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.

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.

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 clinical utility of the middle latency and 40Hz auditory evoked potentials in audiological electrodiagnosis

The two elcctrophysiological tests currently favoured in the clinical measurement of hearing threshold arc the brainstorm evoked potential (BAEP) and the slow vertex response (SVR). However, both tests possess disadvantages. The BAEP is the test of choice in younger patients as it is stable at all levels of arousal, but little information has been obtained to date at a range of frequencies. The SVR is frequency specific but is unreliable in certain adult subjects and is unstable during sleep or in young children. These deficiencies have prompted research into a third group of potentials, the middle latency response (MLR) and the 40HZ responses. This research has compared the SVR and 40HZ response in waking adults and reports that the 40HZ test can provide a viable alternative to the SVR provided that a high degree of subject relaxation is ensured. A second study examined the morphology of the MLR and 40HZ during sleep. This work suggested that these potentials arc markedly different during sleep and that methodological factors have been responsible for masking these changes in previous studies. The clinical possibilities of tone pip BAEPs were then examined as these components were proved to be the only stable responses present in sleep. It was found that threshold estimates to 5OOHz, lOOOHz and 4000Hz stimuli could be made to within 15dBSL in most cases. A final study looked more closely at methods of obtaining frequency specific information in sleeping subjects. Threshold estimates were made using established BAEP parameters and this was compared to a 40HZ procedure which recorded a series of BAEPs over a 100msec. time sweep. Results indicated that the 40mHz procedure was superior to existing techniques in estimating threshold to low frequency stimuli. This research has confirmed a role for the MLR and 40Hz response as alternative measures of hearing capability in waking subjects and proposes that the 40Hz technique is useful in measuring frequency specific thresholds although the responses recorded derive primarily from the brainstem.

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.

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.

Real-time imaging of human cortical activity evoked by painful esophageal stimulation

Background & Aims: Current models of visceral pain processing derived from metabolic brain imaging techniques fail to differentiate between exogenous (stimulus-dependent) and endogenous (non-stimulus-specific) neural activity. The aim of this study was to determine the spatiotemporal correlates of exogenous neural activity evoked by painful esophageal stimulation. Methods: In 16 healthy subjects (8 men; mean age, 30.2 ± 2.2 years), we recorded magnetoencephalographic responses to 2 runs of 50 painful esophageal electrical stimuli originating from 8 brain subregions. Subsequently, 11 subjects (6 men; mean age, 31.2 ± 1.8 years) had esophageal cortical evoked potentials recorded on a separate occasion by using similar experimental parameters. Results: Earliest cortical activity (P1) was recorded in parallel in the primary/secondary somatosensory cortex and posterior insula (∼85 ms). Significantly later activity was seen in the anterior insula (∼103 ms) and cingulate cortex (∼106 ms; P = .0001). There was no difference between the P1 latency for magnetoencephalography and cortical evoked potential (P = .16); however, neural activity recorded with cortical evoked potential was longer than with magnetoencephalography (P = .001). No sex differences were seen for psychophysical or neurophysiological measures. Conclusions: This study shows that exogenous cortical neural activity evoked by experimental esophageal pain is processed simultaneously in somatosensory and posterior insula regions. Activity in the anterior insula and cingulate - brain regions that process the affective aspects of esophageal pain - occurs significantly later than in the somatosensory regions, and no sex differences were observed with this experimental paradigm. Cortical evoked potential reflects the summation of cortical activity from these brain regions and has sufficient temporal resolution to separate exogenous and endogenous neural activity. © 2005 by the American Gastroenterological Association.

Cortical processing of human gut sensation: an evoked potential study

The rectum has a unique physiological role as a sensory organ and differs in its afferent innervation from other gut organs that do not normally mediate conscious sensation. We compared the central processing of human esophageal, duodenal, and rectal sensation using cortical evoked potentials (CEP) in 10 healthy volunteers (age range 21-34 yr). Esophageal and duodenal CEP had similar morphology in all subjects, whereas rectal CEP had two different but reproducible morphologies. The rectal CEP latency to the first component P1 (69 ms) was shorter than both duodenal (123 ms; P = 0.008) and esophageal CEP latencies (106 ms; P = 0.004). The duodenal CEP amplitude of the P1-N1 component (5.0 µV) was smaller than that of the corresponding esophageal component (5.7 µV; P = 0.04) but similar to that of the corresponding rectal component (6.5 µV; P = 0.25). This suggests that rectal sensation is either mediated by faster-conducting afferent pathways or that there is a difference in the orientation or volume of cortical neurons representing the different gut organs. In conclusion, the physiological and anatomic differences between gut organs are reflected in differences in the characteristics of their afferent pathways and cortical processing.

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 use of flash and pattern evoked fields in the diagnosis of Alzheimer's disease

Subjects with Alzheimer's disease (AD) exhibit normal visually evoked potentials (VEP) to pattern reversal stimuli but a delayed P2 flash response. The pattern response may originate in the primary visual cortex via the geniculo-calcarine pathway while the flash P2 may originate in the association areas via the cholinergic-tectal pathway. We now show: a) that the pathology of AD is more prominent in the visual association areas B18/19 than in B17 and b) that the magnetic signal to flash and pattern may originate from B18/19 and B17 respectively.

Normative data for two visually evoked magnetic components

The practicality or recording normative data for two components of the visually evoked magnetic response (VEMR) (P100M and P2M) using a single channel dc-SQUID second order gradiometer in an unshielded environment was investigated. Latency norms of the P100M and P2M were more variable than the corresponding electrical P100 and P2 visual evoked potentials. Methods of improving the normative data for clinical use were discussed.

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.

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.