Maladaptive striatal plasticity and abnormal reward-learning in cervical dystonia

Tom Gilbertson (Lead / Corresponding author), Mark Humphries , Douglas Steele

Research output: Contribution to journalArticle

4 Citations (Scopus)
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Abstract

In monogenetic generalized forms of dystonia, in vitro neurophysiological recordings have demonstrated direct evidence for abnormal plasticity at the level of the cortico-striatal synapse. It is unclear whether similar abnormalities contribute to the pathophysiology of cervical dystonia, the most common type of focal dystonia. We investigated whether abnormal cortico-striatal synaptic plasticity contributes to abnormal reward-learning behavior in patients with focal dystonia. Forty patients and 40 controls performed a reward gain and loss avoidance reversal learning task. Participant's behavior was fitted to a computational model of the basal ganglia incorporating detailed cortico-striatal synaptic learning rules. Model comparisons were performed to assess the ability of four hypothesized receptor specific abnormalities of cortico-striatal long-term potentiation (LTP) and long-term depression (LTD): increased or decreased D1:LTP/LTD and increased or decreased D2: LTP/LTD to explain abnormal behavior in patients. Patients were selectively impaired in the post-reversal phase of the reward task. Individual learning rates in the reward reversal task correlated with the severity of the patient's motor symptoms. A model of the striatum with decreased D2:LTP/ LTD best explained the patient's behavior, suggesting excessive D2 cortico-striatal synaptic depotentiation could underpin biased reward-learning in patients with cervical dystonia. Reversal learning impairment in cervical dystonia may be a behavioral correlate of D2-specific abnormalities in cortico-striatal synaptic plasticity. Reinforcement learning tasks with computational modeling could allow the identification of molecular targets for novel treatments based on their ability to restore normal reward-learning behavior in these patients.

Original languageEnglish
Pages (from-to)3191-3204
Number of pages14
JournalEuropean Journal of Neuroscience
Volume50
Issue number7
Early online date7 Apr 2019
DOIs
Publication statusPublished - 30 Oct 2019

Keywords

  • basal ganglia
  • cervical dystonia
  • cortico-striatal plasticity
  • reinforcement learning
  • reward prediction error

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