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Abstract
Deep brain stimulation (DBS) has shown wide applications for treating various disorders in the central nervous system by using high frequency stimulation (HFS) sequences of electrical pulses. However, upon the onset of HFS sequences, the narrow pulses could induce synchronous firing of action potentials among large populations of neurons and cause a transient phase of “onset response” that is different from the subsequent steady state. To investigate the transient onset phase, the antidromically-evoked population spikes (APS) were used as an electrophysiological marker to evaluate the synchronous neuronal reactions to axonal HFS in the hippocampal CA1 region of anesthetized rats. New stimulation paradigms with time-varying intensity and frequency were developed to suppress the “onset responses”. Results show that HFS paradigms with ramp-up intensity at the onset phase could suppress large APS potentials. In addition, an intensity ramp with a slower ramp-up rate or with a higher pulse frequency had greater suppression on APS amplitudes. Therefore, to reach a desired pulse intensity rapidly, a stimulation paradigm combining elevated frequency and ramp-up intensity was used to shorten the transition phase of initial HFS without evoking large APS potentials. The results of the study provide important clues for certain transient side effects of DBS and for development of new adaptive stimulation paradigms.
Highlights
Electrical stimulation therapy has wide applications in both central and peripheral nervous systems for treating clinic patients
At the onset of A-high-frequency stimulation (HFS), every pulse evoked a large antidromically-evoked population spikes (APS) with an amplitude (>10 mV) similar to the APS evoked by a single pulse stimulation in baseline tests
Two minutes after the end of antidromical HFS (A-HFS), the APS evoked by a test pulse recovered (Figure 3B)
Summary
Electrical stimulation therapy has wide applications in both central and peripheral nervous systems for treating clinic patients. Deep brain stimulation (DBS) has been used to treat brain disorders, such as Parkinson’s disease, essential tremor, epilepsy, addiction, and depression (Udupa and Chen, 2015; Wichmann and DeLong, 2016). A pulse frequency >50 Hz is defined as HFS (Durand and Bikson, 2001). Regular DBS of subthalamic nucleus (STN) utilizes stimulation frequencies of 90 – 185 Hz as efficient frequencies for treating tremor in clinic (Rizzone et al, 2001; Kuncel et al, 2006). Kilohertz frequencies have been used for stimulating peripheral nerves to induce conduction block for therapy (Franke et al, 2014; McGee et al, 2015)
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