Chemical Senses Vol. 30 No. suppl 1 © Oxford University
Press 2005; all rights reserved
ERP, fMRI and Functional Connectivity Studies of Brain Response to Odor in Normal Aging and Alzheimer’s Disease
San Diego State University and the University of California, San Diego School of Medicine, San Diego, CA 92120-4913, USA
Correspondence to be sent to: Claire Murphy, e-mail: cmurphy{at}sciences.sdsu.edu
Key words: event-related potentials, neuroimaging, olfaction, smell impairment
 |
Introduction |
|---|
 Top Introduction MethodsResults and discussionConclusionsAcknowledgementsReferences |
|---|
More than 14 million Americans over 50 suffer from smell impairment (Murphy et al., 2002
). In a series of
studies we have sought the underlying cortical substrates of olfactory loss with aging.
We used psychophysical, neuropsychological, event related potentials (ERPs) and
functional magnetic resonance imaging (fMRI) techniques to address the problem.
Psychophysical investigations have revealed significant losses in olfactory threshold
sensitivity, odor identification and odor memory. These impairments are significantly
worse in patients with neurodegenerative diseases such as Alzheimer’s disease (AD)
(Murphy, 2002). The earliest lesions
of AD are in the mesial temporal regions of the brain critical to olfactory processing,
thus the potential exists for reflection of incipient disease in olfactory tasks. The
investigation of olfactory function in aging and AD is of basic science interest and may
contribute to the development of more sensitive diagnostic batteries for AD (Murphy, 2002).
ERPs provide real-time temporal information about the brain’s response to odor
stimulation. We have used this technique to investigate brain response over the lifespan
in the normally aging brain (Murphy et
al., 2000) and in patients with neurodegenerative diseases such as
Alzheimer’s disease (Morgan and Murphy,
2002). The results suggest that the odor evoked response of the brain is
significantly reduced in amplitude and delayed in its latency in normally aging persons
and dramatically more delayed in Alzheimer’s patients. These results confirm the
importance of considering a central origin for the olfactory loss associated with aging
and AD.
fMRI is a powerful tool for investigation of brain structure and of functional
activation in specific regions of interest (ROIs). We have used fMRI to investigate the
cortical substrate of olfactory impairment in the elderly. The fMRI data were analyzed
with individual, group and ROI analyses. Results are described in
Cerf-Ducastel and Murphy (2003),
Ferdon and Murphy (2003) and
Wiser et al. (2000). Older
adults showed less activation in important olfactory ROIs: entorhinal cortex, amygdala,
insula and piriform cortex. Cerebellar activation was lower in areas Crus I and II.
A number of approaches have been taken to achieve an understanding of integrated
brain activity. Functional connectivity involves correlation between fMRI activity in two
brain regions during performance of a task. The technique permits testing the hypothesis
that interacting brain regions, rather than isolated regions of interest, are the
cortical substrate for performance. We have approached functional connectivity with more
than one analysis strategy.
Calhoun-Haney et al. (2004)
used the seed voxel method to examine correlations between individual voxels in
hippocampus and in ROIs for olfactory processing during an olfactory task.
A number of investigators have conducted connectivity analysis on regional brain
activation using correlational methods (Horwitz,
1989). Here we aimed to identify significant correlations in fMRI activation
among ROIs for olfactory tasks and to test the hypothesis that the pattern of
correlations among these regions is significantly impacted by aging. Activity was
correlated separately for young adults, older adults and AD patients.
|
Methods |
|---|
|
TopIntroductionMethodsResults and discussionConclusionsAcknowledgementsReferences |
|---|
Participants were young adults, older adults who had been screened for dementia and patients with Alzheimer’s disease.
FMRI was accomplished with a 1.5 T Siemens magnet, acquiring 32 sagittal EPI slices
with a voxel size of 4 x 4 x 4 mm and a TR of 4 s.
Functional data were superimposed on structural images acquired for anatomical
verification using Mprage, 180 sagittal slices, 1 mm thick. FMRI activation was
correlated with a perception profile to extract the data (Cerf-Ducastel and Murphy, 2003). Image analysis was
conducted with AFNI. The correlation method was employed for functional connectivity
analysis across ROIs.
|
Results and discussion |
|---|
|
TopIntroductionMethodsResults and discussionConclusionsAcknowledgementsReferences |
|---|
Activation in orbito-frontal cortex was highly correlated with activation in mesial temporal lobe in young adults. Young subjects also showed significantly correlated activity within mesial temporal lobe (Table 1). Older adults showed a breakdown of connectivity between orbito-frontal cortex and mesial temporal lobe (Table 1) and this was especially true in AD. Patients showed lower overall activation, particularly in mesial temporal lobe (Figure 1).
|
|
Results suggest that disconnection of olfactory areas from incoming information and higher processing areas is an important underlying cortical substrate of olfactory impairment in old age and is likely to be especially prominent in patients with AD. The consonant results from Calhoun-Haney et al., (2004) using a different method suggest the robustness of the findings.
|
Conclusions |
|---|
|
TopIntroductionMethodsResults and discussionConclusionsAcknowledgementsReferences |
|---|
The data suggest fronto-temporal disconnection and disruption in mesial temporal lobe connectivity in the aging brain. The functional connectivity analysis suggests that these disruptions may reflect large-scale age-related changes to olfactory network processing in addition to differences in processing in specific regions of interest.
|
Acknowledgements |
|---|
|
TopIntroductionMethodsResults and discussionConclusionsAcknowledgementsReferences |
|---|
Supported by NIH grant AG04085 and DC02064 to C.M. We thank the UCSD ADRC and SDSU Lifespan Human Senses Laboratory. Preliminary results presented at the Gerontological Society of America Meeting, 2003.
|
References |
|---|
|
TopIntroductionMethodsResults and discussionConclusionsAcknowledgementsReferences |
|---|
Calhoun-Haney, R., Ferdon, S., Cerf-Ducastel, B. and Murphy, C. (2004) Functional connectivity of the hippocampus during an olfactory task: differences observed between young and elderly. Submitted.
Cerf-Ducastel, B. and Murphy, C. (2003) fMRI brain activation in response to odors is reduced in primary olfactory areas of elderly subjects. Brain Res., 986, 39–53.[CrossRef][Web of Science][Medline]
Ferdon, S. and Murphy, C. (2003) The cerebellum and olfaction in the aging brain: an fMRI study. Neuroimage, 20, 12–21.[CrossRef][Web of Science][Medline]
Horwitz, B. (1989) Functional neurosystems analyzed by use of interregional correlations of glucose metabolism. In Exert, J.-P. and Arbib, M.A. (eds) Visuomotor Coordination. Plenum Press, New York, pp. 873–892.
Morgan, C.D. and Murphy, C. (2002) Olfactory event-related potentials in Alzheimer’s disease. J. Int. Neuropsychol. Soc., 8, 753–763.[CrossRef][Web of Science][Medline]
Murphy, C. (2002) Olfactory functional testing: sensitivity and specificity for Alzheimer’s disease. Drug Dev. Res., 56, 123–131.[CrossRef]
Murphy, C., Morgan, C.D., Geisler, M.W., et al. (2000). Olfactory event-related potentials and aging: normative data. Int. J. Psychophysiol., 36, 133–145.[CrossRef][Web of Science][Medline]
Murphy, C., Schubert, C.R., et al. (2002) Prevalence of olfactory impairment in older adults. J. Am. Med. Assoc., 288, 2307–2312.
Wiser, A.K., Cerf, B. and Murphy, C. (2000) Effect of aging on the olfactory network: what fMRI combined with psychophysics can tell us. ISOT XIII Abstracts, Brighton, UK.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D R Thiruvady, N Georgiou-Karistianis, G F Egan, S Ray, A Sritharan, M Farrow, A Churchyard, P Chua, J L Bradshaw, T-L Brawn, et al. Functional connectivity of the prefrontal cortex in Huntington's disease J. Neurol. Neurosurg. Psychiatry, February 1, 2007; 78(2): 127 - 133. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||