Neurocognitive networks: altered by dementia but not working memory training

Ripp, Isabelle (2021): Neurocognitive networks: altered by dementia but not working memory training. Dissertation, LMU München: Graduate School of Systemic Neurosciences (GSN)

Abstract

Functional magnetic resonance imaging (fMRI) studies have reported a link between cognitive performance and large-scale neurocognitive networks (NCN). In dementing disorders altered integrity of these NCN have been reported. As of today, no pharmacological treatments exist to slow down, stop or reverse neuronal cell death causing these altered integrities of NCN and cognitive decline. As a consequence, cognitive training programs have become a popular tool to improve cognitive skills in dementia but also in healthy subjects. Especially, working memory (WM) training was observed to lead to a performance improvement in the trained task but also to generalized improvements in non-trained tasks. Hence, these so-called transfer effects developed into an index of the putative effectiveness of WM training. Despite growing interest in cognitive interventions from academia and industry, the literature reports heterogeneous results on transfer effects. Likewise, there is very little evidence of neural correlates underlying transfer. Accordingly, the effects of WM training on NCN remain understudied. Within this cumulative thesis, project one investigated impairments of NCN in AD and bvFTD, the two most common causes of dementia among patients less than 65 years of age. To this end, simultaneous fMRI and FDG-PET data was acquired enabling the comparison of NCN integrity measures between patient groups, as well as between neuroimaging modalities. In project two, we assessed the effectiveness of WM training in regards to transfer effects in healthy middle-aged participants – an age group directly preceding or equivalent to that seen in early-stage dementia. Hypothesized transfer effect-related neural plasticity was evaluated in terms of change in NCN integrity between pre- and post-training. Equivalent to project one, both fMRI and FDG-PET was used to measure two linked but distinct marker of neural plasticity. The additional assessment of an extensive cognitive test battery captured changes in nearest, near and far transfer tasks. To this end, all training induced changes were contrasted to an active control group. Overall, the thesis aims to assess the applicability of WM training to decrease AD and bvFTD specific NCN integrity impairments. Based on the results achieved within project one, we report significant differences in NCN integrity impairments between AD and bvFTD. We could also show that the pattern of network alterations differed between the neuroimaging modalities, with the fMRI-based NCN showing a generally lower disease specificity. The integrity of the anterior default mode network as measured with FDG-PET alone accurately differentiated between patients with AD and bvFTD. Based on the results obtained in project two, we report the lack of WM training induced neural plasticity in NCN in healthy middle-aged participants. Equivalently, on the behavioural level no near or far transfer effects were observed. Thus, WM training-related gains appear not to generalize to other cognitive domains and only to an extremely limited degree to other WM tasks. Overall, these results discourage the potential applicability of WM training in dementia to decrease NCN integrity impairments. However, looking beyond the concept of transfer as revealed by comparing WM training-induced changes in the active control and experimental group, we see positive effects in form of cognitive improvements in some tasks. Thus, I propose to test WM training along with multiple other cognitive training paradigms to maximize the range of cognitive improvements in patients with a mild cognitive impairment.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: FDG-PET, Independent Component Analysis, Resting State Networks, dementia
• Themengebiete: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
• Fakultäten: Graduate School of Systemic Neurosciences (GSN)
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 22. April 2021
• 1. Bericht­erstatter:in: Yakushev, Igor