Thomas P. K. Breckel

Long-term effects of attentional performance on functional brain network topology.

Individuals differ in their cognitive resilience. Less resilient people demonstrate a greater tendency to vigilance decrements within sustained attention tasks. We hypothesized that a period of sustained attention is followed by prolonged changes in the organization of “resting state” brain networks and that individual differences in cognitive resilience are related to differences in post-task network reorganization. We compared the topological and spatial properties of brain networks as derived from functional MRI data (N = 20) recorded for 6 mins before and 12 mins after the performance of an attentional task. Furthermore we analysed changes in brain topology during task performance and during the switches between rest and task conditions. The cognitive resilience of each individual was quantified as the rate of increase in response latencies over the 32-minute time course of the attentional paradigm. On average, functional networks measured immediately post-task demonstrated significant and prolonged changes in network organization compared to pre-task networks with higher connectivity strength, more clustering, less efficiency, and shorter distance connections. Individual differences in cognitive resilience were significantly correlated with differences in the degree of recovery of some network parameters. Changes in network measures were still present in less resilient individuals in the second half of the post-task period (i.e. 6–12 mins after task completion), while resilient individuals already demonstrated significant reductions of functional connectivity and clustering towards pre-task levels. During task performance brain topology became more integrated with less clustering and higher global efficiency, but linearly decreased with ongoing time-on-task. We conclude that sustained attentional task performance has prolonged, “hang-over” effects on the organization of post-task resting-state brain networks; and that more cognitively resilient individuals demonstrate faster rates of network recovery following a period of attentional effort.

Impact of brain networks involved in vigilance on processing irrelevant visual motion

The ability to sustain attention over prolonged periods of time is called vigilance. Vigilance is a fundamental component of attention which impacts on performance in many situations. We here investigate whether similar neural mechanisms are responsible for vigilant attention over long and short durations of time and whether neural activity in brain regions sensitive to vigilant attention is related to processing irrelevant information. Brain activity was measured by means of functional magnetic resonance imaging (fMRI) in a 32 min visual vigilance task with varying inter-target intervals and irrelevant peripheral motion stimuli. Changes in neural activity were analysed as a function of time on task to capture long-term aspects of vigilance and as a function of time between target stimuli to capture short-term aspects of vigilance. Several brain regions including the inferior frontal, posterior parietal, superior and middle temporal cortices and the anterior insular showed decreases in neural activity as a function of time on task. In contrast, increasing inter-target intervals resulted in increased neural activity in a widespread network of regions involving lateral and medial frontal areas, temporal areas, cuneus and precuneus, inferior occipital cortex (right), posterior insular cortices, the thalamus, nucleus accumbens and basal forebrain. A partial least square analysis revealed that neural activity in this latter network covaried with neural activity related to processing irrelevant motion stimuli. Our results provide neural evidence that two separate mechanisms are responsible for sustaining attention over long and short durations. We show that only brain areas involved in sustaining attention over short durations of time are related to processing irrelevant stimuli and suggest that these areas can be segregated into two functionally different networks, one possibly involved in motivation, the other in arousal.

The efficiency of functional brain networks does not differ between smokers and non-smokers

Acute nicotine consumption in smokers impacts on functional brain network topology indicating an increase in the efficiency of information transfer and attentional task performance. The effects of chronic nicotine consumption on functional brain network topology are unknown. We here investigated the effects of chronic smoking-behaviour on functional brain network topology. Minimally-deprived smokers (N=18) and non-smokers (N=17) were measured within an fMRI scanner during a resting state condition. Graph-theoretical metrics of functional network integration (global efficiency and clustering) that have been shown to be affected by acute nicotine administration were compared between both groups. Our results revealed that smoking status did not significantly change functional network integration. Additional tests for non-inferiority confirmed the similarity of regional or nodal network properties. Brain regions such as the left insular and middle frontal gyrus, in which acute nicotine consumption affected network topology, did not reveal any decrease in functional network efficiency following chronic nicotine consumption. Within the limitation of the investigated sample size, our data suggest that the integration of functional brain networks is not altered in minimally-deprived smokers. Our findings are of relevance for clinical studies showing changes in network topology between psychiatric patients with high prevalence of smoking and healthy control subjects.

Variability of fMRI-response patterns at different spatial observation scales

Functional organization units of the cerebral cortex exist over a wide range of spatial scales, from local circuits to entire cortical areas. In the last decades, scale‐space representations of neuroimaging data suited to probe the multi‐scale nature of cortical functional organization have been introduced and methodologically elaborated. For this purpose, responses are statistically detected over a range of spatial scales using a family of Gaussian filters, with small filters being related to fine and large filters—to coarse spatial scales. The goal of the present study was to investigate the degree of variability of fMRI‐response patterns over a broad range of observation scales. To this aim, the same fMRI data set obtained from 18 subjects during a visuomotor task was analyzed with a range of filters from 4‐ to 16‐mm full width at half‐maximum (FWHM). We found substantial observation‐scale‐related variability. For example, using filter widths of 6‐ to 8‐mm FWHM, in the group‐level results, significant responses in the right secondary visual but not in the primary visual cortex were detected. However, when larger filters were used, the responses in the right primary visual cortex reached significance. Often, responses in probabilistically defined areas were significant when both small and large filters, but not intermediate filter widths were applied. This suggests that brain responses can be organized in local clusters of multiple distinct activation foci. Our findings illustrate the potential of multi‐scale fMRI analysis to reveal novel features in the spatial organization of human brain responses. Hum Brain Mapp, 2011.

Nicotinergic Modulation of Attention-Related Neural Activity Differentiates Polymorphisms of DRD2 and CHRNA4 Receptor Genes

Cognitive and neuronal effects of nicotine show high interindividual variability. Recent findings indicate that genetic variations that affect the cholinergic and dopaminergic neurotransmitter system impact performance in cognitive tasks and effects of nicotine. The current pharmacogenetic functional magnetic resonance imaging (fMRI) study aimed to investigate epistasis effects of CHRNA4/DRD2 variations on behavioural and neural correlates of visuospatial attention after nicotine challenge using a data driven partial least squares discriminant analysis (PLS-DA) approach. Fifty young healthy non-smokers were genotyped for CHRNA4 (rs1044396) and DRD2 (rs6277). They received either 7 mg transdermal nicotine or a matched placebo in a double blind within subject design prior to performing a cued target detection task with valid and invalid trials. On behavioural level, the strongest benefits of nicotine in invalid trials were observed in participants carrying both, the DRD2 T- and CHRNA4 C+ variant. Neurally, we were able to demonstrate that different DRD2/CHRNA4 groups can be decoded from the pattern of brain activity in invalid trials under nicotine. Neural substrates of interindividual variability were found in a network of attention-related brain regions comprising the pulvinar, the striatum, the middle and superior frontal gyri, the insula, the left precuneus, and the right middle temporal gyrus. Our findings suggest that polymorphisms in the CHRNA4 and DRD2 genes are a relevant source of individual variability in pharmacological studies with nicotine.

Zur Bedeutung der räumlichen Glättung von funktionellen magnetresonanztomographischen Daten für deren Korrelation mit probabilistisch definierten sensomotorischen und visuellen kortikalen Arealen

Ein fundamentales Ziel funktionell-bildgebender Studien ist die zuverlassige und exakte Korrelation von Funktion mit anatomisch definierten kortikalen Arealen, wie z.B. dem motorischen oder visuellen Kortex. Eine wichtige Forderung an die Zuverlassigkeit solcher Zuordnungen von Funktion und Anatomie ist eine weitgehende Stabilitat gegenuber kleinen Anderungen von Parametern der Daten(vor)verarbeitung innerhalb der fur diese Parameter sinnvollen Grenzen. Auf diesem Hintergrund haben wir in der vorliegenden Studie erstmals den Einfluss der raumlichen Glattung von funktionellen Magnetresonanztomographie (fMRT)-Daten auf die Zuordnung von lokalen Maxima („peaks“) und signifikant aktiviertem Volumen in fMRT-Aktivierungskarten zu probabilistisch definierten anatomischen Arealen beim Menschen untersucht. BOLD-Signale wurden bei 13 gesunden Probanden in einem 3 T Scanner wahrend einer visuomotorischen Aufgabe gemessen und anatomische Zuordnungen der resultierenden Aktivierungskarten bei Glattung mit Filtern mit einer Filterbreite von 3–12mm untersucht. Unsere Ergebnisse zeigen, dass bereits eine Anderung der Filterbreite um 1mm zu drastischen Anderungen in der Peak-Zuordnung im Bereich des primaren sensomotorischen Kortex fuhren kann. Im Gegensatz hierzu erhielten wir fur die Peak-Zuordnung im primaren und sekundaren visuellen Kortex und fur die Volumenzuordnungen sowohl in visuellen als auch im motorischen Kortex konstantere Ergebnisse, mit einer deutlich weniger durch die Breite der Glattungsfilter bedingten Variabilitat. Eine mogliche Ursache fur diese unterschiedlichen Ergebnisse fur den visuellen im Vergleich mit dem sensomotorischen Kortex konnte in der groseren Ausdehnung der visuellen Areale gegeben sein. Hauptschlussfolgerung dieser Studie ist, dass fur exakte anatomische Zuordnungen von fMRT Ergebnissen zu anatomisch definierten Arealen die Robustheit dieser Zuordnungen gegenuber Anderungen in der Datenaufbearbeitung evaluiert und in der Interpretation der Ergebnisse berucksichtigt werden sollte. Zudem deuten unsere Resultate darauf hin, dass volumen-basierte Zuordnungen von Funktion zu Anatomie eine robustere Alternative zu peak-basierten Ansatzen darstellen konnten. Supported by BMBF (Grant 01GQ0420 to BCCN-Freiburg).

„Peak Quality Maps“ für Gruppenergebnisse basierend auf funktioneller Magnetresonanztomographie

Die Interpretation von lokalen Maxima („peaks“) und deren statistischer Signifikanz in Gruppenaktivierungskarten bildet die Grundlage einer Vielzahl von Studien, die mittels funktioneller Magnetresonanztomographie (fMRT) Korrelate neuronaler Aktivitat beim Menschen untersuchen. Ein Nachteil konventioneller Auswertungen von fMRT Daten auf dem Gruppenniveau besteht darin, dass sich nur eingeschrankt Information daruber ableiten lasst, wie viele der einzelnen Versuchpersonen zu den Gruppenergebnissen korrespondierenden Aktivierungspeaks zeigen. Auf diesem Hintergrund haben wir eine nach unserem Wissen neue Auswertungs- und Darstellungsart fur fMRT Gruppenergebnisse entwickelt, die Information uber die inter-individuelle Reproduzierbarkeit von Aktivierungpeaks quantifiziert („Peak Quality Maps“). BOLD-Signale wurden bei 13 gesunden Probanden in einem 3 T Scanner wahrend einer visuomotorischen Aufgabe gemessen und sowohl mittels konventioneller voxel-basierter Methoden als auch mittels Peak Quality Maps analysiert. Wir zeigen, dass Peak Quality Maps zusatzliche Information zu den konventionellen Gruppenergebnissen liefern konnen. So konnen peaks mit relativ geringer Signifikanz eine deutlich hohere inter-individuelle ortliche Reproduzierbarkeit (d.h. hohere Werte in der Peak Quality Map) aufweisen als peaks mit vergleichsweise hoherer Signifikanz in der konventionellen Darstellung. In einem weiteren Schritt haben wir die inter-individuelle Reproduzierbarkeit der anatomischen Zuordnung der peaks der Aktivierungskarten der einzelnen Versuchpersonen als zusatzliches Peak-Qualitatskriterium in die Betrachtung einbezogen. Haufig waren – uber die 13 Versuchpersonen hinweg – peaks in mehreren unterschiedlichen anatomischen Arealen bei der Bildung eines einzelnen peaks in den Gruppenergebnissen beteiligt. Andere Gruppenpeaks hatten demgegenuber korrespondierende peaks mit identischer anatomischer Zuordnung in allen, bzw. nahezu allen individuellen Aktivierungskarten. Zusammenfassend stellen die hier eingefuhrten Mase fur die peak-Qualitat einen Ansatz dar, der zu einer besseren Einschatzung der Aussagekraft von fMRT-Gruppenergebnissen fuhren konnte. Supported by BMBF (Grant 01GQ0420 to BCCN-Freiburg).