Brainstem auditory evoked potentials in chronic renal failure and maintenance hemodialysis.

Brainstem auditory evoked potentials (BAEPs) were recorded in 36 chronic uremic patients maintained on hemodialysis and in 10 normal controls. Both absolute response latencies and central transmission times were affected. There were transitory increases in interpeak latencies of I-II and III-V that were reversed by dialysis. A permanent increase in wave III-V interpeak latency was not reversed by dialysis. Wave II-III interpeak latency was unaffected.

Separating the retinal electrophysiologic effects of vigabatrin: treatment versus field loss.

OBJECTIVE: To separate the retinal electrophysiologic markers associated with vigabatrin-attributed visual field loss (VGB-VFL) from those associated with current vigabatrin therapy. METHODS: A nonrandomly selected cohort of 8 previous and 18 current vigabatrin users and a reference cohort of 8 never vigabatrin-treated patients with epilepsy receiving other antiepilepsy drugs (AED) underwent electro-oculography (EOG), electroretinography (ERG), and automated static threshold perimetry. A cohort of 22 normal subjects underwent ERG. The validity of the retinal electrophysiologic variables to detect the presence and severity of VGB-VFL was assessed using receiver operator characteristic curves. RESULTS: Of 26 patients exposed to vigabatrin, 18 exhibited VGB-VFL. No patients receiving alternative AED showed this type of visual field abnormality. The presence and severity of VGB-VFL was significantly associated with the latency (implicit time) and amplitude of the ERG cone function. The amplitude of the cone flicker response was the strongest predictor of VGB-VFL and revealed a sensitivity of 100% at a specificity of 75%. The EOG, the photopic and scotopic ERG, and the latency of the ERG second oscillatory potential (OP2) were not significantly related to the presence of VGB-VFL. Vigabatrin therapy was significantly associated with the photopic amplitude, the scotopic a-wave latency, and the latency of OP2. CONCLUSION: In patients who cannot perform reliable perimetry, the cone-specific ERG flicker amplitude provides the best screening method for detecting VGB-VFL.

Field-specific visual-evoked potentials: identifying field defects in vigabatrin-treated children.

OBJECTIVE: To derive a visual-evoked potential (VEP) technique for identifying visual field defects in children with epilepsy treated with vigabatrin and unable to perform perimetry. BACKGROUND: Studies have linked vigabatrin to a specific pattern of visual field loss. Few studies have included the pediatric population because of difficulties in assessing the visual field by perimetry below a developmental age of 9 years. METHODS: A field-specific VEP was developed with a central (0 degrees to 5 degrees radius) and peripheral stimulus (30 degrees to 60 degrees radius). Stimuli consisted of black and white checks that increased in size with eccentricity. Checks reversed at different rates, allowing separate central and peripheral responses to be recorded. Five vigabatrin-treated young adults with field defects were identified using this stimulus. Electroretinograms (ERG) were recorded to examine the effects of vigabatrin on retinal function. Thirty-nine children aged 3 to 15 years were included in the study. Twelve patients were examined by both the field-specific stimulus test and perimetry. The diagnostic performance of the field-specific stimulus test was compared with that of perimetry. RESULTS: Thirty-five of 39 children complied with the field-specific stimulus, 26 of 39 complied with the ERG, and 12 of 39 complied with perimetry. Using the summed amplitude of the peripheral response from O(2) and O(1), responses below 10 microV were deemed abnormal. The field-specific stimulus identified 3 of 4 abnormal perimetry results and 7 of 8 normal perimetry results, giving a sensitivity of 75% and a specificity of 87.5%. When comparing perimetry results with the ERG parameters, only the 30-Hz flicker amplitude, with a cutoff below 70 microV, gave a useful indication of visual field loss. CONCLUSION: Field-specific VEP are well tolerated by children older than 2 years of age and are sensitive and specific in identifying vigabatrin-associated peripheral field defects.

Magnetoencephalographic evidence for non-geniculostriate visual input to human cortical area V5.

The aim of this study was to establish whether there is non-geniculostriate input to the extrastriate motion-sensitive area V5 in humans. Responses were measured with a SQUID neuro-magnetometer to motion stimuli presented within the blind hemifield of GY, a well-documented subject with a complete absence of the left primary visual cortical area V1. The motion stimulus was a 0.5c/deg, rapidly drifting (16Hz) achromatic sinusoidal grating. With this stimulus, the magnetic responses recorded over the temporo-parieto-occipital region in normals are well modelled by localized current sources in areas V1 and V5 (Anderson, S. J. et al., Proceedings of the Royal Society, London, Series B, 1996, 263, 423-431). As a control, evoked responses were measured to a 1.0 c/deg, stationary, photometrically isoluminant red/green sinusoidal grating. With the chromatic stimulus, the principal component of the magnetic responses recorded over the occipital pole in normals is well modelled by a current source in area V1 (Fylan, F. et al., Investigative Ophthalmology and Visual Science, 1995, 36, s1053). Both stimuli subtended 4 deg vertically by 6 deg horizontally, positioned such that the stimulus extended beyond the area of macular sparing into the lower field quadrant of the blind (or sighted) hemifield. Chromatic stimuli failed to evoked responses from GY's blind (contralateral) hemifield, consistent with there being no V1 activity in his left cortical hemisphere. However, motion stimuli did evoke responses from GY's blind hemifield, originating from a location consistent with activity in area V5. We further observed that both colour and motion stimuli evoked responses from GY's sighted (ipsilateral) hemifield. We conclude that there is non-geniculostriate input to extrastriate motion-sensitive areas in the human visual system, and that this pathway subserves the residual visual sensitivity to motion in the blind hemifield that has been demonstrated psychophysically in observer GY.

The visually evoked subcortical potential: is related to the electroretinogram?

The visually evoked subcortical potential (VESP) of mean latencies P21-N28-P36 has previously been recorded at an electrode site around the mastoid process. An initial topographical study of the potential indicated that it was independent of the electroretinogram (ERG), and monocular stimulation showed bilateral reduction, which suggests that the VESP is of postchiasmal origin. A more detailed topographical study of the scalp and facial distribution of the ERG and its oscillatory potentials has been carried out, with simultaneous recording of the VESP. Two monocular fields of ERG activity have been demonstrated, each having a wide area of distribution and interacting medially. Remnants of the ERG b-wave have been detected at many electrode sites, but they were of different amplitude and morphology from the VESP. Results are also presented from two atypical control subjects and two patients, providing further evidence of the separate genesis of the ERG and VESP.

The scalp topography of the human visually evoked subcortical potential.

Stimulus and analysis parameters have been adjusted to provide optimum conditions for producing and recording the early components of flash visual evoked potentials. A visual evoked subcortical potential (VESP) of mean latency P23-N28-P34 has been recorded in 86% of subjects. The triphasic wave was maximal at an electrode position slightly posterior to the Rolandic/sylvian fissure and topographically separate from the lid electroretinogram and the visual evoked cortical potential. Monocular stimulation shows bilateral reduction of the amplitude of the VESP, indicating that the wave is independent of the retina and optic nerve and must be arising from a postchiasmal site.

Visual acuity and the flash visually evoked cortical potential in albinos.

The flash visually evoked cortical potential (VECP) was recorded in 18 human albinos. In some individuals P2 (latency 100-120 msec) formed the major component while in others P1 (latency 60-80 msec) was the largest component and dominated the response. The relative amplitude of P1 compared to P2 was calculated, and the results compared to the levels of monocular Snellen Visual Acuity measured. A relationship was found such that the greater the amplitude of P1 compared to P2, the lower the level of acuity. (Group 1: rs = -0.509, P less than 0.05. Group 2: rs = -0.536, P less than 0.05).

Lateralization of the flash visual-evoked cortical potential in human albinos.

Investigations were undertaken to determine which particular components of the flash visual-evoked cortical potential (VECP) lateralize on monocular stimulation in human albinos. Our results demonstrate that only the major positive component shows clear lateralization. Statistical analysis revealed that the latency lateralization was significant (P less than 0.001) while the amplitude lateralization was not.

Localization and functional analysis of human cortical area V5 using magneto-encephalography.

Using a multi-channel SQUID-based neuromagnetometer, we have determined the location, temporal dynamics and functional response properties of the human homologue of the primate cortical area V5 (MT). We provide evidence that area V5 in humans is located near the occipito-temporal border in a minor sulcus immediately below the superior temporal sulcus. this area is selective for low spatial frequencies ( < or = 4.0 c/deg), responds to a wide range of temporal frequencies ( < or = 35 Hz) and shows response saturation for stimulus contrasts greater than 10%. In addition, we find that this area is not responsive to purely chromatic patterns but is responsive to motion-contrast stimuli. Our results are consistent with the hypothesis that area V5 in humans represents a stage of processing within the magnocellular pathway. We discuss our results in relation to the widespread belief that area V5 in humans is specifically concerned with motion perception.

Magnetic source imaging in fixation-off sensitivity: relationship with alpha rhythm.

A patient in whom a variety of abnormal EEG findings can be elicited by elimination of central vision and fixation demonstrates fixation-off sensitivity. The underlying mechanisms of fixation-off sensitivity and its relationship with alpha rhythm remain unclear. To obtain a better understanding of this issue, we used a whole-head magnetoencephalograph to study an epileptic child with fixation-off sensitivity resulting in a 3-Hz, large-amplitude oscillation (300 microV) over the occipital regions on the EEG. Magnetic source localization revealed alpha activity around the calcarine fissure and surrounding parieto-occipital areas. Magnetic sources of abnormalities relating to fixation-off sensitivity, however, usually were located deeper in the brain, suggesting more extensively distributed sources, with involvement of the cingulate gyrus and the basomesial occipitotemporal region. Distributions of the sources of both types of activities show independent clusters but also an appreciable domain of overlap. Our findings indicate that abnormalities related to fixation-off sensitivity can emerge in thalamocortical networks, with larger and more anterior cortical distribution than those that generate alpha rhythm. Transition in the type of oscillation appears not only to depend on a change in cellular dynamics but also to be reflected in a different spatial distribution of the underlying neuronal networks.

Morphology of transient VEPs to luminance and chromatic pattern onset and offset.

Characteristics of the visual evoked response to chromatic and luminance-modulated stimuli reflect the activity of underlying neural mechanisms, although selective neuronal activity depends upon stimulus parameters. In the present study, the behaviour of the transient visual evoked response to low spatial and temporal frequency chromatic stimuli is investigated at a range of colour luminance ratios. Our results show that the response to pattern-offset may be used in addition to the pattern-onset response as part of the signature of the evoked response to luminance-modulated or isoluminant chromatic stimuli.

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.

Assessment of cortical dysfunction in human strabismic amblyopia using magnetoencephalography (MEG).

The aim of this study was to use the technique of magnetoencephalography (MEG) to determine the effects of strabismic amblyopia on the processing of spatial information within the occipital cortex of humans. We recorded evoked magnetic responses to the onset of a chromatic (red/green) sinusoidal grating of periodicity 0.5-4.0 c deg-1 using a 19-channel SQUID-based neuromagnetometer. Evoked responses were recorded monocularly on six amblyopes and six normally-sighted controls, the stimuli being positioned near the fovea in the lower right visual field of each observer. For comparison, the spatial contrast sensitivity function (CSF) for the detection of chromatic gratings was measured for one amblyope and one control using a two alternate forced-choice psychophysical procedure. We chose red/green sinusoids as our stimuli because they evoke strong magnetic responses from the occipital cortex in adult humans (Fylan, Holliday, Singh, Anderson & Harding. (1997). Neuroimage, 6, 47-57). Magnetic field strength was plotted as a function of stimulus spatial frequency for each eye of each subject. Interocular differences were only evident within the amblyopic group: for stimuli of 1-2 c deg-1, the evoked responses had significantly longer latencies and reduced amplitudes through the amblyopic eye (P < 0.05). Importantly, the extent of the deficit was uncorrelated with either Snellen acuity or contrast sensitivity. Localization of the evoked responses was performed using a single equivalent current dipole model. Source localizations, for both normal and amblyopic subjects, were consistent with neural activity at the occipital pole near the V1/V2 border. We conclude that MEG is sensitive to the deficit in cortical processing associated with human amblyopia, and can be used to make quantitative neurophysiological measurements. The nature of the cortical deficit is discussed.

Former chronic methylenedioxymethamphetamine (MDMA or ecstasy) users report mild depressive symptoms.

Previous work has indicated recreational use of methylenedioxymethamphetamine (MDMA or ecstasy) is associated with elevated scores on self-report measures of depression. We sought to examine the long-term effects of consumption on depression in a group of individuals who had consumed large quantities of the drug in the past, but were now leading relatively drug free lives. Respondents to this study (n = 29) had consumed an average of 1.5 ecstasy tablets in the last month, 8.4 in the last 6 months and 23.3 in the last 12 months. The estimated total consumed was 527 tablets, indicating that these respondents were indeed former chronic users of the drug. None of the respondents had consumed ecstasy in the last 14 days. Levels of depression (Beck's Depression Inventory) were significantly (p < 0.01) elevated compared to a matched non-drug using control group. Within the group of former chronic users, these levels of depression were not significantly affected by current use of alcohol, cannabis or amphetamine, but were positively correlated with an external locus of control (p < 0.05), infrequent but severe- (p < 0.05) and frequent but mild- (p < 0.005) self-report measures of life stress. Multiple regression indicated that levels of frequent but mild life stress (p < 0.005) and the quantity of ecstasy tablets respondents consumed over a 12-h period (p < 0.05) were the only variables that were significant predictors of self-reported levels of depression. The results of this study indicate that former chronic ecstasy users report higher levels of depression than their matched controls.

Visual electrophysiology to achromatic and chromatic stimuli in premature and full term infants.

We have previously reported on the development of black/white pattern reversal VEPs in premature babies of more than 30 weeks post-menstrual age (PMA). Unlike the flash VEP, the pattern reversal VEP shows a similar morphology to that of the full term infant and the major positive component (P1) decreased in latency with increasing PMA. The N1 and N2 components were more likely to be present with increasing maturity. In our present study we are examining the development of the transient chromatic pattern VEP. In order to produce a purely chromatic stimulus it is necessary to remove luminance cues. Based on forced choice preferential looking we developed a method of determining the isoluminant point for infants. Preference was tested for a flickering sinusoidal red and green grating over the uniform field. As sensitivity for chromatic flicker is much poorer than for luminance flicker, sensitivity is expected to be least when the residual luminance variation in the stimulus is at a minimum. The red/green luminance ratio at which this occurs represents the isoluminant point. From this method we found the subjective isoluminant point for infants of 2-3 months of age to be very close to the objective measure of isoluminance. Using this information, pattern reversal VEPs to 20 chromatic red/green and achromatic checks were studied and it would appear that pattern reversal VEPs cannot be obtained to isoluminant stimuli before 7 weeks chronological age.

Effect of dopamine and acetylcholine on the visual evoked potential.

Visual evoked potentials were measured on patients with Parkinson's disease and Alzheimer's disease and normal controls to assess the function of dopamine and acetylcholine in the visual system. Dopamine is a neurotransmitter known to be present in the retina of primates and is found to be severely depleted in the substantia nigra of patients with Parkinson's disease. Acetylcholine is also known to be present in the retina, visual cortex, and superior colliculus and is found to be grossly reduced in patients with Alzheimer's disease. Stimuli were designed to preferentially activate functionally separate pathways in the visual system described as magnocellular and parvocellular. The four stimuli were a diffuse flash; an achromatic, 73' check counterphasing at 6 Hz at a contrast of 30%; an achromatic 10' check counterphasing at 2 Hz at a contrast of 85%; and an isoluminant red/green grating of 4 cpd presented using an on and off cosine ramp of 200 ms. The results indicate that an acetylcholine deficit produces a delay to the flash P2 component of the visual evoked potential. No change was detected when other stimuli were used.

Topographic mapping of the pattern onset evoked magnetic response to stimulation of different portions of the visual field.

Visual evoked magnetic responses to pattern onset/offset stimuli were recorded in 5 normal subjects. The outgoing and ingoing magnetic currents were seen maximally over the contralateral visual cortex to the half field stimulated in the majority of subjects. The distribution of magnetic currents with half field stimulation would be consistent with a dipole on the midline with the positive end pointing laterally. Quadrantic stimuli produced dipoles which would be consistent with a vector sum of dipoles situated, in the case of upper quarter field stimulation, in the lingual gyri on the floor of the calcarine fissure. Lower quadrantic stimulation produced a vector consistent with dipoles on the cuneal gyrus and on the ceiling of the calcarine fissure producing a resultant vector. The use of paired octant stimuli to improve localisation was demonstrated on both right left and upper and lower half fields.

Medical technology assessment photic stimulation--standardization of screening methods.

RATIONALE: In many EEG laboratories in Europe, intermittent photic stimulation (IPS) is not performed routinely, and consequently, great variation exists in the type of photo stimulator used, the methodology employed, and the interpretation of the EEG curves, thus leading to different outcomes. METHODOLOGY: It was decided to hold a consensus meeting with experts in the field of photic stimulation from various European countries. This meeting was held at the Stichting Epilepsie Instellingen Nederland, Heemstede, the Netherlands. The consensus reached was presented and discussed at the 9th European Congress of Clinical Neurophysiology in Ljubjana in June 1998. RESULTS: Patients should be positioned at a distance of 30 cm from the photic stimulator (nasion to lamp) with dim surrounding lights, just enough to see the patient. Flashes should be delivered in separate trains of 10 s for each frequency, with intervals of 7 s minimum. First stimulation occurs with eyes open followed after 5 s by eye closure, while starting at 1 Hz progressing to 20 Hz, unless generalised epileptiform discharges are evoked at a lower frequency. Then, frequencies should start at 60 Hz decreasing to 25 Hz. The following frequencies should be used: 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 60, 50, 40, 30 and 25 Hz. The total duration is a maximum of 6 min (patients without a reaction to IPS). In interpreting the evoked responses, a clear distinction should be made between epileptiform responses confined to the occipital area (OSW), starting occipitally and spreading to frontal regions (OGSW), or generalised from the start (GSW). Other responses include generalised spikes (OR). CONCLUSION: This standard is safe, relatively quick, simple and reliable. Comparison of data within patients and between patients of various laboratories will also be possible. This will improve the quality of the care of the individual patient and make collaborative research possible.

Visual and auditory evoked potentials in a case of Marchiafava Bignami Disease.

Brainstem auditory evoked potentials and visual evoked potentials to both flash and pattern reversal stimulation were recorded in a case of clinically diagnosed Marchiafava Bignami Disease (M.B.D.) A CT scan revealed dilation of the supratentorial ventricular system and fairly extensive cortical atrophy. The brainstem potentials showed a non-specific abnormality of the N4 component, (in the region of the caudal pons) and were inconclusive. The visual evoked potentials to flash stimulation were delayed while pattern reversal responses were within normal limits.