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The ability to recognize the prior occurrence of objects can operate effectively even in the absence of successful recollection of episodic contextual detail about a relevant past object encounter. The pertinent process, familiarity assessment, is typically probed in humans with recognition-memory tasks that include an experimentally controlled study phase for a list of items. When meaningful stimuli such as words or pictures of common objects are employed, participants must judge familiarity with reference to the recent experimental encounter rather than their lifetime of autobiographical experience, which may have involved hundreds or thousands of exposures across numerous episodic contexts. Humans can, however, also judge the cumulative familiarity of objects concepts they have encountered over their lifetime. At present, little is known about the cognitive and neural mechanisms that support this ability. Here, we tested an individual (NB) with a rare left anterior temporal-lobe lesion that included perirhinal cortex but spared the hippocampus, who had previously been found to exhibit selective impairments in familiarity assessment on verbal recognition-memory tasks. As NB exhibits normal recollection abilities, her case presents a unique opportunity to examine potential links between both types of familiarity. In Experiment 1, we demonstrated that NB's impairment in making recognition judgments affects cumulative frequency judgments for exposure to concept names in a recent study episode. Experiments 2 and 3 revealed, with a task borrowed from the semantic-memory literature, that NB's impairments do indeed extend to abnormalities in judging cumulative lifetime familiarity for object concepts. These abnormalities were not limited to verbal processing, and were present even when pictures were offered as additional cues. Moreover, they showed sensitivity to concept structure as reflected in semantic feature norms; we only observed them for judgments on object concepts with high feature overlap. In Experiment 4, we found that an amnesic patient (HC) with previously established deficits in autobiographical recollection, due to a selective lesion of the extended hippocampal system, does not exhibit any abnormalities in assessing lifetime familiarity. Together, these findings provide support for a functional link between the assessment of recent changes in familiarity, as probed with experimental study-test paradigms, and cumulative lifetime familiarity based on autobiographical experience accrued outside the laboratory. They argue in favor of the notion that familiarity is closely related to the representation of concept knowledge, likely through computations in perirhinal cortex.

An important theory holds that semantic knowledge can develop independently of episodic memory. One strong source of evidence supporting this independence comes from the observation that individuals with early hippocampal damage leading to developmental amnesia generally perform normally on standard tests of semantic memory, despite their profound impairment in episodic memory. However, one aspect of semantic memory that has not been explored is conceptual structure. We built on the theoretically important distinction between intrinsic features of object concepts (e.g., shape, colour, parts) and extrinsic features (e.g., how something is used, where it is typically located). The accrual of extrinsic feature knowledge that is important for concepts such as chair or spoon may depend on binding mechanisms in the hippocampus. We tested HC, an individual with developmental amnesia due to a well-characterized lesion of the hippocampus, on her ability to generate semantic features for object concepts. HC generated fewer extrinsic features than controls, but a similar number of intrinsic features than controls. We also tested her on typicality ratings. Her typicality ratings were abnormal for nonliving things (which more strongly depend on extrinsic features), but normal for living things (which more strongly depend on intrinsic features). In contrast, NB, who has MTL but not hippocampal damage due to surgery, showed no impairments in either task. These results suggest that episodic and semantic memory are not entirely independent, and that the hippocampus is important for learning some aspects of conceptual knowledge.

Evidence from numerous sources indicates that recognition of the prior occurrence of objects requires computations of perirhinal cortex (PrC) in the medial temporal lobe (MTL). Extant research has primarily probed recognition memory based on item exposure in a recent experimental study episode. Outside the laboratory, however, familiarity for objects typically accrues gradually with learning across many different episodic contexts, which can be distributed over a lifetime of experience. It is currently unknown whether PrC also tracks this cumulative lifetime experience with object concepts. To address this issue, we con- ducted a functional magnetic resonance imaging (fMRI) experiment in healthy individuals in which we compared judgments of the perceived lifetime familiarity with object concepts, a task that has previously been employed in many normative studies on concept knowledge, with frequency judgments for recent laboratory exposure in a study phase. Guided by neurophysiological data showing that neurons in primate PrC signal prior object exposure at multiple time scales, we predicted that PrC responses would track perceived prior experience in both types of judgments. Left PrC and a number of cortical regions that are often co- activated as part of the default-mode network showed an increase in Blood-Oxygen-Level Dependent (BOLD) response in relation to increases in the perceived cumulative lifetime familiarity of object concepts. These regions included the left hippocampus, left mid-lateral temporal cortex, as well as anterior and posterior cortical midline structures. Critically, left PrC was found to be the only region that showed this response in combination with the typically observed decrease in signal for perceived recent exposure in the experimental study phase. These findings provide, to our knowledge, the first evidence that ties signals in human PrC to variations in cumulative lifetime experience with object concepts. They offer a new link between the role of PrC in recognition memory and its broader role in conceptual processing.

It is well established that the medial-temporal lobe (MTL) is critical for recognition memory. The MTL is known to be composed of distinct structures that are organized in a hierarchical manner. At present, it remains controversial whether lower structures in this hierarchy, such as perirhinal cortex, support memory functions that are distinct from those of higher structures, in particular the hippocampus. Perirhinal cortex has been proposed to play a specific role in the assessment of familiarity during recognition, which can be distinguished from the selective contributions of the hippocampus to the recollection of episodic detail. Some researchers have argued, however, that the distinction between familiarity and recollection cannot capture functional specialization within the MTL and have proposed single-process accounts. Evidence supporting the dual-process view comes from demonstrations that selective hippocampal damage can produce isolated recollection impairments. It is unclear, however, whether temporal-lobe lesions that spare the hippocampus can produce selective familiarity impairments. Without this demonstration, single-process accounts cannot be ruled out. We examined recognition memory in NB, an individual who underwent surgical resection of left anterior temporal-lobe structures for treatment of intractable epilepsy. Her resection included a large portion of perirhinal cortex but spared the hippocampus. The results of four experiments based on three different experimental procedures (remember-know paradigm, receiver operating characteristics, and response-deadline procedure) indicate that NB exhibits impaired familiarity with preserved recollection. The present findings thus provide a crucial missing piece of support for functional specialization in the MTL.

We continuously encounter and process novel events in the surrounding world, but only some episodes will leave detailed memory traces that can be recollected after weeks and months. Here, our aim was to monitor brain activity during encoding of events that eventually transforms into long-term stable memories. Previous functional magnetic resonance imaging (fMRI) studies have shown that the degree of activation of different brain regions during encoding is predictive of later recollection success. However, most of these studies tested participants' memories the same day as encoding occurred, whereas several lines of research suggest that extended post-encoding processing is of crucial importance for long-term consolidation. Using fMRI, we tested whether the same encoding mechanisms are predictive of recollection success after hours as after a retention interval of several weeks. Seventy-eight participants were scanned during an associative encoding task and given a source memory test the same day or after ∼6 weeks. We found a strong link between regional activity levels during encoding and recollection success over short time intervals. However, results further showed that durable source memories, i.e., events recollected after several weeks, were not simply the events associated with the highest activity levels at encoding. Rather, strong levels of connectivity between the right hippocampus and perceptual areas, as well as with parts of the self-referential default-mode network, seemed instrumental in establishing durable source memories. Thus, we argue that an initial intensity-based encoding is necessary for short-term encoding of events, whereas additional processes involving hippocampal–cortical communication aid transformation into stable long-term memories.

Varicocele represents the most common cause of male infertility, and most reports indicate that varicocelectomy has a beneficial effect on male fertility and pregnancy outcome. Assisted reproductive technologies (ARTs) are an alternative to varicocelec- tomy for the management of couples with a varicocele. The age of the female partner is important in the decision-making process; how- ever, the true influence of female age on pregnancy outcome follow- ing varicocelectomy or ART in these couples is unknown. We eval- uated the outcomes of 2 cohorts of infertile men with a varicocele and a female partner 35 years of age or older; one group selected varicocelectomy and the other a nonsurgical approach. We reviewed a group of consecutive infertile men who underwent microsurgical varicocelectomy and whose partners are 35 years of age or older (n 5 110). We also reviewed a consecutive group of men with vari- coceles who elected not to have surgery and whose partners are 35 years of age or older (n 5 94). The outcome measures included changes in semen parameters, pregnancy rates (assisted and un- assisted), and use of ART. The surgical and nonsurgical groups had comparable semen parameters and female ages. Mean sperm con- centration and motility increased significantly after varicocelectomy (P , .05). At a mean of 30 months follow-up, 35% of couples in the surgical group achieved a spontaneous pregnancy and an additional 6% achieved a pregnancy via ART (20% of this group attempted ART). In the nonsurgical group, 25% achieved a spontaneous preg- nancy and an additional 16% achieved a pregnancy with ART (40% of this group attempted ART). This study on the natural history of infertile men with varicocele and advanced female age suggests that the surgical and nonsurgical approaches offer comparable pregnan- cy outcome (combined assisted and unassisted pregnancy rates are about 40%). Overall, these data suggest that varicocelectomy is an acceptable option for couples with advanced female age, but other female factors must be considered in the decision-making process.

It is widely accepted that signal-detection mechanisms contribute to item-recognition memory decisions that involve discriminations between targets and lures based on a controlled laboratory study episode. Here, the authors employed mathematical modeling of receiver operating characteristics (ROC) to determine whether and how a signal-detection mechanism contributes to discriminations between moderately famous and fictional names based on lifetime experience. Unique to fame judgments is a lack of control over participants' previous exposure to the stimuli deemed "targets" by the experimenter; specifically, if they pertain to moderately famous individuals, participants may have had no prior exposure to a substantial proportion of the famous names presented. The authors adopted established models from the recognition-memory literature to examine the quantitative fit that could be obtained through the inclusion of signal-detection and threshold mechanisms for two data sets. They first established that a signal-detection process operating on graded evidence is critical to account for the fame judgment data they collected. They then determined whether the graded memory evidence for famous names would best be described with one distribution with greater variance than that for the fictional names, or with two finite mixture distributions for famous names that correspond to items with or without prior exposure, respectively. Analyses revealed that a model that included a d' parameter, as well as a mixture parameter, provided the best compromise between number of parameters and quantitative fit. Additional comparisons between this equal-variance signal-detection mixture model and a dual-process model, which included a high-threshold process in addition to a signal-detection process, also favored the former model. In support of the conjecture that the mixture parameter captures participants' prior experience, the authors found that it was increased when the analysis was restricted to names in occupational categories for which participants indicated high exposure.

Although it is well established that the integrity of the medial temporal lobe (MTL) is critical for declarative memory, the func- tional organization of the MTL remains a matter of intense debate. One issue that has received little consideration so far is whether the hippo- campus can function normally in the presence of a lesion to perirhinal cortex that produces noticeable memory impairments. This question is intriguing as the MTL forms a hierarchical system, in which perirhinal cortex represents one of the critical nodes in the reciprocal projections between neocortical association areas and the hippocampus. Here, we used functional magnetic resonance imaging to examine whether NB, an individual who underwent surgical resection of the left anterior tem- poral lobe that included large aspects of perirhinal and entorhinal cor- tex but spared the hippocampus, exhibits intact hippocampal novelty responses to auditory sentences. Our results revealed such evidence in NB's left and right hippocampus. They complement previous behavioral work in NB, indicating that recollective processes considered to rely on hippocampal integrity are also preserved. Further analyses revealed intact novelty responses in structures that provide neuroanatomical input to the hippocampus, including remaining perirhinal cortex and surgically spared parahippocampal cortex. These findings point to viable neuroanatomical mechanisms as to how functional integrity in the hip- pocampus may be maintained in the face of widespread, but incomplete removal of its input structures. V V C 2010 Wiley-Liss, Inc.