The contribution of novel brain imaging techniques to understanding the neurobiology of mental retardation and developmental disabilities

Studying the biological mechanisms underlying mental retardation and developmental disabilities (MR/DD) is a very complex task. This is due to the wide heterogeneity of etiologies and pathways that lead to MR/DD. Breakthroughs in genetics and molecular biology and the development of sophisticated brain imaging techniques during the last decades have facilitated the emergence of a field called Behavioral Neurogenetics. Behavioral Neurogenetics focuses on studying genetic diseases with known etiologies that are manifested by unique cognitive and behavioral phenotypes. In this review, we describe the principles of magnetic resonance imaging (MRI) techniques, including structural MRI, functional MRI, and diffusion tensor imaging (DTI), and how they are implemented in the study of Williams (WS), velocardiofacial (VCFS), and fragile X (FXS) syndromes. From WS we learn that dorsal stream abnormalities can be associated with visuospatial deficits; VCFS is a model for exploring the molecular and brain pathways that lead to psychiatric disorders for which subjects with MR/DD are at increased risk; and finally, findings from multimodal imaging techniques show that aberrant frontal-striatal connections are implicated in the executive function and attentional deficits of subjects with FXS. By deciphering the molecular pathways and brain structure and function associated with cognitive deficits, we will gain a better understanding of the pathophysiology of MR/DD, which will eventually make possible more specific treatments for this population.     

Child Age and Planum Temporale Asymmetry

Investigations using in vivo magnetic resonance (MR) morphometry have shown that left-right asymmetry of the planum temporale (PT) is a structural correlate of hemispheric functional asymmetries in adult humans (e.g., handedness, language representation). Postmortem studies of brains of fetuses and newborns have demonstrated that PT asymmetry becomes visible as early as in the last gestational trimester. The same studies could not clarify when the full (adult) degree of PT asymmetry is reached during brain development and whether this process may be influenced by functional specialization during childhood. We examined 61 neuropsychiatrically normal right-handed children aged 3 to 14 years (mean age +/-SD, 8.4 +/- 2. 7 years; cross-sectional study). MR morphometry showed no change in PT or planum parietale asymmetry with increasing age or brain volume. An unexpected gender difference of unknown significance emerged, with girls displaying a stronger leftward PT asymmetry, independently of age. For the age range studied, the results suggest that functional differentiation follows a structural asymmetry that is already "preset." Copyright 1999 Academic Press.     

Brain Networks in Schizophrenia

Schizophrenia—a severe psychiatric condition characterized by hallucinations, delusions, loss of initiative and cognitive function—is hypothesized to result from abnormal anatomical neural connectivity and a consequent decoupling of the brain’s integrative thought processes. The rise of in vivo neuroimaging techniques has refueled the formulation of dysconnectivity hypotheses, linking schizophrenia to abnormal structural and functional connectivity in the brain at both microscopic and macroscopic levels. Over the past few years, advances in high-field structural and functional neuroimaging techniques have made it increasingly feasible to reconstruct comprehensive maps of the macroscopic neural wiring system of the human brain, know as the connectome. In parallel, advances in network science and graph theory have improved our ability to study the spatial and topological organizational layout of such neural connectivity maps in detail. Combined, the field of neural connectomics has created a novel platform that provides a deeper understanding of the overall organization of brain wiring, its relation to healthy brain function and human cognition, and conversely, how brain disorders such as schizophrenia arise from abnormal brain network wiring and dynamics. In this review we discuss recent findings of connectomic studies in schizophrenia that examine how the disorder relates to disruptions of brain connectivity.     

Imaging the developing brain: what have we learned about cognitive development?

The human brain undergoes significant changes in both its structural architecture and functional organization across the life span. Advances in neuroimaging techniques over the past decade have allowed us to track these changes safely in the human in vivo. We review the imaging literature on the neurobiology of cognitive development, focusing specifically on cognitive task-dependent changes observed in brain physiology and anatomy across childhood and adolescence. The findings suggest that cortical function becomes fine-tuned with development. Brain regions associated with more basic functions such as sensory and motor processes mature first, followed by association areas involved in top-down control of behavior.     

Application of deep transfer learning for automated brain abnormality classification using MR images

Magnetic resonance imaging (MRI) is the most common imaging technique used to detect abnormal brain tumors. Traditionally, MRI images are analyzed manually by radiologists to detect the abnormal conditions in the brain. Manual interpretation of huge volume of images is time consuming and difficult. Hence, computer-based detection helps in accurate and fast diagnosis. In this study, we proposed an approach that uses deep transfer learning to automatically classify normal and abnormal brain MR images. Convolutional neural network (CNN) based ResNet34 model is used as a deep learning model. We have used current deep learning techniques such as data augmentation, optimal learning rate finder and fine-tuning to train the model. The proposed model achieved 5-fold classification accuracy of 100% on 613 MR images. Our developed system is ready to test on huge database and can assist the radiologists in their daily screening of MR images.     

Exploring the neural basis of cognition: multi-modal links between human fMRI and macaque neurophysiology

Although functional magnetic resonance imaging (fMRI) with sophisticated behavioral paradigms has enabled the investigation of increasingly higher-level cognitive functions in humans, these studies seem to lose touch with neurophysiological studies in macaque monkeys. The application of fMRI and other MRI-based techniques to macaque brains allows studies in the two species to be linked. fMRI in human and macaque subjects using equivalent cognitive tasks enables direct comparisons of the functional brain architecture, even for high-level cognitive functions. Combinations of functional or structural MRI and microelectrode techniques provide ways to explore functional brain networks at multiple spatiotemporal scales. These approaches would illuminate the neurophysiological underpinnings of human cognitive functions by integrating human functional neuroimaging with macaque single-unit recordings.     

Basic principles of optical imaging and application to the study of infant development

New optical methods of studying the infant brain have been developed over the last 20 years. These techniques make use of a window of transparency of biological tissue to near infrared light. Using spectrophotometry new insights have been gained into mechanisms of brain damage in newborn infants undergoing intensive care, and non‐invasive functional activation studies have been pioneered in awake infants. Recently topographic mapping of activated cortex has become possible, and preliminary tomographic images of regional oxygenation in infants have been constructed. This is a rapidly changing field which offers exciting possibilities for studying both normal and abnormal child development.     

Diffusion-tensor imaging of cognitive performance

MR methods have for some years been used to assess cognitive performance. Recently, studies have shown that diffusion-tensor imaging (DTI), which provides noninvasive maps of microscopic structural information of oriented tissue in vivo, is finding utility in studies of cognition in the normal and abnormal aging population. These studies suggest that water proton nonrandom, anisotropic diffusion measured by DTI is highly sensitive to otherwise subtle disease processes not easily seen with conventional MRI tissue contrast mechanisms and raises new issues of the role of MR in assessing cognitive potential.     

文盲文字加工的行为和脑机制

文盲作为一个特殊的被试群体,对其的研究一直备受关注。文盲研究最初集中在文盲的口语加工和语音意识等方面。其后比较关注文盲字词的语音和语义加工。随着脑成像技术的发展,对文盲的文字加工脑认知机制进行了研究,探讨脑功能组织是如何受到早期学习的调制,左侧梭状回在字词识别中的作用及其文盲脑功能偏侧化问题。以后此类研究应关注文盲字词识别学习过程中的脑功能变化和文化认知对认知老化的影响等科学问题。     

聋人早期手语经验对脑功能及结构的塑造作用

语言经验对脑功能和结构发展有重要的塑造作用。然而, 目前的相关证据主要来自对脑损伤导致的失语症病人的语言康复、第二语言学习以及针对成人读者进行的语言训练等方面的研究。幼儿时期的早期语言经验对脑结构与功能发展的影响更加重要, 但直接的研究证据却相当缺乏。本文提出一个研究设想, 拟综合使用多种脑成像技术, 系统探讨有早期手语经验和无早期手语经验的聋人个体在脑皮层语言功能的组织及脑结构发育的差异, 包括语言任务中大脑语言区的激活模式, 静息状态下脑功能联结的默认网络特征, 脑皮层灰质密度, 以及神经纤维束发育状况等, 揭示早期语言经验对大脑功能和结构发育的塑造作用。     

Modeling developmental cognitive neuroscience

In the past few years connectionist models have greatly contributed to formulating theories of cognitive development. Some of these models follow the approach of developmental cognitive neuroscience in exploring interactions between brain development and cognitive development by integrating structural change into learning. We describe two classes of these models. The first focuses on experience-dependent structural elaboration within a brain region by adding or deleting units and connections during learning. The second models the gradual integration of different brain areas based on combinations of experience-dependent and maturational factors. These models provide new theories of the mechanisms of cognitive change in various domains and they offer an integrated framework to study normal and abnormal development, and normal and impaired adult processing.     

Development of the social brain during adolescence

Adolescence is usually defined as the period of psychological and social transition between childhood and adulthood. The beginning of adolescence, around the onset of puberty, is characterized by large hormonal and physical changes. The transition from childhood to adulthood is also characterized by psychological changes in terms of identity, self-consciousness, and cognitive flexibility. In the past decade, it has been demonstrated that various regions of the human brain undergo development during adolescence and beyond. Some of the brain regions that undergo particularly protracted development are involved in social cognitive function in adults. In the first section of this paper, I briefly describe evidence for a circumscribed network of brain regions involved in understanding other people. Next, I describe evidence that some of these brain regions undergo structural development during adolescence. Finally, I discuss recent studies that have investigated social cognitive development during adolescence.     

人类大脑结构和功能的性别差异：来自脑成像研究的证据

大脑的性别差异近年来受到了广泛关注。脑成像技术的出现为脑结构和脑功能性别差异的研究开辟了新的道路。借助结构磁共振成像和弥散张量成像等脑结构信息, 以及脑电图、正电子发射断层扫描技术和功能性磁共振成像等脑功能信息, 当前研究主要探讨了脑灰质、脑白质和大脑的基线活动在脑局部区域、脑子系统、全脑连接组三个层次上的性别差异及其在年龄上的发展变化。此外, 为了更好地理解脑性别差异, 当前文章还探讨了脑性别差异研究领域的一些认识误区。有关脑性别差异的研究虽然已经取得了丰富的成果, 但现有的研究结果存在很多分歧, 仍然有深入挖掘的空间。未来应该加强对具有性别特异性的心理疾病脑机制的研究, 关注基因和环境对脑性别差异的交互作用, 并利用脑功能活动动态变化的特性、以及结合多模态的脑成像技术进一步阐明脑性别差异。     

Anatomic Magnetic Resonance Imaging of the Developing Child and Adolescent Brain and Effects of Genetic Variation

Magnetic resonance imaging studies have begun to map effects of genetic variation on trajectories of brain development. Longitudinal studies of children and adolescents demonstrate a general pattern of childhood peaks of gray matter followed by adolescent declines, functional and structural increases in connectivity and integrative processing, and a changing balance between limbic/subcortical and frontal lobe functions, which extends well into young adulthood. Twin studies have demonstrated that genetic factors are responsible for a significant amount of variation in pediatric brain morphometry. Longitudinal studies have shown specific genetic polymorphisms affect rates of cortical changes associated with maturation. Although over-interpretation and premature application of neuroimaging findings for diagnostic purposes remains a risk, converging data from multiple imaging modalities is beginning to elucidate the influences of genetic factors on brain development and implications of maturational changes for cognition, emotion, and behavior.     

In vivo neuroanatomy of Alzheimer's disease: evidence from structural and functional brain imaging

In vivo structural (CT, MRI) and functional (SPECT, PET) brain imaging techniques have been widely used to study the neuroanatomy and neurophysiology of Alzheimer's disease (AD) and to identify definite biological markers of the disease. We used meta-analytic methods to synthesize this literature to determine what neuroanatomical structures best differentiate patients with AD from healthy normal controls. A total of 125 studies published between 1984 and 2000 that included 3543 patients with AD and 1698 normal healthy controls met inclusion criteria. We found that measures of the temporal cortices, including the amygdala, hippocampus, and inferior temporal lobes, along with the anterior cingulate cortex, associated with the largest magnitudes of effects and, hence, could serve as the most useful structures to help clinicians differentiate AD from healthy normal aging.     

青少年抑郁及其自动情绪调节的研究概述

本文旨在梳理近年来国内外青少年抑郁及其自动情绪调节在相关研究领域的研究成果,以进一步促进青少年抑郁的自动情绪调节研究。首先,阐明了青少年脑发展与抑郁之间的关系,并概括了三种青少年抑郁模型。然后,澄清了自动情绪调节的内涵和经典范式,而且从时间和空间方面,总结了青少年抑郁的自动情绪调节的神经机制的相关文献。最后,未来要加强功能连接研究,采用经颅直流电刺激(t DCS)、重复经颅磁刺激(r TMS)技术开展干预研究。     

Mental retardation genes in drosophila: New approaches to understanding and treating developmental brain disorders

Drosophila melanogaster is emerging as a valuable genetic model system for the study of mental retardation (MR). MR genes are remarkably similar between humans and fruit flies. Cognitive behavioral assays can detect reductions in learning and memory in flies with mutations in MR genes. Neuroanatomical methods, including some at single-neuron resolution, are helping to reveal the cellular bases of faulty brain development caused by MR gene mutations. Drosophila fragile X mental retardation 1 (dfmr1) is the fly counterpart of the human gene whose malfunction causes fragile X syndrome. Research on the fly gene is leading the field in molecular mechanisms of the gene product's biological function and in pharmacological rescue of brain and behavioral phenotypes. Future work holds the promise of using genetic pathway analysis and primary neuronal culture methods in Drosophila as tools for drug discovery for a wide range of MR and related disorders.     

囊虫病诊断技术的发展与临床应用

囊虫病是一种由猪囊尾蚴寄生于人体组织内主要引起脑、眼等重要器官或组织损害的常见寄生虫病。目前对其诊断的实验技术研究已发展到高层水平,但被临床应用的并不多。本文从多个方面较全面地分析和回答了出现此现象的原因,并提出了拟解决临床问题的见解与探索思路。     

Plasticity of brain and cognition in older adults

Aging is typically related to changes in brain and cognition, but the aging process is heterogeneous and differs between individuals. Recent research has started investigating the influence of cognitive and physical training on cognitive performance, functional brain activity, and brain structure in old age. The functional relevance of neural changes and the interactions among these changes following interventions is still a matter of debate. Here we selectively review research on structural and functional brain correlates of training-induced performance changes in healthy older adults and present exemplary longitudinal intervention studies sorted by the type of training applied (i.e., strategy-based training, process-specific training, and physical exercise). Although many training studies have been conducted recently, within each task domain, the number of studies that used comparable methods and techniques to assess behavioral and neural changes is limited. We suggest that future studies should include a multimodal approach to enhance the understanding of the relation between different levels of brain changes in aging and those changes that result from training. Investigating inter-individual differences in intervention-induced behavioral and neuronal changes would provide more information about who would benefit from a specific intervention and why. In addition, a more systematic examination of the time course of training-related structural and functional changes would improve the current level of knowledge about how learning is implemented in the brain and facilitate our understanding of contradictory results.     

性别发展的生物学取向研究述评

当前解释性别发展的理论主要有三种取向：生物学取向、社会化取向、认知取向。近年来,生物学取向日益受到关注并得到认可和接受。解释性别发展的生物学取向研究主要分为两种视角,即进化心理学和进化发展心理学、跨物种比较等远端进化解释,以及行为遗传学研究、染色体异常研究、荷尔蒙研究、大脑结构和功能研究等近端解释。本文总结阐述了这些生物学因素对性别发展的具体影响,并指出了进化心理学研究、行为遗传学研究、荷尔蒙研究、大脑结构和功能的脑成像研究在研究内容、研究方法与技术方面存在的问题,并据此展望未来研究的前景。