Until very recently, knowledge concerning the neural basis of cognitive aging originated on two relatively isolated disciplines: the neuroscience of aging, which investigated the effects of aging on the brain independently of age-related changes in cognition, and the cognitive psychology of aging, which investigated the effects of aging on cognition independently of age-related changes in the brain. This lack of communication is being rapidly resolved as an increasing number of studies in the new discipline of cognitive neuroscience of aging focus on the links between cognitive and cerebral aging (Cabeza, in press). These studies employ a variety of methods, but the most powerful are functional neuroimaging techniques, which can reveal how brain activity during cognitive performance changes as a function of aging (for reviews, see Cabeza, 2001a, 2001b).

• Dennis, N. A., & Cabeza, R. (2008). Neuroimaging of healthy cognitive aging. In F. I. M. Craik & T. A. Salthouse (Eds.), Handbook of aging and cognition: Third edition. Mahwah, NJ: Erlbaum.
• Cabeza, R. (2004). Neuroscience frontiers in cognitive aging. In R. A. Dixon, L. Bäckman, & L. -G. Nilsson (Eds.), New frontiers in cognitive aging (pp. 179-196). New York: Oxford University Press.
• Cabeza, R. (2001a). Cognitive neuroscience of aging: Contributions of functional neuroimaging. Scandinavian Journal of Psychology, 42, 277-286.
  
• Cabeza, R. (2001b). Functional neuroimaging of cognitive aging. In R. Cabeza & A. Kingstone (Eds.), Handbook of functional neuroimaging of cognition. (pp. 331-377). Cambridge, MA: MIT Press.
  

My collaborators and I have made some of the earliest contributions in this new research domain. Currently, we are investigating effects of aging on basic episodic memory processes, emotional memory and aging, and general age effects on cognitive activity.

Effects of Aging on Basic Episodic Memory Processes

Relational memory and recollection. Older adults tend to be more impaired in relational memory and recollection than in item memory and familiarity, and these differential effects have been attributed to age-related deficits in PFC and the hippocampus (for a review, see Cabeza, 2006). Consistent with the PFC hypothesis, in one early study (Cabeza et al., 1997), we found that, compared to young adults, older adults showed weaker left PFC activity while forming semantic associations between unrelated words. In another early study (Cabeza et al., 2000), we found that older adults showed weaker PFC activity during temporal-order memory but not during item memory. More recently we also found evidence supporting the role of the hippocampus (Daselaar et al., 2006b): recollection-related activity in hippocampus was reduced by aging, whereas familiarity-related activity in rhinal cortex was enhanced by aging. A possible explanation of this last finding is that older adults compensate for hippocampus-mediated recollection deficits by relying more on rhinal-mediated familiarity. Consistent with this hypothesis, older adults showed reduced functional connectivity within a hippocampal-retrosplenial/parietotemporal network but increased connectivity within a rhinal-frontal network. The finding of preserved rhinal memory functions in healthy older adults has implications for the early diagnosis of Alzheimer's Disease, which in its initial stages impairs rhinal cortex as much or more than the hippocampus.

• Cabeza, R. (2006) . Prefrontal and medial temporal lobe contributions to relational memory in young and older adults. In D. Zimmer, A. Mecklinger & U. Lindenberger (Eds). Binding in human memory: A neurocognitive approach. New York, Oxford University Press, p. 595-626.
  
• Daselaar, S. M., Fleck, M. S., Dobbins, I. G., Madden, D. J., & Cabeza, R. (2006). Effects of healthy aging on hippocampal and rhinal memory functions: An event-related fMRI study. Cerebral Cortex, 16, 1771-1782. (Must Read label in Faculty of 1000)
  
• Cabeza, R., Anderson, N. D., Mangels, J. A., Nyberg, L., & Houle, S. (2000) Age-related differences in neural activity during item and temporal-order memory retrieval: A positron emission tomography study. Journal of Cognitive Neuroscience, 12, 197-206.
  
• Cabeza, R., Grady, C. L., Nyberg, L., McIntosh, A. R., Tulving, E., Kapur, S., Jennings, J. M., Houle, S., & Craik, F. I. M. (1997) Age-related differences in neural activity during memory encoding and retrieval: A positron emission tomography study. Journal of Neuroscience, 17, 391-400.
  

True vs. false memories.

Compared to young adults, older adults are more likely to forget past events (errors of omission) as well as to remember events that never happened (errors of commission). Age-related increases in false memories have been attributed to a deficit in memory for item-specific information coupled with a reliance on memory for gist (semantic or perceptual features shared by a group of past events). As in the case of relational memory and recollection, these deficits are likely to involve both PFC and MTL mechanisms. In our laboratory, we have been investigating the effects of aging on the neural mechanisms of true and false memories using the aforementioned paradigm based on lists of categorized words. In an encoding study (Dennis et al., submitted), we found that older adults showed reduced activity in regions associated with successful encoding of item-specific information, namely the hippocampus and left ventrolateral PFC, but conversely they showed greater activity in regions associated with semantic processing, naming left lateral temporal cortex. In addition to these age effects during encoding, we also found significant age effects during retrieval (Dennis et al., in preparation): whereas older adults showed reduced activity in the hippocampus for high-confidence true recognition, they showed increased activity in rhinal cortex for high-confidence false recognition. This result suggests that reduced true recognition in older adults reflects a deficit in hippocampal-mediated recollection, whereas their increased false recognition reflects a reliance on rhinal-mediated familiarity. Although older adults' reliance on familiarity may partly compensate for recollection deficits (Daselaar et al., 2006—see above), this new study suggests it may have the negative side effect of increasing false recognition.

• Dennis, N. A., Kim, H., & Cabeza, R. (in press). Age-related differences in brain activity during true and false memory retrieval. Journal of Cognitive Neuroscience.
• Dennis, N. A., Kim, H. K., & Cabeza, R. (2007). Effects of aging on true and false memory formation: An fMRI study. Neuropsychologia, 45, 3157-3166.

Effects of Aging on Emotional Memory

The ability to evaluate the emotional content of stimuli is relatively preserved in older adults. However, there is almost no evidence about whether the neural correlates of emotional processing and emotional memory are affected by aging. To investigate this issue, we compared brain activity in young and older adults during the evaluation and encoding of emotional and neutral pictures (St. Jacques et al., in press). Behavioral evidence suggested that the emotional enhancement of perception and memory was relatively preserved but somewhat attenuated in older adults.  Consistent with these behavioral findings, the fMRI results revealed that emotional evaulation and subsequent memory were associated with common activity in the amygdala, however, there were age-related differences in the negative network involved during evaulation and subsequent memory.  The results of the emotional evaulation analysis suggested that age-related differences in evaluating negatively valenced stimuli might reflect decreased perceptual processing of these stimuli, as well as the engagement of control processes that inhibits the response to negative emotion.  Similarly, the results from the subsequent memory analysis suggested that age-related differences in the emotional memory enhancement might reflect decreased connectivity between the amygdala and typical subsequent memory regions, as well as the engagement of regulatory processes that inhibit emotional responses.

• St. Jacques, P., Dolcos, F., & Cabeza, R. (in press). Effects of aging on functional connectivity of the amygdala during subsequent memory for negative pictures: A network analysis of fMRI data. Psychological Science.
  
• St. Jacques, P., Dolcos, F., & Cabeza, R. (in press). Effects of aging on functional connectivity of the amygdala during negative evaluation: A network analysis of fMRI data. Neurobiology of Aging.

Given that emotion enhances recollection and recollection is impaired in older adults, we plan to investigate if emotion can attenuate age-related memory deficits, and if so, what neural mechanisms are involved. Also, we plan to more directly investigate the effects of aging on valence, in order to examine the neural correlates of older adults' bias towards processing positive emotions. The positivity bias contrasts with the negativity bias displayed by depressed individuals. In collaboration with the laboratory of Dr. Strauman, we started to investigate this effect by directly comparing emotion effects in healthy older adults and depressed individuals. Preliminary results suggest opposing effects of aging and depression on amygdalar activity.

General Effects of Cognitive Aging

Task-specific vs. task-independent age effects. There is much evidence that cognitive functions such as attention, working memory and episodic memory are negatively affected in advanced age. A controversial issue in the cognitive aging literature is whether such age-related deficits can be accounted for by common causes (common factor theories) or whether they have multiple specific causes (specific factor theories). To investigate this issue, we directly compared age-related changes in activity during episodic retrieval, working memory, and visual attention using event-related fMRI (Cabeza et al., submitted). Task-independent age effects included an age-related reduction in occipital activity coupled with an age-related increase in PFC activity. The former finding is consistent with the common factor view that age-related cognitive deficits are partly due to a decline in sensory processing, and the latter finding suggests that some forms of compensatory PFC recruitment are common across tasks. Task-specific age effects were found in several regions, including the parahippocampal gyrus, which showed greater activity in older than in younger adults during episodic retrieval. This activation was associated with familiarity rather than with recollection. Overall, the results showed that both common and specific factors play an important role in cognitive aging.

• Cabeza, R., Daselaar, S. M., Dolcos, F., Prince, S. E., Budde, M., & Nyberg, L. (2004). Task-independent and task-specific age effects on brain activity during working memory, visual attention, and episodic retrieval. Cerebral Cortex, 14, 364-375.

HAROLD and compensation. Recently, we proposed the first integrative theoretical account of the functional neuroimaging of aging. This account, known as the Hemispheric Asymmetry Reductions in Older Adults (HAROLD) model, proposes that under similar circumstances, brain activity during cognitive performances tends to be less lateralized in older adults than in younger adults (Cabeza, 2002). The model is supported by functional neuroimaging, neurophysiological, and behavioral evidence in the domains of episodic memory retrieval, episodic memory encoding/semantic retrieval, working memory, language, perception and inhibitory control. Age-related asymmetry reductions could help counteract age-related neurocognitive decline (compensation hypothesis), as we originally proposed (Cabeza et al., 1997a), or they may reflect a difficulty in recruiting specialized neural mechanisms (dedifferentiation hypothesis). Recently, we tested these two accounts directly by comparing brain activity in high-performing and low-performing older adults (Cabeza et al., 2002a). During source memory, younger adults and low-performing older adults showed right PFC activity, whereas high-performing older adults showed bilateral PFC activity. These results support the compensation hypothesis. They suggest that low-performing older adults recruited a similar network as young adults but used it inefficiently, whereas high-performing older adults counteracted age-related neural decline through a plastic reorganization of neurocognitive networks.

• Cabeza, R. (2002). Hemispheric asymmetry reduction in old adults: The HAROLD model. Psychology and Aging, 17, 85-100.
  
• Cabeza, R., Anderson, N. D., Locantore, J. K., & McIntosh, A. R. (2002). Aging gracefully: Compensatory brain activity in high-performing older adults. Neuroimage, 17, 1394-1402.
• Dolcos, F., Rice, H. J., & Cabeza, R. (2002). Hemispheric asymmetry and aging: Right hemisphere decline or asymmetry reduction. Neuroscience and Biobehavioral Reviews, 26, 819-825.