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Back to Journal »Neuropsychiatric Diseases and Treatment» Volume 17
The comparative effects of repetitive odor recognition and odor memory tasks on elderly olfactory participation: a pilot fMRI study
Author Rai N, Hipolito MM, VanMeter JW, Seth R, Adenuga A, Shelby M, Misiak-Christian M, Nwaokobia C, Manaye KF, Obisesan TO, Nwulia E
Published on April 30, 2021, Volume 2021: 17 pages, 1279-1288 pages
DOI https://doi.org/10.2147/NDT.S298303
Single anonymous peer review
Editor who approved for publication: Dr. Roger Pinder
Narayan Rai,1,* Maria Mananita Hipolito,1,* John W VanMeter,2 Riya Seth,3 Ayokunnumi Adenuga,3 Myeshia Shelby,4 Magdalena Misiak-Christian,5 Charles Nwaokobia,3 Kebreten F Manaye,5 Thomas O Obisesan,6 Evaristus Nwulia1,3 1 Department of Psychiatry and Behavioral Sciences, Howard University, Washington, DC; 2 Department of Neurology, Center for Functional and Molecular Imaging, Georgetown University Medical Center, Washington, DC; 3Evon Medics LLC, Elkridge, MD, USA; 4 Howard, Washington, DC University Graduate School; 5 Department of Science, Howard University, Washington, DC; 6 Department of Medicine, Howard University, Washington, DC *These authors contributed equally to this work. Corresponding author: Evaristus Nwulia, Department of Psychiatry and Behavioral Sciences, Howard University, Washington, DC, USA For memory and odor recognition tasks, blood oxygen level-dependent (BOLD) responses in the primary and advanced olfactory areas of the elderly. The goal is to compare these two odor training tasks to determine which regions of interest in smell and memory are more strongly involved in the elderly population. Methods: Twelve adults aged 55-75 (75% women) with no intranasal or major neurological diseases used a 3 Tesla MRI scanner to perform repetitive odor memory and recognition tasks. The odor appears at 10-second burst intervals with 20-second odorless air intervals in between. The paired t-test was used to compare the difference in activation degree between individual internal odor recognition and odor memory tasks. The FDR cluster level correction of p<0.05 was used for multiple tests (the cluster definition threshold was set to p<0.01 and 10 voxels). Results: Compared with smell recognition and memory (ie smell recognition> smell memory), there are several significantly activated regions, including many classic olfactory brain regions and hippocampus. The opposite contrast (odor memory> smell recognition) includes the pear-shaped cortex, although this is not significant. The two tasks also activate the piriform cortex, so when the two tasks are compared with each other, this activation area does not seem to exist (OI> OM) or is only weakly observed (OM> OI). Conclusion: These findings from mainly African-American samples suggest that odor recognition tasks may be more effective than memory tasks in target olfactory participation in the elderly population. In addition, compared with the odor memory task, repetitive odor recognition has a more significant effect on the hippocampus (area related to Alzheimer's disease). If verified in larger studies, this result may have important implications for the design of olfactory training paradigms. Keywords: blood oxygen level dependent response, BOLD, odor memory, odor recognition, olfactory participation, olfactory training
Functional neuroimaging procedures have greatly promoted the understanding of the neurobiology of olfactory processing and helped clarify the impact of normal and abnormal aging on the risk of Alzheimer's disease development. 1,2 Functional magnetic resonance imaging (fMRI), which measures the level-dependent (BOLD) response of nerve activation in the blood oxygen olfactory cortex, is particularly capable of identifying the cortex and subcortical brain structures involved in olfactory processing. 3,4 The use of fMRI to examine the sense of smell is a sensitive technique 5, used to prove the performance changes of neural correlation in many olfactory tasks, and can be used to detect the selective activation of primary and advanced olfactory regions by olfactory psychophysical tasks. More and more clinical research evidence shows that through repeated odor stimulation with or without odor psychophysical tasks, olfactory training can improve the functional defects of the olfactory nerve structure affected by the pathophysiology of Alzheimer's disease in the early stage. 6-8 Provide empirical support for use. Compared with other specific olfactory psychophysical tasks, as a presumption tool for the treatment or prevention of age-related olfactory compromise, it is very important to compare the relative intensity of psychophysical tasks in the functional participation of these areas of interest.
The psychophysical task of smell is based on presenting an odor to a test subject and then checking the subject’s answers to questions about certain characteristics of the presented odor. 9,10 Olfactory psychophysical tasks include odor recognition, odor memory, odor discrimination, and odor threshold sensitivity tasks. Odor identification (OI) is the number of odorants that participants can correctly identify or name. Odor memory (OM) measures the ability to remember the most recently applied odorant from a selection that includes non-previously applied odors. Odor threshold (OT) measures the lowest concentration of an odorant that can be reliably sensed. Odor discrimination measures the ability to distinguish between two alternate odors. Odor memory tasks are considered to have the highest cognitive needs and have been shown to widely activate olfactory brain regions, such as the piriform and orbitofrontal cortex. 11 The pear-shaped cortex is the most unique and largest part of the primary olfactory cortex. It is interconnected with the advanced olfactory area and other primary olfactory areas. 12-14 fMRI studies have shown that the primary olfactory cortex is inconsistent or not activated at all during passive olfactory stimulation, while the higher olfactory area shows strong activation. 15-17 Poellinger et al. 18 demonstrated from time-series fMRI experiments in the adult population that the primary olfactory cortex becomes more accustomed to odor stimuli, which leads to the inconsistency of odor stimuli to activate pear-shaped and other primary olfactory cortex areas. Specifically, they showed that the primary olfactory cortex will adapt after 10 seconds of odor transmission in the average adult population. Therefore, during the odor processing task, the presentation of odors that depend on the structure and function of the pear-shaped cortex (such as odor memory) must be brief.
The purpose of this study was to examine the relative differences in olfactory participation, and to compare two odor training tasks for memory and recognition in the elderly population, using the olfactory fMRI paradigm in 12 individuals without neurological and nasal diseases. These tasks are used to identify the selective activation of the primary olfactory cortex and higher olfactory areas. Use short bursts of intermittent odor delivery to minimize the habit of odorants used in this study. It is expected that the results of this study will have some impact on the design of olfactory fMRI scanning paradigms, which can be used for future olfactory research in the elderly population, as well as the future development of the olfactory training paradigm for this population.
Twelve adults aged 55-75 were recruited through Howard University’s Geriatric Clinic and the 7th and 8th Districts of Washington, D.C., which are mainly of African American (AA) ethnicity. In accordance with the Declaration of Helsinki, the Howard University Institutional Review Board (IRB) approved research procedures for the ethical conduct of research involving human subjects. Only volunteers who provided written informed consent to participate after a thorough discussion of the study were included in the study. In order to be eligible for this study, participants must have almost no memory impairment, no history of mental illness (based on a detailed psychiatric history and examination conducted by the neuropsychiatrist co-author EN), and no current substance use (according to urine drug toxicology Confirmation) screening and blood alcohol level), no olfactory dysfunction based on odor threshold sensitivity test scores, no cerebrovascular disease or other neurological diseases (such as multiple sclerosis, Parkinson’s disease, dementia with Lewy bodies, frontotemporal dementia) Or traumatic brain injury), no obvious nasal diseases (such as nasal polyps or nasal tumors, nasal septum deviation, nasal surgery, congenital malformations of the nose, chronic nasal congestion and chronic sinusitis), and no serious medical diseases (such as End-stage renal disease and congestive heart failure). For the purpose of exclusion, neurological diseases were identified through detailed neurological examinations, medical record reviews, and structural MRI by a neuropsychiatrist co-author (EN). The neuroradiology co-author (JWV) reviewed structural MRI and excluded people with structural brain disease. In addition to self-reporting and medical history review, all participants also received a comprehensive nasal cavity examination using a flexible rhinoscope. We also performed an olfactory psychophysical task using a validated olfactory meter (described below) to exclude people with reduced odor threshold (OT) sensitivity, defined as a score <6 points, with a maximum score of 10. Detailed social, demographic and medical history were obtained from all participants. A Mini Mental State Examination (MMSE) was performed on all participants to exclude people with Alzheimer's disease or mild cognitive impairment (MCI). This study only included subjects with MMSE scores> 27 points (up to 30 points). A buccal swab from each participant was collected for genotyping of apolipoprotein E (APOE) polymorphism. All subjects were screened before the scan to ensure compatibility with the magnetic resonance (MR) environment; therefore, to be included in this study, the subjects had no claustrophobia, no metal implants, and were able to remove all metals or Magnetic device (if present). In addition, on the day of the MRI scan, all participants completed a detailed MRI safety form to identify and exclude people excluded from the MRI.
This was performed by researchers in a quiet room using a computer-controlled OLFACT-Combo, which is a mobile dilution olfactory meter19. The olfactory meter provides various odorants in the nose for clinical evaluation of odor identification (OI), odor memory (OM), odor threshold (OT) and odor discrimination (OD). 8 OLFACT consists of a two-chamber metal box; a chamber for OT tasks, containing 13 bottles of n-butanol solution of different concentrations and an empty bottle for cleaning the air; the other chamber contains 20 bottles of different essential oils, with For OI, OM and OD tasks. The details of olfactory evaluation with OLFACT-COMBO have been described elsewhere. 20 To prevent cross contamination of odorants, a Teflon tube is connected to each vial and presented through a plastic tube. Participants sat comfortably in front of a laptop connected to an olfactory meter to demonstrate the olfactory task problem. Provide test instructions and practice trials before each olfactory task assessment. The Osmic software installed on the laptop collected and stored the participants' answers. OLFACT's test-retest reliability for OI, OM, OT, and OD are 0.86, 0.84, 0.77, and 0.79, respectively. 21 Only normal participants, that is, individual tasks that get 6 or more points out of the highest 10 points for odor sensitivity , Was included in the study.
The fMRI olfactory paradigm uses an MRI-compatible olfactory meter controlled by a portable laptop computer, called OLFACT-fMRI. 22 OLFACT-fMRI consists of an air delivery system contained in a metal box and an odor delivery system in a plastic box container. The laptop and metal box are placed outside the MRI scanner room, and a detachable non-metallic delivery hose (24 feet × 1.25 inches) connects the metal box with the MRI-compatible plastic box through an open waveguide. The odor delivery system contains six different essential oils, which are placed next to the study participants. A plastic nasal cannula is used to deliver the odorant from the plastic box. The cannula has a Y-shaped Teflon tube at its tip and is placed in the subject's nostril. Teflon tubing is coated with polytetrafluoroethylene (PTFE), a synthetic chemical that provides a non-reactive, non-stick, and almost frictionless surface. 23 Unlike plastic pipes, PTFE-coated pipes have strong chemical resistance, can avoid adhesion, and can flow and accumulate without restriction without deposits. To secure the Teflon tube in place, plastic tubes were placed above the ears and behind the head to ensure the comfort of the study participants and the reliable delivery of odorants. The odor presentation is triggered by the OLFACT software. A constant flow of clean, odorless (maximum flow rate up to 2 liters per minute), unheated and unhumidified air is delivered between the odorant delivery. The olfactory task used the highest concentration of odorants; essential oils were purchased from Save on Scents and Perfumer's Apprentice.
The OM task acquisition (ie smell coding) phase from the fMRI olfactory paradigm starts in the simulated scanning room. Participants were asked to breathe normally and remember the smell that appeared in the simulated scanner. Each participant was asked to smell the three essential oils (lemon, cinnamon and rose) for 3 cycles in sequence; the scent was present for 10 seconds, and then 20 seconds apart to control the odor adaptation. The total duration of the acquisition phase is 280 seconds. Participants were told that the screen inside the MRI scanner would ask them if the odor was one of the three odors they acquired during the acquisition phase; all subjects used the response box to practice.
In the recognition phase of the OM task, performed in an MRI scanner 15 minutes after the acquisition phase, participants will receive six odors (strawberry, rose, coconut, lemon, cherry, and cinnamon). During the 10-second scent presentation, the screen display asked them if they remembered the scent during the collection phase. This was followed by an odorless presentation for 20 seconds, during which time the subject was instructed to breathe normally. The series of six scents are presented three times in the same order, and a total of eighteen scents are presented. The subjects were instructed to press the right-hand button to recall or press the left-hand button not to recall (Figure 1A). The response was limited to a 10-second odor exposure, not during the 20-second rest interval. Include ten seconds of rest/no odor at the beginning and end of the mission. The total duration of the task is 560 seconds. Figure 1 The experimental design of fMRI tasks for odor recognition and odor memory. (A) The odor first appeared outside the scanner, and then the odor and the new odor were displayed for 10 seconds, and questions were asked. The subjects were asked to point out with their fingers that they denied the old odor. The odor performance is interspersed by 20 seconds of odorless airflow at intermittent intervals. (B) Six kinds of odorants appear one at a time for 10 seconds, with no odor at an interval of 20 seconds. Participants were asked to point their fingers to the odor names on the screen that corresponded to the odors they perceive.
Figure 1 The experimental design of fMRI tasks for odor recognition and odor memory. (A) The odor first appeared outside the scanner, and then the odor and the new odor were displayed for 10 seconds, and questions were asked. The subjects were asked to point out with their fingers that they denied the old odor. The odor performance is interspersed by 20 seconds of odorless airflow at intermittent intervals. (B) Six kinds of odorants appear one at a time for 10 seconds, with no odor at an interval of 20 seconds. Participants were asked to point their fingers to the odor names on the screen that corresponded to the odors they perceive.
The entire fMRI OI task is performed in the scanning room. In the scanner, the subject holds a three-button response box in each hand—one button for the index finger, middle finger, and ring finger of each hand, and each finger corresponds to the smell image displayed on the screen during the smell presentation, interspersed Breathe normally for 20 seconds (Figure 1B). The six essential oils (strawberry, rose, coconut, lemon, cherry, and cinnamon) appear in 3 cycles in sequence, with each scent appearing for 10 seconds, and then there is an interval of 20 seconds in between. The subject was instructed to press the button corresponding to the screen image of the sensed smell. For example, when inhaling the odor of strawberry, selecting the strawberry image on the screen and other available odor images is the correct OI response; selecting an image with a different odor instead of the strawberry image is a wrong response. Participants were asked to make a choice every 10 seconds after the odor was exposed. Include ten seconds of rest/no odor at the beginning and end of the mission. The total duration of the task is 560 seconds.
Participants used a functional MRI scan, which was a Siemens 3T Prisma-Fit MRI scanner with a 64-channel head coil using TR/TE = 859/35 ms, a multi-band factor of 6, and FOV. Wave plane imaging pulse sequence obtained = 200 mm2 and 100×100 matrix, and 60 2 mm thick slices, the effective spatial resolution is 2 mm3. For positioning and spatial normalization, use TR/TE/TI = 1900/2.9/900 ms, FOV = 256 mm2 and 256×256 matrix, 176 slices to obtain a high resolution T1-weighted MPRAGE scan with a spatial resolution of 1 mm3.
Analyze the data in SPM12 (Wellcome Trust Center for Neuroimaging, University College London). The analysis includes the following steps: slice time correction to align slices in time, realignment to correct head movement, and average functional scan and high-resolution structure scan , The spatial normalization of the high-resolution structure scan is then applied to the rearranged functional scan and smoothed with a 4 mm3 filter.
Further analysis includes performing repeated measures one-way analysis of variance, combining the two paradigms of odor and odorless first-level comparison chart. Age is input as an uninteresting covariate. Use an uncorrected threshold that defines p <0.001 and a cluster of 10 consecutive voxels, and then use a cluster-level FDR-corrected p-value of 0.05.
The study population consisted of 12 people, 9 of whom (75%) were women, mainly African Americans (Table 1). Table 1 also describes the sociodemographic characteristics and performance of the study population in the fMRI olfactory task. Participants correctly identified 17.9% of odorants during the odor recognition fMRI task, and the recognition percentage ranged from 0% to 39%. During the fMRI scan, the study population correctly identified 62% (range 39-78%) of the odors they had previously been exposed to during the acquisition phase. Table 1 Socio-demographic characteristics and olfactory task performance of the research population
Table 1 Socio-demographic characteristics and olfactory task performance of the research population
The comparison of Odor Recognition (OI)> Odor Memory (OM) shows that several olfactory brain regions have statistically greater activation, including right middle temporal, bilateral precuneus, right hippocampus, upper left apex, and upper right apex , Left middle temporal, left inferior orbital frontal lobe, left upper frontal lobe, left insula and bilateral cerebellum (stem and vermis) (Table 2, Figure 2). Table 2 Comparison results of odor recognition (OI) and odor memory (OM) tasks (ie OI> OM comparison), depicting the olfactory brain regions that are more significantly activated by OI than OM tasks. Figure 2 shows greater activation The olfactory brain regions are compared for odor recognition tasks than for odor memory tasks.
Table 2 Comparison results of odor recognition (OI) and odor memory (OM) tasks (ie, OI> OM comparison), depicting the olfactory brain regions that are more significantly activated by OI than OM tasks
Figure 2 Compared with the odor memory task, the olfactory brain area showed greater activation in the odor recognition task.
In contrast, the odor memory task did not show any areas with significantly greater activation than the odor recognition task. The right and left piriform cortex of OM were slightly more activated than OI, although these did not reach statistical significance (Table 3, Figure 3). Using a one-sample t-test to examine each task individually shows that neither task effectively activates the piriform cortex. Table 3 The piriform cortex activation analysis result of the odor memory (OM) task is greater than the comparison of the odor recognition task (ie, OM> OI). The greater activation of the piriform cortex on the OM> OI contrast is not statistically significant. Figure 3 Compared with the odorless contrast, the activation of the left and right pear-shaped cortex by odor memory and odor recognition tasks. Odor memory activates the piriform slightly more than odor recognition, but this greater activation (OM<OI) is not statistically significant.
Table 3 The piriform cortex activation analysis result of the odor memory (OM) task is greater than the comparison of the odor recognition task (ie, OM> OI). OM has greater activation of the piriform cortex> OI contrast is not statistically significant
Figure 3 Compared with the odorless contrast, the odor memory and odor recognition tasks activate the left and right piriform cortex. Odor memory activates the piriform slightly more than odor recognition, but this greater activation (OM<OI) is not statistically significant.
Finally, it is important to note that both tasks activate the piriform cortex, so when the two tasks are compared with each other, this activation area does not seem to exist (OI> OM) or is only weakly observed (OM> OI). In Supplementary Table 1 (see Supplementary Document), we propose a one-way analysis of variance that uses repeated measurements to combine data from two tasks to prove that this part of the olfactory sensory cortex is activated by these tasks. Use uncorrected clusters with p<0.001 to determine the threshold and cluster range of 10 voxels.
Olfactory training, including repeated daily stimulation with odors, has been proposed as a treatment for several local and intracranial diseases with impaired olfactory function. 7,24,25 In this study, we examined the sequential olfactory areas in which the BOLD activity of the human primary olfactory cortex and higher layers respond to repetitive olfactory cognitive tasks in the elderly to determine their relationship with age-related neurological diseases Potential relevance of olfactory training. The comparison between odor recognition activation and odor memory activation was performed at the individual level, because each participant accepted these two tasks at different points in time. Therefore, compared with group-level studies, individuals serve as controls, some of which are randomly assigned only one or more tasks. Individual internal analysis helps to reduce the impact of heterogeneity caused by individual differences. In the elderly without nasal and nervous system diseases, the odor recognition (OI) task can significantly activate several brain regions than the odor memory (OM) task, including the right middle temporal lobe, bilateral precuneus, and right side Hippocampus, left parietal lobe, right upper parietal lobe, left middle temporal lobe, left inferior orbital frontal lobe, left upper frontal lobe, left insula lobe and bilateral cerebellum (stem and vermis). In contrast, the OM task can activate the piriform cortex more than the OI task, but it is not significant. These two tasks also activate the piriform body, so when comparing these two tasks with each other, within the individual, this activation area does not seem to exist (OI> OM) or is only weakly observed (OM> OI). However, compared with the OM task, OI does give priority to activating the hippocampus. This study provides new evidence that, compared with the OM task, when the OI task is used for olfactory training of elderly subjects, several olfactory regions and the hippocampus are involved.
Although many studies have been conducted on brain activation patterns in the general population, few studies have examined the changes in these activation patterns in the elderly to clarify the effects of aging on the human olfactory system. This study of the elderly showed that the fMRI task of odor recognition activates most of the classic primary and secondary olfactory regions activated by odorants in the general population, including the hippocampus, insula, infraorbital frontal lobe, and medial orbital frontal lobe , Middle temporal lobe, precuneus and parietal area. .18,26–28 Consistent with a previous study by Kareken et al.29, OI activated the temporal lobe, the orbitofrontal cortex, the right hippocampus 27 and the left insula-the area responsible for higher-order mental processing. 30 It is worth noting that at least one study26 found no significant activation in any of these classic olfactory brain regions in elderly subjects in the fMRI odor recognition task. One possible explanation for the lack of olfactory area activation in the latter study is their older cohort: the mean (SD) age of the participants in their study was 73 (5) years, compared to 66 (5) years in our study . Other influencing factors may be differences in methods, such as the use of different odors and the use of longer rest intervals between odor stimuli.
Compared with the extensive activation of odor recognition tasks in the primary and secondary olfactory regions, it has been found that the odor memory (OM) task mainly activates the primary olfactory cortex, especially the piriform cortex. 31 To the best of our knowledge, there is no published study specifically investigating the regional differences in brain activation between elderly and young subjects after the fMRI task of odor memory. We expect that the OM task will activate the piriform cortex more significantly than the OI task, but as we have shown in the supplementary data, these two tasks also activate the piriform cortex to a large extent. One possible reason why the activation of the piriformis in the OM task did not significantly exceed the activation of the piriformis in the OI task is that age-related biological factors may impose a limit on the activation of the piriformis in the memory task. Or, especially considering that OM and OI tasks have a greater tendency for piriform activation, in a larger clinical sample, OM-based piriform activation may be more statistically significant than OI-based piriform activation. Finally, it is also conceivable that the aging pear-shaped cortex can adapt faster than the general population. We used a very brief 10-second burst stimulation sequence, which was used by Poelinger and others to successfully activate the piriform cortex of the general population. To further support our use of the 10-second stimulus, we demonstrated the significant activation of the piriformis by the OM task (Supplementary Table 1). The only problem here is that OI also activated the piriformis of these participants.
This research also has an impact on olfactory training in the elderly using repetitive odor recognition tasks. From this perspective, compared with the repeated presentation of the odor memory task, the repeated presentation of the odor recognition task will produce stronger participation in the primary and secondary olfactory cortex regions and the hippocampus. An important question that arises is why odor memory is greater than odor recognition (ie, OM> OI). The contrast does not show significant differences in the activation of nearby medial temporal regions, such as the parahippocampus and hippocampus, which are usually involved in young populations by odor memory tasks . A possible explanation can be drawn from the previous findings, that is, the secondary and high-level central olfactory structures that contribute to odor recognition show significant age-dependence in middle-age and early aging, while the primary olfactory cortex is very sensitive to odor. Memory is essential-there is no significant age dependence in these age groups. 32 This is further supported by evidence of selective atrophy of secondary olfactory structures (such as the orbitofrontal cortex), but the primary olfactory cortex does not shrink during normal aging, 33 and our findings are compared with odor memory (OM performance score), The task performance of odor recognition (that is, the OI performance score) is relatively poor, as shown in Table 1. Several studies support the view that the target area for odor perception or training tasks is more affected by age-related atrophy is more likely to cause functional changes than tasks that target relatively free areas. 32 It can partly explain why passive odor exposure strongly activates the piriform cortex in our research population, but the odor memory task cannot do so.
This research can be viewed in the context of its many advantages and limitations. The sample size is small, which may affect the odor memory task and the lack of significant differences in the primary olfactory cortex. This also limits our ability to perform subgroup analysis, including gender and ApoE genotype-specific effects. Another limitation is that habits in the fMRI paradigm of odor perception may have an impact on the recognition of primary cortical regions. Our example includes a 10-second long scent display with 20-second intervals in between. A previous study investigating regional activation and habituation patterns showed that the primary olfactory region habituates faster, usually after 10 seconds. 18 Although the 10-second duration used in our study was within the time window before desensitization or habituation in the latter study, the 20-second rest interval may lead to shorter nerve recovery times and greater signal attenuation in the elderly. Despite these limitations, this study has made considerable progress by studying elderly people of African descent in the United States, which are underrepresented in biomedical and neuroscience research, but at the same time, the prevalence of severe neurodegenerative diseases The rate is higher.
This investigation of the BOLD signal response to repeated OI and OM tasks shows that OI is more effectively involved in several olfactory brain regions than OM tasks. Although both tasks activate the piriform cortex, neither task is better than the other in terms of piriform activation.
However, the OI task does have a more significant impact on the hippocampus (a region associated with Alzheimer's disease) than the OM task. The results of this study have important implications for the design of olfactory fMRI scanning paradigms, which can be used for future olfactory research in the elderly. In the future, a larger sample is needed to study whether important biological factors, such as ApoE genetic variation and neurodegenerative changes, contribute to the heterogeneity of the effects of repeated odor recognition tasks on brain function.
BOLD, blood oxygen level dependent; fMRI, functional magnetic resonance imaging; MCI, mild cognitive impairment; MMSE, simple mental status examination; MR, magnetic resonance; OD, odor discrimination; OI, odor recognition; OM, odor memory; OT, odor threshold; polytetrafluoroethylene, polytetrafluoroethylene.
We would like to thank our otolaryngologist Dr. Adedoyin Kalejaiye for providing ear, nose and throat (ENT) advice and consultation for this study.
This research was supported by USPHS grants R43AG061981 (SS and EN) and R01AG063881 (EN, MM, and TO).
During the research period, Mr. Charles Nwaokobia reported the grant from the National Institute of Aging; In addition, Mr. Charles Nwaokobia holds patent 10016473; Dr. Evaristus Nwulia reported on the funding of Evon Medics LLC during the research period. The authors report no other conflicts of interest in this work.
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