Involvement of the subthalamic nucleus in impulse control disorders associated with Parkinson's disease.
Behavioural abnormalities such as impulse control disorders may develop when patients with Parkinson's disease receive dopaminergic therapy, although they can be controlled by deep brain stimulation of the subthalamic nucleus. We have recorded local field potentials in the subthalamic nucleus of 28 patients with surgically implanted subthalamic electrodes. According to the predominant clinical features of each patient, their Parkinson's disease was associated with impulse control disorders (n = 10), dyskinesias (n = 9) or no dopaminergic mediated motor or behavioural complications (n = 9). Recordings were obtained during the OFF and ON dopaminergic states and the power spectrum of the subthalamic activity as well as the subthalamocortical coherence were analysed using Fourier transform-based techniques. The position of each electrode contact was determined in the postoperative magnetic resonance image to define the topography of the oscillatory activity recorded in each patient. In the OFF state, the three groups of patients had similar oscillatory activity. By contrast, in the ON state, the patients with impulse control disorders displayed theta-alpha (4-10 Hz) activity (mean peak: 6.71 Hz) that was generated 2-8 mm below the intercommissural line. Similarly, the patients with dyskinesia showed theta-alpha activity that peaked at a higher frequency (mean: 8.38 Hz) and was generated 0-2 mm below the intercommissural line. No such activity was detected in patients that displayed no dopaminergic side effects. Cortico-subthalamic coherence was more frequent in the impulsive patients in the 4-7.5 Hz range in scalp electrodes placed on the frontal regions anterior to the primary motor cortex, while in patients with dyskinesia it was in the 7.5-10 Hz range in the leads overlying the primary motor and supplementary motor area. Thus, dopaminergic side effects in Parkinson's disease are associated with oscillatory activity in the theta-alpha band, but at different frequencies and with different topography for the motor (dyskinesias) and behavioural (abnormal impulsivity) manifestations. These findings suggest that the activity recorded in parkinsonian patients with impulse control disorders stems from the associative-limbic area (ventral subthalamic area), which is coherent with premotor frontal cortical activity. Conversely, in patients with l-dopa-induced dyskinesias such activity is recorded in the motor area (dorsal subthalamic area) and it is coherent with cortical motor activity. Consequently, the subthalamic nucleus appears to be implicated in the motor and behavioural complications associated with dopaminergic drugs in Parkinson's disease, specifically engaging different anatomo-functional territories.
Department of Neurology, Clinica Universidad de Navarra, Medical School, 31008 Pamplona, Spain. mcroroz@unav.es
Maria C
MC
Rodriguez-Oroz
Jon
J
López-Azcárate
David
D
Garcia-Garcia
Manuel
M
Alegre
Jon
J
Toledo
Miguel
M
Valencia
Jorge
J
Guridi
Julio
J
Artieda
Jose A
JA
Obeso
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use; D058256:Brain Waves / Q000502:physiology*; D046690:Deep Brain Stimulation; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000150:complications / Q000503:physiopathology*; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D004567:Electrodes, Implanted; D004594:Electrophysiology; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D020531:Subthalamic Nucleus / Q000503:physiopathology*
D000978:Antiparkinson Agents; D007980:Levodopa