Abstract
We tested the hypothesis that modulation of monoaminergic tone with deep-brain stimulation (DBS) of subthalamic nucleus would reveal a site of reactivity in the ventromedial prefrontal cortex that we previously identified by modulating serotonergic and noradrenergic mechanisms by blocking serotonin-noradrenaline reuptake sites. We tested the hypothesis in patients with Parkinson's disease in whom we had measured the changes of blood flow everywhere in the brain associated with the deep brain stimulation of the subthalamic nucleus. We determined the emotional reactivity of the patients as the average impact of emotive images rated by the patients off the DBS. We then searched for sites in the brain that had significant correlation of the changes of blood flow with the emotional impact rated by the patients. The results indicate a significant link between the emotional impact when patients are not stimulated and the change of blood flow associated with the DBS. In subjects with a low emotional impact, activity measured as blood flow rose when the electrode was turned on, while in subjects of high impact, the activity at this site in the ventromedial prefrontal cortex declined when the electrode was turned on. We conclude that changes of neurotransmission in the ventromedial prefrontal cortex had an effect on the tissue that depends on changes of monoamine concentration interacting with specific combinations of inhibitory and excitatory monoamine receptors.
Highlights
We have shown that activity in a circumscribed region of the medial prefrontal cortex undergoes a change of activity when the region is challenged by administration of the serotonin-noradrenaline reuptake inhibitor clomipramine
One of the sites at which blood flow underwent this change associated with the deep-brain stimulation (DBS) in correlation with emotional impact coincided with the area at which blood flow underwent a change during the clomipramine challenge reported by Geday and Gjedde [1], in both cases in inverse proportion to the emotional impact of the emotive images presented in the absence of a drug challenge or electrical stimulation
With the mean of the off and on ratings, the significance increased further (P = 0.019). While this implies that the change of emotional impact ratings with stimulation failed utterly to reach significance (P = 0.94), we note that the ratings of emotional impact on and off DBS in five of the seven subjects changed in parallel with the
Summary
We have shown that activity in a circumscribed region of the medial prefrontal cortex undergoes a change of activity when the region is challenged by administration of the serotonin-noradrenaline reuptake inhibitor clomipramine. In this previous study (File S1), the change of activity in each subject correlated inversely with the emotional impact of standardized emotive images presented to the subjects in separate sessions [1]. Because of the close relations between the serotonergic, noradrenergic, and dopaminergic systems, we further speculated that a general mechanism would link monoaminergic tone and emotional reactivity in this specific region. We speculate that the effects of this dopamine release depend on the differential distributions of D1 and D2 receptors that respectively facilitate and inhibit the excitability of the neurons on which these receptors reside
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