Periodic Reporting for period 4 - AgeConsolidate (The Missing Link of Episodic Memory Decline in Aging: The Role of Inefficient Systems Consolidation)
Reporting period: 2021-11-01 to 2023-04-30
Episodic memory function declines with age. About half of older people report worries about their own memory function, and objective memory tests confirm that the ability to learn and retrieve new information declines with age, especially after 60 years. Two reasons for this are the ability to encode new information and the ability to retrieve the same information after a certain time both decline with age. However, a third critical process for successful episodic memory – consolidation of the learned material – is almost not studied in the context of aging. The main hypothesis of the current project is that the brain processes of episodic memory consolidation are less effective in older adults, and this can account for a substantial portion of the episodic memory decline in aging.” To test this hypothesis, the projects will address its two objectives: (1) Use recent advances in memory consolidation theory to yield an elaborate model of episodic memory deficits in aging. (2) Use aging as a model to uncover how structural and functional brain changes affect episodic memory consolidation in general. These questions are important for society, given the aging of the population and the increase in cognitive challenges and demand for learning and memory that come with the rapid development and change in for instance information technology. Thus, healthy, happy and productive older adults will depend on well-functioning episodic memory and the current project will help illuminate the conditions and mechanisms for this.
The project has developed a new paradigm for testing episodic memories with fMRI, which has produced very exciting results. The paradigm is adapted so it can be used to study encoding, consolidation, and retrieval of episodic memories, and can also be used in combination with targeted memory reactivation paradigms during polysomnography or sleep-fMRI.
We have also used major efforts to develop, adapt and implement a processing pipeline for multi-modal neuroimaging. This is customized to the project, allows us to run integrated analyses across may different brain imaging techniques that are used for different purposes is the project. This includes task- and resting state fMRI, structural, diffusion tensor imaging (DTI), positron emission tomography (PET) and electrophysiological (EEG) data, which is a critical part of the project. Following recent standards for reproducible neuroimaging, the organization of MRI, PET and EEG-data collected in the project adheres to the Brain Imaging Data Structure specifications (BIDS - https://bids.neuroimaging.io).
Scientifically, the project has so far contributed with several publications in scientific journals, as well as a number of talks and presentations on conferences, meetings, seminars and workshops. Of the results so far, the followings can be highlighted:
Of the most important, we have shown that sleep patterns are related to accumulation of the Alzheimer’s Disease biomarker beta-amyloid, and this relationship is especially strong in regions with high expression of the HOMER1 gene (Fjell et al., 2020, Cerebral Cortex). HOMER1 is involved both in regulation of the sleep-wake cycle, as well as in processing of beta-amyloid. We also detected a relationship between more sleep problems and worsening of long-term memory, suggesting a link between sleep, beta-amyloid, gene expression and long-term memory in aging. We further found that aspects of sleep were related to changes in microstructural integrity in the hippocampus (Grydeland et al., 2021, Sleep).
In another manuscripts (Fjell et al. 2020 Sleep), we took these analyses further, showing an age-dependent relationship between sleep and brain atrophy in regions known to be heavily involved in consolidation of episodic memories, as well as age-invariant relationships to restricted cortical regions (Fjell et al., 2021, Cerebral Cortex).
Together, the results of these manuscripts add substantially to our knowledge about memory consolidation deficits in aging, sleep and brain atrophy.
Other papers have focused on the role of encoding strategies for consolidation of long-term memories (Amlien et al., Scientific reports, 2019), and on the differential roles played by anterior and posterior parts of the hippocampus (Langnes et al., Hippocampus 2020) in long-term episodic memory encoding and retrieval.
An exciting line of analyses focused on functional connectivity during different memory task states, e.g. how different brain regions communicate during cognitive activity, and whether this has bearings on age-differences in memory consolidation. In one manuscript, we found support a theory of striatal alterations as one cause of cognitive decline in aging and highlighted that age-related changes in episodic memory extend beyond hippocampal-neocortical connections (Ness et al., Cerebral Cortex). Further, we found increased post-encoding functional connectivity between hippocampus and individually localized neocortical regions responsive to stimuli encountered during memory encoding (Folvik et al., 2023, Cerebral Cortex). Post-encoding modulations were manifested as a nearly system-wide upregulation in hippocampal coupling with all major functional networks. The configuration of these extensive modulations resembled hippocampal-neocortical interaction patterns estimated from active encoding operations, suggesting hippocampal post-encoding involvement exceeds perceptual aspects. We concluded that the similarity in hippocampal functional coupling between online memory encoding and offline post-encoding rest suggests that reactivation in humans involves a spectrum of cognitive processes engaged during the experience of an event. In two recent papers we also tested memory-related connectivity during different task states (Raud et al., 2023, Neuroimage; Capogna et al., Cerebral Cortex).
We have also used major efforts to develop, adapt and implement a processing pipeline for multi-modal neuroimaging. This is customized to the project, allows us to run integrated analyses across may different brain imaging techniques that are used for different purposes is the project. This includes task- and resting state fMRI, structural, diffusion tensor imaging (DTI), positron emission tomography (PET) and electrophysiological (EEG) data, which is a critical part of the project. Following recent standards for reproducible neuroimaging, the organization of MRI, PET and EEG-data collected in the project adheres to the Brain Imaging Data Structure specifications (BIDS - https://bids.neuroimaging.io).
Scientifically, the project has so far contributed with several publications in scientific journals, as well as a number of talks and presentations on conferences, meetings, seminars and workshops. Of the results so far, the followings can be highlighted:
Of the most important, we have shown that sleep patterns are related to accumulation of the Alzheimer’s Disease biomarker beta-amyloid, and this relationship is especially strong in regions with high expression of the HOMER1 gene (Fjell et al., 2020, Cerebral Cortex). HOMER1 is involved both in regulation of the sleep-wake cycle, as well as in processing of beta-amyloid. We also detected a relationship between more sleep problems and worsening of long-term memory, suggesting a link between sleep, beta-amyloid, gene expression and long-term memory in aging. We further found that aspects of sleep were related to changes in microstructural integrity in the hippocampus (Grydeland et al., 2021, Sleep).
In another manuscripts (Fjell et al. 2020 Sleep), we took these analyses further, showing an age-dependent relationship between sleep and brain atrophy in regions known to be heavily involved in consolidation of episodic memories, as well as age-invariant relationships to restricted cortical regions (Fjell et al., 2021, Cerebral Cortex).
Together, the results of these manuscripts add substantially to our knowledge about memory consolidation deficits in aging, sleep and brain atrophy.
Other papers have focused on the role of encoding strategies for consolidation of long-term memories (Amlien et al., Scientific reports, 2019), and on the differential roles played by anterior and posterior parts of the hippocampus (Langnes et al., Hippocampus 2020) in long-term episodic memory encoding and retrieval.
An exciting line of analyses focused on functional connectivity during different memory task states, e.g. how different brain regions communicate during cognitive activity, and whether this has bearings on age-differences in memory consolidation. In one manuscript, we found support a theory of striatal alterations as one cause of cognitive decline in aging and highlighted that age-related changes in episodic memory extend beyond hippocampal-neocortical connections (Ness et al., Cerebral Cortex). Further, we found increased post-encoding functional connectivity between hippocampus and individually localized neocortical regions responsive to stimuli encountered during memory encoding (Folvik et al., 2023, Cerebral Cortex). Post-encoding modulations were manifested as a nearly system-wide upregulation in hippocampal coupling with all major functional networks. The configuration of these extensive modulations resembled hippocampal-neocortical interaction patterns estimated from active encoding operations, suggesting hippocampal post-encoding involvement exceeds perceptual aspects. We concluded that the similarity in hippocampal functional coupling between online memory encoding and offline post-encoding rest suggests that reactivation in humans involves a spectrum of cognitive processes engaged during the experience of an event. In two recent papers we also tested memory-related connectivity during different task states (Raud et al., 2023, Neuroimage; Capogna et al., Cerebral Cortex).
The project has developed a new paradigm for testing episodic memories with fMRI, which has produced very exciting results. The paradigm is adapted so it can be used to study encoding, consolidation, and retrieval of episodic memories, and can also be used in combination with targeted memory reactivation paradigms during polysomnography or sleep-fMRI.
The project publications have advanced the research field significantly beyond the state of the art. First, they have contributed to a better understanding of the brain correlates of successful memory in adults, e.g. by demonstrating how hippocampus communicates with the rest of the cerebral cortex during encoding and retrieval of episodic memories. Second, they have shown that the neural correlates of episodic memory over extended time intervals are partly different from memory over intervals usually used in memory research. Especially, the communication between hippocampus and other cortical and subcortical regions plays different roles during consolidation of durable, long-term memories. Finally, they describe the functional and structural brain correlates of successful memory encoding and retrieval in aging.
We continue to work on the data and results from the project, and we are applying for further funding to develop the experiments further. We have also secured some funding to re-test some of the participants to be able to test changes over longer time intervals.
The project publications have advanced the research field significantly beyond the state of the art. First, they have contributed to a better understanding of the brain correlates of successful memory in adults, e.g. by demonstrating how hippocampus communicates with the rest of the cerebral cortex during encoding and retrieval of episodic memories. Second, they have shown that the neural correlates of episodic memory over extended time intervals are partly different from memory over intervals usually used in memory research. Especially, the communication between hippocampus and other cortical and subcortical regions plays different roles during consolidation of durable, long-term memories. Finally, they describe the functional and structural brain correlates of successful memory encoding and retrieval in aging.
We continue to work on the data and results from the project, and we are applying for further funding to develop the experiments further. We have also secured some funding to re-test some of the participants to be able to test changes over longer time intervals.