Effects of clorazepate, diazepam, lorazepam, and placebo on human memory

Healthy adults (N = 10) were given oral doses of lorazepam (1 and 2 mg), diazepam (5 and 10 mg), clorazepate (7.5 and 15 mg), or placebo and tested 30, 60, 90, and 120 minutes later on a word-recall memory task. All subjects received each drug dose once and placebo twice in randomized order at weekly intervals. Testing was double-blind. Lorazepam was found to have a significantly greater effect on memory than placebo. Diazepam and clorazepate did not differ significantly from placebo in their effect on word recall. High doses of lorazepam produced more pronounced memory effects than did low doses; neither diazepam nor clorazepate was found to exert a dose-related effect on memory.     

Influence of aging on the neural correlates of autobiographical, episodic, and semantic memory retrieval

We used fMRI to assess the neural correlates of autobiographical, semantic, and episodic memory retrieval in healthy young and older adults. Participants were tested with an event-related paradigm in which retrieval demand was the only factor varying between trials. A spatio-temporal partial least square analysis was conducted to identify the main patterns of activity characterizing the groups across conditions. We identified brain regions activated by all three memory conditions relative to a control condition. This pattern was expressed equally in both age groups and replicated previous findings obtained in a separate group of younger adults. We also identified regions whose activity differentiated among the different memory conditions. These patterns of differentiation were expressed less strongly in the older adults than in the young adults, a finding that was further confirmed by a barycentric discriminant analysis. This analysis showed an age-related dedifferentiation in autobiographical and episodic memory tasks but not in the semantic memory task or the control condition. These findings suggest that the activation of a common memory retrieval network is maintained with age, whereas the specific aspects of brain activity that differ with memory content are more vulnerable and less selectively engaged in older adults. Our results provide a potential neural mechanism for the well-known age differences in episodic/autobiographical memory, and preserved semantic memory, observed when older adults are compared with younger adults.     

Ventrolateral prefrontal cortex and self-initiated semantic elaboration during memory retrieval

Left ventrolateral prefrontal cortex (LVPFC) is often implicated in neuroimaging studies of context memory retrieval. This activation has been argued to reflect proactive semantic processing that facilitates recollection of past events, or instead to reflect a reactive response to experienced episodic interference. We investigated these characterizations in an fMRI study that manipulated the relative distinctiveness of encoding across subsequent targets and lures by varying encoding task manipulations. Critically, during later testing, retrieval queries and prior target processing where held constant across the distinctive and non-distinctive testing conditions, and therefore any differences in cortical activity would be linked to subject-initiated retrieval strategies. We found that LVPFC activity was specific to context retrieval under distinctive conditions even though this condition demonstrated the least interference. The results suggest that this region is critical for self-initiated semantic elaboration during retrieval, and this conclusion was bolstered by finding that LVPFC activity predicted individual differences in context memory discrimination. In line with Tulving's Encoding Specificity Principle, we suggest that subjects actively construct semantic retrieval cues, reflected in increased VLPFC activation, in an attempt to isolate the distinctive semantic features of hypothetical experiences when possible. If successful, this improves the match between retrieval cue and engram and facilitates performance.     

Analysis of learning and rate of forgetting in age-associated memory differences

This study used a visual free-recall paradigm to examine rate of forgetting in a sample of 255 normal adults (age range 18–91 years). Subjects were administered the Visual Reproduction Subtest (VR) from Form I of the Wechsler Memory Scale, along with a 30-min delayed-recall procedure. Results revealed that older adults performed below levels obtained by younger ones on both phases of the VR. However, analysis revealed no differences among age groups in rate of forgetting. Lower scores for older subjects on the delayed-recall task appeared to reflect differences in initial learning, not an accelerated rate of forgetting. Normative data for rate of forgetting were provided for adults in all age groups.     

Episodic memory,semantic memory,and amnesia

Episodic memory and semantic memory are two types of declarative memory. There have been two principal views about how this distinction might be reflected in the organization of memory functions in the brain. One view, that episodic memory and semantic memory are both dependent on the integrity of medial temporal lobe and midline diencephalic structures, predicts that amnesic patients with medial temporal lobe/diencephalic damage should be proportionately impaired in both episodic and semantic memory. An alternative view is that the capacity for semantic memory is spared, or partially spared, in amnesia relative to episodic memory ability. This article reviews two kinds of relevant data: 1) case studies where amnesia has occurred early in childhood, before much of an individual's semantic knowledge has been acquired, and 2) experimental studies with amnesic patients of fact and event learning, remembering and knowing, and remote memory. The data provide no compelling support for the view that episodic and semantic memory are affected differently in medial temporal lobe/diencephalic amnesia. However, episodic and semantic memory may be dissociable in those amnesic patients who additionally have severe frontal lobe damage. Hippocampus 1998;8:205–211. Published 1998 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America.

     

Profiles of recent autobiographical memory retrieval in semantic dementia, behavioural-variant frontotemporal dementia, and Alzheimer's disease

Episodic autobiographical memory (ABM) comprises recollection for events that are grounded within a specific spatiotemporal context, and usually accompanied by perceptual and emotional information. The neural substrates mediating ABM retrieval are those harbouring significant pathology in semantic dementia (SD) and behavioural-variant frontotemporal dementia (bvFTD), the most common subtypes of FTD. Relatively little is known, however, regarding the differential patterns of contextual details during episodic ABM retrieval across these dementia syndromes. This study investigated episodic ABM retrieval under free and probed recall conditions from 4 time periods with the aim to identify disease-specific profiles of episodic ABM contextual details. Episodic ABM was measured in 25 SD and 15 bvFTD patients and their performance contrasted to that of 17 Alzheimer's disease (AD) patients and 19 age-matched controls. Critically, SD patients showed relatively preserved recent ABM in comparison with remote epochs. In contrast, bvFTD and AD patients showed a reduced capacity to recall specific and contextually rich ABMs across all life epochs, in both free and probed recall conditions. Analyses of the recent period (last 12 months) provided evidence for different profiles of contextual episodic details recalled in dementia syndromes. Following probing, SD patients’ recall deficits emanated exclusively from compromised Emotion/Thoughts and Spatiotemporal details. In contrast, bvFTD patients were significantly impaired across all categories of contextual details whereas AD patients showed deficits for Event and Emotion/Thoughts details only. As the largest study of ABM in FTD to date, these findings emphasise the differential impairment of recent ABM contextual details contingent on the underlying disease pathology. In addition, these results point towards the importance of investigating the constituent elements of emotion processing and strategic retrieval processes as potential variables mediating recent episodic ABM retrieval.     

Insights from semantic dementia on the relationship between episodic and semantic memory

An influential theory of long-term memory, in which new episodic learning is dependent upon the integrity of semantic memory, predicts that a double dissociation between episodic and semantic memory is not possible in new learning. Contrary to this view, we found, in two separate experiments, that patients with impaired semantic memory showed relatively preserved performance on tests of recognition memory if the stimuli were perceptually identical between learning and test. A significant effect of semantic memory was only seen when a perceptual manipulation was introduced in the episodic task. To account for these findings, we propose a revision to current models of long-term memory, in which sensory/perceptual information and semantic memory work in concert to support new learning.     

The hippocampus,medial prefrontal cortex,and selective memory retrieval: Evidence from a rodent model of the retrieval‐induced forgetting effect

Inhibition is an important component of many cognitive functions, including memory. For example, the retrieval‐induced forgetting (RIF) effect occurs when extra practice with some items from a study list inhibits the retrieval of the nonpracticed items relative to a baseline condition that does not involve extra practice. Although counterintuitive, the RIF phenomenon may be important for resolving interference by inhibiting potentially competing retrieval targets. Neuroimaging studies suggest that the hippocampus and prefrontal cortex are involved in the RIF effect, but controlled lesion studies have not yet been performed. We developed a rodent model of the RIF training procedure and trained control rats and rats with temporary inactivation of the hippocampus or medial prefrontal cortex (mPFC). Rats were trained on a list of odor cues, presented in cups of digging medium with a buried reward, followed by additional practice trials with a subset of the cues. We then tested the rats' memories for the cues and their association with reward by presenting them with unbaited cups containing the test odorants and measuring how long they persisted in digging. Control rats exhibited a robust RIF effect in which memory for the nonpracticed odors was significantly inhibited. Thus, extra practice with some odor cues inhibited memory for the others, relative to a baseline condition that involved an identical amount of training. Inactivation of either the hippocampus or the mPFC blocked the RIF effect. We also constructed a computational model of a representational learning circuit to simulate the RIF effect. We show in this model that “sideband suppression” of similar memory representations can reproduce the RIF effect and that alteration of the suppression parameters and learning rate can reproduce the lesion effects seen in our rats. Our results suggest that the RIF effect is widespread and that inhibitory processes are an important feature of memory function. © 2014 Wiley Periodicals, Inc.     

Overlap in the functional neural systems involved in semantic and episodic memory retrieval

Neuroimaging and neuropsychological data suggest that episodic and semantic memory may be mediated by distinct neural systems. However, an alternative perspective is that episodic and semantic memory represent different modes of processing within a single declarative memory system. To examine whether the multiple or the unitary system view better represents the data we conducted a network analysis using multivariate partial least squares (PLS ) activation analysis followed by covariance structural equation modeling (SEM) of positron emission tomography data obtained while healthy adults performed episodic and semantic verbal retrieval tasks. It is argued that if performance of episodic and semantic retrieval tasks are mediated by different memory systems, then there should differences in both regional activations and interregional correlations related to each type of retrieval task, respectively. The PLS results identified brain regions that were differentially active during episodic retrieval versus semantic retrieval. Regions that showed maximal differences in regional activity between episodic retrieval tasks were used to construct separate functional models for episodic and semantic retrieval. Omnibus tests of these functional models failed to find a significant difference across tasks for both functional models. The pattern of path coefficients for the episodic retrieval model were not different across tasks, nor were the path coefficients for the semantic retrieval model. The SEM results suggest that the same memory network/system was engaged across tasks, given the similarities in path coefficients. Therefore, activation differences between episodic and semantic retrieval may ref lect variation along a continuum of processing during task performance within the context of a single memory system.     

The impact of semantic memory impairment on spelling: evidence from semantic dementia

We assessed spelling and reading abilities in 14 patients with semantic dementia (with varying degrees of semantic impairment) and 24 matched controls, using spelling-to-dictation and single-word reading tests which manipulated regularity of the correspondences between spelling and sound, and word frequency. All of the patients exhibited spelling and reading deficits, except at the very earliest stages of disease. Longitudinal study of seven of the patients revealed further deterioration in spelling, reading, and semantic memory. The performance of both subject groups on both spelling and reading was affected by regularity and word frequency, but these effects were substantially larger for the patients. Spelling of words with exceptional (or more precisely, unpredictable) sound-to-spelling correspondences was most impaired, and the majority of errors were phonologically plausible renderings of the target words. Reading of low frequency words with exceptional spelling-to-sound correspondences was also significantly impaired. The spelling and reading deficits were correlated with, and in our interpretation are attributed to, the semantic impairment.     

Common prefrontal activations during working memory,episodic memory,and semantic memory

Regions of the prefrontal cortex (PFC) are typically activated in many different cognitive functions. In most studies, the focus has been on the role of specific PFC regions in specific cognitive domains, but more recently similarities in PFC activations across cognitive domains have been stressed. Such similarities may suggest that a region mediates a common function across a variety of cognitive tasks. In this study, we compared the activation patterns associated with tests of working memory, semantic memory and episodic memory. The results converged on a general involvement of four regions across memory tests. These were located in left frontopolar cortex, left mid-ventrolateral PFC, left mid-dorsolateral PFC and dorsal anterior cingulate cortex. These findings provide evidence that some PFC regions are engaged during many different memory tests. The findings are discussed in relation to theories about the functional contribution of the PFC regions and the architecture of memory.     

Effects of phonological and semantic cuing on encoding and retrieval processes in adolescent psychosis

The aim of this study was to investigate the effects of cuing on encoding and retrieval processes in adolescent psychosis. Patients and controls were instructed to learn word lists under three conditions: no cue, phonological cue, and semantic cue. Memory performance was measured with free and cued recalls. In free recall, both groups showed higher performance with semantic than with phonological encoding cues, but patients had no advantage from semantic cuing relative to no cue, contrary to controls. Patients' performance improved from free to cued recall, but this was not sufficient to normalize their performance. Impaired strategic processes may lead to encoding and retrieval difficulties in patients.     

Effortful verb retrieval from semantic memory drives beta suppression in mesial frontal regions involved in action initiation

The contribution of the motor cortex to the semantic retrieval of verbs remains a subject of debate in neuroscience. Here, we examined whether additional engagement of the cortical motor system was required when access to verbs semantics was hindered during a verb generation task. We asked participants to produce verbs related to presented noun cues that were either strongly associated with a single verb to prompt fast and effortless verb retrieval, or were weakly associated with multiple verbs and more difficult to respond to. Using power suppression of magnetoencephalography beta oscillations (15–30 Hz) as an index of cortical activation, we performed a whole‐brain analysis in order to identify the cortical regions sensitive to the difficulty of verb semantic retrieval. Highly reliable suppression of beta oscillations occurred 250 ms after the noun cue presentation and was sustained until the onset of verbal response. This was localized to multiple cortical regions, mainly in the temporal and frontal lobes of the left hemisphere. Crucially, the only cortical regions where beta suppression was sensitive to the task difficulty, were the higher order motor areas on the medial and lateral surfaces of the frontal lobe. Stronger activation of the premotor cortex and supplementary motor area accompanied the effortful verb retrieval and preceded the preparation of verbal responses for more than 500 ms, thus, overlapping with the time window of verb retrieval from semantic memory. Our results suggest that reactivation of verb‐related motor plans in higher order motor circuitry promotes the semantic retrieval of target verbs.     

Effects of central administration of arginine-vasopressin on aversive memory retrieval

This study examined whether arginine-vasopressin (A-VP), given before the test would produce an improved retrieval of aversive memory, in the same way as pre-exposure to inescapable footshocks, in rats. For this purpose animals conditioned in a T-maze with appetitive (10% sucrose) and aversive (2.0 mA footshock) events were administered (intracerebroventricular) a single dose of 2.5, 5, 10 or 20 ng/rat of A-VP, 20-min before testing. In the retention test conducted with the same training apparatus 72 h after conditioning, the peptide treated rats showed a dose-dependent increase in latencies to enter the previously shocked goalarm, with the absence of such a difference in responding to the non-shocked goalarm. This differential response was not observed in saline treated rats. This effect of peptide on memory retrieval was similar to that seen following inescapable footshock in rats. These results suggest the possible involvement of central vasopressinergic mechanisms in the differential enhancement of memory of helplessness condition.     

Effects of immune activation on the retrieval of spatial memory

Objective

It has been shown that there are extensive interactions between the central nervous system and the immune system. The present study focused on the effects of lipopolysaccharide (LPS) on memory retrieval, to explore the interaction between immune activation and memory.

Methods

C57BL/6J mice (8 weeks old) were first trained in the Morris water maze to reach asymptotic performance. Then mice were tested 24 h after the last training session and LPS was administered (1.25 mg/kg, i.p.) 4 h prior to the testing. The retrieval of spatial memory was tested by probe trial, and the time spent in the target quadrant and the number of platform location crosses were recorded. ELISA was performed to detect interleukin-1β (IL-1β) protein level in the hippocampus of mice tested in the water maze.

Results

Although LPS induced overt sickness behavior and a significant increase in the level of IL-1β in the hippocampus of mice, there was no significant difference in the time spent in the target quadrant or in the number of platform location crosses between LPS-treated and control groups in the probe trial testing.

Conclusion

Immune activation induced by LPS does not impair the retrieval of spatial memory.     

Effects of memory consolidation on human hippocampal activity during retrieval

Day-to-day memories undergo transformation from short-term to long-term storage, a process called memory consolidation. Animal studies showed that memory consolidation requires protein synthesis and the growth of new hippocampal synapses within 24 h. To test for effects of memory consolidation in the human, we examined brain activation during the retrieval of information at 10 min and at 24 h following learning using functional magnetic resonance imaging (fMRI), an indirect measure of synaptic activity. Learning instructions were adjusted to yield a comparable retrieval quantity and retrieval quality at 10 min and 24 h after learning. The left hippocampal formation exhibited enhanced activity during the retrieval at the 24 h lag compared to the retrieval at the 10 min lag. Moreover, the activity in the left anterior hippocampal formation showed stronger correlations with retrieval quantity and retrieval quality at the 24 h lag than at the 10 min lag. This suggests that the relation between left anterior hippocampal activity and retrieval success became closer as consolidation progressed. These fMRI results in the human hippocampal formation may correspond to the neurobiological results in the animal hippocampal formation of a strengthening and growth of synaptic connections within 24 h.     

Effects of event-specific memory training on autobiographical memory retrieval and depressive symptoms in schizophrenic patients

Background and objectivesThis report describes the effects of a specific event group-based training programme on autobiographical memory, self-consciousness of memory retrieval, and depression symptoms in a sample of 24 schizophrenic patients (experimental group).MethodsTwenty-six matched schizophrenic patients who participated in social skills and occupational therapy group sessions constituted the active control group. Participants in the experimental group were trained to complete a diary with specific daily memories, followed by patients’ ratings of the associated emotional arousal of those entries. During training, significant specific events from childhood, adolescence, adulthood and the previous year were also reviewed.ResultsAfter 10 weeks of group-based sessions, the experimental group demonstrated an increase in their degree of specificity for autobiographical retrievals, had a higher level of consciousness of their memories and showed a decrease in their depression scores. Significant changes in measurements of retrieval specificity and autonoetic awareness were maintained when changes in emotional symptomatology were statistically controlled.LimitationsThe present study did not assess the impact of autobiographical memory training on the positive and negative symptoms of schizophrenia.ConclusionsThese results suggest that cognitive training strategies based on event-specific autobiographical memory training should be considered for inclusion in intervention programs for schizophrenic patients.     

The contribution of autobiographical significance to semantic memory: evidence from Alzheimer's disease, semantic dementia, and amnesia

In a previous study [Memory Cognit., in press], we demonstrated that some semantic concepts are more likely than others to be associated with specific personal memories, and that this autobiographical significance gives these concepts special status in long-term memory. In this paper, we explore the possible neural correlates of autobiographically significant semantic knowledge and examine whether or not autobiographical significance is a factor in determining patterns of semantic memory loss caused by brain damage. Using famous names that were rated on various attributes, including autobiographical significance, by control participants in a norming study [Memory Cognit., in press], we found that semantic dementia (SD) patients were more likely to recognize, identify and remember autobiographically significant episodes involving famous names that were rated high in autobiographical significance as compared to equally familiar names that were rated low. By contrast, people with Alzheimer's disease (AD) and people with medial temporal lobe (MTL) amnesia did not exhibit this preference for names rated high in autobiographical significance. Furthermore, in tests of free recall, recognition, fame judgment and speeded reading, semantic dementia patients demonstrated a performance advantage for autobiographically significant famous names, whereas the other patient groups did not. These findings suggest a critical role for medial temporal regions in the mediation of autobiographical memory and the interaction between personal experience and semantic memory. Theoretical implications are discussed.     

Neural correlates of episodic and semantic memory retrieval in borderline personality disorder: An fMRI study

Verbal memory impairment in borderline personality disorder (BPD) is still a matter of debate. In this study we combine investigations of both, memory retrieval as well as underlying neural circuits in BPD. Functional magnetic resonance imaging (fMRI) was used to study regional brain activation in 18 right-handed female patients with BPD and 18 matched controls during the retrieval of an episodic memory retrieval (EMR) task (free recall of a word list) and a semantic memory retrieval (SMR) task (verbal fluency). Despite unaffected performance in EMR and SMR, patients with BPD showed task-specific increased activation compared with controls. During EMR, the increased activation encompassed the posterior cingulate cortex bilaterally, the left middle and superior temporal gyrus, the right inferior frontal gyrus, and the right angular gyrus. SMR was associated with increased activation of the posterior cingulate cortex, of the right fusiform gyrus, of the left anterior cingulate cortex, and of the left postcentral gyrus. Our findings suggest that BPD patients may need to engage larger brain areas to reach a level of performance in episodic and semantic retrieval tasks that is comparable to that of healthy controls.