Dr. Sabato Santaniello’s Research Published in PNAS

January 26, 2015

In a research article available today, Dr. Santaniello, BME core faculty, and collaborators reveal insights in the therapeutic mechanisms of high-frequency stimulation (HFS) in Parkinson’s disease by using computational models of the basal ganglia and the cortico-thalamic system. The study, entitled “Therapeutic Mechanisms of High Frequency Stimulation in Parkinson’s Disease and Neural Restoration via Loop-based Reinforcement”, shows that the stimulation injected in the loop elicits neural perturbations that travel along multiple pathways with different latencies and rendezvous in striatum (one of the basal ganglia). If the stimulation frequency is high enough, these perturbations overlap and cause more regular, stimulus-locked firing patterns in striatum (resonance). Overlap is maximal at clinically relevant HFS and restores more normal activity in the remaining structures of the loop. This suggests that neural restoration and striatal resonance may be a therapeutic merit and mechanism of HFS, respectively.


The image depicts the arrangement of the spikes in striatum following DBS stimuli for multiple stimulation frequencies (20 Hz to 180 Hz). The white line on top shows the therapeutic efficacy of DBS as a function of the stimulation frequency. The study shows that DBS provides the best outcomes when neurons in striatum are entrained in a common spiking pattern, which occurs only for specific stimulation frequencies. This frequency selectivity mechanism resembles the phenomenon of resonance, which is well known in physics, and explains why DBS clinically works only for those specific frequencies.


Full article here