Neural Correlates of Sensory Phenomena in Tourette Syndrome

Recruiting

• Conditions: Tics; Tourette Syndrome; Hypersensitivity; Sensory Disorders
• Interventions: Diagnostic Test: Electroencephalogram (EEG) testing procedure; Diagnostic Test: Autonomic function testing procedure

• Registration Number: NCT03914664
• Lead Sponsor: Vanderbilt University Medical Center

Brief Summary

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.

Detailed Description

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-04-11
• Study First Submitted QC: 2019-04-11
• Study First Posted: 2019-04-16
• Study Start: 2021-07-20
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-02
• Last Update Posted: 2024-07-03
• Primary Completion: 2026-03-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Tourette Syndrome	Electroencephalogram (EEG) testing procedure	Adults (\>18 years of age) with diagnosis of Tourette syndrome
Tourette Syndrome	Autonomic function testing procedure	Adults (\>18 years of age) with diagnosis of Tourette syndrome
Healthy Control	Electroencephalogram (EEG) testing procedure	Adults who are generally healthy with no known neurologic or psychiatric diagnoses
Healthy Control	Autonomic function testing procedure	Adults who are generally healthy with no known neurologic or psychiatric diagnoses

Primary Outcome Measures

Name	Time	Method
Heart rate variability	Baseline	Change beat-to-beat variability in heart rate
Electrodermal activity in response to sensory stimuli	Baseline	Sweat response changes within 1-3 seconds of non-aversive sensory stimulus
Network oscillations in response to sensory stimuli	Baseline	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.

Secondary Outcome Measures

Name	Time	Method
Body Perception Questionnaire - Short Form (BPQ-SF)	Within 1 week of baseline	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.
Yale Global Tic Severity Scale (YGTSS)	Within 1 week of baseline	Validated, gold-standard clinician-administered tic assessment scale, comprised of 11 items. Scale range: 0 (best) - 100 (worst)
Dimensional Obsessive Compulsive Scale (DOCS)	Within 1 week of baseline	Validated self-report questionnaire assessing severity of obsessive and compulsive symptoms, comprised of 20 items. Scale range 0 (least affected) - 80 (most affected)
Patient Reported Outcomes Measurement Information System (PROMIS) Sleep-Related Impairment	Within 1 week of baseline	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).
Adult ADHD Self-Report Screening Scale	Within 1 week of baseline	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)
Patient Health Questionnaire 9 (PHQ-9)	Within 1 week of baseline	Validated self-report scale assessing presence and extent of depression, comprised of 9 items. Scale range 0 (least affected) - 27 (most affected)
Sensory Perception Quotient (SPQ)	Within 1 week of baseline	Validated self-report questionnaire assessing sensory hypo- or hyper-sensitivity, comprised of 35 items. Scale range 0 (highest sensory sensitivity) - 105 (lowest sensory sensitivity).
Multidimensional Assessment of Interoceptive Awareness-2 (MAIA-2)	Within 1 week of baseline	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.
Generalized Anxiety Disorder 7 (GAD-7)	Within 1 week of baseline	Validated self-report scale assessing presence and extent of anxiety, comprised of 7 items. Scale range 0 (least affected) - 21 (most affected)
Sensory Gating Inventory (SGI)	Within 1 week of baseline	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)
Gilles de la Tourette Syndrome - Quality of Life Scale (GTS-QOL)	Within 1 week of baseline	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)
Premonitory Urge to Tic Scale (PUTS)	Within 1 week of baseline	Validated self-report questionnaire comprised of 9 items assessing character and severity of premonitory urges. Scale range: 9 (least affected) - 36 (most affected)

Trial Locations

Locations (1)

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States