S.E. Petersen

Characterizing the Hemodynamic Response: Effects of Presentation Rate, Sampling Procedure, and the Possibility of Ordering Brain Activity Based on Relative Timing

Rapid-presentation event-related functional MRI (ER-fMRI) allows neuroimaging methods based on hemodynamics to employ behavioral task paradigms typical of cognitive settings. However, the sluggishness of the hemodynamic response and its variance provide constraints on how ER-fMRI can be applied. In a series of two studies, estimates of the hemodynamic response in or near the primary visual and motor cortices were compared across various paradigms and sampling procedures to determine the limits of ER-fMRI procedures and, more generally, to describe the behavior of the hemodynamic response. The temporal profile of the hemodynamic response was estimated across overlapping events by solving a set of linear equations within the general linear model. No assumptions about the shape were made in solving the equations. Following estimation of the temporal profile, the amplitude and timing were modeled using a gamma function. Results indicated that (1) within a region, for a given subject, estimation of the hemodynamic response is extremely stable for both amplitude (r(2) = 0.98) and time to peak (r(2) = 0.95), from one series of measurements to the next, and slightly less stable for estimation of time to onset (r(2) = 0.60). (2) As the trial presentation rate changed (from those spaced 20 s apart to temporally overlapping trials), the hemodynamic response amplitude showed a small, but significant, decrease. Trial onsets spaced (on average) 5 s apart showed a 17-25% reduction in amplitude compared to those spaced 20 s apart. Power analysis indicated that the increased number of trials at fast rates outweighs this decrease in amplitude if statistically reliable response detection is the goal. (3) Knowledge of the amplitude and timing of the hemodynamic response in one region failed to predict those properties in another region, even for within-subject comparisons. (4) Across subjects, the amplitude of the response showed no significant correlation with timing of the response, for either time-to-onset or time-to-peak estimates. (5) The within-region stability of the response was sufficient to allow offsets in the timing of the response to be detected that were under a second, placing event-related fMRI methods in a position to answer questions about the change in relative timing between regions.

The Human Connectome Project: A data acquisition perspective

The Human Connectome Project (HCP) is an ambitious 5-year effort to characterize brain connectivity and function and their variability in healthy adults. This review summarizes the data acquisition plans being implemented by a consortium of HCP investigators who will study a population of 1200 subjects (twins and their non-twin siblings) using multiple imaging modalities along with extensive behavioral and genetic data. The imaging modalities will include diffusion imaging (dMRI), resting-state fMRI (R-fMRI), task-evoked fMRI (T-fMRI), T1- and T2-weighted MRI for structural and myelin mapping, plus combined magnetoencephalography and electroencephalography (MEG/EEG). Given the importance of obtaining the best possible data quality, we discuss the efforts underway during the first two years of the grant (Phase I) to refine and optimize many aspects of HCP data acquisition, including a new 7T scanner, a customized 3T scanner, and improved MR pulse sequences.

Resting-state fMRI in the Human Connectome Project

Resting-state functional magnetic resonance imaging (rfMRI) allows one to study functional connectivity in the brain by acquiring fMRI data while subjects lie inactive in the MRI scanner, and taking advantage of the fact that functionally related brain regions spontaneously co-activate. rfMRI is one of the two primary data modalities being acquired for the Human Connectome Project (the other being diffusion MRI). A key objective is to generate a detailed in vivo mapping of functional connectivity in a large cohort of healthy adults (over 1000 subjects), and to make these datasets freely available for use by the neuroimaging community. In each subject we acquire a total of 1h of whole-brain rfMRI data at 3 T, with a spatial resolution of 2×2×2 mm and a temporal resolution of 0.7s, capitalizing on recent developments in slice-accelerated echo-planar imaging. We will also scan a subset of the cohort at higher field strength and resolution. In this paper we outline the work behind, and rationale for, decisions taken regarding the rfMRI data acquisition protocol and pre-processing pipelines, and present some initial results showing data quality and example functional connectivity analyses.

Function in the human connectome: task-fMRI and individual differences in behavior.

The primary goal of the Human Connectome Project (HCP) is to delineate the typical patterns of structural and functional connectivity in the healthy adult human brain. However, we know that there are important individual differences in such patterns of connectivity, with evidence that this variability is associated with alterations in important cognitive and behavioral variables that affect real world function. The HCP data will be a critical stepping-off point for future studies that will examine how variation in human structural and functional connectivity play a role in adult and pediatric neurological and psychiatric disorders that account for a huge amount of public health resources. Thus, the HCP is collecting behavioral measures of a range of motor, sensory, cognitive and emotional processes that will delineate a core set of functions relevant to understanding the relationship between brain connectivity and human behavior. In addition, the HCP is using task-fMRI (tfMRI) to help delineate the relationships between individual differences in the neurobiological substrates of mental processing and both functional and structural connectivity, as well as to help characterize and validate the connectivity analyses to be conducted on the structural and functional connectivity data. This paper describes the logic and rationale behind the development of the behavioral, individual difference, and tfMRI batteries and provides preliminary data on the patterns of activation associated with each of the fMRI tasks, at both group and individual levels.

Functional MRI Studies of Word-Stem Completion: Reliability Across Laboratories and Comparison to Blood Flow Imaging With PET

Functional magnetic resonance imaging (fMRI) based on blood oxygen level‐dependent (BOLD) contrast has become an increasingly popular technique for mapping the brain. The relationship between BOLD‐fMRI imaging and imaging of blood flow activation with positron emission tomography (PET) remains unclear. Moreover, BOLD imaging strategies and analysis procedures vary widely across laboratories. To examine the relationship between these different methods, we compared brain activation maps of a word‐stem completion task obtained both using PET and using fMRI across two separate institutions (Washington University and Massachusetts General Hospital) with different acquisitions (gradient‐refocused echo and asymmetric spin echo) and different analysis techniques. Overall, activation maps were highly similar across both fMRI methods and PET. A set of activated brain areas, in consistent locations in Talairach atlas space, were identified across all three studies, including visual striate and extrastriate, left prefrontal, supplementary motor area (SMA), and right cerebellar areas. Decreases in activation were also consistently observed in medial parietal, posterior insular, and medial inferior frontal areas. Some differences were noted that may be related to the silent performance of the task with fMRI. The largely consistent results suggest that comparisons can be made appropriately across imaging modalities and laboratory methods. A further implication of the consistencies, which extended to both increases and decreases in signal, is that the underlying brain physiology leading to BOLD contrast may be more similar to blood flow than originally appreciated. Hum. Brain Mapping 6:203–215, 1998.

Right Anterior Prefrontal Cortex Activation during Semantic Monitoring and Working Memory

Areas of the adult human brain used for semantic monitoring were identified using positron emission tomography. For a series of tasks, subjects viewed a list of familiar English nouns and monitored the words for names of dangerous animals. The monitoring task used here also contained an instruction to keep track of the number or percentage of targets for report after the scan. Surface characteristics of the tasks such as stimulus rate, number of targets, and whether subjects were asked to count or estimate the number of targets were varied across multiple conditions within and between subjects. A passive word viewing condition was used as the control in all subjects. Reliable activations were identified in anterior and dorsal right prefrontal cortex [Brodmann areas (BA) 9 and 10] and left extrastriate cortex. The right prefrontal cortical locations are similar to areas that have been activated during many episodic memory tasks. This surprising finding led to a thorough review of the literature for examples of other activations within 16-mm vector distance of this right prefrontal area. Activations in the vicinity of right BA10 due to episodic memory retrieval, to various forms of working memory, and to miscellaneous tasks were found. The right prefrontal activations in the current experiment and the additional working memory and miscellaneous tasks demonstrate that, although right BA10 is routinely activated by episodic retrieval tasks, it is not uniquely activated by episodic retrieval tasks.

PET Studies of Parietal Involvement in Spatial Attention: Comparison of Different Task Types

Five experiments are described that concern the mechanisms that direct attention to spatial and non-spatial features of a stimulus and the effects that attention has on the visual systems analysis of that stimulus. Shifts of attention from one spatial location to another activated the superior parietal lobe and this activation was fairly independent of the task performed on the attended object, the response made to the attended object, and whether the shift of attention was controlled endogenously or exogenously. Maintaining attention tonically on a location or a particular visual feature such as shape, colour or motion did not produce a superior parietal response. Tonic attention to a feature (colour, shape, motion) or location, however, did produce enhancements in the response of various regions that are probably specialized for processing the attended visual feature. The activation of superior parietal cortex during shifts of spatial attention as well as the activation of parietal-occipital cortex when attention is tonically maintained on a location suggest that the parietal cortex plays an important role in spatial computations.

Comparison of brain activation during word retrieval done silently and aloud using fMRI.

Using functional MRI we compared the patterns of activation in an effortful word retrieval task (stem completion) performed both silently and aloud. The silent and overt conditions showed expected differences in activation magnitude in regions such as primary motor cortex. Some regions, such as frontal operculum and dorsolateral frontal cortex, showed similar activation magnitude across conditions. Thalamus was more active on the left in both conditions and showed a symmetric drop in activity in the silent compared with the overt condition. Putamen was also more active in the overt condition and showed a larger decrease in activity on the right than on the left in the silent compared with the overt condition. Thus it appears that silent and overt performance of this task engage the thalamus and putamen in different ways.

An assessment of functional-anatomical variability in neuroimaging studies.

A key issue in functional neuroimaging is the amount of variability produced by individual differences in anatomical and functional patterns of activation. This variability affects summed images created when responses are averaged across subjects as well as comparisons between groups of subjects.

Automated method for extracting response latencies of subject vocalizations in event-related fMRI experiments

For functional magnetic resonance imaging studies of the neural substrates of language, the ability to have subjects performing overt verbal responses while in the scanner environment is important for several reasons. Most directly, overt responses allow the investigator to measure the accuracy and reaction time of the behavior. One problem, however, is that magnetic resonance gradient noise obscures the audio recordings made of voice responses, making it difficult to discern subject responses and to calculate reaction times. ASSERT (Adaptive Spectral Subtraction for Extracting Response Times), an algorithm for removing MR gradient noise from audio recordings of subject responses, is described here. The signal processing improves intelligibility of the responses and also allows automated extraction of reaction times. The ASSERT-derived response times were comparable to manually measured times with a mean difference of -8.75 ms (standard deviation of difference = 26.2 ms). These results support the use of ASSERT for the purpose of extracting response latencies and scoring overt verbal responses.