Chapter 7: Stimulus and Response

Basic Nature of Physiological Recording – Evoked Response
Triggering and Synchronization
Averaging and Signal/Noise
Stimulus types: Sight, Sound, Touch, Smell, Taste
Event Related Potentials
Haptic Transducers
Electrical Stimulation Bypasses Body Sensory Organs
Types of Electrical Stimulation- Pulse, Unipolar, Bipolar, Arbitrary, Noise
Applications of Electrical Stimulation
Electrical Stimulation Artifact
Safety and IEC specifications
Stimulus Isolation

Basic Nature of Physiological Recording – Evoked Response

All physiological process are subject to change with applied stimulus. Environmental change precipitates sensory activity which stimulates a person. Change is characterized by derivatives. If one state is changes into another, the point of maximum change per unit time is characterized as a peak excursion in the associated derivative. Human senses are highly sensitive to changes that occur over specific periods of time. If the change occurs too slowly, the senses may be unable to recognize that a change is underway.

Triggering and Synchronization

The physiological response to a specific stimulus can be very subtle. In the case of evoked biopotentials, such as those associated with the Auditory Brainstem Response (ABR), some of the associated response waves may have voltage magnitudes on the order of a few hundred nanovolts. The ABR is recorded on the scalp, similarly to a component measurement in a standard EEG recording. Typically, ABR measurement electrodes are placed at the vertex of the scalp (Cz) and earlobe (A1 or A2). The ground electrode is typically placed on the forehead.

The resting EEG recorded between leads Cz and A1 or A2 is usually on the order of 10-50uV. The ongoing EEG signal magnitude is roughly 100 times greater than the evoked ABR signal. Accordingly, in order to separate and selectively boost the ABR signal level in relation to the background EEG, synchronized averaging methods are used. A short burst of sound, called a “click” or “tone pip” is introduced to the ear being measured. The sound stimulates a electrical signal to originate from the cochlea to arrive at the brainstem, via the pathway of the 8th cranial nerve. The sound is presented many thousands of times and the evoked electrical signal data measured between Cz and A1 or A2 is recorded, stored and then averaged synchronously. Consequently, if able to view the averaging process in real-time, the ABR signal will appear to grow larger in relation to the background EEG. This is because the ABR measurement is evoked by the sound stimulus, but the background EEG is not.

Averaging and Signal/Noise

With each doubling of the number of averages, of the ABR (2, 4, 8, 16, 32, …), the Signal to Noise ratio of the ABR improves by a factor of the square root of 2 (approximately 1.414). This equates to an improvement of 3dB for each doubling of averages. The background noise level, resulting from EEG, is roughly 100 times larger than the ABR. To clearly discriminate the ABR from the EEG, the ABR signal should be boosted to a level roughly 20 times the magnitude of the background EEG. Accordingly, the ABR requires a signal boost of about x2000, in relation to the background EEG.

A Signal to Noise ratio boost of 2000 requires about 11 doublings of averages (2 to the 11th power equals 2048).

Interpreting in log form: 10 log (2000) = 33dB. To improve the Signal to Noise ratio boost beyond 33dB, additional averages are required. However, given that the sounds can only be introduced so quickly to the ear, additional doublings, beyond two thousand averages, greatly add to the overall measurement time.

Sense types: Sight, Hearing, Touch, Smell, Taste

Humans have many senses. Sight, hearing, touch, smell and taste are the five historically recognized. Ancient Ayurvedic writings, associated with the Vedas, have defined the human senses as these five categories. In Buddhist thought and practice, the mind is seen as the principal pathway to a different spectrum of phenomena that differ from physical sense data. Viewed from this perspective, the human sensory system has internal sources of sensation and perception that filters and augments our external world experiences.

Lately, it’s become increasingly clear that the human sensory range is not easily defined. For example, other stimuli detectable by humans include temperature, pain, balance and acceleration. Furthermore, there are a multitude of internal senses in the body, such as the chemoreceptors for detecting oxygen and electrolyte concentrations in the blood. There are a very large number of differing and coupled sensory systems associated with the body, according there is no firm agreement as to the exact number of senses.

Part of the difficulty in determining the number of senses is due to difficulties in definition.

One definition states that a sense is a faculty by which stimuli are perceived. Perhaps a slightly clearer definition might state that a sense is a system that consists of a group of sensory cell types, that responds to a specific physical phenomenon, and corresponds to specific volumes in the brain where the signals are both received and the interpreted.

Perhaps a relatively complete categorisation for human senses includes, photoreception, mechanoreception, thermoception and chemoreception. However, this categorization attempt does not include categories for many commonly understood senses, such as the sense of pain or the sense of time.

Event Related Potential

An Event Related Potential (ERP) is a small potential (voltage), generated in the brain, that results from a sensed environmental change. Neuronal activity, in certain parts of the brain, varies in response to sensory stimuli. An ERP is a measurement of neuronal activity that is synchronized to sensed stimuli. ERPs indicate the superimposed activity of the potentials produced when many cortical neurons synchronously trigger in response to a stimulus. There are two general types of ERPs, early and late. Early ERPs are called “exogenous” and are considered to be related to sensory structure and processing of a stimulus event. Late ERPs are called “endogenous” and are considered to be related to cognitive processing of the sensory data resulting from a stimulus event. There is also a sub-class of ERPs, called “mesogenous”, that reside between early and late ERPs. Early ERPs peak prior to 100ms, following a stimulus event, and are a consequence of the type and level of the stimulus. Late ERPs peak after 100ms, following a stimulus event, and are a consequence of cognitive processing of the stimulus event. With late ERPs, the subject’s interpretation of the stimulus is reflected in the response. Mesogenous responses show aspects of both early and late responses.

Types

P50 wave

The P50 wave reflects the reduction in synchronized neuronal activity, in a subject, to the second of two identical stimuli. The first stimulus is called the conditioning stimulus. The second stimulus is identical, to the first, and thus redundant. The P50 is an indication of a subject’s sensory gating ability. Sensory gating permits the subject to pay attention to important stimuli and ignore redundant stimuli. The P50 is the largest positive peak, between 40 and 75ms, after the conditioning stimulus onset.

N100 wave

The N100 wave reflects the subject’s orienting response. A presented stimulus is matched with previously sensed stimuli. The N100 is the largest magnitude negative peak, between 90 and 200ms, after the stimulus onset. The N100 is observed when an unexpected stimulus is presented to a subject.

P200 wave

The P200 wave reflects the subject’s focus on new information. The P200 is the largest positive peak, between 100-250ms, after the stimulus onset. The P200 may reflect neuronal activity associated with a recollection attempt.

N200 wave

The N200 wave is a negative-going wave, that peaks about 200ms, after the stimulus onset. The N200 has three, time-sequenced, component waves, the N200A, N200B and N200C. The first component wave (N200A) reflects the phenomenon of mismatch negativity (MMN). MNN results from any discernible change in a repetitive sequence of auditory stimulation. The MMN is indicative of the neuronal processes engaged when identifying a difference in stimulus difference. The second component wave (N200B) has slightly longer latency than the N200A and appears when changes in the stimulus’ nature are relevant to the task.

The third component wave (N200C) is generated when differing stimuli need to be classified.

P300 wave

The P300 wave is an stimulus-independent response measured from central-parietal regions of the scalp. The P300 is the largest positive peak, between 250 and 400ms, after the stimulus onset. The P300 wave has two component waves, the P300A and P300B. The P300A wave results from early attention responses stemming from a working-memory change. The P300A stimulates parietal and temporal neuronal complex structures that produce the P300B. Total P300 wave latency is typically considered to be a function of the subject’s speed to classify stimulus-related information resulting from the discrimination between events. Shorter latencies indicate superior mental performance relative to longer latencies, so P300 wave timing is associated with cognitive performance. The P300 amplitude reflects stimulus sequences, in that greater attention generates larger P300 peaks. P300 amplitudes are inversely correlated with the probability of a particular stimulus. The P300 wave increases in amplitude if the stimulus is less probable. A common variant of the P300 is the oddball paradigm. In this case, different stimuli are sequentially presented, in a series, where one of the stimuli has a reduced probability of occurrence and the subject is instructed to respond to the less-frequent stimulus.

N300 wave

The N300 wave is a negative-going wave, that peaks about 300ms, after the stimulus onset. The N300 is generated in stimuli sequences related to expectations and semantic congruity. The N300 is thought to be linked to neuronal activity related to the detection of probable memory prompts.

N400 wave

The N400 wave is thought to indicate a time interval where a certain stimulus response mode leads to many different response modes and this process appears to be associated with long-term memory. The N400 wave is a negative-going wave, that peaks between 300 and 600ms, after the stimulus onset. The N400 occurs when a specific stimulus response synchronously joins with the brain’s larger neuronal system whose state is subject to a wide range of other response inputs. In psycholinguistic studies, the N400 is generated in language-based stimuli sequences related to expectations and semantic incongruity. The N400 wave amplitude is inversely associated with the expectation that a certain word will be used to end a sentence.

P600 wave

The P600 wave is a positive-going wave, that peaks about 600ms, after stimulus onset. The P600 is generated in language-based stimuli sequences related to syntactic errors or complicated / unusual syntactic structure. The P600 is thought to indicate the activity of knowledge-based, neuronal, integrative processes that are required to detect unfamiliar syntax.

Contingent Negative Variation (CNV)

The CNV is event related slow potential that’s generated in the time interval between an orienting (premonitory) stimulus and a subsequent stimulus, where the subject is instructed to make a voluntary response.

Mismatch Negativity (MMV)

The MMN is a neuronal response in the brain that is related to the changing of a rule. The MMN is generated when an unusual stimulus is noted in an otherwise familiar sequence and type of stimuli.

Haptic Transducers

The word “haptic” is an adjective relating to, or based on, the sense of touch. A haptic transducer performs a conversion between electricity and touch. A common example of a haptic transducer is a tactile transducer, such as that manufactured by Crowson Technology. For this transducer, a power amplifier is used to drive an electromagnetic coil which is coupled to a high strength permanent magnet. Current through the coil creates a magnetic field which pushes against, or is attracted to, the permanent magnet. In this fashion, drive current is made proportional to movement. The design is identical to that of a loud speaker, however haptic (tactile) transducers have frequency responses that can extend close to DC (down to 1Hz). This type of tactile transducer is useful for conveying information to the human body which is sub-audible, namely those frequencies under 20Hz.

Electrical Stimulation Bypasses Body Sensory Organs

The senses of sight, hearing, touch, taste and smell all incorporate specialized cells which convert the incident sensory energy to electrical energy. For example, the inner hair cells of the human ear are mechanically modulated by sound wave energy to create a variable pathway for the movement of ions which ultimately results in an electrical signal that travels along the vestibulocochlear nerve (8th cranial nerve) to the brainstem.

If the correct electrical signal can be artificially induced on any of the sensory-related nerves, the brain will perceive that electrical signal as the respective sense driving that nerve. Present technologies which demonstrate this behavior include the cochlear implant. This transducer is used to bypass hair cell operation and allows sound energy to directly electrically stimulate the vestibulocochlear nerve.

Types of Electrical Stimulation: Pulse, Unipolar, Bipolar, Arbitrary, Noise

Electrical stimulation is very useful because of its intrinsic compatibility to the nervous system. The nervous system is the pathway for electricity-mediated communications in the body. The function of the nervous system is to send signals from one part of the body to other parts of the body.

At the cellular level, the nervous system is defined by the presence of neurons, which are a type of cell.

Neurons can send and receive signals to/from other neurons. The signals are in the form of electrochemical waves that travel through the fibers called axons. The action potential is the electrical aspect of the traveling electrochemical wave. Action potentials derive their energy from electrochemical gradients of sodium and potassium ions. Action potentials are travel through axons by means of propagation known as saltatory conduction. The action potentials hop from node to node (Nodes of Ranvier) along the axon. Nodes of Ranvier expose the neuron membrane to the external environment. The nodes have gaps that are rich in ion channels, that are required to form an action potential. The action potential propagates by jumping, from one node of Ranvier to the next, and is regenerated at the each node along the axon.

As the action potential travels through the axon, via electrochemical means, and arrives at the termination point of the axon, these traveling electrochemical waves cause neurotransmitters to be released at cellular junctions called synapses. The synapses are the connecting points where the axon tips of one neuron terminate very close to the dendrites of the next neuron. Neurotransmitters diffuse across the synapses and fit into the receptors that are located on the next neuron. That neuron’s membrane potential will then decrease or increase. If the membrane potential increases, then it excites the neuron. If the membrane potential decreases, then it inhibits the neuron. If the membrane potential is caused to pass the firing threshold then an action potential will be triggered in the neuron, to be propagated along the axon of that neuron.

Action potentials are propagated rapidly. Typical neurons conduct at 10 to 100 meters per second. Conduction speed varies with the diameter of the axon and how well the axon is insulated. The larger the axon’s diameter, the faster the conduction speed. Myelin is an insulating material that is formed in a sheath around axons. if Myelin is present around the axon, the faster the axon conducts an action potential.

In the nervous system, a sensory nerve ending that responds to stimulus is called a sensory receptor. There are many different types of sensory receptors. There are sensory receptors for nearly any kind of physical change in the environment, such as position, temperature, pressure, light intensity or color. In response to stimuli, a sensory receptor creates a change in voltage, in itself or in an adjacent cell, to initiate an action potential which starts the sensory transduction process via traveling electrochemical waves.

An introduced electrical stimulus can be developed to simulate the behavior of a sensory receptor or otherwise initiate the sensory transduction process. The shape of the electrical stimulus, including factors such as variability, repetition rate, amplitude ranges and slopes will help determine the nature of the induced sensory transduction. Furthermore, the location of electrical stimulation, including factors such as size of electrodes and volume of tissue stimulated, will be similarly relevant to the form of sensory transduction.

Applications of Electrical Stimulation

Nerve Conduction Velocity (NCV) / Electroneurography (ENG)

An NCV (also known as ENG) test measures how quickly electrical impulses move along a nerve. A NCV test can determine if a nerve is damaged. During the NCV test, the nerve is typically stimulated via surface electrodes attached to the skin. Two sets of electrodes are placed on the skin over the nerve. One electrode set stimulates the nerve and the other electrode set records the response.

Hoffmann Reflex (H-reflex)

The H-reflex test is used in electrodiagnostic studies of spinal reflexes. The H-reflex is considered a major probe for non-invasive study of sensorimotor integration and plasticity of the central nervous system in humans. H-reflex refers to the time required for an electrical stimulus, applied to a sensory nerve, to travel to the spinal cord and return down the motor nerve. H-reflex is the earliest response of a muscle to stimulation of large afferent fibers in the muscle nerve. If the nerve stimulation also excites large efferent fibers, the H-reflex is typically preceded by an M response (M-wave), which reflects excitation of the muscle by these efferent nerve fibers.

Functional Electrical Stimulation (FES)

FES is a technique that uses low levels of electrical current to stimulate nerves which innervate extremities affected by impairment. FES uses electrical stimulation of the lower motor neuron to activate muscles in a specific order and degree to complete a functional task. FES is a therapeutic modality that can be used effectively in neurological conditions with intact lower motor neurons, healthy neuromuscular junctions and muscle tissue. FES has been applied to impairments such as spinal cord injury, stroke, head injuries, cerebral palsy and multiple sclerosis.

Neuromuscular Electrical Stimulation (NMES)

NMES is the stimulation of muscle contraction using electrical signals. The stimulation signal mimics the action potential, which normally comes from the nervous system, causing the muscles to contract. NMES involves the use of transcutaneous application of electrical currents to cause muscle contractions. The electrical stimulation signal is delivered via electrodes on the skin in close proximity to the muscles to be stimulated. The goal of NMES is to promote reinnervation, to prevent or retard disuse atrophy, to relax muscle spasms, and to promote voluntary control of muscles in patients who have lost muscle function due to surgery, neurological injury, or disabling condition. (Hayes, 2008)

Interferential Therapy Stimulation (IFT)

IFT is a type of transcutaneous electrotherapy. Two slightly different, medium frequency alternating currents are simultaneously applied to the affected area through electrodes. Superposition of the two currents causes the combined electrical current to vary relatively slowly. IFT is proposed to relieve musculoskeletal pain and increase healing in soft tissue injuries and bone fractures. It is theorized that IFT prompts the body to secrete endorphins and other natural painkillers and stimulates parasympathetic nerve fibers to increase blood flow and reduce edema.

Transcranial Direct Current Stimulation (tDCS)

tDCS is a non-invasive, neuro-modulation, electrical stimulation method that is being evaluated for the treatment of depression, epilepsy, pain and facilitating stroke rehabilitation. During tDCS, a small constant current, of 2ma or less, is passed through the brain using scalp electrodes. Such application of direct current, for a greater than 10 minute time period, can lead to lasting changes in neuronal excitability (Nitsche and Paulus, 2000, 2001).

Electrical Stimulation Artifact

Because tissue is conductive, the electrical signal from stimulation sources will often directly appear at the location of the recording electrodes.

Safety and IEC specifications

The harmonized, international regulatory standard relating to the safety of nerve and muscle stimulators is IEC 601-2-10. Certain stimulation equipment is excluded from this standard, such as stimulators intended for cardiac defibrillation. Section 51.104 of the IEC 601-2-10 standard specifies the limitation of output power for a variety of wave types:

1. For stimulus pulse outputs, the maximum energy per pulse shall not exceed 300mJ, when applied to a load resistance of 500 ohms.

2. For stimulus pulse outputs, the maximum output voltage shall not exceed a peak value of 500V, when measured under open circuit conditions.

Stimulus Isolation

Electrical stimulus isolation is important to control the flow of stimulation current in the defined stimulation volume. Stimulation electrodes and recording electrodes should be well electrically isolated in order to prevent the flow of current from the stimulator to the measurement biopotential amplifier. Perfect isolation is impossible, however placement of electrodes can help mitigate the flow of stimulus artifact currents. For example, placing the biopotential ground electrode between the stimulus site and the recording site will help intercept stray stimulus currents before they can affect the recording site.

Non-linear behavior of stimulation impedance