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Neuropsychiatric effects of subthalamic neurostimulation in Parkinson disease

Nature Reviews Neurology volume 6, pages 487–498 (2010)Cite this article

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Abstract

Neurostimulation of the subthalamic nucleus (STN) is an established treatment for motor symptoms in advanced Parkinson disease (PD), although concerns exist regarding the safety of this therapy in terms of cognitive and psychiatric adverse effects. The basal ganglia are considered to be part of distributed cortico-subcortical networks that are involved in the selection, facilitation and inhibition of movements, emotions, behaviors and thoughts. The STN has a central role in these networks, probably providing a global 'no-go' signal. The behavioral and cognitive effects observed following STN high-frequency stimulation (HFS) probably reflect the intrinsic role of this nucleus in nonmotor functional domains. Nevertheless, postoperative behavioral changes are seldom caused by such stimulation alone. PD is a progressive neurodegenerative disorder with motor, cognitive, behavioral and autonomic symptoms. The pattern of neurodegeneration and expression of these symptoms are highly variable across individuals. The preoperative neuropsychiatric state can be further complicated by sensitization phenomena resulting from long-term dopaminergic treatment, which include impulse control disorders, punding, and addictive behaviors (dopamine dysregulation syndrome). Finally, personality traits, the social environment, culture and learned behaviors might be important determinants explaining why behavioral symptoms differ between patients after surgery. Here, we summarize the neuropsychiatric changes observed after STN HFS and try to disentangle their various etiologies.

Key Points

  • The basal ganglia modulate the activity of distinct frontal cortical areas—such as motor and premotor cortices, dorsolateral prefrontal cortex and anterior cingulate cortex—via parallel corticobasal ganglia–thalamocortical loops

  • Clinical findings support the view that the basal ganglia are involved in the selection, facilitation and inhibition of movements, emotions, behaviors and thoughts

  • The subthalamic nucleus (STN) has a central regulatory role in cortico-subcortical networks involving the basal ganglia, providing a global 'no-go' signal

  • Dopaminergic medication and high-frequency stimulation of the STN act synergistically on the various basal ganglia loops

  • Apathy and depression in Parkinson disease (PD) might reflect hypodopaminergic states of the limbic and associative corticobasal ganglia–thalamocortical loops

  • Sensitization and dopaminergic or electrical overstimulation of the limbic and associative corticobasal ganglia–thalamocortical loops probably underlie the development of impulsivity and mania in PD

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Figure 1: The basal ganglia form anatomically and functionally segregated neuronal circuits with thalamic nuclei and frontal cortical areas.
Figure 2: Neural network model of the striato-thalamocortical circuit.
Figure 3: Behavioral effects of dopaminergic medication or high-frequency stimulation.

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Acknowledgements

This work was supported by funding from the German Ministry of Research through the Network of European Funding for Neuroscience Research (ERANET-NEURON) scheme (grant #01EW0902).

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  1. Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Arnold-Heller-Strasse 3, Haus 41, Kiel, 24105, Germany

    Jens Volkmann & Karsten Witt

  2. Department of Psychiatry, Universitätsklinikum Würzburg, Füchsleinstrasse 15, Würzburg, 97080, Germany

    Christine Daniels

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J. Volkmann, C. Daniels and K. Witt all researched the data for the article, provided substantial contributions to discussions of the content, and contributed equally to writing the article and to reviewing and/or editing of the manuscript before submission.

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J. Volkmann has served as a consultant for and has received honoraria for speaking from Medtronic. He has also received research support from this company. The other authors declare no competing interests.

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Volkmann, J., Daniels, C. & Witt, K. Neuropsychiatric effects of subthalamic neurostimulation in Parkinson disease. Nat Rev Neurol 6, 487–498 (2010). https://doi.org/10.1038/nrneurol.2010.111

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