The medial temporal lobe and recognition memory.

The ability to recognize a previously experienced stimulus is supported by two processes: recollection of the stimulus in the context of other information associated with the experience, and a sense of familiarity with the features of the stimulus. Although familiarity and recollection are functionally distinct, there is considerable debate about how these kinds of memory are supported by regions in the medial temporal lobes (MTL). Here, we review evidence for the distinction between recollection and familiarity and then consider the evidence regarding the neural mechanisms of these processes. Evidence from neuropsychological, neuroimaging, and neurophysiological studies of humans, monkeys, and rats indicates that different subregions of the MTL make distinct contributions to recollection and familiarity. The data suggest that the hippocampus is critical for recollection but not familiarity. The parahippocampal cortex also contributes to recollection, possibly via the representation and retrieval of contextual (especially spatial) information, whereas perirhinal cortex contributes to and is necessary for familiarity-based recognition. The findings are consistent with an anatomically guided hypothesis about the functional organization of the MTL and suggest mechanisms by which the anatomical components of the MTL interact to support the phenomenology of recollection and familiarity.

Oscillatory EEG correlates of episodic trace decay.

Recent studies suggest that human theta oscillations appear to be functionally associated with memory processes. It is less clear, however, to what type of memory sub-processes theta is related. Using a continuous word recognition task with different repetition lags, we investigate whether theta reflects the strength of an episodic memory trace or general processing demands, such as task difficulty. The results favor the episodic trace decay hypothesis and show that during the access of an episodic trace in a time window of approximately 200-400 ms, theta power decreases with increasing lag (between the first and second presentation of an item). LORETA source localization of this early theta lag effect indicates that parietal regions are involved in episodic trace processing, whereas right frontal regions may guide the process of retrieval. We conclude that episodic encoding can be characterized by two different stages: traces are first processed at parietal sites at approximately 300 ms, then further processing takes place in regions of the medial temporal lobe at approximately 500 ms. Only the first stage is related to theta, whereas the second is reflected by a slow wave with a frequency of approximately 2.5 Hz.

Mild hypoxia disrupts recollection, not familiarity.

Yonelinas et al. (2002) found that hypoxic patients exhibited deficits in recollection that left familiarity relatively unaffected. In contrast, Manns, Hopkins, Reed, Kitchener, and Squire (2003) studied a group of hypoxic patients who suffered severe and equivalent deficits in recollection and familiarity. We reexamine those studies and argue that the discrepancy in results is likely due to differences in the hypoxic groups that were tested (i.e., differences in amnestic severity, subject sampling methods, and patient etiology). Yonelinas et al. examined memory in 56 cardiac arrest patients who suffered a brief hypoxic event, whereas Manns et al. examined a group of severely amnesic patients that consisted of 2 cardiac arrest patients, 2 heroin overdose patients, 1 carbon monoxide poisoning patient, and 2 patients with unknown etiologies. We also consider an alternative explanation proposed by Wixted and Squire (2004), who argued that the two patient groups suffered similar deficits, but that statistical or methodological artifacts distorted the results of each of Yonelinas et al.'s experiments. A consideration of those results, however, indicates that such an explanation does not account for the existing data. All of the existing evidence indicates that recollection, but not familiarity, is disrupted in mild hypoxic patients. In more severe cases of hypoxia, or those with more complex etiologies such as heroin overdose, more profound deficits may be observed.

The von Restorff effect in amnesia: the contribution of the hippocampal system to novelty-related memory enhancements.

The ability to detect novelty is a characteristic of all mammalian nervous systems (Sokolov, 1963), and it plays a critical role in memory in the sense that items that are novel, or distinctive, are remembered better than those that are less distinct (von Restorff, 1933). Although several brain areas are sensitive to stimulus novelty, it is not yet known which regions play a role in producing novelty-related effects on memory. In the current study, we investigated novelty effects on recognition memory in amnesic patients and healthy control subjects. The control subjects demonstrated better recognition for items that were novel (i.e., presented in an infrequent color), and this effect was found for both recollection and familiarity-based responses. However, the novelty advantage was effectively eliminated in patients with extensive medial temporal lobe damage, mild hypoxic patients expected to have relatively selective hippocampal damage, and in a patient with thalamic lesions. The results indicate that the human medial temporal lobes play a critical role in producing normal novelty effects in memory.

The neural substrates of visual implicit memory: do the two hemispheres play different roles?

Identification of visually presented words is facilitated by implicit memory, or visual priming, for past visual experiences with those words. There is disagreement over the neuro-anatomical substrates of this form of implicit memory. Several studies have suggested that this form of priming relies on a visual word-form system localized in the right occipital lobe, whereas other studies have indicated that both hemispheres are equally involved. The discrepancies may be related to the types of priming tasks that have been used because the former studies have relied primarily on word-stem completion tasks and the latter on tasks like word-fragment completion. The present experiments compared word-fragment and word-stem measurements of visual implicit memory in patients with right occipital lobe lesions and patients with complete callosotomies. The patients showed normal visual implicit memory on fragment completion tests, but essentially no visual priming on standard stem completion tests. However, when we used a set of word stems that had only one correct solution for each test item, as was true of the items in the fragment completion tests, the patients showed normal priming effects. The results indicate that visual implicit memory for words is not solely dependent upon the right hemisphere, rather it reflects changes in processing efficiency in bilateral visual regions involved in the initial processing of the items. However, under conditions of high lexical competition (i.e., multiple completion word stems), the lexical processes, which are dominant in the left hemisphere, overshadow the visual priming supported by the left hemisphere.

Form-specific visual priming in the left and right hemispheres.

Word fragment completion performance was examined for items that were presented in the same or different letter case at study and test. During the study phase words and nonwords were presented at central fixation, then during the test phase a divided visual field technique was used in which word fragments were presented briefly to the right hemisphere (left visual field) or the left hemisphere (right visual field). Previous research using the word stem completion task indicated that only the right hemisphere was sensitive to case changes in words from study to test. In contrast, the current results indicate that in the fragment completion task the priming effects for the test items presented to either hemisphere were greater when the fragments were in the same compared to different letter case at study and test. These results indicate that both hemispheres are capable of supporting form-specific visual implicit memory.

Components of episodic memory: the contribution of recollection and familiarity.

The examination of recognition memory confidence judgements indicates that there are two separate components or processes underlying episodic memory. A model that accounts for these results is described in which a recollection process and a familiarity process are assumed to contribute to recognition memory performance. Recollection is assumed to reflect a threshold process whereby qualitative information about the study event is retrieved, whereas familiarity reflects a classical signal-detection process whereby items exceeding a familiarity response criterion are accepted as having been studied. Evidence from cognitive, neuropsychological and neuroimaging studies indicate that the model is in agreement with the existing recognition results, and indicate that recollection and familiarity are behaviourally, neurally and phenomenologically distinct memory retrieval processes.

Consciousness, control, and confidence: the 3 Cs of recognition memory.

The contributions of recollection and familiarity to recognition memory performance were examined using the process dissociation, remember-know, and receiver operating characteristic (ROC) procedures. Under standard test conditions the 3 measurement procedures led to process estimates that were almost identical and to similar conclusions regarding the effects of different encoding manipulations. Dividing attention led to a large decrease in recollection and a smaller, sometimes nonsignificant, decrease in familiarity. Semantic compared with perceptual processing led to a large increase in recollection and a moderate increase in familiarity. Moreover, the results showed that familiarity was well described by classical signal-detection theory but that recollection reflected a threshold process. The convergence observed across the 3 measurement procedures shows that the 3 procedures tap similar underlying processes and that recollection and familiarity differ in terms of conscious awareness, intentional control, and the manner in which they contribute to the shape of response confidence ROCs.

Visual implicit memory in the left hemisphere: evidence from patients with callosotomies and right occipital lobe lesions.

Identification of visually presented objects and words is facilitated by implicit memory for past visual experiences with those items. Several behavioral and neuroimaging studies suggest that this form of memory is dependent on perceptual processes localized in the right occipital lobe. We tested this claim by examining implicit memory in patients with extensive right occipital lobe lesions, using lexical-decision mirror-reading, picture-fragment, and word-fragment-completion tests, and found that these patients exhibited normal levels of priming. We also examined implicit memory in patients with complete callosotomies, using standard and divided-visual-field word-fragment-completion procedures, and found that the isolated left hemisphere exhibited normal priming effects. The results indicate that the right occipital lobe does not play a necessary role in visual implicit memory, and that the isolated left hemisphere can support normal levels of visual priming in a variety of tasks.

Transfer across modality in perceptual implicit memory.

We examined whether words studied in one modality (visual or auditory) would prime performance in the opposite modality in five different perceptual implicit memory tests: auditory perceptual identification, auditory stem completion, visual perceptual identification, visual stem completion, and visual fragment completion. Significant transfer across modality was observed in all five tasks. However, a large proportion of the subjects reported using explicit retrieval strategies during the implicit tests. Those subjects who claimed not to have used explicit retrieval processes during the test phase demonstrated transfer across modalities in the stem completion tests and the perceptual identification tests, but not in the fragment completion test. The results indicate that implicit visual word-fragment completion is unique, in the sense that it relies exclusively on perceptual memory processes, whereas the other tasks rely, in part, on nonperceptual memory processes.

Comparative electrophysiological and hemodynamic measures of neural activation during memory-retrieval.

The spatial and temporal characteristics of the brain processes underlying memory retrieval were studied with both event-related potentials (ERP) and positron emission tomography (PET) techniques. Subjects studied lists of 20 words and then performed episodic (old/new judgment) or semantic (living/nonliving decision) retrieval tasks on multiple four-item test lists, each lasting 10 sec. The PET and ERP measurements at test were assessed in relation to both the task (episodic vs. semantic) and the item (old vs. new or living vs. nonliving). Episodic retrieval was associated with increased blood flow in the right frontal lobe (Brodmann Area 10) and a sustained, slowly developing positive ERP shift recorded from the right frontopolar scalp. Semantic retrieval was associated with increased blood flow in the left frontal (Area 45) and temporal (Area 21) lobes but no clear ERP concomitant. The two retrieval tasks also differed from each other in the ERPs to single items in an early (300-500 ms) time window. Item-related comparisons yielded convergent results mainly if the retrieved information was relevant to the given task (e.g., old/new items during episodic retrieval and living/nonliving items during semantic retrieval). Episodically retrieved old items were associated with increased blood flow in the left medial temporal lobe and a transient increase in the amplitude of the late positive component (500-700 ms) of the ERP. Semantically retrieved living items were associated with increased blood flow in the left frontal cortex and anterior cingulate and a transient late frontal slow wave (700-1,500 ms) in the ERPs. These results indicate that the brain regions engaged in memory retrieval are active in either a sustained or transient manner. They map task-related processes to sustained and item-related processes to transient neural activity. But they also suggest that task-related factors can transiently affect early stages of item processing.

Hippocampal, parahippocampal and occipital-temporal contributions to associative and item recognition memory: an fMRI study.

The temporal lobe regions involved in memory retrieval were examined using fMRI. During an associative recognition test, participants made memory judgments about the study color of previously presented drawings of objects, and during item recognition tests they made old/new judgments about previously studied objects or new objects. Associative recognition compared with old item recognition led to activations in bilateral hippocampal and parahippocampal regions, as well as in the left middle occipital gyrus. Old item recognition compared with new item recognition led to activation in the left middle occipital gyrus and the left middle temporal gyrus, and relative deactivations in bilateral hippocampal regions. The results indicate that partially distinct temporal lobe regions are involved during recognition memory for item and associative information.

Conceptual implicit memory performance in Alzheimer's disease.

Alzheimer's disease (AD) patients often exhibit deficits on conceptual implicit memory tests such as category exemplar generation and word association. However, these tests rely on word production abilities, which are known to be disrupted by AD. The current study assessed conceptual implicit memory performance in AD patients and elderly control participants using a conceptual priming task that did not require word production (i.e., semantic decision). Memory performance was also examined using a category exemplar generation test (i.e., a conceptual priming task that required word production) and a recognition memory test. AD patients exhibited deficits on the semantic decision task, the category exemplar generation task, and the recognition memory task. The results indicate that the conceptual memory deficits observed in AD patients cannot be attributed completely to word production difficulties.

The contribution of recollection and familiarity to yes-no and forced-choice recognition tests in healthy subjects and amnesics.

Recent reports suggest that some amnesic patients perform relatively normally on forced-choice recognition memory tests. Their preserved performance may reflect the fact that the test relies more heavily on assessments of familiarity, a process that is relatively preserved in these patients, than do other recognition tests such as yes-no tests, which may rely more on recollection. The current study examined recognition memory using yes-no and forced-choice procedures in control and amnesic patients in order to determine whether the two tasks differentially relied on recollection and familiarity, and whether the extent of the recognition memory deficit observed in amnesia was dependent upon the type of recognition test used to measure performance. Results using the remember-know procedure with healthy subjects showed that there were no substantial differences in recognition accuracy or in the contribution of recollection to these two tasks. Moreover, amnesic patients were not found to perform better on a forced-choice test than on a yes-no test, suggesting that familiarity contributed equally to these two types of recognition test.

Predicting individual false alarm rates and signal detection theory: a role for remembering.

The relationships between hit, remember, and false alarm rates were examined across individual subjects in three remember-know experiments in order to determine whether signal detection theory would be consistent with the observed data. The experimental data differed from signal detection predictions in two critical ways. First, remember reports were unrelated, or slightly negatively related, to the commission of false alarms. Second, both response types (remembers and false alarms) were uniquely related to hit rates, which demonstrated that the hit rate cannot be viewed as the result of a single underlying strength process. These results are consistent with the dual-process signal detection model of Yonelinas (1994), in which performance is determined by two independent processes--retrieval of categorical context information (remembering) and discriminations based on continuous item strength. Remember and false alarm rates selectively tap these processes, whereas the hit rate is jointly determined. Monte Carlo simulations in which the dual-process model was used successfully reproduced the pattern in the experimental data, whereas simulations in which a signal detection model, with separate "old" and "remember" criteria, was used, did not. The results demonstrate the utility of examining individual differences in response types when one is evaluating memory models.

The contribution of recollection and familiarity to recognition and source-memory judgments: a formal dual-process model and an analysis of receiver operating characteristics.

A formal dual-process model that assumes that memory judgments can be based on a threshold recollection process and a signal-detection-based familiarity process is proposed to account for both recognition and source-memory performance. The model was tested in 4 experiments by examining recognition and source-memory receiver operating characteristics (ROCs). In agreement with the predictions of the model, recognition and source memory dissociated in certain conditions. Recognition ROCs were curvilinear in probability space and relatively linear in z-space, as expected if recollection and familiarity contributed to performance. In contrast, source ROCs typically were linear and exhibited a pronounced U shape in z-space, as expected if performance primarily relied on recollection. However, in conditions in which familiarity was clearly indicative of an item's source, the source ROC became curvilinear, suggesting that participants could use familiarity as a basis for source judgments. Several alternative models, including the unequal-variance signal-detection model, were found to be inconsistent with the ROC data.

Task-related and item-related brain processes of memory retrieval.

In all cognitive tasks, general task-related processes operate throughout a given task on all items, whereas specific item-related processes operate differentially on individual items. In typical functional neuroimaging experiments, these two sets of processes have usually been confounded. Herein we report a combined positron emission tomography and event-related potential (ERP) experiment that was designed to distinguish between neural correlates of task-related and item-related processes of memory retrieval. Two retrieval tasks, episodic and semantic, were crossed with episodic (old/new) and semantic (living/nonliving) properties of individual items to yield evidence of regional brain activity associated with task-related processes, item-related processes, and their interaction. The results showed that episodic retrieval task was associated with increased blood flow in right prefrontal and posterior cingulate cortex, as well as with a sustained right-frontopolar-positive ERP, but that the semantic retrieval task was associated with left frontal and temporal lobe activity. Retrieval of old items was associated with increased blood flow in the left medial temporal lobe and with a brief late positive ERP component. The results provide converging hemodynamic and electrophysiological evidence for the distinction of task- and item-related processes, show that they map onto spatially and temporally distinct patterns of brain activity, and clarify the hemispheric encoding/retrieval asymmetry (HERA) model of prefrontal encoding and retrieval asymmetry.

Recognition memory for faces: when familiarity supports associative recognition judgments.

Recognition memory for single items can be dissociated from recognition memory for the associations between items. For example, recognition tests for single words produce curvilinear receiver operating characteristics (ROCs), but associative recognition tests for word pairs produce linear ROCs. These dissociations are consistent with dual-process theories of recognition and suggest that associative recognition relies on recollection but that item recognition relies on a combination of recollection and assessments of familiarity. In the present study, we examined associative recognition ROCs for facial stimuli by manipulating the central and external features, in order to determine whether linear ROCs would be observed for stimuli other than arbitrary word pairs. When the faces were presented upright, familiarity estimates were significantly above zero, and the associative ROCs were curvilinear, suggesting that familiarity contributed to associative judgments. However, presenting the faces upside down effectively eliminated the contribution of familiarity to associative recognition, and the ROCs were linear. The results suggest that familiarity can support associative recognition judgments, if the associated components are encoded as a coherent gestalt, as in upright faces.

Recollection and familiarity deficits in amnesia: convergence of remember-know, process dissociation, and receiver operating characteristic data.

Previous studies using the process dissociation and the remember-know procedures led to conflicting conclusions regarding the effects of anterograde amnesia on recollection and familiarity. We argue that these apparent contradictions arose because different models were used to interpret the results and because differences in false-alarm rates between groups biased the estimates provided by those models. A reanalysis of those studies with a dual-process signal-detection model that incorporates response bias revealed that amnesia led to a pronounced reduction in recollection and smaller but consistent reduction in familiarity. To test the assumptions of the model and to further assess recognition deficits in amnesics, we examined receiver operating characteristics (ROCs) in amnesics and controls. The ROCs of the controls were curved and asymmetrical, whereas those of the amnesics were curved and symmetrical. The results supported the predictions of the model and indicated that amnesia was associated with deficits in both recollection and familiarity.

Event-related brain potential correlates of two states of conscious awareness in memory.

We report an event-related potential (ERP) experiment of human recognition memory that explored the relation between conscious awareness and electrophysiological activity of the brain. We recorded ERPs from healthy adults while they made "remember" and "know" recognition judgments about previously seen words. These two kinds of judgments reflect "autonoetic" and "noetic" awareness, respectively. The ERP effects differed between the two kinds of awareness while they were similar for "true" and "false" recognition. Noetic awareness was associated with a temporoparietal positivity in the N400 range (325-600 ms) and a late (600-1,000 ms) frontocentral negativity, whereas autonoetic awareness was associated with a widespread, late, bifrontal and left parietotemporal (600-1000 ms) positivity. In the very late (1,300-1, 900 ms) time window, a right frontal positivity was observed for both remember and know judgments of both true and false targets. These results provide physiological evidence for two types of conscious awareness in episodic memory retrieval.