title: Reduced GABAergic inhibition and abnormal sensory symptoms in children with Tourette syndrome.
abstract: Tourette Syndrome (TS) is characterized by the presence of chronic tics. Individuals with TS often report difficulty with ignoring (habituating to) tactile sensations, and some patients perceive that this contributes to a "premonitory urge" to tic. While common, the physiological basis of impaired tactile processing in TS, and indeed tics themselves, remain poorly understood. It has been well established that GABAergic processing plays an important role in shaping the neurophysiological response to tactile stimulation. Furthermore, there are multiple lines of evidence suggesting that a deficit in GABAergic transmission may contribute to symptoms found in TS. In this study, GABA-edited magnetic resonance spectroscopy (MRS) was combined with a battery of vibrotactile tasks to investigate the role of GABA and atypical sensory processing in children with TS. Our results show reduced primary sensorimotor cortex (SM1) GABA concentration in children with TS compared with healthy control subjects (HC), as well as patterns of impaired performance on tactile detection and adaptation tasks, consistent with altered GABAergic function. Moreover, in children with TS SM1 GABA concentration correlated with motor tic severity, linking the core feature of TS directly to in vivo brain neurochemistry. There was an absence of the typical correlation between GABA and frequency discrimination performance in TS as was seen in HC. These data show that reduced GABA concentration in TS may contribute to both motor tics and sensory impairments in children with TS. Understanding the mechanisms of altered sensory processing in TS may provide a foundation for novel interventions to alleviate these symptoms.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland; F. M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland; nputs1@jhmi.edu.
authors.forename: Nicolaas A J
authors.initials: NA
authors.lastname: Puts
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland; F. M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland;
authors.forename: Ashley D
authors.initials: AD
authors.lastname: Harris
authors.affiliation: Center for Neurodevelopment and Imaging Research, Kennedy Krieger Institute, Baltimore, Maryland;
authors.forename: Deana
authors.initials: D
authors.lastname: Crocetti
authors.affiliation: Center for Neurodevelopment and Imaging Research, Kennedy Krieger Institute, Baltimore, Maryland;
authors.forename: Carrie
authors.initials: C
authors.lastname: Nettles
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland;
authors.forename: Harvey S
authors.initials: HS
authors.lastname: Singer
authors.affiliation: Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Mark
authors.initials: M
authors.lastname: Tommerdahl
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland; F. M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland;
authors.forename: Richard A E
authors.initials: RA
authors.lastname: Edden
authors.affiliation: Center for Neurodevelopment and Imaging Research, Kennedy Krieger Institute, Baltimore, Maryland; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
authors.forename: Stewart H
authors.initials: SH
authors.lastname: Mostofsky
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism*; D002648:Child; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009483:Neuropsychological Tests; D010812:Physical Stimulation; D011930:Reaction Time; D017603:Signal Detection, Psychological / Q000502:physiology*; D055698:Touch Perception / Q000502:physiology*; D005879:Tourette Syndrome / Q000503:physiopathology*; D014732:Vibration; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid
keywords: GABA; Tourette syndrome; inhibition; magnetic resonance spectroscopy; somatosensory function; tactile processing