Cathodic- and anodic-pulses can alternately activate different sub-populations of neurons during sustained high-frequency stimulation of axons in rat hippocampus

Feng, Zhouyan; Zheng, Lvpiao; Yuan, Yue; Yang, Gangsheng; Hu, Yifan; Lu, Chuchu; Wang, Zhaoxiang

doi:10.1088/1741-2552/ac518c

Cited by 2 publications

(1 citation statement)

References 42 publications

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“…Anodic stimulation is relatively more efficient at activating HDP compared to CSBT, but overall cathodic stimulation is more generally efficient. Comparison of cathodic and anodic stimulation in rodent hippocampus similarly demonstrated that the two polarities activate different axonal subpopulations in the same pathway 63 . Different latencies observed for EP2 and EP3 can be explained by HDP being composed from axonal bundles of different sizes as shown in histologic studies 58 .…”

Section: Discussionmentioning

confidence: 95%

Neural pathway activation in the subthalamic region depends on stimulation polarity

Borgheai,

Opri,

Isbaine

et al. 2024

Preprint

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Deep brain stimulation (DBS) is an effective treatment for Parkinsońs disease (PD); however, there is limited understanding of which subthalamic pathways are recruited in response to stimulation. Here, by focusing on the polarity of the stimulus waveform (cathodic vs. anodic), our goal was to elucidate biophysical mechanisms that underlie electrical stimulation in the human brain. In clinical studies, cathodic stimulation more easily triggers behavioral responses, but anodic DBS broadens the therapeutic window. This suggests that neural pathways involved respond preferentially depending on stimulus polarity. To experimentally compare the activation of therapeutically relevant pathways during cathodic and anodic subthalamic nucleus (STN) DBS, pathway activation was quantified by measuring evoked potentials resulting from antidromic or orthodromic activation in 15 PD patients undergoing DBS implantation. Cortical evoked potentials (cEP) were recorded using subdural electrocorticography, DBS local evoked potentials (DLEP) were recorded from non-stimulating contacts and EMG activity was recorded from arm and face muscles. We measured: 1) the amplitude of short-latency cEP, previously demonstrated to reflect activation of the cortico-STN hyperdirect pathway, 2) DLEP amplitude thought to reflect activation of STN-globus pallidus (GP) pathway, and 3) amplitudes of very short-latency cEP and motor evoked potentials (mEP) for activation of cortico-spinal/bulbar tract (CSBT). We constructed recruitment and strength-duration curves for each EP/pathway to compare the excitability for different stimulation polarities. We compared experimental data with the most advanced DBS computational models. Our results provide experimental evidence that subcortical cathodic and anodic stimulation activate the same pathways in the STN region and that cathodic stimulation is in general more efficient. However, relative efficiency varies for different pathways so that anodic stimulation is the least efficient in activating CSBT, more efficient in activating the HDP and as efficient as cathodic in activating STN-GP pathway. Our experiments confirm biophysical model predictions regarding neural activations in the central nervous system and provide evidence that stimulus polarity has differential effects on passing axons, terminal synapses, and local neurons. Comparison of experimental results with clinical DBS studies provides further evidence that the hyperdirect pathway may be involved in the therapeutic mechanisms of DBS.

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Section: Discussionmentioning

confidence: 95%

Neural pathway activation in the subthalamic region depends on stimulation polarity

Borgheai,

Opri,

Isbaine

et al. 2024

Preprint

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Interactions between cathodic- and anodic-pulses during high-frequency stimulations with the monophasic-pulses alternating in polarity at axons—experiment and simulation studies

Hu,

Feng,

Zheng

et al. 2023

J. Neural Eng.

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Background. Electrical neuromodulation therapies commonly utilize high-frequency stimulations (HFS) of biphasic-pulses to treat neurological disorders. The biphasic pulse consists of a leading cathodic-phase to activate neurons and a lagging anodic-phase to balance electrical charges. Because both monophasic cathodic- and anodic-pulses can depolarize neuronal membranes, splitting biphasic-pulses into alternate cathodic- and anodic-pulses could be a feasible strategy to improve stimulation efficiency. Objective. We speculated that neurons in the volume initially activated by both polarity pulses could change to be activated only by anodic-pulses during sustained HFS of alternate monophasic-pulses. To verify the hypothesis, we investigated the interactions of the monophasic pulses during HFS and revealed possible underlying mechanisms. Approach. Different types of pulse stimulations were applied at the alvear fibers (i.e. the axons of CA1 pyramidal neurons) to antidromically activate the neuronal cell bodies in the hippocampal CA1 region of anesthetized rats in-vivo. Sequences of antidromic HFS (A-HFS) were applied with alternate monophasic-pulses or biphasic-pulses. The pulse frequency in the A-HFS sequences was 50 or 100 Hz. The A-HFS duration was 120 s. The amplitude of antidromically-evoked population spike was measured to evaluate the neuronal firing induced by each pulse. A computational model of axon was used to explore the possible mechanisms of neuronal modulations. The changes of model variables during sustained A-HFS were analyzed. Main results. In rat experiments, with a same pulse intensity, the activation volume of a cathodic-pulse was greater than that of an anodic-pulse. In paired-pulse tests, a preceding cathodic-pulse was able to prevent a following anodic-pulse from activating neurons due to refractory period. This indicated that the activation volume of a cathodic-pulse covered that of an anodic-pulse. However, during sustained A-HFS of alternate monophasic-pulses, the anodic-pulses were able to prevail over the cathodic-pulses in activating neurons in the overlapped activation volume. Model simulation results show the mechanisms of the activation failures of cathodic-pulses. They include the excessive membrane depolarization caused by an accumulation of potassium ions, the obstacle of hyperpolarization in the conduction pathway and the interactions from anodic-pulses. Significance. The study firstly showed the domination of anodic-pulses over cathodic-pulses in their competitions to activate neurons during sustained HFS. The finding provides new clues for designing HFS paradigms to improve the efficiency of neuromodulation therapies.

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Cathodic- and anodic-pulses can alternately activate different sub-populations of neurons during sustained high-frequency stimulation of axons in rat hippocampus

Cited by 2 publications

References 42 publications

Neural pathway activation in the subthalamic region depends on stimulation polarity

Neural pathway activation in the subthalamic region depends on stimulation polarity

Interactions between cathodic- and anodic-pulses during high-frequency stimulations with the monophasic-pulses alternating in polarity at axons—experiment and simulation studies

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