Tourette syndrome: a disorder of the social decision-making network

Abstract

Tourette syndrome is a common neurodevelopmental disorder defined by characteristic involuntary movements, tics, with both motor and phonic components. Tourette syndrome is usually conceptualized as a basal ganglia disorder, with an emphasis on striatal dysfunction. While considerable evidence is consistent with these concepts, imaging data suggest diffuse functional and structural abnormalities in Tourette syndrome brain. Tourette syndrome exhibits features that are difficult to explain solely based on basal ganglia circuit dysfunctions. These features include the natural history of tic expression, with typical onset of tics around ages 5 to 7 years and exacerbation during the peri-pubertal years, marked sex disparity with higher male prevalence, and the characteristic distribution of tics. The latter are usually repetitive, somewhat stereotyped involuntary eye, facial and head movements, and phonations. A major functional role of eye, face, and head movements is social signalling. Prior work in social neuroscience identified a phylogenetically conserved network of sexually dimorphic subcortical nuclei, the Social Behaviour Network, mediating many social behaviours. Social behaviour network function is modulated developmentally by gonadal steroids and social behaviour network outputs are stereotyped sex and species specific behaviours. In 2011 O'Connell and Hofmann proposed that the social behaviour network interdigitates with the basal ganglia to form a greater network, the social decision-making network. The social decision-making network may have two functionally complementary limbs: the basal ganglia component responsible for evaluation of socially relevant stimuli and actions with the social behaviour network component responsible for the performance of social acts. Social decision-making network dysfunction can explain major features of the neurobiology of Tourette syndrome. Tourette syndrome may be a disorder of social communication resulting from developmental abnormalities at several levels of the social decision-making network. The social decision-making network dysfunction hypothesis suggests new avenues for research in Tourette syndrome and new potential therapeutic targets.

Dynamic postnatal development of the cellular and circuit properties of striatal D1 and D2 spiny projection neurons

“…This is consistent with the idea that neuronal specification can occur early in development (Lobo et al 2006(Lobo et al , 2008Arlotta et al 2008;Ehrman et al 2013;Lu et al 2014;Zhang et al 2016;Merchan-Sala et al 2017;Kelly et al 2018;Tinterri et al 2018;Xu et al 2018) with further postnatal development guided by, for example, neural activity (Zhang & Poo, 2001;Kozorovitskiy et al 2012;Peixoto et al 2016) and neuromodulation (Kozorovitskiy et al 2015;Lieberman et al 2018). Future work will be able to clarify the precise interaction of these factors during striatal development as well as their differential involvement in neurodevelopmental disorders (Graybiel & Rauch, 2000;Del Campo et al 2011;Langen et al 2011;McNaught & Mink, 2011;Shepherd, 2013;Albin, 2018).…”

“…) and Huntington's disease (Cepeda et al . ), but also those seen in early onset neurodevelopmental disorders such as Tourette's syndrome (McNaught & Mink, ; Albin, ), obsessive–compulsive disorder (Graybiel & Rauch, ; Langen et al . ), attention deficit hyperactivity disorder (Del Campo et al .…”

“…Adult D1 and D2 SPNs exhibit distinct electrical and morphological properties (Gertler et al 2008) and form precise non-random local synaptic connections with each other (Taverna et al 2008;Planert et al 2010;Cepeda et al 2013). Imbalance in the activity of the two pathways is thought to contribute to the cognitive and motor symptoms seen in late onset neurodegenerative disorders such as Parkinson's disease (Taverna et al 2008) and Huntington's disease (Cepeda et al 2013), but also those seen in early onset neurodevelopmental disorders such as Tourette's syndrome (McNaught & Mink, 2011;Albin, 2018), obsessive-compulsive disorder (Graybiel & Rauch, 2000;Langen et al 2011), attention deficit hyperactivity disorder (Del Campo et al 2011) and autism spectrum disorders (Shepherd, 2013). The cellular and neural circuit changes that underpin these neurodevelopmental disorders are major research areas.…”

Early postnatal development of the cellular and circuit properties of striatal D1 and D2 spiny projection neurons

“…Adult D1 and D2 SPNs exhibit distinct electrical and morphological properties (Gertler et al, 2008) and form precise nonrandom local synaptic connections with each other (Taverna et al, 2008;Planert et al, 2010;Cepeda et al, 2013). Imbalances in the activity of the two pathways is thought to contribute to the cognitive and motor symptoms seen in late onset neurodegenerative disorders such as Parkinson's disease (Taverna et al, 2008) and Huntington's disease (Cepeda et al, 2013), but also those seen in early onset neurodevelopmental disorders such as Tourette's syndrome (McNaught & Mink, 2011;Albin, 2018), OCD (Graybiel & Rauch, 2000;Langen et al, 2011), ADHD (Del Campo et al, 2011) and autism spectrum disorders (Shepherd, 2013). The cellular and neural circuit changes that underpin these neurodevelopmental disorders are major research areas.…”

Deep brain stimulation modulates pallidal and subthalamic neural oscillations in Tourette's syndrome

“…Tourette's syndrome (TS) is a neurological disorder manifested by motor and vocal or phonic tics. TS is often accompanied by obsessive compulsive disorder, attention-deficient hyperactive disorder, poor impulse control, and other comorbid behavioral problems (Albin, 2017;Albin & Mink, 2006). Patients with TS have impairments in impulse inhibition which might relate to the reduced inhibitory output of the basal ganglia (Ganos, 2016;Jackson, Draper, Dyke, Pépés, & Jackson, 2015;Jahanshahi & Rothwell, 2017).…”