Task control signals in pediatric tourette syndrome show evidence of immature and anomalous functional activity.

Tourette Syndrome (TS) is a pediatric movement disorder that may affect control signaling in the brain. Previous work has proposed a dual-networks architecture of control processing involving a task-maintenance network and an adaptive control network (Dosenbach et al., 2008). A prior resting-state functional connectivity MRI (rs-fcMRI) analysis in TS has revealed functional immaturity in both putative control networks, with "anomalous" correlations (i.e., correlations outside the typical developmental range) limited to the adaptive control network (Church et al., 2009). The present study used functional MRI (fMRI) to study brain activity related to adaptive control (by studying start-cues signals), and to task-maintenance (by studying signals sustained across a task set). Two hypotheses from the previous rs-fcMRI results were tested. First, adaptive control (i.e., start-cue) activity will be altered in TS, including activity inconsistent with typical development ("anomalous"). Second, group differences found in task-maintenance (i.e., sustained) activity will be consistent with functional immaturity in TS. We examined regions found through a direct comparison of adolescents with and without TS, as well as regions derived from a previous investigation that showed differences between unaffected children and adults. The TS group showed decreased start-cue signal magnitude in regions where start-cue activity is unchanged over typical development, consistent with anomalous adaptive control. The TS group also had higher magnitude sustained signals in frontal cortex regions that overlapped with regions showing differences over typical development, consistent with immature task-maintenance in TS. The results demonstrate task-related fMRI signal differences anticipated by the atypical functional connectivity found previously in adolescents with TS, strengthening the evidence for functional immaturity and anomalous signaling in control networks in adolescents with TS.

Distinct brain networks for adaptive and stable task control in humans.

Control regions in the brain are thought to provide signals that configure the brain's 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.

A method for using blocked and event-related fMRI data to study "resting state" functional connectivity.

Resting state functional connectivity MRI (fcMRI) has become a particularly useful tool for studying regional relationships in typical and atypical populations. Because many investigators have already obtained large data sets of task-related fMRI, the ability to use this existing task data for resting state fcMRI is of considerable interest. Two classes of data sets could potentially be modified to emulate resting state data. These data sets include: (1) "interleaved" resting blocks from blocked or mixed blocked/event-related sets, and (2) residual timecourses from event-related sets that lack rest blocks. Using correlation analysis, we compared the functional connectivity of resting epochs taken from a mixed blocked/event-related design fMRI data set and the residuals derived from event-related data with standard continuous resting state data to determine which class of data can best emulate resting state data. We show that, despite some differences, the functional connectivity for the interleaved resting periods taken from blocked designs is both qualitatively and quantitatively very similar to that of "continuous" resting state data. In contrast, despite being qualitatively similar to "continuous" resting state data, residuals derived from event-related design data had several distinct quantitative differences. These results suggest that the interleaved resting state data such as those taken from blocked or mixed blocked/event-related fMRI designs are well-suited for resting state functional connectivity analyses. Although using event-related data residuals for resting state functional connectivity may still be useful, results should be interpreted with care.

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.

Comparison of sustained and transient activity in children and adults using a mixed blocked/event-related fMRI design.

The ability to make direct comparisons between adult and child neuroimaging data is important to the study of the neural basis of cognitive development. Recent fMRI studies in adults have used mixed blocked/event-related designs to extract activity consistent with separable sustained, task-related processes and transient, trial-related processes. Because brain regions with different time courses of activity may have different roles in cognitive processing, the ability to distinguish between sustained and transient signals would contribute to understanding the functional roles of regions involved in cognitive processing. The developmental profile of such activity would give insight into how cognitive processing develops over time. The purpose of this study was to assess the utility of the mixed design to detect and dissociate sustained and transient activity in children, and to determine if the time courses or magnitudes of the extracted signals differ from those extracted from adults. An fMRI experiment was performed on 10 adults and 10 children (ages 7-8) using counterphase flickering checkerboard stimuli that produced sustained, transient, and a combination of sustained and transient responses in visual cortex. Analyses were performed using the general linear model (GLM) assuming a shape for sustained effects, but not for transient effects. In visual cortex, neither transient nor sustained effects showed significant between-group differences. For both groups, flickering checkerboard stimuli produced robust responses in visual cortex contralateral but not ipsilateral to the stimulus. Results extend the feasibility of direct statistical comparison of adults and children; mixed designs provide a means to examine neural activity in both adults and children related to sustained, task-level processes, likely related to task-level control.