Pattern visual evoked potentials in man and tetrahydrobiopterin metabolism

The P2 visual evoked response in man has a cholinergic component while the P100 response has not. The P100 latency is significantly decreased after an oral dose of phenylalanine in man while the P2 signal is unaffected. Analyses of the P100 decrease shows no correlation with tyrosine levels but a significant positive correlation with plasma ane urine levels. A small group shows a P100 delay which correlated with increased neopterin levels only. Increased plasma total biopterins in man following a phenylalanine dose are due to rapidly increased tetrahydrobiopterin synthesis in the liver.

Study of the cholinergic factors affecting the flash and pattern reversal visual evoked potentials

The effects of cholinergic agents undergoing clinical trials for the treatment of Alzheimer's disease and the anticholinergic agent scopolamine, were investigated on the components of the flash and pattern reversal visual evoked potentials (VEPs) in young healthy volunteers. The effect of recording the flash and pattern reversal VEPs for 13 hours in 5 healthy male volunteers, revealed no statistically significant change in the latency or amplitude measures. Administration of the muscarinic agonist SDZ 210-086 to 16 healthy male volunteers resulted in the reduction of the flash N2-P2 and pattern reversal N75-P100 peak-to-peak amplitudes. These effects on the flash VEP occurred at both doses (0.5 and 1.0 mg/day), but only at the higher dose on the pattern reversal VEP. Administration of the antimuscarinic agent scopolamine to 11 healthy young male volunteers, resulted in a delay of the flash P2 latency but no effect on the pattern reversal P100 latency. The pattern reversal N75-P100 peak-to-peak amplitude was also increased post dosing. The combination of scopolamine with the acetylcholinesterase inhibitor SDZ ENA 713 resulted in no significant effect on the flash and pattern reversal VEPs, suggesting that the effects of scopolamine may have been partially reversed. Topical application of scopolamine in 6 young healthy volunteers also resulted in no statistically significant effects on the flash and pattern reversal VEPs. The selective effect of scopolamine on the flash P2 latency but not on the pattern reversal P100 latency, provided a model whereby new cholinergic agents developed for the treatment of Alzheimer's disease can be investigated on a physiological basis. In addition, the results of this study led to the hypothesis that the selective flash P2 delay in Alzheimer's disease was probably due to a cholinergic deficit in both the tectal pathway from the retina to the visual cortex and the magnocellular path of the geniculostriate pathway, whereas the lack of an effect on the pattern reversal P100 component was probably due to a sparing of the parvocellular geniculostriate pathway.

The association between glycated haemoglobin levels and P100 visual evoked potentials in diabetes mellitus

Diabetes mellitus (DM) is a metabolic disorder which is characterised by hyperglycaemia resulting from defects in insulin secretion, insulin action or both. The long-term specific effects of DM include the development of retinopathy, nephropathy and neuropathy. Cardiac disease, peripheral arterial and cerebrovascular disease are also known to be linked with DM. Type 1 diabetes mellitus (T1DM) accounts for approximately 10% of all individuals with DM, and insulin therapy is the only available treatment. Type 2 diabetes mellitus (T2DM) accounts for 90% of all individuals with DM. Diet, exercise, oral hypoglycaemic agents and occasionally exogenous insulin are used to manage T2DM. The diagnosis of DM is made where the glycated haemoglobin (HbA1c) percentage is greater than 6.5%. Pattern-reversal visual evoked potential (PVEP) testing is an objective means of evaluating impulse conduction along the central nervous pathways. Increased peak time of the visual P100 waveform is an expression of structural damage at the level of myelinated optic nerve fibres. This was an observational cross sectional study. The participants were grouped into two phases. Phase 1, the control group, consisted of 30 healthy non-diabetic participants. Phase 2 comprised of 104 diabetic participants of whom 52 had an HbA1c greater than 10% (poorly controlled DM) and 52 whose HbA1c was 10% and less (moderately controlled DM). The aim of this study was to firstly observe the possible association between glycated haemoglobin levels and P100 peak time of pattern-reversal visual evoked potentials (PVEPs) in DM. Secondly, to assess whether the central nervous system (CNS) and in particular visual function is affected by type and/or duration of DM. The cut-off values to define P100 peak time delay was calculated as the mean P100 peak time plus 2.5 X standard deviations as measured for the non-diabetic control group, and were 110.64 ms for the right eye. The proportion of delayed P100 peak time amounted to 38.5% for both diabetic groups, thus the poorly controlled group (HbA1c > 10%) did not pose an increased risk for delayed P100 peak time, relative to the moderately controlled group (HbA1c ≤ 10%). The P100 PVEP results for this study, do however, reflect significant delay (p < 0.001) of the DM group as compared to the non-diabetic group; thus, subclincal neuropathy of the CNS occurs in 38.5% of cases. The duration of DM and type of DM had no influence on the P100 peak time measurements.

Automated assessment of visual fields and their inter-relation to evoked potentials in visual disorders

The Octopus Automated Perimeter was validated in a comparative study and found to offer many advantages in the assessment of the visual field. The visual evoked potential was investigated in an extensive study using a variety of stimulus parameters to simulate hemianopia and central visual field defects. The scalp topography was recorded topographically and a technique to compute the source derivation of the scalp potential was developed. This enabled clarification of the expected scalp distribution to half field stimulation using different electrode montages. The visual evoked potential following full field stimulation was found to be asymmetrical around the midline with a bias over the left occiput particularly when the foveal polar projections of the occipital cortex were preferentially stimulated. The half field response reflected the distribution asymmetry. Masking of the central 3° resulted in a response which was approximately symmetrical around the midline but there was no evidence of the PNP-complex. A method for visual field quantification was developed based on the neural representation of visual space (Drasdo and Peaston 1982) in an attempt to relate visual field depravation with the resultant visual evoked potentials. There was no form of simple, diffuse summation between the scalp potential and the cortical generators. It was, however, possible to quantify the degree of scalp potential attenuation for M-scaled full field stimuli. The results obtained from patients exhibiting pre-chiasmal lesions suggested that the PNP-complex is not scotomatous in nature but confirmed that it is most likely to be related to specific diseases (Harding and Crews 1982). There was a strong correlation between the percentage information loss of the visual field and the diagnostic value of the visual evoked potential in patients exhibiting chiasmal lesions.

Visual evoked magnetic fields to flash and pattern in 100 normal subjects

The practicality of recording visual evoked magnetic fields in 100 subjects 15-87 yr of age using a single channel d.c. SQUID second order gradiometer in an unshielded environment was investigated. The pattern reversal response showed a major positive component between 90 and 120 msec (P100M) while the response to flash produced a major positive component between 90 and 140 msec (P2M). Latency norms of the P100M were more variable than the corresponding P100 and P2 visual evoked potentials. The latency of the P100M may show a steep increase with age in most subjects after about 55 yr whereas only a small trend of latency with age was detected for the flash P2M.

The chromatic visual evoked response as an indication of visual development

In an endeavour to provide further insight into the maturation of the cortical visual system in human infants, chromatic transient pattern reversal visual evoked potentials to red/green stimuli, were studied in a group of normal full term infants between the ages of 1 and 14 weeks post term in both cross sectional and longitudinal studies. In order to produce stimuli in which luminance cues had been eliminated with an aim to eliciting a chromatic response, preliminary studies of isoluminance determination in adults and infants were undertaken using behavioural and electrophysiological techniques. The results showed close similarity between the isoluminant ratio for adults and infants and all values were close to photometric isoluminance. Pattern reversal VEPs were recorded to stimuli of a range of red/green luminance ratios and an achromatic checkerboard. No transient VEP could be elicited with an isoluminant chromatic pattern reversal stimulus from any infant less than 7 weeks post term and similarly, all infants more than 7 weeks post term showed clear chromatic VEPs. The chromatic response first appeared at that age as a major positive component (P1) of long latency. This was delayed and reduced in comparison to the achromatic response. As the infant grew older, the latency of the P1 component decreased with the appearance of N1 and N by the 10th week post term. This finding was consistent throughout all infants assessed. In a behavioural study, no infant less than 7 weeks post term demonstrated clear discrimination of the chromatic stimulus, while those infants older than 7 weeks could do so. These findings are reviewed with respect to current neural models of visual development.

Visual evoked magnetic responses (VEMR) to flash and pattern reversal stimulation

The problems of using a single channel magnetometer (BTi, Model 601) in an unshielded clinical environment to measure visual evoked magnetic responses (VEMR) were studied. VEMR to flash and pattern reversal stimuli were measured in 100 normal subjects. Two components, the P100M to pattern reversal and P2M to flash, were measured successfully in the majority of patients. The mean latencies of these components in different decades of life were more variable than the visual evoked potentials (VEP) that have been recorded to these stimuli. The latency of the P100M appeared to increase significantly after about 55 years of age whereas little change occurred for the flash P2M. The effects of blur, check size, stimulus size and luminance intensity on the latency and amplitude of the VEMR were studied. Blurring a small (32') check significantly increased latency whereas blurring a large (70') check had little effect on latency. Increasing check size significantly reduced latency of the P100M but had little effect on amplitude. Increasing the field size decreases the latency and increases the amplitude of the P100M. Within a normal subject, most of the temporal variability of the P100M appeared to be associated with run to run variation rather than between recording sessions on the same day or between days. Reproducibility of the P100M was improved to a degree by employing a magnetically shielded room. Increasing flash intensity decreases the latency and increases the amplitude of the P2M component. The magnitude of the effects of varying stimulus parameters on the VEMR were frequently greater than is normally seen in the VEP. The topography of the P100M and P2M varied over the scalp in normal subjects. Full field responses to a large check could be explained as approximately the sum of the half field responses and were consistent with the cruciform model of the visual cortex. Preliminary source localisation data suggested a shallower source in the visual cortex for the flash P2M compared with the P100M. The data suggest that suitable protocols could be devised to obtain normative data of sufficient quality to use the VEMR to flash and pattern clinically.

Topographic studies of scalp potentials evoked by pattern presentation

The waveform and scalp distribution of the visual evoked potentials elicited by stimuli in the foveal and parafoveal regions have been investigated in a group of normal humans using a 16-channel `brain mapping' system. The waveform and topography of the responses to pattern onset and pattern reversal stimulation were investigated, using 4 x 4o full field and 4 x 2o lateral and altitudinal half-field stimuli. The responses were composed of several successive peaks which are in some respects consistent with those demonstrated by other workers using larger field sizes. The differences in the behaviour of these components with respect to the position of the stimulus in the visual field were suggestive of origins in different areas of the visual cortex and/or different visual mechanism. Of particular interest were the major early positive components `P90' and `P95' of the responses to pattern onset and pattern reversal stimulation respectively. More detailed exploration of the behaviour of these major early positive components was carried out using `M-scaled' stimuli selected to activate one square centimetre patches of striate cortex and associated extrastriate re-projections, positioned at different points in the foveal and parafoveal area of the visual field. The inter- and intra-subject variability in amplitude and localisation of the signals elicited by these targets was considered to be a reflection of the individual variations in relationship of visual field projections with the pattern of gyri and fissures on the proximal surface of the occipital lobe. The behaviour of component P90 of the onset response is consistent with a lateral origin in extrastriate visual cortex; that of P95 of the pattern reversal response is consistent in some respects with a striate cortical origin, but in others with a partial origin in extrastriate cortex.

The investigation of the primary response of the flash visual evoked response

The topographical distribution of the early components of the flash visual evoked response (VER) were investigated using a twenty channel brain mapping system. Thirty subjects, ranging in age from 21 to 84 years, had flash VERs recorded using the standard 10-20 electrode system to a balanced non-cephalic reference. The subjects were divided into three age groups: a young group, a middle group and an older group. The P2 component (positive component around 100-120 msec) of the flash VER was recorded consistently over the occipital region throughout the age range, as was a frontal negative component (N120) of about the same latency. Only the young age group had this single negative component on the frontage channels, whilst the middle age group showed an additional negative component at around 75 msec (N75). Neither group had a recordable P1 component (positive component around 60-75 msec) over the occipital region. The older age group showed both P1 and P2 components over the occipital region with the distribution of the P1 component being more widespread anteriorly. The frontal channels showed both the negative N75 and the later N120 components. The frontal negative components were shown not to be related to the electroretinogram or the balanced non-cephalic reference, but were affected by the type of stimulation. Responses recorded to both pattern reversal and onset/offset stimulation did not show the frontal negative potentials seen with flash stimulation. It was shown that the P1 component is more readily recordable in the elderly and is preceded during middle age by the development of a frontal negative component at around the same latency. The changing morphology of the negative activity in the frontal region across the age range suggests that the use of an Fz reference would produce an artificial P1 component in the middle age group and an enhancement of this component in the elderly, as well as enhance the P2 component in all ages.

Visual signs and symptoms of Parkinson's disease

Parkinson's disease (PD) is a common disorder of middle-aged and elderly people, in which there is degeneration of the extra-pyramidal motor system. In some patients, the disease is associated with a range of visual signs and symptoms, including defects in visual acuity, colour vision, the blink reflex, pupil reactivity, saccadic and smooth pursuit movements and visual evoked potentials. In addition, there may be psychophysical changes, disturbances of complex visual functions such as visuospatial orientation and facial recognition, and chronic visual hallucinations. Some of the treatments associated with PD may have adverse ocular reactions. If visual problems are present, they can have an important effect on overall motor function, and quality of life of patients can be improved by accurate diagnosis and correction of such defects. Moreover, visual testing is useful in separating PD from other movement disorders with visual symptoms, such as dementia with Lewy bodies (DLB), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Although not central to PD, visual signs and symptoms can be an important though obscure aspect of the disease and should not be overlooked.

Latency and variability of the visual evoked magnetic response: a comparison of two single channel magnetometers

The latency variation of the P100M from minute to minute, between morning and afternoon and from day to day was investigated in an unshielded environment using two single channel magnetometers. Latency variation was greatest from minute to minute with relatively little longer term variation. The two magnetometers differed both in mean latency and in the degree of variation. This may be attributed to variation in the performance of the filters which were set a narrow bandwidth for recording in an unshielded environment.

Influence of check and field size on the visual evoked magnetic response to a pattern shift stimulus

A decrease in the check size of a pattern shift stimulus increases the latency and amplitude of the visual evoked potential (VEP) P100. In addition, for a given check size, decreasing the size of the stimulus field increases the latency and amplitude of the P100. These results imply that the central regions of the retina make a significant contribution to the generation of the electrical P100. However, the corresponding magnetic P100m may have a different origin. We have studied the effects of check and field size on the P100m in five normal subjects using a DC-Squid, second-order gradiometer. Magnetic responses were recorded at the positive maximum of the P100m over the occipital scalp to six check sizes (10-100') presented in a large (13 degrees 34') and small (5 degrees 14') field and to a large check (100') presented in seven field sizes (1 degree 45' - 15 degrees 10'). No responses were recorded to any check size with a small field. Decreasing the check size presented in a large field increased latency of the P100m by approx. 30 ms while the amplitude of the response decreased with the largest reduction occurring between 70' and 12' checks. Using a large check, latency increased and amplitude decreased as the field size was reduced. The latency changes in response to check and field size were similar to those described for the VEP although the magnitudes of the magnetic changes were greater. Unlike the VEP, amplitude responses were maximal when large checks were presented in a large stimulus field. This suggests that regions outside the central retina make a more significant contribution to the visual evoked magnetic response than they do to the VEP, and that the P100m may be useful clinically in the study of diseases that affect the more peripheral regions of the retina.

Neuropathological differences between areas B17 and B18: implications for visual evoked responses in Alzheimer's disease

The density of senile plaques (SP) and neurofibrillary tangles (NFT) was estimated at post-mortem in areas B17 and B18 of the visual cortex in 18 Alzheimer’s disease (AD) cases which varied in disease onset and duration. The density of SP in B17 and NFT in B17 and B18 declined significantly with age at death of the patient. The density of SP and NFT was greater in B18 than B17 but only in cases of earlier onset and shorter duration. The pathological differences between B17 and B18 could explain the visual evoked responses (VER) that have been reported in AD. However, the differences were small, and changes in the afferent pathways remain the most likely explanation for the VER in AD. © 1994 S. Karger AG, Basel.

Chronotopographical analysis of the pattern onset visual evoked magnetic response (VEMR):Implications for waveform peak identification

The topography of the visual evoked magnetic response (VEMR) to a pattern onset stimulus was studied in five normal subjects using a single channel BTi magnetometer. Topographic distributions were analysed at regular intervals following stimulus onset (chronotopograpby). Two distinct field distributions were observed with half field stimulation: (1) activity corresponding to the C11 m which remains stable for an average of 34 msec and (2) activity corresponding to the C111 m which remains stable for about 50 msec. However, the full field topography of the largest peak within the first 130 msec does not have a predictable latency or topography in different subjects. The data suggest that the appearance of this peak is dependent on the amplitude, latency and duration of the half field C11 m peaks and the efficiency of half field summation. Hence, topographic mapping is essential to correctly identify the C11 m peak in a full field response as waveform morphology, peak latency and polarity are not reliable indicators. © 1993.