Explore the vast range of titles available.

Non-invasive electrical stimulation of the human cortex by means of transcranial direct current stimulation (tDCS) has been instrumental in a number of important discoveries in the field of human cortical function and has become a well-established method for evaluating brain function in healthy human participants. Recently, transcranial alternating current stimulation (tACS) has been introduced to directly modulate the ongoing rhythmic brain activity by the application of oscillatory currents on the human scalp. Until now the efficiency of tACS in modulating rhythmic brain activity has been indicated only by inference from perceptual and behavioural consequences of electrical stimulation. No direct electrophysiological evidence of tACS has been reported. We delivered tACS over the occipital cortex of 10 healthy participants to entrain the neuronal oscillatory activity in their individual alpha frequency range and compared results with those from a separate group of participants receiving sham stimulation. The tACS but not the sham stimulation elevated the endogenous alpha power in parieto-central electrodes of the electroencephalogram. Additionally, in a network of spiking neurons, we simulated how tACS can be affected even after the end of stimulation. The results show that spike-timing-dependent plasticity (STDP) selectively modulates synapses depending on the resonance frequencies of the neural circuits that they belong to. Thus, tACS influences STDP which in turn results in aftereffects upon neural activity.The present findings are the first direct electrophysiological evidence of an interaction of tACS and ongoing oscillatory activity in the human cortex. The data demonstrate the ability of tACS to specifically modulate oscillatory brain activity and show its potential both at fostering knowledge on the functional significance of brain oscillations and for therapeutic application.

Stochastic resonance is said to be observed when increases in levels of unpredictable fluctuations--e.g., random noise--cause an increase in a metric of the quality of signal transmission or detection performance, rather than a decrease. This counterintuitive effect relies on system nonlinearities and on some parameter ranges being \"suboptimal\". Stochastic resonance has been observed, quantified, and described in a plethora of physical and biological systems, including neurons. Being a topic of widespread multidisciplinary interest, the definition of stochastic resonance has evolved significantly over the last decade or so, leading to a number of debates, misunderstandings, and controversies. Perhaps the most important debate is whether the brain has evolved to utilize random noise in vivo, as part of the \"neural code\". Surprisingly, this debate has been for the most part ignored by neuroscientists, despite much indirect evidence of a positive role for noise in the brain. We explore some of the reasons for this and argue why it would be more surprising if the brain did not exploit randomness provided by noise--via stochastic resonance or otherwise--than if it did. We also challenge neuroscientists and biologists, both computational and experimental, to embrace a very broad definition of stochastic resonance in terms of signal-processing \"noise benefits\", and to devise experiments aimed at verifying that random variability can play a functional role in the brain, nervous system, or other areas of biology.

Most P300-based brain-computer interface (BCI) approaches use the visual modality for stimulation. For use with patients suffering from amyotrophic lateral sclerosis (ALS) this might not be the preferable choice because of sight deterioration. Moreover, using a modality different from the visual one minimizes interference with possible visual feedback. Therefore, a multi-class BCI paradigm is proposed that uses spatially distributed, auditory cues. Ten healthy subjects participated in an offline oddball task with the spatial location of the stimuli being a discriminating cue. Experiments were done in free field, with an individual speaker for each location. Different inter-stimulus intervals of 1000 ms, 300 ms and 175 ms were tested. With averaging over multiple repetitions, selection scores went over 90% for most conditions, i.e., in over 90% of the trials the correct location was selected. One subject reached a 100% correct score. Corresponding information transfer rates were high, up to an average score of 17.39 bits/minute for the 175 ms condition (best subject 25.20 bits/minute). When presenting the stimuli through a single speaker, thus effectively canceling the spatial properties of the cue, selection scores went down below 70% for most subjects. We conclude that the proposed spatial auditory paradigm is successful for healthy subjects and shows promising results that may lead to a fast BCI that solely relies on the auditory sense.

Background Aδ and C fibers are the major pain-conducting nerve fibers, activate only partly the same brain areas, and are differently involved in pain syndromes. Whether a stimulus excites predominantly Aδ or C fibers is a commonly asked question in basic pain research but a quick test was lacking so far. Methodology/Principal Findings Of 77 verbal descriptors of pain sensations, “pricking”, “dull” and “pressing” distinguished best (95% cases correctly) between Aδ fiber mediated (punctate pressure produced by means of von Frey hairs) and C fiber mediated (blunt pressure) pain, applied to healthy volunteers in experiment 1. The sensation was assigned to Aδ fibers when “pricking” but neither “dull” nor “pressing” were chosen, and to C fibers when the sum of the selections of “dull” or “pressing” was greater than that of the selection of “pricking”. In experiment 2, with an independent cohort, the three-descriptor questionnaire achieved sensitivity and specificity above 0.95 for distinguishing fiber preferential non-mechanical induced pain (laser heat, exciting Aδ fibers, and 5-Hz electric stimulation, exciting C fibers). Conclusion A three-item verbal rating test using the words “pricking”, “dull”, and “pressing” may provide sufficient information to characterize a pain sensation evoked by a physical stimulus as transmitted via Aδ or via C fibers. It meets the criteria of a screening test by being easy to administer, taking little time, being comfortable in handling, and inexpensive while providing high specificity for relevant information.

During speaking, auditory feedback is used to adjust vocalizations. The brain systems mediating this integrative ability have been investigated using a wide range of experimental strategies. In this report we examined how vocalization alters speech-sound processing within auditory cortex by directly recording evoked responses to vocalizations and playback stimuli using intracranial electrodes implanted in neurosurgery patients. Several new findings resulted from these high-resolution invasive recordings in human subjects. Suppressive effects of vocalization were found to occur only within circumscribed areas of auditory cortex. In addition, at a smaller number of sites, the opposite pattern was seen; cortical responses were enhanced during vocalization. This increase in activity was reflected in high gamma power changes, but was not evident in the averaged evoked potential waveforms. These new findings support forward models for vocal control in which efference copies of premotor cortex activity modulate sub-regions of auditory cortex.

Photosynthetic diatoms are exposed to rapid and unpredictable changes in irradiance and spectral quality, and must be able to acclimate their light harvesting systems to varying light conditions. Molecular mechanisms behind light acclimation in diatoms are largely unknown. We set out to investigate the mechanisms of high light acclimation in Phaeodactylum tricornutum using an integrated approach involving global transcriptional profiling, metabolite profiling and variable fluorescence technique. Algae cultures were acclimated to low light (LL), after which the cultures were transferred to high light (HL). Molecular, metabolic and physiological responses were studied at time points 0.5 h, 3 h, 6 h, 12 h, 24 h and 48 h after transfer to HL conditions. The integrated results indicate that the acclimation mechanisms in diatoms can be divided into an initial response phase (0-0.5 h), an intermediate acclimation phase (3-12 h) and a late acclimation phase (12-48 h). The initial phase is recognized by strong and rapid regulation of genes encoding proteins involved in photosynthesis, pigment metabolism and reactive oxygen species (ROS) scavenging systems. A significant increase in light protecting metabolites occur together with the induction of transcriptional processes involved in protection of cellular structures at this early phase. During the following phases, the metabolite profiling display a pronounced decrease in light harvesting pigments, whereas the variable fluorescence measurements show that the photosynthetic capacity increases strongly during the late acclimation phase. We show that P. tricornutum is capable of swift and efficient execution of photoprotective mechanisms, followed by changes in the composition of the photosynthetic machinery that enable the diatoms to utilize the excess energy available in HL. Central molecular players in light protection and acclimation to high irradiance have been identified.

Rod/cone photoreceptors of the outer retina and the melanopsin-expressing retinal ganglion cells (mRGCs) of the inner retina mediate non-image forming visual responses including entrainment of the circadian clock to the ambient light, the pupillary light reflex (PLR), and light modulation of activity. Targeted deletion of the melanopsin gene attenuates these adaptive responses with no apparent change in the development and morphology of the mRGCs. Comprehensive identification of mRGCs and knowledge of their specific roles in image-forming and non-image forming photoresponses are currently lacking. We used a Cre-dependent GFP expression strategy in mice to genetically label the mRGCs. This revealed that only a subset of mRGCs express enough immunocytochemically detectable levels of melanopsin. We also used a Cre-inducible diphtheria toxin receptor (iDTR) expression approach to express the DTR in mRGCs. mRGCs develop normally, but can be acutely ablated upon diphtheria toxin administration. The mRGC-ablated mice exhibited normal outer retinal function. However, they completely lacked non-image forming visual responses such as circadian photoentrainment, light modulation of activity, and PLR. These results point to the mRGCs as the site of functional integration of the rod/cone and melanopsin phototransduction pathways and as the primary anatomical site for the divergence of image-forming and non-image forming photoresponses in mammals.

In addition to rods and cones, the human retina contains light-sensitive ganglion cells that express melanopsin, a photopigment with signal transduction mechanisms similar to that of invertebrate rhabdomeric photopigments (IRP). Like fly rhodopsins, melanopsin acts as a dual-state photosensitive flip-flop in which light drives both phototransduction responses and chromophore photoregeneration that bestows independence from the retinoid cycle required by rods and cones to regenerate photoresponsiveness following bleaching by light. To explore the hypothesis that melanopsin in humans expresses the properties of a bistable photopigment in vivo we used the pupillary light reflex (PLR) as a tool but with methods designed to study invertebrate photoreceptors. We show that the pupil only attains a fully stabilized state of constriction after several minutes of light exposure, a feature that is consistent with typical IRP photoequilibrium spectra. We further demonstrate that previous exposure to long wavelength light increases, while short wavelength light decreases the amplitude of pupil constriction, a fundamental property of IRP difference spectra. Modelling these responses to invertebrate photopigment templates yields two putative spectra for the underlying R and M photopigment states with peaks at 481 nm and 587 nm respectively. Furthermore, this bistable mechanism may confer a novel form of \"photic memory\" since information of prior light conditions is retained and shapes subsequent responses to light. These results suggest that the human retina exploits fly-like photoreceptive mechanisms that are potentially important for the modulation of non-visual responses to light and highlights the ubiquitous nature of photoswitchable photosensors across living organisms.

Glaucoma is a progressive eye disease and a leading cause of visual disability. Automated assessment of the visual field determines the different stages in the disease process: it would be desirable to link these measurements taken in the clinic with patient's actual function, or establish if patients compensate for their restricted field of view when performing everyday tasks. Hence, this study investigated eye movements in glaucomatous patients when viewing driving scenes in a hazard perception test (HPT). The HPT is a component of the UK driving licence test consisting of a series of short film clips of various traffic scenes viewed from the driver's perspective each containing hazardous situations that require the camera car to change direction or slow down. Data from nine glaucomatous patients with binocular visual field defects and ten age-matched control subjects were considered (all experienced drivers). Each subject viewed 26 different films with eye movements simultaneously monitored by an eye tracker. Computer software was purpose written to pre-process the data, co-register it to the film clips and to quantify eye movements and point-of-regard (using a dynamic bivariate contour ellipse analysis). On average, and across all HPT films, patients exhibited different eye movement characteristics to controls making, for example, significantly more saccades (P<0.001; 95% confidence interval for mean increase: 9.2 to 22.4%). Whilst the average region of 'point-of-regard' of the patients did not differ significantly from the controls, there were revealing cases where patients failed to see a hazard in relation to their binocular visual field defect. Characteristics of eye movement patterns in patients with bilateral glaucoma can differ significantly from age-matched controls when viewing a traffic scene. Further studies of eye movements made by glaucomatous patients could provide useful information about the definition of the visual field component required for fitness to drive.

In blood vessels, the endothelium is a crucial signal transduction interface in control of vascular tone and blood pressure to ensure energy and oxygen supply according to the organs' needs. In response to vasoactive factors and to shear stress elicited by blood flow, the endothelium secretes vasodilating or vasocontracting autacoids, which adjust the contractile state of the smooth muscle. In endothelial sensing of shear stress, the osmo- and mechanosensitive Ca(2+)-permeable TRPV4 channel has been proposed to be candidate mechanosensor. Using TRPV4(-/-) mice, we now investigated whether the absence of endothelial TRPV4 alters shear-stress-induced arterial vasodilation. In TRPV4(-/-) mice, loss of the TRPV4 protein was confirmed by Western blot, immunohistochemistry and by in situ-patch-clamp techniques in carotid artery endothelial cells (CAEC). Endothelium-dependent vasodilation was determined by pressure myography in carotid arteries (CA) from TRPV4(-/-) mice and wild-type littermates (WT). In WT CAEC, TRPV4 currents could be elicited by TRPV4 activators 4alpha-phorbol-12,13-didecanoate (4alphaPDD), arachidonic acid (AA), and by hypotonic cell swelling (HTS). In striking contrast, in TRPV4(-/-) mice, 4alphaPDD did not produce currents and currents elicited by AA and HTS were significantly reduced. 4alphaPDD caused a robust and endothelium-dependent vasodilation in WT mice, again conspicuously absent in TRPV4(-/-) mice. Shear stress-induced vasodilation could readily be evoked in WT, but was completely eliminated in TRPV4(-/-) mice. In addition, flow/reperfusion-induced vasodilation was significantly reduced in TRPV4(-/-) vs. WT mice. Vasodilation in response to acetylcholine, vasoconstriction in response to phenylephrine, and passive mechanical compliance did not differ between genotypes, greatly underscoring the specificity of the above trpv4-dependent phenotype for physiologically relevant shear stress. Genetically encoded loss-of-function of trpv4 results in a loss of shear stress-induced vasodilation, a response pattern critically dependent on endothelial TRPV4 expression. Thus, Ca(2+)-influx through endothelial TRPV4 channels is a molecular mechanism contributing significantly to endothelial mechanotransduction.