Deep brain stimulation of pedunculopontine tegmental nucleus (PPTg) promotes cognitive and metabolic changes: a target-specific effect or response to a low-frequency pattern of stimulation?

Deep brain stimulation (DBS) is a reliable treatment for advanced Parkinson's disease (PD) patients, but a possible risk of worsening cognitive functions, although modest, may postpone or halt DBS clinical indication. In a small cohort of PD patients we have pioneered the simultaneous implantation of both the subthalamic nucleus (STN) and the pedunculopontine tegmental nucleus (PPTg). Here we describe the cognitive test performance and the corresponding cortical metabolic activity, as assessed through 18-fluorodeoxyglucose (FDG)-positron emission tomography (PET), of these six PD patients tested in PPTg-ON vs- PPTg-OFF condition. PPTg-ON condition (at low frequency, 25 Hz) induced better performance in tests exploring both executive and attentive domains, which were coupled with an increased glucose utilization in prefrontal and frontal bilateral cortical areas, including both lateral (i.e., BA9) and more antero-medial cortices (BA 25-32). Moreover, during PPTg-ON, a surprising increase of FDG consumption was also observed in the left ventral striatum. These data are consistent with the hypothesis of a positive effect of 25 Hz PPTg-DBS on PD patients' cognitive profile, probably due to a facilitatory effect exerted by PPTg on both associative and limbic pathways.