Flexible Adaptive Paradigms for fMRI Using a Novel Software Package ‘Brain Analysis in Real-Time’ (BART)

In this work we present a new open source software package offering a unified framework for the real-time adaptation of fMRI stimulation procedures. The software provides a straightforward setup and highly flexible approach to adapt fMRI paradigms while the experiment is running. The general framework comprises the inclusion of parameters from subject’s compliance, such as directing gaze to visually presented stimuli and physiological fluctuations, like blood pressure or pulse. Additionally, this approach yields possibilities to investigate complex scientific questions, for example the influence of EEG rhythms or fMRI signals results themselves. To prove the concept of this approach, we used our software in a usability example for an fMRI experiment where the presentation of emotional pictures was dependent on the subject’s gaze position. This can have a significant impact on the results. So far, if this is taken into account during fMRI data analysis, it is commonly done by the post-hoc removal of erroneous trials. Here, we propose an a priori adaptation of the paradigm during the experiment’s runtime. Our fMRI findings clearly show the benefits of an adapted paradigm in terms of statistical power and higher effect sizes in emotion-related brain regions. This can be of special interest for all experiments with low statistical power due to a limited number of subjects, a limited amount of time, costs or available data to analyze, as is the case with real-time fMRI

Dispelling urban myths about default uncertainty factors in chemical risk assessment - Sufficient protection against mixture effects?

© 2013 Martin et al.; licensee BioMed Central LtdThis article has been made available through the Brunel Open Access Publishing Fund.Assessing the detrimental health effects of chemicals requires the extrapolation of experimental data in animals to human populations. This is achieved by applying a default uncertainty factor of 100 to doses not found to be associated with observable effects in laboratory animals. It is commonly assumed that the toxicokinetic and toxicodynamic sub-components of this default uncertainty factor represent worst-case scenarios and that the multiplication of those components yields conservative estimates of safe levels for humans. It is sometimes claimed that this conservatism also offers adequate protection from mixture effects. By analysing the evolution of uncertainty factors from a historical perspective, we expose that the default factor and its sub-components are intended to represent adequate rather than worst-case scenarios. The intention of using assessment factors for mixture effects was abandoned thirty years ago. It is also often ignored that the conservatism (or otherwise) of uncertainty factors can only be considered in relation to a defined level of protection. A protection equivalent to an effect magnitude of 0.001-0.0001% over background incidence is generally considered acceptable. However, it is impossible to say whether this level of protection is in fact realised with the tolerable doses that are derived by employing uncertainty factors. Accordingly, it is difficult to assess whether uncertainty factors overestimate or underestimate the sensitivity differences in human populations. It is also often not appreciated that the outcome of probabilistic approaches to the multiplication of sub-factors is dependent on the choice of probability distributions. Therefore, the idea that default uncertainty factors are overly conservative worst-case scenarios which can account both for the lack of statistical power in animal experiments and protect against potential mixture effects is ill-founded. We contend that precautionary regulation should provide an incentive to generate better data and recommend adopting a pragmatic, but scientifically better founded approach to mixture risk assessment. © 2013 Martin et al.; licensee BioMed Central Ltd.Oak Foundatio

Intermittent compared to continuous real-time fMRI neurofeedback boosts control over amygdala activation

Real-time fMRI neurofeedback is a feasible tool to learn the volitional regulation of brain activity. So far, most studies provide continuous feedback information that is presented upon every volume acquisition. Although this maximizes the temporal resolution of feedback information, it may be accompanied by some disadvantages. Participants can be distracted from the regulation task due to (1) the intrinsic delay of the hemodynamic response and associated feedback and (2) limited cognitive resources available to simultaneously evaluate feedback information and stay engaged with the task. Here, we systematically investigate differences between groups presented with different variants of feedback (continuous vs. intermittent) and a control group receiving no feedback on their ability to regulate amygdala activity using positive memories and feelings. In contrast to the feedback groups, no learning effect was observed in the group without any feedback presentation. The group receiving intermittent feedback exhibited better amygdala regulation performance when compared with the group receiving continuous feedback. Behavioural measurements show that these effects were reflected in differences in task engagement. Overall, we not only demonstrate that the presentation of feedback is a prerequisite to learn volitional control of amygdala activity but also that intermittent feedback is superior to continuous feedback presentation

Feedforward and feedback pathways of nociceptive and tactile processing in human somatosensory system: A study of dynamic causal modeling of fMRI data

Nociceptive and tactile information is processed in the somatosensory system via reciprocal (i.e., feedforward and feedback) projections between the thalamus, the primary (S1) and secondary (S2) somatosensory cortices. The exact hierarchy of nociceptive and tactile information processing within this ‘thalamus-S1-S2’ network and whether the processing hierarchy differs between the two somatosensory submodalities remains unclear. In particular, two questions related to the ascending and descending pathways have not been addressed. For the ascending pathways, whether tactile or nociceptive information is processed in parallel (i.e., 'thalamus-S1′ and 'thalamus-S2′) or in serial (i.e., 'thalamus-S1-S2′) remains controversial. For the descending pathways, how corticothalamic feedback regulates nociceptive and tactile processing also remains elusive. Here, we aimed to investigate the hierarchical organization for the processing of nociceptive and tactile information in the ‘thalamus-S1-S2’ network using dynamic causal modeling (DCM) combined with high-temporal-resolution fMRI. We found that, for both nociceptive and tactile information processing, both S1 and S2 received inputs from thalamus, indicating a parallel structure of ascending pathways for nociceptive and tactile information processing. Furthermore, we observed distinct corticothalamic feedback regulations from S1 and S2, showing that S1 generally exerts inhibitory feedback regulation independent of external stimulation whereas S2 provides additional inhibition to the thalamic activity during nociceptive and tactile information processing in humans. These findings revealed that nociceptive and tactile information processing have similar hierarchical organization within the somatosensory system in the human brain

Adaptation of cortical activity to sustained pressure stimulation on the fingertip

Background Tactile adaptation is a phenomenon of the sensory system that results in temporal desensitization after an exposure to sustained or repetitive tactile stimuli. Previous studies reported psychophysical and physiological adaptation where perceived intensity and mechanoreceptive afferent signals exponentially decreased during tactile adaptation. Along with these studies, we hypothesized that somatosensory cortical activity in the human brain also exponentially decreased during tactile adaptation. The present neuroimaging study specifically investigated temporal changes in the human cortical responses to sustained pressure stimuli mediated by slow-adapting type I afferents. Methods We applied pressure stimulation for up to 15 s to the right index fingertip in 21 healthy participants and acquired functional magnetic resonance imaging (fMRI) data using a 3T MRI system. We analyzed cortical responses in terms of the degrees of cortical activation and inter-regional connectivity during sustained pressure stimulation. Results Our results revealed that the degrees of activation in the contralateral primary and secondary somatosensory cortices exponentially decreased over time and that intra- and inter-hemispheric inter-regional functional connectivity over the regions associated with tactile perception also linearly decreased or increased over time, during pressure stimulation. Conclusion These results indicate that cortical activity dynamically adapts to sustained pressure stimulation mediated by SA-I afferents, involving changes in the degrees of activation on the cortical regions for tactile perception as well as in inter-regional functional connectivity among them. We speculate that these adaptive cortical activity may represent an efficient cortical processing of tactile information.open

visual attention, syntax and emotion

Im Gegensatz zu klassischen univariaten Verfahren zur Analyse von Daten der funktionellen Magnetresonanztomographie (fMRT) erlaubt das multivariate Verfahren der Multivoxel-Muster-Analyse (MVMA) die simultane Berücksichtigung der Informationen mehrerer Bildpunkte. Somit ist das Verfahren sensitiv gegenüber Information, die in Aktivierungsmustern ausgeprägt ist, selbst dann, wenn statistische Unterschiede innerhalb einzelner Bildpunkte nicht beobachtet werden können. Unter Ausnutzung dieser Eigenschaft der MVMA werden im Rahmen dieser Dissertation aktuell diskutierte Fragestellungen der humanen neurokognitiven Forschung in verschiedenen kognitiven Modalitäten adressiert: (1) Wird in nicht-topographisch organisierten frontalen Arealen des menschlichen Gehirns Information zum Ort der Aufmerksamkeit im visuellen Feld kodiert? (2) Ist Information über die Syntax eines verbalen Stimulus bereits in frühen auditiven kortikalen oder erst in höherrangigen kognitiven Arealen kodiert? (3) Welche Gehirnareale kodieren auch außerhalb des auditorischen Kortex die emotionale Kategorie einer prosodischen Äußerung? Zur Klärung dieser Fragen wurden drei unabhängige Studien an 3-Tesla- Magnetresonanztomographen durchgeführt und die Daten mit Hilfe der MVMA ausgewertet. Im einzelnen wurden folgende Ergebnisse beobachtet: (1) Zusätzlich zu bereits bekannten topographisch organisierten parietalen und frontalen Arealen war erstmals Information über den Ort der visuellen Aufmerksamkeit im rechten mittleren frontalen Gyrus sowie dem rechten ventrolateralen präfrontalen Kortex nachweisbar. Dies unterstützt bestehende Theorien bezüglich eines „Filter“-Signals, das an der Steuerung der visuellen Aufmerksamkeit beteiligt ist. (2) Frühe auditorische Areale kodieren zwar für saliente perzeptuelle Eigenschaften von akustischen Stimuli, Informationen bezüglich der Syntax verbaler Äußerungen sind aber erst in höher-kognitiven und linkslateralisierten Arealen enthalten. (3) Mit Hilfe der MVMA ist in einem aus operculofrontalen und temporalen Strukturen bestehenden Netzwerk und damit auch in Arealen außerhalb des auditorischen Kortex der Nachweis von Information über den Emotionsgehalt perzipierter prosodischer Ausdrücke gelungen. Diese Ergebnisse bestätigen und untermauern bisherige Erkenntnisse zur Beteiligung operculofrontaler Strukturen an emotionaler Kommunikation. Insgesamt belegen die vorgestellten Studien, daß im menschlichen Gehirn Informationen bezüglich der untersuchten experimentellen Bedingungen in lokalen Aktivierungsmustern kodiert sind. Die vorgelegten Arbeiten weisen somit das Verfahren der MVMA in Ergänzung zu klassischen Ansätzen als sensitive Methode zur Auswertung des Informationsgehalts humaner fMRT-Signale multipler kognitiver Modalitäten aus.Contrary to classical univariate analysis of functional magnetic resonance imaging (fMRI) data, the approach of multivariate pattern analysis (MVPA) allows to gather information simultaneously from many voxels. Thus, MVPA is not only sensitive to statistically significant signal changes at single voxels but also to information encoded in activation patterns. Within the framework of my dissertation, MVPA was used to address current issues in the field of human cognitive neuroscience: (1) Do non-topographic human frontal brain areas encode for the locus of visual attention? (2) Do early, or only later, auditory cortical areas encode for the syntax of verbal stimuli? (3) Which brain areas beyond the auditory cortex do encode the emotion of a prosodic utterance? In order to give answers to these questions, three independent data sets were acquired at 3-Tesla magnetic resonance scanners and, hence, analysed by MVPA. The following results were observed: (1) We found information about the locus of visual attention not only in well-known topographic parietal and frontal brain areas but also in the right middle frontal gyrus and the ventrolateral prefrontal cortex. This first-time observation supports the theory of a filter signal that is involved in the control of visual spatial attention. (2) Early auditory brain areas encode for the perceptual saliency of auditory stimuli. However, information about the syntax of a verbal utterance could only be found in higher cognitive and left lateralized brain areas. (3) MVPA shows a network of operculofrontal and temporal brain areas that encodes for the emotion of a prosodic utterance. These findings beyond the auditory cortex support previous hypotheses about an involvement of the operculofrontal cortex in emotional communication. The three presented studies provide evidence that cognitive information is encoded in local activation patterns in the human brain. In addition to classical analysis of fMRI data, MVPA serves accordingly as a sensitive analysis tool for the informational content of human fMRI signals from multiple cognitive modalities

Elektro-Hybridantriebe fuer Strassenfahrzeuge

TIB Hannover: FR 3841 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman