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Neurological disorders

Stimulating side effects

Nature Reviews Neuroscience volume 8, page 913 (2007)Cite this article

Frank et al. used a decision-making task to show that healthy individuals and patients with Parkinson's disease taking dopaminergic medication take longer to make difficult decisions that involve a high degree of conflict than to make easy decisions. By contrast, patients with Parkinson's disease undergoing DBS of the STN responded faster in high-conflict choices, and also made more incorrect decisions. This DBS-induced premature responding was reversed when the stimulator was switched off. Thus, DBS of the STN might increase impulsivity by reducing the time that is taken to make high-conflict decisions.

In a different study, Sharp and colleagues showed that STN stimulation inhibited the firing rate of serotonin neurons in the dorsal raphe nucleus (DRN) in normal rats, as well as in two rat models of Parkinson's disease. They then went on to show that infusion of a GABAA (γ-aminobutyric acid) receptor agonist into the STN produced the same result, indicating that a stimulation-induced reduction in STN activity might cause the inhibition of DRN serotonin neurons. STN stimulation also induced depression-like behaviour in the rats, causing 'behavioural despair' in the forced-swim test. This effect was inhibited by treatment with a selective serotonin reuptake inhibitor, providing additional evidence that the depressive effect of STN stimulation might be due to the inhibition of serotonergic neurotransmission.

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ORIGINAL RESEARCH PAPER

  1. Frank, M. J. et al. Hold your horses: impulsivity, deep brain stimulation, and medication in Parkinsonism. Science 25 Oct 2007 (doi: 10.1126/science.1146157)

  2. Temel, Y. et al. Inhibition of 5-HT neuron activity and induction of depressive-like behavior by high-frequency stimulation of the subthalamic nucleus. Proc. Natl Acad. Sci. USA 104, 17087–17092 (2007)

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  1. Leonie Welberg
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Welberg, L. Stimulating side effects. Nat Rev Neurosci 8, 913 (2007). https://doi.org/10.1038/nrn2289

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