Impaired odor recognition memory in patients with hippocampal lesions

In humans, impaired recognition memory following lesions thought to be limited to the hippocampal region has been demonstrated for a wide variety of tasks. However, the importance of the human hippocampus for olfactory recognition memory has scarcely been explored. We evaluated the ability of memory-impaired patients with damage thought to be limited to the hippocampal region to recognize a list of odors. The patients were significantly impaired after a retention delay of 1 h. Olfactory sensitivity was intact. This finding is in agreement with earlier reports that rats with hippocampal lesions exhibited memory impairment on an odor delayed nonmatching to sample task (after 30 min and 1 h) and that patients with damage thought to be limited to the hippocampal region were impaired on an odor span memory task. Olfactory recognition memory, similar to recognition memory in other sensory modalities, depends on the integrity of the hippocampal region.     

Studies on retrograde and anterograde amnesia of olfactory memory after denervation of the hippocampus by entorhinal cortex lesions

The effect of hippocampal denervation on olfactory memory in rats was tested after interrupting the lateral olfactory tract projections at the level of the entorhinal cortex. When lesioned animals were trained to learn new odors, they showed no evidence of retention 3 h after acquisition. These results confirm earlier data on rapid forgetting in rats after hippocampal deafferentation and are in parallel to the anterograde amnesia typically found in humans with hippocampal damage. On the other hand, preoperatively learned information was minimally impaired after hippocampal deafferentation even if it was acquired within less than 1 h before the lesion. This finding differs from reports on humans as well as monkeys with hippocampal damage where memories formed during a critical time span of months or even years before the lesion are found to be impaired. This may suggest that the consolidation process in humans and rodents has different time scales or that the roles of the human and the rat hippocampal structure in memory formation are somewhat different.     

A specific role for the human amygdala in olfactory memory

The medial temporal lobe is known to play a role in the processing of olfaction and memory. The specific contribution of the human amygdala to memory for odors has not been addressed, however. The role of this region in memory for odors was assessed in patients with unilateral amygdala damage due to temporal lobectomy (n = 20; 11 left, 9 right), one patient with selective bilateral amygdala damage, and in 20 age-matched normal controls. Fifteen odors were presented, followed 1 h later by an odor-name matching test and an odor-odor recognition test. Signal detection analyses showed that both unilateral groups were impaired in their memory for matching odors with names, these patients were not significantly impaired on odor-odor recognition. Bilateral amygdala damage resulted in severe impairment in both odor-name matching as well as in odor-odor recognition memory. Importantly, none of the patients were impaired on an auditory verbal learning task, suggesting that these findings reflect a specific impairment in olfactory memory, and not merely a more general memory deficit. Taken together, the data provide neuropsychological evidence that the human amygdala is essential for olfactory memory.     

Olfactory test performance and its relationship with the perceived location of odors

Odors are generally perceived as arising via the nose when sniffed and as part of an orally located flavor during ingestion. The perceived location of an odor may in part be an attentional phenomenon, with concurrent oral stimulation occurring at the expense of access to the olfactory channel. Two predictions were derived from this account: (a) tasks dependent on a capacity to attend to the olfactory channel--odor discrimination and naming--should be adversely affected by oral localization; and (b) tasks not dependent upon a capacity to attend--incidental learning/recognition memory--should not. Using a procedure to generate oral localization, in which odors were presented via the nose with concurrent oral stimulation (sucrose, a viscous fluid or water), greater reported oral localization was associated with poorer odor discrimination and naming, but not with recognition memory performance. These results support the notion that attentional processes contribute to oral localization of odors by reducing the capacity to attend to the olfactory channel.     

Recall of odors: naming and autobiographical memories illustrate odor aftereffects

In the study phase, subjects had to encode either odors or the names there of by generating autobiographical memories, by judging the quality of the food source of the odors, or by labeling responses to odors. At the testing stage, explicit and implicit olfactory memory performance was assessed. With recognition testing, the provision of odors at study improved performance. Furthermore, recognition depended on elaborative encoding conditions with olfactory stimuli only. Implicit memory was measured by the correctness and speed of labeling responses at the testing stage. Old odors were named more correctly and faster than new ones, but only if subjects had encoded odors in the study phase. These results demonstrate that implicit memory in naming odors depends on olfactory stimulus processing and is not a purely verbal priming effect. As a further measure of implicit memory, the speed of autobiographical memory productions was assessed. We registered shorter reaction times for old versus new odors. But again, this effect of implicit memory was restricted to conditions of odor pre-experiences in the study phase. We conclude that olfactory memory is based on different types of memory traces. Implicit memory measures may prove to be useful in isolating sensory and other attributes of olfaction that seem to be interacting in making explicit memory judgments.     

The role of the dorsal and ventral hippocampus in olfactory working memory

Olfactory working memory and pattern separation for odor information was assessed in male rats using a matching-to-sample for odors paradigm. The odor set consisted of a five aliphatic acids with unbranched carbon chains that varied from two- to six-carbons in length. Each trial consisted of a sample phase followed by a choice phase. During the sample phase, rats would receive one of five different odors. Fifteen seconds later during the choice phase one of the previous odors was presented simultaneously side by side with a different odor that was based on the number of aliphatic acids that varied in the carbon chains from two- to six-carbons in length and rats were allowed to choose between the two odors. The rule to be learned in order to receive a food reward was to always choose the odor that occurred during the study phase. Odor separations of 1, 2, 3 or 4 were selected for each choice phase and represented the carbon chain difference between the study phase odor and the test phase odor. Once an animal reached a criterion of 80–90% correct across all temporal separations based on 40 trials, rats received a control, dorsal hippocampal, or ventral hippocampal lesion and were retested on the task. On postoperative trials, only the ventral hippocampal lesion group was impaired relative to both control and dorsal hippocampal groups groups. There were no effects on odor pattern separation. All groups of rats could discriminate between the odors. The data suggest that the ventral hippocampus, but not dorsal hippocampus, supports working memory for odor information.     

Hippocampal formation lesions impair performance in an odor-odor association task independently of spatial context

The rodent hippocampal system is known to play an important role in memory. Evidence that this role is not limited to spatial memory has come from studies using a variety of non-spatial memory tasks. One example is the social transmission of food preference paradigm, a task in which rats learn an odor-odor association with no explicit spatial memory component. However, because training and testing in this task typically take place in the same environment, it is possible that memory for the spatial context in which odors are experienced during training is critical to subsequent retention performance. If this is the case, it might be expected that lesions of the hippocampal system would impair memory performance by disrupting the establishment of a representation of the training environment. We addressed this issue by training rats in one spatial context and then testing them either in the same or a different spatial context. Normal control rats performed equally well when tested in an environment that was the same or different from that used during training, and the retention impairment exhibited by rats with hippocampus plus subiculum lesions was equivalent in the two test environments. These results support the view that the hippocampal system is necessary for the flexible expression of nonspatial memories even when the spatial context in which the memory is acquired is not critical to retrieval.     

Sensory and semantic factors in recognition memory for odors and graphic stimuli: elderly versus young persons

In four experiments, young (18-26 years, M = 21) and elderly (over 65 years, M = 72) people were compared for recognition memory of (a) graphic stimuli (faces of presidents and vice presidents, engineering symbols, and free forms) and (b) everyday odors. On graphic stimuli, the elderly consistently matched the young, but on odors the performance of the elderly was worse. Their poorer olfactory performance was observed after only 26 s, but became truly marked after 1 hr or more. Somewhere between 1 hr and 2 weeks, their odor performance fell to chance, but their graphic performance remained well above chance. Although the young did forget both graphic and odor materials progressively, their performance always stayed above chance over a 6-month period. Experiments 1 and 2 revealed that the elderly are less sensitive to odors than the young (with thresholds about 10-fold higher), which may explain, in part, their poorer olfactory memory performance. Knowledge that the subjects brought to the tasks by way of familiarity with and ability to name odors and faces played a positive role in recognition memory. Because of this positive role, together with the negative role played by verbal distraction, we conclude that odor recognition memory depends, perhaps heavily, on semantic processing. Impaired semantic processing may result even when odors are simply rendered desaturated, or pastel because of the weakening of olfactory sensitivity with aging.     

Effects of dizocilpine (MK801) on olfactory span in rats

NMDA receptor antagonists interfere with learning and memory in some tasks, but not others. Some recent accounts have suggested that tasks placing demands on working memory are those most likely to be affected, and the present study tested this hypothesis. The purpose of the study was to adapt a recently developed procedure designed to test working memory capacity, the olfactory memory span task, for use in behavioral pharmacology and to then determine the effects of the NMDA receptor antagonist, dizocilpine (MK801) on performance in this task. Rats were trained in a non-match-to-sample procedure under conditions in which they had to remember an increasing number of olfactory stimuli as the session progressed. Simple olfactory discrimination trials were interspersed to provide a performance control. Effects of dizocilpine (.03, .10, .17, .3mg/kg) were determined after stable performances were obtained. Rats were able to sustain stable performances on both the span and simple discrimination tasks with average spans of about 10 items. Accuracy declined as the number of stimuli to remember increased, and dizocilpine impaired accuracy in a dose-dependent and memory-load dependent fashion. The finding that the effects of dizocilpine interacted with the number of stimuli to remember is generally consistent with hypotheses linking NMDA receptors and working memory processes.     

Sex differences in memory performance for odors, tone sequences and colors

Sense of olfaction would seem to be of little importance for human behavior. However, a closer look at this from the psychological point of view reveals many interesting aspects, such as sex differences in olfactory perception, that are of interest to differential psychology. The present study deals with sex differences in the memory for odors; we assume that women will do better here than men while other memory tasks involving acoustical and optical stimuli will show no such differences. Sixty women and 40 men were examined. On the first day, they had to retain 10 odors, 10 random-generated tone-sequences, and 10 colors. On the second day, 20 such stimuli for each memory task were presented, and the subjects had to remember and to tell which were known and which of them were unknown stimuli to them. A significant advantage in the olfaction memory task was found for women, while acoustical and optical memory scores showed no such differences. This expected finding is discussed in two ways. First, the female advantage might result from phylogenetic sources. Second, it might arise because women in general more often than men seem to deal with olfactory cues, so that they might simply have more experience and therefore the greater chance to score higher in an odor memory task.     

Animal cognition and the rat olfactory system

Is smell a 'primitive' sense used primarily to guide biologically basic behaviors or might it be the sensory modality that allows some species to express complex learning and other forms of cognitive behavior? Historically, the olfactory system has been considered primitive and it is not surprising that, until recently, cognitive neuroscientists have ignored odor-guided behavior. However, we now know that the olfactory system has projections to the prefrontal cortex, entorhinal cortex and hippocampus, and that these connections support the acquisition of simple and higher-order instrumental tasks, as well as a robust memory for odors. It appears that animals with a well-developed sense of smell have the neural machinery to think with their noses.     

Olfactory working memory: effects of verbalization on the 2-back task

Working memory for odors, which has received almost no attention in the literature, was investigated in two experiments. We show that performance in a 2-back task with odor stimuli is well above chance. This is true not only for highly familiar odors, as has been shown by Dade, Zatorre, Evans, and Jones-Gotman, NeuroImage, 14, 650–660, (2001), but also for unfamiliar ones that are notoriously difficult to name. We can conclude that information about an olfactory stimulus can be retained in the short term and can continuously be updated for comparison with new olfactory probes along the lines of a functional odor working memory. However, the performance in the working memory task is highly dependent on participants’ verbalization of the odor. In addition, results indicated that odor working memory performance is dependent on the ability to discriminate among the odor stimuli (Experiment 2). The results are discussed in relation to recent ideas of a separate olfactory working memory slave system.     

The hippocampus and memory for "what," "where," and "when"

Previous studies have indicated that nonhuman animals might have a capacity for episodic-like recall reflected in memory for "what" events that happened "where" and "when". These studies did not identify the brain structures that are critical to this capacity. Here we trained rats to remember single training episodes, each composed of a series of odors presented in different places on an open field. Additional assessments examined the individual contributions of odor and spatial cues to judgments about the order of events. The results indicated that normal rats used a combination of spatial ("where") and olfactory ("what") cues to distinguish "when" events occurred. Rats with lesions of the hippocampus failed in using combinations of spatial and olfactory cues, even as evidence from probe tests and initial sampling behavior indicated spared capacities for perception of spatial and odor cues, as well as some form of memory for those individual cues. These findings indicate that rats integrate "what," "where," and "when" information in memory for single experiences, and that the hippocampus is critical to this capacity.     

Olfactory cuing of autobiographical memory

In Experiment 1, subjects were presented with either the odors or the names of 15 common objects. In Experiment 2, subjects were presented with either the odors, photographs, or names of 16 common objects. All subjects were asked to describe an autobiographical memory evoked by each cue, to date each memory, and to rate each memory on vividness, pleasantness, and the number of times that the memory had been thought of and talked about prior to the experiment. Compared with memories evoked by photographs or names, memories evoked by odors were reported to be thought of and talked about less often prior to the experiment and were more likely to be reported as never having been thought of or talked about prior to the experiment. No other effects were consistently found, though there was a suggestion that odors might evoke more pleasant and emotional memories than other types of cues. The relation of these results to the folklore concerning olfactory cuing is discussed.     

Olfactory Information Processing and Temporal Lobe Epilepsy

It has been suggested that olfactory information processing is impaired in patients with temporal lobe epilepsy. However, the existing evidence is not wholly in accordance with this notion. Patients with epileptogenic foci in the left temporal lobe, the right temporal lobe, or other brain regions were compared with normal control subjects in the identification and retention of common odors. All three patient groups were substantially and equally impaired in verbally labelling the odors in question. The patients with epilepsy associated with the left temporal lobe or with nontemporal regions showed no sign of any impairment on a test of immediate recognition memory for common odors. However, the patients with epilepsy associated with the right temporal lobe showed a specific disturbance in their retention of nameable odors. It is suggested that the latter patients were selectively impaired in their retrieval of the episodic memories which provide the context for the encoding of distinctive odors.     

Verbal coding in olfactory versus nonolfactory cognition

Two paired-associate memory experiments were conducted to investigate verbal coding in olfactory versus nonolfactory cognition. Experiment 1 examined the effects of switching/not switching odors and visual items to words between encoding and test sessions. Experiment 2 examined switching/not switching perceptual odors and verbal-imagine versions of odors with each other. Experiment 1 showed that memory was impaired for odors but not visual cues when they were switched to their verbal form at test. Experiment 2 revealed that memory was impaired for both odors and verbal-imagine cues when they were switched in format at test and that odor sensory imagery was not accessed by the instruction to imagine a smell. Together, these findings suggest that olfaction is distinguished from other sensory systems by the degree of verbal coding involved in associated cognitive processing.     

Implicit and explicit memories of odors

The present experiments explore whether there may be some forms of implicit memory for odors. In the first experiment, the elaborateness of olfactory encoding was varied at presentation. For (explicit) recognition memory testing we found positive effects of labeling responses to odors at encoding. Implicit memory measures (temporal and preference judgments) did not reveal reliable effects of prior odor presentation, however. The second experiment corroborated effects of levels of processing on r recognition memory. Again, perceptual or affective judgments remained insensitive for prior odor exposures. Implicit memory could only be detected with verbal measures at the testing stage (labeling accuracy or latency). These results are consistent with the proposal that odor information is represented at different levels of processing that are even with implicit memory measures only partly accessible.     

Perceptual,affective, and cognitive judgments of odors: pleasantness and handedness effects

The present study sought to examine the differential processing of pleasant, neutral, and unpleasant odors. The effects of the nostril stimulated (left or right) and the type of judgment (perceptual, affective, or cognitive) performed on the olfactory stimuli were also studied. To this end, 64 subjects were asked to smell pleasant, neutral, and unpleasant odors under four conditions (detection, intensity, pleasantness, and familiarity tasks). The participants were to perform these tasks as quickly as possible, while response times were recorded. The results showed that (i) unpleasant odors were assessed more rapidly than neutral or pleasant odors, and that this was specifically true (ii) during right nostril stimulation, and (iii) during pleasantness assessment, suggesting possible differential cerebral hemisphere involvement, with a right-side advantage for processing of unpleasant affect in olfaction. A handedness effect on familiarity judgment is also discussed.     

Roles for Drosophila mushroom body neurons in olfactory learning and memory

Olfactory learning assays in Drosophila have revealed that distinct brain structures known as mushroom bodies (MBs) are critical for the associative learning and memory of olfactory stimuli. However, the precise roles of the different neurons comprising the MBs are still under debate. The confusion surrounding the roles of the different neurons may be due, in part, to the use of different odors as conditioned stimuli in previous studies. We investigated the requirements for the different MB neurons, specifically the alpha/beta versus the gamma neurons, and whether olfactory learning is supported by different subsets of MB neurons irrespective of the odors used as conditioned stimuli. We expressed the rutabaga (rut)-encoded adenylyl cyclase in either the gamma or alpha/beta neurons and examined the effects on restoring olfactory associative learning and memory of rut mutant flies. We also expressed a temperature-sensitive shibire (shi) transgene in these neuron sets and examined the effects of disrupting synaptic vesicle recycling on Drosophila olfactory learning. Our results indicate that although we did not detect odor-pair-specific learning using GAL4 drivers that primarily express in gamma neurons, expression of the transgenes in a subset of alpha/beta neurons resulted in both odor-pair-specific rescue of the rut defect as well as odor-pair-specific disruption of learning using shi(ts1).