Compound Action Potential (CAP)

Definition

• Eric Kandel, Principles of Neural Science, 6th ed., p. 460

Why Multiple Peaks Form

1. All fibers above threshold fire (all-or-none law applies to each fiber individually)
2. Large, heavily myelinated fibers conduct fastest and arrive first
3. Smaller, lightly myelinated and unmyelinated fibers arrive progressively later
4. Each group of fibers "clusters" into a distinct wave or peak on the recording

Fiber Classification and CAP Peaks

• Campbell's Operative Orthopaedics, 15th ed., eTable 46.1
• Costanzo Physiology, 7th ed., Table 3.1

• Large myelinated fibers: velocity (m/s) ≈ 6 × diameter (μm)
• Thinly myelinated: ≈ 5 × diameter
• Unmyelinated: ≈ 1.5-2.5 × diameter

The Classic CAP Waveform (Erlanger and Gasser, 1938)

• Weak shock - Only Aα fibers activated → single early peak; sensation barely perceptible
• Medium shock - Aα + Aβ recruited → two peaks; sensation is tingling
• Strong shock - Aα + Aβ + Aδ → three peaks; pricking pain
• Very strong shock - All A fibers + C fibers → the late broad C-fiber hump appears; pricking pain followed by burning pain

Sensations Corresponding to Each Wave

• Kandel, Principles of Neural Science, 6th ed., pp. 460-461

Compound Muscle Action Potential (CMAP)

• Amplitude (in millivolts) reflects the number of functional motor axons and the innervated muscle volume; reduced amplitude = axonal loss
• Latency to CMAP onset = basis for calculating motor nerve conduction velocity
• Motor NCV = distance between two stimulation sites ÷ difference in latencies
• Normal motor NCV: 40-75 m/s (slower in legs than arms; lower in infants, normalized by age 2-4 years; reduced with cold)
• Demyelinating lesions reduce peak amplitude and slow conduction (differential arrival times); axonal loss reduces amplitude more specifically
• Adams and Victor's Principles of Neurology, 12th ed., p. 51

CAP in the Auditory System (Electrocochleography)

• A transient response at the onset of a click stimulus
• Reflects synchronous firing of auditory nerve fibers (8th nerve)
• Appears as negative deflections N1 and N2, synonymous with waves I and II of the ABR
• The SP/AP ratio is used in diagnosis of Ménière disease: >50% (TIPtrode) or >35% (Tymptrode) is abnormal
• Electrically evoked CAP (ECAP) is used in cochlear implant recipients via Neural Response Telemetry (NRT)
• K.J. Lee's Essential Otolaryngology

Clinical Significance of CAP Analysis

• Kandel, Principles of Neural Science, 6th ed., p. 461
• Adams and Victor's Principles of Neurology, 12th ed., p. 51

Differential Sensitivity to Local Anesthetics

• B and C fibers blocked first (0.25-0.5% concentration)
• Aδ blocked next (0.5%)
• Aβ/Aγ blocked next
• Aα (large motor) blocked last (requires 1%)

• Campbell's Operative Orthopaedics, 15th ed., eTable 46.1

Strength-Duration (S-D) Curve

Definition

It is the product of strength × duration (i.e., charge = current × time) that determines excitability. Therefore, strength and duration are inversely related - a brief strong pulse and a long weak pulse can both be at threshold.

• Medical Physiology (Boron & Boulpaep), p. 275

The Curve

• Horizontal asymptote (x-axis side): No matter how long the stimulus duration, there is a minimum intensity below which stimulation will never succeed - this is the rheobase
• Vertical asymptote (y-axis side): No matter how strong the stimulus, there is a minimum duration below which stimulation will never succeed - this is the utilization time (or minimum duration)

Key Parameters

1. Rheobase

• The minimum current (or voltage) that can just excite the tissue when the pulse duration is infinitely long (practically estimated at ~1.5-2.0 ms in pacemaker studies)
• Represents the horizontal asymptote of the S-D curve
• Units: milliamps (mA) or volts (V)
• Physiologically: the smallest sustained depolarization that can bring the membrane to threshold

2. Chronaxie

• The pulse duration required to excite the tissue when stimulus strength = 2 × rheobase
• A measure of the excitability of the tissue - shorter chronaxie = more excitable
• Units: milliseconds (ms)
• Clinical significance: chronaxie is the most practically useful parameter because it falls near the "knee" of the curve where the energy cost of stimulation is most efficient

3. Utilization Time (Minimum Duration)

• The minimum pulse duration below which no stimulus - regardless of strength - can excite the tissue
• Forms the vertical asymptote of the S-D curve
• Medical Physiology (Boron & Boulpaep), N7-2, p. 277
• Ganong's Review of Medical Physiology, 26th ed., p. 101

Pacemaker S-D Curve

• Capture occurs above and to the right of the S-D curve
• Rheobase is estimated at pulse widths of 1.5-2.0 ms
• At very short pulse widths (<0.1-0.2 ms), the curve rises steeply - increasing voltage is ineffective
• The energy curve (gold) is U-shaped: minimum energy is consumed near the chronaxie
• The charge curve (blue) increases linearly with pulse width
• Optimal pacing: set pulse width near chronaxie for the best balance of safety margin and battery efficiency
• Braunwald's Heart Disease, 2-Vol Set, p. 590 (Fig. 69.8)

Accommodation (Adaptation)

Slowly rising stimuli fail to trigger an action potential even if their final intensity exceeds the threshold predicted by the S-D curve.

• Ganong's Review of Medical Physiology, 26th ed., p. 101

Normal vs. Denervated Muscle: Diagnostic Use

• After nerve injury, denervated muscle loses the fast-conducting nerve input. Muscle membrane is less excitable (higher rheobase, longer chronaxie) and cannot be activated by short pulses
• The curve shifts to the right and upward
• As reinnervation occurs, the curve gradually returns toward normal - the S-D curve can track recovery before voluntary contraction returns
• Galvanic (DC) stimulation is used to plot the S-D curve; faradic (AC/short pulse) stimulation specifically tests for nerve-mediated response
• Campbell's Operative Orthopaedics, 15th ed.

Factors That Affect the S-D Curve / Excitability

Summary Points

1. S-D curve = rectangular hyperbola; strength and duration are inversely related
2. Rheobase = minimum current for infinite duration (horizontal asymptote)
3. Chronaxie = pulse width at 2× rheobase; inversely proportional to excitability
4. Utilization time = minimum duration (vertical asymptote)
5. Accommodation = slowly rising stimuli are less effective due to Na⁺ channel inactivation
6. Denervation shifts the curve right and prolongs chronaxie - detected earlier than clinical signs
7. Optimal stimulation (and pacing) occurs near the chronaxie for minimum energy cost