Neurophysiologic mechanisms of deep-brain stimulation unveiled

By Eleanor McDermid, Senior medwireNews Reporter

The beneficial effects of subthalamic nucleus (STN) stimulation in patients with Parkinson's disease (PD) are partly down to compensatory activation of nonmotor dopamine pathways during exercise, research suggests.

This is consistent with the reduced dopamine needs of patients treated with deep-brain stimulation (DBS), say study author Yasuomi Ouchi (Hamamatsu University School of Medicine) and colleagues.

"Exercise" for the 12 patients in the study consisted of them extending and flexing their right foot at their preferred pace while undergoing positron emission tomography. After 30 and 60 minutes of this activity, the speed was higher and the angle of the foot when flexed smaller if patients were on stimulation rather than off, illustrating that DBS facilitated motor function.

The patients were aged an average of 64.9 years and had an average Hoehn and Yahr stage of 2.8 on stimulation and 4.4 off.

Binding of radiolabelled raclopride (a dopamine antagonist) during exercise was significantly reduced in the nucleus accumbens (NA) and the caudate when DBS was switched on compared with off, indicating increased dopamine binding in these areas when DBS was on. The reductions averaged 17.8% and 15.0% in the left and right NA, respectively, and 11.2% and 8.3% in the left and right caudate, respectively.

By contrast, there was no change in the ventral or dorsal putamen. This suggests that STN stimulation activates pathways involved with the reward system - the mesolimbic and mesocortical dopamine systems - rather than the motor-related nigrostriatal dopamine system, say the researchers.

The increased dopamine binding did not occur if the patients did not exercise, leading the team to suggest that "STN-DBS itself may not be sufficient to activate dopamine neurons directly or indirectly without concomitant voluntary movement."

The greater patients' foot motion was (faster with more flexion) the smaller was the reduction in raclopride binding. "This indicated that patients with greater difficulties with motor exercise needed greater dopaminergic activation in the mesolimbocortical projection system," say Ouchi et al in the Journal of Cerebral Blood Flow and Metabolism.

Likewise, the more patients' motor symptoms improved under stimulation the smaller was the raclopride binding reduction during exercise; therefore, greater motor benefits from DBS meant less compensatory activation of nonmotor dopaminergic pathways was required to perform motor tasks.

"Even with the disease progression that occurs before Hoehn and Yahr stage III-IV, the caudate and NA remain relatively lightly affected," says the team. "This heterogeneous progression of PD may benefit from the therapeutic intervention of STN-DBS."

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