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  • 1.

    【2hr】No Evidence that Predictions and Attention Modulate the First Feedforward Sweep of Cortical Information Processing

    包量

    机译 没有证据表明预测和注意力会调节皮层信息处理的前馈扫描
    摘要：Predictive coding models propose that predictions (stimulus likelihood) reduce sensory signals as early as primary visual cortex (V1), and that attention (stimulus relevance) can modulate these effects. Indeed, both prediction and attention have been shown to modulate V1 activity, albeit with fMRI, which has low temporal resolution. This leaves it unclear whether these effects reflect a modulation of the first feedforward sweep of visual information processing and/or later, feedback-related activity. In two experiments, we used electroencephalography and orthogonally manipulated spatial predictions and attention to address this issue. Although clear top-down biases were found, as reflected in pre-stimulus alpha-band activity, we found no evidence for top-down effects on the earliest visual cortical processing stage (<80 ms post-stimulus), as indexed by the amplitude of the C1 event-related potential component and multivariate pattern analyses. These findings indicate that initial visual afferent activity may be impenetrable to top-down influences by spatial prediction and attention.
  • 2.

    【2hr】Deletion of the KH1 Domain of Fmr1 Leads to Transcriptional Alterations and Attentional Deficits in Rats

    包量

    机译 Fmr1的KH1域的删除导致大鼠的转录改变和注意缺陷。
    摘要：Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by mutations in the FMR1 gene. It is a leading monogenic cause of autism spectrum disorder and inherited intellectual disability and is often comorbid with attention deficits. Most FXS cases are due to an expansion of CGG repeats leading to suppressed expression of fragile X mental retardation protein (FMRP), an RNA-binding protein involved in mRNA metabolism. We found that the previously published Fmr1 knockout rat model of FXS expresses an Fmr1 transcript with an in-frame deletion of exon 8, which encodes for the K-homology (KH) RNA-binding domain, KH1. Notably, 3 pathogenic missense mutations associated with FXS lie in the KH domains. We observed that the deletion of exon 8 in rats leads to attention deficits and to alterations in transcriptional profiles within the medial prefrontal cortex (mPFC), which map to 2 weighted gene coexpression network modules. These modules are conserved in human frontal cortex and enriched for known FMRP targets. Hub genes in these modules represent potential therapeutic targets for FXS. Taken together, these findings indicate that attentional testing might be a reliable cross-species tool for investigating FXS and identify dysregulated conserved gene networks in a relevant brain region.
  • 3.

    【2hr】The Hyperpolarization-Activated HCN4 Channel is Important for Proper Maintenance of Oscillatory Activity in the Thalamocortical System

    包量

    机译 超极化激活的HCN4通道对于正确维持丘脑皮层系统的振荡活动很重要。
    摘要：Hyperpolarization-activated cation channels are involved, among other functions, in learning and memory, control of synaptic transmission and epileptogenesis. The importance of the HCN1 and HCN2 isoforms for brain function has been demonstrated, while the role of HCN4, the third major neuronal HCN subunit, is not known. Here we show that HCN4 is essential for oscillatory activity in the thalamocortical (TC) network. HCN4 is selectively expressed in various thalamic nuclei, excluding the thalamic reticular nucleus. HCN4-deficient TC neurons revealed a massive reduction of Ih and strongly reduced intrinsic burst firing, whereas the current was normal in cortical pyramidal neurons. In addition, evoked bursting in a thalamic slice preparation was strongly reduced in the mutant mice probes. HCN4-deficiency also significantly slowed down thalamic and cortical oscillations during active wakefulness. Taken together, these results establish that thalamic HCN4 channels are essential for the production of rhythmic intrathalamic oscillations and determine regular TC oscillatory activity during alert states.
  • 4.

    【2hr】Between Perfectly Critical and Fully Irregular: A Reverberating Model Captures and Predicts Cortical Spike Propagation

    包量

    机译 在完全临界和完全不规则之间：一个回荡模型捕获并预测皮质峰值传播
    摘要：Knowledge about the collective dynamics of cortical spiking is very informative about the underlying coding principles. However, even most basic properties are not known with certainty, because their assessment is hampered by spatial subsampling, i.e., the limitation that only a tiny fraction of all neurons can be recorded simultaneously with millisecond precision. Building on a novel, subsampling-invariant estimator, we fit and carefully validate a minimal model for cortical spike propagation. The model interpolates between two prominent states: asynchronous and critical. We find neither of them in cortical spike recordings across various species, but instead identify a narrow “reverberating” regime. This approach enables us to predict yet unknown properties from very short recordings and for every circuit individually, including responses to minimal perturbations, intrinsic network timescales, and the strength of external input compared to recurrent activation “thereby informing about the underlying coding principles for each circuit, area, state and task.
  • 5.

    【2hr】Spatial Patterns of Brain Activity Preferentially Reflecting Transient Pain and Stimulus Intensity

    包量

    机译 脑活动的空间模式优先反映暂时性疼痛和刺激强度。
    摘要：How pain emerges in the human brain remains an unresolved question. Neuroimaging studies have suggested that several brain areas subserve pain perception because their activation correlates with perceived pain intensity. However, painful stimuli are often intense and highly salient; therefore, using both intensity- and saliency-matched control stimuli is crucial to isolate pain-selective brain responses. Here, we used these intensity/saliency-matched painful and non-painful stimuli to test whether pain-selective information can be isolated in the functional magnetic resonance imaging responses elicited by painful stimuli. Using two independent datasets, multivariate pattern analysis was able to isolate features distinguishing the responses triggered by (1) intensity/saliency-matched painful versus non-painful stimuli, and (2) high versus low-intensity/saliency stimuli regardless of whether they elicit pain. This indicates that neural activity in the so-called “pain matrix” is functionally heterogeneous, and part of it carries information related to both painfulness and intensity/saliency. The response features distinguishing these aspects are spatially distributed and cannot be ascribed to specific brain structures.
  • 6.

    【2hr】Preventing a Thought from Coming to Mind Elicits Increased Right Frontal Beta Just as Stopping Action Does

    包量

    机译 像阻止行动一样，防止思想浮出水面会导致右额叶Beta值增加
    摘要：In the stop-signal task, an electrophysiological signature of action-stopping is increased early right frontal beta band power for successful vs. failed stop trials. Here we tested whether the requirement to stop an unwanted thought from coming to mind also elicits this signature. We recorded scalp EEG during a Think/No-Think task and a subsequent stop signal task in 42 participants. In the Think/No-Think task, participants first learned word pairs. In a second phase, they received the left-hand word as a reminder and were cued either to retrieve the associated right-hand word (“Think”) or to stop retrieval (“No-Think”). At the end of each trial, participants reported whether they had experienced an intrusion of the associated memory. Finally, they received the left-hand reminder word and were asked to recall its associated target. Behaviorally, there was worse final recall for items in the No-Think condition, and decreased intrusions with practice for No-Think trials. For EEG, we reproduced increased early right frontal beta power for successful vs. failed action stopping. Critically, No-Think trials also elicited increased early right frontal beta power and this was stronger for trials without intrusion. These results suggest that preventing a thought from coming to mind also recruits fast prefrontal stopping.
  • 7.

    【2hr】Distinct Structure of Cortical Population Activity on Fast and Infraslow Timescales

    包量

    机译 快速和次慢时标上的皮质种群活动的不同结构。
    摘要：Cortical activity is organized across multiple spatial and temporal scales. Most research on the dynamics of neuronal spiking is concerned with timescales of 1 ms–1 s, and little is known about spiking dynamics on timescales of tens of seconds and minutes. Here, we used frequency domain analyses to study the structure of individual neurons’ spiking activity and its coupling to local population rate and to arousal level across 0.01–100 Hz frequency range. In mouse medial prefrontal cortex, the spiking dynamics of individual neurons could be quantitatively captured by a combination of interspike interval and firing rate power spectrum distributions. The relative strength of coherence with local population often differed across timescales: a neuron strongly coupled to population rate on fast timescales could be weakly coupled on slow timescales, and vice versa. On slow but not fast timescales, a substantial proportion of neurons showed firing anticorrelated with the population. Infraslow firing rate changes were largely determined by arousal rather than by local factors, which could explain the timescale dependence of individual neurons’ population coupling strength. These observations demonstrate how neurons simultaneously partake in fast local dynamics, and slow brain-wide dynamics, extending our understanding of infraslow cortical activity beyond the mesoscale resolution of fMRI.
  • 8.

    【2hr】Hippocampal and Retrosplenial Goal Distance Coding After Long-term Consolidation of a Real-World Environment

    包量

    机译 长期整合现实环境后的海马和脾后目标距离编码
    摘要：Recent research indicates the hippocampus may code the distance to the goal during navigation of newly learned environments. It is unclear however, whether this also pertains to highly familiar environments where extensive systems-level consolidation is thought to have transformed mnemonic representations. Here we recorded fMRI while University College London and Imperial College London students navigated virtual simulations of their own familiar campus (>2 years of exposure) and the other campus learned days before scanning. Posterior hippocampal activity tracked the distance to the goal in the newly learned campus, as well as in familiar environments when the future route contained many turns. By contrast retrosplenial cortex only tracked the distance to the goal in the familiar campus. All of these responses were abolished when participants were guided to their goal by external cues. These results open new avenues of research on navigation and consolidation of spatial information and underscore the notion that the hippocampus continues to play a role in navigation when detailed processing of the environment is needed for navigation.
  • 9.

    【2hr】Aberrant Excitatory–Inhibitory Synaptic Mechanisms in Entorhinal Cortex Microcircuits During the Pathogenesis of Alzheimer’s Disease

    包量

    机译 阿尔茨海默氏病发病机理中内嗅皮层微回路中异常的兴奋抑制性突触机制
    摘要：Synaptic dysfunction is widely proposed as an initial insult leading to the neurodegeneration observed in Alzheimer’s disease (AD). We hypothesize that the initial insult originates in the lateral entorhinal cortex (LEC) due to deficits in key interneuronal functions and synaptic signaling mechanisms, in particular, Wnt (Wingless/integrated). To investigate this hypothesis, we utilized the first knock-in mouse model of AD (AppNL-F/NL-F), expressing a mutant form of human amyloid-β (Aβ) precursor protein. This model shows an age-dependent accumulation of Aβ, neuroinflammation, and neurodegeneration. Prior to the typical AD pathology, we showed a decrease in canonical Wnt signaling activity first affecting the LEC in combination with synaptic hyperexcitation and severely disrupted excitatory–inhibitory inputs onto principal cells. This synaptic imbalance was consistent with a reduction in the number of parvalbumin-containing (PV) interneurons, and a reduction in the somatic inhibitory axon terminals in the LEC compared with other cortical regions. However, targeting GABAA receptors on PV cells using allosteric modulators, diazepam, zolpidem, or a nonbenzodiazepine, L-838,417 (modulator of α2/3 subunit-containing GABAA receptors), restored the excitatory–inhibitory imbalance observed at principal cells in the LEC. These data support our hypothesis, providing a rationale for targeting the synaptic imbalance in the LEC for early stage therapeutic intervention to prevent neurodegeneration in AD.
  • 10.

    【2hr】Corrigendum: Neurexins 1–3 Each Have a Distinct Pattern of Expression in the Early Developing Human Cerebral Cortex

    包量

    机译 更正：神经毒素1–3在人类大脑皮层的早期发育中均具有不同的表达模式
    摘要：
  • 11.

    【2hr】Disruption of Cortical Dopaminergic Modulation Impairs Preparatory Activity and Delays Licking Initiation

    包量

    机译 皮质多巴胺能调节的破坏削弱了准备活动并延迟了舔舔的开始。
    摘要：Dysfunction of motor cortices is thought to contribute to motor disorders such as Parkinson’s disease (PD). However, little is known on the link between cortical dopaminergic loss, abnormalities in motor cortex neural activity and motor deficits. We address the role of dopamine in modulating motor cortical activity by focusing on the anterior lateral motor cortex (ALM) of mice performing a cued-licking task. We first demonstrate licking deficits and concurrent alterations of spiking activity in ALM of head-fixed mice with unilateral depletion of dopaminergic neurons (i.e., mice injected with 6-OHDA into the medial forebrain bundle). Hemilesioned mice displayed delayed licking initiation, shorter duration of licking bouts, and lateral deviation of tongue protrusions. In parallel with these motor deficits, we observed a reduction in the prevalence of cue responsive neurons and altered preparatory activity. Acute and local blockade of D1 receptors in ALM recapitulated some of the key behavioral and neural deficits observed in hemilesioned mice. Altogether, our data show a direct relationship between cortical D1 receptor modulation, cue-evoked, and preparatory activity in ALM, and licking initiation.
  • 12.

    【2hr】Functional Alteration of Cerebello–Cerebral Coupling in an Experimental Mouse Model of Parkinson’s Disease

    包量

    机译 实验性帕金森氏病小鼠模型中的脑-脑耦合功能改变
    摘要：In Parkinson’s disease, the degeneration of the midbrain dopaminergic neurons is consistently associated with modified metabolic activity in the cerebellum. Here we examined the functional reorganization taking place in the cerebello–cerebral circuit in a murine model of Parkinson’s disease with 6-OHDA lesion of midbrain dopaminergic neurons. Cerebellar optogenetic stimulations evoked similar movements in control and lesioned mice, suggesting a normal coupling of cerebellum to the motor effectors after the lesion. In freely moving animals, the firing rate in the primary motor cortex was decreased after the lesion, while cerebellar nuclei neurons showed an increased firing rate. This increase may result from reduced inhibitory Purkinje cells inputs, since a population of slow and irregular Purkinje cells was observed in the cerebellar hemispheres of lesioned animals. Moreover, cerebellar stimulations generated smaller electrocortical responses in the motor cortex of lesioned animals suggesting a weaker cerebello–cerebral coupling. Overall these results indicate the presence of functional changes in the cerebello–cerebral circuit, but their ability to correct cortical dysfunction may be limited due to functional uncoupling between the cerebellum and cerebral cortex.
  • 13.

    【2hr】Thalamocortical Afferents Innervate the Cortical Subplate much Earlier in Development in Primate than in Rodent

    包量

    机译 丘脑传入神经在灵长类动物中发育的皮层亚板比啮齿动物要早得多。
    摘要：The current model, based on rodent data, proposes that thalamocortical afferents (TCA) innervate the subplate towards the end of cortical neurogenesis. This implies that the laminar identity of cortical neurons is specified by intrinsic instructions rather than information of thalamic origin. In order to determine whether this mechanism is conserved in the primates, we examined the growth of thalamocortical (TCA) and corticofugal afferents in early human and monkey fetal development. In the human, TCA, identified by secretagogin, calbindin, and ROBO1 immunoreactivity, were observed in the internal capsule of the ventral telencephalon as early as 7–7.5 PCW, crossing the pallial/subpallial boundary (PSB) by 8 PCW before the calretinin immunoreactive corticofugal fibers do. Furthermore, TCA were observed to be passing through the intermediate zone and innervating the presubplate of the dorsolateral cortex, and already by 10–12 PCW TCAs were occupying much of the cortex. Observations at equivalent stages in the marmoset confirmed that this pattern is conserved across primates. Therefore, our results demonstrate that in primates, TCAs innervate the cortical presubplate at earlier stages than previously demonstrated by acetylcholinesterase histochemistry, suggesting that pioneer thalamic afferents may contribute to early cortical circuitry that can participate in defining cortical neuron phenotypes.
  • 14.

    【2hr】I See Your Effort: Force-Related BOLD Effects in an Extended Action Execution–Observation Network Involving the Cerebellum

    包量

    机译 我看到了您的努力：涉及小脑的扩展动作执行-观察网络中与力相关的大胆效果
    摘要：Action observation (AO) is crucial for motor planning, imitation learning, and social interaction, but it is not clear whether and how an action execution–observation network (AEON) processes the effort of others engaged in performing actions. In this functional magnetic resonance imaging (fMRI) study, we used a “squeeze ball” task involving different grip forces to investigate whether AEON activation showed similar patterns when executing the task or observing others performing it. Both in action execution, AE (subjects performed the visuomotor task) and action observation, AO (subjects watched a video of the task being performed by someone else), the fMRI signal was detected in cerebral and cerebellar regions. These responses showed various relationships with force mapping onto specific areas of the sensorimotor and cognitive systems. Conjunction analysis of AE and AO was repeated for the “0th” order and linear and nonlinear responses, and revealed multiple AEON nodes remapping the detection of actions, and also effort, of another person onto the observer’s own cerebrocerebellar system. This result implies that the AEON exploits the cerebellum, which is known to process sensorimotor predictions and simulations, performing an internal assessment of forces and integrating information into high-level schemes, providing a crucial substrate for action imitation.
  • 15.

    【2hr】Waves of Maturation and Senescence in Micro-structural MRI Markers of Human Cortical Myelination over the Lifespan

    包量

    机译 在整个寿命中人类皮质髓鞘形成的微结构MRI标记中的成熟波和衰老波。
    摘要：Seminal human brain histology work has demonstrated developmental waves of myelination. Here, using a micro-structural magnetic resonance imaging (MRI) marker linked to myelin, we studied fine-grained age differences to deduce waves of growth, stability, and decline of cortical myelination over the life-cycle. In 484 participants, aged 8–85 years, we fitted smooth growth curves to T1- to T2-weighted ratio in each of 360 regions from one of seven cytoarchitectonic classes. From the first derivatives of these generally inverted-U trajectories, we defined three milestones: the age at peak growth; the age at onset of a stable plateau; and the age at the onset of decline. Age at peak growth had a bimodal distribution comprising an early (pre-pubertal) wave of primary sensory and motor cortices and a later (post-pubertal) wave of association, insular and limbic cortices. Most regions reached stability in the 30-s but there was a second wave reaching stability in the 50-s. Age at onset of decline was also bimodal: in some right hemisphere regions, the curve declined from the 60-s, but in other left hemisphere regions, there was no significant decline from the stable plateau. These results are consistent with regionally heterogeneous waves of intracortical myelinogenesis and age-related demyelination.
  • 16.

    【2hr】Sex Differences Along the Autism Continuum: A Twin Study of Brain Structure

    包量

    机译 自闭症连续性的性别差异：对大脑结构的双重研究
    摘要：Females might possess protective mechanisms regarding autism spectrum disorder (ASD) and require a higher detrimental load, including structural brain alterations, before developing clinically relevant levels of autistic traits. This study examines sex differences in structural brain morphology in autism and autistic traits using a within-twin pair approach. Twin design inherently controls for shared confounders and enables the study of gene-independent neuroanatomical variation. N = 148 twins (62 females) from 49 monozygotic and 25 dizygotic same-sex pairs were included. Participants were distributed along the whole continuum of autism including twin pairs discordant and concordant for clinical ASD. Regional brain volume, surface area, and cortical thickness were computed. Within-twin pair increases in autistic traits were related to decreases in cortical volume and surface area of temporal and frontal regions specifically in female twin pairs, in particular regions involved in social communication, while only two regions were associated with autistic traits in males. The same pattern was detected in the monozygotic twin pairs only. Thus, non-shared environmental factors seem to impact female more than male cerebral architecture associated with autistic traits. Our results are in line with the hypothesis of a female protective effect in autism and highlights the need to study ASD in females separately from males.
  • 17.

    【2hr】Temporally Unconstrained Decoding Reveals Consistent but Time-Varying Stages of Stimulus Processing

    包量

    机译 暂时不受限制的解码揭示了刺激处理的一致但随时间变化的阶段
    摘要：In this article, we propose a method to track trial-specific neural dynamics of stimulus processing and decision making with high temporal precision. By applying this novel method to a perceptual template-matching task, we tracked representational brain states associated with the cascade of neural processing, from early sensory areas to higher order areas that are involved in integration and decision making. We address a major limitation of the traditional decoding approach: that it relies on consistent timing of these processes over trials. Using a TUDA approach, we found that the timing of the cognitive processes involved in perceptual judgments can vary considerably over trials. This revealed that the sequence of processing states was consistent for all subjects and trials, even when the timing of these states varied. Furthermore, we found that the specific timing of states on each trial was related to the quality of performance over trials. Altogether, this work not only highlights the serious pitfalls and misleading interpretations that result from assuming stimulus processing to be synchronous across trials but can also open important avenues to investigate learning and quantify plasticity.
  • 18.

    【2hr】Early Loss of Vision Results in Extensive Reorganization of Plasticity-Related Receptors and Alterations in Hippocampal Function That Extend Through Adulthood

    包量

    机译 早期视力丧失导致可塑性相关受体的广泛重组和成年后海马功能的改变
    摘要：Although by adulthood cortical structures and their capacity for processing sensory information have become established and stabilized, under conditions of cortical injury, or sensory deprivation, rapid reorganization occurs. Little is known as to the impact of this kind of adaptation on cellular processes related to memory encoding. However, imaging studies in humans suggest that following loss or impairment of a sensory modality, not only cortical but also subcortical structures begin to reorganize. It is likely that these processes are supported by neurotransmitter receptors that enable synaptic and cortical plasticity. Here, we explored to what extent the expression of plasticity-related proteins (GABA-A, GABA-B, GluN1, GluN2A, GluN2B) is altered following early vision loss, and whether this impacts on hippocampal function. We observed that in the period of 2–4 months postnatally in CBA/J-mice that experience hereditary postnatal retinal degeneration, systematic changes of GABA-receptor and NMDA-receptor subunit expression occurred that emerged first in the hippocampus and developed later in the cortex, compared to control mice that had normal vision. Changes were accompanied by significant impairments in hippocampal long-term potentiation and hippocampus-dependent learning. These data indicate that during cortical adaptation to early loss of vision, hippocampal information processing is compromised, and this status impacts on the acquisition of spatial representations.
  • 19.

    【2hr】Direct Electrophysiological Correlates of Body Ownership in Human Cerebral Cortex

    包量

    机译 人类大脑皮层中身体所有权的直接电生理相关性
    摘要：Over the past decade, numerous neuroimaging studies based on hemodynamic markers of brain activity have examined the feeling of body ownership using perceptual body-illusions in humans. However, the direct electrophysiological correlates of body ownership at the cortical level remain unexplored. To address this, we studied the rubber hand illusion in 5 patients (3 males and 2 females) implanted with intracranial electrodes measuring cortical surface potentials. Increased high-γ (70–200 Hz) activity, an index of neuronal firing rate, in premotor and intraparietal cortices reflected the feeling of ownership. In both areas, high-γ increases were intimately coupled with the subjective illusion onset and sustained both during and in-between touches. However, intraparietal activity was modulated by tactile stimulation to a higher degree than the premotor cortex through effective connectivity with the hand-somatosensory cortex, which suggests different functional roles. These findings constitute the first intracranial electrophysiological characterization of the rubber hand illusion and extend our understanding of the dynamic mechanisms of body ownership.
  • 20.

    【2hr】The Concurrence of Cortical Surface Area Expansion and White Matter Myelination in Human Brain Development

    包量

    机译 人脑发育中皮质表面积扩大和白质髓鞘形成的并发
    摘要：The human brain undergoes dramatic structural changes during childhood that co-occur with behavioral development. These age-related changes are documented for the brain’s gray matter and white matter. However, their interrelation is largely unknown. In this study, we investigated age-related effects in cortical thickness (CT) and in cortical surface area (SA) as parts of the gray matter volume as well as age effects in T1 relaxation times in the white matter. Data from N = 170 children between the ages of 3 and 7 years contributed to the sample. We found a high spatial overlap of age-related correlations between SA and T1 relaxation times of the corresponding white matter connections, but no such relation between SA and CT. These results indicate that during childhood the developmental expansion of the cortical surface goes hand-in-hand with age-related increase of white matter fiber connections terminating in the cortical surface.
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