Reinforcement Learning and Motor Biases in Children with Tourette Syndrome

Grant Type
Grant Year
Institution Location
Institution Organization Name
Columbia University
Investigators Name
Maia, Tiago Vaz, PhD

Tourette syndrome (TS) is associated with abnormalities in striatal dopaminergic neurotransmission, but the extent to which those abnormalities affect tonic dopamine, phasic dopamine, or both remains controversial. We will address this issue using a recently developed task that has been shown through neurocomputational modeling to be able to distinguish the behavioral effects of tonic and phasic dopamine. Briefly, the task assesses both (a) the general tendency for motor responding, which neurocomputational models suggest depends on tonic dopamine, and (b) the tendency to learn from rewards versus punishments, which neurocomputational models suggest depend on phasic dopamine bursts and dips, respectively. We hypothesize that patients with TS, relative to healthy controls, will exhibit (a) an increased tendency for motor responding, reflecting increased tonic dopamine, and (b) an increased sensitivity to rewards, reflecting increased phasic dopamine. We will test these hypotheses by recruiting 20 unmedicated children with TS and 20 age- and sex-matched children without TS, all of whom will perform the aforementioned task. A subset of the children will undergo functional magnetic resonance imaging (fMRI) scanning as they perform the task. The fMRI scanning will enable us to assess prediction-error-related BOLD activity in the striatum, which is widely thought to reflect phasic dopaminergic signaling in the nigrostriatal pathway. Positive prediction errors are associated with phasic bursting of dopaminergic neurons and negative prediction errors are associated with phasic pauses in firing of dopaminergic neurons (in most, though not all, dopaminergic neurons). We therefore hypothesize that the children with TS, relative to the healthy children, will have increased BOLD activity in the striatum for positive, but not for negative, prediction errors, reflecting increased phasic dopaminergic innervation in TS. Understanding whether TS involves abnormalities in tonic dopamine, phasic dopamine, or both is important for the development of novel medications, as medications may – and often do – affect tonic and phasic dopamine differently. Tiago Vaz Maia, Ph.D., Bradley Scott Peterson, M.D., Wang Zhishun, Ph.D. Columbia University, New York, NY Award: $75,000 Commentary: Neurotransmitters – the chemicals that carry messages between nerve cells – are at the core of brain function. Substantial evidence implicates abnormalities in a specific neurotransmitter system – the dopaminergic system – in the generation of tics in Tourette syndrome (TS). However, the exact nature of these abnormalities remains unclear. The authors will investigate whether the abnormalities concern alterations in the amount of dopamine in the brain (baseline levels of dopamine) or in the response of the dopaminergic system to specific events (i.e., ‘tonic’ or ‘phasic’ dopamine levels, respectively). This distinction is important for the development of better medications for TS, as different drugs affect tonic and phasic dopamine levels differently. Tourette Association of America Inc. – Research Grant Award 2011-2012