@phdthesis{Thams2022,
  author    = {Friederike Thams},
  title     = {Noninvasive Modulation of Cognition in Older Adults – Neural Correlates and Behavioral Outcomes},
  journal    = {Nicht-invasive Modulation von Kognition bei {\"a}lteren Erwachsenen – Korrelate auf Hirn- und Verhaltensebene},
  url       = {https://nbn-resolving.org/urn:nbn:de:gbv:9-opus-61670},
  pages     = {140},
  year      = {2022},
  abstract  = {Background: The worldwide population will grow older in the upcoming years. Aging, even in the absence of pathological processes, is associated with decline in cognitive functioning. Age-related cognitive decline is not a uniform process affecting every function in the same way. Research should thus examine specific functions, such as episodic memory or executive functions differentially, especially in older samples. Neural correlates of these functions are well characterized in young adults. However, research on functional and structural neural substrates underlying specific cognitive functions in older adults is scarce, but needed for example to identify targets for noninvasive interventions against cognitive decline. Current advances in this field point towards the effectiveness of combined noninvasive interventions of cognitive training and transcranial direct current stimulation (tDCS). So far, evidence regarding such combined interventions in older adults is inconclusive and neural mechanisms of successful interventions are still unclear. This line of research could advance the development of noninvasive methods to modulate cognitive functions and therefore address the unmet need for treatment options against age-related cognitive decline. Aims: The main aims of the present thesis were (i) to characterize functional and structural neural network correlates of two cognitive functions with high relevance for daily living, namely working memory updating and value-based decision making, (ii) to map out interventions of combined cognitive training and tDCS to modulate these cognitive functions in healthy older adults and adults with prodromal AD and (iii) to assess behavioral and neural outcomes of combined cognitive training (of either executive functions or visuo-spatial memory) and tDCS interventions. Methods: In order to address these aims, the present thesis includes five papers. Paper I assessed functional and structural neural correlates of working memory updating and value-based decision-making performance in healthy older adults using functional magnetic resonance imaging and diffusion tensor imaging. Papers II and III comprise study protocols of a three-week cognitive training of working memory updating and value-based decision-making abilities with concurrent tDCS over the left dorsolateral prefrontal cortex in healthy older adults and adults with prodromal AD. Paper IV used mixed-model analysis to compute behavioral outcomes of this combined intervention in healthy older adults, including outcome measures of the trained tasks, measures of transfer to untrained tasks and assessment of long-term effects at four weeks and half a year after the intervention. In paper V neural alterations after cognitive training of visuo-spatial memory and active stimulation compared to the training and sham (placebo) stimulation were assessed in older adults using measures of functional network centrality and diffusion tensor imaging-derived measures of grey matter microstructure. Results: Analyses revealed distinct functional and structural connectivity correlates of performance on the two cognitive tasks assessing working memory updating and value-based decision-making (paper I). Moreover, results showed a combined contribution of a specific white matter pathway (cingulum bundle) and frontoparietal functional connectivity to working memory updating performance, thereby providing information on possible network targets for modulation of working memory updating and value-based decision-making. The combined modulatory intervention of cognitive training and tDCS (papers II and IV) did not demonstrate group differences between concurrent active tDCS over sham tDCS in the trained tasks. However, analysis of a working memory transfer task revealed a beneficial effect of training and active tDCS over training and sham tDCS at post intervention and follow-up. Findings from paper V showed reduced functional network centrality after visuo-spatial memory training and active tDCS compared to training and sham tDCS in the stimulated brain area and its contralateral homologue. Additionally, after the training, measures of grey matter microstructural plasticity in the stimulated brain area were associated with beneficial training outcomes for the active but not the sham stimulation group. Conclusion: Taken together, cognitive performance, functional and structural networks as well as the possibility of their modulation through combined cognitive training and tDCS interventions were investigated in older adults with and without cognitive impairment. The present thesis therefore contributes to the field of noninvasive neuromodulation in older adults by characterizing distinct neural correlates of two age-sensitive executive functions, which may be altered through modulatory interventions. Moreover, the present work shows that cognitive training with concurrent tDCS holds the potential to elicit transfer effects to untrained tasks and further may evoke neural plasticity on the functional and microstructural level. This work thus promotes the development of modulatory interventions against age-associated cognitive decline and holds promising implications for translation to clinical application.},
  language  = {en}
}