Discover the most talked about and latest scientific content & concepts.

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience


Intracellular Ca(2+) signals control the development and regeneration of spinal axons downstream of chemical guidance cues, but little is known about the roles of mechanical cues in axon guidance. Here we show that transient receptor potential canonical 1 (TRPC1) subunits assemble mechanosensitive (MS) channels on Xenopus neuronal growth cones that regulate the extension and direction of axon outgrowth on rigid, but not compliant, substrata. Reducing expression of TRPC1 by antisense morpholinos inhibits the effects of MS channel blockers on axon outgrowth and local Ca(2+) transients. Ca(2+) influx through MS TRPC1 activates the protease calpain, which cleaves the integrin adaptor protein talin to reduce Src-dependent axon outgrowth, likely through altered adhesion turnover. We found that talin accumulates at the tips of dynamic filopodia, which is lost upon cleavage of talin by active calpain. This pathway may also be important in axon guidance decisions since asymmetric inhibition of MS TRPC1 is sufficient to induce growth cone turning. Together our results suggest that Ca(2+) influx through MS TRPC1 on filopodia activates calpain to control growth cone turning during development.

Concepts: Nervous system, Neuron, Developmental biology, Action potential, Axon, Axon guidance, Growth cone, Filopodia


Due to capacity limits on perception, conditions of high perceptual load lead to reduced processing of unattended stimuli (Lavie et al., 2014). Accumulating work demonstrates the effects of visual perceptual load on visual cortex responses, but the effects on auditory processing remain poorly understood. Here we establish the neural mechanisms underlying “inattentional deafness”-the failure to perceive auditory stimuli under high visual perceptual load. Participants performed a visual search task of low (target dissimilar to nontarget items) or high (target similar to nontarget items) load. On a random subset (50%) of trials, irrelevant tones were presented concurrently with the visual stimuli. Brain activity was recorded with magnetoencephalography, and time-locked responses to the visual search array and to the incidental presence of unattended tones were assessed. High, compared to low, perceptual load led to increased early visual evoked responses (within 100 ms from onset). This was accompanied by reduced early (∼100 ms from tone onset) auditory evoked activity in superior temporal sulcus and posterior middle temporal gyrus. A later suppression of the P3 “awareness” response to the tones was also observed under high load. A behavioral experiment revealed reduced tone detection sensitivity under high visual load, indicating that the reduction in neural responses was indeed associated with reduced awareness of the sounds. These findings support a neural account of shared audiovisual resources, which, when depleted under load, leads to failures of sensory perception and awareness.

Concepts: Psychology, Brain, Understanding, Cognition, Perception, Sense, Mind, Evoked potential


It is well-established that active rehearsal increases the efficacy of memory consolidation. It is also known that complex events are interpreted with reference to prior knowledge. However, comparatively little attention has been given to the neural underpinnings of these effects. In healthy adults humans, we investigated the impact of effortful, active rehearsal on memory for events by showing people several short video clips and then asking them to recall these clips, either aloud (Experiment 1) or silently while in an MRI scanner (Experiment 2). In both experiments, actively rehearsed clips were remembered in far greater detail than unrehearsed clips when tested a week later. In Experiment 1, highly similar descriptions of events were produced across retrieval trials, suggesting a degree of semanticization of the memories had taken place. In Experiment 2, spatial patterns of BOLD signal in medial temporal and posterior midline regions were correlated when encoding and rehearsing the same video. Moreover, the strength of this correlation in the posterior cingulate predicted the amount of information subsequently recalled. This is likely to reflect a strengthening of the representation of the video’s content. We argue that these representations combine both new episodic information and stored semantic knowledge (or “schemas”). We therefore suggest that posterior midline structures aid consolidation by reinstating and strengthening the associations between episodic details and more generic schematic information. This leads to the creation of coherent memory representations of lifelike, complex events that are resistant to forgetting, but somewhat inflexible and semantic-like in nature.

Concepts: Memory, Cerebrum, Hippocampus, Episodic memory, Semantic memory, Cingulate cortex, Memory consolidation, Video clip


Despite extensive research on inhibitory control (IC) and its neural systems, the questions of whether IC can be improved with training and how the associated neural systems change are understudied. Behavioral evidence suggests that performance on IC tasks improves with training but that these gains do not transfer to other tasks, and almost nothing is known about how activation in IC-related brain regions changes with training. Human participants were randomly assigned to receive IC training (N = 30) on an adaptive version of the stop-signal task (SST) or an active sham-training (N = 30) during 10 sessions across 3 weeks. Neural activation during the SST before and after training was assessed in both groups using functional magnetic resonance imaging. Performance on the SST improved significantly more in the training group than in the control group. The pattern of neuroimaging results was consistent with a proactive control model such that activity in key parts of the IC network shifted earlier in time within the trial, becoming associated with cues that anticipated the upcoming need for IC. Specifically, activity in the inferior frontal gyrus decreased during the implementation of control (i.e., stopping) and increased during cues that preceded the implementation of IC from pretraining to post-training. Also, steeper behavioral improvement in the training group correlated with activation increases during the cue phase and decreases during implementation in the dorsolateral prefrontal cortex. These results are the first to uncover the neural pathways for training-related improvements in IC and can explain previous null findings of IC training transfer.

Concepts: Better, Brain, Improve, Magnetic resonance imaging, Cerebrum, Attention versus memory in prefrontal cortex, Frontal lobe, Brodmann area


We previously found that Mertk and its ligand Gas6, astrocytic genes involved in phagocytosis, are upregulated after acute sleep deprivation. These results suggested that astrocytes may engage in phagocytic activity during extended wake, but direct evidence was lacking. Studies in humans and rodents also found that sleep loss increases peripheral markers of inflammation, but whether these changes are associated with neuroinflammation and/or activation of microglia, the brain’s resident innate immune cells, was unknown. Here we used serial block-face scanning electron microscopy to obtain 3D volume measurements of synapses and surrounding astrocytic processes in mouse frontal cortex after 6-8 h of sleep, spontaneous wake, or sleep deprivation (SD) and after chronic (∼5 d) sleep restriction (CSR). Astrocytic phagocytosis, mainly of presynaptic components of large synapses, increased after both acute and chronic sleep loss relative to sleep and wake. MERTK expression and lipid peroxidation in synaptoneurosomes also increased to a similar extent after short and long sleep loss, suggesting that astrocytic phagocytosis may represent the brain’s response to the increase in synaptic activity associated with prolonged wake, clearing worn components of heavily used synapses. Using confocal microscopy, we then found that CSR but not SD mice show morphological signs of microglial activation and enhanced microglial phagocytosis of synaptic elements, without obvious signs of neuroinflammation in the CSF. Because low-level sustained microglia activation can lead to abnormal responses to a secondary insult, these results suggest that chronic sleep loss, through microglia priming, may predispose the brain to further damage.SIGNIFICANCE STATEMENT We find that astrocytic phagocytosis of synaptic elements, mostly of presynaptic origin and in large synapses, is upregulated already after a few hours of sleep deprivation and shows a further significant increase after prolonged and severe sleep loss, suggesting that it may promote the housekeeping of heavily used and strong synapses in response to the increased neuronal activity of extended wake. By contrast, chronic sleep restriction but not acute sleep loss activates microglia, promotes their phagocytic activity, and does so in the absence of overt signs of neuroinflammation, suggesting that like many other stressors, extended sleep disruption may lead to a state of sustained microglia activation, perhaps increasing the brain’s susceptibility to other forms of damage.

Concepts: Immune system, Neuron, Brain, Sleep deprivation, Human brain, Cerebral cortex, Cerebrum, Frontal lobe


Noninvasive brain stimulation provides a potential tool for affecting brain functions in the typical and atypical brain and offers in several cases an alternative to pharmaceutical intervention. Some studies have suggested that transcranial electrical stimulation (TES), a form of noninvasive brain stimulation, can also be used to enhance cognitive performance. Critically, research so far has primarily focused on optimizing protocols for effective stimulation, or assessing potential physical side effects of TES while neglecting the possibility of cognitive side effects. We assessed this possibility by targeting the high-level cognitive abilities of learning and automaticity in the mathematical domain. Notably, learning and automaticity represent critical abilities for potential cognitive enhancement in typical and atypical populations. Over 6 d, healthy human adults underwent cognitive training on a new numerical notation while receiving TES to the posterior parietal cortex or the dorsolateral prefrontal cortex. Stimulation to the the posterior parietal cortex facilitated numerical learning, whereas automaticity for the learned material was impaired. In contrast, stimulation to the dorsolateral prefrontal cortex impaired the learning process, whereas automaticity for the learned material was enhanced. The observed double dissociation indicates that cognitive enhancement through TES can occur at the expense of other cognitive functions. These findings have important implications for the future use of enhancement technologies for neurointervention and performance improvement in healthy populations.

Concepts: Psychology, Brain, Cognition, Cerebrum, Educational psychology, Knowledge, Frontal lobe, Parietal lobe


Increased preference for immediate over delayed and for risky over certain rewards has been associated with unhealthy behavioral choices. Motivated by evidence that enhanced cognitive control can shift choice behavior away from immediate and risky rewards, we tested whether training executive cognitive function could influence choice behavior and brain responses. In this randomized controlled trial, 128 young adults (71 male, 57 female) participated in 10 weeks of training with either a commercial web-based cognitive training program or web-based video games that do not specifically target executive function or adapt the level of difficulty throughout training. Pre- and post-training, participants completed cognitive assessments and functional magnetic resonance imaging (fMRI) during performance of validated decision-making tasks: delay discounting (choices between smaller rewards now vs. larger rewards in the future) and risk sensitivity (choices between larger riskier rewards vs. smaller certain rewards). Contrary to our hypothesis, we found no evidence that cognitive training influences neural activity during decision-making, nor did we find effects of cognitive training on measures of delay discounting or risk sensitivity. Participants in the commercial training condition improved with practice on the specific tasks they performed during training, but participants in both conditions showed similar improvement on standardized cognitive measures over time. Moreover, the degree of improvement was comparable to that observed in individuals who were reassessed without any training whatsoever. Commercial adaptive cognitive training appears to have no benefits in healthy young adults above those of standard video games for measures of brain activity, choice behavior, or cognitive performance.Registry: NCT01252966, www.clinicaltrials.govSIGNIFICANCE STATEMENTEngagement of neural regions and circuits important in executive cognitive function can bias behavioral choices away from immediate rewards. Activity in these regions may be enhanced through adaptive cognitive training. Commercial brain training programs claim to improve a broad range of mental processes; however, evidence for transfer beyond trained tasks is mixed. We undertook the first randomized controlled trial of the effects of commercial adaptive cognitive training (Lumosity®) on neural activity and decision-making in young adults (N = 128), compared to an active control (playing online video games). We found no evidence for relative benefits of cognitive training with respect to changes in decision-making behavior or brain response, or for cognitive task performance beyond those specifically trained.

Concepts: Psychology, Brain, Randomized controlled trial, Magnetic resonance imaging, Cognition, Cognitive science, Thought, Neuropsychology


In human participants, the intensive practice of particular cognitive activities can induce sustained improvements in cognitive performance, which in some cases transfer to benefits on untrained activities. Despite the growing body of research examining the behavioral effects of cognitive training in children, no studies have explored directly the neural basis of these training effects in a systematic, controlled fashion. Therefore, the impact of training on brain neurophysiology in childhood, and the mechanisms by which benefits may be achieved, are unknown. Here, we apply new methods to examine dynamic neurophysiological connectivity in the context of a randomized trial of adaptive working memory training undertaken in children. After training, connectivity between frontoparietal networks and both lateral occipital complex and inferior temporal cortex was altered. Furthermore, improvements in working memory after training were associated with increased strength of neural connectivity at rest, with the magnitude of these specific neurophysiological changes being mirrored by individual gains in untrained working memory performance.

Concepts: Psychology, Brain, Neuroscience, Human brain, Cerebral cortex, Cerebrum, Hippocampus, Skull


How much we like something, whether it be a bottle of wine or a new film, is affected by the opinions of others. However, the social information we receive can be contradictory and vary in its reliability. Here we test whether the brain incorporates these statistics when judging value and confidence. Participants provided value judgments about consumer goods in the presence of online reviews. We found participants updated their initial value and confidence judgments in a Bayesian fashion, taking into account both the uncertainty of their initial beliefs and the reliability of the social information. Activity in dorsomedial prefrontal cortex tracked the degree of belief update. We find, analogous to how lower-level perceptual information is integrated, that when judging value and confidence the human brain integrates social information according to its reliability.SIGNIFICANCE STATEMENTThe field of perceptual decision making has shown that the sensory system integrates different sources of information according to their respective reliability, as predicted by a Bayesian inference scheme. In this work we hypothesized that a similar coding scheme is implemented by the human brain to process social signals and guide complex value-based decisions. We provide experimental evidence that the human prefrontal cortex’s activity is consistent with a Bayesian computation that integrate social information that differs in reliability and that this integration affects the neural representation of value and confidence.

Concepts: Scientific method, Neuron, Brain, Human brain, Cerebral cortex, Cerebellum, Frontal lobe, Prefrontal cortex


The need to breathe links the mammalian olfactory system inextricably to the respiratory rhythms that draw air through the nose. In rodents and other small animals, slow oscillations of local field potential activity are driven at the rate of breathing (∼2-12 Hz) in olfactory bulb and cortex, and faster oscillatory bursts are coupled to specific phases of the respiratory cycle. These dynamic rhythms are thought to regulate cortical excitability and coordinate network interactions, helping to shape olfactory coding, memory, and behavior. However, while respiratory oscillations are a ubiquitous hallmark of olfactory system function in animals, direct evidence for such patterns is lacking in humans. In this study, we acquired intracranial EEG data from rare patients (Ps) with medically refractory epilepsy, enabling us to test the hypothesis that cortical oscillatory activity would be entrained to the human respiratory cycle, albeit at the much slower rhythm of ∼0.16-0.33 Hz. Our results reveal that natural breathing synchronizes electrical activity in human piriform (olfactory) cortex, as well as in limbic-related brain areas, including amygdala and hippocampus. Notably, oscillatory power peaked during inspiration and dissipated when breathing was diverted from nose to mouth. Parallel behavioral experiments showed that breathing phase enhances fear discrimination and memory retrieval. Our findings provide a unique framework for understanding the pivotal role of nasal breathing in coordinating neuronal oscillations to support stimulus processing and behavior.

Concepts: Psychology, Brain, Cerebrum, Hippocampus, Olfactory bulb, Olfaction, Limbic system, Nasal cavity