Joeran Lepsien

Eigenvector Centrality Mapping for Analyzing Connectivity Patterns in fMRI Data of the Human Brain

Functional magnetic resonance data acquired in a task-absent condition (“resting state”) require new data analysis techniques that do not depend on an activation model. In this work, we introduce an alternative assumption- and parameter-free method based on a particular form of node centrality called eigenvector centrality. Eigenvector centrality attributes a value to each voxel in the brain such that a voxel receives a large value if it is strongly correlated with many other nodes that are themselves central within the network. Googles PageRank algorithm is a variant of eigenvector centrality. Thus far, other centrality measures - in particular “betweenness centrality” - have been applied to fMRI data using a pre-selected set of nodes consisting of several hundred elements. Eigenvector centrality is computationally much more efficient than betweenness centrality and does not require thresholding of similarity values so that it can be applied to thousands of voxels in a region of interest covering the entire cerebrum which would have been infeasible using betweenness centrality. Eigenvector centrality can be used on a variety of different similarity metrics. Here, we present applications based on linear correlations and on spectral coherences between fMRI times series. This latter approach allows us to draw conclusions of connectivity patterns in different spectral bands. We apply this method to fMRI data in task-absent conditions where subjects were in states of hunger or satiety. We show that eigenvector centrality is modulated by the state that the subjects were in. Our analyses demonstrate that eigenvector centrality is a computationally efficient tool for capturing intrinsic neural architecture on a voxel-wise level.

Sex-Dependent Influences of Obesity on Cerebral White Matter Investigated by Diffusion-Tensor Imaging

Several studies have shown that obesity is associated with changes in human brain function and structure. Since women are more susceptible to obesity than men, it seems plausible that neural correlates may also be different. However, this has not been demonstrated so far. To address this issue, we systematically investigated the brains white matter (WM) structure in 23 lean to obese women (mean age 25.5 y, std 5.1 y; mean body mass index (BMI) 29.5 kg/m2, std 7.3 kg/m2) and 26 lean to obese men (mean age 27.1 y, std 5.0 y; mean BMI 28.8 kg/m2, std 6.8 kg/m2) with diffusion-weighted magnetic resonance imaging (MRI). There was no significant age (p>0.2) or BMI (p>0.7) difference between female and male participants. Using tract-based spatial statistics, we correlated several diffusion parameters including the apparent diffusion coefficient, fractional anisotropy (FA), as well as axial (λ∥) and radial diffusivity (λ⊥) with BMI and serum leptin levels. In female and male subjects, the putative axon marker λ∥ was consistently reduced throughout the corpus callosum, particularly in the splenium (r = −0.62, p<0.005). This suggests that obesity may be associated with axonal degeneration. Only in women, the putative myelin marker λ⊥ significantly increased with increasing BMI (r = 0.57, p<0.005) and serum leptin levels (r = 0.62, p<0.005) predominantly in the genu of the corpus callosum, suggesting additional myelin degeneration. Comparable structural changes were reported for the aging brain, which may point to accelerated aging of WM structure in obese subjects. In conclusion, we demonstrate structural WM changes related to an elevated body weight, but with differences between men and women. Future studies on obesity-related functional and structural brain changes should therefore account for sex-related differences.

Attentional orienting to mnemonic representations: Reduction of load-sensitive maintenance-related activity in the intraparietal sulcus

The orienting of attention to internal or mnemonic representations held in visual working memory (VWM) has recently become a field of increasing interest. While a number of studies support the hypothesis that attention to selected representations in VWM reduces memory load, conclusive findings are still missing. In this event-related functional magnetic resonance imaging (fMRI) study, we directly investigated whether attentional orienting to mnemonic representations reduces activity in VWM storage-related areas of the brain. VWM load was manipulated by asking subjects to memorize two, four or six items. A retro-cue during the subsequent delay period asked subjects to attend to just one of these items for a subsequent test. This was compared to trials where subjects were required to continue attending to all items for the subsequent test. Data show reduction of load-sensitive maintenance-related activity along the right intraparietal sulcus (IPS), directly linked to attentional orienting. While activity in the anterior IPS reflected the number of representations in the focus of attention, the activation pattern in the posterior IPS suggested residual activation related to unattended items. This dissociation is in line with a functional subdivision of the right IPS according to attentional and mnemonic properties.

Changes of Hand Switching Costs during Bimanual Sequential Learning

Many tasks in our daily life demand not only the use of different fingers of one hand in a serial fashion, but also to alternate from one hand to the other. Here, we investigated performance in a bimanual serial reaction time task (SRTT) with particular emphasis on learning-related changes in reaction time (RT) for consecutive button presses for homologous index- and middle fingers. The bimanual SRTT consisted of sequential button presses either with the left or right index- and middle-finger to a series of visual letters displayed on a computer screen. Each letter was assigned a specific button press with one of four fingers. Two outcome measures were investigated: (a) global sequence learning as defined by the time needed to complete a 15-letter SRTT sequence and (b) changes in hand switch costs across learning. We found that bimanual SRTT resulted in a global decrease in RT during the time course of learning that persisted for at least two weeks. Furthermore, RT to a button press showed an increase when the previous button press was associated with another hand as opposed to the same hand. This increase in RT was defined as switch costs. Hand switch costs significantly decreased during the time course of learning, and remained stable over a time of approximately two weeks. This study provides evidence for modulations of switch costs during bimanual sequence learning, a finding that might have important implications for theories of bimanual coordination and learning.

Neural correlates of mirror visual feedback-induced performance improvements: a resting-state fMRI study

Mirror visual feedback (MVF) is a promising approach to enhance motor performance without training in healthy adults as well as in patients with focal brain lesions. There is preliminary evidence that a functional modulation within and between primary motor cortices as assessed with transcranial magnetic stimulation (TMS) might be one candidate mechanism mediating the observed behavioral effects. Recently, studies using task-based functional magnetic resonance imaging (fMRI) have indicated that MVF-induced functional changes might not be restricted to the primary motor cortex (M1) but also include higher order regions responsible for perceptual-motor coordination and visual attention. However, aside from these instantaneous task-induced brain changes, little is known about learning-related neuroplasticity induced by MVF. Thus, in the present study, we assessed MVF-induced functional network plasticity with resting-state fMRI (rs-fMRI). We performed rs-fMRI of 35 right-handed, healthy adults before and after performing a complex ball-rotation task. The primary outcome measure was the performance improvement of the untrained left hand (LH) before and after right hand (RH) training with MVF (mirror group [MG], n = 17) or without MVF (control group [CG], n = 18). Behaviorally, the MG showed superior performance improvements of the untrained LH. In resting-state functional connectivity (rs-FC), an interaction analysis between groups showed changes in left visual cortex (V1, V2) revealing an increase of centrality in the MG. Within group comparisons showed further functional alterations in bilateral primary sensorimotor cortex (SM1), left V4 and left anterior intraparietal sulcus (aIP) in the MG, only. Importantly, a correlation analysis revealed a linear positive relationship between MVF-induced improvements of the untrained LH and functional alterations in left SM1. Our results suggest that MVF-induced performance improvements are associated with functional learning-related brain plasticity and have identified additional target regions for non-invasive brain stimulation techniques, a finding of potential interest for neurorehabilitation.