Superconducting quantum interference device

A superconducting quantum interference device (SQUID) is one of the most sensitive sensors for measuring extremely weak magnetic fields, such as those that are generated by electric neural activity in the brain. The technique has found increasing use as a research tool in recent years. It is complementary to VEP, but being much more laborious and expensive, it is available only at some major physics research facilities.

Visual pathways and clinical investigation

Although we have described examples of striking co-variation between psychophysical behavior and neural processes, demonstrating this convincingly is usually a time-consuming process. Therefore, it is not always straightforward to exploit such correlates in clinical investigation of visual function. Clinical tests must be simple, easy to administer, and fast.

In some forms of reading impairment, called dyslexia, there have been repeated suggestions that there is a correspondence between the disturbed visual function and neural deficits in the magnocellular pathways. Dyslexia is mainly a reading disability, and those who suffer from it often report that they see letters moving and interchanging positions, or experience other visual disturbances that indicate impaired temporal processing. The suggested connection to a deficit in the MC pathway has led to the application of moving visual stimuli for probing the function of the MC system. Other tests can be envisaged as well, taking advantage of the difference between MC and opponent cells. As we have repeatedly seen, exclusive activation of MC cells is likely to require achromatic stimuli of low spatial frequency and low luminance contrasts. This applies to a broad range of temporal frequencies. However, as yet, there is no conclusive data on how people who suffer from dyslexia perform under such tests.

Isolation of PC cell responses can be achieved by using low red–green contrasts of low spatial and temporal frequencies, since high red–green contrasts may elicit the MC cells’ second-harmonic response. Moreover, isoluminant yellow–blue color contrasts along a tritanopic confusion direction activate only S-cones of the KC pathway. It is also possible to calculate pairs of light stimuli that will silence the activity of one or more receptor type. Abnormal differences in the temporal behavior of different photoreceptor classes have been found in ERG recordings of retinitis pigmentosa using cone-isolating stimuli, a fact that can be utilized for early diagnosis of the disease (Kremers, 2003).

Several studies have concluded that the larger-bodied MC cells and their neural pathways are the first to be affected when the ocular pressure increases above normal, a condition known as glaucoma (Quigely et al., 1988). It is expected that the larger size of MC cells and their thick axons render them more vulnerable to the mechanical effects of elevated intraocular pressure. Reduced functionality in the MC pathways is

likely to reduce achromatic luminance contrast sensitivity and sensitivity to movement for low contrasts. However, KC cells with excitatory S-cone inputs also appear to be large (DeMonasterio and Gouras, 1975), and can therefore be injured before the smaller PC cells. Psychophysical tests, such as measuring the extent of the visual field by blue–yellow perimetry (which determines the threshold for a short-wavelength light on a high luminance yellow background), seem to indicate that this sensitivity decreases in glaucoma. Such tests may help diagnose glaucoma in its early stages of development.

The electroretinogram

The electroretinogram (ERG) is a tool for monitoring activity in the retina. Flashing bright light onto the retina modifies the electric currents through the retinal layers and, as a result, brings about a change in the electric potential at the cornea, starting with an early negative change at the back of the eye relative to the cornea, followed by a positivity. The Swedish physiologist Ragnar Granit (Nobel Prize winner in 1954) analyzed the ERG into three components P-I, P-II and P-III (Granit, 1933), and although this component analysis has been slightly modified over the years, it remains a basis for our understanding of the ERG.

ERG are typically recorded in response to a bright flash that floods the entire retina. The earliest negative waveform in the response is attributed to the receptors themselves (the a-wave). This potential is generated by hyperpolarization of the photoreceptor inner segments. An a-wave may still be recorded even when the inner retina is destroyed but the outer retina is intact. Using cone-isolating techniques (silent substitution), it is possible to measure ERG to single cone types, a method that has been proven useful in the early diagnosis of retinitis pigmentosa (Kremers, 2003), an eye disease that damages rods and leaves the patient with foveal tunnel vision before he finally becomes blind. The subsequent positive b-wave is thought to be generated by the activity of bipolar cells.

A pattern ERG can be recorded to reversing checkerboard patterns of black and white squares, and this ERG response is thought to reflect the activity of ganglion cells. More recently, a method has been developed which makes it possible to record many simultaneous ERGs from a large number of small areas distributed over the retina. This method, referred to as multifocal ERG (mfERG), can be used for locating retinal scotomas – retina areas with severely compromised vision – or retinal areas in which the response to light modulation deviates in some way from that of the surrounding retina. This method promises to be highly informative in future studies of retinal function.

Visual evoked potentials

In light of the proposed link between dyslexia and impaired function of the MCpathway, it might be of clinical relevance to be able to distinguish the responses of the

Figure 8.13 The P120 waveform in Figure 8.12 is here plotted as a function of Weber contrast. The response increases with increasing contrast up to a plateau, flattens out and increases again after 50–60% stimulus contrast. This behavior has been interpreted in terms of the contribution of MC and opponent cells to the response: the more sensitive MC cells are thought to be responsible for the initial, low-contrast part of the curve, with PC cells dominating the response for the higher contrasts.

about 20 percent contrast and increases thereafter, as we would expect if the slower opponent cells took over at higher contrast.

A similar distinction between responses of MC cells and the less contrast-sensitive opponent cells can be made for VEP waveforms recorded to the ON/OFF presentation of chromatic gratings (Nyga˚rd et al., 2002).

Cortical visual impairment

Cortical visual impairment (CVI) is a term used for injuries or developmental problems in or after the optic chiasm, for instance in the geniculate nucleus, the optic radiation, or in the visual cortex. Sometimes these injuries result in symptoms that are similar to those of defects in the peripheral visual apparatus, such as visual field defects and low acuity. The foveal retina is greatly over-represented in primary visual cortex and low acuity may result from injuries to this area. In other cases acuity

is not reduced, but the individual has perceptual or cognitive problems, such as difficulty in interpreting visual inputs and integrating them with other brain functions. Visual agnosia refers to an impairment of processes leading to object detection and recognition, although other vital visual functions are preserved. This may be described as ‘seeing without meaning’. This description may be apply to deficiencies in the perception of space (depth, distance, perspective, etc.) that is found in people who lost their sight at a very early age but regained it much later in life (von Senden, 1960; Sacks, 1995; and the case of Virgil mentioned in the Introduction). Prosopagnosia is a failure to recognize faces, despite correct identification of the eyes, the nose, the mouth, etc.

The failure to perceive movement (akinetopsia) or to determine direction of movement is another example of CVI. Simultanagnosia refers to problems with the perception of more than one object at a time. Brain injuries following accidents can also lead to loss of color perception (achromatopsia). Hemianopia is characterized by the loss of half of the visual field, either to the right or to the left of the mid-line, in both eyes. This reflects the loss of visual function in half of the brain, as a result of stroke, head trauma or a tumor. A person who is unable to see objects in his blind field may have problems orientating himself in space. A common cause of CVI is head trauma from car accidents or an oxygen deficit resulting from diminished blood supply to the brain. The circulation of blood may be interrupted by cardiac arrest or at birth. The effects on the brain of neonates can be diagnosed fairly early by ultrasound or MRI.

Other causes of CVI may be prenatal or postnatal exposure to infections or toxic agents, or to substances that affect the central nervous system, such as alcohol and narcotics. CVI is seldom seen during a regular eye examination; it often requires an interdisciplinary approach. One reason for studying the impairments that follow brain injuries is that it provides us with insight into the functioning of the normal brain. For instance, we may learn more about the organization of the brain in the specialized subsystems, or modules that are required for us to recognize and be aware of different attributes of visual stimuli.

People who have lost a limb often report pain in some part of the missing limb, in a toe, for example. This ‘phantom pain’, which usually subsides in a matter of months or years, is usually explained in terms of nerves in the brain associated with the lost organ, and with pain, still being active and ‘projecting’ the pain into the brain’s body space, an external map completed early in life. Imagine a similar situation in vision: contact with some visual center in the brain is disconnected because of injury, e.g. after stroke or the removal of a tumor, or even after a visual loss due to retinal damage, such as in AMD. Although the normal visual input signals to a visual center are missing, the center may still have some level of spontaneous activity. In such a case, the analogy to phantom pain might be that the person experiences phantom images in terms of color patterns, movements or other attributes of vision that bear no relation to objects in the external world. This may explain why people with maculopathy occasionally report seeing ‘strange things’.