抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Adaptive control of thought–rational (ACT–R; J. R. Anderson & C. Lebiere, 1998) has evolved into a theory that consists of multiple modules but also explains how these modules are integrated to produce coherent cognition. The perceptual-motor modules, the goal module, and the declarative memory module are presented as examples of specialized systems in ACT–R. These modules are associated with distinct cortical regions. These modules place chunks in buffers where they can be detected by a production system that responds to patterns of information in the buffers. At any point in time, a single production rule is selected to respond to the current pattern. Subsymbolic processes serve to guide the selection of rules to fire as well as the internal operations of some modules. Much of learning involves tuning of these subsymbolic processes. A number of simple and complex empirical examples are described to illustrate how these modules function singly and in concert.

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An Integrated Theory of the Mind.

Hedonic experience is arguably at the heart of what makes us human. In recent neuroimaging studies of the cortical networks that mediate hedonic experience in the human brain, the orbitofrontal cortex has emerged as the strongest candidate for linking food and other types of reward to hedonic experience. The orbitofrontal cortex is among the least understood regions of the human brain, but has been proposed to be involved in sensory integration, in representing the affective value of reinforcers, and in decision making and expectation. Here, the functional neuroanatomy of the human orbitofrontal cortex is described and a new integrated model of its functions proposed, including a possible role in the mediation of hedonic experience.

The human orbitofrontal cortex: linking reward to hedonic experience.

The electrodermal system

Social cognition in humans is distinguished by psychological processes that allow us to make inferences about what is going on inside other people—their intentions, feelings, and thoughts. Some of these processes likely account for aspects of human social behavior that are unique, such as our culture and civilization. Most schemes divide social information processing into those processes that are relatively automatic and driven by the stimuli, versus those that are more deliberative and controlled, and sensitive to context and strategy. These distinctions are reflected in the neural structures that underlie social cognition, where there is a recent wealth of data primarily from functional neuroimaging. Here I provide a broad survey of the key abilities, processes, and ways in which to relate these to data from cognitive neuroscience.

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The Social Brain: Neural Basis of Social Knowledge

Translating advances in neuroscience into benefits for patients with mental illness presents enormous challenges because it involves both the most complex organ, the brain, and its interaction with a similarly complex environment. Dealing with such complexities demands powerful techniques. Computational psychiatry combines multiple levels and types of computation with multiple types of data in an effort to improve understanding, prediction and treatment of mental illness. Computational psychiatry, broadly defined, encompasses two complementary approaches: data driven and theory driven. Data-driven approaches apply machine-learning methods to high-dimensional data to improve classification of disease, predict treatment outcomes or improve treatment selection. These approaches are generally agnostic as to the underlying mechanisms. Theory-driven approaches, in contrast, use models that instantiate prior knowledge of, or explicit hypotheses about, such mechanisms, possibly at multiple levels of analysis and abstraction. We review recent advances in both approaches, with an emphasis on clinical applications, and highlight the utility of combining them.

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Computational psychiatry as a bridge from neuroscience to clinical applications

Reinforcement learning models have provided insight into the functions of dopamine and cortico-basal ganglia-thalamo-cortical circuits. Here the authors review the literature suggesting that these models can also be applied to improving our understanding of dysfunction in this system, particularly in the context of disease. Over the last decade and a half, reinforcement learning models have fostered an increasingly sophisticated understanding of the functions of dopamine and cortico-basal ganglia-thalamo-cortical (CBGTC) circuits. More recently, these models, and the insights that they afford, have started to be used to understand important aspects of several psychiatric and neurological disorders that involve disturbances of the dopaminergic system and CBGTC circuits. We review this approach and its existing and potential applications to Parkinson's disease, Tourette's syndrome, attention-deficit/hyperactivity disorder, addiction, schizophrenia and preclinical animal models used to screen new antipsychotic drugs. The approach's proven explanatory and predictive power bodes well for the continued growth of computational psychiatry and computational neurology.

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From reinforcement learning models to psychiatric and neurological disorders

‡Bechara, Damasio, and coworkers [Bechara, A., Damasio, H., Tranel, D. & Damasio, A. R. (1997) Science 275, 1293–1295] have reported that normal participants decide advantageously before knowing the advantageous strategy in a simple card game designed to mimic real-life decision-making. Bechara et al. have used this result to support their view that nonconscious somatic markers can guide advantageous behavior. By using more sensitive methods, we show that participants have much more knowledge about the game than previously thought. In fact, participants report knowledge of the advantageous strategy more reliably than they behave advantageously. Furthermore, when they behave advantageously, their verbal reports nearly always reveal evidence of quantitative knowledge about the outcomes of the decks that would be sufficient to guide such advantageous behavior. In addition, there is evidence that participants also have access to more qualitative reportable knowledge. These results are compatible with the view that, in this task, both overt behavior and verbal reports reflect sampling from consciously accessible knowledge; there is no need to appeal to nonconscious somatic markers. We also discuss the findings of other studies that similarly suggest alternative interpretations of other evidence previously used to support a role for somatic markers in decision-making.

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A reexamination of the evidence for the somatic marker hypothesis: What participants really know in the Iowa gambling task

Functional imaging studies have reported with remarkable consistency hyperactivity in the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and caudate nucleus of patients with obsessive-compulsive disorder (OCD). These findings have often been interpreted as evidence that abnormalities in cortico-basal ganglia-thalamo-cortical loops involving the OFC and ACC are causally related to OCD. This interpretation remains controversial, however, because such hyperactivity may represent either a cause or a consequence of the symptoms. This article analyzes the evidence for a causal role of these loops in producing OCD in children and adults. The article first reviews the strong evidence for anatomical abnormalities in these loops in patients with OCD. These findings are not sufficient to establish causality, however, because anatomical alterations may themselves be a consequence rather than a cause of the symptoms. The article then reviews three lines of evidence that, despite their own limitations, permit stronger causal inferences: the development of OCD following brain injury, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection, and neurosurgical lesions that attenuate OCD. Converging evidence from these various lines of research supports a causal role for the cortico-basal ganglia-thalamo-cortical loops that involve the OFC and ACC in the pathogenesis of OCD in children and adults.

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The neural bases of obsessive-compulsive disorder in children and adults.

Objective:The purpose of this study was to examine neural activity and connectivity within cortico-striato-thalamo-cortical circuits and to reveal circuit-based neural mechanisms that govern tic generation in Tourette's syndrome. Method:Functional magnetic resonance imaging data were acquired from 13 individuals with Tourette's syndrome and 21 healthy comparison subjects during spontaneous or simulated tics. Independent component analysis with hierarchical partner matching was used to isolate neural activity within functionally distinct regions of cortico-striato-thalamo-cortical circuits. Granger causality was used to investigate causal interactions among these regions. Results:The Tourette's syndrome group exhibited stronger neural activity and interregional causality than healthy comparison subjects throughout all portions of the motor pathway, including the sensorimotor cortex, putamen, pallidum, and substantia nigra. Activity in these areas correlated positively with the severity of tic symptoms. Act...

Tiago V. Maia

Papers

Computational psychiatry as a bridge from neuroscience to clinical applications

From reinforcement learning models to psychiatric and neurological disorders

A reexamination of the evidence for the somatic marker hypothesis: What participants really know in the Iowa gambling task

The neural bases of obsessive-compulsive disorder in children and adults.

The Neural Circuits That Generate Tics in Tourette's Syndrome