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.

BackgroundThe effectiveness of transcranial magnetic stimulation (TMS) depends highly on the coil orientation relative to the subject’s head. This implies that the direction of the induced electric field has a large effect on the efficiency of TMS. To improve future protocols, knowledge about the relationship between the coil orientation and the direction of the induced electric field on the one hand, and the head and brain anatomy on the other hand, seems crucial. Therefore, the induced electric field in the cortex as a function of the coil orientation has been examined in this study.MethodsThe effect of changing the coil orientation on the induced electric field was evaluated for fourteen cortical targets. We used a finite element model to calculate the induced electric fields for thirty-six coil orientations (10 degrees resolution) per target location. The effects on the electric field due to coil rotation, in combination with target site anatomy, have been quantified.ResultsThe results confirm that the electric field perpendicular to the anterior sulcal wall of the central sulcus is highly susceptible to coil orientation changes and has to be maximized for an optimal stimulation effect of the motor cortex. In order to obtain maximum stimulation effect in areas other than the motor cortex, the electric field perpendicular to the cortical surface in those areas has to be maximized as well. Small orientation changes (10 degrees) do not alter the induced electric field drastically.ConclusionsThe results suggest that for all cortical targets, maximizing the strength of the electric field perpendicular to the targeted cortical surface area (and inward directed) optimizes the effect of TMS. Orienting the TMS coil based on anatomical information (anatomical magnetic resonance imaging data) about the targeted brain area can improve future results. The standard coil orientations, used in cognitive and clinical neuroscience, induce (near) optimal electric fields in the subject-specific head model in most cases.Electronic supplementary materialThe online version of this article (doi:10.1186/s12984-015-0036-2) contains supplementary material, which is available to authorized users.

The benefits of combining a cochlear implant (CI) and a hearing aid (HA) in opposite ears on speech perception were examined in 15 adult unilateral CI recipients who regularly use a contralateral HA. A within-subjects design was carried out to assess speech intelligibility testing, listening effort ratings, and a sound quality questionnaire for the conditions CI alone, CIHA together, and HA alone when applicable. The primary outcome of bimodal benefit, defined as the difference between CIHA and CI, was statistically significant for speech intelligibility in quiet as well as for intelligibility in noise across tested spatial conditions. A reduction in effort on top of intelligibility at the highest tested signal-to-noise ratio was found. Moreover, the bimodal listening situation was rated to sound more voluminous, less tinny, and less unpleasant than CI alone. Listening effort and sound quality emerged as feasible and relevant measures to demonstrate bimodal benefit across a clinically representative range of bimodal users. These extended dimensions of speech perception can shed more light on the array of benefits provided by complementing a CI with a contralateral HA.

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Summary Reactive oxygen metabolites are implicated in the initiation and promotion of cancer. In addition, oxidant scavengers, such as manganese -(Mn-SOD) and copper/zinc -superoxide dismutase (Cu/Zn-SOD), are thought to contribute to colorectal cancer treatment response. In the present study, the prognostic significance of the Mn-and Cu/Zn-SOD antigen content of normal mucosa and carcinomas of 163 patients with colorectal cancer was evaluated in comparison with major clinicopathological parameters, with respect to the 5-year overall survival. The Mn-SOD content of carcinomas was found to be significantty higher than that of normal mucosa, whereas there was no difference in the Cu/Zn-SOD content between the normal mucosa and carcinomas. No association was demonstrable between the Mn-SOD and Cu/Zn-SOD content of the tissues and the assessed clinicopathological parameters (gender, age, localization, differentiation grade, diameter and Dukes' stage), with the exception of the Cu/Zn-SOD and the differentiation grade of the carcinomas. Univariate analysis showed that a high Mn-SOD content of carcinomas was associated with a poor 5-year overall survival of the patients with colorectal cancer. Multivariate analysis including all clinicopathological parameters revealed that this Mn-SOD parameter was prognostically independent. The Mn-and Cu/Zn-SOD content of normal mucosa and the Cu/Zn-SOD content of carcinomas were not associated with the overall survival of the patients. In conclusion, this study demonstrates that for patients with colorectal cancer the Mn-SOD content of colorectal carcinomas has a significant prognostic value that is independent from major clinicopathological parameters, including Dukes' stage.

Our study indicates that the development of neoplasia in the human colorectum is accompanied by major changes in the level and activity of Mn-SOD. This observation illustrates that Mn-SOD might have a functional role in human colorectal carcinogenesis.

Metallothionein (MT) is a small thiol-rich metalloprotein with antioxidant properties, involved in tumour pathophysiology and therapy resistance. In order to assess the contribution of MT in gastrointestinal carcinogenesis, this study examined both the MT content by radioimmunoassay and the MT localization by immunohistochemistry in pairs of neoplastic and normal-appearing human gastrointestinal tissues. In addition, the relationship between MT expression and major clinicopathological parameters was assessed. The MT concentration of gastric carcinomas and of colorectal adenomas, carcinomas, and liver metastases was found to be significantly lower than that of corresponding normal-appearing tissue. A relatively high MT content, however, was found to be associated with the villous character of colorectal adenomas and with the Dukes' stage of colorectal carcinomas, indicating a relationship between MT level and malignant potential. Immunohistochemical evaluation showed a fairly good correlation with these quantitative data. MT was found to be expressed at a low level and in a patchy pattern in the gastrointestinal neoplastic and metastatic tissues, whereas in normal-appearing gastrointestinal mucosa MT was uniformly distributed in the cytoplasm and/or nucleus of apical cells. Although in the gastric cancer patients no association was found between the MT concentration and the clinicopathological parameters, the strong MT expression in areas with intestinal metaplasia, known to have neoplastic potential, further points to a relationship between this antioxidant metalloprotein and the malignant character of cells. Gastrointestinal neoplasms are apparently accompanied by a low level and decreased expression of MT, but those with a relatively high level seem to have an increased malignant potential. Further studies will be required to determine the clinical relevance of these observations.

Red blood cells (RBCs) undergo extensive deformation when travelling through the microcapillaries. Deformability, the combined result of properties of the membrane-cytoskeleton complex, the surface area-to-volume ratio, and the hemoglobin content, is a critical determinant of capillary blood flow. During blood bank storage and in many pathophysiological conditions, RBC morphology changes, which has been suggested to be associated with decreased deformability and removal of RBC. While various techniques provide information on the rheological properties of stored RBCs, their clinical significance is controversial. We developed a microfluidic approach for evaluating RBC deformability in a physiologically meaningful and clinically significant manner. Unlike other techniques, our method enables a high-throughput determination of changes in deformation capacity to provide statistically significant data, while providing morphological information at the single-cell level. Our data show that, under conditions that closely mimic capillary dimensions and flow, the capacity to deform and the capacity to relax are not affected during storage in the blood bank. Our data also show that altered cell morphology by itself does not necessarily affect deformability.