Visual Evoked Potentials Amplitude Research Articles

Altered cortical visual processing in individuals with a spreading photoparoxysmal EEG response

Photosensitive individuals respond with epileptiform electroencephalography (EEG) discharges to intermittent photic stimulation. The pathogenetic mechanisms underlying this photoparoxysmal response (PPR) remain to be clarified. We investigated the involvement of magnocellular and parvocellular pathways in the processing of nonprovocative visual stimuli in healthy subjects with different phenotypic expressions of PPR (15 individuals with a local PPR, i.e. occipital discharges only, and 15 with a PPR propagating to anterior brain regions) and in 17 PPR-negative healthy controls using pattern-reversal visual evoked potentials (VEP). Checkerboard stimulation was performed at a low and a high spatial frequency to preferentially activate the magnocellular and parvocellular pathways. VEP habituation was also assessed over 15 blocks (each 100 trials) of recording. PPR-positive individuals with propagating PPR showed an increase in the N75-P100 and P100-N135 VEP components for both spatial frequencies, whereas individuals with a local PPR had normal VEP amplitudes. Individuals with propagating PPR also showed a stronger VEP habituation and reported more aversive sensations during continuous visual stimulation with the high spatial frequency checkerboard. The selective increase in VEP amplitudes in individuals with propagating PPR corroborates the notion that PPR with propagation is pathophysiologically distinct from local PPR. The increase in VEP amplitudes was independent of the spatial frequency of visual stimulation, indicating an increased neuronal excitability in both the parvocellular and magnocellular pathways. The stronger habituation in these individuals may reflect a compensatory mechanism to stabilize excitability in the visual system.

Abnormal spatial frequency processing in high-functioning children with pervasive developmental disorder (PDD)

Objective Basic abnormalities in visual information processing could be associated with the local visual bias often found in subjects with PDD. Therefore, the present study investigated the existence of deficits in spatial frequency processing at an early sensory level in children with PDD. Methods Visual evoked potentials (VEPs) and VEP dipole sources elicited by high and low spatial frequency gratings were analyzed in high-functioning children with PDD and matched controls. Results Around 80 ms (N80-latency) children with PDD did not show the same robust differences between high and low spatial frequencies in VEP amplitude and VEP brain sources as controls, because of atypical processing of high frequencies. Analyses at the P1-latency (130 ms) revealed that, although similar inferior–medial brain sources were activated for the processing of both spatial frequencies in the PDD and control group, source strength in response to both frequencies was weaker in the PDD compared to control group. Moreover, additional superior–lateral brain sources were activated during the processing of both frequencies in the PDD group. Conclusions Decreased specialized processing of high and low spatial frequencies might be a robust characteristic of PDD. Early in processing abnormalities in high spatial frequency processing seem to occur in PDD. At a later phase in processing there seems to be both atypical high and low spatial frequency processing. Considering that the processing of specific spatial frequencies plays an important role in the processing of global and local aspects of hierarchical stimuli and faces and of emotions, present data suggest that peculiarities in PDD subjects with respect to these stimuli might be related to an abnormality in more fundamental visual processes. Significance A basic abnormality in visual frequency processing is established in children with PDD.

Neuroprotective Effect of Transcorneal Electrical Stimulation on the Acute Phase of Optic Nerve Injury

Traumatic optic neuropathy often induces a loss of vision that proceeds rapidly within several hours, together with retinal ganglion cell death, in a much slower time course. Electrical stimulation has previously been shown to rescue injured retinal ganglion cells from cell death. The present study tests whether transcorneal electrical stimulation could preserve visual function after an optic nerve crush. Transcorneal electrical stimulation was given immediately after a calibrated optic nerve crush. We measured visually evoked potentials (VEPs) in the visual cortex of rats before and immediately after the optic nerve crush and after the transcorneal stimulation to estimate an extent of damage and effects of stimulation in individual animals. In addition, the retinal axons were labeled with a fluorescent anterograde tracer to determine whether the transcorneal electrical stimulation can protect the retinal axons from degeneration. The optic nerve crush was made at an intensity that does not allow a spontaneous recovery of VEP for 1 week. The transcorneal stimulation immediately increased VEP amplitude impaired by the optic nerve crush, and this augmentation was often preserved after 1 week. In the stimulated animals, a larger amount of retinal axons projected centrally beyond the crushed region in comparison to the unstimulated animals. Transcorneal electrical stimulation would restore the functional impairment of optic nerve by traumatic injury at a very early stage and protect retinal axons from the ensuing degeneration.

Evaluating the NMDA-Glutamate Receptor as a Site of Action for Toluene, In Vivo

Acute exposure to toluene and other volatile organic solvents results in neurotoxicity characterized by nervous system depression, cognitive and motor impairment, and alterations in visual function. In vitro, toluene disrupts the function of N-methyl-D-aspartate (NMDA)-glutamate receptors, indicating that effects on NMDA receptor function may contribute to toluene neurotoxicity. NMDA-glutamate receptors are widely present in the visual system and contribute to pattern-elicited visual-evoked potentials (VEPs) in rodents, a measure that is altered by toluene exposure. The present study tested the hypothesis that effects on NMDA receptors contribute to toluene-induced alterations in pattern-elicited VEPs. Prior to examining the effects of NMDA receptor agonists and antagonists on toluene-exposed animals, a dose-range study was conducted to determine the optimal dose for NMDA (agonist) and MK801 (antagonist). Dose levels of 2.5 mg/kg NMDA and 0.1 mg/kg MK801 were selected from these initial studies. In the second study, Long-Evans rats were exposed to toluene by inhalation, and VEPs were measured during toluene exposure in the presence or absence of NMDA or MK801. Pattern-elicited VEPs were collected by exposing rats to a sinusoidal pattern modulated at a temporal frequency of 4.55 Hz. Following collection of baseline VEPs, rats were injected with either saline, NMDA (2.5 mg/kg, ip), or MK801 (0.1 mg/kg, ip) and 10 min later were exposed to air or toluene (2000 ppm). VEP amplitudes were calculated for 1x (F1) and 2x stimulus frequency (F2). The F2 amplitude was reduced by approximately 60, 60, and 50% in the toluene-exposed groups (TOL): SALINE/TOL (n = 11), NMDA/TOL (2.5 mg/kg; n = 13), and NMDA/TOL (10 mg/kg, n = 11), respectively. Thus, NMDA (2.5 and 10 mg/kg) did not significantly affect toluene-mediated F2 amplitude effects. Administration of 0.1 mg/kg MK801 prior to toluene exposure blocked the F2 amplitude decreases caused by toluene (n = 9). However, when 0.1 mg/kg MK801 was administered 20 min after the onset of toluene exposure, toluene-mediated F2 amplitude decreases persisted despite the challenge by MK801. These data support the hypothesis that acute actions of toluene on pattern-elicited VEPs involve NMDA receptors.

Long-Term Plasticity of Visually Evoked Potentials in Humans is Altered in Major Depression

Long-term synaptic plasticity is a ubiquitous form of neuronal plasticity that regulates the strength of synaptic transmission in many brain areas. However, most data on long-term potentiation and long-term depression rely on research in animal brain slices. The role of synaptic plasticity in physiology and pathology of the functioning human brain remains obscure. Considering recent studies that provided evidence for a dysfunction of brain plasticity as the neurobiological basis of affective disorders, we assessed neural transmission and its plastic modulation in the visual pathway in healthy control subjects and patients with major depression. Recordings of visually evoked potentials (VEPs) in humans. Prolonged visual presentation of checkerboard reversals resulted in a sustained amplitude modulation of early components of subsequent VEPs. After a 10-min block of visual stimulation (two checkerboard reversals per second), the C1 component was reduced, whereas P1 and N1 were both significantly increased for >30 min. Chronic application of the selective serotonin reuptake inhibitor sertraline in healthy control subjects augmented these effects, whereas the polarity of the modulation was inverted in patients with severe major depression. Moreover, early VEP amplitudes were decreased in depressed patients when compared with matched control subjects and increased in normal control subjects after chronic intake of an antidepressant. Our results demonstrate that stimulus-induced response plasticity of VEPs can be induced in the human brain and is sharing properties with hebbian forms of synaptic plasticity. Major depression and antidepressant treatment of healthy control subjects differentially modulate amplitude and plasticity of evoked potentials. This study provides direct evidence in humans for a central role of synaptic plasticity in the pathophysiology of depression.

Exercise Improves Visual Deficits Tested by Visual Evoked Potentials in Streptozotocin-Induced Diabetic Rats

Visual evoked potentials (VEP) can be used as an objective non-invasive method to study the electrical activity of the visual system. Latency and amplitude measurements of VEP demonstrated that diabetes mellitus has been associated with increases in the latencies whereas the amplitude measurements revealed contradictory results. Although physical exercise has been reported to reduce the complications of diabetes mellitus, the effect of exercise on the visual system remains unknown. We investigated the effects of long-term moderate physical exercise on VEP in streptozotocin (STZ)-diabetic rats. We also measured brain thiobarbituric acid-reactive substances (TBARS) to explore the possible contribution of lipid peroxidation on the visual system. Animals were divided into four groups: control (C), control exercise (CE), diabetic (D) and diabetic exercise (DE) groups. Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg). Three days after the confirmation of diabetes, DE and CE groups were trained by running on a motor-driven treadmill with a progressive eight-week programme. The animals began running at 10 m/min, 0 degrees slope, 10 min/day and reached a level of 28 m/min, 6 degrees slope, 60 min/day by week 8. TBARS were elevated and VEP latencies were delayed in diabetic rats, indicating diabetes-induced defects in the optic pathway. These prolonged latencies were restored by exercise training. VEP amplitudes of the DE group were found unaltered with the exception of a decrement in P(2)N(2) which represents an early component of VEP, suggesting that exercise improves visual system defects in diabetic animals at different levels of the optic pathway.

Comparison of Pattern Visual-Evoked Potentials to Perimetry in the Detection of Visual Loss In Children With Optic Pathway Gliomas

We sought to compare visual evoked potentials (VEPs) with standard visual field testing in children with visual pathway gliomas. Fifteen of 40 children with visual pathway gliomas verified on magnetic resonance imaging scan who cooperated with Goldmann visual field (GVF) and 3-channel VEPs were studied. GVFs were obtained in 25 eyes with adequate vision. VEP amplitudes, latencies, and signal-to-noise ratios (SNRs) were compared with control subjects. Four of the patients (5 eyes) also had Humphrey visual field testing. Twenty-two of 25 eyes had a field defect, 15 eyes showed a relative or absolute hemianopia, 7 eyes showed a central or generalized depression, and 3 eyes were normal. In hemianopic eyes, 87% showed a depression (GVF) or reduced sensitivity (Humphrey field) in the opposite hemifield. VEP amplitudes and SNRs, normally largest at the midline electrode, were significantly reduced in all eyes with visual field loss. By comparison, lateral electrodes showed significantly lower amplitudes and SNRs in patients and controls. Interhemispheric VEP asymmetry (>2:1 ratio) was seen in 67% of patients with hemianopia and 53% of controls. Reduction of amplitude and SNR at the midline VEP electrode was a sensitive indicator of visual field loss. Interhemispheric VEP asymmetry was not reliable in detection of a hemianopic field defect. VEPs can be a reliable and objective alternative for the detection of visual loss due to optic pathway glioma in children who are intolerant to visual field testing. We recommend the test protocol include pattern-onset and check reversal stimuli of at least one high and one low spatial frequency.

Simultaneous VEP and transcranial Doppler ultrasound recordings to investigate activation-flow coupling in humans

Simultaneous assessment of electrical as well as hemodynamic responses in visual stimulation tasks is a relatively new approach to investigate activation-flow coupling in humans. To investigate the relation of both signals, we compared visually evoked potentials (VEP) with evoked flow velocity responses in the posterior cerebral artery by performing different visual stimulation tasks in healthy students. Check sizes and flickering frequency of a checkerboard pattern and the radial visual field section of a dartboard pattern were varied. VEPs were expressed in amplitude differences. Hemodynamic changes were given in terms of a control system model specifying the gain, attenuation, natural frequency and rate time parameters. From the typical VEP amplitude differences, we found the early N75-P100 amplitude difference significantly correlated to the gain parameter of the hemodynamic response. Both parameters increased with higher complexity of the checkerboard pattern and increasing visual field sections, whereas they remained nearly stable in the chosen frequency range. To corroborate the hypothesis of a tight coupling, further studies have to prove if the strength of this coupling could be used in clinical conditions. (E-mail: manfred.kaps@neuro.med.uni-giessen.de)

Effects of repetitive TMS on visually evoked potentials and EEG in the anaesthetized cat: dependence on stimulus frequency and train duration

Repetitive transcranial magnetic stimulation (rTMS) has been shown to alter cortical excitability that lasts beyond the duration of rTMS application itself. High-frequency rTMS leads primarily to facilitation, whereas low-frequency rTMS leads to inhibition of the treated cortex. However, the contribution of rTMS train duration is less clear. In this study, we investigated the effects of nine different rTMS protocols, including low and high frequencies, as well as short and long applications (1, 3 and 10 Hz applied for 1, 5 and 20 min), on visual cortex excitability in anaesthetized and paralysed cats by means of visual evoked potential (VEP) and electroencephalography (EEG) recordings. Our results show that 10 Hz rTMS applied for 1 and 5 min significantly enhanced early VEP amplitudes, while 1 and 3 Hz rTMS applied for 5 and 20 min significantly reduced them. No significant changes were found after 1 and 3 Hz rTMS applied for only 1 min, and 10 Hz rTMS applied for 20 min. EEG activity was only transiently (<20 s) affected, with increased delta activity after 1 and 3 Hz rTMS applied for 1 or 5 min. These findings indicate that the effects of rTMS on cortical excitability depend on the combination of stimulus frequency and duration (or total number of stimuli): short high-frequency trains seem to be more effective than longer trains, and low-frequency rTMS requires longer applications. Changes in the spectral composition of the EEG were not correlated to changes in VEP size.

Normal and dichromatic color discrimination measured with transient visual evoked potential

It would be informative to have an electrophysiological method to study, in an objective way, the effects of mercury exposure and other neurotoxics on human color vision performance. The purpose of the present work was to study human color discrimination by measuring chromatic difference thresholds with visual evoked potential (VEP). Six young normal trichromats (24 +/- 1 years old) and one deutan (26 years old) were tested. The stimuli consisted of sinusoidal isoluminant chromatic gratings made from chromaticity pairs located along four different color directions centered on two reference points. Heterochromatic flicker photometry (HFP) protocol was used to obtain the isoluminance condition for every subject and for all chromaticity pairs. Spatial frequency was 2 cycles/deg. Presentation mode comprised onset (300 ms)/offset (700 ms) periods. As previously described, we found a negative deflection in the VEP which was related to the chromatic difference: as chromatic difference increased, amplitude increased and latency decreased. VEP response amplitude was plotted against distance in the CIE 1976 color space between the grating chromaticities and fitted with a regression line. We found color thresholds by extrapolating the fitting to null amplitude values. The thresholds were plotted in the CIE 1976 color space as MacAdam ellipses. In normal trichromats the ellipses had small size, low ellipticity, and were vertically oriented. In the deutan subject, the ellipses had large size, high ellipticity, and were oriented towards the deutan copunctal locus. The VEP thresholds were similar to those obtained using grating stimuli and psychophysical procedures, however smaller than those obtained using pseudoisochromatic stimuli (Mollon-Reffin method). We concluded that transient VEP amplitude as a function of contrast can be reliably used in objective studies of chromatic discrimination performance in normal and altered human subjects.

Deep brain stimulation of the subthalamic nucleus affects resting EEG and visual evoked potentials in Parkinson's disease

Objective We studied changes of the EEG spectral power induced by deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD). Also analyzed were changes of visual evoked potentials (VEP) with DBS on and off. Methods Eleven patients with advanced PD treated with bilateral DBS STN were examined after an overnight withdrawal of L-DOPA and 2 h after switching off the neurostimulators. All underwent clinical examination followed by resting EEG and VEP recordings, a procedure repeated after DBS STN was switched on. Results With DBS switched on, the dominant EEG frequency increased from 9.44±1.3 to 9.71±1.3 Hz ( P<0.01) while its relative spectral power dropped by 11% on average ( P<0.05). Switching on the neurostimulators caused a decrease in the N70/P100 amplitude of the VEP ( P<0.01), which inversely correlated with the intensity of DBS (black-and-white pattern: P<0.01; color pattern: P<0.05). Conclusions Despite artifacts generated by neurostimulators, the VEP and resting EEG were suitable for the detection of effects related to DBS STN. The acceleration of dominant frequency in the alpha band may be evidence of DBS STN influence on speeding up of intracortical oscillations. The spectral power decrease, seen mainly in the fronto-central region, might reflect a desynchronization in the premotor and motor circuits, though no movement was executed. Similarly, desynchronization of the cortical activity recorded posteriorly may by responsible for the VEP amplitude decrease implying DBS STN-related influence even on the visual system. Significance Changes in idling EEG activity observed diffusely over scalp together with involvement of the VEP suggest that the effects of DBS STN reach far beyond the motor system influencing the basic mechanisms of rhythmic cortical oscillations.

Optic nerve atrophy and retinal nerve fibre layer thinning following optic neuritis: Evidence that axonal loss is a substrate of MRI-detected atrophy

Magnetic resonance imaging (MRI) measures of brain atrophy are often considered to be a marker of axonal loss in multiple sclerosis (MS) but evidence is limited. Optic neuritis is a common manifestation of MS and results in optic nerve atrophy. Retinal nerve fibre layer (RNFL) imaging is a non-invasive way of detecting axonal loss following optic neuritis. We hypothesise that if the optic nerve atrophy that develops following optic neuritis is contributed to by axonal loss, it will correlate with thinning of the RNFL. Twenty-five patients were studied at least 1 year after a single unilateral attack of optic neuritis without recurrence, with a selection bias towards incomplete recovery. They had MR quantification of optic nerve cross-sectional area and optic nerve lesion length, as well as optical coherence tomography (OCT) measurement of mean RNFL thickness and macular volume, quantitative visual testing, and visual evoked potentials (VEPs). Fifteen controls were also studied. Significant optic nerve atrophy (mean decrease 30% versus controls), RNFL thinning (mean decrease 33% versus controls), and macular volume loss occurred in patients' affected eyes when compared with patients' unaffected eyes and healthy controls. The optic nerve atrophy was correlated with the RNFL thinning, macular volume loss, visual acuity, visual field mean deviation, and whole field VEP amplitude but not latency. These findings suggest that axonal loss contributes to optic nerve atrophy following a single attack of optic neuritis. By inference, axonal loss due to other post-inflammatory brain lesions is likely to contribute to the global MRI measure of brain atrophy in multiple sclerosis.

Multifocal Visual Evoked Potential Analysis of Inflammatory or Demyelinating Optic Neuritis

To determine the sensitivity of multifocal visual evoked potentials (mVEP) in optic neuritis of an inflammatory or demyelinating nature. Cross-sectional study. Sixty-four patients participated who had a confirmed diagnosis of optic neuritis (ON) (past and acute). Based on the McDonald multiple sclerosis (MS) criteria, 25 patients (27 eyes with ON) were deemed to have isolated optic neuritis and thus not have MS (i.e., the not-MS group), and 19 patients (24 eyes with ON) had a diagnosis of MS (i.e., the MS group). The remaining 20 patients (25 eyes with ON) were at a high risk of MS, but diagnostic evaluation was equivocal, and thus were classified as the possible MS group. A control group of 20 normal patients was enrolled. The mVEP test was performed using the Accumap. All ON patients had recent magnetic resonance imaging scans of the brain and spinal cord. Multifocal visual evoked potentials amplitude and latency values were analyzed within each group and were compared with the normal controls. No abnormality was recorded on mVEP in the control group. Of all the ON eyes, 74 (97.3%) were abnormal on mVEP testing. Amplitude values were abnormal in 92.6% of not-MS eyes, 92.0% of possible MS eyes, and 100% of those with MS, and latency was abnormal in 33.3%, 76.0%, and 100%, respectively. There was a significant difference in the mVEP latency z-scores among all ON groups (P<0.01; Kruskal-Wallis test). Although distribution graphs of latency z-scores in the not-MS and MS groups had single peaks and were clearly separate from each other, the latency z-score distribution within the possible MS group in postacute patients was bimodal, with each peak corresponding to the distribution of the not-MS and MS group, respectively. The mVEP latency z-scores had a sensitivity and specificity of 100% in detecting patients with ON due to MS when compared with normal patients. The mVEP test is a sensitive and specific tool for detecting optic neuritis. There was a significant difference in latency analysis findings between patient groups as classified according to the McDonald MS criteria. Latency results suggest a role in identifying a patient's risk for future MS.

Pattern electroretinography and visual evoked potentials in optic nerve diseases

Background To evaluate transient pattern electroretinography (PERG) and pattern visual evoked potential (VEP) for the diagnosis, differential diagnosis and follow-up of optic nerve diseases. Methods Twenty-nine consecutive patients (14 female, 15 male) with the diagnosis of ischaemic optic neuropathy ( n = 14) and optic neuritis ( n = 15) were included in this study. Mean age of the patients with ischaemic optic neuropathy was 63.3 ± 3.3 (60–78) years and the mean age of the patients with optic neuritis was 28.3 ± 8.4 (19–43) years. In each patient ophthalmological examination and systemic evaluation were done and VEP and PERG were recorded. As a control group, VEP recordings of 35 healthy subjects were included. Results In the ischaemic optic neuropathy group (group 1), mean VEP amplitude (±SD) (1.96 ± 0.95 μV) was found to be decreased significantly in the affected eyes in comparison to the control group and the unaffected eyes. The delay in latency (116.3 ± 20.14 msec in the affected eyes compared with 101.31 ± 6.19 msec in unaffected eyes) was statistically significant when compared with the healthy subjects. In the optic neuritis group (group 2), VEP amplitude was decreased (4.13 ± 4.04 μV vs 6.97 ± 3.35 μV and 6.97 ± 4.43 μV) and latency was increased (122.59 ± 20.09 msec vs 101.31 ± 6.19 msec and 108.76 ± 13.57 msec) in affected eyes significantly in comparison to the unaffected eyes and control group, respectively. Even though there were no significant differences for P50 latency and N95/P50 ratios between affected and unaffected eyes in both groups, N95 amplitude decreased significantly in the affected eyes of the ischaemic optic neuropathy patients and N95 latency was found to be decreased in optic neuritis patients. There was no correlation between VEP and PERG findings in both groups. Conclusion VEP amplitude decreased significantly in ischaemic optic neuropathies while latency delay was more significant in patients with optic neuritis. PERG findings showed decreased N95 amplitude in ischemic optic neuropathy without associated latency changes.

Investigating neurophysiological correlates of metacontrast masking with magnetoencephalography

Early components of visual evoked potentials (VEP) in EEG seem to be unaffected by target visibility in visual masking studies. Bridgeman’s reanalysis of Jeffreys and Musselwhite’s (1986) data suggests that a later visual component in the VEP, around 250 ms reflects the perceptual effect of masking. We challenge this view on the ground that temporal interactions between targets and masks unrelated to stimulus visibility could account for Bridgeman’s observation of a U-shaped time course in VEP amplitudes for this later component. In an MEG experiment of metacontrast masking with variable stimulus onset asynchrony, we introduce a proper control, a pseudo mask. In contrast to an effective mask, the pseudomask should produce neither behavioral masking nor amplitude modulations of late VEPs. Our results show that effective masks produced a strong U-shaped perceptual effect of target visibility while performance remained virtually perfect when a pseudomask was used. The visual components around 250 ms after target onset did not show a distinction between mask and pseudomask conditions. The results indicate that these visual evoked potentials do not reveal neurophysiological correlates of stimulus visibility but rather reflect dynamic interactions between superimposed potentials elicited by stimuli in close temporal proximity. However, we observed a postperceptual component around 340 ms after target onset, located over temporal-parietal cortex, which shows a clear effect of visibility. Based on P300 ERP literature, this finding could indicate that working memory related processes contribute to metacontrast masking.

Role of NMDA, nicotinic, and GABA receptors in the steady-state visual-evoked potential in rats

Agonists and antagonists at the NMDA, GABA, and nicotinic acetylcholine receptors were administered to adult male rats to evaluate the contribution of these pathways to the visual-evoked potential (VEP). Rats were presented with an onset/offset pattern at a temporal frequency (4.55 Hz) resulting in a steady-state VEP. Averaged VEPs were Fourier transformed and VEP amplitudes were calculated at 1× stimulus frequency (F1) and 2× stimulus frequency (F2). About 30 min after administration, NMDA (10 mg/kg, i.p.; n = 9) increased F1 amplitude by 350% and decreased F2 amplitude by 48%. Memantine (4.5 mg/kg, i.p.; n = 10) increased F1 amplitude by 50%, 10 min post-injection. Similarly, nicotine (0.1 mg/kg, s.c.; n = 9) increased F1 amplitude by 55%, 20 min after drug administration. Muscimol (1 mg/kg, i.p.; n = 10) increased F1 amplitude significantly from 20 to 45 min post-injection. Mecamylamine (6 mg/kg, i.p.; n = 10) decreased F2 amplitude by 70% during the 60-min testing session. Bicuculline (0–0.5 mg/kg, i.p.; n = 8–10 rats/dose) did not significantly alter either F1 or F2 amplitudes. Results indicate important roles for glutamate and nicotinic acetylcholine receptors in both F1 and F2, while GABA receptors contribute to F1.

Retinal nerve fiber layer axonal loss and visual dysfunction in optic neuritis

Visual recovery after optic neuritis, as with recovery from other forms of multiple sclerosis relapse, is often clinically complete. Axonal loss is thought to be a likely cause of persistent disability after a multiple sclerosis relapse and optic nerve axonal loss may be a major substrate of poor visual recovery observed in about 5% of optic neuritis; noninvasive in vivo markers specific for axonal loss would be extremely helpful in predicting recovery. The authors used optic neuritis as a model of multiple sclerosis relapse to quantify axonal loss of the retinal nerve fiber layer (RNFL) and secondary retinal ganglion cell loss in the macula with optical coherence tomography (OCT). They studied 25 patients who had a previous single episode of optic neuritis with a recruitment bias to those with incomplete recovery and 15 control subjects. OCT measurement of RNFL thickness and macular volume, quantitative visual testing, and electrophysiological examination were performed. The authors found highly significant reductions (P < .001) of RNFL thickness and macular volume in affected patient eyes compared with control eyes and clinically unaffected fellow eyes. There were significant relationships among RNFL thickness and visual acuity, visual field, color vision, and visual-evoked potential amplitude. According to the authors, this study has demonstrated functionally relevant changes indicative of axonal loss and retinal ganglion cell loss in the RNFL and macula, respectively, after optic neuritis. They suggest that noninvasive RNFL imaging technique be used in trials of experimental treatments that aim to protect optic nerves from axonal loss.—Valérie Biousse

Visual evoked potentials for reversals of red–green gratings with different chromatic contrasts: Asymmetries with respect to isoluminance

Human visual evoked potentials (VEPs) were recorded for abrupt 6.25-Hz reversals of 2 c/deg square-wave gratings combining red-green contrast with different levels of luminance contrast. Response characteristics-- amplitudes and peak latencies as a function of luminance contrast--were compared for four different pairs of red-green colors and an isochromatic yellow grating. For each of the red-green color pairs, the plots of VEP amplitudes and latencies were nonsymmetrical with respect to isoluminance. The amplitude dropped to a minimum within a region of rapid phase change, at a different contrast for each color pair but always at a luminance contrast for which the greener color had the higher luminance. When the contrast-response curve for each of the four red-green pairs was modeled by a simple |CL - CM| opponency of L- and M-cone contrast using a fixed CL/CM weighting ratio of about two, there was a close correspondence between the contrast giving a null in the modeled response and that giving a minimum in the VEP amplitude. So for the stimulus parameters applied here, the reversal VEP appeared to be dominated by L/M-opponent response contributions for which the signed CL/CM-cone weighting ratio was close to a value of minus two rather than to a value of minus one, which is characteristic of the psychophysical red-green detection mechanism and representative of CL/CM weighting ratios for precortical cells in the parvocellular pathway.

Visual evoked potentials for red–green gratings reversing at different temporal frequencies: Asymmetries with respect to isoluminance

Human visual evoked potentials (VEPs) were recorded for abrupt reversals of 2 cycles/deg (c/deg) square-wave gratings combining high red-green contrast with different levels of luminance contrast. Response characteristics--2nd harmonic amplitudes and peak latencies as a function of luminance contrast--were compared for four different reversal rates ranging from 6.25 Hz to 12.5 Hz. At every reversal frequency, the VEP amplitude and latency plots were nonsymmetrical with respect to isoluminance. The amplitude dropped to a minimum within a region of rapid phase change, always at a red-green luminance contrast for which the green color had the higher luminance, at about 40% or 50% Michelson luminance contrast. The rapid phase shift around this contrast suggested a sudden change in the relative impact of VEP generators with different latencies, possibly dominated by parvocellular or magnocellular input. The most prominent VEP waveform through most of the luminance contrast range, P110, is interpreted in terms of a parvo-mediated response that is attenuated with increasing reversal frequency. Contrast-dependent changes in the P110 amplitude appear to be responsible for the VEP asymmetries reported here.

Heterogeneous Oxygen Extraction in the Visual Cortex during Activation in Mild Hypoxic Hypoxia Revealed by Quantitative Functional Magnetic Resonance Imaging

Functional magnetic resonance imaging (fMRI) techniques were used to study haemodynamic and metabolic responses in human visual cortex during varying arterial blood oxygen saturation levels (Y(sat), determined by pulse-oximeter) and stimulation with contrast-reversing checkerboards. The visual-evoked potential amplitude remained constant at lowered Y(sat) of 0.82+/-0.03. Similarly, fMRI cerebral blood flow (CBF) responses were unchanged during reduced Y(sat). In contrast, visual cortex volume displaying blood oxygen level-dependent (BOLD) fMRI response decreased as a function of Y(sat), but the BOLD signal change of 3.6%+/-1.4% was constant. Oxygen extraction ratio (OER) during visual activation showed values of 0.26+/-0.03 for normal Y(sat). At lowered Y(sat), two OER patterns were observed. Firstly, a reduced OER of 0.14+/-0.03 in the visual cortex structures showing BOLD in hypoxia was observed. Secondly, signs of much higher OER in other parts of visual cortex were obtained. T2*-weighted magnetic resonance imaging revealed signal increases by 0.8%+/-0.4% with visual activation during lowered Y(sat) in the visual cortex structures, which showed BOLD of 3.6% in magnitude under normoxia. Because the CBF response in the visual cortex was quantitatively similar during stimulation in normoxia and hypoxia, attenuated T2*-weighted signal increase in parts of visual cortex indicated high OER during visual activation in hypoxia, which was close to that encountered in the resting brain. These spatially localised regions of tissue oxygen extraction and metabolism argue for dissociation between CBF and BOLD fMRI signals in mild hypoxia. The findings point to heterogeneity with regard to oxygen requirement and its coupling to the haemodynamic response in the brain.