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Studies of childhood memory typically show that our earliest memories come from between three and four years of age. This finding is not universal, however. The age estimate varies across cultures and is affected by social influences. Research from the judgments and decision-making literature suggests that these estimates might also involve a judgment under uncertainty. Therefore, they might be susceptible to less social influences such as heuristics and biases. To investigate this possibility, we conducted two experiments that used anchoring paradigms to influence participants' estimates of their age during early autobiographical memories. In Experiment 1, participants answered either a high-anchor or a low-anchor question, and were warned that the anchor was uninformative; they went on to estimate their age during their earliest autobiographical memory. In Experiment 2, we replicated Experiment 1 and extended the design to examine additional early autobiographical memories. In both experiments, participants in the low-anchor condition gave earlier age estimates than those in the high-anchor condition. These results provide new insights into the methods used to investigate autobiographical memory. Moreover, they show that reports of early autobiographical memories can be influenced by a relatively light touch - a change to a single digit in a single question.

Semantic dementia (SD) is a progressive neurological disorder characterized by temporal lobe atrophy and the gradual decline of semantic memory (Snowden, Goulding, & Neary, 1989). Individuals with SD also have impaired autobiographical event memory (AM), but the extent of this impairment has been controversial. Some investigations have found that older memories tend to be impoverished while those from more recent periods tend to be intact (Graham et al., 2003; Moss et al., 2003; Nestor et al., 2002; Piolino et al., 2003; Snowden, Griffiths, & Neary, 1996), which is the reverse of the Ribot gradient seen in Alzheimer’s disease (e. g. Piolino et al., 2003). Others have found that AM drops off precipitously for events beyond the last few years, suggesting that a step function better describes the impairment (Graham & Hodges, 1997; Hou, Miller, & Kramer, 2005). Under some testing conditions, the impairment is ungraded (Ivaniou et al., 2006) or entirely absent (McKinnon et al., 2006; Moss et al., 2003; Westmacott et al., 2001). Data on the temporal gradient in SD have been used to refine neuropsychological models of memory (Moscovitch et al., 2005), so this issue is of theoretical importance. Several factors could account for the differences across studies. First, some reports suggest that patients with mild SD have a graded impairment while those with moderate SD show a step function instead (Ivaniou et al., 2006, Matuszewski et al., 2009), meaning that the results of a particular investigation may depend on the severity of the disorder in the patient or patients tested. Moreover, in mild SD, additional retrieval support (i.e., detailed cues) can elevate performance to normal or near-normal levels (McKinnon et al., 2006; Moss et al., 2003), perhaps because retrieval support helps patients overcome strategic-retrieval deficits secondary to frontal pathology (Moss et al., 2003; Nestor et al., 2002). The choice of test modality can also influence the pattern of AM impairment. Most AM tests are essentially verbal; in the Galton-Crovitz test, for example, memories are cued with single keywords such as HORSE. SD patients have particular difficulty with verbal material, however, and it would be unsurprising to find that a patient cannot generate a detailed memory to the keyword HORSE if he or she no longer knows what horses are. Moreover, SD patients can relearn words (Snowden & Neary, 2002), and these words might be disproportionately linked to recent experiences (Moss et al., 2003). Therefore, the apparent temporal gradient found in cue-word studies might reflect the degradation and reacquisition of semantic knowledge rather than the integrity of AM. Two studies tried to circumvent these problems by using visual stimuli. Westmacott and colleagues (2001) cued AMs of an SD patient with family photographs. The patient seemed to perform well (there was no normal control group, but performance was at 85% or higher) and no temporal gradient was found. Graham and colleagues (2003), however, tested a patient using family photographs and found that he scored about 50% during the remote period. They did not test the recent period and therefore could not assess the temporal gradient. Although these studies suggested that visual cues might facilitate recall in SD, they did not completely resolve the question. The main limitation arises from fundamental differences between the visual and verbal cues that have been used to test AM in SD. The nouns used in Galton-Crovitz tasks are generally high-frequency and easily imageable, but not personally relevant. Family photographs, by contrast, are more personally relevant than a noun, and they contain additional cues (such as the people involved) that might help patients construct appropriate stories. Accordingly, existing studies suffer from a confound between cue modality and retrieval support. Other nonverbal cues have not been investigated. Odors, for example, can evoke autobiographical memories (Rubin, Groth, & Goldsmith, 1984), particularly memories that are older (Willander & Larson, 2006), more emotional (Herz & Cupchik, 1995; Rubin et al., 1984), and more detailed (Chu & Downes, 2002); additionally, odor-evoked memories have not been thought about or talked about as frequently (Rubin et al., 1984; Willander & Larsson, 2006). While odor identification is impaired in SD (Luzzi et al., 2007), an odor can trigger a memory even if a participant cannot identify it (Rubin et al., 1984). Thus, odors tend to elicit the very memories that SD patients find hardest to retrieve. We therefore tested a group of SD patients and controls with a Galton-Crovitz paradigm that used words, simple pictures, and odors as cues. We hypothesized that pictures and words would be equally effective, while odors would be superior; we also predicted a temporal gradient with superior recall for recent memories.

We sought to map the time course of autobiographical memory retrieval, including brain regions that mediate phenomenological experiences of reliving and emotional intensity. Participants recalled personal memories to auditory word cues during event-related functional magnetic resonance imaging (fMRI). Participants pressed a button when a memory was accessed, maintained and elaborated the memory, and then gave subjective ratings of emotion and reliving. A novel fMRI approach based on timing differences capitalized on the protracted reconstructive process of autobiographical memory to segregate brain areas contributing to initial access and later elaboration and maintenance of episodic memories. The initial period engaged hippocampal, retrosplenial, and medial and right prefrontal activity, whereas the later period recruited visual, precuneus, and left prefrontal activity. Emotional intensity ratings were correlated with activity in several regions, including the amygdala and the hippocampus during the initial period. Reliving ratings were correlated with activity in visual cortex and ventromedial and inferior prefrontal regions during the later period. Frontopolar cortex was the only brain region sensitive to emotional intensity across both periods. Results were confirmed by time-locked averages of the fMRI signal. The findings indicate dynamic recruitment of emotion-, memory-, and sensory-related brain regions during remembering and their dissociable contributions to phenomenological features of the memories.

Major predictors of Alzheimer's disease (AD) include apolipoprotein E (APOE)-epsilon4, hippocampal atrophy on magnetic resonance imaging (MRI), and memory dysfunction prior to diagnosis. We examined 159 normal elderly subjects with MRI and the California Verbal Learning Test (CVLT); 84 returned for longitudinal follow-up 5 years later. Analyses at baseline revealed significant variance in hippocampal volume accounted for by cerebral volume and age but not by APOE isoform. However, interactions involving APOE isoform and laterality were observed. As hypothesized, an APOE x time interaction was revealed for CVLT long-delay free recall: APOE-epsilon3/4 subjects had significantly poorer performance than APOE-epsilon3/3 subjects at follow-up. Forward stepwise multiple regression analysis predicting follow-up long-delay free recall selected baseline recall, followed by number of APOE-epsilon4 alleles, followed by left-hippocampal volume. Age and sex did not enter into the model. We conclude that APOE-epsilon4 predicts longitudinal memory decline in healthy controls and that MRI morphometry of hippocampus adds slightly to predictive value.

BACKGROUND Although protease-activated receptors (PARs) have been described to play a role in different malignancies, their expression and biological activity in prostate cancer are mostly unknown. METHODS PAR expression in radical prostatectomy specimens was investigated by immunohistochemistry (IHC, 40 patients) and RT-PCR. Their role in LNCaP prostate cancer cell migration and Rac1/Cdc42 signaling was assessed with Boyden chamber analysis and Western blot, respectively. RESULTS PAR mRNA expression was higher in cancer, and protein expression was increased in PAR-1 (45%), PAR-2 (42%), and PAR-4 (68%), compared to normal glands. Increased PAR-1 (periglandular stroma) was associated with higher rates of biochemical recurrence (median follow-up, 5 years; P = 0.006). LNCaP migration was enhanced twofold and Rac1/Cdc42 signaling was activated by stimulation of PAR-1 and PAR-2. CONCLUSIONS PARs are overexpressed in prostate cancer and may serve as potential predictors of recurrence. The data suggest potential role of PARs in autocrine and paracrine mechanisms of prostate cancer. Prostate 67: 743–756, 2007. © 2007 Wiley-Liss, Inc.

Functional MRI was used to investigate the role of medial temporal lobe and inferior frontal lobe regions in autobiographical recall. Prior to scanning, participants generated cue words for 50 autobiographical memories and rated their phenomenological properties using our autobiographical memory questionnaire (AMQ). During scanning, the cue words were presented and participants pressed a button when they retrieved the associated memory. The autobiographical retrieval task was interleaved in an event-related design with a semantic retrieval task (category generation). Region-of-interest analyses showed greater activation of the amygdala, hippocampus, and right inferior frontal gyrus during autobiographical retrieval relative to semantic retrieval. In addition, the left inferior frontal gyrus showed a more prolonged duration of activation in the semantic retrieval condition. A targeted correlational analysis revealed pronounced functional connectivity among the amygdala, hippocampus, and right inferior frontal gyrus during autobiographical retrieval but not during semantic retrieval. These results support theories of autobiographical memory that hypothesize co-activation of frontotemporal areas during recollection of episodes from the personal past.

Amnesia typically results from trauma to the medial temporal regions that coordinate activation among the disparate areas of cortex that represent the information that make up autobiographical memories. We proposed that amnesia should also result from damage to these regions, particularly regions that subserve long-term visual memory [Rubin, D. C., & Greenberg, D. L. (1998). Visual memory-deficit amnesia: A distinct amnesic presentation and etiology. Proceedings of the National Academy of Sciences of the USA, 95, 5413-5416]. We previously found 11 such cases in the literature, and all 11 had amnesia. We now present a detailed investigation of one of these patients. M.S. suffers from long-term visual memory loss along with some semantic deficits; he also manifests a severe retrograde amnesia and moderate anterograde amnesia. The presentation of his amnesia differs from that of the typical medial-temporal or lateral-temporal amnesic; we suggest that his visual deficits may be contributing to his autobiographical amnesia.

A total of 30 undergraduates recalled the same 20 autobiographical memories at two sessions separated by 2 weeks. At each session they dated their memories and rated them on 18 properties commonly studied in autobiographical memory experiments. Individuals showed moderate stability in their ratings on the 18 scales (r approximately .5), with consistency of dating being much higher (r = .96). There was more stability in the individuals' average rating on each scale (r approximately .8), even when the averages were calculated on different memories in the different sessions. The results are consistent with a constructive view of autobiographical memory, in which stable individual differences in cognitive style are important.

In three experiments, undergraduates rated autobiographical memories on scales derived from existing theories of memory. In multiple regression analyses, ratings of the degree to which subjects recollected (i.e., relived) their memories were predicted by visual imagery, auditory imagery, and emotions, whereas ratings of belief in the accuracy of their memories were predicted by knowledge of the setting. Recollection was predicted equally well in between- and within-subjects analyses, but belief consistently had smaller correlations and multiple regression predictions between subjects; individual differences in the cognitive scales that we measured could not account well for individual differences in belief. In contrast, measures of mood (Beck Depression Index) and dissociation (Dissociative Experience Scale) added predictive value for belief, but not for recollection. We also found that highly relived memories almost always had strong visual images and that remember/know judgments made on autobiographical memories were more closely related to belief than to recollection.

© 2014, Psychonomic Society, Inc. Visual imagery plays a fundamental role in autobiographical memory, but several aspects of this role remain unclear. We conducted three experiments to explore this relationship. In the first experiment, we examined the relation between the phenomenological properties of autobiographical memory and several measures of visual-imagery ability. We found no significant positive relation between imagery ability and autobiographical memory, except on a measure of cognitive style. In a second experiment, we examined the autobiographical memories of people with different cognitive styles—namely, visualizers and verbalizers. We found that, for both kinds of participant, visual imagery was correlated with the feeling that they were reliving their memories, but auditory imagery played a greater role in verbalizers. In a third experiment, we examined the memories of individuals who had a congenital absence of visual imagery. We found that they had a deficit of auditory imagery, as well; moreover, they were much less likely than controls to feel as though they were reliving their memories. The results support the idea that visual imagery plays a vital and irreplaceable role in autobiographical recall.

This study compared the effects of fixed- and varied-context repetition on associative recognition in amnesia. Controls and amnesic participants were presented with a set of three-word phrases. Each was presented three times. In the varied-context condition, the verb changed with each presentation; in the fixed-context condition, it remained constant. At test, participants performed an associative-recognition task in which they were shown pairs of words from the study phase and asked to distinguish between intact and recombined pairs. For corrected recognition (hits – false alarms), controls performed better in the varied-context than in the fixed-context repetition condition, whereas amnesic participants’ performance did not differ between conditions. Similarly, controls had lower false-alarm rates in the varied-context condition, but there was no significant effect of condition for the amnesic participants. Thus, varied-context repetition does not improve amnesic participants’ performance on a recollection-dependent associative-recognition task, possibly because the amnesic participants were unable to take advantage of the additional cues that the varied-context encoding condition provided. (JINS, 2010, 16, 596–602.)

Studies of depression and hippocampal volume have yielded inconsistent results. This inconsistency could stem from the heterogeneity of depressive disorders. We conducted cross-sectional and longitudinal analyses of hippocampal volumes in atypical depressive, melancholic depressive, and control subjects. We found no effect of depression subtype on hippocampal volume or memory performance.

We sought to examine the relations between age, gender and brain volumes in an elderly population; we also sought to examine ways of measuring these relations. Three sets of analyses were used: correlational analyses, in which correlations between independent variables and brain volumes were calculated without correction for intracranial volume (ICV); covariational analyses, in which ICV was used as a covariate in regression equations; and ratio analyses, in which the dependent variable was the ratio of brain volume to ICV. These analyses yielded similar results, except that (as expected) adjusting for ICV altered estimates of gender differences. Analyses of age showed decreases in left caudate, putamen, and right hippocampus and an increase in CSF, a result generally in accord with previous findings. However, we also found a significant decrease of white-matter volumes and no significant decrease in total gray-matter volumes. Correlational analyses showed that men did not always have larger volumes despite their larger head size; women generally had larger volumes after adjusting for ICV. We found no age-gender interactions.

Numerous studies have shown gender differences in the brain volumes of elderly adults. Some evidence shows that higher estrogen levels may be neuroprotective, suggesting that hormone therapy (HT) may in part be responsible for these gender differences; however, few studies have examined the relation between HT and brain volumes. Brain volumes of caudate, putamen, hippocampus, gray matter, white matter, white-matter lesions, and cerebrospinal fluid were measured on magnetic resonance imaging scans. A comprehensive neuropsychological battery was administered. Women were separated into two groups based on HT use, and we used multiple regression analyses to compare these groups with one another and with men. Results of brain-volume measurements showed that HT users had significantly less gray matter and more cerebrospinal fluid than nonusers. Results of the neuropsychological testing showed that HT users performed better on the Shipley Vocabulary Test than males did.

The authors investigated the role of baseline hippocampal volume on later clinical emergence of dementia in a group of older, non-demented depressed individuals. Subjects were 115 depressed, non-demented participants in a mental health clinical research center. All subjects were screened for dementia and agreed to have a magnetic resonance imaging (MRI) brain scan at baseline. Subjects were clinically evaluated by geriatric psychiatrists quarterly for up to 5 years and received annual neuropsychological testing. Bivariate analyses examined age, gender, race, educational level, baseline depression severity, age at depression onset, baseline Mini-Mental State Exam (MMSE), left and right hippocampal volume, and total cerebral volume. Age, baseline MMSE, total cerebral volume, and having a small left hippocampal volume were associated with later dementia and were included in subsequent survival analysis. Small left hippocampal volume was significantly associated with later dementia (hazard ratio=2.762). Small left hippocampal size on neuroimaging may be a marker for dementia in depressed patients who have not yet met criteria for a clinical diagnosis of a dementing disorder.

Background: There is a growing literature on the importance of hippocampal volume in geriatric depression. Methods: We examined hippocampal volume in a group of elderly depressed patients and a group of elderly control subjects ( N = 66 geriatric depressed patients and 18 elderly nondepressed control subjects) recruited through Duke's Mental Health Clinical Research Center for the Study of Depression in the Elderly. The subjects received a standardized evaluation, including a magnetic resonance imaging scan of the brain. Patients had unipolar major depression and were free of comorbid major psychiatric illness and neurologic illness. Differences were assessed using t tests and linear regression modeling. Results: Accounting for the effects of age, gender, and total brain volume, depressed patients tended to have smaller right hippocampal volume ( p = .014) and left hippocampal volume ( p = .073). Among depressed patients, age of onset was negatively but not significantly related to right hippocampal volume ( p = .052) and to left hippocampal volume ( p = .062). We noted that among subjects with either right or left hippocampal volume of 3 mL or less, the vast majority were patients rather than control subjects. Conclusions: These results support a role for hippocampal dysfunction in depression, particularly in late-age onset depression. Longitudinal studies examining both depressive and cognitive outcomes are needed to clarify the relationships between the hippocampus, depression, and dementia.

Functional neuroimaging studies of episodic memory retrieval generally measure brain activity while participants remember items encountered in the laboratory (“controlled laboratory condition”) or events from their own life (“open autobiographical condition”). Differences in activation between these conditions may reflect differences in retrieval processes, memory remoteness, emotional content, retrieval success, self-referential processing, visual/spatial memory, and recollection. To clarify the nature of these differences, a functional MRI study was conducted using a novel “photo paradigm,” which allows greater control over the autobiographical condition, including a measure of retrieval accuracy. Undergraduate students took photos in specified campus locations (“controlled autobiographical condition”), viewed in the laboratory similar photos taken by other participants (controlled laboratory condition), and were then scanned while recognizing the two kinds of photos. Both conditions activated a common episodic memory network that included medial temporal and prefrontal regions. Compared with the controlled laboratory condition, the controlled autobiographical condition elicited greater activity in regions associated with self-referential processing (medial prefrontal cortex), visual/ spatial memory (visual and parahippocampal regions), and recollection (hippocampus). The photo paradigm provides a way of investigating the functional neuroanatomy of real-life episodic memory under rigorous experimental control.