Neural Correlates of Sensory Phenomena in Tourette Syndrome

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.

• Premonitory Urge to Tic Scale (PUTS) [Time frame: Within 1 week of baseline]
• Yale Global Tic Severity Scale (YGTSS) [Time frame: Within 1 week of baseline]
• Dimensional Obsessive Compulsive Scale (DOCS) [Time frame: Within 1 week of baseline]
• Adult ADHD Self-Report Screening Scale [Time frame: Within 1 week of baseline]
• Generalized Anxiety Disorder 7 (GAD-7) [Time frame: Within 1 week of baseline]
• Patient Health Questionnaire 9 (PHQ-9) [Time frame: Within 1 week of baseline]
• Sensory Gating Inventory (SGI) [Time frame: Within 1 week of baseline]
• Sensory Perception Quotient (SPQ) [Time frame: Within 1 week of baseline]
• Gilles de la Tourette Syndrome - Quality of Life Scale (GTS-QOL) [Time frame: Within 1 week of baseline]
• Patient Reported Outcomes Measurement Information System (PROMIS) Sleep-Related Impairment [Time frame: Within 1 week of baseline]
• Multidimensional Assessment of Interoceptive Awareness-2 (MAIA-2) [Time frame: Within 1 week of baseline]
• Body Perception Questionnaire - Short Form (BPQ-SF) [Time frame: Within 1 week of baseline]