Synchronous Responses of Population Neurons to the Changes of Inter-Pulse-Intervals during Stimulations of Afferent Fibers.

Abstract

Deep brain stimulation (DBS) has been used to treat many brain disorders. Studies have shown that in DBS therapies, high frequency stimulation (HFS) with a constant pulse frequency over ~90 Hz can obtain better efficacy than stimulations with irregular inter-pulse-interval (IPI). The reasons are not clear yet. We hypothesized that irregular IPI might cause synchronous firing in target neurons thereby weakening the DBS efficacy. To test this hypothesis, stimulation trains of orthodromic-HFS (O-HFS) with different IPI were applied on the Schaffer collaterals, i.e., the afferent fiber tracts of the hippocampal CA1 region in anaesthetized rats. The amplitude of evoked population spikes (PS) in the downstream region was used as an electrophysiological index to evaluate the synchronicity of neuronal firing. The results showed that 100 Hz O-HFS with constant IPI induced de-synchronized firing of downstream neurons without PS events, whereas O-HFS with sparse prolonged IPI (20 or 100 ms) or with irregular IPI (1.7 - 50 ms) generated large PS events. Presumably, the longer IPI in O-HFS trains might provide adequate time to allow axons to recover from HFS-induced block and to respond the next coming pulse, synchronously. Therefore, following longer IPI, the population neurons in the target region could receive synchronous impulses from a lot of axonal fibers thereby generating action potentials synchronously. These findings are important for revealing new underlying mechanisms of DBS and for advancing the application of DBS.