Double dissociation of a latent working memory process

Background. The study explored the construct validity of a computational model of working memory (WM) by determining whether model parameters manifested double dissociations of lesion laterality with type of material studied. The data set modeled involved psychometrically matched verbal and figural WM tasks on which a double dissociation between test version and lesion laterality failed to emerge when total test scores were used as the laterality marker. Method. This re-analysis of a previously published study involved investigating the WM performance of 15 demographically matched controls with 15 adult patients with left-hemispheric (LH) lesions and 15 adult patients with right-hemispheric (RH) lesions. Each participant was given verbal and figural versions of a continuous paired associates test (CPAT). The two versions had previously been psychometrically matched in a larger sample of healthy individuals. A WM model composed of encoding, displacement, and episodic memory parameters was fit to each individual’s performance profiles for both versions of the CPAT. Results. Replicating the previous results for raw scores, rank transformed values of total score performance failed to reveal a double dissociation. Nonetheless an absolute double dissociation was observed for the model’s displacement parameter: RH patients demonstrated deficits on the figural but not verbal WM displacement parameter, whereas LH patients demonstrated deficits on the verbal but not figural WM displacement parameter. Additionally, both LH and RH patients were impaired on the figural encode parameter, perhaps explaining the absence of a double dissociation in total score performance. Conclusions. By combining different patterns of profile and level data into theoretically motivated model parameters, computational models of neurocognition can enhance the construct validity of interpretations of neuropsychological performance.     

Assessing the criterion validity of four highly abbreviated measures from the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS)

Objective: Cognitive dysfunction is prevalent in multiple sclerosis. As self-reported cognitive functioning is unreliable, brief objective screening measures are needed. Utilizing widely used full-length neuropsychological tests, this study aimed to establish the criterion validity of highly abbreviated versions of the Brief Visuospatial Memory Test – Revised (BVMT-R), Symbol Digit Modalities Test (SDMT), Delis–Kaplan Executive Function System (D-KEFS) Sorting Test, and Controlled Oral Word Association Test (COWAT) in order to begin developing an MS-specific screening battery. Method: Participants from Holy Name Medical Center and the Kessler Foundation were administered one or more of these four measures. Using test-specific criterion to identify impairment at both ?1.5 and ?2.0 SD, receiver-operating-characteristic (ROC) analyses of BVMT-R Trial 1, Trial 2, and Trial 1 + 2 raw data (N = 286) were run to calculate the classification accuracy of the abbreviated version, as well as the sensitivity and specificity. The same methods were used for SDMT 30-s and 60-s (N = 321), D-KEFS Sorting Free Card Sort 1 (N = 120), and COWAT letters F and A (N = 298). Results: Using these definitions of impairment, each analysis yielded high classification accuracy (89.3 to 94.3%). Conclusions: BVMT-R Trial 1, SDMT 30-s, D-KEFS Free Card Sort 1, and COWAT F possess good criterion validity in detecting impairment on their respective overall measure, capturing much of the same information as the full version. Along with the first two trials of the California Verbal Learning Test – Second Edition (CVLT-II), these five highly abbreviated measures may be used to develop a brief screening battery.     

Everyday functioning and cognitive correlates in healthy older adults with subjective cognitive concerns

Objective: Few studies have examined functional abilities and complaints in healthy older adults (HOAs) with subjective cognitive concerns (SCC). The aims of this study were to assess everyday functioning in HOAs reporting high and low amounts of SCC and examine cognitive correlates of functional abilities. Method: Twenty-six HOAs with high SCC and 25 HOAs with low SCC, as well as their knowledgeable informants, completed the Instrumental Activities of Daily Living-Compensation (IADL-C), a questionnaire measure of everyday functioning. Results: After controlling for depression, the high-SCC group self-reported significantly more everyday difficulties on the IADL-C, including all subdomains. Compared to the low-SCC group, informants for the high-SCC group endorsed more difficulties on the IADL-C and specifically the social skills subdomain. For the high-SCC group, poorer self-report of everyday functioning was related to poorer executive functioning and temporal order memory. Conclusions: These findings indicate that there may be subtle functional changes that occur early in the spectrum of cognitive decline in individuals with high SCC, and these functional changes are evident to informants. Further work is needed to investigate whether individuals with both SCC and functional difficulties are at an even higher risk for progression to mild cognitive impairment.     

镍钛记忆合金锁骨钩环抱器治疗新鲜重度肩锁关节脱位

目的 评估镍钛记忆合金锁骨钩环抱器治疗新鲜重度肩锁关节脱位的临床疗效。方法 选择16例新鲜重度肩锁关节脱位患者，其中3例合并锁骨远端骨折，应用镍钛记忆合金锁骨钩环抱器治疗并进行临床疗效观察。随访6～12个月，平均7.6个月。结果 所有患者肩关节肌肉无萎缩，外观正常，肩关节活动范围正常，x线片示无再脱位征象。采用Karlsson术后疗效分级：A级15例，B级1例。结论 镍钛记忆合金锁骨钩环抱器治疗新鲜重度肩锁关节脱位创伤小，简便易行，疗效好，对合并锁骨远端骨折病人更具有独特优点，具有临床推广应用价值。     

三种内固定治疗上肢长骨干骨折的临床比较研究

目的观察天鹅记忆接骨器(swan-likememoryconnector,SMC)治疗上肢长骨干骨折的疗效,并与加压接骨板(dynamiccompressiveplate,DCP)和带锁髓内针(lockedintramedullarynail,LIN)进行临床对比研究。方法随机选择1997年8月～2001年8月入院的新鲜上肢长骨干骨折148例,分别采用SMC(49例)与DCP(50例)、LIN(49例)进行内固定治疗,术后常规抗炎治疗1周,定期拍片并随访患肢功能恢复情况。结果SMC组的手术时间明显低于LIN组与DCP组(P<0.05),三组伤口感染率无差异。SMC组骨愈合时间和骨不连发生率显著短于DCP组和LIN组(P<0.05),而术后功能优良率高于DCP组和LIN组。在SMC固定下,骨折愈合直接由解剖型或类解剖型的骨样骨板状直接替代连接,固定段无应力遮挡和骨质疏松。结论SMC是治疗上肢长骨干骨折的有效方法,优于DCP和LIN。SMC的几何构形和力学特性有利于骨折愈合。在本器固定下,可能存在一种新的尚未被认知的骨折愈合方式。     

新型记忆合金节段内固定器治疗腰椎峡部裂的实验研究

目的 :设计一种治疗腰椎峡部裂的新型记忆合金节段内固定器 ,测试其材料力学特性 ,并评价其生物力学稳定性。方法 :测量 2 0具干燥完整成人腰椎标本获得数据 ,按数据采用镍钛记忆合金设计固定器并行材料力学测试。取 6具新鲜成人腰椎标本 ,先后形成正常脊柱组、峡部裂组、横突棘突钢丝捆绑组、钩螺钉固定组、Buck螺钉固定组、新研制记忆合金固定器固定组 6组实验模型。利用脊柱三维运动实验机 ,分别测试 6组的前屈 /后伸、左 /右侧弯及左 /右轴向旋转 6种运动的活动范围。结果 :材料力学测试表明其形态记忆功能良好 ,体温状态下会产生稳定可靠的回复力。 6组在前屈、后伸及左右旋转状态 ,峡部裂组稳定性最差 ,同其他 5组差别明显。而使用新研制记忆合金内固定器组可明显恢复腰椎稳定性 ,同正常脊柱组及其他 3种内固定组均无显著差别。另两种状态左右侧弯 6组均无显著性差别。结论 :新设计的内固定器符合腰椎的生物力学要求 ,较先前的半环状内固定器优势明显 ,具有很好应用前景     

Long‐term effects of chronic nicotine on emotional and cognitive behaviors and hippocampus cell morphology in mice: comparisons of adult and adolescent nicotine exposure

Nicotine dependence is associated with increased risk for emotional, cognitive and neurological impairments later in life. This study investigated the long‐term effects of nicotine exposure during adolescence and adulthood on measures of depression, anxiety, learning and hippocampal pyramidal cell morphology. Mice (C57BL/6J) received saline or nicotine for 12 days via pumps implanted on postnatal day 32 (adolescent) or 54 (adults). Thirty days after cessation of nicotine/saline, mice were tested for learning using contextual fear conditioning, depression‐like behaviors using the forced swim test or anxiety‐like behaviors with the elevated plus maze. Brains from nicotine‐ or saline‐exposed mice were processed with Golgi stain for whole neuron reconstruction in the CA1 and CA3 regions of the hippocampus. Results demonstrate higher depression‐like responses in both adolescent and adult mice when tested during acute nicotine withdrawal. Heightened depression‐like behaviors persisted when tested after 30 days of nicotine abstinence in mice exposed as adolescents, but not adults. Adult, but not adolescent, exposure to nicotine resulted in increased open‐arm time when tested after 30 days of abstinence. Nicotine exposure during adolescence caused deficits in contextual fear learning indicated by lower levels of freezing to the context as compared with controls when tested 30 days later. In addition, reduced dendritic length and complexity in the apical CA1 branches in adult mice exposed to nicotine during adolescence were found. These results demonstrate that nicotine exposure and withdrawal can have long‐term effects on emotional and cognitive functioning, particularly when nicotine exposure occurs during the critical period of adolescence.     

Previous Midlife Oestradiol Treatment Results in Long‐Term Maintenance of Hippocampal Oestrogen Receptor α Levels in Ovariectomised Rats: Mechanisms and Implications for Memory

Ovariectomised rats that have received previous administration of oestradiol in midlife display enhanced cognition and increased hippocampal levels of oestrogen receptor (ER)α months after oestradiol treatment ended compared to ovariectomised controls. The present study aimed to investigate the mechanisms by which ERα levels are maintained following midlife oestradiol exposure and the role of ERα in memory in ageing females in the absence of circulating oestrogens. Unliganded ERα has increased interaction with the ubiquitin ligase, C‐terminus of Hsc‐70 interacting protein (CHIP), leading to increased degradation of the receptor. In our first experiment, we tested the hypothesis that midlife oestradiol exposure in ovariectomised rats results in decreased interaction between CHIP and hippocampal ERα, leading to increased levels of ERα. Middle‐aged rats were ovariectomised and received oestradiol or vehicle implants. After 40 days, implants were removed. One month later, rats were killed and hippocampi were processed for whole protein western blotting and co‐immunoprecipitation, in which ERα was immunoprecipitated from lysate. As expected, ERα protein expression was increased in rats previously treated with oestradiol compared to vehicle‐treated rats. In rats treated with oestradiol, there was a decrease in CHIP–ERα interaction, suggesting that previous oestradiol treatment reduces interaction, slowing the degradation of ERα. In a second experiment, we determined the impact on memory of antagonism of ER in the absence of circulating oestrogens. Rats were ovariectomised and implanted with oestradiol capsules. Capsules were removed after 40 days. Rats received chronic i.c.v. infusion of ER antagonist, ICI 182 780, or artificial cerebrospinal fluid vehicle and were tested on a spatial memory radial‐maze task. Rats treated with ICI 182 780 had significantly worse performance (more errors). These experiments provide evidence that previous midlife oestradiol treatment maintains hippocampal ERα by decreasing its interaction with CHIP and that activation of these receptors provides cognitive benefits in the absence of circulating oestrogens.     

Deficits in hippocampal‐dependent transfer generalization learning accompany synaptic dysfunction in a mouse model of amyloidosis

Elevated β‐amyloid and impaired synaptic function in hippocampus are among the earliest manifestations of Alzheimer's disease (AD). Most cognitive assessments employed in both humans and animal models, however, are insensitive to this early disease pathology. One critical aspect of hippocampal function is its role in episodic memory, which involves the binding of temporally coincident sensory information (e.g., sights, smells, and sounds) to create a representation of a specific learning epoch. Flexible associations can be formed among these distinct sensory stimuli that enable the “transfer” of new learning across a wide variety of contexts. The current studies employed a mouse analog of an associative “transfer learning” task that has previously been used to identify risk for prodromal AD in humans. The rodent version of the task assesses the transfer of learning about stimulus features relevant to a food reward across a series of compound discrimination problems. The relevant feature that predicts the food reward is unchanged across problems, but an irrelevant feature (i.e., the context) is altered. Experiment 1 demonstrated that C57BL6/J mice with bilateral ibotenic acid lesions of hippocampus were able to discriminate between two stimuli on par with control mice; however, lesioned mice were unable to transfer or apply this learning to new problem configurations. Experiment 2 used the APP_swePS1 mouse model of amyloidosis to show that robust impairments in transfer learning are evident in mice with subtle β‐amyloid‐induced synaptic deficits in the hippocampus. Finally, Experiment 3 confirmed that the same transfer learning impairments observed in APPswePS1 mice were also evident in the Tg‐SwDI mouse, a second model of amyloidosis. Together, these data show that the ability to generalize learned associations to new contexts is disrupted even in the presence of subtle hippocampal dysfunction and suggest that, across species, this aspect of hippocampal‐dependent learning may be useful for early identification of AD‐like pathology. © 2015 Wiley Periodicals, Inc.     

Retrieval flexibility and reinstatement in the developing hippocampus

Episodic memory improves during childhood and this improvement has been associated with age differences in hippocampal function, but previous research has not manipulated the possible underlying mechanisms. We tested the hypothesis that age‐related differences in hippocampal activation may reflect changes in retrieval flexibility. We expected these activation differences to be observed most prominently in the anterior hippocampus. Functional magnetic resonance imaging (fMRI) data were collected from children ages 8 and 10, and adults (N = 63) during an associative recognition task that required participants to recognize pairs of pictures which either appeared in the same location as during encoding (Same location), or in a flipped location, such that each picture switched their location with the other member of the pair (Flipped location). Recognition of same‐location pairs placed lower demands on flexible retrieval compared to recognition of flipped‐location pairs. Behaviorally, 8‐year‐olds exhibited the strongest correct recognition gains for same‐location compared to flipped‐location pairs, and females unexpectedly outperformed males across all ages. When we examined correct recognition, adults recruited the hippocampal head more strongly for flipped‐ versus same‐location pairs compared to both groups of children; in contrast both adults and 10‐year‐olds recruited the hippocampal tail more strongly for flipped‐ versus same‐location pairs compared to 8‐year‐olds. This pattern was stronger in the left hippocampus and for females. Moreover hippocampal discrimination between recognized and forgotten items in the same‐location condition was stronger in 8‐year‐olds compared to adults, and was stronger in the flipped‐location condition in adults compared to 8‐year‐olds; this pattern was stronger in the left hippocampus. Individual differences in this discrimination contrast for flipped‐location trials in the head and body predicted performance on an index of creative thinking. Overall, these results lend new support to the idea that hippocampal development may reflect change in retrieval flexibility with implications for additional forms of flexible cognition. © 2015 Wiley Periodicals, Inc.