The influence of age and cognitive status on large-scale brain networks in episodic memory

The present synopsis summarizes three scientific articles published or submitted to international scientific journals. All three articles relevant to this dissertation are tied by the question to what extent healthy aging and cognitive impairment influence brain activation in regard to episodic memo...

Ausführliche Beschreibung

Gespeichert in:
1. Verfasser: Oedekoven, Christiane Sophie Helene
Beteiligte: Leube, Dirk (PD Dr.) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Sprache:Englisch
Veröffentlicht: Philipps-Universität Marburg 2013
Nervenheilkunde
Ausgabe:http://dx.doi.org/10.17192/z2013.0584
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Zusammenfassung:The present synopsis summarizes three scientific articles published or submitted to international scientific journals. All three articles relevant to this dissertation are tied by the question to what extent healthy aging and cognitive impairment influence brain activation in regard to episodic memory encoding and retrieval. Here, our interest focuses on the role of parietal lobe and changes occurring within underlying large-scale brain networks. The data in all articles consist of the same groups of participants, healthy young, healthy elderly and patients with mild cognitive impairment (MCI). We adapted the memory tasks for our fMRI study to control for age-related changes in memory function. This allowed us to consider the differences in activation with a given standardized performance level. We were interested in the differences and overlaps in activation concerning memory encoding (Paper #3), face memory retrieval (Paper #1) and associative memory retrieval (Paper #2). Furthermore, in Paper #1 and Paper #2, we also focused on functional connectivity, examining interactions and correlations between relevant brain regions. We were especially interested in the connections of parietal lobe and hippocampus, since these are two brain regions essential for episodic memory. Our main goal was to distinguish changes occurring in healthy elderly and MCI patients regarding their activation in large-scale brain networks involving parietal lobe. In all three episodic memory tasks we found overlapping patterns of activation across groups, indicating participation of similar networks regardless of age and cognitive decline. Changes were seen regarding magnitude of activations within these networks. The networks involved were two large-scale brain networks relevant for episodic memory: a frontoparietal task positive network (TPN) and the default mode network (DMN), which is a task negative network. Our results demonstrate that DMN regions such as lateral and medial parietal as well as prefrontal regions show deactivation during encoding and activation during retrieval, which constitutes an encoding/retrieval flip. Only hippocampus, as part of the DMN, was activated during both encoding and retrieval. Spatial extent and magnitude of DMN deactivation during encoding was related to age and cognitive status. Young showed more deactivation in posteromedial cortex and inferior parietal lobe than healthy elderly, whereas only healthy elderly showed additional activation of hippocampus and posterior DMN regions. In retrieval tasks, healthy elderly showed more activation in DMN regions, whereas MCI patients showed lower hippocampal activation during a face-name recognition task, corresponding to lower associative memory performance. Moreover, age-related DMN impairment was reflected in functional connectivity measures. Analyses of functional connectivity revealed fewer correlations of parietal DMN brain regions for healthy elderly than young. In contrast, there were more correlations with a hippocampal seed in healthy elderly than young, indicating a more extensive network with age involving hippocampus and striatal regions. Regarding TPN activation, spatial extent and magnitude of activation was increased in all older adults compared to young. In all three episodic memory tasks healthy elderly and MCI - regardless of memory status - showed increased activation within TPN regions. Especially pre- and postcentral as well as striatal regions were involved. In conclusion, we were able to distinguish age-related effects from changes occurring with MCI in large-scale-brain networks involving parietal lobe. Even in healthy aging we found functional connectivity of parietal lobe to be impaired in comparison to young. For the first time, changes in large-scale brain networks DMN and TPN were described for MCI. Healthy elderly and MCI may be distinguished by their activation patterns in DMN regions. The overrecruitment of DMN regions suggests compensatory processes present in healthy elderly but not in MCI. Since connectivity analysis of posterior DMN regions imply impaired connectivity with age, increased DMN activation may indicate a compensatory process for a less extensive functional network in healthy elderly. Furthermore, healthy elderly and MCI can be distinguished by their hippocampal DMN activation, MCI generally showing less hippocampal activation in accordance with an impaired memory performance. During associative retrieval, healthy elderly and MCI patients showed different patterns of functional connectivity to a hippocampal seed. TPN overrecruitment was present in both healthy elderly and MCI, thus indicating dedifferentiation processes with age. By distinguishing healthy elderly and MCI based on their activation within large-scale brain networks, our study facilitates early recognition of dementia.
DOI:http://dx.doi.org/10.17192/z2013.0584