Global and Multi-Focal Changes in Cerebral Blood Flow during Subthalamic Nucleus Stimulation in Parkinson’s disease

There is an increased focus on the electrical stimulation of the subthalamic nucleus (STN) for the treatment of Parkinson’s disease (PD). Although the deep brain stimulation (DBS) of the STN (DBS-STN) effectively controls movement disabilities in patients suffering from PD, the physiological mechanism of this neuro-modulatory therapy is not known. Previous studies have suggested that DBS-STN alters the neurophysiological activity in the basal ganglia via the desynchronization of abnormal oscillations, interference with neural signals, modulation of neurotransmitter and hormonal signaling, and alteration of inhibition and excitation within neural networks. Although recent studies have established a link between DBS-STN and changes in cerebral blood flow (CBF), there is a dearth of information on the characteristics of CBF changes induced by DBS-STN.

Recently scientists at Nathan Kline Institute for Psychiatric Research in New York, Asim Mubeen, Babak Ardekani and led by John Sidtis in collaboration with Michele Tagliati from the Cedars-Sinai Medical Center and Ron Alterman from Beth Israel Deaconess Medical Center, and Vijay Dhawan and David Eidelberg from Feinstein Center for Neurosciences demonstrated that a combination of voxel-based principal component analysis (PCA) and Fisher’s linear discriminant analysis (FLDA) can be used to explore the characteristics of CBF changes induced by DBS-STN and distinguish between DBS-STN on and off CBF PET scans. Their research work is now published in Journal of Cerebral Blood Flow & Metabolism.

The research team observed that the PCA- FLDA method resulted in widespread CBF-changes. This approach discriminated DBS-STN on and off cerebral blood flow (CBF) images with a high degree of specificity, sensitivity, and accuracy. They also observed that the PCA component of the analysis identified global CBF changes during DBS-STN while the FLDA component identified wide-spread multi-focal CBF changes during DBS-STN.

On the one hand, the authors identified a positive correlation between the on-off difference scores of the whole-brain CBF values and the first principal component values for the DBS-STN on-condition. On the other hand, they observed a negative correlation between the whole-brain CBF values and the first principal component values for the DBS-STN off-condition. In addition, they discovered that there was a positive correlation between the CBF values obtained from the PCA-FLDA analysis and the clinical measures in the DBS-STN off condition while there was a negative correlation between the CBF values obtained from the PCA-FLDA analysis and the clinical measures in the DBS-STN on condition. They also discovered that certain CBF measurements were related to various CBF characteristics when the DBS-STN was off and suggested that neuromodulation may disrupt the relationship between behavior and CBF.

In a nutshell, Professor John Sidtis and colleagues successfully developed a novel approach to characterize the CBF changes induced by DBS-STN. Their approach discriminated the status of DBS-STN with 90% accuracy, sensitivity, and specificity. Their findings will advance further studies on the local, network global, and regional characterization of CBF changes induced by DBS-STN and the development of therapeutic strategies for the treatment of PD.