Neural dynamics of autistic behaviors: cognitive, emotional, and timing substrates

What brain mechanisms underlie autism, and how do they give rise to autistic behavioral symptoms? This article describes a neural model, called the Imbalanced Spectrally Timed Adaptive Resonance Theory (iSTART) model, that proposes how cognitive, emotional, timing, and motor processes that involve brain regions such as the prefrontal and temporal cortex, amygdala, hippocampus, and cerebellum may interact to create and perpetuate autistic symptoms. These model processes were originally developed to explain data concerning how the brain controls normal behaviors. The iSTART model shows how autistic behavioral symptoms may arise from prescribed breakdowns in these brain processes, notably a combination of underaroused emotional depression in the amygdala and related affective brain regions, learning of hyperspecific recognition categories in the temporal and prefrontal cortices, and breakdowns of adaptively timed attentional and motor circuits in the hippocampal system and cerebellum. The model clarifies how malfunctions in a subset of these mechanisms can, through a systemwide vicious circle of environmentally mediated feedback, cause and maintain problems with them all.     

Mouse vocal communication system: Are ultrasounds learned or innate?

Mouse ultrasonic vocalizations (USVs) are often used as behavioral readouts of internal states, to measure effects of social and pharmacological manipulations, and for behavioral phenotyping of mouse models for neuropsychiatric and neurodegenerative disorders. However, little is known about the neurobiological mechanisms of rodent USV production. Here we discuss the available data to assess whether male mouse song behavior and the supporting brain circuits resemble those of known vocal non-learning or vocal learning species. Recent neurobiology studies have demonstrated that the mouse USV brain system includes motor cortex and striatal regions, and that the vocal motor cortex sends a direct sparse projection to the brainstem vocal motor nucleus ambiguous, a projection previously thought be unique to humans among mammals. Recent behavioral studies have reported opposing conclusions on mouse vocal plasticity, including vocal ontogeny changes in USVs over early development that might not be explained by innate maturation processes, evidence for and against a role for auditory feedback in developing and maintaining normal mouse USVs, and evidence for and against limited vocal imitation of song pitch. To reconcile these findings, we suggest that the trait of vocal learning may not be dichotomous but encompass a broad spectrum of behavioral and neural traits we call the continuum hypothesis, and that mice possess some of the traits associated with a capacity for limited vocal learning.     

基于非侵入性脑刺激的认知增强：方法、伦理和应用

作为人类追求卓越的方式之一,基于非侵入性脑刺激的认知增强成为众多学科和公众关注的问题。首先阐述了非侵入性脑刺激的两种主要技术手段(经颅磁刺激和经颅直流刺激)的技术原理及其在提升健康个体认知功能上的应用,并分析了这两种技术可能带来的安全、自主选择、公平等伦理问题,最后总结了该认知增强技术在体育和军事等两个具体领域的应用。未来可进一步提高技术手段的深部脑区刺激能力及该增强技术的持续和真实效果。     

抑郁症的脑结构与功能异常:来自静息态下多模态脑影像的研究证据

传统单一模态、单一分析方法在揭示抑郁症脑机制上存在较多局限;而新近多种模态、多种分析方法的结合可在一定程度上较好地促进对抑郁症脑功能和结构的全面探索、挖掘,可以更加有效地运用和实施于早期辅助诊断、干预治疗当中。因此,本文首先简要介绍了多种模态下的脑影像指标及其分析技术,而后分别从结构及功能神经影像数据融合等方面,概述了抑郁症脑结构和功能的研究现状,发现抑郁症患者存在诸多脑区及相关环路结构及功能的异常。同时,通过对抑郁症多模态研究现状的梳理和总结,结合我们已有的相关前期研究工作,对未来抑郁症等情感障碍的进一步研究工作提出了一些思考和展望。     

Motor Cortex Plasticity in Children With Spastic Cerebral Palsy: A Systematic Review

A review of the literature was performed to answer the following questions: Does motor cortex excitability correlate with motor function? Do motor cortex excitability and cortex activation change after a rehabilitation program that results in improvements in motor outcomes? Can the 10–20 electroencephalography (EEG) system be used to locate the primary motor cortex when employing transcranial direct current stimulation? Is there a bihemispheric imbalance in individuals with cerebral palsy similar to what is observed in stroke survivors? the authors found there is an adaptation in the geometry of motor areas and the cortical representation of movement is variable following a brain lesion. The 10–20 EEG system may not be the best option for locating the primary motor cortex and positioning electrodes for noninvasive brain stimulation in children with cerebral palsy.     

Working memory improvement with non-invasive brain stimulation of the dorsolateral prefrontal cortex: A systematic review and meta-analysis

Recent studies have used non-invasive brain stimulation (NIBS) techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), to increase dorsolateral prefrontal cortex (DLPFC) activity and, consequently, working memory (WM) performance. However, such experiments have yielded mixed results, possibly due to small sample sizes and heterogeneity of outcomes. Therefore, our aim was to perform a systematic review and meta-analyses on NIBS studies assessing the n-back task, which is a reliable index for WM. From the first data available to February 2013, we looked for sham-controlled, randomized studies that used NIBS over the DLPFC using the n-back task in PubMed/MEDLINE and other databases. Twelve studies (describing 33 experiments) matched our eligibility criteria. Active vs. sham NIBS was significantly associated with faster response times (RTs), higher percentage of correct responses and lower percentage of error responses. However, meta-regressions showed that tDCS (vs. rTMS) presented only an improvement in RT, and not in accuracy. This could have occurred in part because almost all tDCS studies employed a crossover design, possibly due to the reliable tDCS blinding. Study design was also associated with no improvement in correct responses in the active vs. sham groups. To conclude, rTMS of the DLPFC significantly improved all measures of WM performance whereas tDCS significantly improved RT, but not the percentage of correct and error responses. Mechanistic insights on the role of DLPFC in WM are further discussed, as well as how NIBS techniques could be used in neuropsychiatric samples presenting WM deficits, such as major depression, dementia and schizophrenia.     

空间导航的脑网络基础和调控机制

空间导航在生活中时刻发生,空间能力衰退是阿尔兹海默症的重要早期表现。早期关于空间导航神经机制的研究主要关注单个脑区的特异性功能,但这些脑区如何交互以整合不同模态的信息支持复杂导航行为尚不清楚。脑成像技术、脑网络建模方法和神经调控手段的发展,为在脑网络水平理解人类空间导航的认知神经机制提供了重要研究手段。本研究试图融合空间导航认知神经机制研究的最新进展,借助脑网络建模、大数据分析、微电流刺激等前沿研究手段,研究空间导航脑网络的关键拓扑属性特征(如模块化、核心节点等),探寻该功能特异性神经网络的重要影响因素和调控机制,并构建空间导航的脑网络理论模型。研究成果将有利于理解人类复杂导航行为的脑网络基础,为阿尔兹海默症等相关认知障碍脑疾病的筛查和诊断提供重要参考。     

Improving executive function using transcranial infrared laser stimulation

Transcranial infrared laser stimulation is a new non‐invasive form of low‐level light therapy that may have a wide range of neuropsychological applications. It entails using low‐power and high‐energy‐density infrared light from lasers to increase metabolic energy. Preclinical work showed that this intervention can increase cortical metabolic energy, thereby improving frontal cortex‐based memory function in rats. Barrett and Gonzalez‐Lima (2013, Neuroscience, 230, 13) discovered that transcranial laser stimulation can enhance sustained attention and short‐term memory in humans. We extend this line of work to executive function. Specifically, we ask whether transcranial laser stimulation enhances performance in the Wisconsin Card Sorting Task that is considered the gold standard of executive function and is compromised in normal ageing and a number of neuropsychological disorders. We used a laser of a specific wavelength (1,064 nm) that photostimulates cytochrome oxidase – the enzyme catalysing oxygen consumption for metabolic energy production. Increased cytochrome oxidase activity is considered the primary mechanism of action of this intervention. Participants who received laser treatment made fewer errors and showed improved set‐shifting ability relative to placebo controls. These results suggest that transcranial laser stimulation improves executive function and may have exciting potential for treating or preventing deficits resulting from neuropsychological disorders or normal ageing.     

Transcranial magnetic stimulation as a tool for cognitive studies

Transcranial Magnetic Stimulation (TMS) is a tool for the non-invasive stimulation of the human brain. It allows the activation of arbitrary sites of the superficial cortex and, combined with other brain-imaging techniques such as EEG, PET, and fMRI, it can be used to evaluate cortical excitability and connectivity. This is of major importance in, for example, the study of cognitive processes such as language, learning, memory and self-representation, which are thought to be represented in multiple brain areas. The mechanisms of action of TMS are known on a basic level, but its effect on the activation state of brain tissue is still poorly understood. Clinical applications of TMS have also been proposed and guidelines for its safe use drafted.     

Dorsolateral prefrontal cortex mediates working memory processes in motor skill learning

Neuroimaging studies have shown that the dorsolateral prefrontal cortex (DLPFC) is recruited during motor skill learning, which suggests the involvement of the DLPFC in working memory (WM) processes, such as selection and integration of motor representations temporarily stored in WM. However, direct evidence linking activation of the DLPFC to WM storage and manipulation during motor skill learning in real-time is rare. In this study, we conducted two experiments to investigate the causal role of DLPFC activity in WM storage and manipulation during motor skill learning under low and high WM-demand conditions. Participants received continuous theta burst stimulation (cTBS) and sham stimulation (crossover design) over the left DLPFC (experiment 1) or right DLPFC (experiment 2). Before and after stimulation, participants in both experiments performed a sequential finger-tapping (SFT) task containing repeated sequence (low-WM demand) and non-repeated sequence (high-WM demand) conditions which are used to study WM processes. The number of correct sequences (NoCS) and reproduction error rate were analyzed. Learning gains in NoCS improved significantly with the practice for both sequence types in the presence of either stimulation type. Compared to sham stimulation, cTBS over the left DLPFC resulted in significantly reduced learning gains in NoCS for non-repeated sequences. These results suggest that the left DLPFC contributes to WM manipulation during motor skill learning.     

The Role of the Cerebellum in Cognition and Emotion: Personal Reflections Since 1982 on the Dysmetria of Thought Hypothesis,and Its Historical Evolution from Theory to Therapy

The cognitive neuroscience of the cerebellum is now an established multidisciplinary field of investigation. This essay traces the historical evolution of this line of inquiry from an emerging field to its current status, with personal reflections over almost three decades on this journey of discovery. It pays tribute to early investigators who recognized the wider role of the cerebellum beyond motor control, traces the origins of new terms and concepts including the dysmetria of thought theory, the universal cerebellar transform, and the cerebellar cognitive affective syndrome, and places these developments within the broader context of the scientific efforts of a growing community of cerebellar cognitive neuroscientists. This account considers the converging evidence from theoretical, anatomical, physiological, clinical, and functional neuroimaging approaches that have resulted in the transition from recognizing the cerebellar incorporation into the distributed neural circuits subserving cognition and emotion, to a hopeful new era of treatment of neurocognitive and neuropsychiatric manifestations of cerebellar diseases, and to cerebellar-based interventions for psychiatric disorders.     

左侧背外侧前额叶在程序性运动学习中的作用

程序性运动学习包括序列学习和随机学习。神经影像学研究表明背外侧前额叶皮层(DLPFC)和初级运动皮层(M1)在程序性运动学习中发挥重要作用, 但DLPFC和M1之间的联通性及其与不同程序性运动学习的关系尚不明确。本研究采用连续反应时间任务, 结合经颅磁刺激(TMS)方法, 探讨左侧DLPFC到M1的联通性在不同程序性运动学习中的差异。实验1采用两连发TMS探测DLPFC到M1的最佳投射时间点; 实验2, 被试分为2组, 分别进行序列学习和随机学习, 在学习前、后采集行为学数据, 以及M1的运动诱发电位和DLPFC-M1联通性的电生理学数据。行为学结果发现序列学习组的学习效果更佳; 电生理学结果发现, 两组被试学习前、后M1的运动诱发电位均未发生改变; 在最佳时间投射点、适当刺激强度下, 序列学习组DLPFC-M1联通性发生改变, 且与学习成绩相关, 而随机学习组没有改变。结果说明DLPFC到M1的联通性增强可能是序列学习成绩更佳的重要原因, 这一结果从电生理角度为DLPFC在运动学习中的作用提供了重要证据。     

Sensori‐motor experience leads to changes in visual processing in the developing brain

Since Broca’s studies on language processing, cortical functional specialization has been considered to be integral to efficient neural processing. A fundamental question in cognitive neuroscience concerns the type of learning that is required for functional specialization to develop. To address this issue with respect to the development of neural specialization for letters, we used functional magnetic resonance imaging (fMRI) to compare brain activation patterns in pre‐school children before and after different letter‐learning conditions: a sensori‐motor group practised printing letters during the learning phase, while the control group practised visual recognition. Results demonstrated an overall left‐hemisphere bias for processing letters in these pre‐literate participants, but, more interestingly, showed enhanced blood oxygen‐level‐dependent activation in the visual association cortex during letter perception only after sensori‐motor (printing) learning. It is concluded that sensori‐motor experience augments processing in the visual system of pre‐school children. The change of activation in these neural circuits provides important evidence that ‘learning‐by‐doing’ can lay the foundation for, and potentially strengthen, the neural systems used for visual letter recognition.     

Application of pharmacological fMRI to developmental psychiatric disorders

Functional magnetic resonance imaging of neural activity induced by pharmacological stimulation (phMRI) is a promising technique for revealing pathophysiology and etiology of developmental psychiatric disorders. Recent investigations of the dopaminergic system have made possible the use of phMRI as a non‐invasive assay for neurotransmitter function. This paper explores applications of phMRI for identification of neurophysiological trait‐dependent and clinical state‐dependent mechanisms that can define biologically valid diagnostic criteria for developmental psychiatric disorders. Further, applications of phMRI for investigations of neurochemical changes induced by long‐term drug exposure, alternative therapies and normal brain maturation are discussed. The paper ends by highlighting methodological challenges posed by experimental control of pharmacological stimulation that is essential for valid interpretation of phMRI results.     

Does transcranial direct current stimulation during writing alleviate upper limb freezing in people with Parkinson’s disease? A pilot study

Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) can boost motor performance in Parkinson’s disease (PD) when it is applied at rest. However, the potential supplementary therapeutic effect of the concurrent application of tDCS during the training of motor tasks is largely unknown. The present study examined the effects of tDCS on upper limb motor blocks during a freezing-provoking writing task (the funnel task) requiring up- and down-stroke movements at alternating amplitudes. Ten PD patients and 10 age-matched controls underwent two sessions of writing combined with 20 min of anodal or sham tDCS on the left M1 in a randomized cross-over design. The primary outcome was the number of upper limb freezing episodes during five trials of the funnel task on a touch-sensitive tablet. PD patients showed a significant reduction in freezing episodes during tDCS compared to sham. No effects of tDCS were found for the amplitude, variability and speed of the strokes outside the freezing episodes. However, patients who reported freezing episodes in daily life (N = 6) showed a beneficial effect of tDCS on stroke characteristics. These results indicate a subgroup-dependent variability in response to non-invasive brain stimulation applied during the performance of motor tasks in PD. This warrants future studies to examine tDCS as an adjuvant tool for training programs aimed to reduce motor deficits related to freezing.     

不同感觉功能对抑郁的影响及其神经机制

大脑通过视觉、听觉、嗅觉、味觉和触觉等感官通道接收来自外界的信息。不同感觉功能受损涉及抑郁发生的中枢机制,而基于不同感官通道进行适当刺激以及多感官联合干预也可能发挥显著的抑郁治疗作用。笔者以症状-脑区-机制-治疗为逻辑主线,首次系统梳理了五种主要感觉障碍人群的抑郁临床症状、抑郁神经机制以及基于感觉刺激的抗抑郁治疗。结果表明,不同感觉功能障碍对抑郁相关神经机制的影响可能表征了不同的抑郁病理,涉及神经元电活动(某些神经元放电和神经环路激活等)和神经生化改变(神经可塑性和神经发生、炎症免疫和HPA轴、神经激素和神经递质等),且主要发生在边缘系统及其附近脑区,涉及岛叶、颞叶、额叶等。因此,未来研究可聚焦于机体对不同感觉信息的提取,这将为人类抑郁的病因和治疗提供新的研究视角。     

Role of norepinephrine in the pathophysiology of neuropsychiatric disorders

The concatenation of convergent lines of evidence from basic to clinical research continues to reveal that norepinephrine (NE) is a crucial regulator of a myriad of behaviors ranging from stress response to memory formation. Furthermore, many neuropsychiatric disorders involve neurocircuitry that is directly modulated by NE. This report summarizes the physiological roles of NE, as well as the main findings implicating a role for NE system dysfunction in mood and anxiety disorders, posttraumatic stress disorder, attention-deficit/hyperactivity disorder, and Alzheimer's disease. In each of these disorders, there appears to be a complex dysregulation of NE function, with changes in locus ceruleus firing, NE availability, and both pre- and postsynaptic receptor regulation. Many symptoms of these disorders are attributable to abnormalities within distributed neural circuits regulated by NE. Appreciation of NE's role in modulating the neural circuitry mediating cognition and affect should help elucidate the pathophysiology of a variety of neuropsychiatric disorders and the development of novel treatments.     

口香糖咀嚼的脑机制

该研究采用功能性核磁共振(fMRI)技术,考察了咀嚼口香糖时大脑的活动。结果发现,与休息相比,口香糖咀嚼显著增加了脑的BOLD(血氧依赖水平)信号;与口香糖咀嚼相关的脑区有初级运动皮层,右侧后顶叶,双侧小脑,以及双侧前额叶的部分区域。ROI(感兴趣区域)分析发现,咀嚼时不同脑区的对血氧含量有不同程度的提高,其中中央前回的血氧依赖水平信号变化量高达46.3%,说明口香糖咀嚼增强了某些脑区的活动,显著提高了这些脑区的血流和供氧水平。     

The Effects of Brain Lateralization on Motor Control and Adaptation

ABSTRACT

Lateralization of mechanisms mediating functions such as language and perception is widely accepted as a fundamental feature of neural organization. Recent research has revealed that a similar organization exists for the control of motor actions, in that each brain hemisphere contributes unique control mechanisms to the movements of each arm. The authors review present research that addresses the nature of the control mechanisms that are lateralized to each hemisphere and how they impact motor adaptation and learning. In general, the studies suggest an enhanced role for the left hemisphere during adaptation, and the learning of new sequences and skills. The authors suggest that this specialization emerges from a left hemisphere specialization for predictive control—the ability to effectively plan and coordinate motor actions, possibly by optimizing certain cost functions. In contrast, right hemisphere circuits appear to be important for updating ongoing actions and stopping at a goal position, through modulation of sensorimotor stabilization mechanisms such as reflexes. The authors also propose that each brain hemisphere contributes its mechanism to the control of both arms. They also discuss the potential advantages of such a lateralized control system.     

言语想象的神经机制

言语想象不仅在大脑预处理机制方面起到重要的作用,还是目前脑机接口领域研究的热点。与正常言语产生过程相比,言语想象的理论模型、激活脑区、神经传导路径等均与其有较多相似之处。而言语障碍群体的言语想象、想象有意义的词语和句子时的脑神经机制与正常言语产生存在差异。鉴于人类言语系统的复杂性,言语想象的神经机制研究还面临一系列挑战,未来研究可在言语想象质量评价工具及神经解码范式、脑控制回路、激活通路、言语障碍群体的言语想象机制、词语和句子想象的脑神经信号等方面进一步探索,为有效提高脑机接口的识别率提供依据,为言语障碍群体的沟通提供便利。