Neural substrates of self-regulatory control in children and adults with Tourette syndrome.

OBJECTIVE: To identify the neural substrate of self-regulatory control in children and adults with Tourette syndrome (TS). METHOD: We used event-related functional magnetic resonance imaging (fMRI) to study the neural correlates of cognitive self-regulation during the Simon task. Forty-two people from The Tic Disorder Specialty Clinic who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for diagnosis with TS (24 children; 18 adults) were compared with 37 control subjects (19 children; 18 adults). Patients with TS were excluded from participation if they had any Axis I psychiatric disorder other than obsessive-compulsive disorder (OCD) or attention-deficit hyperactivity disorder (ADHD) prior to the onset of TS. Control participants were excluded if they reported a history of tic disorder, OCD, ADHD, or if they met diagnostic criteria for any Axis I disorder at the time of interview. RESULTS: We detected greater overall fMRI activation in adults than in children across both diagnostic groups, primarily in frontal and striatal regions. In both groups we also detected an age-related shift away from more general cortical activation toward a more specific reliance on frontostriatal activity, a developmental correlate that was exaggerated in the TS group despite behavioural performances similar to those of control subjects. Moreover, the severity of tics correlated positively with frontal activations across age groups. CONCLUSION: Frontostriatal circuits support cognitive and behavioural control. These circuits likely contribute both to optimal performance in this self-regulatory task and to the regulation of the severity of tics. Adults with persistent TS likely possess deficient activity in these circuits, attributable to either a failure of prefrontal plasticity or to disturbances in striatal functioning.

The risks and benefits of searching for incidental findings in MRI research scans.

We weigh the presumed benefits of routinely searching all research scans for incidental findings (IFs) against its substantial risks, including false-positive and false-negative findings, and the possibility of triggering unnecessary, costly evaluations and perhaps harmful treatments. We argue that routinely searching for IFs may not maximize benefits and minimize risks to participants.

Hippocampus and amygdala morphology in attention-deficit/hyperactivity disorder.

CONTEXT: Limbic structures are implicated in the genesis of attention-deficit/hyperactivity disorder (ADHD) by the presence of mood and cognitive disturbances in affected individuals and by elevated rates of mood disorders in family members of probands with ADHD. OBJECTIVE: To study the morphology of the hippocampus and amygdala in children with ADHD. DESIGN: A cross-sectional case-control study of the hippocampus and amygdala using anatomical magnetic resonance imaging. SETTINGS: University research institute. PATIENTS: One hundred fourteen individuals aged 6 to 18 years, 51 with combined-type ADHD and 63 healthy controls. MAIN OUTCOME MEASURES: Volumes and measures of surface morphology for the hippocampus and amygdala. RESULTS: The hippocampus was larger bilaterally in the ADHD group than in the control group (t = 3.35; P < .002). Detailed surface analyses of the hippocampus further localized these differences to an enlarged head of the hippocampus in the ADHD group. Although conventional measures did not detect significant differences in amygdalar volumes, surface analyses indicated the presence of reduced size bilaterally over the area of the basolateral complex. Correlations with prefrontal measures suggested abnormal connectivity between the amygdala and prefrontal cortex in the ADHD group. Enlarged subregions of the hippocampus tended to accompany fewer symptoms. CONCLUSIONS: The enlarged hippocampus in children and adolescents with ADHD may represent a compensatory response to the presence of disturbances in the perception of time, temporal processing (eg, delay aversion), and stimulus seeking associated with ADHD. Disrupted connections between the amygdala and orbitofrontal cortex may contribute to behavioral disinhibition. Our findings suggest involvement of the limbic system in the pathophysiology of ADHD.

Voxel-wise comparisons of the morphology of diffusion tensors across groups of experimental subjects.

Water molecules in the brain diffuse preferentially along the fiber tracts within white matter that form the anatomical connections across spatially distant brain regions. A diffusion tensor (DT) is a probabilistic ellipsoid composed of three orthogonal vectors, each having a direction and an associated scalar magnitude, that represent the probability of water molecules diffusing in each of those directions. The 3D morphologies of DTs can be compared across groups of subjects to reveal disruptions in structural organization and neuroanatomical connectivity of the brains of persons with various neuropsychiatric illnesses. Comparisons of tensor morphology across groups have typically been performed on scalar measures of diffusivity, such as Fractional Anisotropy (FA) rather than directly on the complex 3D morphologies of DTs. Scalar measures, however, are related in nonlinear ways to the eigenvalues and eigenvectors that create the 3D morphologies of DTs. We present a mathematical framework that permits the direct comparison across groups of mean eigenvalues and eigenvectors of individual DTs. We show that group-mean eigenvalues and eigenvectors are multivariate Gaussian distributed, and we use the Delta method to compute their approximate covariance matrices. Our results show that the theoretically computed mean tensor (MT) eigenvectors and eigenvalues match well with their respective true values. Furthermore, a comparison of synthetically generated groups of DTs highlights the limitations of using FA to detect group differences. Finally, analyses of in vivo DT data using our method reveal significant between-group differences in diffusivity along fiber tracts within white matter, whereas analyses based on FA values failed to detect some of these differences.

Increased number of subcortical hyperintensities on MRI in children and adolescents with Tourette's syndrome, obsessive-compulsive disorder, and attention deficit hyperactivity disorder.

OBJECTIVE: To investigate whether cerebral hyperintensities on T2-weighted magnetic resonance images (MRI) are associated with childhood neuropsychiatric disorders. METHOD: The authors compared the frequency of cortical and subcortical cerebral hyperintensities in 100 children and adolescents with Tourette's syndrome, obsessive-compulsive disorder (OCD), or attention deficit hyperactivity disorder (ADHD) and 32 healthy comparison subjects. RESULTS: The frequency of cerebral hyperintensities was significantly higher in subjects with Tourette's syndrome, OCD, or ADHD than in healthy comparison subjects; each diagnostic group seemed to contribute to this effect. Among the patient groups, the likelihood of detecting cerebral hyperintensities in the subcortex (primarily the basal ganglia and thalamus) was significantly greater than in the cortex. CONCLUSIONS: A childhood diagnosis of Tourette's syndrome, OCD, or ADHD significantly increased the likelihood of detecting cerebral hyperintensities, particularly in the subcortex, supporting the notion that subcortical injury may play a role in the pathophysiology of these conditions.

Correlates of intellectual ability with morphology of the hippocampus and amygdala in healthy adults.

Several prior imaging studies of healthy adults have correlated volumes of the hippocampus and amygdala with measures of general intelligence (IQ), with variable results. In this study, we assessed correlations between volumes of the hippocampus and amygdala and full-scale IQ scores (FSIQ) using a method of image analysis that permits detailed regional mapping of this correlation throughout the surface contour of these brain structures. We delineated the hippocampus and amygdala in high-resolution magnetic resonance images of the brain from 34 healthy individuals. We then correlated FSIQ with overall volumes and with the surface morphologies of each of these structures. Hippocampus volumes correlated significantly and inversely with FSIQ independently of gender, age, socioeconomic status, and whole brain volume. Left and right hippocampus volumes correlated respectively with verbal and performance IQ subscales. Higher IQs were significantly associated with large inward deformations of the surface of the anterior hippocampus bilaterally. These findings suggest that a smaller anterior hippocampus contributes to an increased efficiency of neural processing that subserves overall intelligence.

Neuroimaging of tic disorders with co-existing attention-deficit/hyperactivity disorder.

BACKGROUND: Tourette syndrome (TS) and Attention-Deficit/Hyperactivity Disorder (ADHD) are common and debilitating neuropsychiatric illnesses that typically onset in the preschool years. Recently, both conditions have been subject to neuroimaging studies, with the aim of understanding their underlying neurobiological correlates. OBJECTIVE: The relation of TS and ADHD is discussed against the background of findings from previous Magnetic Resonance Imaging (MRI) studies. METHODS: We review the designs and major findings of previous studies that have examined TS with comorbid ADHD, and we briefly contrast these findings with those in ADHD without comorbid tic disorders. RESULTS: The frequent comorbidity of TS and ADHD may reflect a common underlying neurobiological substrate, and studies confirm the hypothesized involvement of fronto-striatal circuits in both TS and ADHD. However, poor inhibitory control and volumetric reductions in fronto-striatal circuits appear to be core features of ADHD, whereas reduced volumes of the caudate nucleus, together with activation and hypertrophy of prefrontal regions that likely help to suppress tics, seem to be core features of TS. CONCLUSION: The etiological relationship between TS and ADHD must be clarified further with cross-sectional and, if possible, longitudinal imaging studies that examine samples of substantial size, including subgroups with pure TS and ADHD, as well as with comorbid conditions.

A developmental fMRI study of self-regulatory control.

We used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of self-regulatory control across development in healthy individuals performing the Stroop interference task. Proper performance of the task requires the engagement of self-regulatory control to inhibit an automatized response (reading) in favor of another, less automatic response (color naming). Functional MRI scans were acquired from a sample of 70 healthy individuals ranging in age from 7 to 57 years. We measured task-related regional signal changes across the entire cerebrum and conducted correlation analyses to assess the associations of signal activation with age and with behavioral performance. The magnitude of fMRI signal change increased with age in the right inferolateral prefrontal cortex (Brodmann area [BA] 44/45) and right lenticular nucleus. Greater activation of the right inferolateral prefrontal cortex also accompanied better performance. Activity in the right frontostriatal systems increased with age and with better response inhibition, consistent with the known functions of frontostriatal circuits in self-regulatory control. Age-related deactivations in the mesial prefrontal cortex (BA 10), subgenual anterior cingulate cortex (BA 24), and posterior cingulate cortex (BA 31) likely represented the greater engagement of adults in self-monitoring and free associative thought processes during the easier baseline task, consistent with the improved performance on this task in adults compared with children. Although we cannot exclude the possibility that age-related changes in reading ability or in the strategies used to optimize task performance were responsible for our findings, the correlations of brain activation with performance suggest that changes in frontostriatal activity with age underlie the improvement in self-regulatory control that characterizes normal human development.