Dynamics of neuronal firing modulated by high-frequency electrical pulse stimulations at axons in rat hippocampus.

OBJECTIVE: The development of electrical pulse stimulations in brain, including deep brain stimulation (DBS), is promising for treating various brain diseases. However, the mechanisms of brain stimulations are not yet fully understood. Previous studies have shown that the commonly used high-frequency stimulation (HFS) can increase the firing of neurons and modulate the pattern of neuronal firing. Because the generation of neuronal firing in brain is a nonlinear process, investigating the characteristics of nonlinear dynamics induced by HFS could be helpful to reveal more mechanisms of brain stimulations. The aim of present study is to investigate the fractal properties in the neuronal firing generated by HFS.

METHODS: HFS pulse sequences with a constant frequency 100 Hz were applied in the afferent fiber tracts of rat hippocampal CA1 region. Unit spikes of both the pyramidal cells and the interneurons in the downstream area of stimulations were recorded. Two fractal indexes - the Fano factor and Hurst exponent were calculated to evaluate the changes of long-range temporal correlations (LRTCs), a typical characteristic of fractal process, in spike sequences of neuronal firing.

RESULTS: Neuronal firing at both baseline and during HFS exhibited LRTCs over multiple time scales. In addition, the LRTCs significantly increased during HFS, which was confirmed by simulation data of both randomly shuffled sequences and surrogate sequences.

CONCLUSION: The purely periodic stimulation of HFS pulses, a non-fractal process without LRTCs, can increase rather than decrease the LRTCs in neuronal firing.

SIGNIFICANCE: The finding provides new nonlinear mechanisms of brain stimulation and suggests that LRTCs could be a new biomarker to evaluate the nonlinear effects of HFS.