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Decoding the complex brain: multivariate and multimodal analyses of neuroimaging data
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). (Umeå Center for Functional Brain Imaging (UFBI))
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Functional brain images are extraordinarily rich data sets that reveal distributed brain networks engaged in a wide variety of cognitive operations. It is a substantial challenge both to create models of cognition that mimic behavior and underlying cognitive processes and to choose a suitable analytic method to identify underlying brain networks.

Most of the contemporary techniques used in analyses of functional neuroimaging data are based on univariate approaches in which single image elements (i.e. voxels) are considered to be computationally independent measures. Beyond univariate methods (e.g. statistical parametric mapping), multivariate approaches, which identify a network across all regions of the brain rather than a tessellation of regions, are potentially well suited for analyses of brain imaging data. A multivariate method (e.g. partial least squares) is a computational strategy that determines time-varying distributed patterns of the brain (as a function of a cognitive task). Compared to its univariate counterparts, a multivariate approach provides greater levels of sensitivity and reflects cooperative interactions among brain regions. Thus, by considering information across more than one measuring point, additional information on brain function can be revealed.

Similarly, by considering information across more than one measuring technique, the nature of underlying cognitive processes become well-understood. Cognitive processes have been investigated in conjunction with multiple neuroimaging modalities (e.g. fMRI, sMRI, EEG, DTI), whereas the typical method has been to analyze each modality separately. Accordingly, little work has been carried out to examine the relation between different modalities. Indeed, due to the interconnected nature of brain processing, it is plausible that changes in one modality locally or distally modulate changes in another modality.

This thesis focuses on multivariate and multimodal methods of image analysis applied to various cognitive questions. These methods are used in order to extract features that are inaccessible using univariate / unimodal analytic approaches. To this end, I implemented multivariate partial least squares analysis in study I and II in order to identify neural commonalities and differences between the available and accessible information in memory (study I), and also between episodic encoding and episodic retrieval (study II). Study I provided evidence of a qualitative differences between availability and accessibility signals in memory by linking memory access to modality-independent brain regions, and availability in memory to elevated activity in modality-specific brain regions. Study II provided evidence in support of general and specific memory operations during encoding and retrieval by linking general processes to the joint demands on attentional, executive, and strategic processing, and a process-specific network to core episodic memory function. In study II, III, and IV, I explored whether the age-related changes/differences in one modality were driven by age-related changes/differences in another modality. To this end, study II investigated whether age-related functional differences in hippocampus during an episodic memory task could be accounted for by age-related structural differences. I found that age-related local structural deterioration could partially but not entirely account for age-related diminished hippocampal activation. In study III, I sought to explore whether age-related changes in the prefrontal and occipital cortex during a semantic memory task were driven by local and/or distal gray matter loss. I found that age-related diminished prefrontal activation was driven, at least in part, by local gray matter atrophy, whereas the age-related decline in occipital cortex was accounted for by distal gray matter atrophy. Finally, in study IV, I investigated whether white matter (WM) microstructural differences mediated age-related decline in different cognitive domains. The findings implicated WM as one source of age-related decline on tasks measuring processing speed, but they did not support the view that age-related differences in episodic memory, visuospatial ability, or fluency were strongly driven by age-related differences in white-matter pathways.

Taken together, the architecture of different aspects of episodic memory (e.g. encoding vs. retrieval; availability vs. accessibility) was characterized using a multivariate partial least squares. This finding highlights usefulness of multivariate techniques in guiding cognitive theories of episodic memory. Additionally, competing theories of cognitive aging were investigated by multimodal integration of age-related changes in brain structure, function, and behavior. The structure-function relationships were specific to brain regions and cognitive domains. Finally, we urged that contemporary theories on cognitive aging need to be extended to longitudinal measures to be further validated.

Place, publisher, year, edition, pages
Umeå: Umeå University , 2012. , 94 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1479
Keyword [en]
multivariate analysis, univariate analysis, multimodal imaging, episodic memory, aging, functional magnetic resonance imaging, diffusion tensor imaging
National Category
Research subject
biology; Psychology; Computerized Image Analysis
URN: urn:nbn:se:umu:diva-51842ISBN: 978-91-7459-362-4OAI: diva2:489540
Public defence
2012-02-24, BiA 201, Biologihuset, Umeå, 09:00 (English)
Available from: 2012-02-03 Created: 2012-02-03 Last updated: 2012-10-19Bibliographically approved
List of papers
1. Characterizing the neural correlates of modality-specific and modality-independent accessibility and availability signals in memory using partial-least squares
Open this publication in new window or tab >>Characterizing the neural correlates of modality-specific and modality-independent accessibility and availability signals in memory using partial-least squares
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2010 (English)In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 52, no 2, 686-698 p.Article in journal (Refereed) Published
Abstract [en]

Previous studies have shown that information that currently cannot be retrieved but will be retrieved on a subsequent, more supported task (i.e. is available but not accessible) has a distinct neural signature compared with non-available information. For verbal paired-associates, an availability signal has been revealed in left middle temporal cortex, an area potentially involved in the storage of such information, raising the possibility that availability signals are expressed in modality-specific storage sites. In the present study subjects encoded pictures and sounds representing concrete objects. One day later, during fMRI scanning, a verbal cued-recall task was administrated followed by a post-scan recognition task. Items remembered on both tasks were classified as accessible; items not remembered on the first but on the second task were classified as available; and items not remembered on any of the tasks were classified as not available. Multivariate partial-least-squares analyses revealed a modality-independent accessibility network with dominant contributions of left inferior parietal cortex, left inferior frontal cortex, and left hippocampus. Additionally, a modality-specific availability network was identified which included increased activity in visual regions for available pictorial information and in auditory regions for available sound information. These findings show that availability in memory, at least in part, is characterized by systematic changes in brain activity in sensory regions whereas memory access reflects differential activity in a modality-independent, conceptual network, thus indicating qualitative differences between availability and accessibility in memory.

National Category
Physiology Neurosciences
urn:nbn:se:umu:diva-35071 (URN)10.1016/j.neuroimage.2010.04.195 (DOI)000279160200030 ()20420925 (PubMedID)
Available from: 2010-07-05 Created: 2010-07-05 Last updated: 2013-10-24Bibliographically approved
2. Opposing effects of aging on large-scale brain systems for memory encoding and cognitive control
Open this publication in new window or tab >>Opposing effects of aging on large-scale brain systems for memory encoding and cognitive control
2012 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 32, no 31, 10749-10757 p.Article in journal (Refereed) Published
Abstract [en]

Episodic memory declines with advancing age. Neuroimaging studies have associated such decline to age-related changes in general cognitive-control networks as well as to changes in process-specific encoding or retrieval networks. To assess the specific influence of aging on encoding and retrieval processes and associated brain systems, it is vital to dissociate encoding and retrieval from each other and from shared cognitive-control processes. We used multivariate partial-least-squares to analyze functional magnetic resonance imaging data from a large population-based sample (n = 292, 25-80 years). The participants performed a face-name paired-associates task and an active baseline task. The analysis revealed two significant network patterns. The first reflected a process-general encoding-retrieval network that included frontoparietal cortices and posterior hippocampus. The second pattern dissociated encoding and retrieval networks. The anterior hippocampus was differentially engaged during encoding. Brain scores, representing whole-brain integrated measures of how strongly an individual recruited a brain network, were correlated with cognitive performance and chronological age. The scores from the general cognitive-control network correlated negatively with episodic memory performance and positively with age. The encoding brain scores, which strongly reflected hippocampal functioning, correlated positively with episodic memory performance and negatively with age. Univariate analyses confirmed that bilateral hippocampus showed the most pronounced activity reduction in older age, and brain structure analyses found that the activity reduction partly related to hippocampus atrophy. Collectively, these findings suggest that age-related structural brain changes underlie age-related reductions in the efficient recruitment of a process-specific encoding network, which cascades into upregulated recruitment of a general cognitive-control network.

National Category
urn:nbn:se:umu:diva-51906 (URN)10.1523/JNEUROSCI.0278-12.2012 (DOI)000307125900030 ()

Originally included in thesis in manuscript form.

Available from: 2012-02-03 Created: 2012-02-03 Last updated: 2014-07-17Bibliographically approved
3. Longitudinal evidence for diminished frontal cortex function in aging
Open this publication in new window or tab >>Longitudinal evidence for diminished frontal cortex function in aging
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2010 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 107, no 52, 22682-22686 p.Article in journal (Refereed) Published
Abstract [en]

Cross-sectional estimates of age-related changes in brain structure and function were compared with 6-y longitudinal estimates. The results indicated increased sensitivity of the longitudinal approach as well as qualitative differences. Critically, the cross-sectional analyses were suggestive of age-related frontal overrecruitment, whereas the longitudinal analyses revealed frontal underrecruitment with advancing age. The cross-sectional observation of overrecruitment reflected a select elderly sample. However, when followed over time, this sample showed reduced frontal recruitment. These findings dispute inferences of true age changes on the basis of age differences, hence challenging some contemporary models of neurocognitive aging, and demonstrate age-related decline in frontal brain volume as well as functional response.

attrition, frontal lobe, multimodal, reorganization
National Category
Physiology Neurosciences
urn:nbn:se:umu:diva-38932 (URN)10.1073/pnas.1012651108 (DOI)000285684200062 ()21156826 (PubMedID)
Available from: 2011-01-11 Created: 2011-01-11 Last updated: 2014-07-18Bibliographically approved
4. Age-related white matter microstructural differences partly mediate age-related decline in processing speed but not cognition
Open this publication in new window or tab >>Age-related white matter microstructural differences partly mediate age-related decline in processing speed but not cognition
2012 (English)In: Biochimica et Biophysica Acta, ISSN 0006-3002, Vol. 1822, no 3, 408-415 p.Article in journal (Refereed) Published
Abstract [en]

Aging is associated with declining cognitive performance as well as structural changes in brain gray and white matter (WM). The WM deterioration contributes to a disconnection among distributed brain networks and may thus mediate age-related cognitive decline. The present diffusion tensor imaging (DTI) study investigated age-related differences in WM microstructure and their relation to cognition (episodic memory, visuospatial processing, fluency, and speed) in a large group of healthy subjects (n=287) covering 6 decades of the human life span. Age related decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were observed across the entire WM skeleton as well as in specific WM tracts, supporting the WM degeneration hypothesis. The anterior section of the corpus callosum was more susceptible to aging compared to the posterior section, lending support to the anterior-posterior gradient of WM integrity in the corpus callosum. Finally, and of critical interest, WM integrity differences were found to mediate age-related reductions in processing speed but no significant mediation was found for episodic memory, visuospatial ability, or fluency. These findings suggest that compromised WM integrity is not a major contributing factor to declining cognitive performance in normal aging. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

white matter, cognition, aging, mediation, DTI
National Category
Neurosciences Physiology
urn:nbn:se:umu:diva-47517 (URN)10.1016/j.bbadis.2011.09.001 (DOI)21930202 (PubMedID)
Available from: 2011-09-22 Created: 2011-09-22 Last updated: 2013-10-28Bibliographically approved

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