models are used to simulate tDCS of the human brain. With the detailed anisotropic head model presented in this study, we provide accurate predictions of tDCS in the human brain for six of the practically most-used setups in clinical and cognitive research, targeting the primary motor cortex, dorsolateral prefrontal cortex, inferior frontal gyrus, occipital cortex, and cerebellum. We present the resulting electric field strengths in the complete brain and introduce new methods to evaluate the effectivity in the target area specifically, where we have analyzed both the strength and direction of the field. For all cerebral targets studied, the currently accepted configurations produced sub-optimal field strengths. The configuration for cerebellum stimulation produced relatively high field strengths in its target area, but it needs higher input currents than cerebral stimulation does. This study suggests that improvements in the effects of transcranial direct current stimulation are achievable.

Our results allow us to formulate a guideline for volume conductor modeling in tDCS. We recommend to accurately model the major tissues between the stimulating electrodes and the target areas, while for efficient yet accurate modeling, an exact representation of other tissues is less important. Because for the low-frequency regime in electrophysiology the quasi-static approach is justified, our results should also be valid for at least low-frequency (e.g., below 100 Hz) transcranial alternating current stimulation.

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All known guanine-sensing riboswitches regulate gene expression by specifically binding to guanine (G) or related analogs with high affinity to switch off transcription. The aptamers of this class of riboswitches are characterized by three helices (P1-P3), surrounding a central core of phylogenetically conserved nucleotides and a long-range loop-loop interaction. To gain more insight into the switching mechanism, we present here a comparison between the solution-state structures of the G-free and G-bound forms of the guanine aptamer from the xpt-pbuX operon of Bacillus subtilis, as derived from NMR chemical shifts and magnetic-field-induced residual dipolar couplings. The high-resolution NMR analysis shows the G-free aptamer is highly structured with parallel P2 and P3 helices and the long-range loop-loop interaction already present, implying that the structure is largely preformed to bind the ligand. Structural changes upon guanine binding are found to be localized to the central core. In the free state, the G-quadruple interaction and two base pairs of the P1 stem flanking the central core appear to be largely disordered. The ligand thus binds via a combined predetermined-induced fit mechanism, involving a previously unstructured five-residue loop of the J2-3 junction that folds over the ligand. These limited additional interactions within a preorganized setting possibly explain how the aptamer rapidly responds to ligand binding, which is necessary to switch the structural state of the expression platform within a narrow time frame before the RNA polymerase escapes the 59-UTR.

Volume conduction models can help in acquiring knowledge about the distribution of the electric field induced by transcranial magnetic stimulation (TMS). One aspect of a detailed model is an accurate description of the cortical surface geometry. Since its estimation is difficult, it is important to know how accurate the geometry has to be represented. Previous studies only looked at the differences caused by neglecting the complete boundary between the CSF and GM (Thielscher et al. 2011; Bijsterbosch et al. 2012), or by resizing the whole brain (Wagner et al. 2008). However, due to the high conductive properties of the CSF, it can be expected that alterations in sulcus width can already have a significant effect on the distribution of the electric field. To answer this question, the sulcus width of a highly realistic head model, based on T1-, T2- and diffusion-weighted magnetic resonance images (MRI), was altered systematically. This study shows that alterations in the sulcus width do not cause large differences in the majority of the electric field values. However, considerable overestimation of sulcus width produces an overestimation of the calculated field strength, also at locations distant from the target location.

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In modeling the effect of transcranial direct current stimulation, the representation of the skull is an important factor. In a spherical model, we compared a realistic skull modeling approach, in which the skull consisted of three isotropic layers, to anisotropic and isotropic single-layer approximations. We simulated direct current stimulation for a range of conductivity values and investigated differences in the resulting current densities. Our results demonstrate that both approximation methods perform well, provided that the optimal conductivity values are used. We found that for both the anisotropic and the isotropic approximations the optimal conductivity values are largely dictated by the equivalent radial conductivity of the three-layered skull.

Recent studies suggest that binocular rivalry at stimulus onset, so called onset rivalry, differs from rivalry during sustained viewing. These observations raise the interesting question whether there is a relation between onset rivalry and rivalry in the presence of eye movements. We therefore studied binocular rivalry when stimuli jumped from one visual hemifield to the other, either through a saccade or through a passive stimulus displacement, and we compared rivalry after such displacements with onset and sustained rivalry. We presented opponent motion, orthogonal gratings and face/house stimuli through a stereoscope. For all three stimulus types we found that subjects showed a strong preference for stimuli in one eye or one hemifield (Experiment 1), and that these subject-specific biases did not persist during sustained viewing (Experiment 2). These results confirm and extend previous findings obtained with gratings. The results from the main experiment (Experiment 3) showed that after a passive stimulus jump, switching probability was low when the preferred eye was dominant before a stimulus jump, but when the non-preferred eye was dominant beforehand, switching probability was comparatively high. The results thus showed that dominance after a stimulus jump was tightly related to eye dominance at stimulus onset. In the saccade condition, however, these subject-specific biases were systematically reduced, indicating that the influence of saccades can be understood from a systematic attenuation of the subjects' onset rivalry biases. Taken together, our findings demonstrate a relation between onset rivalry and rivalry after retinal shifts and involvement of extra-retinal signals in binocular rivalry.