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.

Inclusion criteria for TS arm:

• Diagnosis of Tourette syndrome or other chronic tic disorder
• ≥ 18 years of age
• Ability to complete survey instruments
• English fluency (given that all scales are validated in English)

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.)

• Use of anti-seizure medications, stimulants, or other psychotropic medications known to alter EEG signal
• Recreational substance use within past 30 days

Inclusion criteria for healthy control arm:

• ≥ 18 years of age AND age within 5 years of a participant in the TS arm of same biological sex (for purposes of age- and sex-matching)
• Ability to complete survey instruments
• English fluency (given that all scales are validated in English)

Exclusion criteria for healthy control arm:

• Any neurologic or psychiatric diagnoses
• History of tics
• Use of any psychotropic medications within the past 30 days
• Recreational substance use within past 30 days

The two groups of participants will include:

1. adult with Tourette syndrome or other chronic tic disorder
2. healthy controls

De-identified clinical variables, EEG data, and autonomic data metrics may be shared with other researchers.

The above information will be available for sharing within 6 months of publication.

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.