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Neural Mechanisms Determining Visuospatial Working Memory Tasks: Biophysical Modeling, Functional MRI and EEG
KTH, School of Computer Science and Communication (CSC), Numerical Analysis and Computer Science, NADA.
2007 (English)Doctoral thesis, comprehensive summary (Other scientific)
Abstract [en]

Visuospatial working memory (vsWM) is the ability to temporarily retain goal-relevant visuospatial information in memory. It is a key cognitive function related to general intelligence, and it improves throughout childhood and through WM training. Information is maintained in vsWM through persistent neuronal activity in a fronto-parietal network that consists of the intraparietal sulcus (IPS) and the frontal eye field (FEF). This network is regulated by the dorsolateral prefrontal cortex (dlPFC).

The features of brain structure and activity that regulate the access to and storage capacity of visuospatial WM (vsWM) are still unknown. The aim of my doctoral work has been to find such features by combining a biophysically based model of vsWM activity with functional MRI (fMRI) and EEG experiments.

In study I, we combined modeling and fMRI and showed that stronger fronto-parietal synaptic connections result in developmental increases in brain activity and in improved vsWM during development. This causal relationship was established by ruling out other previously suggested mechanisms, such as myelination or synaptic pruning,

In study II, we combined modeling and EEG to further explore the connectivity of the network. We showed that FEF→IPS connections are stronger than IPS→FEF connections, and that stimuli enter IPS. This arrangement of connections prevents distracting stimuli from being stored.

Study III was a theoretical study showing that errors in measurements of the amplitude of brain activity affect the estimation of effective connection strength.

In study IV, we analyzed EEG data from WM training in children with epilepsy. Improvements on the trained task were accompanied by increased frontal and parietal signal power, but not fronto-parietal coherence. This indicates that local changes in FEF and IPS could underlie improvements on the trained task.

dlPFC is important for the performance on a large variety of cognitive tasks.

In study V, we combined modeling with fMRI to test the hypothesis that dlPFC improves vsWM capacity by providing stabilizing excitatory inputs to IPS, and that dlPFC filters distracters by specifically lowering the capacity of neurons storing distracters. fMRI data confirmed the model hypothesis. We further showed that a dysfunctional dlPFC could explain the link between vsWM capacity and distractibility, as is found in ADHD. The model suggests that dlPFC carries out its multifaceted behavior not by performing advanced calculations itself, but by providing bias signals that control operations performed in the regions it connects to.

A specific aim of this thesis has been to describe the mechanistic model in a way that is accessible to people without a modeling background.

Place, publisher, year, edition, pages
Stockhollm: KTH , 2007. , vi, 57 p.
Series
Trita-CSC-A, ISSN 1653-5723 ; 2007:23
National Category
Computer Science
Identifiers
URN: urn:nbn:se:kth:diva-4577ISBN: 978-91-7178-832-0 (print)OAI: oai:DiVA.org:kth-4577DiVA: diva2:12946
Public defence
2008-01-11, Sal D2, KTH, Lindstedtsvägen 5, Stockholm, 13:00
Opponent
Supervisors
Note
QC 20100705Available from: 2007-12-12 Created: 2007-12-12 Last updated: 2010-07-05Bibliographically approved
List of papers
1. Stronger synaptic connectivity as a mechanism behind development of working memory-related brain activity during childhood
Open this publication in new window or tab >>Stronger synaptic connectivity as a mechanism behind development of working memory-related brain activity during childhood
Show others...
2007 (English)In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 19, no 5, 750-760 p.Article in journal (Refereed) Published
Abstract [en]

The cellular maturational processes behind cognitive development during childhood, including the development of working memory capacity, are still unknown. By using the most standard computational model of visuospatial working memory, we investigated the consequences of cellular maturational processes, including myelination, synaptic strengthening, and synaptic pruning, on working memory-related brain activity and performance. We implemented five structural developmental changes occurring as a result of the cellular maturational processes in the biophysically based computational network model. The developmental changes in memory activity predicted from the simulations of the model were then compared to brain activity measured with functional magnetic resonance imaging in children and adults. We found that networks with stronger fronto-parietal synaptic connectivity between cells coding for similar stimuli, but not those with faster conduction, stronger connectivity within a region, or increased coding specificity, predict measured developmental increases in both working memory-related brain activity and in correlations of activity between regions. Stronger fronto-parietal synaptic connectivity between cells coding for similar stimuli was thus the only developmental process that accounted for the observed changes in brain activity associated with development of working memory during childhood.

Keyword
PRIMATE PREFRONTAL CORTEX; HUMAN FRONTAL-CORTEX; COGNITIVE-DEVELOPMENT; PERSISTENT ACTIVITY; PARIETAL CORTEX; CEREBRAL-CORTEX; WHITE-MATTER; IN-VIVO; CHILDREN; FMRI
National Category
Biological Sciences
Identifiers
urn:nbn:se:kth:diva-7808 (URN)10.1162/jocn.2007.19.5.750 (DOI)000246339900003 ()2-s2.0-34248398031 (Scopus ID)
Note

QC 20100705

Available from: 2007-12-12 Created: 2007-12-12 Last updated: 2012-09-04Bibliographically approved
2. Fronto-Pariatal connection asymmetry regulates working memory distractibility
Open this publication in new window or tab >>Fronto-Pariatal connection asymmetry regulates working memory distractibility
2007 (English)In: Journal of Integrative Neuroscience, ISSN 0219-6352, Vol. 6, no 4, 567-596 p.Article in journal (Refereed) Published
Abstract [en]

Recent functional magnetic resonance imaging studies demonstrate that increased task-related neural activity in parietal and frontal cortex during development and training is positively correlated with improved visuospatial working memory (vsWM) performance. Yet, the analysis of the corresponding underlying functional reorganization of the fronto-parietal network has received little attention. Here, we perform an integrative experimental and computational analysis to determine the effective balance between the superior frontal sulcus (SFS) and intraparietal sulcus (IPS) and their putative role(s) in protecting against distracters. To this end, we performed electroencephalographic (EEG) recordings during a vsWM task. We utilized a biophysically based computational cortical network model to analyze the effects of different neural changes in the underlying cortical networks on the directed transfer function (DTF) and spiking activity. Combining a DTF analysis of our EEG data with the DTF analysis of the computational model, a directed strong SFS → IPS network was revealed. Such a configuration offers protection against distracters, whereas the opposite is true for strong IPS → SFS connections. Our results therefore suggest that the previously demonstrated improvement of vsWM performance during development could be due to a shift in the control of the effective balance between the SFS-IPS networks.

Keyword
Computational neuroscience; Connectivity; Cortico-cortical interactions; Directed transfer function; Distractibility; EEG; Frontal cortex; Neuronal circuits; Parietal cortex; Working memory
National Category
Biological Sciences
Identifiers
urn:nbn:se:kth:diva-7809 (URN)10.1142/S0219635207001702 (DOI)2-s2.0-38049042894 (Scopus ID)
Note
QC 20100705. Uppdaterad från InPress till Published i DiVA 20100705.Available from: 2007-12-12 Created: 2007-12-12 Last updated: 2010-09-21Bibliographically approved
3. Scaling errors in measures of brain activity cause erroneous estimates of effective connectivity
Open this publication in new window or tab >>Scaling errors in measures of brain activity cause erroneous estimates of effective connectivity
2010 (English)In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 49, no 1, 621-630 p.Article in journal (Refereed) Published
Abstract [en]

Effective connectivity (EC) is the collective term for various measures of the interaction between the nodes in a network of neurons or neural populations during a certain experimental condition. Here, I investigated three types of EC that differ with respect to signal normalization, and therefore measure different aspects of neural interactions. Unnormalized EC measures pure connection strength. Amplitude-scaled EC measures the combined influence of signal amplitude and connection strength on neural activity. Finally, normalized EC measures the influence of one node on the activity of another relative to all influences on that node. With a theoretical analysis, I investigated the sensitivity of EC to signal scaling (the ratio of the amplitude of the measured signal and the underlying neural activity) and found that scaling affects the conclusions of the analysis of unnormalized EC severely, whereas normalized EC is not affected by the scaling problem. In an analysis of previously published hemodynamic response functions (Handwerker, D. A., Ollinger, J. M., D'Esposito, M., 2004. Variation of BOLD hemodynamic responses across subjects and brain regions and their effects on statistical analyses. Neuroimage 21, 1639-1651), I tested the predictions of the theoretical analysis. The empirical analysis indicated that signal scaling contributes to a large extent to measurement errors of unnormalized EC, although hemodynamic response function shape variability also contributed. Normalized EC, on the other hand, was only affected by shape differences and not by scaling. In addition to being more accurate, normalized EC is also an appropriate type of measure of neural interactivity if one is interested in the relative influence of one node on another, rather than absolute connection strengths per se.

Keyword
amplitude modulation; article; brain function; brain region; controlled study; nerve cell network; nuclear magnetic resonance imaging; priority journal
National Category
Biological Sciences
Identifiers
urn:nbn:se:kth:diva-7810 (URN)10.1016/j.neuroimage.2009.07.007 (DOI)000272031700062 ()2-s2.0-70349971123 (Scopus ID)
Note
QC 20100705. Uppdaterad från Accepted till Published i DiVA 20100705.Available from: 2007-12-12 Created: 2007-12-12 Last updated: 2010-09-21Bibliographically approved
4. Alpha synchronization after training of visuospatial working memory in patients with epilepsy
Open this publication in new window or tab >>Alpha synchronization after training of visuospatial working memory in patients with epilepsy
(English)Manuscript (Other academic)
National Category
Biological Sciences
Identifiers
urn:nbn:se:kth:diva-7811 (URN)
Note
QC 20100705Available from: 2007-12-12 Created: 2007-12-12 Last updated: 2011-02-01Bibliographically approved
5. Flexible Prefrontal Bias Signals Regulate Capacity and Access to Working Memory
Open this publication in new window or tab >>Flexible Prefrontal Bias Signals Regulate Capacity and Access to Working Memory
2008 (English)Manuscript (preprint) (Other academic)
National Category
Biological Sciences
Identifiers
urn:nbn:se:kth:diva-7812 (URN)
Note

QC 20100705

Available from: 2007-12-12 Created: 2007-12-12 Last updated: 2016-02-02Bibliographically approved

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