ABSTRACT Structural connections (SC) between distant regions of the brain support synchronized function known as functional connectivity (FC) and give rise to the large-scale brain networks that enable cognition and behavior. Understanding how SC enables FC is important to understand how injuries to structural connections may alter brain function and cognition. Previous work evaluating whole-brain SC-FC relationships showed that SC explained FC well in unimodal visual and motor areas, but only weakly in association areas, suggesting a unimodal-heteromodal gradient organization of SC-FC coupling. However, this work was conducted in group-averaged SC/FC data. Thus, it could not account for inter-individual variability in the locations of cortical areas and white matter tracts. We evaluated the correspondence of SC and FC within three highly sampled healthy participants. For each participant, we collected 78 minutes of diffusion-weighted MRI for SC and 360 minutes of resting state fMRI for FC. We found that FC was best explained by SC in visual and motor systems, as well as in anterior and posterior cingulate regions. A unimodal-to-heteromodal gradient could not fully explain SC-FC coupling. We conclude that the SC-FC coupling of the anterior-posterior cingulate circuit is more similar to unimodal areas than to heteromodal areas. SIGNIFICANCE STATEMENT Structural connections between distant regions of the human brain support networked function that enables cognition and behavior. Improving our understanding of how structure enables function could allow better insight into how brain disconnection injuries impair brain function. Previous work using neuroimaging suggested that structure-function relationships vary systematically across the brain, with structure better explaining function in basic visual/motor areas than in higher-order areas. However, this work was conducted in group-averaged data, which may obscure details of individual-specific structure-function relationships. Using individual-specific densely sampled neuroimaging data, we found that in addition to visual/motor regions, structure strongly predicts function in specific circuits of the higher-order cingulate gyrus. The cingulate’s structure-function relationship suggests that its organization may be unique among higher-order cortical regions.
Abstract Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics. TS is complex, with symptoms that involve sensory, motor, and top-down control processes and that fluctuate over the course of development. While many have studied atypical brain structure and function associated with TS, the neural substrates supporting the complex range and time-course of symptoms is largely understudied. Here, we used functional connectivity MRI to examine functional networks across the whole-brain in children and adults with TS. To investigate the functional neuroanatomy of childhood and adulthood TS, we separately considered the sets of connections within each functional network and those between each pair of functional networks. We tested whether developmental stage (child, adult), diagnosis (TS, control), or an interaction between these factors was present among these connections. We found that developmental changes for most functional networks in TS were unaltered (i.e., developmental differences in TS were similar to those in typically developing children and adults). However, there were several within-network and cross-network connections that exhibited either “divergent” or “attenuated” development in TS. Connections involving the somatomotor, cingulo-opercular, auditory, dorsal attention, and default mode networks diverged from typical development in TS, demonstrating enhanced functional connectivity in adulthood TS. In contrast, connections involving the basal ganglia, thalamus, cerebellum, auditory, visual, reward, and ventral attention networks showed attenuated developmental differences in TS. These results suggest that adulthood TS is characterized by increased functional connectivity among functional networks that support cognitive control and attention, which may be implicated in suppressing, producing, and attending to tics. In contrast, subcortical systems that have been implicated in the initiation and production of tics may be immature in adulthood TS. Jointly, our results reveal how several cortical and subcortical functional networks interact and differ across development in TS.
Tics manifest as brief, purposeless and unintentional movements or noises that, for many individuals, can be suppressed temporarily with effort. Previous work has hypothesized that the chaotic temporal nature of tics could possess an inherent fractality, that is, have neighbour-to-neighbour correlation at all levels of timescale. However, demonstrating this phenomenon has eluded researchers for more than two decades, primarily because of the challenges associated with estimating the scale-invariant, power law exponent—called the fractal dimension D f —from fractional Brownian noise. Here, we confirm this hypothesis and establish the fractality of tics by examining two tic time series datasets collected 6–12 months apart in children with tics, using random walk models and directional statistics. We find that D f is correlated with tic severity as measured by the YGTTS total tic score, and that D f is a sensitive parameter in examining the effect of several tic suppression conditions on the tic time series. Our findings pave the way for using the fractal nature of tics as a robust quantitative tool for estimating tic severity and treatment effectiveness, as well as a possible marker for differentiating typical from functional tics.
The child with recent onset of tics is a common patient in a pediatrics or child neurology practice. If the child’s first tic was less than a year in the past, the diagnosis is usually Provisional Tic Disorder (PTD). Published reviews by experts reveal substantial consensus on prognosis in this situation: the tics will almost always disappear in a few months, having remained mild while they lasted. Surprisingly, however, the sparse existing data may not support these opinions.PTD may have just as much importance for science as for clinical care. It provides an opportunity to prospectively observe the spontaneous remission of tics. Such prospective studies may aid identification of genes or biomarkers specifically associated with remission rather than onset of tics. A better understanding of tic remission may also suggest novel treatment strategies for Tourette syndrome, or may lead to secondary prevention of tic disorders.This review summarizes the limited existing data on the epidemiology, phenomenology, and outcome of PTD, highlights areas in which prospective study is sorely needed, and proposes that tic disorders may completely remit much less often than is generally believed.
Previous studies of brain structure in Tourette syndrome (TS) have produced mixed results, and most had modest sample sizes. In the present multicenter study, we used structural magnetic resonance imaging (MRI) to compare 103 children and adolescents with TS to a well-matched group of 103 children without tics. We applied voxel-based morphometry methods to test gray matter (GM) and white matter (WM) volume differences between diagnostic groups, accounting for MRI scanner and sequence, age, sex and total GM+WM volume. The TS group demonstrated lower WM volume bilaterally in orbital and medial prefrontal cortex, and greater GM volume in posterior thalamus, hypothalamus and midbrain. These results demonstrate evidence for abnormal brain structure in children and youth with TS, consistent with and extending previous findings, and they point to new target regions and avenues of study in TS. For example, as orbital cortex is reciprocally connected with hypothalamus, structural abnormalities in these regions may relate to abnormal decision making, reinforcement learning or somatic processing in TS.
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