Showing papers by "Serge A.R.B. Rombouts published in 2010"

Toward discovery science of human brain function

Abstract: Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (<0.1 Hz) fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's "functional connectome." Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/.

Whole brain resting-state analysis reveals decreased functional connectivity in major depression

Abstract: Recently, both increases and decreases in resting-state functional connectivity have been found in major depression. However, these studies only assessed functional connectivity within a specific network or between a few regions of interest, while comorbidity and use of medication was not always controlled for. Therefore, the aim of the current study was to investigate whole-brain functional connectivity, unbiased by a priori definition of regions or networks of interest, in medication-free depressive patients without comorbidity. We analyzed resting-state fMRI data of 19 medication-free patients with a recent diagnosis of major depression (within 6 months before inclusion) and no comorbidity, and 19 age- and gender-matched controls. Independent component analysis was employed on the concatenated data sets of all participants. Thirteen functionally relevant networks were identified, describing the entire study sample. Next, individual representations of the networks were created using a dual regression method. Statistical inference was subsequently done on these spatial maps using voxel-wise permutation tests. Abnormal functional connectivity was found within three resting-state networks in depression: (1) decreased bilateral amygdala and left anterior insula connectivity in an affective network, (2) reduced connectivity of the left frontal pole in a network associated with attention and working memory, and (3) decreased bilateral lingual gyrus connectivity within ventromedial visual regions. None of these effects were associated with symptom severity or gray matter density. We found abnormal resting-state functional connectivity not previously associated with major depression, which might relate to abnormal affect regulation and mild cognitive deficits, both associated with the symptomatology of the disorder.

Loss of 'small-world' networks in Alzheimer's disease: graph analysis of FMRI resting-state functional connectivity.

Abstract: BACKGROUND: Local network connectivity disruptions in Alzheimer's disease patients have been found using graph analysis in BOLD fMRI. Other studies using MEG and cortical thickness measures, however, show more global long distance connectivity changes, both in functional and structural imaging data. The form and role of functional connectivity changes thus remains ambiguous. The current study shows more conclusive data on connectivity changes in early AD using graph analysis on resting-state condition fMRI data. METHODOLOGY/PRINCIPAL FINDINGS: 18 mild AD patients and 21 healthy age-matched control subjects without memory complaints were investigated in resting-state condition with MRI at 1.5 Tesla. Functional coupling between brain regions was calculated on the basis of pair-wise synchronizations between regional time-series. Local (cluster coefficient) and global (path length) network measures were quantitatively defined. Compared to controls, the characteristic path length of AD functional networks is closer to the theoretical values of random networks, while no significant differences were found in cluster coefficient. The whole-brain average synchronization does not differ between Alzheimer and healthy control groups. Post-hoc analysis of the regional synchronization reveals increased AD synchronization involving the frontal cortices and generalized decreases located at the parietal and occipital regions. This effectively translates in a global reduction of functional long-distance links between frontal and caudal brain regions. CONCLUSIONS/SIGNIFICANCE: We present evidence of AD-induced changes in global brain functional connectivity specifically affecting long-distance connectivity. This finding is highly relevant for it supports the anterior-posterior disconnection theory and its role in AD. Our results can be interpreted as reflecting the randomization of the brain functional networks in AD, further suggesting a loss of global information integration in disease.

What Motivates the Adolescent? Brain Regions Mediating Reward Sensitivity across Adolescence

Abstract: The relation between brain development across adolescence and adolescent risky behavior has attracted increasing interest in recent years. It has been proposed that adolescents are hypersensitive to reward because of an imbalance in the developmental pattern followed by the striatum and prefrontal cortex. To date, it is unclear if adolescents engage in risky behavior because they overestimate potential rewards or respond more to received rewards and whether these effects occur in the absence of decisions. In this study, we used a functional magnetic resonance imaging paradigm that allowed us to dissociate effects of the anticipation, receipt, and omission of reward in 10- to 12-year-old, 14- to 15-year-old, and 18- to 23-year-old participants. We show that in anticipation of uncertain outcomes, the anterior insula is more active in adolescents compared with young adults and that the ventral striatum shows a reward-related peak in middle adolescence, whereas young adults show orbitofrontal cortex activation to omitted reward. These regions show distinct developmental trajectories. This study supports the hypothesis that adolescents are hypersensitive to reward and adds to the current literature in demonstrating that neural activation differs in adolescents even for small rewards in the absence of choice. These findings may have important implications for understanding adolescent risk-taking behavior.

Do you like me? Neural correlates of social evaluation and developmental trajectories.

Abstract: Social acceptance is of key importance for healthy functioning. We used functional magnetic resonance imaging (fMRI) to examine age-related changes in the neural correlates of social acceptance and rejection processing. Participants from four age groups participated in the study: pre-pubertal children (8-10 years), early adolescents (12-14 years), older adolescents (16-17 years) and young adults (19-25 years). During the experiment, participants were presented with unfamiliar faces of peers and were asked to predict whether they expected to be liked or disliked by the other person, followed by feedback indicating acceptance or rejection. Results showed that activation in the ventral mPFC and striatum to social feedback was context-dependent; there was increased activation when participants had positive expectations about social evaluation, and increased activation following social acceptance feedback. Age-related comparisons revealed a linear increase in activity with age in these brain regions for positive expectations of social evaluation. Similarly, a linear increase with age was found for activation in the striatum, ventral mPFC, OFC, and lateral PFC for rejection feedback. No age-related differences in neural activation were shown for social acceptance feedback. Together, these results provide important insights in the developmental trajectories of brain regions implicated in social and affective behavior.

The contribution of MRI in assessing cognitive impairment in multiple sclerosis.

Abstract: Cognitive impairment affects a large proportion of patients with multiple sclerosis (MS) and has a profound impact on their daily-life activities. Improving the knowledge of the pathophysiology of cognitive impairment in MS and of the mechanisms responsible for its evolution over time might contribute to development of better outcome measures and targets for innovative treatment strategies. Due to their ability to detect MS-related abnormalities, MRI techniques are a valuable tool to achieve these goals. Following an updated overview of the assessment methods and profile of cognitive impairment in patients with MS, this review provides a state-of-the-art summary of the main results obtained from the application of conventional and modern magnetic resonance– based techniques to quantify MS-related damage, in terms of macroscopic lesions, as well as involvement of the normal-appearing white matter and gray matter and their association with cognitive impairment. The possible role of brain cortical reorganization in limiting the clinical consequences of disease-related damage is also discussed. Finally, the utility of the previous techniques to monitor the progression of cognitive deficits over time and the efficacy of possible therapeutic strategies is considered.

Unfair? It depends: Neural correlates of fairness in social context

Abstract: Fairness is a key concept in social interactions and is influenced by intentionality considerations. In this functional magnetic resonance imaging study, we investigated the neural correlates of fairness by focusing on responder behavior to unfair offers in an Ultimatum Game paradigm with conditions that differed in their intentionality constraints. Brain activity underlying rejection vs acceptance of unfair offers appeared highly dependent on intentionality. Rejection of unfair offers when the proposer had no-alternative as well as acceptance of offers when the proposer had a fair- or hyperfair-alternative was associated with activation in a network of regions including the insula and the dorsal medial prefrontal cortex. These activations were interpreted as neural responses to norm violations because they were mostly involved when behavior was inconsistent with socially accepted behavior patterns. Rejection of unfair offers in the no-alternative condition further resulted in activity in the anterior medial prefrontal cortex and the temporoparietal junction, which was interpreted in terms of higher moral mentalizing demands required in social decision-making when rejection could not be readily justified. Together, results highlight the significance of intentionality considerations in fairness-related social decision-making processes.