LOS ANGELES— A growing body of studies using functional, neurochemical, and structural imaging is giving researchers and clinicians new insights into the pathology and genetic features of Tourette’s syndrome, according to Kirk A. Frey, MD, PhD, who presented an overview of landmark Tourette’s syndrome neuroimaging studies at the 34th National Meeting of the Child Neurology Society.

Dr. Frey, Professor of Neurology and Radiology at the University of Michigan, Ann Arbor, highlighted several functional imaging studies that have investigated synaptic activity in the brains of patients with Tourette’s syndrome. "Differences in resting metabolic activity particularly stand out in Tourette’s syndrome subjects when compared to normal controls," he noted.

METABOLIC BEHAVIOR

A study by Braun et al analyzed [¹⁸F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans of 18 drug-free patients with Tourette’s syndrome to evaluate relationships between cerebral metabolism and complex cognitive and behavioral features commonly associated with Tourette’s syndrome. Obsessions and compulsions, impulsivity, self-injurious behavior, depression, and attention deficits were associated with significant metabolic activity increases in the orbitofrontal cortices. Less pronounced increases were observed in the putamen and, in the case of attentional and visuospatial measures, in the inferior portions of the insula.

However, behavioral and cognitive features were not associated with metabolic rates in other midbrain, ventral striatum, paralimbic, or sensorimotor regions, in which metabolism had differentiated the patients with Tourette’s syndrome from controls. "The results suggest that a subset of regions in which metabolic activity appears to be associated with the diagnosis of Tourette’s syndrome may be explicitly associated with the emergence of complex behavioral and cognitive features of the illness," commented Dr. Frey.

In a follow-up study, he continued, Braun et al found that an altered relationship between limbic-related regions of the cortex and striatum and cortical regions involved in the initiation of movement may play a role in the pathogenesis of Tourette’s syndrome.

In this study, the researchers compared regional metabolic rates for glucose in 16 drug-free patients with Tourette’s syndrome and 16 controls matched for age and gender. Using FDG-PET, they found that patients with Tourette’s syndrome had decreased metabolic rates in the paralimbic and ventral prefrontal cortices, as well as in the subcortical regions. "The changes were more pronounced and occurred with greater frequency in the left hemisphere," Dr. Frey noted. "They were associated with concomitant bilateral increases in metabolic activity in the supplementary motor, lateral premotor, and rolandic cortices."

IMAGING ANATOMY

The functional brain networks underlying Tourette’s syndrome are little understood, Dr. Frey pointed out. "A study by Eidelberg et al set out to identify these networks." The study included 10 drug-free adult patients with Tourette’s syndrome and 10 normal volunteers. FDG-PET was used to calculate global, regional, and normalized rates of glucose in all subjects, he elaborated. The researchers found that global and regional metabolic rates were normal in the patients with Tourette’s syndrome. Further analysis identified two Tourette’s syndrome–related brain networks.

"One pattern was characterized by covariate bilateral metabolic increases in lateral premotor and supplementary motor association cortices and in the midbrain," Dr. Frey related. "A second pattern was characterized by decreases in caudate and thalamic metabolism and reductions in lentiform and hippocampal metabolic activity." The researchers concluded that metabolic features of Tourette’s syndrome include increased motor cortical activity that has been identified in other hyperkinetic disorders, and that Tourette’s syndrome is also associated with a specific brain network characterized by a reduction in the activity of limbic basal ganglia–thalamocortical projection systems, he noted.

TIC ETIOLOGY

"Imaging studies on the cause of involuntary tics in Tourette’s syndrome have been limited but enlightening," said Dr. Frey. For example, Stern et al combined PET with time-synchronized audiotaping and videotaping to determine duration, frequency, and radiotracer input during tics in each of 72 scans from six patients with Tourette’s syndrome. "Brain regions where activity was significantly correlated with tics included the medial and lateral premotor cortices, anterior cingulate cortex, dorsolateral-rostral prefrontal cortex, inferior parietal cortex, putamen, and caudate, as well as primary motor cortex, Broca’s area, superior temporal gyrus, insula, and claustrum," he noted.

"In a patient with pronounced coprolalia, such vocal tics were matched with activity in the pre-rolandic and post-rolandic language regions, insula, caudate, thalamus, and cerebellum, while activity in the sensorimotor cortex was noted with motor tics," he added. The investigators concluded that "aberrant activity in the interrelated sensorimotor, language, executive, and paralimbic circuits may account for the diverse motor and vocal behaviors that characterize tics in Tourette’s syndrome and the urges that often accompany them."

BASAL GANGLIA CHANGES

An MRI study led by Harvey S. Singer, MD, examined basal ganglia structures and lateral ventricles of 37 children with Tourette’s syndrome and 18 controls to determine more about the disorder’s pathology. "There were significant differences in symmetry in the putamen and the lenticular region. Virtually all controls had a left-sided predominance of the putamen, whereas in 13 of 37 Tourette’s syndrome subjects, a right predominance exceeded that of any control," Dr. Frey related. Statistical comparisons among patients with Tourette’s syndrome and controls showed significant differences in volume of the left globus pallidus and for lenticular asymmetry.

Additionally, in an analysis of a subgroup of patients with Tourette’s syndrome and ADHD, the volume of the left globus pallidus was significantly smaller than the volume of the right, and this lenticular asymmetry was due to a greater right-sided predominance, he noted.

"This study lends support to the hypothesis that the basal ganglia are involved in the pathogenesis of Tourette’s syndrome and suggests that the comorbid problem of ADHD is related to regional changes that differ from those associated with tics," said Dr. Frey.

—Kathy Stone

Suggested Reading
Braun AR, Randolph C, Stoetter B, et al. The functional neuroanatomy of Tourette’s syndrome: an FDG-PET study. II: Relationships between regional cerebral metabolism and associated behavioral and cognitive features of the illness. Neuropsychopharmacology. 1995;13:151-168.
Braun AR, Stoetter B, Randolph C, et al. The functional neuroanatomy of Tourette’s syndrome: an FDG-PET study. I. Regional changes in cerebral glucose metabolism differentiating patients and controls. Neuropsychopharmacology. 1993;9:277-291.
Eidelberg D, Moeller JR, Antonini A, et al. The metabolic anatomy of Tourette’s syndrome. Neurology. 1997;48:927-934.
Singer HS, Reiss AL, Brown JE, et al. Volumetric MRI changes in basal ganglia of children with Tourette’s syndrome. Neurology. 1993;43:950-956.
Stern E, Silbersweig DA, Chee KY, et al. A functional neuroanatomy of tics in Tourette syndrome. Arch Gen Psychiatry. 2000;57:741-748.
Thompson PM, Cannon TD, Narr KL, et al. Genetic influences on brain structure. Nat Neurosci. 2001;4:1253-1258.

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