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Electrical Brain Stimulation: Mechanisms and Modulation of Neuronal Activity

  • Open Access
  • 2026
  • Open Access
  • Book
Author
Zhouyan Feng
Publisher
Springer Nature Singapore
Part of
Springer Professional "Business + Economics & Engineering + Technology"
Springer Professional "Engineering + Technology"
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About this book

This open access book explores the mechanisms and modulation of invasive neural electrical stimulation in the brain. Drawing from the author's extensive research experience, it offers in-depth yet accessible content, enriched with vivid illustrations and practical applications. Notably, the book provides detailed techniques for animal experiments and methods for recording and processing neural electrical signals with a depth rare in similar works. The book is divided into two parts. Part I introduces fundamental electrophysiological theories and experimental methods. It covers the basic electrical properties of neuronal membranes, the famous Hodgkin-Huxley mathematical model, hippocampal neural networks and electrically evoked potentials, in-vivo rat experimental methods and equipment, and techniques for recording and processing neural electrical signals. Part II focuses on neural modulation through various electrical stimulations. It examines how various patterns of high-frequency pulse stimulations affect individual neurons, neuronal populations, and neural networks. In addition to exploring neuronal responses to electrical stimulation under normal physiological conditions, this part also investigates the inhibitory effects of high-frequency stimulation on epileptiform activity. This comprehensive book can serve as a valuable reference for researchers, teachers, students, and enthusiasts in the fields of neurophysiology, neural signal analysis, neural engineering, neuromodulation, brain stimulation, and brain-computer interfaces. It also provides excellent supplementary material for undergraduate and graduate courses in biomedical signal processing, neural engineering, and neuroscience.

Table of Contents

  1. Frontmatter

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  2. Fundamentals and Experimental Methods

    1. Frontmatter

    2. 1. Fundamentals of Neuro-electrophysiology

      • Open Access
      Zhouyan Feng
      Abstract
      This chapter describes the fundamentals of neuro-electrophysiology. The electrical properties of neuronal membranes can be simulated by equivalent circuits composed of resistance and capacitance. Ion concentration differences across the membrane, combined with varying membrane permeability to ions, form the basis of resting and action potentials. The chapter introduces quantitative membrane indices (including time constant, space constant, rheobase and chronaxie), membrane cable equations, and Hodgkin-Huxley computational model. It also covers electrical stimulation approaches for brain neurons, including intracellular versus extracellular modes, current versus voltage modes, and unipolar versus bipolar modes. Finally, it addresses stimulation safety rules to prevent tissue damage and electrode corrosion.
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    3. 2. Neural Circuits and Evoked Potentials

      • Open Access
      Zhouyan Feng
      Abstract
      The animal experiments described in this book focus on the rat hippocampus. This chapter introduces hippocampal structures and neural circuits. It explains the generations of various evoked potentials in neuronal population responses to pulse stimulations, including orthodromically and antidromically evoked potentials. The chapter also explores the effects of feedforward and feedback inhibitory circuits through paired-pulse stimulations in the hippocampal CA1 and CA3 regions.
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    4. 3. Experimental Methods and Setup

      • Open Access
      Zhouyan Feng
      Abstract
      This chapter covers animal surgical methods, electrodes, and experimental setup for in-vivo rat neuro-electrophysiological studies. It details the use of stereotaxic instruments, methods for accurate electrode positioning, and the usages of amplifiers, recorders, and electrical stimulators. It also describes a custom-designed electrical stimulation system capable of producing diverse signals and achieving closed-loop stimulation.
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    5. 4. Neural Signal Recording and Processing

      • Open Access
      Zhouyan Feng
      Abstract
      This chapter introduces methods for detecting and analyzing extracellularly recorded action potentials from individual neurons, also known as unit spikes. It describes the settings of appropriate recording frequency band, sampling rate and resolution for spike recordings. It introduces window-based detection and multiple-channel sorting algorithms for spikes, along with analysis methods for spike sequences (including inter-spike-interval histogram, autocorrelation histogram, cross-correlation histogram, and so on). The chapter also covers spectrum analysis methods for local field potentials and EEG signals. Finally, it presents the current source density analysis for tracking transmembrane current during neuronal activation and provides methods for removing stimulation artifacts from both sinusoidal and pulse electrical stimulations.
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  3. Neuromodulation Effects of Electrical Stimulations on Axons

    1. Frontmatter

    2. 5. Neuronal Responses to Axonal High-Frequency Pulse Stimulations

      • Open Access
      Zhouyan Feng
      Abstract
      Among neuronal structures, the axonal membrane has the shortest chronaxie, making it most susceptible to narrow pulses commonly used in neuromodulation techniques like deep brain stimulation (DBS). This chapter details our experiments in the rat hippocampal CA1 region, which verify intermittent axonal block caused by high-frequency stimulations (HFS). The experiments include both antidromic HFS (A-HFS) applied to the axons of recorded pyramidal neurons and orthodromic HFS (O-HFS) applied to presynaptic afferent fibers. The results showed that the axonal HFS can extend the refractory period of axons and alter the excitability of somata, causing a silent period without firing immediately after HFS cessation. The experiments also showed non-uniform clustered firing produced by HFS with constant pulse intervals.
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    3. 6. Neuronal Responses to Axonal HFS with Time-Varying Parameters

      • Open Access
      Zhouyan Feng
      Abstract
      This chapter presents our findings from different HFS paradigms using time-varying parameters, including gradient changes in pulse frequency and intensity, alternating pulses with dual parameters, inserting and deleting pulses in regular stimulation, and randomly varying inter-pulse-intervals within a small range. Under HFS-induced axonal block, stimulations with time-varying parameters can produce diverse neuronal responses. This creates opportunities for developing novel stimulation paradigms that can address a wide range of neuromodulation needs.
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    4. 7. Neuronal Responses to Both Negative and Positive Pulses During HFS

      • Open Access
      Zhouyan Feng
      Abstract
      This chapter presents our findings that challenge the conventional view—that negative pulses are more effective than positive pulses in extracellular stimulations. During sustained high-frequency stimulations (HFS) with alternating monophasic pulses of opposite polarities, the firing induced by positive pulses became comparable to that induced by negative pulses. Furthermore, the two types of pulses activated different subpopulations of neurons. For neurons that responded to both types of pulses at baseline, positive pulses actually surpassed negative pulses during HFS. Our computational simulations revealed complex interactions between the two pulse types in their activation mechanisms on axonal membrane.
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    5. 8. Effects of High-Frequency Stimulations on Epileptiform Discharges

      • Open Access
      Zhouyan Feng
      Abstract
      This chapter presents our studies on the inhibitory effects of electrical stimulations on the epileptiform discharges generated by three methods: brief high-frequency stimulation and two epileptogenic agents (4-aminopyridine and picrotoxin). Results showed that both pulse and sinusoidal high-frequency stimulations (HFS) at the Schaffer collaterals (the hippocampal CA1 afferent fibers), can suppress epileptiform spikes induced by these methods. The stimulation patterns and action mechanisms can vary with the epileptogenic methods, involving processes such as desynchronization and depolarization block. The findings suggest customizing stimulation parameters (e.g., duration) and modes (e.g., open-loop and closed-loop) is essential for effectively suppressing various types of epileptiform discharges.
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    6. 9. Neuromodulation Through Axonal Stimulations in Brain

      • Open Access
      Zhouyan Feng
      Abstract
      This chapter summarizes our research on axonal electrical stimulations described in Part II. It presents the critical role of axonal responses in brain stimulations, discusses the high-frequency stimulation (HFS)-induced axonal block and its resulting neuronal responses, analyzes the effects of different time-varying stimulations under the situation of axonal block, and explores the potential post-stimulation effects of DBS, applications of closed-loop stimulations, and the relations between DBS and brain-computer interfaces.
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  4. Backmatter

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Title
Electrical Brain Stimulation: Mechanisms and Modulation of Neuronal Activity
Author
Zhouyan Feng
Copyright Year
2026
Publisher
Springer Nature Singapore
Electronic ISBN
978-981-9541-45-4
Print ISBN
978-981-9541-44-7
DOI
https://doi.org/10.1007/978-981-95-4145-4

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