A novel method of combining blood oxygenation and blood flow sensitive magnetic resonance imaging techniques to measure the cerebral blood flow and oxygen metabolism responses to an unknown neural stimulus.

Simultaneous implementation of magnetic resonance imaging methods for Arterial Spin Labeling (ASL) and Blood Oxygenation Level Dependent (BOLD) imaging makes it possible to quantitatively measure the changes in cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO(2)) that occur in response to neural stimuli. To date, however, the range of neural stimuli amenable to quantitative analysis is limited to those that may be presented in a simple block or event related design such that measurements may be repeated and averaged to improve precision. Here we examined the feasibility of using the relationship between cerebral blood flow and the BOLD signal to improve dynamic estimates of blood flow fluctuations as well as to estimate metabolic-hemodynamic coupling under conditions where a stimulus pattern is unknown. We found that by combining the information contained in simultaneously acquired BOLD and ASL signals through a method we term BOLD Constrained Perfusion (BCP) estimation, we could significantly improve the precision of our estimates of the hemodynamic response to a visual stimulus and, under the conditions of a calibrated BOLD experiment, accurately determine the ratio of the oxygen metabolic response to the hemodynamic response. Importantly we were able to accomplish this without utilizing a priori knowledge of the temporal nature of the neural stimulus, suggesting that BOLD Constrained Perfusion estimation may make it feasible to quantitatively study the cerebral metabolic and hemodynamic responses to more natural stimuli that cannot be easily repeated or averaged

Task-related edge density (TED) - a new method for revealing large-scale network formation in fMRI data of the human brain

The formation of transient networks in response to external stimuli or as a reflection of internal cognitive processes is a hallmark of human brain function. However, its identification in fMRI data of the human brain is notoriously difficult. Here we propose a new method of fMRI data analysis that tackles this problem by considering large-scale, task-related synchronisation networks. Networks consist of nodes and edges connecting them, where nodes correspond to voxels in fMRI data, and the weight of an edge is determined via task-related changes in dynamic synchronisation between their respective times series. Based on these definitions, we developed a new data analysis algorithm that identifies edges in a brain network that differentially respond in unison to a task onset and that occur in dense packs with similar characteristics. Hence, we call this approach "Task-related Edge Density" (TED). TED proved to be a very strong marker for dynamic network formation that easily lends itself to statistical analysis using large scale statistical inference. A major advantage of TED compared to other methods is that it does not depend on any specific hemodynamic response model, and it also does not require a presegmentation of the data for dimensionality reduction as it can handle large networks consisting of tens of thousands of voxels. We applied TED to fMRI data of a fingertapping task provided by the Human Connectome Project. TED revealed network-based involvement of a large number of brain areas that evaded detection using traditional GLM-based analysis. We show that our proposed method provides an entirely new window into the immense complexity of human brain function.Comment: 21 pages, 11 figure

Dynamic models in fMRI

Most statistical methods for assessing activated voxels in fMRI experiments are based on correlation or regression analysis. In this context the main assumptions are that the baseline can be described by a few known basis-functions or variables and that the effect of the stimulus, i.e. the activation, stays constant over time. As these assumptions are in many cases neither necessary nor correct, a new dynamic approach that does not depend on those suppositions will be presented. This allows for simultaneous nonparametric estimation of the baseline as well as the time-varying effect of stimulation. This method of estimating the stimulus related areas of the brain furthermore provides the possibility of an analysis of the temporal and spatial development of the activation within an fMRI-experiment

Differential recruitment of brain networks following route and cartographic map learning of spatial environments.

An extensive neuroimaging literature has helped characterize the brain regions involved in navigating a spatial environment. Far less is known, however, about the brain networks involved when learning a spatial layout from a cartographic map. To compare the two means of acquiring a spatial representation, participants learned spatial environments either by directly navigating them or learning them from an aerial-view map. While undergoing functional magnetic resonance imaging (fMRI), participants then performed two different tasks to assess knowledge of the spatial environment: a scene and orientation dependent perceptual (SOP) pointing task and a judgment of relative direction (JRD) of landmarks pointing task. We found three brain regions showing significant effects of route vs. map learning during the two tasks. Parahippocampal and retrosplenial cortex showed greater activation following route compared to map learning during the JRD but not SOP task while inferior frontal gyrus showed greater activation following map compared to route learning during the SOP but not JRD task. We interpret our results to suggest that parahippocampal and retrosplenial cortex were involved in translating scene and orientation dependent coordinate information acquired during route learning to a landmark-referenced representation while inferior frontal gyrus played a role in converting primarily landmark-referenced coordinates acquired during map learning to a scene and orientation dependent coordinate system. Together, our results provide novel insight into the different brain networks underlying spatial representations formed during navigation vs. cartographic map learning and provide additional constraints on theoretical models of the neural basis of human spatial representation

The neural basis of responsibility attribution in decision-making

Social responsibility links personal behavior with societal expectations and plays a key role in affecting an agent's emotional state following a decision. However, the neural basis of responsibility attribution remains unclear. In two previous event-related brain potential (ERP) studies we found that personal responsibility modulated outcome evaluation in gambling tasks. Here we conducted a functional magnetic resonance imaging (fMRI) study to identify particular brain regions that mediate responsibility attribution. In a context involving team cooperation, participants completed a task with their teammates and on each trial received feedback about team success and individual success sequentially. We found that brain activity differed between conditions involving team success vs. team failure. Further, different brain regions were associated with reinforcement of behavior by social praise vs. monetary reward. Specifically, right temporoparietal junction (RTPJ) was associated with social pride whereas dorsal striatum and dorsal anterior cingulate cortex (ACC) were related to reinforcement of behaviors leading to personal gain. The present study provides evidence that the RTPJ is an important region for determining whether self-generated behaviors are deserving of praise in a social context

Inverse transformed encoding models - A solution to the problem of correlated trial-by-trial parameter estimates in fMRI decoding

Techniques of multivariate pattern analysis (MVPA) can be used to decode the discrete experimental condition or a continuous modulator variable from measured brain activity during a particular trial. In functional magnetic resonance imaging (fMRI), trial-wise response amplitudes are sometimes estimated from the measured signal using a general linear model (GLM) with one onset regressor for each trial. When using rapid event-related designs with trials closely spaced in time, those estimates are highly variable and serially correlated due to the temporally extended shape of the hemodynamic response function (HRF). Here, we describe inverse transformed encoding modelling (ITEM), a principled approach of accounting for those serial correlations and decoding from the resulting estimates, at low computational cost and with no loss in statistical power. We use simulated data to show that ITEM outperforms the current standard approach in terms of decoding accuracy and analyze empirical data to demonstrate that ITEM is capable of visual reconstruction from fMRI signals

Revisiting Multi-Subject Random Effects in fMRI: Advocating Prevalence Estimation

Random Effects analysis has been introduced into fMRI research in order to generalize findings from the study group to the whole population. Generalizing findings is obviously harder than detecting activation in the study group since in order to be significant, an activation has to be larger than the inter-subject variability. Indeed, detected regions are smaller when using random effect analysis versus fixed effects. The statistical assumptions behind the classic random effects model are that the effect in each location is normally distributed over subjects, and "activation" refers to a non-null mean effect. We argue this model is unrealistic compared to the true population variability, where, due to functional plasticity and registration anomalies, at each brain location some of the subjects are active and some are not. We propose a finite-Gaussian--mixture--random-effect. A model that amortizes between-subject spatial disagreement and quantifies it using the "prevalence" of activation at each location. This measure has several desirable properties: (a) It is more informative than the typical active/inactive paradigm. (b) In contrast to the hypothesis testing approach (thus t-maps) which are trivially rejected for large sample sizes, the larger the sample size, the more informative the prevalence statistic becomes. In this work we present a formal definition and an estimation procedure of this prevalence. The end result of the proposed analysis is a map of the prevalence at locations with significant activation, highlighting activations regions that are common over many brains

Brain connectivity Patterns Dissociate action of specific Acupressure Treatments in Fatigued Breast cancer survivors

Funding This work was supported by grants R01 CA151445 and 2UL1 TR000433-06 from the National Institutes of Health. The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. We thank the expert assistance by Dr. Bradley Foerster in acquisition of 1H-MRS and fMRI data.Peer reviewedPublisher PD

Encoding of temporal probabilities in the human brain

Anticipating the timing of future events is a necessary precursor to preparing actions and allocating resources to sensory processing. This requires elapsed time to be represented in the brain and used to predict the temporal probability of upcoming events. While neuropsychological, imaging, magnetic stimulation studies, and single-unit recordings implicate the role of higher parietal and motor-related areas in temporal estimation, the role of earlier, purely sensory structures remains more controversial. Here we demonstrate that the temporal probability of expected visual events is encoded not by a single area but by a wide network that importantly includes neuronal populations at the very earliest cortical stages of visual processing. Moreover, we show that activity in those areas changes dynamically in a manner that closely accords with temporal expectations