|Year : 2014 | Volume
| Issue : 3 | Page : 140-144
Evoked potentials: Visual evoked potentials (VEPs): Clinical uses, origin, and confounding parameters
Department of Physiology, Regional Institute of Medical Sciences, Imphal, Manipur, India
|Date of Web Publication||5-Jan-2015|
Department of Physiology, Regional Institute of Medical Sciences, Imphal - 795 004, Manipur
Source of Support: None, Conflict of Interest: None
Background: A study of visual evoked potentials (VEPs) is an important diagnostic tool used equally by neurophysiologist, ophthalmologist, neurologists, and neurosurgeons. Many neurological disorders present with visual abnormalities and detection of subclinical lesions affecting the visual system which are poorly visualized by MRI or in unreliable clinical examination or ruling out of psychogenic origin, depends mainly on the VEPs. Its prognostic utility are also under investigations. Objectives: To review the clinical utility, brief history, origin, and generator sites of VEPs. Data Sources: Published, peer-reviewed literature on VEPs available both in print or online. Conclusion: VEPs have emerged as an important diagnostic tool in demyelinating diseases of the CNS in the current era. An awareness of the conditions where it can be utilized along with a sound knowledge of origin and generator sites will help the clinician or the neurologist to identify the possible sites of abnormalities and thereby effectively influence the management and treatment outcome in patients with neurological disorders.
Keywords: Clinical applications, Evoked potentials, Generator sites, VEPs
|How to cite this article:|
Phurailatpam J. Evoked potentials: Visual evoked potentials (VEPs): Clinical uses, origin, and confounding parameters. J Med Soc 2014;28:140-4
|How to cite this URL:|
Phurailatpam J. Evoked potentials: Visual evoked potentials (VEPs): Clinical uses, origin, and confounding parameters. J Med Soc [serial online] 2014 [cited 2020 Oct 29];28:140-4. Available from: https://www.jmedsoc.org/text.asp?2014/28/3/140/148494
| Introduction|| |
Among the recently advancing Neurologic Diagnostic Tools, the role of Evoked Potential studies (EPs) has been in flux during the past few decades. They were often essential in the diagnosis of Neurological Diseases like Multiple Sclerosis (MS) because of their ability to detect subclinical lesions and are being applied increasingly to other areas too. 
Recently, its prognostic importance are also being studied. 
EPs represent a non-invasive low-cost method to assess in real time the processing of sensory information in the human central nervous system (CNS). The EP traces consist of a succession of waves or peaks, which reflect the neuronal responses at the different levels of the sensory pathways. This technique permits assessment of the conduction times of the sensory impulses in the CNS.  In general, the value of all evoked potential studies is related to the fact that they are the central analogies of conduction times in the peripheral nervous system and indirectly reflect conduction in the central neural pathways. Their usefulness parallels the usefulness of conduction-time studies in the peripheral neural pathways. 
EPs proved to be helpful in
- Testing sensory functions when clinical examination is not reliable;
- Investigating purely subjective symptoms and detect whether they have an organic origin;
- Better assessing the causative mechanisms of neurological deficits and functional recovery;
- Monitoring cerebral functions when the patient's condition is critical or at risk in the operating theatre or during intensive care. 
An abnormal EP in clinical cases may furnish objective evidence to an unsuspected or suspected but not proven abnormality. It also allows one to quantify and objectively follow-up a known lesion.  Besides, they provide a means of detecting lesion in the afferent pathways under study and assess the functional integrity of these pathways whereas imaging techniques such as MRI evaluate mostly their anatomical basis. Thus EP studies sometimes reveal abnormalities missed by MRI and these findings may be important for diagnostic purposes, in following the course of certain neurological disorders or for determining the extent of pathological involvement.  In patients with known pathological processes involving the CNS, EPs help to detect and localize lesions. Besides, they are helpful in the evaluation of ill-defined complaints to categorize more precisely the functional integrity of any afferent pathways that may be responsible for the symptoms in question. 
One of the most remarkable properties of EPs is their resistance to anesthesia, sedative drugs and in comparison with EEG activity - even damage of the cerebral hemispheres. This permits their use for monitoring the integrity of the cerebral pathways in situations that render the EEG useless. 
Many clinical neurophysiology laboratory are rapidly emerging in our country and have added average EP studies to their routine procedures as these methods are non-invasive, low cost, real time, highly objective, and informative. These have lately proved to be valuable clinical tools for objectively testing afferent functions in patients with neurological and sensory disorders. Certain abnormalities in EPs reflect sub-clinical involvement of the CNS even before the disease clinically manifests. 
Several sensory modalities can be investigated by EPs; the most commonly studied are the visual, auditory, and somato-sensory systems.  The Visual Evoked Potentials or the Visual Evoked Responses are the evoked potentials generated in the cortical and sub-cortical visual areas when the retina is stimulated with light (flashes/pattern stimulation) and best recorded over the occipital region. It is a very important non-invasive tool in detecting abnormalities of visual system. It is not only useful for clinical neurophysiologist or ophthalmologist but also for neurologists and neurosurgeons, since many of the neurological disorders present with visual abnormalities. 
The major use of VEPs is in the detection of sub-clinical lesions within the visual system; asymptomatic optic neuritis is easily detected and its presence may aid in the diagnosis of MS. Optic nerves abnormalities are poorly visualized by MRI, making VEPs an important adjunct when the diagnosis of demyelinating disease is in doubt.  VEPs can also help distinguish blindness from hysteria and malingering: if a patient reports visual loss, a normal VEP strongly favors a psychogenic disorder. 
In infants, VEPs has been used to assess integrity of the visual system when blindness is suspected and also to detect unilateral amblyopia at an early age when recovery may still be possible. Paradigms to determine refractive error are also under investigation. 
However, before EP studies can be applied clinically, acceptable limits of variability in normal control groups must be established. In doing so, it is important to control for non-pathological factors producing variability in the normative groups such as the nature of the stimulus and the person's age and sex as well as recording derivatives and techniques.  Besides, there are various physical and physiological factors influencing VEP. Physical parameters of visual stimuli - size of checker board, frequency of stimulation, contrast and luminance, size of the pupil and state of refraction, field of vision and visual acuity ,, affect VEP. Physiological factors are age, sex, head (occipito-frontal) circumference, ,,,,,,,, body temperature, and physical exercise.  Therefore, it becomes imperative on the part of any clinical neurophysiology laboratory to control these parameters rigidly in order to obtain reasonable, reproducible, and reliable data of VEP in a normative study before using it as a diagnostic tool. These parameters will be subsequently discussed in a separate review.
Attempts have been on for the past century or more to record the electrical changes occurring throughout the body and developments in electronics have allowed the appearance of highly sophisticated measuring devices which permit measurement of ever smaller changes, even sometimes at a marked distance from the organ of origin. The visual pathway has been an important centre for investigation in this respect and minute electrical impulses can now be recorded from the eye and visual cortex in an astonishing manner. The basis of all this electrical changes is the bioelectrical potential which is defined as the potential difference across a cell membrane. All cells show this resting potential and a marked change in the potential may occur when the cell is stimulated, cumulating into a flow of electrical current. As they are often picked up from a site remote from its source, these potentials are very small and must be amplified in order to be detected by a suitable recording instrument. 
The eye itself provides the clinicians with a view of tissues that are normally covered by opaque skin. The ophthalmoscope allows one to directly examine blood vessels and nerves. It is also possible to place electrodes on and around the eye to record the electrical changes that occur when diffused light is flashed on the retina or when the retina is exposed to different forms of light stimulus. So far, at least the electrical changes in the optic nerve have not been recorded directly and changes in the optic tracts, lateral geniculate bodies and optic radiations still remain beyond the reach of the clinicians. However, electrical changes over the visual cortex in response to visual stimuli can now be measured. This has become increasingly useful in clinical practice and complements the subjective test of visual function by providing 'that' small piece of extra evidence that may sometimes be conclusive in reaching a firm diagnosis.
Recording the spontaneous electrical activity of the brain from electrodes placed on the scalp has been a clinical practice for many years now and is known that this activity is modifiable by the action of light on the eye. The VEP is one of the several evoked potentials that can be recorded from the scalp electrodes.
| Historical Aspects|| |
Several forms of electrodiagnosis used in neurology are based on fundamental neurophysiology and have much shorter histories than electrotherapy. Among them only electroencephalography (EEG), electromyography (EMG), nerve action potential and the evoked cortical potential have a history which they largely share, essentially steming from the discoveries of intrinsic animal electricity in frog  by Luigi Galvani.
EMG was borned when Du-Bois Reymond  and Hermann  recorded normal surface electric potentials in human muscles. Richard Caton  discovered the cerebral counter parts and not only found the EEG but also the evoked potential changes on sensory stimulation especially with visual stimuli. He provided for the first time the method for mapping the localization of sensory areas in cortex. The positions of electrodes that gave a response to light and a faint response to sound were marked by Adolf Beck.  The first photograph of an cortical evoked potential recorded was provided by Neminsky. 
Hans Berger  named the spontaneous ongoing activity of the brain as "Das Elektrenkephalogram' and in 1940 launched EEG as a clinical neurologic test which is now used worldwide.
The changes evoked by visual stimuli were first recorded in animals directly from the surface of the pia mater in the 1930s. The alpha rhythm seen in the normal EEG traces could be accentuated by exposing the eyes to a light flashing at a similar frequency but when exposed to repeated flashes of varying frequencies, the electrical changes recorded from the scalp electrodes become small and more or less lost against the background of the normal spontaneous activity of the brain. At first, discrimination of these small electrical signals from irrelevant cortical activity was difficult but later made possible by the introduction of averaging techniques. 
From the clinical point of view, this is an important development as it allows recording of VEPs as small as 2 or 3 μV and the nature of the response, its amplitude and waveform can be related to the type of visual stimulus in a way never before possible. Normal cortical responses are obtained if the entire visual system is intact and disturbances anywhere in the visual system can produce abnormal VEPs.
The commonly used Pattern reversal method for VEP stimulation was developed and popularized in the early 1960s. 
| Anatomical and Physiological Basis of Vep|| |
The visual receptors, rods and cones present in the retina, are stimulated by light impulses and synapse with the inner nuclear or bipolar layers, which in turn synapses with the ganglion cell layer. The axons of the ganglion cell form the optic nerve which joins the retina with the brain. At the origin in the retina and optic nerve head, the unmyelinated nerve as they pass through the lamina cribosa becomes myelinated.
The two optic nerves from both sides unite over the sella turcica to form the optic chiasma where decussation of the medial fibers occurs while the lateral fibers proceed as such forming the optic tracts which terminate in the Lateral Geniculate Body (LGB), while some fibers project to the Edinger Westphal nucleus. Projections from the LGB form the Optic radiation which pass posteriorly and end in the striate cortex in the occipital lobe (Area no. 17). From this primary visual cortex, the fibers project to the visual association areas (Area 18, 19) and Mid-Temporal (MT). From areas 17 and MT, it gets transmitted to the posterior parietal cortex.
The optic nerve fibers primarily carry the visual impulses and also impulses responsible for accommodation and reflex responses to light and other stimuli. There is a larger cortical representation of the foveal area than the peripheral retina which is known as the foveal magnification. The upper half of the retinal fibers relay superior and the lower half inferior to the calcarine fissure.
Segregation of the visual information starts from the neuronal circuitry of the retina itself.  Here, particular features such as color, contrast, luminance, and other parameters of the stimuli are extracted and processed. Out of the 10 cortical visual areas described in humans, over one-third of the cerebral cortex is devoted primarily to visual function.  This multiplicity of visual cortical areas is explained by an analogy of breaking down a large computation into a collection of smaller independent modules ,, and may provide the basis of development of new information capabilities in the course of evolution simplifying the problem of inter-connecting functionally related groups of neurons. 
| Origins of Visual Evoked Potential|| |
The exact generator sources and the temporal sequences of the VEP waveforms are not well defined. The VEP is primarily a reflection of activity originating in the central 3 o to 6 o of the visual field as the retinal projections from this area is relayed to the surface of the occipital lobe  while those from the peripheral areas are directed to deeper regions within the calcarine fissure. Therefore, when scalp electrode picks up the signals directly from the cortical tissue that receives the central inputs. Another reason is due to the foveal magnification between the human retina and the visual cortex. One millimeter of occipital lobe tissue receiving inputs from the fovea processes information from 2 minutes of visual angle at the retinal surface while processing about 18 minutes of visual angle for inputs from those just 5 o peripheral to the fovea.  Therefore, VEPs tends to be attenuated or even unrecordable when the peripheral retina is stimulated. This also means that VEP is mainly a reflection of the cone activity and VEPs arising from the rod receptors are recorded with difficulty.
The processing of the visual information in parallel pathways infers that (i) visual stimuli not only activate the occipital lobes but also involve large areas of the temporal and parietal lobes. This is clear from the findings of Phelps  et al., that on giving visual stimuli, there is increased metabolism not only in the primary visual area but also in the visual association areas 18 and 19. Fox and Rachile have also found the cerebral blood flow to increase with increase in stimulation rate up to 8 Hz but declines gradually thereafter.  VEPs therefore, can be recorded from a large region from the scalp essentially from the vertex to the inion. Accordingly, the reference electrode should be located anterior to the vertex or away from these active regions. (ii) Different structures of the retina and visual pathways can be preferentially activated by changing the characteristics of the visual stimulus. This indicates the importance of selecting the proper visual stimulus and recording techniques for analysis of specific functions within the visual pathways. , Large check sizes greater than 30' of arc when used as the stimulus will allow the recording of signals outside the central 3 o but not beyond 10 o of the visual field.
In patients with well-defined cortical lesions, VEP studies have provided additional information about the generator sources. Bodis-Wollner et al., (1977) reported normal VEPs in patients with isolated damage to bilateral visual association areas with preserved primary visual cortex.  Celesia et al, Frank and Torres and Spehlmann et al., reported yet normal VEPs in patients with damaged primary visual cortex with preserved visual association area as well as in patients with cortical blindness following extensive infarction of the visual cortex. ,, However, Ducati et al., reported preserved VEPs in patients undergoing stereotactic surgery of the nucleus ventralis lateralis thalami for movement disorders.  Using intracerebral recording in awake humans, they found that P100 appears to be generated by the pyramidal cells in layer IV of area 17. Imaging studies point to the source of the early phase of the P100 peak as being in dorsal extrastriate cortex of the middle occipital gyrus, whereas the late phase of P100 appears to be generated by the ventral extrastriate cortex of the fusiform gyrus.  These results suggest the cortical generation of VEP waveforms.
Ikeda  et al., (1998) studied the generators of VEP by dipole tracing in the human occipital cortex and investigated the current source generators (dipole) of pattern-onset stimuli. They analysed that the topographic localization of the dipoles area around the calcarine fissure which was comparable to the retinotopy of the human occipital lobe based on clinicopathological studies.
| Conclusion|| |
VEPs have emerged as an important diagnostic tool in demyelinating diseases of the central nervous system in the current era. An awareness of the conditions where it can be utilized along with a sound knowledge of origin and generator sites will help the clinician or the neurologist to identify the possible sites of abnormalities and thereby effectively influence the management and treatment outcome in patients with neurological disorders.
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