Francis M. Miezin

A PET study of visuospatial attention

Positron emission tomography (PET) was used to identify the neural systems involved in shifting spatial attention to visual stimuli in the left or right visual field along foveofugal or foveocentric directions. Psychophysical evidence indicated that stimuli at validly cued locations were responded to faster than stimuli at invalidly cued locations. Reaction times to invalid probes were faster when they were presented in the same than in the opposite direction of an ongoing attention movement. PET evidence indicated that superior parietal and superior frontal cortex were more active when attention was shifted to peripheral locations than when maintained at the center of gaze. Both regions encoded the visual field and not the direction of an attention shift. In the right superior parietal lobe, two distinct responses were localized for attention to left and right visual field. Finally, the superior parietal region was active when peripheral locations were selected on the basis of cognitive or sensory cues independent of the execution of an overt response. The frontal region was active only when responses were made to stimuli at selected peripheral locations. These findings indicate that parietal and frontal regions control different aspects of spatial selection. The functional asymmetry in superior parietal cortex may be relevant for the pathophysiology of unilateral neglect.

Distinct brain networks for adaptive and stable task control in humans

Control regions in the brain are thought to provide signals that configure the brains moment-to-moment information processing. Previously, we identified regions that carried signals related to task-control initiation, maintenance, and adjustment. Here we characterize the interactions of these regions by applying graph theory to resting state functional connectivity MRI data. In contrast to previous, more unitary models of control, this approach suggests the presence of two distinct task-control networks. A frontoparietal network included the dorsolateral prefrontal cortex and intraparietal sulcus. This network emphasized start-cue and error-related activity and may initiate and adapt control on a trial-by-trial basis. The second network included dorsal anterior cingulate/medial superior frontal cortex, anterior insula/frontal operculum, and anterior prefrontal cortex. Among other signals, these regions showed activity sustained across the entire task epoch, suggesting that this network may control goal-directed behavior through the stable maintenance of task sets. These two independent networks appear to operate on different time scales and affect downstream processing via dissociable mechanisms.

Common blood flow changes across visual tasks: Ii. decreases in cerebral cortex

Nine previous positron emission tomography (PET) studies of human visual information processing were reanalyzed to determine the consistency across experiments of blood flow decreases during active tasks relative to passive viewing of the same stimulus array. Areas showing consistent decreases during active tasks included posterior cingulate/precuneous (Brodmann area, BA 31/7), left (BAS 40 and 39/19) and right (BA 40) inferior parietal cortex, left dorsolateral frontal cortex (BA S), left lateral inferior frontal cortex (BA 10/47), left inferior temporal gyrus @A 20), a strip of medial frontal regions running along a dorsal-ventral axis (BAs 8, 9, 10, and 32), and the right amygdala. Experiments involving language-related processes tended to show larger decreases than nonlanguage experiments. This trend mainly reflected blood flow increases at certain areas in the passive conditions of the language experiments (relative to a fixation control in which no task stimulus was present) and slight blood flow decreases in the passive conditions of the nonlanguage experiments. When the active tasks were referenced to the fixation condition, the overall size of blood flow decreases in language and nonlanguage tasks were the same, but differences were found across cortical areas. Decreases were more pronounced in the posterior cingulate/precuneous (BAS 31/7) and right inferior parietal cortex (BA 40) during language-related tasks and more pronounced in left inferior frontal cortex (BA 10/47) during nonlanguage tasks. Blood flow decreases did not generally show significant differences across the active task states within an experiment, but a verb-generation task produced larger decreases than a read task in right and left inferior parietal lobe (BA 40) and the posterior cingulate/precuneous (BA 31/7), while the read task produced larger decreases in left lateral inferior frontal cortex (BA 10/47). These effects mirrored those found between experiments in the language-nonlanguage comparison. Consistent active minus passive decreases may reflect decreased activity caused by active task processes that generalize over tasks or increased activity caused by passive task processes that are suspended during the active tasks. Increased activity during the passive condition might reflect ongoing processes, such as unconstrained verbally mediated thoughts and monitoring of the external environment, body, and emotional state.

A Core System for the Implementation of Task Sets

When performing tasks, humans are thought to adopt task sets that configure moment-to-moment data processing. Recently developed mixed blocked/event-related designs allow task set-related signals to be extracted in fMRI experiments, including activity related to cues that signal the beginning of a task block, set-maintenance activity sustained for the duration of a task block, and event-related signals for different trial types. Data were conjointly analyzed from mixed design experiments using ten different tasks and 183 subjects. Dorsal anterior cingulate cortex/medial superior frontal cortex (dACC/msFC) and bilateral anterior insula/frontal operculum (aI/fO) showed reliable start-cue and sustained activations across all or nearly all tasks. These regions also carried the most reliable error-related signals in a subset of tasks, suggesting that the regions form a core task-set system. Prefrontal regions commonly related to task control carried task-set signals in a smaller subset of tasks and lacked convergence across signal types.

The maturing architecture of the brain's default network

In recent years, the brains “default network,” a set of regions characterized by decreased neural activity during goal-oriented tasks, has generated a significant amount of interest, as well as controversy. Much of the discussion has focused on the relationship of these regions to a “default mode” of brain function. In early studies, investigators suggested that, the brains default mode supports “self-referential” or “introspective” mental activity. Subsequently, regions of the default network have been more specifically related to the “internal narrative,” the “autobiographical self,” “stimulus independent thought,” “mentalizing,” and most recently “self-projection.” However, the extant literature on the function of the default network is limited to adults, i.e., after the system has reached maturity. We hypothesized that further insight into the networks functioning could be achieved by characterizing its development. In the current study, we used resting-state functional connectivity MRI (rs-fcMRI) to characterize the development of the brains default network. We found that the default regions are only sparsely functionally connected at early school age (7–9 years old); over development, these regions integrate into a cohesive, interconnected network.

Functional Brain Networks Develop from a “Local to Distributed” Organization

The mature human brain is organized into a collection of specialized functional networks that flexibly interact to support various cognitive functions. Studies of development often attempt to identify the organizing principles that guide the maturation of these functional networks. In this report, we combine resting state functional connectivity MRI (rs-fcMRI), graph analysis, community detection, and spring-embedding visualization techniques to analyze four separate networks defined in earlier studies. As we have previously reported, we find, across development, a trend toward ‘segregation’ (a general decrease in correlation strength) between regions close in anatomical space and ‘integration’ (an increased correlation strength) between selected regions distant in space. The generalization of these earlier trends across multiple networks suggests that this is a general developmental principle for changes in functional connectivity that would extend to large-scale graph theoretic analyses of large-scale brain networks. Communities in children are predominantly arranged by anatomical proximity, while communities in adults predominantly reflect functional relationships, as defined from adult fMRI studies. In sum, over development, the organization of multiple functional networks shifts from a local anatomical emphasis in children to a more “distributed” architecture in young adults. We argue that this “local to distributed” developmental characterization has important implications for understanding the development of neural systems underlying cognition. Further, graph metrics (e.g., clustering coefficients and average path lengths) are similar in child and adult graphs, with both showing “small-world”-like properties, while community detection by modularity optimization reveals stable communities within the graphs that are clearly different between young children and young adults. These observations suggest that early school age children and adults both have relatively efficient systems that may solve similar information processing problems in divergent ways.

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.

Development of distinct control networks through segregation and integration

Human attentional control is unrivaled. We recently proposed that adults depend on distinct frontoparietal and cinguloopercular networks for adaptive online task control versus more stable set control, respectively. During development, both experience-dependent evoked activity and spontaneous waves of synchronized cortical activity are thought to support the formation and maintenance of neural networks. Such mechanisms may encourage tighter “integration” of some regions into networks over time while “segregating” other sets of regions into separate networks. Here we use resting state functional connectivity MRI, which measures correlations in spontaneous blood oxygenation level-dependent signal fluctuations between brain regions to compare previously identified control networks between children and adults. We find that development of the proposed adult control networks involves both segregation (i.e., decreased short-range connections) and integration (i.e., increased long-range connections) of the brain regions that comprise them. Delay/disruption in the developmental processes of segregation and integration may play a role in disorders of control, such as autism, attention deficit hyperactivity disorder, and Tourettes syndrome.

Hemispheric specialization in human dorsal frontal cortex and medial temporal lobe for verbal and nonverbal memory encoding

The involvement of dorsal frontal and medial temporal regions during the encoding of words, namable line-drawn objects, and unfamiliar faces was examined using functional magnetic resonance imaging (fMRI). Robust dorsal frontal activations were observed in each instance, but lateralization was strongly dependent on the materials being encoded. Encoding of words produced left-lateralized dorsal frontal activation, whereas encoding of unfamiliar faces produced homologous right-lateralized activation. Encoding of namable objects, which are amenable to both verbal and nonverbal encoding, yielded bilateral dorsal frontal activation. A similar pattern of results was observed in the medial temporal lobe. These results indicate that regions in both hemispheres underlie human long-term memory encoding, and these regions can be engaged differentially according to the nature of the material being encoded.

Direction- and Velocity-Specific Responses from beyond the Classical Receptive Field in the Middle Temporal Visual Area (MT):

The true receptive field of more than 90% of neurons in the middle temporal visual area (MT) extends well beyond the classical receptive field (crf), as mapped with conventional bar or spot stimuli, and includes a surrounding region that is 50 to 100 times the area of the crf. These extensive surrounds are demonstrated by simultaneously stimulating the crf and the surround with moving stimuli. The surrounds commonly have directional and velocity-selective influences that are antagonistic to the response from the crf. The crfs of MT neurons are organized in a topographic representation of the visual field. Thus MT neurons are embedded in an orderly visuotopic array, but are capable of integrating local stimulus conditions within a global context. The extensive surrounds of MT neurons may be involved in figure–ground discrimination, preattentive vision, perceptual constancies, and depth perception through motion cues.