Finn Årup Nielsen

On Clustering fMRI Time Series

Analysis of fMRI time series is often performed by extracting one or more parameters for the individual voxels. Methods based, e.g., on various statistical tests are then used to yield parameters corresponding to probability of activation or activation strength. However, these methods do not indicate whether sets of voxels are activated in a similar way or in different ways. Typically, delays between two activated signals are not identified. In this article, we use clustering methods to detect similarities in activation between voxels. We employ a novel metric that measures the similarity between the activation stimulus and the fMRI signal. We present two different clustering algorithms and use them to identify regions of similar activations in an fMRI experiment involving a visual stimulus.

Persistence of Web references in scientific research

The lack of persistence of Web references has called into question the increasingly common practice of citing URLs in scientific papers. It is argued that although few critical resources have been lost to date, new strategies to manage Internet resources and improved citation practices are necessary to minimize the future loss of information.

Modeling the hemodynamic response in fMRI using smooth FIR filters

Modeling the hemodynamic response in functional magnetic resonance (fMRI) experiments is an important aspect of the analysis of functional neuroimages. This has been done in the past using parametric response function, from a limited family. In this contribution, the authors adopt a semi-parametric approach based on finite impulse response (FIR) filters. In order to cope with the increase in the number of degrees of freedom, the authors introduce a Gaussian process prior on the filter parameters. They show how to carry on the analysis by incorporating prior knowledge on the filters, optimizing hyper-parameters using the evidence framework, or sampling using a Markov Chain Monte Carlo (MCMC) approach. The authors present a comparison of their model with standard hemodynamic response kernels on simulated data, and perform a full analysis of data acquired during an experiment involving visual stimulation.

Generalizable patterns in neuroimaging: how many principal components?

Generalization can be defined quantitatively and can be used to assess the performance of principal component analysis (PCA). The generalizability of PCA depends on the number of principal components retained in the analysis. We provide analytic and test set estimates of generalization. We show how the generalization error can be used to select the number of principal components in two analyses of functional magnetic resonance imaging activation sets.

Frontolimbic Serotonin 2A Receptor Binding in Healthy Subjects Is Associated with Personality Risk Factors for Affective Disorder

BACKGROUND Serotonergic dysfunction has been associated with affective disorders. High trait neuroticism, as measured on personality inventories, is a risk factor for major depression. In this study we investigated whether neuroticism is associated with serotonin 2A receptor binding in brain regions of relevance for affective disorders. METHODS Eighty-three healthy volunteers completed the standardized personality questionnaire NEO-PI-R (Revised NEO Personality Inventory) and underwent [(18)F]altanserin positron emission tomography imaging for assessment of serotonin 2A receptor binding. The correlation between the neuroticism score and frontolimbic serotonin 2A receptor binding was evaluated by multiple linear regression analysis with adjustment for age and gender. RESULTS Neuroticism correlated positively with frontolimbic serotonin 2A receptor binding [r(79) = .24, p = .028]. Post hoc analysis of the contributions from the six constituent traits of neuroticism showed that the correlation was primarily driven by two of them: vulnerability and anxiety. Indeed, vulnerability, defined as a persons difficulties in coping with stress, displayed the strongest positive correlation, which remained significant after correction for multiple comparisons (r = .35, p = .009). CONCLUSIONS In healthy subjects the personality dimension neuroticism and particularly its constituent trait, vulnerability, are positively associated with frontolimbic serotonin 2A binding. Our findings point to a neurobiological link between personality risk factors for affective disorder and the serotonergic transmitter system and identify the serotonin 2A receptor as a biomarker for vulnerability to affective disorder.

Mining the posterior cingulate: Segregation between memory and pain components

We present a general method for automatic meta-analyses in neuroscience and apply it on text data from published functional imaging studies to extract main functions associated with a brain area-the posterior cingulate cortex (PCC). Abstracts from PubMed are downloaded, words extracted and converted to a bag-of-words matrix representation. The combined data are analyzed with hierarchical non-negative matrix factorization. We find that the prominent themes in the PCC corpus are episodic memory retrieval and pain. We further characterize the distribution in PCC of the Talairach coordinates available in some of the articles. This shows a tendency to functional segregation between memory and pain components where memory activations are predominantly in the caudal part and pain in the rostral part of PCC.

Seasonal changes in brain serotonin transporter binding in short serotonin transporter linked polymorphic region-allele carriers but not in long-allele homozygotes.

BACKGROUND A polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) has been associated with seasonality both in patients with seasonal affective disorder and in the general population. METHOD We used in vivo molecular imaging to measure cerebral serotonin transporter (5-HTT) binding in 57 healthy Scandinavians and related the outcome to season of the year and to the 5-HTTLPR carrier status. RESULTS We found that the number of daylight minutes at the time of scanning correlated negatively with 5-HTT binding in the putamen and the caudate, with a similar tendency in the thalamus, whereas this association was not observed for the midbrain. Furthermore, in the putamen, an anatomic region with relatively dense serotonin innervation, we found a significant gene x daylight effect, such that there was a negative correlation between 5-HTT binding and daylight minutes in carriers of the short 5-HTTLPR allele but not in homozygote carriers of the long allele. CONCLUSIONS Our findings are in line with S-carriers having an increased response in neural circuits involved in emotional processing to stressful environmental stimuli but here demonstrated as a endophenotype with dynamic changes in serotonin reuptake.

The personality trait openness is related to cerebral 5-HTT levels

Potentiation of serotonergic transmission increases cognitive flexibility, but can in other circumstances increase sensitivity to stressful environmental cues. The personality trait Openness to Experience reflects and is also associated with an increased risk for mood disorders. We hypothesized that the personality trait has an association with a biomarker of serotonergic transmission, the plasma membrane serotonin transporter (5-HTT). In 50 healthy volunteers, we tested for correlations between scores on the NEO-PI-R scale Openness to Experience and its subscales, and cerebral binding of the 5-HTT selective PET radioligand [11C]DASB. Subjects were genotyped for the 5-HTT long/short polymorphism, and for a single nucleotide polymorphism in the long allele, designated LA/LG. Midbrain [11C]DASB binding correlated negatively with scores for Openness to Experience and its two subscales, Openness to Actions and Openness to Values. The latter subscore was negatively correlated with [11C]DASB binding in all brain regions in which [11C]DASB binding was quantified. Genetic analysis showed that homozygote LA carriers had significantly higher [11C]DASB binding in the caudate nucleus, but no significant differences in openness scores. Thus, high scores in personality facets indicative of cognitive flexibility and openness to change are associated with lower [11C]DASB binding. Lower abundance of 5-HTT sites may result in potentiation of serotonergic signaling, which occurs during treatment with SSRIs. We speculate that the set-point of serotonergic signaling in an individual represents a trade-off between flexibility and vulnerability when exposed to environmental stress.

Modeling of activation data in the BrainMap™ database: Detection of outliers

We describe a system for meta‐analytical modeling of activation foci from functional neuroimaging studies. Our main vehicle is a set of density models in Talairach space capturing the distribution of activation foci in sets of experiments labeled by lobar anatomy. One important use of such density models is identification of novelty, i.e., low probability database events. We rank the novelty of the outliers and investigate the cause for 21 of the most novel, finding several outliers that are entry and transcription errors or infrequent or non‐conforming terminology. We briefly discuss the use of atlases for outlier detection. Hum. Brain Mapping 15:146–156, 2002.

The sum of all human knowledge: A systematic review of scholarly research on the content of Wikipedia

Wikipedia may be the best‐developed attempt thus far to gather all human knowledge in one place. Its accomplishments in this regard have made it a point of inquiry for researchers from different fields of knowledge. A decade of research has thrown light on many aspects of the Wikipedia community, its processes, and its content. However, due to the variety of fields inquiring about Wikipedia and the limited synthesis of the extensive research, there is little consensus on many aspects of Wikipedias content as an encyclopedic collection of human knowledge. This study addresses the issue by systematically reviewing 110 peer‐reviewed publications on Wikipedia content, summarizing the current findings, and highlighting the major research trends. Two major streams of research are identified: the quality of Wikipedia content (including comprehensiveness, currency, readability, and reliability) and the size of Wikipedia. Moreover, we present the key research trends in terms of the domains of inquiry, research design, data source, and data gathering methods. This review synthesizes scholarly understanding of Wikipedia content and paves the way for future studies.