Brain mechanisms for prepulse inhibition in adults with Tourette syndrome: Initial findings

Abstract

Prepulse inhibition (PPI) of the startle reflex is disrupted in a number of developmental neuropsychiatric disorders, including Tourette syndrome (TS). This disruption is hypothesized to reflect abnormalities in sensorimotor gating. We applied whole-brain functional magnetic resonance imaging (fMRI) to elucidate the neural correlates of PPI in adult TS subjects using airpuff stimuli to the throat to elicit a tactile startle response. We used a cross-sectional, case-control study design and a blocked-design fMRI paradigm. There were 33 participants: 17 with TS and 16 healthy individuals. As a measure of PPI-related brain activity, we looked for differential cerebral activation to prepulse-plus-pulse stimuli versus activation to pulse-alone stimuli. In healthy subjects, PPI was associated with increased activity in multiple brain regions, of which activation in the left middle frontal gyrus in the healthy controls showed a significant linear correlation with the degree of PPI measured outside of the magnet. Group comparisons identified nine regions where brain activity during PPI differed significantly between TS and healthy subjects. Among the TS subjects, activation in the left caudate was significantly correlated with current tic severity as measured by the total score on the Yale Global Tic Severity Scale. Differential activation of the caudate nucleus associated with current tic severity is consistent with neuropathological data and suggests that portions of cortical-striatal circuits may modulate the severity of tic symptoms in adulthood.

Evaluation of Basal Ganglia and Thalamic Inflammation in Children With Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infection and Tourette Syndrome

“…Preferential involvement of the caudate in patients with Tourette syndrome has been demonstrated by various previous studies. [24][25][26][27] A particularly large cohort study showed a decreased volume of caudate nuclei in the Tourette syndrome-only group as compared to a Tourette syndrome þ obsessive compulsive disorder group, which demonstrated both a decrease in volume of the caudate and lentiform nuclei and implied that obsessive compulsive disorder symptomatology was more highly correlated with lentiform nuclei involvement. 28 This finding was supported by another study involving children with only obsessive compulsive disorder without comorbid behavioral or movement disorders, which found reduced volume of globus pallidus in these children.…”

Sensorimotor gating of the startle reflex: what we said 25 years ago, what has happened since then, and what comes next

“…Over the ensuing decades, a number of studies have tested our speculation of PPI deficits across multiple brain disorders and confirmed that – in addition to the reduction of PPI in schizophrenia populations, PPI is also impaired in cohorts of patients with OCD (Ahmari et al, 2012; Hoenig et al, 2005; Kohl et al, 2015; Swerdlow et al, 1993b), TS (Buse et al, 2016; Castellan Baldan et al, 2014; Castellanos et al, 1996; Swerdlow et al., 2001b; Zebardast et al, 2013), and HD (Munoz et al, 2003; Swerdlow et al, 1995; Valls-Solé et al, 2004). In addition, PPI deficits have been identified in other patient populations, including individuals with nocturnal enuresis (Ornitz et al, 1992), Asperger’s syndrome (Howlin and Murphy, 2002; McAlonan et al, 2002), 22q11 syndrome (Sobin et al, 2005), Kleinfelter syndrome (van Rijn et al., 2011), fragile-X syndrome (Frankland et al, 2004; Renoux et al, 2014; Yuhas et al, 2011), and blepharospasm (Gomez-Wong et al, 1998).…”

Functional neuroimaging in Tourette syndrome: recent perspectives

“…27 Two studies have investigated the neural correlates of prepulse inhibition (PPI). 28,29 PPI is a neurological phenomenon in which a weaker prestimulus (prepulse) inhibits the reaction of an organism to a subsequent strong startling stimulus (pulse). A couple of studies indicate sensorimotor gating deficits in patients with TS.…”

“…A couple of studies indicate sensorimotor gating deficits in patients with TS. 28,29 Buse et al 29 showed increased activity in five regions of the brain during PPI (middle frontal gyrus, the postcentral gyrus, the superior parietal cortex/ precuneus, the anterior cingulated gyrus, and the caudate body), and they suggested that this deficient sensorimotor gating in patients with TS might be associated with reduced recruitment of brain regions responsible for the higher-order integration of somatosensory stimuli.…”