Familiarity-based Memory Research Articles

We remember the good things: Age differences in learning and memory

We combined a feedback-based learning task with a recognition memory paradigm to investigate how reward-based learning affects the event-related potential (ERP) correlates of recognition memory in younger and older adults. We found that positive, but not negative learning improves memory and results in an increased early ERP old–new effect, which is typically associated with familiarity-based memory. This indicates that reward-based learning supports a fast and relatively automatic memory retrieval process. Furthermore, we found age-related impairments in reward-based learning, whereas memory for the learned information was intact in the elderly, suggesting that declarative memory might be less affected by aging.

Age differences in the contribution of recollection and familiarity to false‐memory formation: a new paradigm to examine developmental reversals

Using a new method for studying the development of false-memory formation, we examined developmental differences in the rates at which 6-, 7-, 9-, 10-, and 18-year-olds made two types of memory errors: backward causal-inference errors (i.e. falsely remembering having viewed the non-viewed cause of a previously viewed effect), and gap-filling errors (i.e. falsely remembering having viewed a script-consistent event that was not actually witnessed). Previous research suggests that backward causal-inference errors are supported by recollection, whereas gap-filling errors are supported by familiarity. We hypothesized that age differences in these errors would parallel the developmental trajectories of these processes. As predicted, age-related increases in backward causal-inference errors were observed, while gap-filling errors were age-invariant, suggesting that recollection-based memory distortions increase with age while familiarity-based memory distortions are relatively stable from middle childhood through adulthood.

Familiarity-based recognition in the young, healthy elderly, mild cognitive impaired and Alzheimer's patients

This study investigates the possible existence of deficits in familiarity in five samples of participants spanning a broad range of ages and cognitive states. Five groups of 16 participants with a diagnosis of multi-domain cognitive impairment with a slight or no deficit in memory, 16 multi-domain amnestic, and 16 Alzheimer's disease patients were compared in a recognition test with equivalent samples of old and young healthy participants. In one of the tests, participants studied words extracted from a restricted set of letters of the alphabet that were later mixed with new words from a different set. The unconscious use of the fluency produced by the repeated use of the set of letters was compared with a condition in which the same letter set did not play a role. Results indicated that amnestic mild cognitive impaired and Alzheimer's patients were unable to use letter fluency to improve recognition. However, young and old controls did not differ among themselves, whereas the multi-domain sample, whose memory performance was almost at the same level as that of controls showed slight levels of deficit in familiarity in the forced choice test but not in the recognition test. These results contrast sharply with those reported by Westerberg et al. [Westerberg, C. E., Paller, K. E., Holdstock, J. S., Mayes, A. R., & Reber, p. J. (2006). When memory does not fail: Familiarity-based recognition in mild cognitive impairment and Alzheimer's disease. Neuropsychology, 20, 193–205] and Anderson et al. [Anderson, N. D., Ebert, P. L., Jennings, J. M., Grady, C. L., Cabeza, R., & Graham, S. J. (2008). Recollection- and familiarity-based memory in healthy aging and amnestic mild cognitive impairment. Neuropsychology, 22, 177–187], who concluded that there were no deficits in familiarity in these types of pre-dementia and dementia patients.

Effect of intranasally administered cholecystokinin on encoding of controlled and automatic memory processes

The neuropeptide cholecystokinin (CCK) is present in abundance in the central nervous system, where it is involved in the regulation of a wide range of functions. It also takes part in the modulation of memory processes, but its effect on human memory systems and processes is not yet well understood. The present experiment was conducted to examine the influence of CCK when present during encoding on later controlled and automatic recognition memory processes in humans. A version of the process dissociation procedure was used to separate the contributions of controlled and automatic memory processes to participants' recognition memory performance. Data were analyzed within a multinomial modeling framework. Participants (N = 64) received either 40 microg CCK-8S or placebo intranasally. The learning and test phases began 30 min after substance application. Behavioral, physiological, and self-report control variables were measured at three points of time during the experiment. Compared to placebo, CCK increased the automatic, familiarity-based recognition memory component, while the parameter representing controlled, retrieval-based processes did not differ between groups. Also, in the exclusion condition of the test phase, the guessing parameter was reduced by CCK. None of the control variables were affected by the peptide. This result-the enhancement of the automatic recognition memory component when CCK is applied before encoding (and thus present during encoding and retrieval)-complements earlier results indicating that CCK decreases controlled, recollection-based recognition memory when applied during consolidation. The possible neuronal systems and processes mediating these effects are discussed.

Episodic-like and procedural memory impairments in histamine H1 Receptor knockout mice coincide with changes in acetylcholine esterase activity in the hippocampus and dopamine turnover in the cerebellum

We investigated episodic-like (ELM) and procedural memory (PM) in histamine H1 receptor knockout (H1R-KO) mice. In order to relate possible behavioral deficits to neurobiological changes, we examined H1R-KO and wild-type (WT) mice in terms of acetylcholine esterase (AChE) activity in subregions of the hippocampus and AChE and tyrosine hydroxylase (TH) expression in the striatum. Furthermore, we analyzed acetylcholine (ACh), 5-HT and dopamine (DA) levels, including metabolites, in the cerebellum of H1R-KO and WT mice. The homozygous H1R-KO mice showed impaired ELM as compared with the heterozygous H1R-KO and WT mice. The performance of homozygous H1R-KO mice in the ELM task was primarily driven by familiarity-based memory processes. While the homozygous H1R-KO mice performed similar to the heterozygous H1R-KO and WT mice during the acquisition of a PM, as measured with an accelerating rotarod, after a retention interval of 7 days their performance was impaired relative to the heterozygous H1R-KO and WT mice. These findings suggest that, both, ELM and long-term PM are impaired in the homozygous H1R-KO mice. Neurochemical assays revealed that the H1R-KO mice had significantly lower levels of AChE activity in the dentate gyrus (DG) and CA1 subregions of the hippocampus as compared with the WT mice. The homozygous H1R-KO mice also displayed significantly reduced dihydroxyphenylacetic acid (DOPAC) levels and a reduced DOPAC/DA ratio in the cerebellum, suggesting that the DA turnover in the cerebellum is decelerated in homozygous H1R-KO mice. In conclusion, homozygous H1R-KO mice display severe long-term memory deficits in, both, ELM and PM, which coincide with changes in AChE activity in the hippocampus as well as DA turnover in the cerebellum. The importance of these findings for Alzheimer's (AD) and Parkinson's disease (PD) is discussed.

Recollection- and familiarity-based memory in healthy aging and amnestic mild cognitive impairment.

Little is known about the cognitive mechanisms of the memory impairment associated with amnestic mild cognitive impairment (aMCI). We explored recollection and familiarity in 27 healthy young adults, 45 healthy older adults, and 17 individuals with aMCI. Relative to the younger adults, recollection was reduced in the older adults, especially among those with aMCI. Familiarity did not differ among groups. In the healthy younger and older adults, better performance on a set of clinical memory measures that are sensitive to medial temporal lobe functioning was associated with greater recollection. In addition, among the healthy older adults better executive functioning was also associated with greater recollection. These results are consistent with the notion that recollection is a product of strategic processes mediated by the prefrontal cortex that suppport the retrieval of context-dependent memories from the hippocampus. Hippocampal atrophy associated with aMCI may disrupt this brain network, and thereby interfere with recollection.

Recollection- and familiarity-based decisions reflect memory strength

We used event-related fMRI to investigate whether recollection- and familiarity-based memory judgments are modulated by the degree of visual similarity between old and new art paintings. Subjects performed a flower detection task, followed by a Remember/Know/New surprise memory test. The old paintings were randomly presented with new paintings, which were either visually similar or visually different. Consistent with our prediction, subjects were significantly faster and more accurate to reject new, visually different paintings than new, visually similar ones. The proportion of false alarms, namely remember and know responses to new paintings, was significantly reduced with decreased visual similarity. The retrieval task evoked activation in multiple visual, parietal and prefrontal regions, within which remember judgments elicited stronger activation than know judgments. New, visually different paintings evoked weaker activation than new, visually similar items in the intraparietal sulcus. Contrasting recollection with familiarity revealed activation predominantly within the precuneus, where the BOLD response elicited by recollection peaked significantly earlier than the BOLD response evoked by familiarity judgments. These findings suggest that successful memory retrieval of pictures is mediated by activation in a distributed cortical network, where memory strength is manifested by differential hemodynamic profiles. Recollection- and familiarity-based memory decisions may therefore reflect strong memories and weak memories, respectively.

Distinguishing familiarity-based from source-based memory performance in patients with schizophrenia

Background There is substantial current interest in the cognitive deficits associated with schizophrenia, particularly those in the realm of memory. Yet the exact nature of these deficits remains a matter of some debate. This study sought to examine performance on two distinct aspects of memory performance: familiarity-based and source-based memory processes. Methods Eighteen medicated outpatients with schizophrenia and eighteen healthy adult control subjects performed an external source memory task. Key measures included the ability to distinguish old (previously experienced) items from new items, the ability to correctly identify the source (male voice or female voice) of previously experienced items, and the reaction time associated with these responses. Results Patients with schizophrenia showed an impaired ability to distinguish old from new items, but intact performance in correctly identifying the source of items recognized as old. Whereas control subjects showed a rapid response to items deemed unfamiliar, particularly in rejecting novel items, these responses were slowed in patients with schizophrenia. This was not attributable to a generalized diminution in processing speed, as reaction times to correctly recognized old items (regardless of source accuracy) did not differ between the two groups. Conclusions Patients with schizophrenia demonstrated impaired familiarity-based and intact source-based memory performance. In addition, the reaction time for novelty detection, an important component of familiarity-based memory, was significantly delayed in patients compared to controls, while the response times for source-based decisions were completely overlapping. Considered together, these findings suggest a deficit in the familiarity-based aspect of episodic memory in at least some patients with schizophrenia.

Bridging the gap between the semantic N400 and the early old/new memory effect

We set out to investigate the extent to which semantic integration processes during language comprehension indexed by the N400 component affect subsequent declarative memory processes as revealed by the putative event-related potential correlates of familiarity and recollection. To this end we designed an incidental recognition memory test whose study material was composed of sentences that were either correct or contained a semantic or syntactic violation. By this means it was possible to examine the mnemonic consequences of the N400 amplitude at study. We found a significant correlation between the amplitude of the N400 at encoding and the magnitude of the familiarity-related early old/new effect at test. It is argued that the processes that contributed to N400 generation increase the likelihood of familiarity-based recognition memory.

Hippocampal contributions to recollection in retrograde and anterograde amnesia

Lesions restricted to the hippocampal formation and/or extended hippocampal system (hippocampal formation, fornix, mammillary bodies, and anterior thalamic nuclei) can disrupt conscious recollection in anterograde amnesia, while leaving familiarity-based memory relatively intact. Familiarity may be supported by extra-hippocampal medial temporal lobe (MTL) structures. Within-task dissociations in recognition memory best exemplify this distinction in anterograde amnesia. The authors report for the first time comparable dissociations within recognition memory in retrograde amnesia. An amnesic patient (A.D.) with bilateral fornix and septal nuclei lesions failed to recognize details pertaining to personal past events only when recollection was required, during recognition of episodic details. His intact recognition of generic and semantic details pertaining to the same events was ascribed to intact familiarity processes. Recollective processes in the controls were reflected by asymmetrical Receiver's Operating Characteristic curves, whereas the patient's Receiver's Operating Characteristic was symmetrical, suggesting that his inferior recognition performance on episodic details was reliant on familiarity processes. Anterograde and retrograde memories were equally affected, with no temporal gradient for retrograde memories. By comparison, another amnesic person (K.C.) with extensive MTL damage (involving extra-hippocampal MTL structures in addition to hippocampal and fornix lesions) had very poor recognition and no recollection of either episodic or generic/semantic details. These data suggest that the extended hippocampal system is required to support recollection for both anterograde and retrograde memories, regardless of their age.

Effects of retention intervals on receiver operating characteristics in artificial grammar learning

Current theories of memory suggest that recognition is composed of separate processes of familiarity and recollection (e.g. [Yonelinas, A. P. (2002). The nature of recollection and familiarity: a review of 30 years of research. Journal of Memory and Language, 46, 441–517]). A key feature of these two processes is that they decay, or are forgotten at different rates. The dual-process model has also been useful in understanding artificial grammar learning. We obtained evidence for recollection and familiarity in artificial grammar learning by analyses of receiver operating characteristics (ROC). Furthermore we found that these were dissociated by retention intervals of 14 days. The slope of the zROC curves deviated reliably from 1 immediately after study and increased towards 1 suggesting that recollection contributed to recognition decisions but declined over the 14-day period leaving familiarity as the only basis for recognition. These data show similar patterns to those observed in word-recognition [Gardiner, J. M., & Java, R. I. (1991). Forgetting in recognition memory with and without recollective experience. Memory &Cognition, 19, 617–623; Tunney, R. J. (submitted for publication). Changes in the subjective experience of recognition over time suggest independent processes] and confirm the view that recollection and familiarity are implicated in artificial grammar learning. Moreover, the data confirm the finding that recollection and familiarity-based memory show different patterns of forgetting.

Relationship between Hippocampal Structure and Memory Function in Elderly Humans

With progressing age, the ability to recollect personal events declines, whereas familiarity-based memory remains relatively intact. It has been hypothesized that age-related hippocampal atrophy may contribute to this pattern because of its critical role for recollection in younger humans and after acute injury. Here, we show that hippocampal volume loss in healthy older persons correlates with gray matter loss (estimated with voxel-based morphometry) of the entire limbic system and shows no correlation with an electrophysiological (event-related potential [ERP]) index of recollection. Instead, it covaries with more substantial and less specific electrophysiological changes of stimulus processing. Age-related changes in another complementary structural measure, hippocampal diffusion, on the other hand, seemed to be more regionally selective and showed the expected correlation with the ERP index of recollection. Thus, hippocampal atrophy in older persons accompanies limbic atrophy, and its functional impact on memory is more fundamental than merely affecting recollection.

Different functions for different medial temporal lobe structures?

Since the landmark study of the globally amnesic patient H.M. by Scoville and Milner (1957), the essential role of the medial temporal lobes (MTL) in long-term memory has been well established. Considerable success has been made dissociating declarative memory processes (explicit memory for events and facts), which rely on the integrity of the MTL, from nondeclarative memory processes, which rely on other cortical, subcortical, and cerebellar structures (Gabrieli 1998). There has also been progress in distinguishing frontal-lobe and MTL contributions to declarative memory. Determining the precise contributions of the structures within the MTL to declarative memory, however, has proved challenging. The MTL is comprised of multiple structures including the hippocampal formation (the dentate gyrus, CA fields, and the subiculum), the amygdala, entorhinal cortex, and surrounding perirhinal and parahippocampal cortices. The focal role of the amygdala in the emotional modulation of memory appears clear (Phelps and Anderson 1997), but there is little consensus about how to characterize the differential contributions of specific MTL structures to declarative memory. Isolating the function of each of these structures, however, is central to understanding declarative memory processing and how damage or disease disrupts such processing. Different MTL structures must be mediating different component processes underlying declarative memory, but the unanswered question is what are those different processes? One emerging idea about differential functions within the MTL is that the hippocampal formation is necessary for declarative memory tasks that require the processing of relations between multiple stimuli, whereas surrounding cortices mediate performance on tasks that rely on stimulus familiarity (or the converse, novelty). This hypothesis is consistent with the hierarchical connectivity of this region (Fig. 1A). Information from unimodal and polymodal association cortices enters the MTL through the perirhinal and parahippocampal cortices, which project to the entorhinal cortex, which in turn provides the major input to the hippocampal formation. This connectional anatomy suggests that the representational capacity of the perirhinal and parahippocampal cortices may be highly related to the incoming sensory information. These cortices may mediate familiarity-based memory processes linked to sensory aspects of items. In contrast, the hippocampus may generate a more abstract representation that integrates or binds multiple cortical sources of information, which is an important aspect of relational memory processes. According to this view, the degree to which a memory task recruits relational versus familiarity processes would determine its relative reliance on hippocampal versus nonhippocampal MTL structures. Tasks that rely greatly on relational processing, such as paired-associate learning, would be greatly impaired by damage to the hippocampal formation. In contrast, tasks that can be performed on the basis of stimulus familiarity, such as tests of item recognition, could be supported by the function of the surrounding MTL cortices in the absence of hippocampal function. Several convergent findings have supported this hypothesis, including evidence from lesion and electrophysiological studies in animals (for review, see Brown and Aggleton 2001; Eichenbaum 2001), and from neuropsychological (Vargha-Khadem et al. 1997), and neuroimaging (Eldridge et al. 2000; Yonelinas et al. 2001) studies in humans. A provocative challenge to this idea is set forth in a study by Stark et al. (2002) examining amnesic patients with bilateral MTL lesions thought to be limited to the hippocampal formation. By using patients with well-characterized lesions, the authors add an important contribution to the ongoing efforts to characterize MTL function in declarative memory. Examining patients with focal hippocampal damage allows the authors to test how damage to this structure affects memory tasks that differentially require relational and familiarity processing. In this study, hippocampal patients performed both single-item and associative recognition tasks. For single-item recognition, patients studied pictures of single faces or houses and after a delay, performed a yes/no recognition memory judgment. For associative recognition, patients studied face-house paired associates and after a delay, were presented with pairs of items. In this associative task, patients had to discriminate items that had been studied together (intact pairs) from items that had not been studied together (recombined pairs). These tasks differentially focus on the processing of relations between test items compared with the processing Corresponding author. E-MAIL gabrieli@psych.stanford.edu; FAX (650) 725-5699. Article and publication are at http://www.learnmem.org/cgi/doi/ 10.1101/lm.54702.

Different forms of human odor memory: a developmental study

Recognizing odors is an important biological function, both in the animal kingdom as well as for humans. It has been debated whether there exist different forms of human odor memory. For verbal memory, the concept of recollection and familiarity for conscious and unconscious recognition is widely accepted. Here we introduce a similar model for human odor memory. We use a combination of an odor naming and odor recognition memory task to estimate the relationship between depth of processing and retention of olfactory information. A developmental approach with children, young adults, middle aged adults and elderly subjects was chosen in order to study the influence of age. Our results indicate the existence of two separable forms of odor memory depending on whether the odors were correctly or incorrectly named during the naming task. These two forms of odor memory were differently represented across the human age range. Intact familiarity-based memory was found in all age groups, whereas memory based on recollection was impaired in the elderly and not yet fully developed in children. Our data show, for the first time, two different forms of human odor memory across the human life span.