On the basis of world-wide prescription numbers, which are approximately twofold higher for zolpidem (1,338,774,000 tablets from June 2001 to June 2002 in Europe, Japan and United States) than for zopiclone (664,897,000 tablets during the same period in Europe and Japan), the relative incidence of reported dependence similar for both drugs and remarkably lower than that of benzodiazepines used for the treatment of disturbed sleep. The findings offer the conclusion that zolpidem and zopiclone are relatively safe drugs. However, as both drugs are psychotropic drugs, patients with a history of abuse or dependence and those with psychiatric diseases seem to be at increased risk of abuse of these agents.

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www.isrctn.org: ISRCTN49376288.

Our results suggest that the way of breathing decisively influences autonomic and pain processing, thereby identifying DSB in concert with relaxation as the essential feature in the modulation of sympathetic arousal and pain perception.

What mechanisms underlie the flexible formation, adaptation, synchronization, and dissolution of large-scale neural assemblies from the 10 10 densely interconnected, continuously active neurons of the human brain? Nonlinear dynamics provides a unifying perspective on self-organization. It shows that the emergence of patterns in open, nonequilibrium systems is governed by their stability in response to small disturbances and predicts macroscopic transitions between patterns of differing stability. Here, we directly demonstrate that such transitions can be elicited in the human brain by interference at the neural level. As a probe, we used a classic motor coordination paradigm exhibiting well described movement states of differing stability. Functional neuroimaging identified premotor (PMA) and supplementary motor (SMA) cortices as having neural activity linked to the degree of behavioral instability. These regions then were transiently disturbed with graded transcranial magnetic stimulation, which caused sustained and macroscopic behavioral transitions from the less stable out-of-phase to the stable in-phase movement, whereas the stable pattern could not be affected. Moreover, the strength of the disturbance needed (a measure of neural stability) was linked to the degree of behavioral stability, demonstrating the applicability of nonlinear system theory as a powerful predictor of the dynamical repertoire of the human brain.I maging of the living human brain routinely reveals patterns corresponding to the synchronized action of billions of neurons (1). The brain's formation of these large-scale distributed neural assemblies and the rapid transition between them is a striking example of self-organization. In complex systems far from equilibrium, nonlinear systems theory has proposed that the decisive parameter governing such collective emergent behavior is stability to small-scale disturbances; which dynamic patterns get selected from the vast array of possible combinations depends on their relative stability (2). Nonlinear systems exhibit pronounced susceptibility to small disturbances due to a hallmark property called ''sensitive dependence on initial conditions,'' meaning that minute changes to the system's state result in large-scale alterations.A further fundamental prediction of this approach is that self-organization depends on the occurrence of sudden macroscopic transitions between states of differing stability (usually called phase transitions; ref. 3). Therefore, if the presence of transitions between differentially stable patterns could be established, this would uncover a fundamental determinant of the dynamic repertoire of the central nervous system (4). Consequently, transition, synchronization and stability phenomena in neuronal membranes, cells, and small assemblies have been studied intensively (5-7). In humans, correlative evidence comes from the observation of electrophysiological changes as a consequence of alterations of stability in motor behavior, an area to which this theory has been applie...

These parallels in the pathophysiology of tinnitus and depression argue against comorbidity by chance and against depression as pure reaction on tinnitus. Instead, they stand for a complex interplay between tinnitus and depression. Implications for tinnitus treatment are discussed.

Background: The mesolimbic dopaminergic reward system seems to play a crucial role in reinforcing effects of nicotine. Recently, acute highfrequency repetitive transcranial magnetic stimulation (rTMS) of frontal brain regions has been shown to efficiently modulate the mesostriatal and mesolimbic dopaminergic system in both animals and humans. For this reason, we investigated whether high-frequency rTMS would be able to influence nicotine-related behavior by studying rTMS effects on craving and cigarette smoking. Method: Fourteen treatment-seeking smokers were included in a double-blind crossover trial, conducted in 2002, comparing single days of active versus sham stimulation. Outcome measures were rTMS effects on number of cigarettes smoked during an ad libitum smoking period and effects on craving after a period of acute abstinence. Results: High-frequency (20-Hz) rTMS of left dorsolateral prefrontal cortex reduced cigarette smoking significantly (p < .01) in an active stimulation compared with sham stimulation. Levels of craving did not change significantly. Conclusion: High-frequency rTMS may be useful for treatment in smoking cessation.