Table 1.

Summary of TS studies with notes of methods and limitations

Reference	Technique	N (TS)	Primary results	Comments
Structural studies
Peterson et al., 2003	Volumetric MRI	154	Reduced caudate volume in TS	Post hoc analyses by age, meds, comorbidity
Hyde et al., 1995	Volumetric MRI	10	Reduced right caudate volume correlated with symptom severity	Twin study; no control for age, treatment, or common comorbidities
Bloch et al., 2005	Volumetric MRI	43	Caudate volume in childhood varies inversely with tic severity in adulthood	Longitudinal design; includes assessment of OCD but not ADHD effects; no follow-up imaging
Roessner et al., 2011	Volumetric MRI	49	Enlarged putamen and corpus callosum in TS	Children/adolescents only, controlled for age and IQ; exclusion criteria included prior treatment and comorbid ADHD/OCD
Kassubek et al., 2006	Voxel-based morphometry	14	Enlarged putamen in TS	Children only; controlled for age and gender, not treatment; assessed ADHD but not OCD effects
Singer et al., 1993	Volumetric MRI	37	Altered hemispheric asymmetry of putamen and globus pallidus	Children only; controlled for age; post hoc analysis of ADHD comorbidity
Zimmerman et al., 2000	Volumetric MRI	19	No putamen asymmetry in girls with TS	Controlled for age; assessed for ADHD effect
Makki et al., 2008	Diffusion tensor imaging	23	Microstructural abnormalities in thalamus in TS	Controlled for age; no analysis of medication or comorbidity effects
Neuner et al., 2011	Diffusion tensor imaging	28	Correlation of BG diffusivity and symptom severity	Adults only; excluded comorbidities
Peterson et al., 2007	Volumetric MRI	154	Larger hippocampus and amygdala in TS	Post hoc analyses by age, meds, comorbidity
Peterson et al., 2001	Volumetric MRI	155	Enlarged dorsofrontal and parieto-occipital cortices; diminished inferior occipital cortex	Post hoc analyses by age, meds, comorbidity
Müller-Vahl et al., 2009	Voxel-based morphometry	19	Decreased prefrontal, sensorimotor, anterior cingulate, and left caudate gray matter; decreased white matter in right inferior frontal gyrus, left superior frontal gyrus, and anterior corpus callosum	Adult males only; untreated at least 1 year; no significant comorbidities in population
Müller-Vahl et al., 2009	Magnetization transfer imaging	19	White matter reductions in right medial frontal gyrus, inferior frontal gyrus bilaterally, and right cingulate gyrus	Adult males only; untreated at least 1 year; no significant comorbidities in population
Baumgardner et al., 1996	Volumetric MRI	37	Larger corpus callosum in TS	Children; controlled for age, gender, overall brain volume
Mostofsky et al., 1999	Volumetric MRI	19	No difference in corpus callosum	Girls only; assessed effect of ADHD comorbidity
Plessen et al., 2004	Volumetric MRI	158	Alterations of corpus callosum, variable with age	Post hoc analyses by age, meds, comorbidity
Cavanna et al., 2010	DTI	1	Lower fractional anisotropy of corpus callosum	Twin comparison
Draganski et al., 2010	Voxel-based morphometry and DWI	40	Cortical thinning diffusely, modulated based on comorbidity and symptom severity; increases in primary somatosensory cortex correlated with premonitory sensations	Post hoc analysis of comorbidities; infers ongoing structural plasticity based on a single study
Jackson et al., 2011	DWI	13	Diffuse abnormalities in white matter microstructure; enhanced motor control in TS patients	Adults; excluded comorbidities; wide range of tic severity
Functional studies
Ziemann et al., 1997	Transcranial magnetic stimulation	20	Shortened cortical silent period and reduced intracortical inhibition	Adolescent/adult; post hoc analysis by age, sex, comorbidity, and treatment
Moll et al., 1999	Transcranial magnetic stimulation	21	Shortened cortical silent period	Children; post hoc analyses of age, OCD, neuroleptic treatment
Gilbert et al., 2004	Transcranial magnetic stimulation	36	Correlation of cortical disinhibition with tic and ADHD severity	Children and adults; assessed effects of ADHD and OCD comorbidities
Stern et al., 2000	PET	6	Tic correlation with activity in cortex, putamen, and caudate	Adults; no control for medication; no discussion of comorbidity
Peterson et al., 1998	fMRI	22	Increased cortical activity with decreased striatal and thalamic activity during active tic suppression	Adults; post hoc analyses of gender, treatment, and comorbidity
Braun et al., 1993	PET	16	Increased activity of sensorimotor cortex; reduction of activity in limbic cortex and striatum	Adults; nonmedicated
Eidelberg et al., 1997	PET	10	Increased activity in sensorimotor cortex; decreased in caudate and thalamus	Adults; nonmedicated; no assessment of comorbidity effects
Biswal et al., 1998	fMRI	5	Increased motor cortex activity during voluntary motor tasks in TS	Adults, few from same pedigree; variable severity and comorbidities
Church et al., 2009b	fMRI	33	Abnormal maturation of functional networks	Adolescents; included comorbidities
Marsh et al., 2007	fMRI	66	Abnormal age-related activation of neural circuits	Adults and children; post hoc analysis of medication and comorbidity effects
Baym et al., 2008	fMRI	18	Tic severity correlated with enhanced activation of dopaminergic nuclei and slower response time	Children; mostly medication-naive; post hoc analysis of comorbidity;
Neurotransmitter studies
Wong et al., 2008	PET	16	Increased phasic dopamine release in ventral striatum	Adults; included assessment of OCD comorbidity
Steeves et al., 2010	PET	8	More widespread phasic dopamine release compared to controls	Adults; controlled for medication exposure and comorbidity
Liu et al., 2010	SPECT	18	Higher dopamine transporter expression	Adolescents and adults; drug-naive; no discussion of comorbidities
Behen et al., 2007	PET	29	Abnormal tryptophan metabolism in dorsolateral prefrontal cortex and thalamus	Children; subgroup analyses of medication and comorbidities
Haugbøl et al., 2007	PET	20	Increased serotonin receptor binding in TS	Adult; no assessment of medication or comorbidity effects