秀丽线虫记忆的分子调控机制

模式无脊椎动物秀丽线虫已经成为揭示记忆复杂行为的理想研究模型之一.线虫具有三种简单的记忆形式对温度感知的记忆、对化学物质感知的记忆以及对于机械刺激感知的记忆.在对机械刺激感知的记忆研究中,短时程、中时程与长时程记忆均得到了系统的分析.其中短时程与中时程记忆可能定位于感觉神经元的前突触,而长时程记忆可能定位于中间神经元的后突触.本文针对线虫中记忆的遗传与分子调控机制近些年的研究进展进行了总结与讨论.     

Memory function in normal aging

Basic findings obtained on memory functions in normal aging are presented and discussed with respect to five separate but interacting memory systems. These systems are: episodic memory, semantic memory, short-term memory, perceptual representation system and procedural memory. All available evidence from cross-sectional research shows that there is a linear, decreasing memory performance as a function of age for episodic memory. Longitudinal studies suggest, however, that this age deficit may be an overestimation, by showing a relatively stable performance level up to middle age, followed by a sharp decline. Studies on semantic memory, short-term memory, perceptual representation system, and procedural memory show a relatively constant performance level across the adult life span, although some tasks used to assess short-term memory and procedural memory have revealed an age deficit. Disregarding the mixed results for these latter two memory systems, it can be concluded that episodic memory is unique in showing an age deficit. Episodic memory is also unique in the sense that it is the only memory system showing gender differences in performance throughout the adult life span with a significantly higher performance for women.     

Distinct memory profiles in Alzheimer's disease

Memory impairment is a prominent defining feature of Alzheimer's disease (AD), yet the degree to which the profile of memory impairment is uniform across patients is not fully resolved. The study examined patterns of memory impairment in a large cohort of AD patients, with particular attention to the relationship between working and long-term declarative memory. Tests of working memory, visual and verbal recall and recognition, and recent personal memory were administered to 67 AD patients in the early to moderate stages of disease and to 30 age-matched controls. Performance on all measures was significantly poorer in patients than in controls. Factor analysis of test scores delineated five factors representing the domains of working memory, visual recall, verbal recall, recognition, and personal memory, indicating that these aspects of memory can break down separately. Cluster analysis revealed distinct memory profiles. Some patients showed predominant problems in working memory, with relatively superior long term retention, whereas other patients showed the reverse pattern. Qualitatively distinct profiles arose at comparable levels of severity. Problems in working memory, but not long term memory were associated with the presence of language and perceptuospatial deficits. The results reinforce previous findings that both working and long term memory failure contribute to the memory symptoms of AD patients, and demonstrate dissociations in memory breakdown across the cohort. The link between working memory and language performance, together with findings of posterior hemisphere abnormalities on neuroimaging, lead us to reassess the nature of working memory deficits in AD.     

Memory functions in depression.

In an attempt to elucidate the memory deficit in depression, short-term memory and long-term memory were examined by means of a memory test battery in 26 hospitalized depressed patients. Their performance was compared with a matched control group and with the performance of those 20 patients who improved after 26 days of treatment with antidepressants. Results indicate that depressed patients show marked impairment in short-term memory without an impairment in long-term memory. The greater the improvement of the clinical state, the greater the improvement in short-term memory, whereas long-term memory was not influenced by the therapeutic success.     

Visuospatial declarative learning despite profound verbal declarative amnesia in Korsakoff’s syndrome

Korsakoff's syndrome (KS) is a neuropsychiatric disorder characterised by severe amnesia. Although the presence of impairments in memory has long been acknowledged, there is a lack of knowledge about the precise characteristics of declarative memory capacities in order to implement memory rehabilitation. In this study, we investigated the extent to which patients diagnosed with KS have preserved declarative memory capacities in working memory, long-term memory encoding or long-term memory recall operations, and whether these capacities are most preserved for verbal or visuospatial content. The results of this study demonstrate that patients with KS have compromised declarative memory functioning on all memory indices. Performance was lowest for the encoding operation compared to the working memory and delayed recall operation. With respect to the content, visuospatial memory was relatively better preserved than verbal memory. All memory operations functioned suboptimally, although the most pronounced disturbance was found in verbal memory encoding. Based on the preserved declarative memory capacities in patients, visuospatial memory can form a more promising target for compensatory memory rehabilitation than verbal memory. It is therefore relevant to increase the number of spatial cues in memory rehabilitation for KS patients.     

Selective memory and memory deficits in depressed inpatients

We investigated memory impairment and mood-congruent memory bias in depression, using an explicit memory test and an implicit one. Thirty-six severely depressed inpatients that fulfilled DSM-IV criteria for major depressive disorder and 36 healthy controls matched for sex, age, and educational level participated in the study. Explicit memory was assessed with a free recall task and implicit memory with an anagram solution task. Results showed that depressed and controls differed in explicit memory performance, depending on the amount of cognitive distraction between incidental learning and testing. Implicit memory was not affected. In addition, severely depressed patients showed a mood-congruent memory bias in implicit memory but not in explicit memory. The complex pattern of results is discussed with regard to relevant theories of depression.     

Prospective memory in multiple sclerosis.

There is considerable evidence that multiple sclerosis (MS) is associated with impaired retrospective memory. However, although preliminary evidence suggests that prospective memory is also affected by the disorder, the degree and nature of the impairment remains to be clarified. Twenty participants with MS were compared with 20 matched controls on Virtual Week, a measure of prospective memory that closely represents the types of prospective memory tasks that actually occur in everyday life, and provides an opportunity to investigate the different sorts of prospective memory failures that occur. The results indicated that irrespective of the specific prospective memory task demands, MS participants' performance was significantly impaired relative to controls. MS deficits could not be attributed to problems with retrospective memory because MS participants in the present study did not differ significantly from controls on measures of long- and short-term memory, and significant impairment was observed on a prospective memory task, which imposed only minimal demands on retrospective memory. These results therefore suggest that individuals with MS may experience general difficulties with prospective memory. The practical and theoretical implications of these findings are discussed.     

Concurrent impairments in sleep and memory in amnestic mild cognitive impairment

Whereas patients with Alzheimer's disease (AD) experience difficulties forming and retrieving memories, their memory impairments may also partially reflect an unrecognized dysfunction in sleep-dependent consolidation that normally stabilizes declarative memory storage across cortical areas. Patients with amnestic mild cognitive impairment (aMCI) exhibit circumscribed declarative memory deficits, and many eventually progress to an AD diagnosis. Whether sleep is disrupted in aMCI and whether sleep disruptions contribute to memory impairment is unknown. We measured sleep physiology and memory for two nights and found that aMCI patients had fewer stage-2 spindles than age-matched healthy adults. Furthermore, aMCI patients spent less time in slow-wave sleep and showed lower delta and theta power during sleep compared to controls. Slow-wave and theta activity during sleep appear to reflect important aspects of memory processing, as evening-to-morning change in declarative memory correlated with delta and theta power during intervening sleep in both groups. These results suggest that sleep changes in aMCI patients contribute to memory impairments by interfering with sleep-dependent memory consolidation.     

Short-term and working memory impairments in aphasia

The aim of the present study is to investigate short-term memory and working memory deficits in aphasics in relation to the severity of their language impairment. Fifty-eight aphasic patients participated in this study. Based on language assessment, an aphasia score was calculated for each patient. Memory was assessed in two modalities, verbal and spatial. Mean scores for all memory tasks were lower than normal. Aphasia score was significantly correlated with performance on all memory tasks. Correlation coefficients for short-term memory and working memory were approximately of the same magnitude. According to our findings, severity of aphasia is related with both verbal and spatial memory deficits. Moreover, while aphasia score correlated with lower scores in both short-term memory and working memory tasks, the lack of substantial difference between corresponding correlation coefficients suggests a possible primary deficit in information retention rather than impairment in working memory.     

Memory impairment in methamphetamine dependent patients

The authors examined the verbal memory and visual memory of 19 patients with methamphetamine dependence and 18 normal controls to assess the memory impairment due to the use of methamphetamine. There was no significant difference in the verbal memory, but a significant difference was detected in the visual memory. The results that the methamphetamine selectively impairs visual memory seem to be because visual memory tasks are more sensitive to the damage of the executive function.     

Activity-Based Prospective Memory in Schizophrenia

The study reports activity-based prospective memory as well as its clinical and neuropsychological correlates in schizophrenia. A total of 42 persons diagnosed with schizophrenia and 42 healthy controls were administered prospective memory, set-shifting, and verbal working memory tasks. The schizophrenia group was additionally administered various psychopathology rating scales. Group differences, with poorer performances of the schizophrenia group, were observed on the measures of prospective memory, working memory, and set shifting. The performance on prospective memory tasks correlated with the performance levels on verbal working memory and set-shifting tasks but not with the clinical measures. This study demonstrated impaired activity-based prospective memory in schizophrenia. The impairment can be due to deficits in various neuropsychological domains.     

Memory beliefs and function in fibromyalgia patients

OBJECTIVE: The aim of this study was to investigate memory beliefs and their relationship to actual memory function in fibromyalgia (FM) patients. METHODS: Twenty-three FM patients, 23 age- and education-matched controls, and 22 older controls completed the Metamemory in Adulthood (MIA) questionnaire, which assessed beliefs about seven aspects of memory function. Group differences on the seven scales were assessed, and scores on the capacity scale were correlated with objective memory performance. RESULTS: FM patients reported lower memory capacity and more memory deterioration than did either control group. Patients reported lower control or self-efficacy over memory, higher achievement motivation, higher strategy use, and higher anxiety about memory than age-matched controls did. Among the patients, perceived capacity, achievement motivation, and self-efficacy were significantly correlated with objective memory performance on a recall task. CONCLUSION: FM patients' complaints about memory function have some accuracy.     

Decline in verbal memory in non-demented older adults

Decline in memory function was detected in 30% of healthy community-dwelling elderly over 6 years using a task assessing delayed word list recall. Individuals with memory decline over time also demonstrated relative deficits on additional tasks of memory and learning, a task of working memory and executive function, and on a verbal (category) fluency task at their most recent assessment. These relative deficits in the performance of individuals with memory decline cannot be explained by age-related changes, education, intelligence, mood, health-related factors, or the individuals' APOE epsilon 4 status. Decline in memory performance did not result in greater complaints of cognitive difficulties when compared with normal elderly, nor did it limit overall participation in life activities. Although the significance of memory decline in the current study was not determined quantitatively, memory decline is consistent with the early deterioration characteristic of mild cognitive impairment and preclinical Alzheimer's disease and confirms the need to monitor individuals with objective memory decline, even when these individuals fall within normal limits for a given neuropsychological task.     

Working, declarative and procedural memory in specific language impairment

According to the Procedural Deficit Hypothesis (PDH), abnormalities of brain structures underlying procedural memory largely explain the language deficits in children with specific language impairment (SLI). These abnormalities are posited to result in core deficits of procedural memory, which in turn explain the grammar problems in the disorder. The abnormalities are also likely to lead to problems with other, non-procedural functions, such as working memory, that rely at least partly on the affected brain structures. In contrast, declarative memory is expected to remain largely intact, and should play an important compensatory role for grammar. These claims were tested by examining measures of working, declarative and procedural memory in 51 children with SLI and 51 matched typically-developing (TD) children (mean age 10). Working memory was assessed with the Working Memory Test Battery for Children, declarative memory with the Children's Memory Scale, and procedural memory with a visuo-spatial Serial Reaction Time task. As compared to the TD children, the children with SLI were impaired at procedural memory, even when holding working memory constant. In contrast, they were spared at declarative memory for visual information, and at declarative memory in the verbal domain after controlling for working memory and language. Visuo-spatial short-term memory was intact, whereas verbal working memory was impaired, even when language deficits were held constant. Correlation analyses showed neither visuo-spatial nor verbal working memory was associated with either lexical or grammatical abilities in either the SLI or TD children. Declarative memory correlated with lexical abilities in both groups of children. Finally, grammatical abilities were associated with procedural memory in the TD children, but with declarative memory in the children with SLI. These findings replicate and extend previous studies of working, declarative and procedural memory in SLI. Overall, we suggest that the evidence largely supports the predictions of the PDH.     

A meta-analysis of task-related influences in prospective memory in traumatic brain injury

Prospective memory is the ability to remember to do something in the future and it is essential to every-day functional independence. Traumatic brain injury is associated with frequent and persistent prospective memory deficits. This study presents a review and meta-analysis investigating the effects of task parameters on prospective memory performance of individuals with TBI. Individual studies using continuous behavioural measures of prospective memory with a sample of adults with TBI and matched controls were included. Consistent with previous research, a random effects meta-analysis indicated that TBI groups demonstrated lower prospective memory performance than control groups (d?=?1.10, SE?=?0.12, 95% CI?=?0.86–1.34). In addition, we found that type of prospective memory cue, saliency of cues, and complexity of the ongoing task significantly moderated the difference in prospective memory performance between TBI and control groups. These findings suggest that prospective memory task parameters should be considered in the assessment of prospective memory in individuals with cognitive impairment. In addition, considering the influence of these task parameters would be useful to develop effective compensatory strategies to reduce prospective memory failures.     

Memory functions following surgery for temporal lobe epilepsy in children

Surgical treatment appears to improve the cognitive prognosis in children undergoing surgery for temporal lobe epilepsy (TLE). The beneficial effects of surgery on memory functions, particularly on material-specific memory, are more difficult to assess because of potentially interacting factors such as age range, intellectual level, left-handedness, type of surgery and seizure outcome. This study investigated memory functions in 20 right-handed children who had left or right-temporal lobe surgery - including hippocampectomy - and became seizure-free. The neuropsychological evaluation included tests measuring verbally and visually mediated episodic memory, everyday memory as well as attention/working memory and language/semantic memory. We also assessed the relationships between age of seizure onset, general cognitive ability and memory functions. Children with TLE showed poor memory efficiency before surgery that tended to improve about 1 year after surgery. We found a material-specific memory effect, especially after surgery-9 (out of 12) children with left TLE had worse verbal memory results while 5 (out of 8) with right TLE had worse visual memory results. Post-operatively, most children had poor everyday memory performance on the Rivermead Behavioural Memory Test. No significant relationship was observed between episodic memory scores and age of epilepsy onset but children with early onset remained with lower Performance IQ values, Rey's figure copy scores and naming performances after surgery. Surgery significantly improved all the attention/working memory scores, some verbal episodic memory tasks and naming test performances. A different pattern of episodic and semantic memory limitations related to left or right TLE was observed.     

Associative working memory and subsequent episodic memory in Alzheimer's disease

Recent studies indicate deficits in associative working memory in patients with medial-temporal lobe amnesia. However, it is unclear whether these deficits reflect working memory processing or are due to hippocampally mediated long-term memory impairment. We investigated associative working memory in relation to subsequent episodic memory formation in patients with early Alzheimer's disease to examine whether these findings reflect deficits in long-term encoding rather than 'pure' working memory processing. Nineteen patients with Alzheimer's disease and 21 controls performed a working memory task in which objects had to be searched at different locations. The subsequent episodic memory test required participants to reposition objects to their original locations. Patients with Alzheimer's disease were impaired on associative working memory and subsequent episodic memory, but they performed above chance at high-load episodic memory trials. This suggests that when working memory capacity is exceeded, long-term memory compensates.     

Fluctuations in plasma dopamine level impair memory in Parkinson's disease

We found a causal relationship between variation in plasma dopamine level and memory impairment in Parkinson's disease. If the level of dopamine was changed between the time of original learning and a later time of attempted memory retrieval, memory performance was impaired when compared with a maintenance of similar dopamine levels on both occasions. The absolute level of dopamine did not influence memory performance. Side-effects of levodopa-carbidopa therapy include variation in dopamine level, parkinsonian symptoms, and possibly "state-dependent" impairment of memory.     

Episodic memory in animals: Remembering which occasion

Episodic memory, the recollection of past events in one's life, has often been considered a memory specific to humans. Recent work in a variety of species has challenged this view, and has raised important questions about the nature of episodic memory itself. We present a review of the types of task proposed as episodic-like in animals and consider that these tasks require animals to demonstrate memory for specific occasions in the past. We propose that identifying episodic memory as the memory for what happened where on a specific occasion is a more encompassing definition than one that relies on information about when an event occurred. These episodic-like tasks in animals support the view that the hippocampal system is necessary for episodic memory, and that the neural substrates of episodic memory can be dissociated from those of other forms of declarative memory.     

Cognitive Training for Memory Deficits in Stroke Patients

This study was set up to evaluate the efficacy of a memory training programme in a group of stroke patients. Berg, Koning-Haanstra, and Deelman (1991) developed a training procedure which successfully improved the memory performance of a group of closed head injury patients. The training programme consists of six simple memory strategies, which are applied to daily memory problems that are selected with the patient. Two groups of stroke patients with demonstrable memory deficits were randomly assigned to the training programme or a non-specific training programme involving repetitive practice on memory tasks. After a four week training period retesting showed a significant improvement of the trained memory skills, but there was no improvement on control memory tasks. Subjective ratings of everyday memory functioning did not differ between the two groups.