Abstract
BackgroundElectrical pulse stimulations have been applied in brain for treating certain diseases such as movement disorders. High-frequency stimulations (HFS) of biphasic pulses have been used in clinic stimulations, such as deep brain stimulation (DBS), to minimize the risk of tissue damages caused by the electrical stimulations. However, HFS sequences of monophasic pulses have often been used in animal experiments for studying neuronal responses to the stimulations. It is not clear yet what the differences of the neuronal responses to the HFS of monophasic pulses from the HFS of biphasic pulses are.MethodsTo investigate the neuronal responses to the two types of pulses, orthodromic-HFS (O-HFS) and antidromic-HFS (A-HFS) of biphasic and monophasic pulses (1-min) were delivered by bipolar electrodes, respectively, to the Schaffer collaterals (i.e., afferent fibers) and the alveus fibers (i.e., efferent fibers) of the rat hippocampal CA1 region in vivo. Evoked population spikes of CA1 pyramidal neurons to the HFSs were recorded in the CA1 region. In addition, single pulses of antidromic- and orthodromic-test stimuli were applied before and after HFSs to evaluate the baseline and the recovery of neuronal activity, respectively.ResultsSpreading depression (SD) appeared during sequences of 200-Hz monophasic O-HFS with a high incidence (4/5), but did not appear during corresponding 200-Hz biphasic O-HFS (0/6). A preceding burst of population spikes appeared before the SD waveforms. Then, the SD propagated slowly, silenced neuronal firing temporarily and resulted in partial recovery of orthodromically evoked population spikes (OPS) after the end of O-HFS. No SD events appeared during the O-HFS with a lower frequency of 100 Hz of monophasic or biphasic pulses (0/5 and 0/6, respectively), neither during the A-HFS of 200-Hz pulses (0/9). The antidromically evoked population spikes (APS) after 200-Hz biphasic A-HFS recovered to baseline level within ~ 2 min. However, the APS only recovered partially after the 200-Hz A-HFS of monophasic pulses.ConclusionsThe O-HFS with a higher frequency of monophasic pulses can induce the abnormal neuron activity of SD and the A-HFS of monophasic pulses can cause a persisting attenuation of neuronal excitability, indicating neuronal damages caused by monophasic stimulations in brain tissues. The results provide guidance for proper stimulation protocols in clinic and animal experiments.
Highlights
Electrical pulse stimulations have been applied in brain for treating certain diseases such as movement disorders
Spreading depression appeared during orthodromic‐High-frequency stimulations (HFS) with monophasic but not biphasic pulses To investigate the different effects between biphasic and monophasic pulses, HFS sequences of pulses were delivered through the stimulation electrodes placed at the Schaffer collaterals for the orthodromic-HFS (O-HFS) and at the alveus fibers for the antidromic-HFS (A-HFS), respectively (Fig. 1a)
After the disappearance of orthodromically evoked population spike (OPS), multiple unit activity (MUA) continued to the end of the O-HFS with a firing rate of unit spikes higher than baseline
Summary
Electrical pulse stimulations have been applied in brain for treating certain diseases such as movement disorders. Charge-balanced biphasic pulses (with a preceding negative pulse immediately followed by a positive one) are usually utilized in clinical DBS for safety [3, 4], while negative monophasic pulses are used in animal studies for investigating brain stimulations [5,6,7]. It is not clear whether HFS sequences of monophasic pulses could induce abnormal neuronal responses different from biphasic pulses. Sequences of monophasic negative pulses could result in irreversible chemical reactions to generate toxic products to damage the brain tissue [8]
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