老年学习记忆减退的神经行为学基础

用改良Ｍｏｒｒｉｓ水迷宫将老年大鼠分为老年学习记忆减退组和老年学习记忆正常组,并与青年组对照,检测其空间参考记忆和空间工作记忆,并对海马结构内胶质纤维酸性蛋白（ＧＦＡＰ）阳性胶质细胞和ＧＡＢＡ能中间神经元在光镜和电镜水平进行定量分析。结果显示老年学习记忆减退大鼠的空间参考记忆能力明显下降,并且其行为模式发生了改变,空间工作记忆改变不明显;齿状回分子层的病理改变非常明显,表现为ＧＡＢＡ能神经元丢失和     

The strength-dexterity test as a measure of dynamic pinch performance

We have developed a method to quantify the dynamic interaction between fingertip force magnitude (strength) and directional control (dexterity) during pinch with a novel strength-dexterity (S-D) test based on the principle of buckling of compression springs. The test consists of asking participants to use key and opposition pinch to attempt to fully compress springs, in random order, with a wide range of combinations of strength and dexterity requirements. The minimum force required to fully compress the spring and the propensity of the spring to buckle define the strength and dexterity requirements, respectively. The S-D score for each pinch style was the sum of the strength values of all springs successfully compressed fully. We tested 3 participant groups: 18 unimpaired young adults (40yr), and 14 adults diagnosed with carpo-metacarpal osteoarthritis (CMC OA) (>or = 36yr). We investigated the repeatability of the S-D test with 74 springs by testing 14 young adults twice on different days. The per-spring repeatability across subjects was >or = 94%. A minimum performance score for young adults was found as they all could compress a subset of 39 springs. Using this subset of springs, we compared the ability of the S-D score vs. maximal pinch force values to distinguish unimpaired hands from those with CMC OA of the thumb. The score for this 39-spring S-D test distinguished between CMC OA and asymptomatic older adults, whereas pinch meter readings did not (p<0.05). We conclude that the S-D test is repeatable and applicable to clinical research. We propose including the S-D test in studies aiming to quantify impairment and compare treatment outcomes in orthopaedic and neurological afflictions that degrade dynamic manipulation.     

Young dentate granule cells mediate pattern separation, whereas old granule cells facilitate pattern completion

Adult-born granule cells (GCs), a minor population of cells in the hippocampal dentate gyrus, are highly active during the first few weeks after functional integration into the neuronal network, distinguishing them from less active, older adult-born GCs and the major population of dentate GCs generated developmentally. To ascertain whether young and old GCs perform distinct memory functions, we created a transgenic mouse in which output of old GCs was specifically inhibited while leaving a substantial portion of young GCs intact. These mice exhibited enhanced or normal pattern separation between similar contexts, which was reduced following ablation of young GCs. Furthermore, these mutant mice exhibited deficits in rapid pattern completion. Therefore, pattern separation requires adult-born young GCs but not old GCs, and older GCs contribute to the rapid recall by pattern completion. Our data suggest that as adult-born GCs age, their function switches from pattern separation to rapid pattern completion.     

Do Aging and Dual-Tasking Impair the Capacity to Store and Retrieve Visuospatial Information Needed to Guide Perturbation-Evoked Reach-To-Grasp Reactions?

A recent study involving young adults showed that rapid perturbation-evoked reach-to-grasp balance-recovery reactions can be guided successfully with visuospatial-information (VSI) retained in memory despite: 1) a reduction in endpoint accuracy due to recall-delay (time between visual occlusion and perturbation-onset, PO) and 2) slowing of the reaction when performing a concurrent cognitive task during the recall-delay interval. The present study aimed to determine whether this capacity is compromised by effects of aging. Ten healthy older adults were tested with the previous protocol and compared with the previously-tested young adults. Reactions to recover balance by grasping a small handhold were evoked by unpredictable antero-posterior platform-translation (barriers deterred stepping reactions), while using liquid-crystal goggles to occlude vision post-PO and for varying recall-delay times (0-10s) prior to PO (the handhold was moved unpredictably to one of four locations 2s prior to vision-occlusion). Subjects also performed a spatial- or non-spatial-memory cognitive task during the delay-time in a subset of trials. Results showed that older adults had slower reactions than the young across all experimental conditions. Both age groups showed similar reduction in medio-lateral end-point accuracy when recall-delay was longest (10s), but differed in the effect of recall delay on vertical hand elevation. For both age groups, engaging in either the non-spatial or spatial-memory task had similar (slowing) effects on the arm reactions; however, the older adults also showed a dual-task interference effect (poorer cognitive-task performance) that was specific to the spatial-memory task. This provides new evidence that spatial working memory plays a role in the control of perturbation-evoked balance-recovery reactions. The delays in completing the reaction that occurred when performing either cognitive task suggest that such dual-task situations in daily life could increase risk of falling in seniors, particularly when combined with the general age-related slowing that was observed across all experimental conditions.     

Electrophysiological Correlates of Subitizing in Healthy Aging

To understand the nature of age-related changes in enumeration abilities we measured two ERP responses -N2pc and CDA, associated respectively to attentive individuation and VWM- and posterior alpha band (8-15 Hz) event-related desynchronization (ERD), traditionally linked to enhanced target processing. Two groups of old and young participants enumerated a variable number (1-6) of targets presented among distractors. Older participants were less accurate in enumerating targets. ERP results in old participants showed a suppression of N2pc amplitudes for all numerosities, and a decrease in CDA only for the largest set (4-6 targets). In contrast with the pattern for young adults, time/frequency results on older adults revealed neither a modulation of alpha oscillations as a function of target numerosity, nor an effect of ERD lateralization. These patterns indicate that both attention and working memory contribute to the age-related decline in enumeration, and point to an overall decrease in the activity of the visual areas responsible for the processing of the hemifield where the relevant objects are presented.     

Gender-Specific Differences in the Relationship between Autobiographical Memory and Intertemporal Choice in Older Adults

As the population of older adults grows, their economic choices will have increasing impact on society. Research on the effects of aging on intertemporal decisions shows inconsistent, often opposing results, indicating that yet unexplored factors might play an essential role in guiding one''s choices. Recent studies suggest that episodic future thinking, which is based on the same neural network involved in episodic memory functions, leads to reductions in discounting of future rewards. As episodic memory functioning declines with normal aging, but to greatly variable degrees, individual differences in delay discounting might be due to individual differences in the vitality of this memory system in older adults. We investigated this hypothesis, using a sample of healthy older adults who completed an intertemporal choice task as well as two episodic memory tasks. We found no clear evidence for a relationship between episodic memory performance and delay discounting in older adults. However, when additionally considering gender differences, we found an interaction effect of gender and autobiographical memory on delay discounting: while men with higher memory scores showed less delay discounting, women with higher memory scores tended to discount the future more. We speculate that this gender effect might stem from the gender-specific use of different modal representation formats (i.e. temporal or visual) during assessment of intertemporal choice options.     

Age impairs sit-to-walk motor performance

Sit-to-walk (STW) is a common functional and transitional task which challenges an individual's postural control systems. As aging is associated with an increased risk of falls during transitional movements, we biomechanically investigated the STW movement task in 12 healthy young and 12 healthy elderly individuals. Performance was evaluated utilizing motion analysis and two force plates. The principal finding of this study was the impaired performance of the healthy older adults. The older adults generated significantly less momentum prior to rising (p=0.011) and further delayed (p<0.001) the initiation of gait until standing more upright (p=0.036). The young adults successfully merged the component tasks shortly after seat-off and displayed significantly greater step length (p<0.001), step velocity (p<0.001), and tolerated greater separation of the center of pressure and center of mass at the end single support phase of the initial step (p=0.001). While the young adults fluidly merged the standing and walking task components, the older adults displayed a conservative movement performance during the STW task thereby limiting threats to their postural stability.     

Circadian phase-shifting effects of nocturnal exercise in older compared with young adults

Exercise can phase shift the circadian rhythms of young adults if performed at the right time of day. Similar research has not been done in older adults. This study examined the circadian phase-delaying effects of a single 3-h bout of low-intensity nocturnal exercise in older (n = 8; 55-73 yr old) vs. young (n = 8; 20-32 yr old) adults. The exercise occurred at the beginning of each subject's habitual sleep time, and subjects sat in a chair in dim light during the corresponding time in the control condition. The dim-light melatonin onset (DLMO) was used as the circadian phase marker. The DLMO phase delayed more after the exercise than after the control condition. On average, the difference in phase shift between the exercise and control conditions was similar for older and young subjects, demonstrating that the phase-shifting effects of exercise on the circadian system are preserved in older adults. Therefore, exercise may potentially be a useful treatment to help adjust circadian rhythms in older and young adults.     

Heart Rate Recovery Predicts Memory Performance in Older Adults

The current study examined cardiovascular reactivity and recovery during memory testing in a sample of 28 younger and 28 older adults. Heart rate (HR) levels were measured before, during, and after a memory test (word list recall). Contrary to prediction, older adults did not have a blunted cardiovascular response to memory tasks compared to younger adults. Word list recall performance was predicted by both Age and an Age × HR recovery interaction. As expected, younger adults performed better on the word list task than older adults. In addition, older adults with better posttest HR recovery performed significantly better than older adults with poor posttest HR recovery, whereas HR recovery differences in younger adults were inconsequential. These relationships were not affected by subjective appraisals of anxiety and task difficulty. Overall, cardiac dysregulation, seen here as low HR recovery, represents an important, potentially modifiable, factor in memory performance in older adults. In addition to being beneficial to overall health, interventions designed to help older adults regulate their HR responses may help offset certain memory declines.     

Age changes in the external dimensions of adult bone

Humeri from a large, ossuary-derived sample are used to demonstrate that considerable size variability is introduced to transverse skeletal measurements when young adults and older adults are pooled. Humeri from young adults (epiphyseal lines still visible, N ≈? 25) are smaller in transverse dimensions than those of older adults (N ≈? 300). Among left humeri, only shaft diameters demonstrate statistically significant differences. The right humeri, however, show statistically significant differences for six of the eight measurements. The increased size of the older adult humeri reflects the fact that appositional growth continues throughout adulthood. The more pronounced differences seen on the right side probably reflect developing dominance asymmetry. Recognition of this source of intrasample variability will influence the choice of skeletal measurements used for population comparisons and/or indicators of robusticity.     

Preserved neural correlates of priming in old age and dementia

Implicit memory, including priming, can be preserved in aging and dementia despite impairment of explicit memory. To explore the neural correlates of preserved memory ability, whole-brain functional MRI (fMRI) was used during a repetition priming paradigm to study 34 young adults, 33 older adults without dementia, and 24 older adults in the early stages of dementia of the Alzheimer type (DAT). Both older adult groups showed repetition-based response time benefits (priming) and changes in activation along inferior frontal gyrus similar to those shown by young adults. Across all three groups, repetition-related response time reductions correlated with prefrontal activity reductions, demonstrating a direct relation between priming and fMRI-measured activity change. These results suggest that despite difficulties with deliberate memory, both older adults without dementia and those with early-stage DAT can modify behavior mediated by prefrontal contributions, making these preserved abilities an attractive target for cognitive training and rehabilitation.     

Adopting a spatially explicit perspective to study the mysterious fairy circles of Namibia

The mysterious ‘fairy circles’ are vegetation‐free discs that cover vast areas along the pro‐Namib Desert. Despite 30 yr of research their origin remains unknown. Here we adopt a novel approach that focuses on analysis of the spatial patterns of fairy circles obtained from representative 25‐ha aerial images of north‐west Namibia. We use spatial point pattern analysis to quantify different features of their spatial structures and then critically inspect existing hypotheses with respect to their ability to generate the observed circle patterns. Our working hypothesis is that fairy circles are a self‐organized vegetation pattern. Finally, we test if an existing partial‐differential‐equation model, that was designed to describe vegetation pattern formation, is able to reproduce the characteristic features of the observed fairy circle patterns. The model is based on key‐processes in arid areas such as plant competition for water and local resource‐biomass feedbacks. The fairy circles showed at all three study areas the same regular spatial distribution patterns, characterized by Voronoi cells with mostly six corners, negative correlations in their size up to a distance of 13 m, and remarkable homogeneity over large spatial scales. These results cast doubts on abiotic gas‐leakage along geological lines or social insects as causal agents of their origin. However, our mathematical model was able to generate spatial patterns that agreed quantitatively in all of these features with the observed patterns. This supports the hypothesis that fairy circles are self‐organized vegetation patterns that emerge from positive biomass‐water feedbacks involving water transport by extended root systems and soil‐water diffusion. Future research should search for mechanisms that explain how the different hypotheses can generate the patterns observed here and test the ability of self‐organization to match the birth‐ and death dynamics of fairy circles and their regional patterns in the density and size with respect to environmental gradients.     

Musical experience and the aging auditory system: implications for cognitive abilities and hearing speech in noise

Much of our daily communication occurs in the presence of background noise, compromising our ability to hear. While understanding speech in noise is a challenge for everyone, it becomes increasingly difficult as we age. Although aging is generally accompanied by hearing loss, this perceptual decline cannot fully account for the difficulties experienced by older adults for hearing in noise. Decreased cognitive skills concurrent with reduced perceptual acuity are thought to contribute to the difficulty older adults experience understanding speech in noise. Given that musical experience positively impacts speech perception in noise in young adults (ages 18-30), we asked whether musical experience benefits an older cohort of musicians (ages 45-65), potentially offsetting the age-related decline in speech-in-noise perceptual abilities and associated cognitive function (i.e., working memory). Consistent with performance in young adults, older musicians demonstrated enhanced speech-in-noise perception relative to nonmusicians along with greater auditory, but not visual, working memory capacity. By demonstrating that speech-in-noise perception and related cognitive function are enhanced in older musicians, our results imply that musical training may reduce the impact of age-related auditory decline.     

The Relevance of Short-Range Fibers to Cognitive Efficiency and Brain Activation in Aging and Dementia

The integrity of structural connectivity in a functional brain network supports the efficiency of neural processing within relevant brain regions. This study aimed to quantitatively investigate the short- and long-range fibers, and their differential roles in the lower cognitive efficiency in aging and dementia. Three groups of healthy young, healthy older adults and patients with Alzheimer''s disease (AD) participated in this combined functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) study on prospective memory (PM). Short- and long-range fiber tracts within the PM task engaged brain networks were generated. The correlation between the fMRI signal change, PM performance and the DTI characters were calculated. FMRI results showed that the PM-specific frontal activations in three groups were distributed hierarchically along the rostrocaudal axis in the frontal lobe. In an overall PM condition generally activated brain network among the three groups, tractography was used to generate the short-range fibers, and they were found impaired in both healthy older adults and AD patients. However, the long-range fiber tracts were only impaired in AD. Additionally, the mean diffusivity (MD) of short-range but not long-range fibers was positively correlated with fMRI signal change and negatively correlated with the efficiency of PM performance. This study suggests that the disintegrity of short-range fibers may contribute more to the lower cognitive efficiency and higher compensatory brain activation in healthy older adults and more in AD patients.     

Impaired spatial learning in the APPSwe + PSEN1DeltaE9 bigenic mouse model of Alzheimer's disease

Mice co-expressing the Swedish amyloid precursor protein mutation (APP(Swe)) and exon 9 deletion (DeltaE9) of the PSEN1 gene begin to develop amyloid plaques at 6-7 months of age. We demonstrate here a spatial learning deficit in 7-month-old APP(Swe) + PSEN1DeltaE9 bigenic mice using an adaptation of the Barnes maze. Mice were first trained on a cued target followed by a hidden-target condition. Although bigenic mice quickly learned the cued-target version of the task, they were significantly impaired when switched to the hidden-target version. In contrast, a separate group of double-transgenic mice trained first on the spatial hidden-target version of the task were unimpaired relative to wild-type controls. We propose that processes such as general rule learning, context learning and exploratory habituation exert a greater influence when the testing environment is novel and overshadow the spatial memory deficit in naive bigenic mice. However, when cued-target training is conducted first, these processes habituate and the spatial learning deficit is unmasked. Seven-month-old APP(Swe) + PSEN1DeltaE9 mice were unimpaired on tests of memory that did not involve learning the rules governing spatial associations.     

Modulation of activity in human visual area V1 during memory masking

Neurons in the primary visual cortex, V1, are specialized for the processing of elemental features of the visual stimulus, such as orientation and spatial frequency. Recent fMRI evidence suggest that V1 neurons are also recruited in visual perceptual memory; a number of studies using multi-voxel pattern analysis have successfully decoded stimulus-specific information from V1 activity patterns during the delay phase in memory tasks. However, consistent fMRI signal modulations reflecting the memory process have not yet been demonstrated. Here, we report evidence, from three subjects, that the low V1 BOLD activity during retention of low-level visual features is caused by competing interactions between neural populations coding for different values along the spectrum of the dimension remembered. We applied a memory masking paradigm in which the memory representation of a masker stimulus interferes with a delayed spatial frequency discrimination task when its frequency differs from the discriminanda with ±1 octave and found that impaired behavioral performance due to masking is reflected in weaker V1 BOLD signals. This cross-channel inhibition in V1 only occurs with retinotopic overlap between the masker and the sample stimulus of the discrimination task. The results suggest that memory for spatial frequency is a local process in the retinotopically organized visual cortex.     

Effect of walking speed on inter-joint coordination differs between young and elderly adults

Investigating inter-joint coordination at different walking speeds in young and elderly adults could provide insights to age-related changes in neuromuscular control of gait. We examined effects of walking speed and age on the pattern and variability of inter-joint coordination. Gait analyses of 10 young and 10 elderly adults were performed with different self-selected speeds, including a preferred, faster, and slower speed. Continuous relative phase (CRP), derived from phase planes of two adjacent joints, was used to assess the inter-joint coordination. CRP patterns were examined with cross-correlation measures and root-mean-square (RMS) differences when comparing ensemble mean curves of the faster or slower speed to preferred speed walking. Variability of coordination for each participant was assessed with the average value of all standard deviations calculated for each data point over a gait cycle from all CRP curves, namely the deviation phase (DP). For hip-knee CRP pattern, RMS differences were significantly greater between the slower and preferred walking speeds than between the faster and preferred walking speeds in young adults, but this was not found in elderly adults. Significant group differences in RMS differences and cross-correlation measures were detected in hip-knee CRP patterns between the slower and preferred walking speeds. No significant walking speed or age effects were detected for the knee-ankle CRP. Significant walking speed effects were also detected in hip-knee DP values. However, no significant group differences were detected for all three speeds. These findings suggested that young and elder adults compromise changes of walking speed with different neuromuscular control strategies.     

Advanced Parental Age Impaired Fear Conditioning and Hippocampal LTD in Adult Female Rat Offspring

Advanced maternal or paternal age is associated with increased risks of cognitive and emotional disorders. Chronic stress is also a common experience in human life that causes psychiatric diseases. However, the synergistic effects of these two factors on offspring are rarely studied. In the present study, the offspring of both young (3–4 months) and old (12–14 months) rat parents were given CUMS for 21 days at the age of 4 weeks. The effects of advanced parental age and chronic unpredictable mild stress (CUMS) on emotional and cognitive behaviors and the related cellular mechanisms were investigated by using behavioral and electrophysiological techniques. We found that CUMS decreased sucrose consumption, increased anxiety, and impaired learning and memory in offspring from both old and young breeders. However, advanced parental age impaired fear memory and spatial memory mainly in female offspring. The serum corticosterone of female offspring was lower than males, but advanced parental age significantly elevated serum corticosterone in female offspring in response to electrical foot shocks. In addition, hippocampal LTD was severely impaired in female offspring from older parents. Our results indicated that female offspring from older breeders might be more sensitive to stress, and the hippocampal function was more vulnerable. These results might provide experimental basis for the prevention and treatment of advanced parental age related psychiatric disorders in future.