Neuroimaging of declarative memory in schizophrenia

The past three decades have seen tremendous growth in our understanding of the cerebral underpinnings of schizophrenia. including the neural correlates of the cognitive impairment seen in this syndrome. In this article we review the role that structural and functional neuroimaging has played in elucidating the cerebral basis for the declarative memory deficits associated with schizophrenia. Memory impairment in schizophrenia appears to involve abnormal connectivity between the prefrontal cortex and three regions important in normal learning and memory: the hippocampus, thalamus, and cerebellum.     

The developmental cognitive neuroscience of functional connectivity

Developmental cognitive neuroscience is a rapidly growing field that examines the relationships between biological development and cognitive ability. In the past decade, there has been ongoing refinement of concepts and methodology related to the study of ‘functional connectivity’ among distributed brain regions believed to underlie cognition and behavioral control. Due to the recent availability of relatively easy-to-use tools for functional connectivity analysis, there has been a sharp upsurge of studies that seek to characterize normal and psychopathologically abnormal brain functional integration. However, relatively few studies have applied functional and effective connectivity analysis techniques to developmental cognitive neuroscience. Functional and effective connectivity analysis methods are ideally suited to advance our understanding of the neural substrates of cognitive development, particularly in understanding how and why changes in the functional ‘wiring’ of neural networks promotes optimal cognitive control throughout development. The purpose of this review is to summarize the central concepts, methods, and findings of functional integration neuroimaging research to discuss key questions in the field of developmental cognitive neuroscience. These ideas will be presented within a context that merges relevant concepts and proposals from different developmental theorists. The review will outline a few general predictions about likely relationships between typical ‘executive’ cognitive maturation and changes in brain network functional integration during adolescence. Although not exhaustive, this conceptual review also will showcase some of recent findings that have emerged to support these predictions.     

Organization, development and function of complex brain networks

Recent research has revealed general principles in the structural and functional organization of complex networks which are shared by various natural, social and technological systems. This review examines these principles as applied to the organization, development and function of complex brain networks. Specifically, we examine the structural properties of large-scale anatomical and functional brain networks and discuss how they might arise in the course of network growth and rewiring. Moreover, we examine the relationship between the structural substrate of neuroanatomy and more dynamic functional and effective connectivity patterns that underlie human cognition. We suggest that network analysis offers new fundamental insights into global and integrative aspects of brain function, including the origin of flexible and coherent cognitive states within the neural architecture.     

Neurophysiology and neuroanatomy of reflexive and volitional saccades: evidence from studies of humans

This review provides a summary of the contributions made by human functional neuroimaging studies to the understanding of neural correlates of saccadic control. The generation of simple visually guided saccades (redirections of gaze to a visual stimulus or pro-saccades) and more complex volitional saccades require similar basic neural circuitry with additional neural regions supporting requisite higher level processes. The saccadic system has been studied extensively in non-human (e.g., single-unit recordings) and human (e.g., lesions and neuroimaging) primates. Considerable knowledge of this system’s functional neuroanatomy makes it useful for investigating models of cognitive control. The network involved in pro-saccade generation (by definition largely exogenously-driven) includes subcortical (striatum, thalamus, superior colliculus, and cerebellar vermis) and cortical (primary visual, extrastriate, and parietal cortices, and frontal and supplementary eye fields) structures. Activation in these regions is also observed during endogenously-driven voluntary saccades (e.g., anti-saccades, ocular motor delayed response or memory saccades, predictive tracking tasks and anticipatory saccades, and saccade sequencing), all of which require complex cognitive processes like inhibition and working memory. These additional requirements are supported by changes in neural activity in basic saccade circuitry and by recruitment of additional neural regions (such as prefrontal and anterior cingulate cortices). Activity in visual cortex is modulated as a function of task demands and may predict the type of saccade to be generated, perhaps via top-down control mechanisms. Neuroimaging studies suggest two foci of activation within FEF - medial and lateral - which may correspond to volitional and reflexive demands, respectively. Future research on saccade control could usefully (i) delineate important anatomical subdivisions that underlie functional differences, (ii) evaluate functional connectivity of anatomical regions supporting saccade generation using methods such as ICA and structural equation modeling, (iii) investigate how context affects behavior and brain activity, and (iv) use multi-modal neuroimaging to maximize spatial and temporal resolution.     

Neurophysiology and neuroanatomy of reflexive and volitional saccades: Evidence from studies of humans

This review provides a summary of the contributions made by human functional neuroimaging studies to the understanding of neural correlates of saccadic control. The generation of simple visually guided saccades (redirections of gaze to a visual stimulus or pro-saccades) and more complex volitional saccades require similar basic neural circuitry with additional neural regions supporting requisite higher level processes. The saccadic system has been studied extensively in non-human (e.g., single-unit recordings) and human (e.g., lesions and neuroimaging) primates. Considerable knowledge of this system’s functional neuroanatomy makes it useful for investigating models of cognitive control. The network involved in pro-saccade generation (by definition largely exogenously-driven) includes subcortical (striatum, thalamus, superior colliculus, and cerebellar vermis) and cortical (primary visual, extrastriate, and parietal cortices, and frontal and supplementary eye fields) structures. Activation in these regions is also observed during endogenously-driven voluntary saccades (e.g., anti-saccades, ocular motor delayed response or memory saccades, predictive tracking tasks and anticipatory saccades, and saccade sequencing), all of which require complex cognitive processes like inhibition and working memory. These additional requirements are supported by changes in neural activity in basic saccade circuitry and by recruitment of additional neural regions (such as prefrontal and anterior cingulate cortices). Activity in visual cortex is modulated as a function of task demands and may predict the type of saccade to be generated, perhaps via top-down control mechanisms. Neuroimaging studies suggest two foci of activation within FEF - medial and lateral - which may correspond to volitional and reflexive demands, respectively. Future research on saccade control could usefully (i) delineate important anatomical subdivisions that underlie functional differences, (ii) evaluate functional connectivity of anatomical regions supporting saccade generation using methods such as ICA and structural equation modeling, (iii) investigate how context affects behavior and brain activity, and (iv) use multi-modal neuroimaging to maximize spatial and temporal resolution.     

Brain network interactions in auditory, visual and linguistic processing

In the paper, we discuss the importance of network interactions between brain regions in mediating performance of sensorimotor and cognitive tasks, including those associated with language processing. Functional neuroimaging, especially PET and fMRI, provide data that are obtained essentially simultaneously from much of the brain, and thus are ideal for enabling one to assess interregional functional interactions. Two ways to use these types of data to assess network interactions are presented. First, using PET, we demonstrate that anterior and posterior perisylvian language areas have stronger functional connectivity during spontaneous narrative production than during other less linguistically demanding production tasks. Second, we show how one can use large-scale neural network modeling to relate neural activity to the hemodynamically-based data generated by fMRI and PET. We review two versions of a model of object processing - one for visual and one for auditory objects. The regions comprising the models include primary and secondary sensory cortex, association cortex in the temporal lobe, and prefrontal cortex. Each model incorporates specific assumptions about how neurons in each of these areas function, and how neurons in the different areas are interconnected with each other. Each model is able to perform a delayed match-to-sample task for simple objects (simple shapes for the visual model; tonal contours for the auditory model). We find that the simulated electrical activities in each region are similar to those observed in nonhuman primates performing analogous tasks, and the absolute values of the simulated integrated synaptic activity in each brain region match human fMRI/PET data. Thus, this type of modeling provides a way to understand the neural bases for the sensorimotor and cognitive tasks of interest.     

Functional Brain Connectivity Using fMRI in Aging and Alzheimer’s Disease

Normal aging and Alzheimer’s disease (AD) cause profound changes in the brain’s structure and function. AD in particular is accompanied by widespread cortical neuronal loss, and loss of connections between brain systems. This degeneration of neural pathways disrupts the functional coherence of brain activation. Recent innovations in brain imaging have detected characteristic disruptions in functional networks. Here we review studies examining changes in functional connectivity, measured through fMRI (functional magnetic resonance imaging), starting with healthy aging and then Alzheimer’s disease. We cover studies that employ the three primary methods to analyze functional connectivity—seed-based, ICA (independent components analysis), and graph theory. At the end we include a brief discussion of other methodologies, such as EEG (electroencephalography), MEG (magnetoencephalography), and PET (positron emission tomography). We also describe multi-modal studies that combine rsfMRI (resting state fMRI) with PET imaging, as well as studies examining the effects of medications. Overall, connectivity and network integrity appear to decrease in healthy aging, but this decrease is accelerated in AD, with specific systems hit hardest, such as the default mode network (DMN). Functional connectivity is a relatively new topic of research, but it holds great promise in revealing how brain network dynamics change across the lifespan and in disease.     

抑郁症的脑功能整合异常-来自有效连接的证据

摘 要：抑郁症是一种常见的精神障碍。从疾病负担看,目前抑郁症已经成为世界第四大疾病,患病人数呈逐年上升的态势,给家庭和社会带来了沉重的负担。以往大多数对抑郁症的研究关注的是单个脑区结构或功能的损伤,而抑郁症通常伴随多脑区、多系统的异常,而不是单一脑区的损伤。近年来研究者开始关注抑郁症多个脑区之间的功能整合。利用功能整合的方法,动态监测抑郁症多个脑区间的相互作用,能进一步揭示抑郁症的脑网络机制。功能整合的研究方法主要包括功能连接和有效连接。有效连接刻画的是两个（或多个）脑区之间相互作用的因果关系,主要包括结构方程模型、动态因果模型、Granger 因果分析、生理心理交互作用等方法。通过对新近研究的梳理,总体而言,抑郁症的认知控制系统(如背外侧前额叶)和边缘系统（如杏仁核）的之间的有效连接减弱,即背外侧前额叶对杏仁核的抑制作用减弱,使得杏仁核对负性刺激的反应增强,出现了情绪加工偏差和认知偏差。认知控制系统和边缘系统之间有效连接的减弱能够解释抑郁症执行认知控制任务和情绪任务中的异常表现。     

Brain network dysfunction in bipolar disorder

Bipolar disorder is a common psychiatric condition with significant associated morbidity and mortality. Despite its significance, the neurophysiology and neuropathology of this illness is incompletely understood. Recent advances in neuroimaging techniques have helped to begin clarifying these areas. Specifically, bipolar disorder appears to arise from abnormalities within discrete brain networks (eg, the anterior limbic network). The expression of the symptoms of bipolar disorder does not appear to result from single, localized brain lesions, but rather are emergent properties of dysfunction of these brain networks. As neuroimaging techniques continue to improve, the underlying neural basis of bipolar disorder will be clarified.     

Neuroplastic Changes Following Social Cognition Training in Schizophrenia: A Systematic Review

Social cognitive impairment is a key feature of schizophrenia and social cognition training (SCT) is a promising tool to address these deficits. Neurobiological dysfunction in schizophrenia has been widely researched, but neuronal changes induced by SCT have been scarcely explored. This review aims to assess the neuroplastic effects of SCT in patients with schizophrenia spectrum disorders. PubMed and Web of Science databases were searched for clinical trials testing the effects of SCT in functional and structural brain measurements of adult patients with schizophrenia or schizoaffective disorders. A total of 11 studies were included: five used fMRI, two used EEG and ERP, one used ERP only, two used MEG and one study used MRI. Data extracting and processing regarding sociodemographic and clinical variables, intervention characteristics, neuroimaging procedures, neuroplastic findings, effect sizes and study quality criteria was completed by two raters. Results indicate a wide range of structural and functional changes in numerous regions and circuits of the social brain, including early perceptual areas, the limbic system and prefrontal regions. Despite the small number of trials currently available, evidence suggests that SCT is associated with neuroplastic changes in the social brain and concomitant improvements in social cognitive performance. There is a lack of extensive knowledge about the neural mechanisms that underlie social cognitive enhancement after treatment, but the reported findings may shed light on the neural substrates of social cognitive impairment in schizophrenia and how improved treatment procedures can be developed and applied.     

The temporal organization of functional brain connectivity is abnormal in schizophrenia but does not correlate with symptomatology

Previous work employing graph theory and nonlinear analysis has found increased spatial and temporal disorder, respectively, of functional brain connectivity in schizophrenia. We present a new method combining graph theory and nonlinear techniques that measures the temporal disorder of functional brain connections. Multichannel electroencephalographic data were windowed and functional networks were reconstructed using the minimum spanning trees of correlation matrices. Using a method based on Shannon entropy, we found elevated connection entropy in gamma activity of patients with schizophrenia; however, gamma connection entropy remained elevated in patients with schizophrenia even after a reduction in symptoms due to treatment with antipsychotics. Our results are consistent with several possibilities: (1) aberrant functional connectivity is epiphenomenal to schizophrenia, (2) aberrant functional connectivity is a central feature but antipsychotics reduce symptoms by an independent mechanism, or (3) connection entropy is not an appropriately sensitive measure of brain abnormalities in schizophrenia.     

Dynamics of alpha oscillations elucidate facial affect recognition in schizophrenia

Impaired facial affect recognition is characteristic of schizophrenia and has been related to impaired social function, but the relevant neural mechanisms have not been fully identified. The present study sought to identify the role of oscillatory alpha activity in that deficit during the process of facial emotion recognition. Neuromagnetic brain activity was monitored while 44 schizophrenia patients and 44 healthy controls viewed 5-s videos showing human faces gradually changing from neutral to fearful or happy expressions or from the neutral face of one poser to the neutral face of another. Recognition performance was determined separately by self-report. Relative to prestimulus baseline, controls exhibited a 10- to 15-Hz power increase prior to full recognition and a 10- to 15-Hz power decrease during the postrecognition phase. These results support recent proposals about the function of alpha-band oscillations in normal stimulus evaluation. The patients failed to show this sequence of alpha power increase and decrease and also showed low 10- to 15-Hz power and high 10- to 15-Hz connectivity during the prestimulus baseline. In light of the proposal that a combination of alpha power increase and functional disconnection facilitates information intake and processing, the finding of an abnormal association of low baseline alpha power and high connectivity in schizophrenia suggests a state of impaired readiness that fosters abnormal dynamics during facial affect recognition.     

Race, Behavior, and the Brain: The Role of Neuroimaging in Understanding Complex Social Behaviors

Recent advances in brain imaging techniques have allowed us to explore the neural basis of complex human behaviors with more precision than was previously possible. As we begin to uncover the neural systems of behaviors that are socially and culturally important, we need to be clear about how to integrate this new approach with our psychological understanding of these behaviors. This article reviews findings about the neural systems involved in processing race group information, in particular the recognition of same-race versus other-race faces and the explicit and implicit evaluation of race groups. Combining the psychological and neural approaches can advance our understanding of these complex human behaviors more rapidly and with more clarity than could be achieved with either approach alone. However, it is inappropriate to assume that the results of neuroimaging studies of a given behavior are more informative than the results of psychological studies of that behavior.     

The Neural Architecture of General Knowledge

Cognitive performance varies widely between individuals and is highly influenced by structural and functional properties of the brain. In the past, neuroscientific research was principally concerned with fluid intelligence, while neglecting its equally important counterpart crystallized intelligence. Crystallized intelligence is defined as the depth and breadth of knowledge and skills that are valued by one's culture. The accumulation of crystallized intelligence is guided by information storage capacities and is likely to be reflected in an individual's level of general knowledge. In spite of the significant role general knowledge plays for everyday life, its neural foundation largely remains unknown. In a large sample of 324 healthy individuals, we used standard magnetic resonance imaging along with functional magnetic resonance imaging and diffusion tensor imaging to examine different estimates of brain volume and brain network connectivity and assessed their predictive power with regard to both general knowledge and fluid intelligence. Our results demonstrate that an individual's level of general knowledge is associated with structural brain network connectivity beyond any confounding effects exerted by age or sex. Moreover, we found fluid intelligence to be best predicted by cortex volume in male subjects and functional network connectivity in female subjects. Combined, these findings potentially indicate different neural architectures for information storage and information processing. © 2019 European Association of Personality Psychology     

Neurodisruption of selective attention: insights and implications

Mechanisms of selective attention are vital for coherent perception and action. Recent advances in cognitive neuroscience have yielded key insights into the relationship between neural mechanisms of attention and eye movements, and the role of frontal and parietal brain regions as sources of attentional control. Here we explore the growing contribution of reversible neurodisruption techniques, including transcranial magnetic stimulation and microelectrode stimulation, to the cognitive neuroscience of spatial attention. These approaches permit unique causal inferences concerning the relationship between neural processes and behaviour, and have revealed fundamental mechanisms of attention in the human and animal brain. We conclude by suggesting that further advances in the neuroscience of attention will be facilitated by the combination of neurodisruption techniques with established neuroimaging methods.     

数字加工的脑功能成像研究进展及其皮层定位

数字加工是人类最重要的认知功能之一。当前的脑功能成像研究有助于对数字加工与皮层之间的联系进行更精确的定位。基于对上世纪80年代来有关数字加工脑功能成像研究的主要成果的回顾,尤其是一些重要区域,如双侧顶叶与前额叶等在数字加工中的地位与作用,以及不同脑区之间的关系进行了探讨,并对一个广泛运用的数字加工神经机制模型进行了简要评述。在此基础上,对数字加工的皮层定位问题进行了简要的总结。     

Connecting the Dots: A Review of Resting Connectivity MRI Studies in Attention-Deficit/Hyperactivity Disorder

Psychopathology is increasingly viewed from a circuit perspective in which a disorder stems not from circumscribed anomalies in discrete brain regions, but rather from impairments in distributed neural networks. This focus on neural circuitry has rendered resting state functional connectivity MRI (rs-fcMRI) an increasingly important role in the elucidation of pathophysiology including attention-deficit/hyperactivity disorder (ADHD). Unlike many other MRI techniques that focus on the properties of discrete brain regions, rs-fcMRI measures the coherence of neural activity across anatomically disparate brain regions, examining the connectivity and organization of neural circuits. In this review, we explore the methods available to investigators using rs-fcMRI techniques, including a discussion of their relative merits and limitations. We then review findings from extant rs-fcMRI studies of ADHD focusing on neural circuits implicated in the disorder, especially the default mode network, cognitive control network, and cortico-striato-thalamo-cortical loops. We conclude by suggesting future directions that may help advance subsequent rs-fcMRI research in ADHD.     

Development of the Brain’s Functional Network Architecture

A full understanding of the development of the brain’s functional network architecture requires not only an understanding of developmental changes in neural processing in individual brain regions but also an understanding of changes in inter-regional interactions. Resting state functional connectivity MRI (rs-fcMRI) is increasingly being used to study functional interactions between brain regions in both adults and children. We briefly review methods used to study functional interactions and networks with rs-fcMRI and how these methods have been used to define developmental changes in network functional connectivity. The developmental rs-fcMRI studies to date have found two general properties. First, regional interactions change from being predominately anatomically local in children to interactions spanning longer cortical distances in young adults. Second, this developmental change in functional connectivity occurs, in general, via mechanisms of segregation of local regions and integration of distant regions into disparate subnetworks.     

The development of gyrification in childhood and adolescence

Gyrification is the process by which the brain undergoes changes in surface morphology to create sulcal and gyral regions. The period of greatest development of brain gyrification is during the third trimester of pregnancy, a period of time in which the brain undergoes considerable growth. Little is known about changes in gyrification during childhood and adolescence, although considering the changes in gray matter volume and thickness during this time period, it is conceivable that alterations in the brain surface morphology could also occur during this period of development. The formation of gyri and sulci in the brain allows for compact wiring that promotes and enhances efficient neural processing. If cerebral function and form are linked through the organization of neural connectivity, then alterations in neural connectivity, i.e., synaptic pruning, may also alter the gyral and sulcal patterns of the brain. This paper reviews developmental theories of gyrification, computational techniques for measuring gyrification, and the potential interaction between gyrification and neuronal connectivity. We also present recent findings involving alterations in gyrification during childhood and adolescence.     

The Implications of Brain Connectivity in the Neuropsychology of Autism

Autism is a neurodevelopmental disorder that has been associated with atypical brain functioning. Functional connectivity MRI (fcMRI) studies examining neural networks in autism have seen an exponential rise over the last decade. Such investigations have led to the characterization of autism as a distributed neural systems disorder. Studies have found widespread cortical underconnectivity, local overconnectivity, and mixed results suggesting disrupted brain connectivity as a potential neural signature of autism. In this review, we summarize the findings of previous fcMRI studies in autism with a detailed examination of their methodology, in order to better understand its potential and to delineate the pitfalls. We also address how a multimodal neuroimaging approach (incorporating different measures of brain connectivity) may help characterize the complex neurobiology of autism at a global level. Finally, we also address the potential of neuroimaging-based markers in assisting neuropsychological assessment of autism. The quest for a neural marker for autism is still ongoing, yet new findings suggest that aberrant brain connectivity may be a promising candidate.