Neural indices of improved attentional modulation over middle childhood.

The ability to control the focus of attention relies on top-down modulation of cortical activity in areas involved in stimulus processing, and this ability is critical for maintaining items in working memory in the presence of distraction. Prior research demonstrates that children are less capable of focusing attention, relative to adults, and that this ability develops significantly during middle childhood. Here, using fMRI and a face/scene working memory task adapted from Gazzaley and colleagues (Gazzaley et al. 2005), we compared top-down modulation in fifteen children (aged 8-13) and fifteen young adults (aged 19-26). Replicating prior results, in young adults, attention to scenes modulated activity in the parahippocampal place area (PPA). In addition, modulation of PPA activity increased as a function of age in children. PPA activity was also related to performance in this group, on the working memory task as well on a test of subsequent memory. Dorsolateral PFC also demonstrated increasing task-specific activation, as a function of age, in children. The present findings support the idea that children's reduced ability to maintain items in working memory, especially in the presence of distraction, is driven by weaker top-down modulation of activity in areas involved in stimulus processing.

Examining cortisol rhythmicity and responsivity to stress in children with Tourette syndrome.

BACKGROUND: Tourette syndrome (TS) is characterized by motor and vocal tics, which are often exacerbated by stress. The hypothalamic-pituitary-adrenocortical (HPA) axis, a major stress response system is thus of interest for understanding TS. METHODS: Diurnal cortisol rhythms were estimated in medication-free children 7-13 years with TS (N=20) and healthy age-matched controls (N=16). Salivary samples were collected on 3 consecutive days from the home. HPA responsivity was assessed by examining cortisol in response to a mock and real MRI scan. RESULTS: The results of diurnal rhythmicity revealed a trend showing marginally lower evening cortisol for the TS group. By contrast, the TS group had higher cortisol levels in response to the stressor. There were strong, negative correlations between evening cortisol and tic severity as well as diurnal cortisol and anxiety. CONCLUSIONS: The children with TS showed increased cortisol in response to the MRI environment, supporting a model of enhanced HPA responsivity. The lower evening cortisol may be the result of chronic daily stress. Alternatively, the negative associations between cortisol and reported anxiety and tics may reflect biologically based anxiolytic properties of tic expression. Taken together, the results clearly implicate involvement of the HPA axis in the neuropathology of TS.

Neural correlates of tic severity and cognitive control in children with Tourette syndrome.

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by involuntary motor and phonic tics. It is hypothesized that excess dopamine leads to an imbalance in the pathways through the basal ganglia, resulting in unchecked movements via thalamic disinhibition. It has been unclear whether TS is associated with cognitive control deficits as well as pure motor control deficits, or whether cognitive deficits are associated with the presence of comorbid conditions. Furthermore, little is known about the neural underpinnings of TS in childhood, prior to the long-term effects of medication on brain function. Here, children with TS and typically developing children performed a cognitive control task during event-related fMRI data acquisition. The study included 18 native English-speaking 7-13-year-old children with TS (M = 10.42; 15 males), and 19 healthy, age-matched native English-speaking volunteers (M = 10.33; 11 males). The task involved three separate manipulations of cognitive control. Behaviourally, higher tic severity was correlated with slower task performance on the most demanding task conditions. Neurally, higher tic severity was associated with enhanced activation of dopaminergic nuclei (substantia nigra/ventral tegmental area) and cortical, striatal and thalamic regions in the direct pathway. Heightened tic severity was also associated with greater engagement of the subthalamic nucleus area, suggestive of a compensatory mechanism. Overall, patients engaged left prefrontal cortex more strongly than typicals during task performance. These data suggest that children aged 7-13 unmedicated for TS exhibit increased activation in the direct pathway through the basal ganglia, as well as increased compensatory activation in prefrontal cortex and the subthalamic nucleus.