Clinical Features That Evoke the Concept of Disinhibition in Tourette Syndrome

Abstract

The capacity to efficiently control motor output, by either refraining from prepotent actions or disengaging from ongoing motor behaviors, is necessary for our ability to thrive in a stimulus-rich and socially complex environment. Failure to engage in successful inhibitory motor control could lead to aberrant behaviors typified by an excess of motor performance. In tic disorders and Tourette syndrome (TS)the most common tic disorder encountered in clinicssurplus motor output is rarely the only relevant clinical sign. A range of abnormal behaviors is often encountered which are historically viewed as "disinhibition phenomena". Here, we present the different clinical features of TS from distinct categorical domains (motor, sensory, complex behavioral) that evoke the concept of disinhibition and discuss their associations. We also present evidence for their consideration as phenomena of inhibitory dysfunction and provide an overview of studies on TS pathophysiology which support this view. We then critically dissect the concept of disinhibition in TS and illuminate other salient aspects, which should be considered in a unitary pathophysiological approach. We briefly touch upon the dangers of oversimplification and emphasize the necessity of conceptual diversity in the scientific exploration of TS, from disinhibition and beyond.

Aggression Toward Others Misdiagnosed as Primary Tics

“…Largely owing to the seminal syndromic description of Georges Gilles de la Tourette 2 and their common prevalence in people with primary tics and TS, an array of further and pathophysiologically poorly understood behaviors, such as echo-, pali-and coprophenomena are also currently classified as complex tics. 3 In stark contrast, the cases illustrated here document a different range of complex behaviors, specifically episodes of alloaggression, which until now had been misinterpreted as complex tics by medical personnel and by patients themselves. These striking allo-aggressive incidents, such as sudden and repetitive kicking, hitting, slapping and biting others, or grabbing items from other people and darting them about, or even pushing someone off a bike, do not belong to the spectrum of the behavioral manifestations of primary tics.…”

Electrophysiology Echoes Brain Dynamics in Children and Adolescents With Tourette Syndrome—A Developmental Perspective

“…Motor and vocal tics can be viewed as signs of hypermotoric behavior where fragments of normal movements are released because of non-successful automatic inhibitory control. The disinhibition concept of TS was recently broadly discussed by Kurvits et al ( 20 ), who emphasized “the necessity of conceptual diversity in the scientific exploration of TS, from disinhibition and beyond.” Specifically, this holds true because different functional domains (e.g., motor, sensory, cognitive) as well as developmental considerations have to be taken into account.…”

“…The concept of non-voluntary neuronal disinhibition as the main pathophysiological background in TS along the lifetime is still a matter of debate ( 20 ). Specifically, this holds for qualitative and quantitative aspects during child development and how disinhibition can be counteracted/compensated via voluntary cognitive inhibitory processes.…”

Dissociation of tic generation from tic expression during the sleep-wake cycle

“…The basal ganglia (BG) play a key role in the pathophysiology of tic disorders ( Peterson et al., 2003 ; Bloch et al., 2005 ; Kalanithi et al., 2005 ; Worbe et al., 2015 ; Ramkiran et al., 2019 ), particularly through the reduced inhibition in its primary input nucleus, the striatum ( Mink, 2001 ; Albin and Mink, 2006 ; Kurvits et al., 2020 ). Animal models mimicking this disinhibition may be generated by microinjection or infusion of GABA A antagonists such as bicuculline or picrotoxin into the motor parts of the striatum, which lead to the expression of motor tics phasically over tens of minutes ( Tarsy et al., 1978 ; Crossman et al., 1988 ; McCairn et al., 2009 ; Worbe et al., 2009 ; Bronfeld et al., 2013b ; Pogorelov et al., 2015 ) or tonically over days or weeks ( Vinner et al., 2017 ).…”