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

Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

Information processing in the cerebral cortex involves interactions among distributed areas. Anatomical connectivity suggests that certain areas form local hierarchical relations such as within the visual system. Other connectivity patterns, particularly among association areas, suggest the presence of large-scale circuits without clear hierarchical relations. In this study the organization of networks in the human cerebrum was explored using resting-state functional connectivity MRI. Data from 1,000 subjects were registered using surface-based alignment. A clustering approach was employed to identify and replicate networks of functionally coupled regions across the cerebral cortex. The results revealed local networks confined to sensory and motor cortices as well as distributed networks of association regions. Within the sensory and motor cortices, functional connectivity followed topographic representations across adjacent areas. In association cortex, the connectivity patterns often showed abrupt transitions between network boundaries. Focused analyses were performed to better understand properties of network connectivity. A canonical sensory-motor pathway involving primary visual area, putative middle temporal area complex (MT+), lateral intraparietal area, and frontal eye field was analyzed to explore how interactions might arise within and between networks. Results showed that adjacent regions of the MT+ complex demonstrate differential connectivity consistent with a hierarchical pathway that spans networks. The functional connectivity of parietal and prefrontal association cortices was next explored. Distinct connectivity profiles of neighboring regions suggest they participate in distributed networks that, while showing evidence for interactions, are embedded within largely parallel, interdigitated circuits. We conclude by discussing the organization of these large-scale cerebral networks in relation to monkey anatomy and their potential evolutionary expansion in humans to support cognition.

The organization of the human cerebral cortex estimated by intrinsic functional connectivity

Resting state functional connectivity reveals intrinsic, spontaneous networks that elucidate the functional architecture of the human brain. However, valid statistical analysis used to identify such networks must address sources of noise in order to avoid possible confounds such as spurious correlations based on non-neuronal sources. We have developed a functional connectivity toolbox Conn (www.nitrc.org/projects/conn) that implements the component-based noise correction method (CompCor) strategy for physiological and other noise source reduction, additional removal of movement, and temporal covariates, temporal filtering and windowing of the residual blood oxygen level-dependent (BOLD) contrast signal, first-level estimation of multiple standard functional connectivity magnetic resonance imaging (fcMRI) measures, and second-level random-effect analysis for resting state as well as task-related data. Compared to methods that rely on global signal regression, the CompCor noise reduction method all...

Conn: A Functional Connectivity Toolbox for Correlated and Anticorrelated Brain Networks

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is characterized by dopamine depletion in the striatum. One consistent pathophysiological hallmark of PD is an increase in spontaneous oscillatory activity in the basal ganglia thalamocortical networks. We evaluated these effects using resting state functional connectivity MRI (fcMRI) in mild to moderate stage Parkinson’s patients on and off L-DOPA and age-matched controls using six different striatal seed regions. We observed an overall increase in the strength of cortico-striatal functional connectivity in PD patients off L-DOPA compared to controls. This enhanced connectivity was down-regulated by L-DOPA as shown by an overall decrease in connectivity strength, particularly within motor cortical regions. We also performed a frequency content analysis of the BOLD signal time course extracted from the six striatal seed regions. PD off L-DOPA exhibited increased power in the frequency band 0.02 – 0.05 Hz compared to controls and to PD on L-DOPA. The L-DOPA associated decrease in the power of this frequency range modulated the L-DOPA associated decrease in connectivity strength between striatal seeds and the thalamus. In addition, the L-DOPA associated decrease in power in this frequency band also correlated with the L-DOPA associated improvement in cognitive performance. Our results demonstrate that PD and L-DOPA modulate striatal resting state BOLD signal oscillations and corticostriatal network coherence.

/pdf/altered-resting-state-cortico-striatal-connectivity-in-mild-2uxe5t3ybf.pdf

Altered Resting State Cortico-Striatal Connectivity in Mild to Moderate Stage Parkinson's Disease

Although sensorimotor adaptation is typically thought of as an implicit form of learning, it has been shown that participants who gain explicit awareness of the nature of the perturbation during adaptation exhibit more learning than those who do not With rare exceptions, however, explicit awareness is typically polled at the end of the study Here, we provided participants with either an explicit spatial strategy or no instructions before learning Early in learning, explicit instructions greatly reduced movement errors but also resulted in increased trial-to-trial variability and longer reaction times Late in adaptation, performance was indistinguishable between the explicit and implicit groups, but the mechanisms underlying performance improvements remained fundamentally different, as revealed by catch trials The progression of implicit recalibration in the explicit group was modulated by the use of an explicit strategy: these participants showed a lower level of recalibration as well as decreased aftereffects This phenomenon may be due to the reduced magnitude of errors made to the target during adaptation or inhibition of implicit learning mechanisms by explicit processing

https://www.physiology.org/doi/pdf/10.1152/jn.00002.2011

A spatial explicit strategy reduces error but interferes with sensorimotor adaptation

Studies have suggested that cognitive processes such as working memory and temporal control contribute to motor sequence learning. These processes engage overlapping brain regions with sequence learning, but concrete evidence has been lacking. In this study, we determined whether limits in visuospatial working memory capacity and temporal control abilities affect the temporal organization of explicitly acquired motor sequences. Participants performed an explicit sequence learning task, a visuospatial working memory task, and a continuous tapping timing task. We found that visuospatial working memory capacity, but not the CV from the timing task, correlated with the rate of motor sequence learning and the chunking pattern observed in the learned sequence. These results show that individual differences in short-term visuospatial working memory capacity, but not temporal control, predict the temporal structure of explicitly acquired motor sequences.

https://www.physiology.org/doi/pdf/10.1152/jn.00006.2009

Visuospatial Working Memory Capacity Predicts the Organization of Acquired Explicit Motor Sequences

The purpose of this study was to determine whether elderly adults exhibit deficits in the performance of multi-joint movements. Two groups of subjects (mean ages, 68.9 and 30.1 years, respectively) participated in this experiment. Subjects performed planar arm pointing movements to various targets. One target could be achieved via elbow extension only, while the remaining 3 required both elbow extension and horizontal shoulder flexion, thus requiring coordination at the 2 joints. In contrast to the young adults, the elderly adults produced movements that became less smooth and less accurate with increasing shoulder joint contribution. The results imply a selective coordination deficit for the elderly adults. In addition, the elderly adults coactivated opposing muscles more than the young adults for the single-joint movement. However, the elderly adults reduced coactivation at both joints for the 2-joint actions, while the young adults did not. These data suggest a relationship between high coactivation levels and good performance for elderly adults. It may be more difficult for the elderly to implement high coactivation levels for multi-joint movements because of the increased energy costs and complexity of planning required in comparison to the single joint actions. Thus, to achieve motor performance, elderly persons appear to use coactivation in a manner that is fundamentally different than young adults.

Changes in multi-joint performance with age.

Researchers have begun to delineate the precise nature and neural correlates of the cognitive processes that contribute to motor skill learning. The authors review recent work from their laboratory designed to further understand the neurocognitive mechanisms of skill acquisition. The authors have demonstrated an important role for spatial working memory in 2 different types of motor skill learning, sensorimotor adaptation and motor sequence learning. They have shown that individual differences in spatial working memory capacity predict the rate of motor learning for sensorimotor adaptation and motor sequence learning, and have also reported neural overlap between a spatial working memory task and the early, but not late, stages of adaptation, particularly in the right dorsolateral prefrontal cortex and bilateral inferior parietal lobules. The authors propose that spatial working memory is relied on for processing motor error information to update motor control for subsequent actions. Further, the...

Rachael D. Seidler

Papers

Altered Resting State Cortico-Striatal Connectivity in Mild to Moderate Stage Parkinson's Disease

A spatial explicit strategy reduces error but interferes with sensorimotor adaptation

Visuospatial Working Memory Capacity Predicts the Organization of Acquired Explicit Motor Sequences

Changes in multi-joint performance with age.

Neurocognitive Contributions to Motor Skill Learning: The Role of Working Memory