Connectivity measures suggest a sub-cortical generator of myoclonus in Angelman syndrome

ObjectiveThe clinical and neurophysiological characteristics of myoclonus in Angelman syndrome (AS) have been evaluated in single case or small cohorts, with contrasting results. We evaluated the features of myoclonus in a wide cohort of AS patients.MethodsWe performed polygraphic EEG-EMG recording in 24 patients with genetically confirmed AS and myoclonus. Neurophysiological investigations included jerk-locked back-averaging (JLBA), cortico-muscular coherence (CMC) and generalised partial directed coherence (GPDC). CMC and GPDC analyses were compared to those obtained from 10 healthy controls (HC).ResultsTwenty-four patients (aged 3–35 years, median 20) were evaluated. Sequences of quasi-continuous rhythmic jerks mostly occurred at alpha frequency or just below (mean 8.4 ± 1.4 Hz), without EEG correlate. JLBA did not show any clear transient preceding the jerks. CMC showed bilateral over-threshold CMC in alpha band that was prominent on the contralateral hemisphere in the patient group as compared to HC group. GPDC showed a significantly higher alpha outflow from both hemispheres toward activated muscles in the patient group, and a significantly higher beta outflow from contralateral hemisphere in the HC group.ConclusionsThese neurophysiological findings suggest a subcortical generator of myoclonus in AS.SignificanceMyoclonus in AS has not a cortical origin as previously hypothesised.     

Corticosterone-mediated microglia activation affects dendritic spine plasticity and motor learning functions in minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) is characterized as cognitive deficits including memory and learning dysfunctions after liver injuries or hepatic diseases. Our understandings of neurological mechanisms of MHE-associated cognitive syndromes, however, are far from complete. In the current study we generated a mouse MHE model by repetitive administrations of thioacetamide (TAA), which induced hyperammonemia plus elevated proinflammatory cytokines in both the general circulation and motor cortex. MHE mice presented prominent motor learning deficits, which were associated with excess dendritic spine pruning in the motor cortex under 2-photon in vivo microscopy. The pharmaceutical blockade of glucocorticoid receptor or suppression of its biosynthesis further rescued motor learning deficits and synaptic protein loss. Moreover, MHE mice presented microglial activation, which can be alleviated after glucocorticoid pathway inhibition. In sum, our data demonstrates corticosterone-induced microglial activation, synaptic over-pruning and motor learning impairments in MHE, providing new insights for MHE pathogenesis and potential targets of clinical interventions.     

The discrepancy between verbal and visuoperceptual IQ in children with a specific learning disorder: An analysis of 1624 cases

Children with a specific learning disorder (SLD) are often characterized by marked intellectual strengths and weaknesses. In the last few years, research has focused on a common discrepancy between low working memory and processing speed on the one hand, and high verbal and visuoperceptual intelligence on the other. SLD profiles featuring a specific discrepancy between verbal and visuoperceptual abilities have been only marginally considered, however, and their systematic comparison vis-à-vis typically-developing (TD) populations has yet to be conducted. The present study examined a dataset of 1624 WISC-IV profiles of children with a diagnosis of SLD. It emerged that the proportion of children with a Verbal Comprehension Index (VCI) at least 1.5 SD (22 standardized points) lower than their scores on the Perceptual Reasoning Index (PRI) was larger than the proportion of SLD children with the opposite discrepant profile; it was also larger than the same proportion found among TD children. Comparing the two discrepant profiles revealed that the children also differed by type of learning difficulty, gender, and performance in the WISC-IV Symbol search task. Further examination suggested that children who were discrepant and also distinctly poor in visuoperceptual intelligence were particularly slow in general processing.     

Dorsal hippocampus infusions of CNQX into the dentate gyrus disrupt expression of trace fear conditioning

The hippocampus is essential for the consolidation of some explicit long‐term memories, including trace conditioning. Lesions and pharmacological manipulations of the dorsal hippocampus (DH) have provided strong evidence for its involvement in the acquisition and expression of trace fear memories. However, no studies have specifically targeted DH subregions [CA1 and dentate gyrus (DG)] to determine their involvement in trace fear conditioning. In the present study, rats received bilateral cannulation targeting either the DG or CA1 of the DH. Following surgery, animals were trace fear conditioned. Forty‐eight hours following training, rats received bilateral infusions of the AMPA/kainate glutamate receptor antagonist, CNQX, or vehicle. Following the infusion, rats were placed in a novel context for the tone test. Rats that received CNQX into the DG froze significantly less during the tone and trace interval as compared to controls. Rats that received CNQX into the DH CA1 showed no difference in freezing during the tone or trace interval as compared to controls. These data support a role for the DG in the expression of trace tone fear conditioning. © 2015 Wiley Periodicals, Inc.     

以问题为基础教学法在急性脑血管病合并肺炎教学中的应用

目的  探讨急性脑血管病合并肺炎教学过程中应用以问题为基础学习（problem-based learning,PBL）教学法的实践经验。 方法  以7年制临床医学专业30名学生作为教学对象,随机分入PBL教学组或传统教学组。在急性脑血管病合并肺炎的诊断和治疗方案确定过程中分别对两组采用PBL教学法和传统教学法,以问卷调查方法对两组的教学效果进行评价。 结果  PBL教学法与传统教学相比,学生在自主学习能力、提出问题能力、解决问题能力、临床实践能力、医患沟通能力、团队合作能力和医学知识扩展各方面均显著提升。 结论  PBL教学法可以提高学生在急性脑血管病合并肺炎诊断和治疗过程中发现问题和解决问题的能力。     

基于问题学习教学法结合传统教学法在血管神经病学教学中的应用

目的 总结基于问题学习 （problem-based learning, PBL） 教学法结合传统教学法 （lesson-based learning, LBL） 在医学生临床学习中的作用。 方法 对2011年-2014年在首都医科大学附属北京天坛医院神经内科进行临床学习的7年制医学生, 采用PBL结合LBL的教学模式, 教学后对学生进行问卷调查, 统计学生对教学方法的意见。 结果 共发放并收回合格问卷200份, 统计显示学生对PBL结合LBL的教学模式在激发学习兴趣, 加 深对理论知识的理解, 拓展临床逻辑思维能力、 提高分析解决问题的能力, 理论联系实际能力、 提高 独立思考能力、 提高沟通协作能力等方面认可度较高 （84.3%～92.3%） , 85.3%的学生认为有必要继 续采用这种教学方法。 结论 医学生对PBL结合LBL的临床教学模式的接受度较高, 有利于提高学生的学习积极性。     

Transcutaneous spinal direct current stimulation improves locomotor learning in healthy humans

Background

Ambulation is an essential aspect of daily living and is often impaired after brain and spinal cord injuries. Despite the implementation of standard neurorehabilitative care, locomotor recovery is often incomplete.

Patients with Parkinson's disease learn to control complex systems-an indication for intact implicit cognitive skill learning

Implicit memory and learning mechanisms are composed of multiple processes and systems. Previous studies demonstrated a basal ganglia involvement in purely cognitive tasks that form stimulus response habits by reinforcement learning such as implicit classification learning. We will test the basal ganglia influence on two cognitive implicit tasks previously described by Berry and Broadbent, the sugar production task and the personal interaction task. Furthermore, we will investigate the relationship between certain aspects of an executive dysfunction and implicit learning. To this end, we have tested 22 Parkinsonian patients and 22 age-matched controls on two implicit cognitive tasks, in which participants learned to control a complex system. They interacted with the system by choosing an input value and obtaining an output that was related in a complex manner to the input. The objective was to reach and maintain a specific target value across trials (dynamic system learning). The two tasks followed the same underlying complex rule but had different surface appearances. Subsequently, participants performed an executive test battery including the Stroop test, verbal fluency and the Wisconsin card sorting test (WCST). The results demonstrate intact implicit learning in patients, despite an executive dysfunction in the Parkinsonian group. They lead to the conclusion that the basal ganglia system affected in Parkinson's disease does not contribute to the implicit acquisition of a new cognitive skill. Furthermore, the Parkinsonian patients were able to reach a specific goal in an implicit learning context despite impaired goal directed behaviour in the WCST, a classic test of executive functions. These results demonstrate a functional independence of implicit cognitive skill learning and certain aspects of executive functions.     

Contralesional neural plasticity and functional changes in the less-affected forelimb after large and small cortical infarcts in rats

Some studies have found that unilateral cerebral damage produces significant deficits in the ipsilesional, "less-affected", body side. Other studies have found that such damage results in a paradoxical hyperfunctionality of the ipsilesional body side and a facilitation of learning-induced neuroplastic changes in the contralesional motor cortex. The purpose of this study was to determine whether these effects co-exist and/or vary with lesion severity. After small or large unilateral ischemic lesions of the sensorimotor cortex (SMC) or sham operations, adult male rats were trained for 20 days to acquire a motor task, skilled reaching for food, for the first time with the ipsilesional forelimb. Analyses of movement patterns indicated lesion-size-dependent ipsilesional abnormalities in grasping, retrieving and releasing food pellets. Despite these impairments, success rates were significantly increased and aiming errors reduced in lesion groups compared with sham operates. Performance was best in rats with small lesions that had more minor ipsilesional impairments. In the motor cortex contralateral to the lesion and trained limb, there were significant increases in the density of dendrites immunoreactive for microtubule-associated protein-2 (MAP2) and of N-methyl-D-aspartate receptor subunit 1 (NMDAR1) immunoreactivity compared with sham operates. These effects were correlated with reaching performance. Therefore, enhanced motor skill learning in the "less-affected" forelimb and contralesional neuroplastic changes are muted after larger lesions and co-exist with ipsilesional impairments. These effects may be related to a denervation-induced neural restructuring of the contralesional cortex that both disrupts pre-existing motor engrams and facilitates the establishment of new ones.