Table 1.

Published TS neuroimaging studies in 2014–2015

	Subjects	Method	Findings
Muellner et al. [9]	52 adults with TS 52 adult controls	T1-weighted MRI Measures: sulcal cortical thickness, mean depth, length, cortical fold opening	Diminished sulcal depth and sulcal cortical thickness in frontal and pre- and post-central sulci in TS
Ganos et al. [6]	14 adults with TS 15 adults controls	T1-weighted MRI Measures: VBM gray matter and white matter volume	Reduced gray matter volume in prefrontal regions in TS. No differences in white matter volume and no significant correlations with clinical scores.
Debes et al. [7]	22 adolescents and young adults with TS 21 adolescent and young adult controls	T1-weighted MRI and Diffusion-weighted imaging Measures: VBM gray matter density, FA, mean diffusivity, parallel and perpendicular diffusivity Longitudinal study	Decreased gray matter volume in putamen over time in controls, but no such change in TS. Parallel and perpendicular diffusivity increased over time in controls, but decreased over time in TS. Decrease in mean diffusivity in right striatum, right thalamus, and right frontal lobe more pronounced in TS.
Jeppesen et al. [8]	24 children with TS 18 child controls	T1-weighted MRI and Diffusion-weighted imaging Measures: VBM gray matter density, FA, ADC, parallel and perpendicular diffusivity	No differences found in the seven regions of interest: cingulate, corpus callosum, optic radiation, forcep minor, thalamus, striatum, middle cerebral peduncle
Muller-Vahl et al. [14]	19 adults with TS 20 adult controls	Diffusion-weighted imaging Measures: FA, ADC	Microstructural alterations in white matter in frontal regions, corpus callosum, cingulate, thalamus, and putamen in TS
Cheng et al. [15]	15 adults with TS 15 adult controls	Diffusion-weighted imaging Measures: probabilistic tractography	Reduced connectivity between cortical and subcortical motor control regions in TS
Worbe et al. [13]	49 adults with TS 28 adult controls	Diffusion-weighted imaging Measures: probabilistic tractography	Atypical connectivity between striatum/thalamus and cortical regions in TS, primarily enhanced connectivity.
Ganos et al. [18]	14 adults with TS 15 adult controls	fMRI during a stop signal task Measures: task performance, fMRI activity during task conditions	Behavioral performance did not differ between TS and controls, but activity in dorsal premotor cortex differed; stronger activity for successful stop than successful go trials in controls, while stronger activity for successful go than successful stop trials in TS.
Thomalla et al. [19]	15 adults with TS 15 adult controls	fMRI during a Go/NoGo task Measures: task performance, fMRI activity during task conditions	Slower RT on Go trials accompanied by reduced activity in motor regions (M1, SMA, dorsal premotor cortex) in TS
Ganos et al. [23]	14 adults with TS	fMRI during tic inhibition and free ticcing Measures: resting state fMRI regional homogeneity	Increased regional homogeneity in left inferior frontal gyrus during tic inhibition vs. free ticcing
Cui et al. [22]	17 children with TS 15 child controls	Resting state fMRI Measures: amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF)	Decreased ALFF and fALFF in frontal and parietal regions; increased fALFF in subcortical regions (correlated with tic severity in thalamus)
Neuner et al. [24]	16 adults with TS (subset of 10 used for tic-related fMRI analysis)	fMRI Measures: tic-related fMRI activity 2 sec before a tic, 1 sec before a tic, and at tic onset, resting state networks (RSN) analysis	Cortical regions were active before subcortical regions during tics. Tic severity correlated with RSN network integrity in SMA regions
Shprecher et al. [25]	9 adults with TS 10 adult controls	Resting state fMRI Measures: functional connectivity in 116 regions from the AAL atlas	Increased short distance connectivity and decreased long distance connectivity in TS (note that this result is consistent with motion artifacts)
Tinaz et al. [26]	13 adults with TS 13 adult controls	Resting state fMRI Measures: functional connectivity in 35 nodes constituting a “urge-tic network”, graph theory metrics	Functional connectivity reduced in dorsomedial frontal regions, but increased in thalamus, putamen, insula and between dorsomedial frontal regions and dorsal anterior insula
Deckersbach et al. [41]	8 adults with TS 8 adult controls	fMRI during a visuospatial priming task Measures: task activity pre and post CBIT	Greater activity in putamen in TS pre CBIT. Reduced activity in putamen in TS post CBIT.
Wu et al. [35]	12 children to young adults (10–22 years); half in active group, half in sham control group	fMRI during finger tapping task Measures: task activity pre and post TMS over the SMA, tic severity pre and post TMS	Improvement in tic severity in both active and sham groups. Reduced fMRI activity in motor regions in active group vs. sham group
Abi-Jaoude et al. [55]	11 adults with TS 11 adult controls	[11C]raclopride PET and [11C]-(+)-PHNO PET Measures: striatal binding potential	No group differences in striatal binding potential, and no significant correlations with symptom severity.
Kumar et al. [56]	12 children with TS 17 children with PANDAS 15 adult controls	11C-[R]-PK11195 PET Measures: ligand TSPO receptor binding in basal ganglia and thalamus	Increased binding potential in the caudate in TS, and increased binding potential in the caudate and lentiform in PANDAS, compared to controls.
Black et al. [57]	5 adults with TS 5 adult controls(pilot study)	[11C]raclopride PET Measures: synaptic dopamine release before and during levodopa or placebo infusion, [11C]raclopride (RAC*) binding potential	In the midbrain, levodopa displaced RAC* by 59% in controls, but increased RAC* binding potential by 74% in TS. No differences in the striatum.
Draper et al. [43]	15 adolescents with TS 15 adolescent controls	Multimodal: GABA MRS, T1-weighted MRI, fMRI during finger tapping, TMS, diffusion-weighted imaging Measures: GABA concentration, CSF, gray matter, and white matter volume, finger tapping activity, cortical-spinal excitability, FA Focus on M1, SMA, primary visual cortex	Elevated GABA in SMA, but not in M1 or visual cortex, in TS. Increased GABA in SMA related to decreased fMRI activity in SMA and cortical excitability. Increased GABA in SMA related to increased motor tic severity and FA within a region of the corpus callosum that projects to the SMA.
Tinaz et al. [42]	15 adults with TS 15 adult controls	Multimodal: T1-weighted MRI, resting state fMRI, GABA MRS, MEG Measures: cortical volume and thickness, seed-based functional connectivity, GABA concentration(?), beta band power Focus on sensorimotor cortex	In the sensorimotor cortex, no significant group differences in GABA or beta band power, but the relationship between was opposite in TS. Trend for increase functional connectivity between the insula and sensorimotor cortex in TS.

Subject numbers refer to those subjects included in final analyses; ADC = apparent diffusion coefficient, CBIT = comprehensive behavioral intervention for tics, FA = fractional anisotropy, M1 = primary motor cortex, MEG = magnetoencephalography, MRS = magnetic resonance spectroscopy, PET = Positron emission tomorgraphy, SMA = supplementary motor cortex, TMS = transcranial magnetic stimulation, VBM = voxel-based morphometry