An observational study in Tourette Syndrome, Sensory Disorders and Hypersensitivity, sponsored by Vanderbilt University Medical Center. Enrolling by invitation at 1 site in United States. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-01-14.
Sponsored by Vanderbilt University Medical Center · Observational
The most pervasive sensory manifestation of TS is sensory over-responsivity (SOR). SOR is defined as excessive behavioral response to commonplace environmental stimuli. SOR is an integral but poorly understood facet of the TS phenotype, one intertwined with core elements of the disorder and worse QOL. This proposal seeks to clarify the mechanistic bases of SOR in TS. Adults with with TS will be recruited 1) to complete a standardized clinical symptom assessment battery and 2) to undergo electroencephalogram (EEG), autonomic, and audio-visual monitoring during tactile and auditory stimuli paradigms, as well as at rest.
Tourette syndrome (TS) is a multifaceted disorder that affects 0.6-1% of the global population. Across the lifespan, individuals with TS suffer worse quality of life (QOL) than the general population. While tics are the defining feature of TS, it is the widespread psychiatric and sensory symptoms that exert greater impact on QOL: more than 85% of individuals with TS are diagnosed with a psychiatric disorder, and 90% experience distressing sensory symptoms. The latest TS disease models and practice guidelines account for common psychiatric symptoms, but sensory symptoms remain under-recognized and under-studied. Progress in understanding and treating TS requires deepening insight into the disorder's sensory dimension.
The most pervasive sensory manifestation of TS is sensory over-responsivity (SOR). SOR is defined as excessive behavioral response to commonplace environmental stimuli. SOR is associated with avoidant behavior and functional impairment. More than 50% of children and 80% of adults with TS report SOR. Across age groups, SOR is positively correlated with severity of tics and psychiatric symptoms and negatively correlated with QOL. Thus, SOR is an integral facet of the TS phenotype, one intertwined with core elements of the disorder and worse QOL. This proposal seeks to clarify the mechanistic bases of SOR in TS (Aims 1 and 2).
Enhanced understanding of SOR's neurobiological basis is crucial to a more complete knowledge of TS pathophysiology. Two neurophysiologic mechanisms are implicated in SOR: sensory gating impairment and autonomic hyperarousal. Sensory gating is the physiologic process whereby redundant environmental stimuli are filtered out in the early stages of perception. Impairment of sensory gating gives rise to altered sensory perception. Autonomic hyperarousal is a state of excessive sympathetic tone and/or reduced parasympathetic tone, which hampers behavioral adaptation to sensory input. In TS, multiple lines of evidence suggest both sensory gating and autonomic function are impaired. However, prior investigations have suffered from methodologic limitations and have not examined the link between neurophysiologic dysfunction and sensory symptoms.
Aim 1. Identify an electroencephalographic (EEG) signature of SOR in TS. Hypotheses: (1a) relative to healthy controls, TS adults exhibit impaired sensory gating; (1b) extent of impaired sensory gating in TS correlates with degree of SOR. We will recruit 60 TS adults and 60 age- and sex-matched healthy controls to complete rating scales for SOR, psychiatric symptoms, and tics. Subjects will then be monitored on dense-array scalp EEG during sequential auditory and tactile sensory gating paradigms.
Aim 2. Identify an autonomic signature of SOR in TS. Hypotheses: (2a) relative to healthy controls, TS adults exhibit autonomic hyperarousal in response to non-aversive sensory stimuli; (2b) extent of autonomic hyperarousal correlates with SOR severity in TS. Heart rate and electrodermal activity will be monitored during the Aim 1 sensory gating paradigms and during a 10-minute rest period. Heart rate variability and electrodermal activity will serve as indices of parasympathetic and sympathetic activity, respectively.
Impact: Results will clarify the extent of sensory gating impairment in TS, the nature of autonomic dysfunction in TS, and the clinical correlates of neurophysiologic dysfunction in TS.
240 studies on the registry are indexed under Tourette Syndrome; 40 are open to participants now.
This study's planned enrollment of 50 is below the median of 60 across 46 observational studies indexed under Tourette Syndrome.
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The two groups of participants will include:
Inclusion criteria for TS arm:
Exclusion criteria for TS arm:
- Known diagnosis of autism spectrum disorder, developmental delay, cerebral palsy, other significant neurologic disease, schizophrenia, or psychotic disorders will be excluded, in order to lessen potentially confounding factors.
(Note: Patients with OCD, ADHD, anxiety, and/or depression will be permitted, given that these diagnoses are widely prevalent in the adult TS population.)
Inclusion criteria for healthy control arm:
Exclusion criteria for healthy control arm:
Adults (\>18 years of age) with diagnosis of Tourette syndrome
Diagnostic Test: Electroencephalogram (EEG) testing procedure · Diagnostic Test: Autonomic function testing procedure
Adults who are generally healthy with no known neurologic or psychiatric diagnoses
Diagnostic Test: Electroencephalogram (EEG) testing procedure · Diagnostic Test: Autonomic function testing procedure
EEG testing procedure, comprised of somatosensory and auditory event-related potential paradigms, as well as resting state EEG
Autonomic function testing procedure, comprised of electrodes to determine heart rate variability and electrodermal activity (EDA)
Network oscillations in response to sensory stimuli
Neural activity captured on EEG can be spectrally decomposed into various frequency constituencies. Neural activity in the gamma frequency range, so-called gamma band oscillations (GBOs), are associated with sensory processing and integration and are postulated to underlie sensory phenomena in TS.
Time frame: Baseline
Heart rate variability
Change beat-to-beat variability in heart rate
Time frame: Baseline
Electrodermal activity in response to sensory stimuli
Sweat response changes within 1-3 seconds of non-aversive sensory stimulus
Time frame: Baseline
Premonitory Urge to Tic Scale (PUTS)
Validated self-report questionnaire comprised of 9 items assessing character and severity of premonitory urges. Scale range: 9 (least affected) - 36 (most affected)
Time frame: Within 1 week of baseline
Yale Global Tic Severity Scale (YGTSS)
Validated, gold-standard clinician-administered tic assessment scale, comprised of 11 items. Scale range: 0 (best) - 100 (worst)
Time frame: Within 1 week of baseline
Dimensional Obsessive Compulsive Scale (DOCS)
Validated self-report questionnaire assessing severity of obsessive and compulsive symptoms, comprised of 20 items. Scale range 0 (least affected) - 80 (most affected)
Time frame: Within 1 week of baseline
Adult ADHD Self-Report Screening Scale
Validated self-report scale, developed since release of Diagnostic and Statistical Manual-V, comprised of 6 items. Scale range 0 (least affected) - 24 (most affected)
Time frame: Within 1 week of baseline
Generalized Anxiety Disorder 7 (GAD-7)
Validated self-report scale assessing presence and extent of anxiety, comprised of 7 items. Scale range 0 (least affected) - 21 (most affected)
Time frame: Within 1 week of baseline
Patient Health Questionnaire 9 (PHQ-9)
Validated self-report scale assessing presence and extent of depression, comprised of 9 items. Scale range 0 (least affected) - 27 (most affected)
Time frame: Within 1 week of baseline
Sensory Gating Inventory (SGI)
Validated self-report questionnaire assessing sensory hypo- or hyper-sensitivity, comprised of 36 items. The 4 sub-scales include Perceptual Modulation, Distractability, Over-Inclusion, and Fatigue and Stress Vulnerability. Total scale range 0 (least affected) - 180 (most affected)
Time frame: Within 1 week of baseline
Sensory Perception Quotient (SPQ)
Validated self-report questionnaire assessing sensory hypo- or hyper-sensitivity, comprised of 35 items. Scale range 0 (highest sensory sensitivity) - 105 (lowest sensory sensitivity).
Time frame: Within 1 week of baseline
Gilles de la Tourette Syndrome - Quality of Life Scale (GTS-QOL)
Validated self-report questionnaire assessing health-related quality of life for patients with Tourette syndrome, comprised of 27 items. Scale range 0 (best quality of life) - 108 (worst quality of life)
Time frame: Within 1 week of baseline
Patient Reported Outcomes Measurement Information System (PROMIS) Sleep-Related Impairment
Validated self-report questionnaire to measures sleep-related impairments, consisting of 8 items. Scale range 0 - 100 (t-score scaled with lower values indicating less impairment).
Time frame: Within 1 week of baseline
Multidimensional Assessment of Interoceptive Awareness-2 (MAIA-2)
Validated self-report questionnaire assessing interoceptive sensibility, comprised of 37 items. Each scale item is a statement to which respondents must select "never" (0) to "always" (5) on a six-point Likert scale. No total MAIA-2 score exists. Rather, individual scale items belong to one of eight MAIA-2 subscales. For each subscale, higher score signifies more of that construct.
Time frame: Within 1 week of baseline
Body Perception Questionnaire - Short Form (BPQ-SF)
Validated self-report questionnaire assessing interoceptive sensibility, comprised of 46 items total, divided into 3 sections: Body Awareness (raw total score 26-130), Supradiaphragmatic Reactivity (raw total score 15-69), and Subdiaphragmatic Reactivity (raw total score 6-28). Raw scores are converted to T-scores. Higher raw and T-scores indicate greater maladaptive body awareness.
Time frame: Within 1 week of baseline
Plan to share: Yes — De-identified clinical variables, EEG data, and autonomic data metrics may be shared with other researchers.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report, Analytic code
Time frame: The above information will be available for sharing within 6 months of publication.
Access criteria: Researchers wishing to access the above information should contact the investigative team and provide: 1) hypothesis-driven scientific question for which the data will be analyzed and 2) proposed methods for responsibly analyzing the data.
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