Recognition memory for single items and for associations is similarly impaired following damage to the hippocampal region

The formation of new associations between items is critical for establishing episodic memories. It has been suggested that the hippocampus is essential for creating such associations but is not involved, or is much less involved, in memory for single items. In Experiment 1, we tested controls and amnesic patients with bilateral lesions thought to be limited primarily to the hippocampal region in both single-item and associative recognition memory tasks. In the single-item task, a conventional recognition memory task was administered in which participants studied either houses or faces and were tested for their ability to recognize the individual items. In the associative task, participants studied paired pictures of houses and faces with instructions that encouraged associating the two stimuli, and were tested for their ability to recognize the specific pairings that were presented at study. Like the controls, the amnesic patients performed more poorly on the associative task. Relative to the controls, the amnesic patients were impaired to a similar extent on the single-item and associative tasks. In Experiment 2, the performance of the amnesic patients was improved by increasing the number of presentations of the study lists (eight presentations instead of one). On both the single-item and associative tests, the performance of the amnesic patients after eight presentations was now identical to the performance of the controls who had been given only one presentation of the study list. Thus, the associative condition was not disproportionally difficult for the amnesic patients. These results are consistent with the idea that the hippocampus is similarly involved in single-item and associative memory.     

Differential effects of PACAP-38 on synaptic responses in rat hippocampal CA1 region

Pituitary adenylate cyclase-activating polypeptide (PACAP-38) is a member of the vasointestinal polypeptide (VIP)/secretin/glucagon family of neuropeptides for which neuroregulatory functions have been postulated. PACAP-38 receptors are expressed in different brain regions, including hippocampus. In this study, we examined the dose-dependent effects of PACAP-38 on the excitatory postsynaptic field potential (fEPSP) evoked at the Schaffer collateral-CA1 synapse in rat hippocampal slices. Bath application of low dose (0.05 nM) of PACAP-38 induced long-lasting facilitation of the fEPSP. This enhancement was blocked by the cholinergic receptor antagonist atropine and partially by the NMDA receptor antagonist 2-amino-5-phosphonovalerate (APV) and therefore, shares a common mechanism with LTP. In contrast, a high dose (1 μM) of PACAP-38 induced a persistent depression of the fEPSP that was not blocked by antagonists of cholinergic receptors (i.e., atropine and mecamylamine), adenosine receptors (i.e., DCPCX), or glutamatergic NMDA receptors (APV). Intermediate doses (0.1–0.5 μM) of PACAP-38 produced an initial decrease of the fEPSP followed by an enhancement. This decrease was not blocked by atropine whereas the facilitation was. These results show that PACAP-38 modulates CA1 synaptic transmission in a dose-dependent manner and that the peptide interacts with cholinergic and glutamatergic systems.     

Simple and associative recognition memory in the hippocampal region

Although it is well established that the hippocampal region is involved in the formation of declarative memory, the exact nature of its involvement is unclear. One view is that the hippocampal region is involved only in tasks that require the formation or use of associations. According to this view, the hippocampal region is not involved in traditional tests of recognition memory. An alternative view is that the hippocampal region combines and extends the processing carried out by structures in the parahippocampal gyrus and that it is involved in all forms of declarative memory, including recognition memory. Using event-related functional magnetic resonance imaging (fMRI), we observed hippocampal activity during both traditional and associative recognition memory tasks. Critically, the hippocampal region was no more active in the associative recognition task than in the traditional recognition task.     

The effects of hippocampal lesions on learning, memory, and reward expectancies

The hippocampus appears to be critical for the formation of certain types of memories. Hippocampal-lesioned animals fail to exhibit some spatial, contextual, and relational associations. After aspiration lesions of the hippocampus and/or cortex, male rats were allowed to recover for three weeks before being trained on a matching-to-position task. The matching-to-position task was altered to influence the type of cognitive strategies a subject would use to solve the task. The main behavioral manipulation was the reinforcement contingency assignment: Use of a differential outcomes procedure (DOP) or a nondifferential outcomes procedure (NOP). The DOP involves correlating each to-be-remembered event with a distinct reward condition via Pavlovian trace conditioning, whereas the NOP results in random reward contingency. We found that hippocampal lesions did retard learning the matching rule, regardless of the reinforcement contingency assignment. However, when delay intervals were added to the task memory performance of subjects with hippocampal lesions was dramatically impaired--if subjects were not trained with the DOP. When subjects were trained with the DOP, the hippocampal lesion had a marginal effect on delayed memory performance. These findings demonstrate two important points regarding lesions of the hippocampus: (1) hippocampal lesions have a minimal effect on the on the ability of rats to use reward information to solve a delayed discrimination task; (2) rats with hippocampal lesions have the ability to learn about reward information using Pavlovian trace conditioning procedures.     

Integrating incremental learning and episodic memory models of the hippocampal region

By integrating previous computational models of corticohippocampal function, the authors develop and test a unified theory of the neural substrates of familiarity, recollection, and classical conditioning. This approach integrates models from 2 traditions of hippocampal modeling, those of episodic memory and incremental learning, by drawing on an earlier mathematical model of conditioning, SOP (A. Wagner, 1981). The model describes how a familiarity signal may arise from parahippocampal cortices, giving a novel explanation for the finding that the neural response to a stimulus in these regions decreases with increasing stimulus familiarity. Recollection is ascribed to the hippocampus proper. It is shown how the properties of episodic representations in the neocortex, parahippocampal gyrus, and hippocampus proper may explain phenomena in classical conditioning. The model reproduces the effects of hippocampal, septal, and broad hippocampal region lesions on contextual modulation of classical conditioning, blocking, learned irrelevance, and latent inhibition.     

The effects of aging and dorsal hippocampal lesions: performance on spatial and nonspatial comparable versions of the water maze

Aged intact and young hippocampal-lesioned rats show similar deficits on the spatial water maze. However, this does not necessitate that the source of these deficits in the aged animals is due to hippocampal damage. These water maze deficits may arise from other aging factors such as changes in thermoregulation, muscle fatigue, swim ability, and response to stress. Consequently, it is imperative to examine the performance of aged rats on a comparable nonhippocampal version of this task. Past attempts to develop a hippocampus-independent version of the water maze were confounded because these tasks were easier (i.e., the rats spent much less time swimming in the water) than the spatial versions of the task. The current study examined performance on a hippocampus-independent task comparable in difficulty to the spatial water one. Middle-aged (16-m) and old (25-m) male F344 rats were given sham or dorsal hippocampus lesions and tested on both a spatial and a nonspatial water maze. The middle-aged rats with hippocampal lesions were impaired on the spatial task but not on the nonspatial task. Conversely, aged animals showed a similar impairment on both types of water maze tasks. Additionally, hippocampal lesions exacerbated the age-related impairment on both tasks. These findings indicate that caution must be used when interpreting the results of water maze tasks for aged animals.     

The effects of natural category size on memory for episodic encodings

Previous findings indicate that natural category size affects cued recall but not recognition performance. Words that define or belong to larger categories are not as likely to be recalled in the presence of an extralist cue. However, category size has no effect on recognition in the presence of the target as the cue. Theoretically, this difference could be due to inherent differences between these tasks, to the use of different types of test cues, or to differences in the nature of the required responses (naming compared with “yes/no”decisions). Three experiments indicated that none of these factors is a sole determinant. Natural category size effects were found in cued-recall and recognition tasks, with extralist and target cues and regardless of the required response. The critical factor is whether the testing conditions require or encourage subjects to search the category defined by the cue. With the initiation of such a search, information represented in semantic memory is likely to influence memory for episodic information.     

Differential effects of alcohol on associative versus item memory

Alcohol has detrimental effects on a range of cognitive processes, the most prominent being episodic memory. These deficits appear functionally similar to those observed within the normal aging population. We investigated whether an associative memory deficit, as found in older adults, would also be evident in young adults moderately intoxicated by alcohol. Participants were shown unrelated word pairs and then tested on both their item recognition (old/new item?) and associative recognition (intact/recombined pair?). Half the participants were under the influence of alcohol whereas the other half were sober. Alcohol impaired memory performance but significantly more so for associative than for item memory. Moreover, within the alcohol group, the associative memory deficit was significantly related to the amount of alcohol consumed. The findings suggest that not all aspects of episodic memory are equally impaired by alcohol, which may have practical implications for criminal investigations involving eye witnesses who have consumed alcohol.     

Differential role of the hippocampal endocannabinoid system in the memory consolidation and retrieval mechanisms

CB1 cannabinoid receptors are abundantly expressed in the brain, with large concentrations present in the hippocampus, a brain structure essential for memory processing. In the present study, we have investigated the possible modulatory role of the endocannabinoid system in the dorsal hippocampus upon the different phases of memory processing of an aversive task. AM251, a selective antagonist of CB1 receptors, and anandamide, an endogenous agonist of cannabinoid receptors, were bilaterally infused into the dorsal hippocampus of male Wistar rats either before training, immediately after training, or before test in the step-down inhibitory avoidance (IA) task. Results showed that pre-training infusion of CB1 drugs did not influence the acquisition of the task. In contrast, post-training infusion of the CB1 antagonist disrupted while the antagonist facilitated memory consolidation of IA. The post-training results demonstrate that memory consolidation depends on the integrity of the endocannabinoid system in the CA1 region of the dorsal hippocampus. While we still have no direct proof of endocannabinoids released there after an aversive task such as IA, these results suggests that (a) AM251 acts blocking the binding of endogenously released cannabinoids and (b) exogenously supplemented anandamide may be adding its contribution to the action of the endogenously released pool. Considering our data and the higher density of CB1 receptors present in the GABAergic interneurons, we propose them as the putative target of the endocannabinoid modulation of memory, a hypothesis that needs to be proven. In addition, pre-test infusion of the CB1 receptor antagonist facilitated while infusion of the agonist did not affect memory retrieval of IA. The completely opposite action of the same drug upon memory at the post-training (consolidation) and pre-test (recall) contexts suggests that some durable change took place in the CA1 region during the consolidation process that modified the logical attributes of the pharmacological response, i.e., the drug response changed from memory disruption to memory facilitation. A similar phenomenon was previously described by us in the M4 cholinergic muscarinic subsystem in the hippocampus for the same task (Diehl, F., Fürstenau, L. O., Sanchez, G., Camboim, C., de Oliveira Alvares, L., Lanziotti, V. B., et al. (2007). Facilitatory effect of the intra-hippocampal pretest administration of MT3 in the inhibitory avoidance task. Behavioral Brain Research, 177(2), 227-231), but the biological nature of such change in the local neural circuitry remains to be investigated.     

Computational models of the hippocampal region: linking incremental learning and episodic memory

The hippocampal region, a group of brain structures important for learning and memory, has been the focus of a large number of computational models. These tend to fall into two groups: (1) models of the role of the hippocampal region in incremental learning, which focus on the development of new representations that are sensitive to stimulus regularities and environmental context; (2) models that focus on the role of the hippocampal region in the rapid storage and retrieval of episodic memories. Rather than being in conflict, it is becoming apparent that both approaches are partially correct and might reflect the different functions of substructures of the hippocampal region. Future computational models will help to elaborate how these different substructures interact.     

The effect of spatial and nonspatial contextual information on visual object memory

Recent research has found visual object memory can be stored as part of a larger scene representation rather than independently of scene context. The present study examined how spatial and nonspatial contextual information modulate visual object memory. Two experiments tested participants’ visual memory by using a change detection task in which a target object's orientation was either the same as it appeared during initial viewing or changed. In addition, we examined the effect of spatial and nonspatial contextual manipulations on change detection performance. The results revealed that visual object representations can be maintained reliably after viewing arrays of objects. Moreover, change detection performance was significantly higher when either spatial or nonspatial contextual information remained the same in the test image. We concluded that while processing complex visual stimuli such as object arrays, visual object memory can be stored as part of a comprehensive scene representation, and both spatial and nonspatial contextual changes modulate visual memory retrieval and comparison.     

Dissociation of the neural systems for working memory maintenance of verbal and nonspatial visual information

Working memory for names and faces was investigated to ascertain whether verbal and nonspatial visual information is maintained in working memory by separate neural systems. The subjects performed a delayed match-to-sample task for famous or unfamous faces and names and a sensorimotor control task. Several occipital, temporal, parietal, and prefrontal areas were activated during all memory delays, in comparison with the control delays. Greater delay activity for unfamous faces than for names was obtained in the right fusiform gyrus, right inferior frontal gyrus (IFG), right IFG/ precentral gyrus, and right medial superior frontal gyrus, whereas greater delay activity for unfamous names than for faces was observed in the precuneus, left insula/postcentral gyrus, and left IFG/ precentral gyrus. There was no significant difference in the prefrontal activity in the comparison between famous faces and names. Greater delay activity for famous names than for faces was obtained in visual association and parietal areas. The results indicate that there is a functional dissociation based on information type within the neural system that is responsible for working memory maintenance of verbal and nonspatial visual information.     

Differential effects of cue dependency on item and source memory

The authors investigated the cue dependency of source and item memory. Individuals listened to words spoken by a man or a woman and later determined whether a test word was previously presented by a man or by a woman, or whether it was a new word. Cue dependent effects were assessed by presenting test words with (a) the same voice (match condition) that originally presented the word, (b) a different but familiar voice (mismatch condition), (c) a novel test voice (novel condition), and (d) no test voice (control condition). Compared with the control condition, source recollection was facilitated in matching-context conditions, disrupted in mismatching-context conditions, and not affected in novel test conditions. By contrast, item recognition was not affected by the match-mismatch manipulation but was significantly worse in novel test voice conditions. The authors propose an associative source interference view to account for the voice match-mismatch effects observed in source recollection.     

Differential age effects for implicit and explicit conceptual associative memory

Older adults show disproportionate declines in explicit memory for associative relative to item information. However, the source of these declines is still uncertain. One explanation is a generalized impairment in the processing of associative information. A second explanation is a more specialized impairment in the strategic, effortful recollection of associative information, leaving less effortful forms of associative retrieval preserved. Assessing implicit memory of new associations is a way to distinguish between these viewpoints. To date, mixed findings have emerged from studies of associative priming in aging. One factor that may account for the variability is whether the manipulations inadvertently involve strategic, explicit processes. In two experiments we present a novel paradigm of conceptual associative priming in which subjects make speeded associative judgments about unrelated objects. Using a size classification task, Experiment 1 showed equivalent associative priming between young and older adults. Experiment 2 generalized the results of Experiment 1 to an inside/outside classification task, while replicating the typical age-related impairment in associative but not item recognition. Taken together, the findings support the viewpoint that older adults can incidentally encode and retrieve new meaningful associations despite difficulty with the intentional recollection of the same information.     

Differential effects of repetition on pre- and postcategorical memory traces

The effect of list repetition on immediate recall for aurally presented nine-letter lists was studied under two conditions. In the first, a redundant stimulus item was presented as the tenth item in each list, while the suffix was not included in a control condition. As in previous research (Crowder & Morton, 1969), the stimulus suffix selectively interfered with recall at the terminal presentation serial positions, indicating the presence of precategorical acoustic storage. Repetition had a nonselective effect on performance. This result and an analysis of acoustic errors support the inference that qualitative differences in the memory code may lead to differences in other functional properties of the memory trace, such as responsiveness to repetition.     

Differential time-dependent effects of emotion on recollective experience and memory for contextual information

Emotion has been suggested to slow forgetting via a mechanism that enhances memory consolidation. Here, we investigate whether this time dependent process influences the subjective experience of recollection as well as the ability to retrieve specific contextual details of the study event. To do so we examined recognition for emotional and neutral pictures at two retention intervals and collected remember/know reports and reports about the task that had been performed with the item during encoding. Recollective experience was enhanced for emotional compared to neutral photos after a 24-h delay, but not immediately after encoding. In contrast, memory for the task performed during encoding did not differ between emotional and neutral photos at either time point. The findings indicate that emotion slows the effects of forgetting on the recollective experience associated with studied events, without necessarily slowing the forgetting of specific contextual details of those events.     

Prior knowledge: the effects of natural category size on memory for implicitly encoded concepts

Studying a familiar word activates its associates, and these associates affect the likelihood of recalling the studied word in a cued recall task. These experiments examined variables that normally affect memory for the studied word to determine if they have similar effects on memory for the word's associates. Memory for associates was tested by cued recall (Experiments 1-3) or by recognition (Experiments 4-5), with the number and strength of the associates varied in all experiments. In different experiments, test instructions (direct-indirect), distractor tasks, lag, and amount of practice were manipulated. Provided that subjects were not distracted prior to test, the probability of recalling associates of the studied word decreased with the number of associates activated and with their strength under all conditions. The strength of the associates but not their number affected recognition. In general, variables that affected recall and recognition of studied words had parallel effects on their associates.     

Differential effects of age on item and associative measures of memory: a meta-analysis

In this meta-analysis, the authors evaluated recent suggestions that older adults' episodic memory impairments are partially due to a reduced ability to encode and retrieve associated/bound units of information. Results of 90 studies of episodic memory for both item and associative information in 3,197 young and 3,192 older adults provided support for the age-related associative/binding deficit suggestion, indicating a larger effect of age on memory for associative information than for item information. Moderators assessed included the type of associations, encoding instructions, materials, and test format. Results indicated an age-related associative deficit in memory for source, context, temporal order, spatial location, and item pairings, in both verbal and nonverbal material. An age-related associative deficit was quite pronounced under intentional learning instructions but was not clearly evident under incidental learning instructions. Finally, test format was also found to moderate the associative deficit, with older adults showing an associative/binding deficit when item memory was evaluated via recognition tests but not when item memory was evaluated via recall tests, in which case the age-related deficits were similar for item and associative information.     

Sex and post-menopause hormone therapy effects on hippocampal volume and verbal memory

Many studies suggest sex differences in memory and hippocampal size, and that hormone therapy (HT) may positively affect these measures in women; however, the parameters of HT use that most likely confer benefits are debated. We evaluated the impact of sex and postmenopausal HT use on verbal learning and memory and hippocampal size in 94 cognitively intact women and 49 men. Using analysis of covariance that controlled for age and education, women had better total word learning and delayed verbal memory performance than men. HT analyses showed that non-HT users performed similarly to men, while HT users performed better than men in Delayed Memory regardless of whether use was current or in the past. Women had larger hippocampal volumes than men regardless of whether they were HT users. Using univariate linear models, we assessed group differences in the predictive value of hippocampal volumes for verbal learning and memory. Hippocampal size significantly predicted memory performance for men and non-HT users, but not for HT users. This lack of relationship between hippocampal size and verbal learning and memory performance in HT users suggests HT use may impact memory through extra-hippocampal neural systems.     

Effects of frontal lobe damage on interference effects in working memory

Working memory is hypothesized to comprise a collection of distinct components or processes, each of which may have a unique neural substrate. Recent neuroimaging studies have isolated a region of the left inferior frontal gyrus that appears to be related specifically to one such component: resolving interference from previous items in working memory. In the present study, we examined working memory in patients with unilateral frontal lobe lesions by using a modified version of an item recognition task in which interference from previous trials was manipulated. In particular, we focused on patient R.C., whose lesion uniquely impinged on the region identified in the neuroimaging studies of interference effects. We measured baseline working memory performance and interference effects in R.C. and other frontal patients and in age-matched control subjects and young control subjects. Comparisons of each of these groups supported the following conclusions. Normal aging is associated with changes to both working memory and interference effects. Patients with frontal damage exhibited further declines in working memory but normal interference effects, with the exception of R.C., who exhibited a pronounced interference effect on both response time and accuracy. We propose that the left inferior frontal gyrus subserves a general, nonmnemonic function of selecting relevant information in the face of competing alternatives and that this function may be required by some working memory tasks.