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Biomedical subjects

Paul E Gilbert

Publications and source records attributed to Paul E Gilbert.

At least 19 recordsLinked to original sources

Laterality of the olfactory event-related potential response.

In experimental practice, odors are commonly applied to only one nostril for recordings of olfactory event-related potentials (OERPs), but the lateralization aspect of the OERP response is unclear regarding both stimulated nostril and cortical topography. The purpose of the present study was to investigate whether stimulated-nostril side affects OERP amplitudes and latencies and whether these potentials indicate lateralization of brain response in healthy, right-handed, young adults. OERPs were recorded from nine electrode sites in response to monorhinal stimulation with amyl acetate in 28 participants. The results showed a general increase in amplitude from frontal to parietal electrode sites (in particular for N1/P3) and generally larger amplitudes on the left hemisphere and midline than on the right hemisphere. There was no main effect of stimulated-nostril side on amplitude. Interactions indicated that N1/P2 amplitude was larger for left- than right-nostril stimulation and larger on the left hemisphere and midline than on the right hemisphere in left-nostril stimulation. No main effect or interactions of stimulated-nostril side over latencies were found and no effects on latencies of sagittal or coronal sites. These findings suggest a general parietal, left-hemisphere predominance in response amplitude to odorous stimulation and imply that either the left or the right nostril may be sufficient for accurate assessment of OERP latency in right-handed, young adults.

Adolescent↗

The role of the dorsal CA3 hippocampal subregion in spatial working memory and pattern separation.

A delayed-match-to-sample for spatial location task was used to measure spatial pattern separation and working memory. On each trial, an object covered a baited food well in one of 15 spatial locations along a row of food wells perpendicular to the start box. Once the rat exited the start box, displaced the object to receive a food reward and then returned to the startbox, the same food well was then quickly re-baited, an identical object was positioned to cover the food well and another identical object was positioned in a different location along the row of food wells covering a different unbaited food well. On the ensuing choice phase, the animal was allowed to choose between the two objects. The object that covered the same food well as the object in the sample phase was the correct choice and the second foil object was the incorrect choice. Five spatial separations (15-105 cm) were randomly used to separate the correct object from the foil object during the choice phase. Once a preoperative criterion was met, each rat received bilateral intracranial infusions of either ibotenic acid or the vehicle into the CA3 subregion of the dorsal hippocampus. Following surgery, rats with CA3 lesions were significantly impaired relative to controls across all spatial separations suggesting that CA3 lesions impaired working memory. Although the dorsal CA3 subregion of the hippocampus may play a role in pattern separation, the data suggest that this region is critically involved in spatial working memory.

Animals↗

Estrogen and performance in recognition memory for olfactory and visual stimuli in females diagnosed with Alzheimer's disease.

Patients with Alzheimer's disease (AD) exhibit a deficit in episodic recognition memory for odors. It is hypothesized that the higher rate of AD in women may be due to estrogen-deprivation in postmenopausal women. Research suggests that estrogen may help to minimize cognitive decline in AD as well as postmenopausal olfactory loss. The current study examined the effects of estrogen replacement therapy (ERT) on performance of a recognition memory task for olfactory and visual stimuli in women AD patients. Participants included 24 women AD patients who were ERT users and 77 women AD patients who never used ERT. Compared with the ERT non-users, the ERT users committed significantly less false-positive memory errors for olfactory stimuli, whereas performance for visual stimuli did not differentiate between ERT users and non-users. The results suggest benefits of ERT could help ameliorate the earliest symptoms of AD, olfactory dysfunction, and memory impairment.

Aged↗

The effects of normal aging on source memory for odors.

Source and item memory for olfactory stimuli were assessed in healthy older (65+) and young adults. During the study phase, a male and a female source presented 16 odors to each participant one at a time. Each source presented 8 odors to the participant. As a way to assess source memory, the participant was asked to indicate whether an odor from the study phase was presented by the male or female. As a way to assess item memory, a study phase odor and a novel odor were presented and the participant was asked to indicate which was presented previously. Source memory for odors was impaired in older adults compared with young adults. However, there were no significant differences in odor item memory between young and older adults. Thus, source memory for olfactory stimuli may be a task that is particularly sensitive to age-related changes in the brain.

Adolescent↗

The role of the medial caudate nucleus, but not the hippocampus, in a matching-to sample task for a motor response.

A delayed-match-to-sample task was used to assess memory for motor responses in rats with control, hippocampus, or medial caudate nucleus (MCN) lesions. All testing was conducted on a cheeseboard maze in complete darkness using an infrared camera. A start box was positioned in the centre of the maze facing a randomly determined direction on each trial. On the sample phase, a phosphorescent object was randomly positioned to cover a baited food well in one of five equally spaced positions around the circumference of the maze forming a 180-degree arc 60 cm from the box. The rat had to displace the object to receive food and return to the start box. The box was then rotated to face a different direction. An identical baited phosphorescent object was placed in the same position relative to the start box. A second identical object was positioned to cover a different unbaited well. On the choice phase, the rat must remember the motor response made on the sample phase and make the same motor response on the choice phase to receive a reward. Hippocampus lesioned and control rats improved as a function of increased angle separation used to separate the correct object from the foil (45, 90, 135, and 180 degrees) and matched the performance of controls. However, rats with MCN lesions were impaired across all separations. Results suggest that the MCN, but not the hippocampus, supports working memory and/or a process aimed at reducing interference for motor response selection based on vector angle information.

Animals↗

Source and item memory for odors and objects in children and young adults.

Recall and recognition memory for odors are poorer in children than in adolescents. In addition, children perform worse than young adults on source memory tasks using visual and auditory stimuli. However, source memory for odor stimuli has not been examined in children. This study investigated source and item memory for odors and objects in children (7-10 years old) and young adults (18-24 years old). During the study phase, 1 male and 1 female experimenter (sources) randomly presented either 16 odors or 16 objects to the participant. Presentation alternated between sources so that each source presented 8 stimuli. Once the 16 stimuli were presented, the sources exited and a third experimenter began the test phase. To assess item recognition memory, a stimulus from the study phase and a novel stimulus were presented to the participant who was asked to choose the stimulus presented during the study phase. Source memory was assessed with the 8 stimuli from the study phase not used in the item memory task. The experimenter presented a stimulus and asked whether the male or female experimenter had presented the stimulus during the study phase. Results indicate that difference scores between item and source memory for odors were significantly larger for children than for young adults, indicating poorer source memory for children than adults. Difference scores for objects did not distinguish between groups. It has been suggested that the frontal lobes play a critical role in source memory and odor memory--a brain region that continues to develop into adolescence. Poor performance among children on the source memory task for odors may be due in part to immaturity of the frontal lobes.

Adolescent↗

The role of the hippocampus in the retrieval of a spatial location.

Based on computational models of the hippocampus, it has been suggested that a possible mechanism for memory retrieval is pattern completion, wherein an autoassociative network recalls previous patterns of activity given noisy or degraded cues. However, there are few behavioral data examining pattern completion per se in the hippocampus. Here, we present a study in which rats were tested on a spatial location retrieval paradigm, each trial of which consisted of a sample and choice phase. During the sample phase, rats were trained to displace an object in one of 15 possible locations to retrieve a food reward and return to the start-box on a cheeseboard maze. The object was then removed and the same location was re-baited for the choice phase. The rats' accuracy in returning to the correct location was recorded. On test trials, visual extramaze cues, vestibular cues, or both were manipulated to assess pattern completion in normal rats. Subjects were then randomly assigned to receive a cortical control, a sham, or a dorsal and ventral hippocampal lesion and were retested on the task. Control and unoperated rats were able to perform the task when visual extramaze or vestibular cues were reliable, but not when they were manipulated. Rats with hippocampal lesions were impaired in the baseline condition, as well as during all manipulations. These results support the hypothesis that the hippocampus supports the retrieval of a spatial location, possibly through a process of pattern completion.

Animals↗

The role of CA1 in the acquisition of an object-trace-odor paired associate task.

This experiment was designed to determine whether adding a temporal component to an object-odor association task would recruit the hippocampus. The rats were given CA1, CA3, or control lesions prior to learning the object-trace-odor task. Rats were presented with an object for 10 s, after which the object was removed, followed by a 10-s trace period, followed by the presentation of an odor 50 cm away. If the odor and the object were paired, rats were to dig in the odor cup for a reward. If unpaired, rats were to refrain from digging. Rats that had CA1 lesions were unable to make the association, whereas rats that had CA3 lesions performed as well as controls. These results support the idea that the hippocampus is involved in forming arbitrary associations that do not necessarily involve space as long as they involve a temporal component.

Animals↗

Differences between recognition memory and remote memory for olfactory and visual stimuli in nondemented elderly individuals genetically at risk for Alzheimer's disease.

Recognition and remote memory for olfactory and visual stimuli were assessed in nondemented elderly individuals positive for the apolipoprotein E 4 allele and in 4 negative controls to examine whether the 4 allele differentially affects recognition and/or remote memory depending on the modality of stimulus to be remembered. Compared to controls, 4 positive individuals committed more false positive recognition memory errors for olfactory but not visual stimuli suggesting that 4 positive individuals may show false positive errors for olfactory stimuli before deficits for other stimuli are detectable. There were no significant differences in familiarity ratings (a proposed measure of remote memory) suggesting that brain areas involved in remote memory are not affected in nondemented 4 positive individuals. The results suggest that neuropathological changes in nondemented individuals genetically at risk for Alzheimer's disease may differentially affect memory processes.

Aged↗

Memory for objects and their locations: the role of the hippocampus in retention of object-place associations.

Computational models of hippocampal function have suggested that the hippocampus is involved in the formation and storage of arbitrary associations. Previous studies have shown that rats with hippocampal lesions are impaired in object-place associative learning. However, few studies have examined the role of the hippocampus in the retention of previously learned arbitrary associations. In the present study, male Long-Evans rats with either cortical control or hippocampal lesions were tested on a task measuring the retention of previously learned arbitrary associations using an object-place paired-associate task. To assess retention, each animal was trained on the paired-associate task for 360 trials, then received a lesion, and was retested to examine retention of the previously learned associations. The results indicate that all rats learned the task prior to surgery. Following surgery, rats with cortical control lesions were not impaired in the retention of object-place associations. In contrast, hippocampal lesions resulted in an initial deficit in retention of the paired-associate task followed by recovery. Therefore, the hippocampus may play a role in the retrieval of previously learned arbitrary association.

Animals↗

Differences in olfactory and visual memory in patients with pathologically confirmed Alzheimer's disease and the Lewy body variant of Alzheimer's disease.

Recognition and remote memory for odors, faces, and symbols were assessed in patients with pathologically confirmed Lewy body variant of Alzheimer's disease (LBV), patients with pathologically confirmed Alzheimer's disease (AD), and healthy elderly controls. On recognition memory tasks, LBV and AD patients showed significantly lower discriminability (d') than controls, particularly for olfactory stimuli. However no significant differences were found in the bias measure (c). When participants rated familiarity (a proposed measure of remote memory) of olfactory stimuli LBV and AD patients reported significantly lower familiarity than controls. Familiarity ratings were significantly lower in LBV patients than in AD patients for olfactory, but not for visual stimuli. Consistent with prior reports, the LBV patients showed significantly poorer odor thresholds than AD patients. The results suggest that recognition memory for olfactory stimuli is impaired in LBV and AD. However, patients with LBV are more impaired than patients with AD on tasks requiring remote memory for olfactory but not visual stimuli. The findings suggest that odor memory tasks may be useful in the assessment of LBV and AD.

Aged↗

The effect of the ApoE epsilon4 allele on recognition memory for olfactory and visual stimuli in patients with pathologically confirmed Alzheimer's disease, probable Alzheimer's disease, and healthy elderly controls.

Episodic recognition memory for odors, faces, and unfamiliar symbols was assessed in apolipoprotein episilon4 positive and epsilon4 negative individuals with pathologically-confirmed Alzheimer's disease (AD), individuals diagnosed with probable AD, and healthy age- and gender-matched controls. The analyses revealed significant differences in performance between the AD patients and nondemented elderly controls based on the presence of the epsilon4 allele and the modality of the stimulus to be remembered. Measures of hits did not discriminate among groups but an analysis of false positive errors revealed significant differences, particularly for olfactory stimuli. Nondemented epsilon4 positive controls committed fewer false positive errors for olfactory stimuli compared to all other groups. In contrast, nondemented epsilon4 positive controls committed false positive errors for olfactory stimuli at rates similar to the AD patients. The performance of epsilon4 positive and epsilon4 negative controls was indistinguishable on the visual recognition memory tasks suggesting the particular vulnerability of olfactory memory to the early neuropathology of AD resulting in false positive errors in recognition memory for olfactory stimuli. The results of the present study offer new insight into how recognition memory is affected by AD, the epsilon4 allele, and the modality of the stimulus to be remembered.

Aged↗

The role of the amygdala in conditioned flavor preference.

Long-Evans rats with control or amygdala lesions were tested in a conditioned flavor preference task. Half of the rats in each lesion group received an unsweetened grape-flavored solution on odd-numbered days and a sweetened cherry-flavored solution on even-numbered days. The remaining rats received a sweetened grape-flavored solution on odd-numbered days and an unsweetened cherry-flavored solution on even-numbered days. The appropriate solution was presented once a day for 15 min to each rat in the homecage. After six days of testing, each rat received unsweetened cherry and grape flavored solutions simultaneously for 15 min daily across four days. When the two unsweetened flavored solutions were presented simultaneously control rats showed a significant preference for the flavor that was sweetened during training compared to the unsweetened solution. However, amygdala-lesioned rats did not show a preference. The data suggest that the amygdala may be critically involved in mediating reward-based conditioned flavor preference.

Amygdala↗

Localization of function within the dorsal hippocampus: the role of the CA3 subregion in paired-associate learning.

Computational models and electrophysiological data suggest that the CA3 subregion of the hippocampus supports the formation of arbitrary associations; however, no behavioral studies have been conducted to test this hypothesis. Rats with neurotoxin-induced lesions of dorsal dentate gyrus (DG), CA3, or CA1 were tested on object-place and odor-place paired-associate tasks to test whether the mechanism that supports paired-associate learning is localized to the CA3 subregion of the dorsal hippocampus or whether all hippocampal subregions contribute to paired-associate learning. The data indicate that rats with DG or CA1 lesions learned the tasks as well as controls; however, CA3-lesioned rats were impaired in learning the tasks. Thus, the CA3 subregion of the dorsal hippocampus contains a mechanism to support paired-associate learning.

Animals↗

The amygdala but not the hippocampus is involved in pattern separation based on reward value.

A total of 32 male Long-Evans rats were tested on a modified version of Flaherty, Turovsky, and Krauss's (1994) anticipatory contrast paradigm to assess pattern separation for reward value. Prior to testing, each rat received either a control, a hippocampal, or an amygdala lesion. In the home cage, each rat was allowed to drink a water solution containing 2% sucrose for 3 min followed by a water solution containing 32% sucrose for 3 min. Across 10 days of testing, the rats in each lesion group showed significantly increased anticipatory discriminability as a function of days. To assess the operation of a pattern separation mechanism, each rat was then tested using the same procedure except the 2% solution was followed by a 16% solution for 10 days and then by an 8% solution for 10 days. Control and hippocampal-lesioned rats continued to show high discriminability when the 2% solution was followed by a 16% solution; however, the amygdala-lesioned rats showed low anticipatory discriminability. On trials where the 2% sucrose solution was followed by an 8% sucrose solution, all groups showed low discriminability scores, suggesting that when two reward values are very similar even control animals are not able to separate the reward values in memory. However, the results of a preference task revealed that all groups can perceptually discriminate between a 2% and an 8% sucrose solution. The data suggest that the amygdala but not the hippocampus is involved in the separation of patterns based on reward value.

Amygdala↗

Role of the rodent hippocampus in paired-associate learning involving associations between a stimulus and a spatial location.

The ability of rats with control or hippocampal lesions to learn an object-place, odor-place, or object-odor paired-associate task was assessed in a cheeseboard maze apparatus. The data indicate that rats with hippocampal lesions were significantly impaired, compared with controls, in learning both the object-place and the odor-place paired-associate tasks. However, rats with hippocampal lesions learned the object-odor paired-associate task as readily as did controls. The data suggest that the rodent hippocampus is involved in paired-associate learning when a stimulus must be associated with a spatial location. However, the hippocampus is not involved in paired-associate learning when the association does not involve a spatial component.

Animals↗

The role of the hippocampus in memory for the temporal order of a sequence of odors.

Memory for the temporal order of a sequence of odors was assessed in rats. A sequence of 5 odors mixed in sand was presented in digging cups, 1 at a time, to each rat in a sequence that varied on each trial. A reward was buried in each cup. After the 5th odor, 2 of the previous 5 odors were presented simultaneously; to receive a reward, the rat had to choose the odor that occurred earliest in the sequence. Temporal separations of 1, 2, or 3 represented the number of odors that occurred between the 2 odors in the sequence. Once a preoperative criterion was reached, each rat received a hippocampal (HIP) or cortical control lesion and was retested on the task. On postoperative trials, the HIP group was impaired relative to controls. However, the HIP group could discriminate between the odors. The data suggest that the hippocampus is involved in separating sensory events in time so that I event can be remembered separately from another event.

Animals↗