Comprehensive Treatise on Clinical Neurophysiology: Electroencephalography, Nerve Conduction, Electromyography, and Evoked Potentials

The Biophysical Foundations of Electrodiagnosis

The practice of electrodiagnostic medicine is fundamentally an exercise in applied physics and cellular physiology. It requires the clinician to visualize the microscopic behavior of ion channels and membrane potentials through the lens of macroscopic signal processing. Whether recording the microvolt-level potentials of the cerebral cortex or the millivolt-level discharges of skeletal muscle, the underlying principles remain rooted in the generation of transmembrane currents and their propagation through biological volume conductors.

Cellular Generators of Electrical Fields

To interpret electrodiagnostic data, one must first distinguish between the two primary generators of extracellular electrical fields: the action potential (AP) and the postsynaptic potential (PSP). The AP is the fundamental unit of information transmission in the peripheral nervous system. It is a regenerative, all-or-none depolarization mediated by voltage-gated sodium channels. In Nerve Conduction Studies (NCS) and Electromyography (EMG), the AP is the primary signal of interest. However, due to its extremely short duration (1–2 milliseconds), the AP contributes negligibly to the signal recorded by scalp Electroencephalography (EEG) electrodes. The temporal summation required to generate a signal visible through the skull is physiologically impossible with asynchronous action potentials.

In contrast, the PSP serves as the primary generator for EEG. When a presynaptic neuron releases neurotransmitters, it induces a graded potential at the postsynaptic membrane—either an Excitatory Postsynaptic Potential (EPSP) or an Inhibitory Postsynaptic Potential (IPSP). These potentials last significantly longer than action potentials (tens to hundreds of milliseconds), allowing for temporal summation. The EEG signal, therefore, represents the spatiotemporal summation of thousands of synchronous PSPs generated by pyramidal neurons in the cerebral cortex.

Volume Conduction and the Dipole Theory

The concept of the dipole is central to understanding how intracellular currents produce extracellular fields detectable by surface electrodes. In the cerebral cortex, pyramidal neurons are arranged in a cytoarchitecturally unique manner: their apical dendrites extend upward toward the cortical surface, while their somas reside in deeper layers (primarily layers III and V), oriented parallel to one another and perpendicular to the cortical surface. When an afferent input causes an EPSP at the apical dendrite, positive ions (Na+) flow into the cell, creating a local "sink" (negativity) in the extracellular fluid at the superficial cortex. Simultaneously, a passive return current flows out of the cell body, creating a "source" (positivity) in the deeper layers. This charge separation creates a dipole vertically oriented to the cortical surface.

Electroencephalography (EEG): Rhythms, Dynamics, and Pathology

EEG remains the gold standard for evaluating the physiological state of the cerebrum, offering millisecond-level temporal resolution that imaging modalities cannot match. The analysis of EEG involves characterizing background frequencies, identifying transient waveforms, and correlating these findings with the patient's level of consciousness and metabolic state.

Frequency Domain Analysis and Neural Networks

The brain's electrical output is traditionally categorized into frequency bands. These bands are not arbitrary; they reflect distinct oscillatory modes of thalamocortical and corticocortical networks.

The Physics of Epileptogenesis: The 3Hz Spike-and-Wave

One of the most distinct and clinically relevant waveforms in EEG is the generalized 3Hz spike-and-wave discharge (SWD), the hallmark of typical Absence Epilepsy (childhood onset). The generation of this waveform provides a fascinating case study in circuit physics. The 3Hz SWD is not a random paroxysm but an oscillation of a specific thalamocortical loop. The circuit involves reciprocal connections between excitatory thalamocortical relay neurons and inhibitory neurons of the Reticular Thalamic Nucleus (RTN).

• The Spike: During the paroxysm, a hyperexcitable cortex sends a massive excitatory volley to the thalamus. This results in the surface-negative "spike" seen on EEG, representing synchronous depolarization of apical dendrites.
• The Wave: This excitation triggers the RTN neurons to fire, releasing GABA onto the thalamic relay neurons. This induces a profound Inhibitory Postsynaptic Potential (IPSP), mediated largely by GABA-B receptors. Simultaneously, intrinsic currents (calcium-activated potassium channels) contribute to hyperpolarization. This massive synchronous inhibition is recorded at the cortex as the slow "wave" component.
• The Rebound: The critical biophysical component is the T-type calcium channel in the thalamic neurons. These channels are de-inactivated by hyperpolarization. As the inhibition fades, the T-type channels open, causing a low-threshold calcium spike (rebound burst firing) that re-excites the cortex, initiating the next cycle. This "ping-pong" mechanism locks the brain into a 3Hz rhythm, arresting consciousness.

Clinical Differentiation:

• Typical Absence: Strictly 3Hz, regular, abrupt onset/offset. Associated with Childhood Absence Epilepsy (CAE).
• Atypical Absence: Slower (<2.5 Hz), irregular, often with polyspikes. This reflects a more diffuse, disorganized network failure, typically seen in Lennox-Gastaut Syndrome or other symptomatic generalized epilepsies. The biophysics here implies damage to the thalamocortical synchronization mechanism itself.

Patterns of Encephalopathy and Structural Injury

EEG is arguably most valuable in the evaluation of altered mental status, where it can distinguish between structural and metabolic etiologies.

Triphasic Waves and Metabolic Derangement

Triphasic waves (TWs) are high-amplitude, bilaterally synchronous waveforms characterized by three phases: a small negative deflection, a large positive deflection, and a slow negative after-wave. In uremia, lithium toxicity, septic encephalopathy, and Hashimoto's encephalopathy, their presence in an obtunded patient confirms a metabolic etiology rather than a structural one (like a stroke). However, distinguishing TWs from non-convulsive status epilepticus (NCSE) can be difficult, often requiring a trial of benzodiazepines to see if the pattern resolves.

• Mechanism: While the exact cellular mechanism remains debated, TWs likely represent a functional alteration in thalamocortical oscillation due to metabolic toxins affecting synaptic transmission times. They classically display an anterior-to-posterior lag, meaning the wave appears in the frontal leads slightly before the occipital leads.
• Clinical Correlation: Historically termed "hepatic waves," they are non-specific and occur in uremia, lithium toxicity, septic encephalopathy, and Hashimoto's encephalopathy. Their presence in an obtunded patient confirms a metabolic etiology rather than a structural one (like a stroke).

Lateralized Periodic Discharges (LPDs/PLEDs)

Formerly known as Periodic Lateralized Epileptiform Discharges (PLEDs), these are sharp transients occurring at quasi-periodic intervals (e.g., every 1-2 seconds) over one hemisphere.

• Pathophysiology: LPDs represent an acute, destructive disconnection of a cortical area from its normal input/output loops, leading to a "condensation" of the local field potential spectra. This results from a combination of enhanced excitability and a failure of local inhibition.
• Etiology: They are strongly predictive of an acute structural lesion. The most common causes are Herpes Simplex Encephalitis (often temporal LPDs), acute ischemic stroke, or rapidly growing glioblastomas.
• Prognosis: LPDs are highly epileptogenic. A significant portion of patients with LPDs will have clinical seizures. Furthermore, LPDs of acute onset (e.g., stroke) carry a higher mortality risk compared to those from chronic static lesions, reflecting the severity of the underlying insult.

Focal vs. Generalized Slowing

The distinction between focal and generalized slowing is the most fundamental localization tool in EEG.

• Generalized Slowing: Indicates a global insult. In the context of metabolic encephalopathy, the background rhythm slows from alpha to theta, and then to delta as the condition worsens. The slowing is typically polymorphic and unreactive.
• Focal Slowing: A persistent focus of delta activity (PDA) is a reliable indicator of a structural lesion in the white matter underlying that electrode. Unlike the rhythmic slowing of epilepsy or encephalopathy, structural slowing is often polymorphic and irregular, reflecting the disruption of afferent connections to the cortex.
• Intermittent Rhythmic Delta Activity (IRDA): This curious pattern (Frontal/FIRDA in adults, Occipital/OIRDA in children) consists of bursts of high-voltage rhythmic delta. Unlike PDA, IRDA does not localize to a specific lesion but indicates a projection phenomenon, often due to deep midline pathology, hydrocephalus, or generalized encephalopathy.

Nerve Conduction Studies (NCS): Analysis of Signal Propagation

While EEG listens to the "hum" of the central processor, Nerve Conduction Studies (NCS) actively interrogate the transmission lines of the peripheral nervous system. By electrically stimulating a nerve and recording the response downstream, clinicians can deduce the structural integrity of the myelin sheath and the axon.

The Physics of Neural Transmission and Recording

NCS data relies on the propagation of the action potential via saltatory conduction. In myelinated fibers, voltage-gated sodium channels are clustered at the Nodes of Ranvier. The myelin sheath acts as an electrical insulator, increasing transmembrane resistance and decreasing capacitance. This forces the depolarizing current to flow axially down the center of the axon to the next node, where it triggers a new action potential. This "jumping" mechanism increases conduction velocity by orders of magnitude compared to unmyelinated fibers.

• Thermal Noise Limits: Biophysical constraints impose limits on axon size. Theoretical models suggest that axons smaller than 0.1 µm would be functionally useless for information transfer because the thermal noise inherent in ion channel proteins would drown out the signal. This signal-to-noise ratio constraint dictates the minimum caliber of functional nerves.
• Temperature Dependence: Temperature is the single most critical extrinsic variable in NCS. Cooling a nerve slows the kinetics of sodium channel opening and closing. While this slows conduction velocity (by ~1.5–2.5 m/s per degree Celsius), it also delays channel inactivation. This prolonged open state allows more sodium influx, increasing the duration and area of the individual action potential. Consequently, cold nerves exhibit falsely elevated amplitudes and prolonged latencies, which can mimic pathology or mask axonal loss.

Skin Impedance and Signal Optimization

The interface between the recording electrode and the patient's skin acts as a capacitor and resistor in parallel. High skin impedance creates a voltage divider effect, attenuating the recorded signal and introducing 60Hz mains noise.

• The "Scrubbing" Effect: Research demonstrates that gentle abrasion of the skin (scrubbing with conductive paste) is the most effective method for reducing impedance. Studies using standard Ag-AgCl electrodes show that scrubbing significantly lowers the noise VRMS (root mean square voltage) compared to no treatment or simple degreasing. Furthermore, the impedance continues to drop for approximately 15 minutes after application as the electrolyte gel permeates the stratum corneum, stabilizing the connection. This emphasizes the importance of skin preparation in obtaining reliable microvolt-level sensory potentials.

Differentiating Axonal Loss from Demyelination

The "holy grail" of NCS is distinguishing between axonopathy (e.g., diabetic neuropathy, vasculitis) and demyelination (e.g., Guillain-Barré Syndrome, CIDP). This distinction dictates treatment (immunotherapy vs. risk factor management).

Conduction Block vs. Temporal Dispersion

One of the most specific findings in neurophysiology is Conduction Block (CB). CB represents a failure of the action potential to propagate past a focal lesion, despite the axon being anatomically intact. This is the hallmark of acquired demyelinating neuropathies (like Multifocal Motor Neuropathy).

• Defining CB: A reduction in CMAP amplitude (or area) of >50% between distal and proximal stimulation sites is generally accepted as definite conduction block, provided that the duration of the negative peak does not increase by more than 30%.
• Temporal Dispersion (TD): If the amplitude drops but the duration increases significantly, this is Temporal Dispersion, not Block. TD implies that all the axons are conducting, but at vastly different speeds due to patchy demyelination. The phase cancellation of the desynchronized potentials reduces the amplitude.

Late Responses: Investigating the Proximal Pathway

Routine NCS only assesses the distal nerve segments. Late responses allow for the interrogation of proximal segments and nerve roots.

F-Waves

The F-wave is produced by the antidromic (backward) propagation of an action potential up the motor axon to the anterior horn cell. This stimulates the cell to "backfire" an orthodromic potential down to the muscle.

• Utility: Because the impulse travels the entire length of the nerve (distal to cord and back), F-wave latency is the most sensitive measure for proximal demyelination (e.g., early Guillain-Barré Syndrome) where distal studies might be normal.
• F-Ratio: Comparing the F-wave latency to the distal motor latency (the F-ratio) can help localize lesions. An increased F-ratio suggests proximal slowing, while a decreased ratio suggests distal entrapment.

H-Reflex

The H-reflex is the electrical equivalent of the deep tendon reflex (monosynaptic). It involves stimulating the Ia sensory afferents (Tibial nerve) which synapse on the alpha motor neurons (S1 pool).

• Clinical Specificity: It is highly specific for S1 radiculopathy. An absent or prolonged H-reflex on one side compared to the other strongly supports S1 root pathology, often before EMG changes appear. Unlike the F-wave, the H-reflex assesses the sensory root.

Carpal Tunnel Syndrome: Beyond Simple Compression

Carpal Tunnel Syndrome (CTS) is the most common entrapment neuropathy. The classic finding is focal slowing of the median nerve across the wrist (prolonged distal latency). However, recent research has challenged the simple "distal compression" model.

• Retrograde Degeneration: Studies have shown that in severe CTS, conduction velocity is slowed in the forearm segment of the median nerve as well. This is not due to proximal compression but likely represents retrograde axonal atrophy or "dying back" of the axon due to the distal constriction. This finding challenges the traditional "double crush" hypothesis and suggests that the distal lesion fundamentally alters the health of the entire neuron.

Needle Electromyography (EMG): The Motor Unit in Health and Disease

While NCS assesses the highway (nerve), Needle EMG assesses the destination (muscle) and the vehicle (motor unit). By inserting a needle electrode directly into the muscle belly, the clinician evaluates the electrical stability of the muscle fiber membrane and the architecture of the motor unit.

Spontaneous Activity: The Language of the Muscle Membrane

In a healthy muscle, the membrane is stable at rest. Insertional activity (a brief burst of noise caused by the needle breaking fibers) stops immediately when needle movement ceases. Continued activity is pathological.

Fibrillation Potentials and Positive Sharp Waves (PSWs)

These are the hallmarks of denervation. When a muscle fiber loses its innervation, it undergoes "denervation hypersensitivity." The acetylcholine receptors (AChRs), normally clustered at the neuromuscular junction, spread out across the entire sarcolemma (extrajunctional receptors). This destabilizes the resting membrane potential, making the fiber susceptible to spontaneous depolarization from circulating acetylcholine or mechanical irritation.

• Mechanism: When a muscle fiber loses its innervation, it undergoes "denervation hypersensitivity." The acetylcholine receptors (AChRs), normally clustered at the neuromuscular junction, spread out across the entire sarcolemma (extrajunctional receptors). This destabilizes the resting membrane potential, making the fiber susceptible to spontaneous depolarization from circulating acetylcholine or mechanical irritation.
• Morphology:
  • Fibrillation: A short duration, biphasic spike (initial phase positive).
  • PSW: A sharp positive deflection followed by a slow, long-duration negative phase.

Fasciculations

A fasciculation is the spontaneous discharge of an entire motor unit (the neuron and all the muscle fibers it innervates). Unlike fibrillations, fasciculations are visible to the naked eye as skin twitches.

• The ALS Connection: While benign fasciculations are common (e.g., eyelid twitching, post-exercise cramps), "malignant" fasciculations are a key feature of Amyotrophic Lateral Sclerosis (ALS). In ALS, fasciculations are widespread and often complex.
• Origin: In ALS, fasciculations likely arise from the instability of the distal axon terminal or the anterior horn cell itself due to mitochondrial dysfunction and altered excitability.

Myokymia and Neuromyotonia

These are grouped discharges that have distinct auditory signatures.

• Myokymia: Clinically appears as "bag of worms" rippling under the skin. On EMG, it presents as rhythmic bursts of normal motor unit potentials.
  • The Sound: It has a characteristic "marching soldiers" sound on the audio monitor.
  • Clinical Associations: Facial myokymia is strongly associated with pontine lesions (e.g., Multiple Sclerosis glioma). Limb myokymia is a classic sign of radiation-induced plexopathy; its presence helps differentiate radiation damage (myokymia present) from tumor infiltration (myokymia usually absent).
• Neuromyotonia: This involves very high frequency (150-250 Hz) decrementing bursts that sound like a "pinging" or "motorcycle engine." It is seen in channelopathies like Isaac's Syndrome (antibodies against voltage-gated potassium channels).

Motor Unit Action Potential (MUAP) Remodeling

When the patient voluntarily contracts the muscle, the electromyographer analyzes the shape of the MUAPs. The morphology tells the story of the muscle's history.

The Neuropathic Motor Unit (Collateral Sprouting)

In diseases like radiculopathy or peripheral neuropathy, some motor axons die. The muscle fibers they innervated are orphaned. The remaining healthy axons detect this and sprout new collateral branches to reinnervate the orphans. A single motor neuron now drives many more muscle fibers than normal (increased innervation ratio).

• EMG Signature: The resulting MUAP is large amplitude (more fibers summing up), long duration (greater spatial dispersion of fibers), and polyphasic (the new sprouts conduct slowly and asynchronously). This process takes months; therefore, large MUAPs indicate chronic neuropathy.
• Recruitment: Because there are fewer motor units left, the central nervous system must drive the remaining ones at very high firing rates to generate force. This is termed reduced recruitment.

The Myopathic Motor Unit (Fiber Dropout)

In primary muscle diseases (dystrophy, myositis), the nerve is healthy, but individual muscle fibers die or become non-functional. The motor unit remains intact, but it has fewer functioning muscle fibers.

• EMG Signature: The MUAP is small amplitude (fewer fibers summing) and short duration. It is often polyphasic due to fiber size variation and fibrosis.
• Recruitment: To generate even a small amount of force, the brain must activate many weak motor units simultaneously. This is termed early or rapid recruitment—a full interference pattern appears with minimal effort. Recent quantitative techniques analyzing MUAP energy content have confirmed that myopathic units have significantly lower energy compared to neurogenic units, providing a physically meaningful metric for diagnosis.

Differentiating Radiculopathy from Plexopathy

A common clinical dilemma is distinguishing a C8 radiculopathy from a lower trunk brachial plexopathy (or ulnar neuropathy). Electrodiagnosis provides the answer through the SNAP Amplitude Rule.

• Anatomy: The cell bodies of sensory neurons reside in the Dorsal Root Ganglion (DRG). The DRG is located within the neural foramen.
• The Rule:
  • Radiculopathy: The pathology (disc herniation) is usually proximal to the DRG (preganglionic). Therefore, the sensory axon distal to the DRG remains connected to its cell body and does not degenerate. The SNAP amplitude remains normal, even if the patient has numbness.
  • Plexopathy: The pathology (trauma, tumor) is distal to the DRG (postganglionic). The axon is disconnected from the cell body and undergoes Wallerian degeneration. The SNAP amplitude is reduced or absent.
• Paraspinal Mapping: Additionally, because the paraspinal muscles are innervated by the posterior rami (which branch off immediately after the root exits the foramen), denervation in the paraspinals places the lesion at the root level, proximal to the plexus.

Evoked Potentials (EP): Assessing Central Pathways

Evoked Potentials measure the integrity of sensory pathways through the CNS. They are particularly useful for detecting "silent" lesions in Multiple Sclerosis (MS) and for monitoring neural integrity during surgery.

Visual Evoked Potentials (VEP)

VEP tests the optic nerve and anterior visual pathways. The standard stimulus is a reversing checkerboard pattern.

• The P100: The hallmark waveform is the P100, a large positive potential recorded over the occiput (Oz) at approximately 100 ms.
• Demyelination vs. Axonal Loss:
  • Prolonged Latency: In optic neuritis (MS), the P100 latency is significantly prolonged (e.g., >115 ms). This reflects demyelination of the optic nerve. The latency delay persists even after visual acuity recovers, serving as a "footprint" of previous attacks.
  • Amplitude Loss: Reduced amplitude implies axonal loss or conduction block and correlates better with permanent visual impairment.
  • Neurodegeneration Marker: Recent studies suggest that P100 latency/amplitude changes can track systemic neurodegeneration in MS, even in eyes without a history of optic neuritis.

Brainstem Auditory Evoked Potentials (BAEP)

BAEPs track the auditory signal from the cochlea to the midbrain. They are extremely robust and resistant to anesthesia and metabolic encephalopathy, making them ideal for assessing brainstem function in comatose patients.

Waveform Generators:

• Wave I: Distal Auditory Nerve (Action potential of the spiral ganglion). This is the only wave generated in the periphery.
• Wave II: Proximal Auditory Nerve / Cochlear Nucleus.
• Wave III: Superior Olivary Complex (trapezoid body) in the lower Pons.
• Wave IV: Lateral Lemniscus tracts.
• Wave V: Inferior Colliculus (Midbrain). Wave V is the most prominent wave and is used to determine hearing threshold.

Clinical Application:

• Acoustic Neuroma (Vestibular Schwannoma): The hallmark is a prolongation of the I-III or I-V interpeak interval. Since the tumor compresses the nerve between the cochlea (Wave I) and the pons (Wave III), the delay occurs in this segment. An interaural Wave V latency difference of >0.3 ms is highly suspicious.
• Brainstem Death: In brainstem death, Wave I is preserved (peripheral ear function is intact), but all subsequent waves (II–V) are absent. This provides objective confirmation of the clinical diagnosis.

Somatosensory Evoked Potentials (SSEP)

SSEPs assess the dorsal column-medial lemniscus pathway.

• Upper Limb (Median Nerve) Obligate Peaks:
  • N9: Brachial Plexus (Erb's Point).
  • N13: Cervical Cord (Post-synaptic dorsal horn potential).
  • N20: Primary Somatosensory Cortex (Parietal sensory strip).
• Intraoperative Monitoring (IOM): SSEP is the workhorse of spinal monitoring (e.g., scoliosis surgery). It provides continuous feedback on spinal cord perfusion and integrity.

Safety, Ethics, and Patient Management

The performance of electrodiagnostic procedures carries specific risks that must be managed through rigorous adherence to safety protocols.

Implantable Cardiac Devices (Pacemakers and ICDs)

A major concern is whether the electrical stimulation from NCS can inhibit a pacemaker or trigger an ICD shock.

• Physics of Interference: Unipolar sensing configurations (common in older devices) detect the voltage difference between the lead tip and the device can (a large antenna). These are susceptible to "oversensing" the NCS impulse as cardiac activity, potentially causing pacemaker inhibition.
• Evidence-Based Safety: Studies demonstrate that routine NCS is safe in patients with bipolar pacemakers and ICDs. The electrical impulses are generally not detected by the sensing amplifiers. However, stimulation should not be performed directly over the device or leads (e.g., Erb's point stimulation).
• Recommendations: Avoid stimulation proximal to the device. In patients with unipolar devices or external pacing wires, NCS is relatively contraindicated. For ICDs, some protocols suggest reprogramming detection to "off" during the study, though evidence suggests this may not be strictly necessary for peripheral stimulation.

Anticoagulation and Needle EMG

Needle EMG involves intramuscular vascular injury. In patients on anticoagulants (Warfarin, DOACs), there is a theoretical risk of compartment syndrome or uncontrolled hemorrhage.

• The Data: The actual risk of clinically significant hematoma is extremely low (~1.35%). Compartment syndrome is virtually unheard of in routine practice.
• AANEM Guidelines:
  • Needle EMG is generally safe for patients with an INR < 3.0, though caution is advised if INR > 1.5–2.0 or platelets < 50,000.
  • DOACs (e.g., Apixaban): There is no established "INR equivalent," but the safety profile appears similar to Warfarin.
  • High-Risk Muscles: Deep muscles that cannot be easily compressed (e.g., paraspinals, diaphragm, iliopsoas) should be avoided or approached with extreme caution in anticoagulated patients. The gluteus, being a large bulk muscle, poses a lower risk but hematomas there can be painful.

Infection Control

• Prion Diseases: The risk of transmitting Creutzfeldt-Jakob Disease (CJD) via concentric needle electrodes (which are difficult to sterilize) led to the universal adoption of disposable needle electrodes. Reuse of needles is strictly prohibited.

• Pneumothorax: This is the most serious acute complication, typically resulting from needling the serratus anterior, diaphragm, or thoracic paraspinals. The "danger zone" is the medial scapular border. Ultrasound guidance is increasingly used for high-risk muscles (e.g., diaphragm) to mitigate this risk.

Conclusion

Electrodiagnostic medicine is the bridge between the structural anatomy of the nervous system and its functional reality. Through the precise application of physics—whether analyzing the dipole fields of the EEG, the saltatory conduction of the peripheral nerve, or the discharge patterns of the motor unit—the clinician can localize lesions with millimeter precision and define pathologies at the molecular level. From the 3Hz spike-and-wave of absence epilepsy to the conduction block of multifocal motor neuropathy, these waveforms are not abstract signals but direct representations of cellular physiology. As technology advances, with quantitative MUAP analysis and intraoperative monitoring becoming standard, the field continues to refine its ability to protect neural function and diagnose disease. The integration of these physiological insights with rigorous safety standards ensures that electrodiagnosis remains a cornerstone of modern neurological practice.