Temporal patterns of human cortical activity reflect tone sequence structure

Despite growing interest in temporal aspects of auditory neural processing, little is known about large-scale timing patterns of brain activity during the perception of auditory sequences. This is partly because it has not been possible to distinguish stimulus-related activity from other, endogenous brain signals recorded by electrical or magnetic sensors. Here we use amplitude modulation of unfamiliar, approximately 1-minute-long tone sequences to label stimulus-related magnetoencephalographic neural activity in human subjects. We show that temporal patterns of activity recorded over particular brain regions track the pitch contour of tone sequences, with the accuracy of tracking increasing as tone sequences become more predictable in structure. In contrast, temporal synchronization between recording locations, particularly between sites over the left posterior hemisphere and the rest of the brain, is greatest when sequences have melody-like statistical properties, which may reflect the perceptual integration of local and global pitch patterns in melody-like sequences. This method is particularly well suited to studying temporal neural correlates of complex auditory sequences (such as speech or music) which engage multiple brain areas as perception unfolds in time.     

Perception of sniff phase in mouse olfaction

Olfactory systems encode odours by which neurons respond and by when they respond. In mammals, every sniff evokes a precise, odour-specific sequence of activity across olfactory neurons. Likewise, in a variety of neural systems, ranging from sensory periphery to cognitive centres, neuronal activity is timed relative to sampling behaviour and/or internally generated oscillations. As in these neural systems, relative timing of activity may represent information in the olfactory system. However, there is no evidence that mammalian olfactory systems read such cues. To test whether mice perceive the timing of olfactory activation relative to the sniff cycle ('sniff phase'), we used optogenetics in gene-targeted mice to generate spatially constant, temporally controllable olfactory input. Here we show that mice can behaviourally report the sniff phase of optogenetically driven activation of olfactory sensory neurons. Furthermore, mice can discriminate between light-evoked inputs that are shifted in the sniff cycle by as little as 10 milliseconds, which is similar to the temporal precision of olfactory bulb odour responses. Electrophysiological recordings in the olfactory bulb of awake mice show that individual cells encode the timing of photoactivation in relation to the sniff in both the timing and the amplitude of their responses. Our work provides evidence that the mammalian olfactory system can read temporal patterns, and suggests that timing of activity relative to sampling behaviour is a potent cue that may enable accurate olfactory percepts to form quickly.     

Humans use internal models to estimate gravity and linear acceleration

Because sensory systems often provide ambiguous information, neural processes must exist to resolve these ambiguities. It is likely that similar neural processes are used by different sensory systems. For example, many tasks require neural processing to distinguish linear acceleration from gravity, but Einstein's equivalence principle states that all linear accelerometers must measure both linear acceleration and gravity. Here we investigate whether the brain uses internal models, defined as neural systems that mimic physical principles, to help estimate linear acceleration and gravity. Internal models may be used in motor contro, sensorimotor integration and sensory processing, but direct experimental evidence for such models is limited. To determine how humans process ambiguous gravity and linear acceleration cues, subjects were tilted after being rotated at a constant velocity about an Earth-vertical axis. We show that the eye movements evoked by this post-rotational tilt include a response component that compensates for the estimated linear acceleration even when no actual linear acceleration occurs. These measured responses are consistent with our internal model predictions that the nervous system can develop a non-zero estimate of linear acceleration even when no true linear acceleration is present.     

自传体记忆研究的若干新进展

总结了自传体记忆研究中新近出现的功能研究取向以及自传体记忆脑机制的神经心理学研究和脑成像研究结果。功能取向的研究表明,自传体记忆具有自我、社会和指导这3类主要功能。神经心理学和脑成像研究发现自传体记忆主要定位于颞叶与海马,但这2方面研究的结果之间却存在着很大的不一致：以脑损伤病人进行的神经心理学研究发现自传体记忆主要表现为右侧颞叶与海马的功能,而对正常人的脑成像研究却表明提取自传体记忆事件时主要的激活部位是左侧颞叶与海马。目前尚无关于这种不一致现象的评论与解释,由于自传体记忆的脑成像研究数量较少且结论并不一致,在进行更多的脑成像研究之后再来比较神经心理学与脑成像的研究结果可能更为合适。     

New advances in the neural correlates of insight: A decade in review of the insightful brain

The first neuroimaging study of real-time brain activity during insight problem solving was conducted almost ten years ago. Many subsequent studies have used high-resolution event-related potentials (ERPs) and event-related functional magnetic resonance imaging (fMRI) to investigate the temporal dynamics and neural correlates of insight. Recent results on the neural underpinnings of insight have led researchers to propose a neural framework referred to as the "insightful brain". This putative framework represents the neural basis of the cognitive and affective processes that are involved in insight. The insightful brain may involve numerous brain regions, including the lateral prefrontal cortex, cingulate cortex, hippocampus, superior temporal gyrus, fusiform gyrus, precuneus, cuneus, insula and cerebellum. Functional studies have demonstrated that the lateral prefrontal cortex is responsible for mental set shifting and breaking during insight problem solving. The cingulate cortex is involved in the cognitive conflict between new and old ideas and progress monitoring. The hippocampus, superior temporal gyrus and fusiform gyrus form an integrated functional network that specializes in the formation of novel and effective associations. The effective transformation of problem representations depends on a non-verbal visuospatial information-processing network that comprises the precuneus and cuneus. The insula reflects cognitive flexibility and the emotional experience that is associated with insight. The cortical control of finger movements relies on the cerebellum.     

Gut hormones and the regulation of energy homeostasis

Food intake, energy expenditure and body adiposity are homeostatically regulated. Central and peripheral signals communicate information about the current state of energy balance to key brain regions, including the hypothalamus and brainstem. Hunger and satiety represent coordinated responses to these signals, which include neural and hormonal messages from the gut. In recent years our understanding of how neural and hormonal brain-gut signalling regulates energy homeostasis has advanced considerably. Gut hormones have various physiological functions that include specifically targeting the brain to regulate appetite. New research suggests that gut hormones can be used to specifically regulate energy homeostasis in humans, and offer a target for anti-obesity drugs.     

Neurophysiological investigation of the basis of the fMRI signal.

Functional magnetic resonance imaging (fMRI) is widely used to study the operational organization of the human brain, but the exact relationship between the measured fMRI signal and the underlying neural activity is unclear. Here we present simultaneous intracortical recordings of neural signals and fMRI responses. We compared local field potentials (LFPs), single- and multi-unit spiking activity with highly spatio-temporally resolved blood-oxygen-level-dependent (BOLD) fMRI responses from the visual cortex of monkeys. The largest magnitude changes were observed in LFPs, which at recording sites characterized by transient responses were the only signal that significantly correlated with the haemodynamic response. Linear systems analysis on a trial-by-trial basis showed that the impulse response of the neurovascular system is both animal- and site-specific, and that LFPs yield a better estimate of BOLD responses than the multi-unit responses. These findings suggest that the BOLD contrast mechanism reflects the input and intracortical processing of a given area rather than its spiking output.     

Temporal dissociation of parallel processing in the human subcortical outputs.

Many tasks require rapid and fine-tuned adjustment of motor performance based on incoming sensory information. This process of sensorimotor adaptation engages two parallel subcorticocortical neural circuits, involving the cerebellum and basal ganglia, respectively. How these distributed circuits are functionally coordinated has not been shown in humans. The cerebellum and basal ganglia show very similar convergence of input-output organization, which presents an ideal neuroimaging model for the study of parallel processing at a systems level. Here we used functional magnetic resonance imaging to measure the temporal coherence of brain activity during a tactile discrimination task. We found that, whereas the prefrontal cortex maintained a high level of activation, output activities in the cerebellum and basal ganglia showed different phasic patterns. Moreover, cerebellar activity significantly correlated with the activity of the supplementary motor area but not with that of the primary motor cortex; in contrast, basal ganglia activity was more strongly associated with the activity of the primary motor cortex than with that of the supplementary motor area. These results demonstrate temporally partitioned activity in the cerebellum and basal ganglia, implicating functional independence in the parallel subcortical outputs. This further supports the idea of task-related dynamic reconfiguration of large-scale neural networks.     

Odour-plume dynamics influence the brain's olfactory code

The neural computations used to represent olfactory information in the brain have long been investigated. Recent studies in the insect antennal lobe suggest that precise temporal and/or spatial patterns of activity underlie the recognition and discrimination of different odours, and that these patterns may be strengthened by associative learning. It remains unknown, however, whether these activity patterns persist when odour intensity varies rapidly and unpredictably, as often occurs in nature. Here we show that with naturally intermittent odour stimulation, spike patterns recorded from moth antennal-lobe output neurons varied predictably with the fine-scale temporal dynamics and intensity of the odour. These data support the hypothesis that olfactory circuits compensate for contextual variations in the stimulus pattern with high temporal precision. The timing of output neuron activity is constantly modulated to reflect ongoing changes in stimulus intensity and dynamics that occur on a millisecond timescale.     

Disruption of neurotransmission in Drosophila mushroom body blocks retrieval but not acquisition of memory

Surgical, pharmacological and genetic lesion studies have revealed distinct anatomical sites involved with different forms of learning. Studies of patients with localized brain damage and work in rodent model systems, for example, have shown that the hippocampal formation participates in acquisition of declarative tasks but is not the site of their long-term storage. Such lesions are usually irreversible, however, which has limited their use for dissecting the temporal processes of acquisition, storage and retrieval of memories. Studies in bees and flies have similarly revealed a distinct anatomical region of the insect brain, the mushroom body, that is involved specifically in olfactory associative learning. We have used a temperature-sensitive dynamin transgene, which disrupts synaptic transmission reversibly and on the time-scale of minutes, to investigate the temporal requirements for ongoing neural activity during memory formation. Here we show that synaptic transmission from mushroom body neurons is required during memory retrieval but not during acquisition or storage. We propose that the hebbian processes underlying olfactory associative learning reside in mushroom body dendrites or upstream of the mushroom body and that the resulting alterations in synaptic strength modulate mushroom body output during memory retrieval.     

A resetting signal between Drosophila pacemakers synchronizes morning and evening activity

The biochemical machinery that underlies circadian rhythms is conserved among animal species and drives self-sustained molecular oscillations and functions, even within individual asynchronous tissue-culture cells. Yet the rhythm-generating neural centres of higher eukaryotes are usually composed of interconnected cellular networks, which contribute to robustness and synchrony as well as other complex features of rhythmic behaviour. In mammals, little is known about how individual brain oscillators are organized to orchestrate a complex behavioural pattern. Drosophila is arguably more advanced from this point of view: we and others have recently shown that a group of adult brain clock neurons expresses the neuropeptide PDF and controls morning activity (small LN(v) cells; M-cells), whereas another group of clock neurons controls evening activity (CRY+, PDF- cells; E-cells). We have generated transgenic mosaic animals with different circadian periods in morning and evening cells. Here we show, by behavioural and molecular assays, that the six canonical groups of clock neurons are organized into two separate neuronal circuits. One has no apparent effect on locomotor rhythmicity in darkness, but within the second circuit the molecular and behavioural timing of the evening cells is determined by morning-cell properties. This is due to a daily resetting signal from the morning to the evening cells, which run at their genetically programmed pace between consecutive signals. This neural circuit and oscillator-coupling mechanism ensures a proper relationship between the timing of morning and evening locomotor activity.     

Interactive memory systems in the human brain.

Learning and memory in humans rely upon several memory systems, which appear to have dissociable brain substrates. A fundamental question concerns whether, and how, these memory systems interact. Here we show using functional magnetic resonance imaging (FMRI) that these memory systems may compete with each other during classification learning in humans. The medial temporal lobe and basal ganglia were differently engaged across subjects during classification learning depending upon whether the task emphasized declarative or nondeclarative memory, even when the to-be-learned material and the level of performance did not differ. Consistent with competition between memory systems suggested by animal studies and neuroimaging, activity in these regions was negatively correlated across individuals. Further examination of classification learning using event-related FMRI showed rapid modulation of activity in these regions at the beginning of learning, suggesting that subjects relied upon the medial temporal lobe early in learning. However, this dependence rapidly declined with training, as predicted by previous computational models of associative learning.     

Directing neural stem cell fate with biomaterial parameters for injured brain regeneration

The discovery of neural stem cells (NSCs), which have the ability to self-renew and differentiate into all types of neural lineages, offers promising prospect for the treatment of brain neurological disorders such as stroke/cerebral ischemia, traumatic brain injury and neurodegenerative disorders. However, only limited number of NSCs could survive or propagate due to tissue inflammation or blood-brain barrier. Therefore, it is necessary to develop an appropriate culture system that highly mimics the natural NSCs niche to direct stem cell fate and behavior for nerve regeneration. Both biophysical and biochemical properties of the NSC niche, including topology, mechanical properties, bioactive molecules, and their spatial and temporal presentations should be considered for the design of functionalized scaffolds, which could not only serve as the delivery vehicles of NSCs but also stimulate specific cellular responses at the molecular level, such as support endogenous or exogenous cells proliferation, migration and homing, even promote the growth of axon at the injured brain site. This review attempts to outline the varieties of biomaterial     

Non-classical receptive field mediates switch in a sensory neuron's frequency tuning

Animals have developed stereotyped communication calls to which specific sensory neurons are well tuned. These communication calls must be discriminated from environmental signals such as those produced by prey. Sensory systems might have evolved neural circuitry to encode both categories. In weakly electric fish, prey and communication signals differ in their spatial extent and frequency content. Here we show that stimuli of different spatial extents mimicking prey and communication signals cause a switch in the frequency tuning and spike-timing precision of electrosensory pyramidal neurons, resulting in the selective and optimal encoding of both stimulus categories. As in other sensory systems, pyramidal neurons respond only to stimuli located within a restricted region of space known as the classical receptive field (CRF). In some systems, stimulation outside the CRF but within a non-classical receptive field (nCRF) can modulate the neural response to CRF stimulation even though nCRF stimulation alone fails to elicit responses. We show that pyramidal neurons possess a nCRF and that it can modulate the response to CRF stimuli to induce this neurobiological switch in frequency tuning.     

PYY modulation of cortical and hypothalamic brain areas predicts feeding behaviour in humans

The ability to maintain adequate nutrient intake is critical for survival. Complex interrelated neuronal circuits have developed in the mammalian brain to regulate many aspects of feeding behaviour, from food-seeking to meal termination. The hypothalamus and brainstem are thought to be the principal homeostatic brain areas responsible for regulating body weight. However, in the current 'obesogenic' human environment food intake is largely determined by non-homeostatic factors including cognition, emotion and reward, which are primarily processed in corticolimbic and higher cortical brain regions. Although the pleasure of eating is modulated by satiety and food deprivation increases the reward value of food, there is currently no adequate neurobiological account of this interaction between homeostatic and higher centres in the regulation of food intake in humans. Here we show, using functional magnetic resonance imaging, that peptide YY3-36 (PYY), a physiological gut-derived satiety signal, modulates neural activity within both corticolimbic and higher-cortical areas as well as homeostatic brain regions. Under conditions of high plasma PYY concentrations, mimicking the fed state, changes in neural activity within the caudolateral orbital frontal cortex predict feeding behaviour independently of meal-related sensory experiences. In contrast, in conditions of low levels of PYY, hypothalamic activation predicts food intake. Thus, the presence of a postprandial satiety factor switches food intake regulation from a homeostatic to a hedonic, corticolimbic area. Our studies give insights into the neural networks in humans that respond to a specific satiety signal to regulate food intake. An increased understanding of how such homeostatic and higher brain functions are integrated may pave the way for the development of new treatment strategies for obesity.     

Watching cartoons activates the medial prefrontal cortex in children

The medial prefrontal cortex (MPFC) of human adults is involved in attributing mental states to real human agents but not to virtual artificial characters. This study examined whether such differential MPFC activity can be observed in children who are more fascinated by cartoons than adults. We measured brain activity using functional magnetic resonance imaging (fMRI) while 10-year-old children watched movie and cartoon clips, simulating real and virtual visual worlds, respectively. We showed neuroimaging evidence that, in contrast to adults, the MPFC of children was activated when perceiving both human agents and artificial characters in coherent visual events. Our findings suggest that, around the age of 10 years, the MPFC activity in children is different from that in adults in that it can be spontaneously activated by non-human agents in a virtual visual world.     

Empathic neural responses are modulated by the perceived fairness of others

The neural processes underlying empathy are a subject of intense interest within the social neurosciences. However, very little is known about how brain empathic responses are modulated by the affective link between individuals. We show here that empathic responses are modulated by learned preferences, a result consistent with economic models of social preferences. We engaged male and female volunteers in an economic game, in which two confederates played fairly or unfairly, and then measured brain activity with functional magnetic resonance imaging while these same volunteers observed the confederates receiving pain. Both sexes exhibited empathy-related activation in pain-related brain areas (fronto-insular and anterior cingulate cortices) towards fair players. However, these empathy-related responses were significantly reduced in males when observing an unfair person receiving pain. This effect was accompanied by increased activation in reward-related areas, correlated with an expressed desire for revenge. We conclude that in men (at least) empathic responses are shaped by valuation of other people's social behaviour, such that they empathize with fair opponents while favouring the physical punishment of unfair opponents, a finding that echoes recent evidence for altruistic punishment.     

Temporal dynamics of a neural solution to the aperture problem in visual area MT of macaque brain

A critical step in the interpretation of the visual world is the integration of the various local motion signals generated by moving objects. This process is complicated by the fact that local velocity measurements can differ depending on contour orientation and spatial position. Specifically, any local motion detector can measure only the component of motion perpendicular to a contour that extends beyond its field of view. This "aperture problem" is particularly relevant to direction-selective neurons early in the visual pathways, where small receptive fields permit only a limited view of a moving object. Here we show that neurons in the middle temporal visual area (known as MT or V5) of the macaque brain reveal a dynamic solution to the aperture problem. MT neurons initially respond primarily to the component of motion perpendicular to a contour's orientation, but over a period of approximately 60 ms the responses gradually shift to encode the true stimulus direction, regardless of orientation. We also report a behavioural correlate of these neural responses: the initial velocity of pursuit eye movements deviates in a direction perpendicular to local contour orientation, suggesting that the earliest neural responses influence the oculomotor response.     

ON and OFF pathways in Drosophila motion vision

Motion vision is a major function of all visual systems, yet the underlying neural mechanisms and circuits are still elusive. In the lamina, the first optic neuropile of Drosophila melanogaster, photoreceptor signals split into five parallel pathways, L1-L5. Here we examine how these pathways contribute to visual motion detection by combining genetic block and reconstitution of neural activity in different lamina cell types with whole-cell recordings from downstream motion-sensitive neurons. We find reduced responses to moving gratings if L1 or L2 is blocked; however, reconstitution of photoreceptor input to only L1 or L2 results in wild-type responses. Thus, the first experiment indicates the necessity of both pathways, whereas the second indicates sufficiency of each single pathway. This contradiction can be explained by electrical coupling between L1 and L2, allowing for activation of both pathways even when only one of them receives photoreceptor input. A fundamental difference between the L1 pathway and the L2 pathway is uncovered when blocking L1 or L2 output while presenting moving edges of positive (ON) or negative (OFF) contrast polarity: blocking L1 eliminates the response to moving ON edges, whereas blocking L2 eliminates the response to moving OFF edges. Thus, similar to the segregation of photoreceptor signals in ON and OFF bipolar cell pathways in the vertebrate retina, photoreceptor signals segregate into ON-L1 and OFF-L2 channels in the lamina of Drosophila.     

Sheep don't forget a face.

The human brain has evolved specialized neural mechanisms for visual recognition of faces, which afford us a remarkable ability to discriminate between, remember and think about many hundreds of different individuals. Sheep also recognize and are attracted to individual sheep and humans by their faces, as they possess similar specialized neural systems in the temporal and frontal lobes for assisting in this important social task, including a greater involvement of the right brain hemisphere. Here we show that individual sheep can remember 50 other different sheep faces for over 2 years, and that the specialized neural circuits involved maintain selective encoding of individual sheep and human faces even after long periods of separation.