Dopamine-dependent prediction errors underpin reward-seeking behaviour in humans

Theories of instrumental learning are centred on understanding how success and failure are used to improve future decisions. These theories highlight a central role for reward prediction errors in updating the values associated with available actions. In animals, substantial evidence indicates that the neurotransmitter dopamine might have a key function in this type of learning, through its ability to modulate cortico-striatal synaptic efficacy. However, no direct evidence links dopamine, striatal activity and behavioural choice in humans. Here we show that, during instrumental learning, the magnitude of reward prediction error expressed in the striatum is modulated by the administration of drugs enhancing (3,4-dihydroxy-L-phenylalanine; L-DOPA) or reducing (haloperidol) dopaminergic function. Accordingly, subjects treated with L-DOPA have a greater propensity to choose the most rewarding action relative to subjects treated with haloperidol. Furthermore, incorporating the magnitude of the prediction errors into a standard action-value learning algorithm accurately reproduced subjects' behavioural choices under the different drug conditions. We conclude that dopamine-dependent modulation of striatal activity can account for how the human brain uses reward prediction errors to improve future decisions.     

Early dispersal of modern humans in Europe and implications for Neanderthal behaviour

The appearance of anatomically modern humans in Europe and the nature of the transition from the Middle to Upper Palaeolithic are matters of intense debate. Most researchers accept that before the arrival of anatomically modern humans, Neanderthals had adopted several 'transitional' technocomplexes. Two of these, the Uluzzian of southern Europe and the Chatelperronian of western Europe, are key to current interpretations regarding the timing of arrival of anatomically modern humans in the region and their potential interaction with Neanderthal populations. They are also central to current debates regarding the cognitive abilities of Neanderthals and the reasons behind their extinction. However, the actual fossil evidence associated with these assemblages is scant and fragmentary, and recent work has questioned the attribution of the Chatelperronian to Neanderthals on the basis of taphonomic mixing and lithic analysis. Here we reanalyse the deciduous molars from the Grotta del Cavallo (southern Italy), associated with the Uluzzian and originally classified as Neanderthal. Using two independent morphometric methods based on microtomographic data, we show that the Cavallo specimens can be attributed to anatomically modern humans. The secure context of the teeth provides crucial evidence that the makers of the Uluzzian technocomplex were therefore not Neanderthals. In addition, new chronometric data for the Uluzzian layers of Grotta del Cavallo obtained from associated shell beads and included within a Bayesian age model show that the teeth must date to ~45,000-43,000 calendar years before present. The Cavallo human remains are therefore the oldest known European anatomically modern humans, confirming a rapid dispersal of modern humans across the continent before the Aurignacian and the disappearance of Neanderthals.     

An RNA gene expressed during cortical development evolved rapidly in humans

The developmental and evolutionary mechanisms behind the emergence of human-specific brain features remain largely unknown. However, the recent ability to compare our genome to that of our closest relative, the chimpanzee, provides new avenues to link genetic and phenotypic changes in the evolution of the human brain. We devised a ranking of regions in the human genome that show significant evolutionary acceleration. Here we report that the most dramatic of these 'human accelerated regions', HAR1, is part of a novel RNA gene (HAR1F) that is expressed specifically in Cajal-Retzius neurons in the developing human neocortex from 7 to 19 gestational weeks, a crucial period for cortical neuron specification and migration. HAR1F is co-expressed with reelin, a product of Cajal-Retzius neurons that is of fundamental importance in specifying the six-layer structure of the human cortex. HAR1 and the other human accelerated regions provide new candidates in the search for uniquely human biology.     

Homing behaviour of axons in the embryonic vertebrate brain

In embryonic nervous systems, growing axons must often travel long distances through diverse extracellular terrains to reach their postsynaptic partners. In most embryos, axons grow to their appropriate targets along particular tracts or nerves, as though they were following guidance cues confined to specific pathways. For example, in all vertebrates, axons from the retina invariably grow to the tectum along the well-defined optic tract. Yet, transplant experiments demonstrate that retinal axons make tectal projections even though they enter the brain at locations which are distinctly off the optic tract. Only recently has it become possible to label discreet growing projections in the embryonic vertebrate brain. Thus, it is not yet known whether displaced retinal axons grow directly towards the tectum or find it accidently, through random extension. To resolve this question, pioneering axons from normal and transplanted eyes in embryonic Xenopus were labelled using a short-survival horseradish peroxidase (HRP) method, and their orientation during growth was quantitatively assessed. The finding that the ectopic fibres head towards their distant targets implies that guidance cues are not restricted to specific pathways but are distributed throughout the embryonic brain. The significance of this result is discussed with respect to the ontogeny and evolution of the visual pathway.     

Small modulation of ongoing cortical dynamics by sensory input during natural vision

During vision, it is believed that neural activity in the primary visual cortex is predominantly driven by sensory input from the environment. However, visual cortical neurons respond to repeated presentations of the same stimulus with a high degree of variability. Although this variability has been considered to be noise owing to random spontaneous activity within the cortex, recent studies show that spontaneous activity has a highly coherent spatio-temporal structure. This raises the possibility that the pattern of this spontaneous activity may shape neural responses during natural viewing conditions to a larger extent than previously thought. Here, we examine the relationship between spontaneous activity and the response of primary visual cortical neurons to dynamic natural-scene and random-noise film images in awake, freely viewing ferrets from the time of eye opening to maturity. The correspondence between evoked neural activity and the structure of the input signal was weak in young animals, but systematically improved with age. This improvement was linked to a shift in the dynamics of spontaneous activity. At all ages including the mature animal, correlations in spontaneous neural firing were only slightly modified by visual stimulation, irrespective of the sensory input. These results suggest that in both the developing and mature visual cortex, sensory evoked neural activity represents the modulation and triggering of ongoing circuit dynamics by input signals, rather than directly reflecting the structure of the input signal itself.     

Cortical ensemble activity increasingly predicts behaviour outcomes during learning of a motor task

When an animal learns to make movements in response to different stimuli, changes in activity in the motor cortex seem to accompany and underlie this learning. The precise nature of modifications in cortical motor areas during the initial stages of motor learning, however, is largely unknown. Here we address this issue by chronically recording from neuronal ensembles located in the rat motor cortex, throughout the period required for rats to learn a reaction-time task. Motor learning was demonstrated by a decrease in the variance of the rats' reaction times and an increase in the time the animals were able to wait for a trigger stimulus. These behavioural changes were correlated with a significant increase in our ability to predict the correct or incorrect outcome of single trials based on three measures of neuronal ensemble activity: average firing rate, temporal patterns of firing, and correlated firing. This increase in prediction indicates that an association between sensory cues and movement emerged in the motor cortex as the task was learned. Such modifications in cortical ensemble activity may be critical for the initial learning of motor tasks.     

基于互信息的帕金森病脑皮层功能连接

帕金森病的早期症状是很难察觉的,目前还没有一个明确的生物标志物可以准确地检测出早期的帕金森病。本文为了探究帕金森病的潜在生物标志物,分析15名帕金森病患者和15名健康对照者闭眼状态下的溯源后的脑电信号。首先,使用互信息测量两组受试者的大脑各个区域之间的功能连接。之后,对两组受试者之间的每个连接对的互信息值进行独立样本t检验,检测两组受试者之间显著差异的连接边。最后,将具有显著差异的连接边作为特征进行分类。结果表明,帕金森病患者的大脑各个区域之间的互信息值整体小于健康对照组,并发现在额顶叶和顶枕叶之间的功能连接差异十分显著（p<0.01）。利用互信息功能连接指标对帕金森病患者和健康对照组分类时,测试准确率为76.7%,验证了基于互信息的脑功能连接对帕金森病研究的有效性。这些发现表明额顶叶和顶枕叶之间功能连接性的降低可能是帕金森病的一个潜在生物标志物。本文系首次使用互信息这一功能连接指标对帕金森病进行研究,这为帕金森病的神经机制研究提供了一个新的途径。     

A functional circuit underlying male sexual behaviour in the female mouse brain

In mice, pheromone detection is mediated by the vomeronasal organ and the main olfactory epithelium. Male mice that are deficient for Trpc2, an ion channel specifically expressed in VNO neurons and essential for VNO sensory transduction, are impaired in sex discrimination and male-male aggression. We report here that Trpc2-/- female mice show a reduction in female-specific behaviour, including maternal aggression and lactating behaviour. Strikingly, mutant females display unique characteristics of male sexual and courtship behaviours such as mounting, pelvic thrust, solicitation, anogenital olfactory investigation, and emission of complex ultrasonic vocalizations towards male and female conspecific mice. The same behavioural phenotype is observed after VNO surgical removal in adult animals, and is not accompanied by disruption of the oestrous cycle and sex hormone levels. These findings suggest that VNO-mediated pheromone inputs act in wild-type females to repress male behaviour and activate female behaviours. Moreover, they imply that functional neuronal circuits underlying male-specific behaviours exist in the normal female mouse brain.