Amygdala lesions selectively impair familiarity in recognition memory.
ABSTRACT: A major controversy in the study of memory concerns whether there are distinct medial temporal lobe (MTL) substrates of recollection and familiarity. Studies using receiver operating characteristics analyses of recognition memory indicate that the hippocampus is essential for recollection, but not for familiarity. We found the converse pattern in the amygdala, wherein damage impaired familiarity while sparing recollection. Combined with previous findings, these results dissociate recollection and familiarity by selective MTL damage.
Project description:The neural basis of memory is highly distributed, but the thalamus is known to play a particularly critical role. However, exactly how the different thalamic nuclei contribute to different kinds of memory is unclear. Moreover, whether thalamic connectivity with the medial temporal lobe (MTL), arguably the most fundamental memory structure, is critical for memory remains unknown. We explore these questions using an fMRI recognition memory paradigm that taps familiarity and recollection (i.e., the two types of memory that support recognition) for objects, faces, and scenes. We show that the mediodorsal thalamus (MDt) plays a material-general role in familiarity, while the anterior thalamus plays a material-general role in recollection. Material-specific regions were found for scene familiarity (ventral posteromedial and pulvinar thalamic nuclei) and face familiarity (left ventrolateral thalamus). Critically, increased functional connectivity between the MDt and the parahippocampal (PHC) and perirhinal cortices (PRC) of the MTL underpinned increases in reported familiarity confidence. These findings suggest that familiarity signals are generated through the dynamic interaction of functionally connected MTL-thalamic structures.
Project description: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.
Project description:The fornix is the main tract between the medial temporal lobe (MTL) and medial diencephalon, both of which are critical for episodic memory. The precise involvement of the fornix in memory, however, has been difficult to ascertain since damage to this tract in human amnesics is invariably accompanied by atrophy to surrounding structures. We used diffusion-weighted imaging to investigate whether individual differences in fornix white matter microstructure in neurologically healthy participants were related to differences in memory as assessed by two recognition tasks. Higher microstructural integrity in the fornix tail was found to be associated with significantly better recollection memory. In contrast, there was no significant correlation between fornix microstructure and familiarity memory or performance on two non-mnemonic tasks. Our findings support the idea that there are distinct MTL-diencephalon pathways that subserve differing memory processes.
Project description:Recognition memory is thought to depend on two distinct processes: recollection and familiarity. There is debate as to whether damage to the hippocampus selectively impairs recollection or whether it impairs both recollection and familiarity. If hippocampal damage selectively impairs recollection but leaves familiarity intact, then patients with circumscribed hippocampal lesions should exhibit the full normal range of low-confidence and high-confidence familiarity-based recognition. High-confidence, familiarity-based decisions are ordinarily accompanied by successful recollection (when memory is intact). However, patients with hippocampal lesions, if recollection is impaired, should frequently experience high-confidence, familiarity-based recognition in the absence of recollection, and this circumstance (termed the "butcher-on-the-bus" phenomenon) should occur more often in patients than in healthy controls. We tested five patients with circumscribed hippocampal damage, asking them to recognize recently studied words as well as to remember the context in which the items were studied. Relative to controls, the patients exhibited no increased tendency to experience the butcher-on-the-bus phenomenon. The simplest explanation of the results is that hippocampal damage impairs familiarity as well as recollection. The same conclusion was suggested when two competing models of recognition memory were used to analyze the data.
Project description:Models of recognition memory have postulated that the mammillo-thalamic tract (MTT)/anterior thalamic nucleus (AN) complex would be critical for recollection while the Mediodorsal nucleus (MD) of the thalamus would support familiarity and indirectly also be involved in recollection (Aggleton et al., 2011). 12 patients with left thalamic stroke underwent a neuropsychological assessment, three verbal recognition memory tasks assessing familiarity and recollection each using different procedures and a high-resolution structural MRI. Patients showed poor recollection on all three tasks. In contrast, familiarity was spared in each task. No patient had significant AN lesions. Critically, a subset of 5 patients had lesions of the MD without lesions of the MTT. They also showed impaired recollection but preserved familiarity. Recollection is therefore impaired following MD damage, but familiarity is not. This suggests that models of familiarity, which assign a critical role to the MD, should be reappraised.
Project description:A major controversy in memory research concerns whether recognition is subdivided into distinct cognitive mechanisms of recollection and familiarity that are supported by different neural substrates. Here we developed a new associative recognition protocol for rats that enabled us to show that recollection is reduced, whereas familiarity is increased following hippocampal damage. These results provide strong evidence that these processes are qualitatively different and that the hippocampus supports recollection and not familiarity.
Project description:Alcohol and other pharmacologically similar sedatives (i.e., GABAA positive allosteric modulators or PAMs) impair the encoding of new episodic memories but retroactively facilitate the consolidation of recently encoded memories. These effects are consistent for recollection (i.e., the retrieval of details) but some mixed results have been reported for familiarity (i.e., a feeling of knowing a stimulus was presented). Here, with dual-process models, we reanalyzed prior work testing the effects of GABAA PAMs at encoding or consolidation. Contrary to previous conclusions, we show that GABAA PAMs at encoding consistently impair both recollection and familiarity when an independence correction is applied to familiarity-based responses. These findings were further confirmed and extended in a dual-process signal detection analysis of a recent study on the effects of alcohol during encoding or consolidation: Alcohol at encoding impaired both recollection and familiarity, whereas alcohol at consolidation enhanced both recollection and familiarity. These findings speak to the ability of alcohol and other GABAA PAMs to induce 'blackouts,' highlighting the importance of dual-process approaches when analyzing drug manipulations at different phases of episodic memory.
Project description:There is continuing controversy about the extent to which the rodent medial prefrontal cortical area (mPFC) is functionally homologous to the dorsolateral prefrontal cortex in humans and nonhuman primates. Previous studies have compared the effects of mPFC lesions in rats to those of dorsolateral prefrontal lesions in working memory, strategy switching, and temporal ordering. None, however, has examined the role of the rodent mPFC in recognition memory, wherein, in humans, dorsolateral prefrontal damage results in a deficit in source monitoring resulting in impaired recollection. In the present study, we examined recognition memory in rats with bilateral mPFC lesions (prelimbic/infralimbic regions; ibotenic acid) using a variant of a non-match-to-sample task with manipulations of response bias that allowed for a signal detection analysis that distinguishes recollection and familiarity contributions to recognition memory. Animals with medial prefrontal lesions had a modest overall deficit in recognition with no general change in their tendency to elicit "old" or "new" responses. Signal detection analyses indicated that rats with mPFC damage had a curvilinear and symmetrical receiver operating characteristic (ROC) curve, compared with a curvilinear and asymmetrical ROC curve in control subjects, indicating that mPFC damage severely reduced recollection-based performance, while sparing familiarity. The recollection failure was associated with an impaired ability to reject new items (increased false alarm rate), whereas the identification of old items (hit rate) was normal. This pattern of findings is similar to that observed in humans with dorsolateral prefrontal damage and is complementary to the selective deficit in hit rate observed after hippocampal damage.
Project description:Episodic memories allow us to remember not only that we have seen an item before but also where and when we have seen it (context). Sometimes, we can confidently report that we have seen something (familiarity) but cannot recollect where or when it was seen. Thus, the two components of episodic recall, familiarity and recollection, can be behaviorally dissociated. It is not clear, however, whether these two components of memory are represented separately by distinct brain structures or different populations of neurons in a single anatomical structure. Here, we report that the spiking activity of single neurons in the human hippocampus and amygdala [the medial temporal lobe (MTL)] contain information about both components of memory. We analyzed a class of neurons that changed its firing rate to the second presentation of a previously novel stimulus. We found that the neuronal activity evoked by the presentation of a familiar stimulus (during retrieval) distinguishes stimuli that will be successfully recollected from stimuli that will not be recollected. Importantly, the ability to predict whether a stimulus is familiar is not influenced by whether the stimulus will later be recollected. We thus conclude that human MTL neurons contain information about both components of memory. These data support a continuous strength of memory model of MTL function: the stronger the neuronal response, the better the memory.