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Previous studies in healthy volunteers reported a possible impact of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) on stress hormones, like cortisol. In this sham-controlled, "single blind", crossover study, we examined whether HF-rTMS had an effect on the hypothalamic-pituitary-adrenal (HPA) axis, by analysing salivary cortisol levels. Two studies were conducted. First, HF-rTMS on the left dorsolateral prefrontal cortex (DLPFC) was performed in 28 young healthy female volunteers. Second, in a comparable, but different group of 26 healthy females, HF-rTMS was performed on the right DLPFC. Salivary cortisol levels were assessed before, immediately after and 30 min after real and sham HF-rTMS. We found no support for the hypothesis that one single session of HF-rTMS on the left or the right DLPFC has an immediate or delayed impact on the HPA-axis, as measured by salivary cortisol. Although we controlled for several methodological problems in HF-rTMS research, the hypothesis that one single session of HF-rTMS on the left or on the right DLPFC can influence the HPA-axis in healthy volunteers was not supported.

Depressed patients are impaired in the ability to shift their focus of attention. This attentional control process is related to dysfunctions in the dorsolateral prefrontal cortex (DLPFC). It has been proposed that a dorsal circuit plays an important role in the interaction between emotional and attentional information processing. However, because the different emphasis of fundamental cognitive neuroscience research and clinical research of repetitive transcranial magnetic stimulation (rTMS) over the DLPFC, little research has been done on the effects of rTMS on cognitive functioning after a single stimulation session to explore the neural systems underlying depression. This study was conducted as a double-blind, placebo-controlled, crossover, within subjects design. Sixteen depressed patients performed a modified task switching paradigm, before and after receiving high frequency (HF) versus placebo rTMS over the left DLPFC. One session of HF-rTMS over the left DLPFC had a specific beneficial effect on task-switching performance, whereas mood remained stable. Antidepressant effects of rTMS could be related to the same neurochemical changes that underlie cognitive functioning. Therefore, task switching performance may provide a unique window into the extent of antidepressant effects which can be considered as second-order long-term effects possibly related to primary alternations in cognitive functioning.

Objective: High Frequency repetitive Transcranial Magnetic Stimulation (HF-rTMS) has yielded divergent results concerning its effect on mood in normal volunteers. In a former study, we were unable to demonstrate negative mood effects after one session of HF-rTMS on the left dorsolateral prefrontal cortex (DLPFC) in a large group of healthy female volunteers: researchers had focused mainly on negative mood changes, overlooking a possible positive mood induction, while no studies had yet examined mood effects of HF-rTMS delivered on the right prefrontal cortex. In this study, we have tried to replicate our previous HF-rTMS findings on the left DLPFC in a new (large) group of healthy female subjects, and we focused especially on positive mood changes. We also extended our former research by stimulating the right DLPFC in a different but comparable (large) group of healthy female volunteers with the same HF-rTMS parameters., Methods: In this sham-controlled, single blind, crossover HF-rTMS study, stimulus parameters were an exact copy of our previous healthy volunteer study. To exclude individual anatomical differences, the left and right DLPFC were targeted under magnetic resonance (MRI) guidance. To examine subjective mood changes we used Visual Analogue Scales (VAS), the Profile of Mood States (POMS), and the Positive Affect and Negative Affect Schedule (PANAS), the latter to assure assessment of positive emotions. To detect any delayed mood changes, assessments were also re-administered 30min post-HF-rTMS., Results: We were unable to demonstrate immediate or delayed mood changes after one single active HF-rTMS session on the left or right DLPFC., Conclusions: Although we took into account several methodological problems which might have confounded previous rTMS mood induction studies, the hypothesis that one single session of HF-rTMS on the left or on the right DLPFC can influence mood in healthy female volunteers was not supported., Significance: One HF-rTMS session has no effect on subjective mood in healthy female volunteers.

Repetitive Transcranial Magnetic Stimulation (rTMS) provides a unique opportunity to study causal relationships between activity in the dorsolateral prefrontal cortex (DLPFC) and executive functioning, by modulating brain activity in SHAM controlled designs. We devised a new Stroop task paradigm in which subjects must engage in both strategic and automatic attentional processes. In the current experiment, we manipulated subjects' expectancies for incongruent stimuli. Previous research demonstrated that when subjects have a high level of expectancy that a stimulus will be incongruent, they are able to strategically adjust the relative influence of word reading on color naming. The effect of high frequency (HF) rTMS on Stroop performance of 20 right-handed healthy female volunteers was tested using a double blind within subjects design by counterbalanced crossover sham (placebo) and active rTMS over the right DLPFC. Since mood remained unchanged after rTMS, the Stroop data could be evaluated independent of mood changes. Only in the high expectancy condition, we found a decreased response time to both congruent and incongruent trials on the Stroop task performance after HF rTMS. The SHAM placebo condition yielded no effects. We conclude that high frequency stimulation over the right DLPFC has an effect on top-down attentional processes by modulating the attentional set.

High frequency (HF) repetitive transcranial magnetic stimulation (rTMS) has an excitatory effect on neurons of a specific brain area. The dorsolateral prefrontal cortex (DLPFC) has been associated with executive functions, such as task set switching. One important experimental paradigm for investigating such higher order cognitive control is the task-switching (TS) paradigm. A TS paradigm requires switching between two conditional response tasks with mutually incompatible response-selection rules. In the present study, the influence of HF rTMS over the right DLPFC in healthy female volunteers on a modified TS paradigm was investigated. As expected, reaction time on cued switching trials decreased significant after rTMS, as compared to non-cued switch trials. No changes emerged after the placebo sham condition. Mood remained unchanged after rTMS. These findings demonstrate the role of the right DLPFC in cued intentional set switch initiation.

The microbial phototaxis receptor sensory rhodopsin II (NpSRII, also named phoborhodopsin) mediates the photophobic response of the haloarchaeon Natronomonas pharaonis by modulating the swimming behaviour of the bacterium. After excitation by blue-green light NpSRII triggers, by means of a tightly bound transducer protein (NpHtrII), a signal transduction chain homologous with the two-component system of eubacterial chemotaxis. Two molecules of NpSRII and two molecules of NpHtrII form a 2:2 complex in membranes as shown by electron paramagnetic resonance and X-ray structure analysis. Here we present X-ray structures of the photocycle intermediates K and late M (M2) explaining the evolution of the signal in the receptor after retinal isomerization and the transfer of the signal to the transducer in the complex. The formation of late M has been correlated with the formation of the signalling state. The observed structural rearrangements allow us to propose the following mechanism for the light-induced activation of the signalling complex. On excitation by light, retinal isomerization leads in the K state to a rearrangement of a water cluster that partly disconnects two helices of the receptor. In the transition to late M the changes in the hydrogen bond network proceed further. Thus, in late M state an altered tertiary structure establishes the signalling state of the receptor. The transducer responds to the activation of the receptor by a clockwise rotation of about 15 degrees of helix TM2 and a displacement of this helix by 0.9 A at the cytoplasmic surface.

Several studies have demonstrated that repetitive transcranial magnetic stimulation (rTMS) can improve cognitive processing. Neuroimaging studies have shown the engagement of the left dorsolateral prefrontal cortex (DLPFC) in executive functioning, and more specifically during selective attention. In the present study, the influence of high-frequency rTMS over the left DLPFC on Stroop task performance in healthy female volunteers was investigated. As expected, reaction time on both the incongruent and congruent trials decreased significantly after stimulation, and there was no difference with regard to the Stroop interference effect. Mood remained unchanged after rTMS. Such a pattern is consistent with the role of the left DLPFC in implementing top-down attentional control.

Background: High Frequency repetitive Transcranial Magnetic Stimulation (HF-rTMS) is currently used as an experimental tool to induce mood changes in normal volunteers and as a treatment option for depression. However, HF-rTMS, mostly performed on the left dorsolateral prefrontal cortex (DLPFC), has yielded divergent results and effects on mood which seem to be oppositely lateralized between these two groups. The inconsistent results that have been reported might be explained by methodological heterogeneity and drawbacks., Methods: In this sham-controlled, single blind, crossover study, we tried to reproduce previous HF-rTMS findings of a negative mood induction in 28 healthy female subjects. To exclude individual anatomical differences, the left DLPFC was localised under magnetic resonance guidance (MRI). Mood assessment was performed before and just after HF-rTMS with Visual Analogue Scales and the Profile of Mood States. To detect possible delayed mood changes, ratings were also performed 30 min post HF-rTMS., Results: We were unable to demonstrate significant mood changes from baseline after one single active HF-rTMS session on the left DLPFC., Conclusions: Although this study controlled for several methodological problems, the hypothesis that one single session of HF-rTMS on the left DLPFC has negative mood effects in healthy female volunteers was not supported.

5-HT2A receptors have been implicated in the pathophysiology of mood disorders and in the therapeutic effect of the so-called atypical antipsychotics. Recently, a new radioiodinated ligand with high affinity and selectivity for serotonin 5-HT2A receptors, 123iodinated 4-amino-N-1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl] 5-iodo-2-methoxybenzamide (123I-5-I-R91150), has been developed and has been shown to be suitable for single-photon emission tomography (SPET) imaging. In this study the influence of age and gender on the ligand binding was investigated in normal volunteers. One hundred and fifty MBq of 123I-5-I-R91150 was administered to 26 normal volunteers (13 females and 13 males) with an age range of 23-60 years. SPET imaging was performed with a triple-headed gamma camera. For semi-quantitative analysis, ratios of ligand binding in different regions of interest to the binding in the cerebellum were calculated. Mean ratios of 1.7 were obtained. No gender difference was demonstrated. 5-HT2A binding was shown to decline with age. Over an age range of 40 years a reduction in ligand binding of 42% +/- 7% was found. These results are in agreement w in vitro and positron emission tomography findings of a decline in 5-HT2A receptor binding with age. The findings confirm the suitability of 123I-5-I-R91150 for SPET imaging of 5-HT2A receptors, and highlight the necessity for age-matched controls in clinical studies.