Loss of cortical function in mice after decapitation, cervical dislocation, potassium chloride injection, and CO2 inhalation

Electroencephalograms (EEG) and visual evoked potentials (VEP) in mice were recorded to evaluate loss of cortical function during the first 30 s after euthanasia by various methods. Tracheal cannulae (for positive-pressure ventilation, PPV) and cortical surface electrodes were placed in mice anesthetized with inhaled halothane. Succinylcholine was used to block spontaneous breathing in the mice, which then underwent continuous EEG recording. Photic stimuli (1 Hz) were presented to produce VEPs superimposed on the EEG. Anesthesia was discontinued immediately before euthanasia. Compared with that obtained before euthanasia, EEG activity during the 30-s study period immediately after euthanasia was significantly decreased after cervical dislocation (at 5 to 10 s), 100% PPV-CO2 (at 10 to 15 s), decapitation (at 15 to 20 s), and cardiac arrest due to KCl injection (at 20 to 25 s) but not after administration of 70% PPV-CO2. Similarly, these euthanasia methods also reduced VEP amplitude, although 100% PPV-CO2 treatment affected VEP amplitude more than it did EEG activity. Thus, 100% PPV-CO2 treatment significantly decreased VEP beginning 5 to 10 s after administration, with near abolition of VEP by 30 s. VEP amplitude was significantly reduced at 5 to 10 s after cervical dislocation and at 10 to 15 s after decapitation but not after either KCl or 70% PPV-CO2 administration. The data demonstrate that 100% PPV-CO2, decapitation, and cervical dislocation lead to rapid disruption of cortical function as measured by 2 different methods. In comparison, 70% PPV-CO2 and cardiac arrest due to intracardiac KCl injection had less rapid effects on cortical function.     

Neurophysiological effects of recombinant interferon-gamma and -alpha in man

Treatment of malignant tumors with interferon (IFN) is in some patients accompanied by serious neurological side effects. The present study assessed neurophysiological changes in spontaneous EEG activity, visual-evoked cortical potentials (VEPs), and brainstem auditory-evoked potentials (BAEPs) during IFN-gamma or IFN-alpha therapy in 9 patients. In addition, blood pressure, heart rate and body temperature were monitored. In all sessions under IFN, the latency of the P100 component of the VEP was shortened as compared to baseline conditions. IFN also reduced latencies of BAEP components, and diminished amplitudes of the spontaneous EEG activity within the alpha and beta frequency band. These latter effects were somewhat less consistent than those on VEPs. The major neurophysiological changes appeared to be similar for IFN-gamma and IFN-alpha. The results are in accord with an excitatory effect of IFN on central nervous activity. The magnitude of changes excludes a neurotoxicity of IFN-gamma or IFN-alpha at the doses used in this study.     

Subclinical VEP abnormalities in patients on chronic deferoxamine therapy: longitudinal studies

As deferoxamine (DFO) appeared to have certain toxic effects on the sensory pathways in some of our patients on nightly subcutaneous deferoxamine (DFO) for transfusion-dependent anemia, treatment was stopped in all of these patients to obtain a comprehensive baseline assessment of sensory function. Visual evoked potentials (VEPs) were studied in all patients; the 77 described in this report all had normal ophthalmological examinations. Abnormally prolonged VEP lantecies were found in 21%. The patients remained off DFO for 2–6 months, and most of those with abnormal VEPs who were retested showed improvement in their VEPs over this period with the VEPs returning to within normal range in half the cases; two showed no change. Since restarting DFO, VEP latencies in 10 of these patients have increased again beyond normal limits, as have the VEPs in 7 who had previously normal VEPs. Although most of the 77 patients have VEPs that are currently normal and stable while on DFO, a significant sub-group have abnormal VEPs that appear sensitive to the administration of DFO and may reflect a vulnerability to DFO neurotoxicity. These data suggest that the VEPs can detect subclinical toxic effects of DFO on the visual system and should be considered as a monitor for patients receiving chronic DFO therapy.     

Human cortical traveling waves: dynamical properties and correlations with responses

The spatiotemporal behavior of human EEG oscillations is investigated. Traveling waves in the alpha and theta ranges are found to be common in both prestimulus and poststimulus EEG activity. The dynamical properties of these waves, including their speeds, directions, and durations, are systematically characterized for the first time, and the results show that there are significant changes of prestimulus spontaneous waves in the presence of an external stimulus. Furthermore, the functional relevance of these waves is examined by studying how they are correlated with reaction times on a single trial basis; prestimulus alpha waves traveling in the frontal-to-occipital direction are found to be most correlated to reaction speeds. These findings suggest that propagating waves of brain oscillations might be involved in mediating long-range interactions between widely distributed parts of human cortex.     

Brain potentials associated with pattern displacement and saccadic eye movements in humans and rhesus monkeys

Visual evoked potentials (VEPs) to the onset of motion of visual patterns and brain responses associated with saccadic eye movements (SRPs) were compared in human subjects and in rhesus monkeys. Three different velocities of pattern motion were employed. In humans, brain responses were recorded from six scalp areas. In monkeys, transcortical recordings were obtained from chronically implanted electrodes in the occipital, temporo-parietal, and frontal areas. In humans there was a clear difference in VEPs to the pattern motion between the anterior (Fz, Cz) and posterior (Pz, Oz) scalp regions. The earliest component was a positive peak at 85 ms at Oz followed by a negativity around 110 ms. In the fronto-central leads the VEP was characterized by a negativity at 145 ms and a subsequent broad positive component around 250 ms. SRP responses differed in the early components from the VEPs to pattern motion but a good correspondence was found in the morphology of the late components of the two types of brain potentials. Furthermore, flashed-on VEPs and SRPs elicited a late positivity of more pronounced amplitude than VEPs to pattern displacement. In monkeys similar findings were found: an early negative component of the pattern-displacement VEP could not be observed in the SRP responses over the visual cortex while the late portion of the SRP waveform was greater than the late positivity of the VEP to motion-onset.     

The effect of the phase of prestimulus alpha activity on the averaged visual evoked response

The relationship between the latencies and amplitudes of the N1 and P2 components of the averaged visual evoked potential (EP) and the phase of the alpha activity immediately preceding the time of the stimulus, has been investigated in 7 male subjects. Low intensity flashes, delivered randomly between 2 and 6 whole seconds, were used as the stimuli. The phase angle of the EEG at the moment of stimulation was computed for all trials containing more than 100 μV² of prestimulus alpha power. The single trials were grouped into 8 classes on the basis of the phase angle value, and averaged EPs for each individual were computed from these groups. In addition, averaged EPs were computed in 3 ways: (1) a grand average consisting of all artifact-free trials, (2) an ‘alpha average’ consisting of all trials containing more than 100 μV² of prestimulus alpha power, and (3) a ‘non-alpha average’ consisting of all trials with less than 100 μV² of prestimulus alpha power. Each of these 3 averages were cross-correlated with the phase-selective averages. It was found that the particular N1 component assessed in this experiment may possibly be entrained alpha activity, and that the measured P2 component is not an alpha process, yet it is influenced by the amount of prestimulus alpha activity.     

Effects of age and sex on pattern electroretinograms and visual evoked potentials

Pattern-electroretinograms (P-ERGs) and visual evoked potentials (VEPs) were simulataneously recorded in 112 normal individuals aged 20–75. Two sized checks subtending 15′ and 31′ were used as stimuli. A weighted regression analysis was used to determine which of the variables, sex or age, was significant. The latency of the a and b wave of the P-ERGs showed a progressive increase with age but no difference between sexes. The effect was statistically significant for both 15′ and 31′ checks. There was no statistically significant aging effects for VEPs elicited by 31′ checks. Aging, however, affected N70, P100, and the interpeak interval between b wave to N70 and b wave to P100 for responses to 15′ checks. Shorter VEP latencies were noted in females for both 15′ and 31′ checks.The simultaneous recording of P-ERGs and VEPs has demonstrated that aging is a major variable at the retinal level. The effects on the a and b waves are mostly due to optic changes with aging and only partially to aging changes in the neuronal retinal circuitry. The effect of aging on VEPs is different for different size stimuli. The cause is a random neuronal cell loss in the visual pathways from the optic nerve to the visual cortex as the individual ages.The difference in VEP data between sexes may be related to anatomical size and hormonal influences.     

Changes in visual evoked potentials after phosphene electrostimulation in children suffering from myopia

We recorded visual evoked potentials (VEPs) in children suffering from medium and high myopia (3.0 to 6.0 and more than 6.0 D; 28 and 21 patients, respectively); a light flash was used as the stimulus. The VEPs were recorded before and after a curative course of phosphene electrostimulation (PhES; frequency 15 sec⁻¹, 10 to 15 10-min-long everyday sessions). The above course resulted in clear trends toward decreases in the peak latencies of the P60 and P100 VEP components; changes in the latencies of other components were expressed to a lesser extent. In children with medium myopia, the latency of the P60 component decreased, on average, by more than 21% (P < 0.05); in patients with high myopia, the respective decrease was about 12% (P > 0.05). These shifts were accompanied by increases in the mean amplitudes of the P60 and, to a lesser degree, P100 (more expressed in medium myopia). The data obtained allow us to suppose that the PhES course provides increases in the transmission velocity through relay structures of the visual analyzer and in neuronal networks of the visual cortex and also in the number of neuronal units whose activity is reflected in generation of VEPs. Application of the PhES technique is much more effective in relatively moderate myopia. Neirofiziologiya/Neurophysiology, Vol. 40, No. 3, pp. 228–235, May–June, 2008.     

Hemispheric asymmetry of visual evoked potentials during human recognition of facial emotional expressions

Visual evoked potentials (VEP) in standard 16 EEG derivations were recorded in 26 young men and 20 women during recognition of facial emotional expressions and geometric figures. The stimuli were presented on a computer screen in the center of the visual field or randomly in the right or left vision hemifields. Peak VEP latency and mean amplitude in 50-ms epochs were measured; spatiotemporal VEP dynamics was analyzed in a series of topographic maps. The right hemisphere was shown to be more important in processing emotional faces. The character of the asymmetry was dynamic: at earlier stages of emotion processing the electrical activity was higher in the right inferior temporal region compared to the left symmetrical site. Later on the activity was higher in the right frontal and central areas. The dynamic mapping of "face-selective" component N180 of VEPs revealed the onset of activation over the right frontal areas that was followed by the fast activation of symmetrical left zones. Notably, this dynamics didn't correlate with the hemifield of stimuli exposition. The degree of asymmetry was lower during presentation of figures, especially in the inferior temporal and frontal regions. The prominent asymmetry of information processes in the inferior temporal and frontal areas was suggested to be specific for recognition of facial expression.     

Clinical Utility and Limitations of Intraoperative Monitoring of Visual Evoked Potentials

Objectives

During surgeries that put the visual pathway at risk of injury, continuous monitoring of the visual function is desirable. However, the intraoperative monitoring of the visual evoked potential (VEP) is not yet widely used. We evaluate here the clinical utility of intraoperative VEP monitoring.

Methods

We analyzed retrospectively 46 consecutive surgeries in 2011-2013. High luminance stimulating devices delivered flash stimuli on the closed eyelid during intravenous anesthesia. We monitored VEP features N75 and P100 and took patients'' preoperative and postoperative visual function from patient charts. Postoperative ophthalmologic workup was performed in 25 (54%) patients and preoperatively in 28 (61%) patients.

Results

VEP recordings were feasible in 62 of 85 eyes (73%) in 46 patients. All 23 eyes without VEP had impaired vision. During surgery, VEPs remained stable throughout surgery in 50 eyes. In 44 of these, visual function did not deteriorate and three patients (6 eyes) developed hemianopia. VEP decreased transiently in 10 eyes and visual function of all was preserved. VEPs were lost permanently in 2 eyes in two patients without new postoperative visual impairment.

Conclusions

Satisfactory intraoperative VEP monitoring was feasible in all patients except in those with severe visual impairment. Preservation of VEPs predicted preserved visual function. During resection of lesions in the visual cortex, VEP monitoring could not detect new major visual field defects due to injury in the posterior visual pathway. Intraoperative VEPs were sensitive enough to detect vascular damage during aneurysm clipping and mechanical manipulation of the anterior visual pathway in an early reversible stage. Intraoperative VEP monitoring influenced surgical decisions in selected patients and proved to be a useful supplement to the toolbox of intraoperative neurophysiological monitoring.     

EEG characteristics determining the quality of subsequent recognition of visual images

Recognition of noisy pictures of Arabic numerals was accompanied by an increase in EEG coherence in the frontal cortical regions, especially in the left hemisphere, and between the frontal and occipital areas in both left and right hemispheres. Coherence values decreased in the temporo-centro-occipital areas of both hemispheres. A correlation was found between the coherence pattern in the prestimulus period and the quality of subsequent activity. Correct recognition was preceded by left-side asymmetry of the EEG coherence. Before erroneous recognition, EEG coherence levels were higher than before a correct response, and the increase in coherence was widely generalized over the cortex (especially in the Δ, ?, and α₁ frequency bands). The frequency of expression of an increased integral EEG coherence was higher before erroneous recognition than before a correct response. These changes in coherence were symmetrical.     

Time-frequency analysis of visual evoked potentials for interhemispheric transfer time and proportion in callosal fibers of different diameters

This study is an extension of the experimental research of Nalçac et al., who presented 16 subjects with a reversal of checkerboard pattern as stimuli in the right visual field or left visual field and recorded EEG at O1, O2, P3, and P4. They applied the chosen bandpass filters (4–8, 8–15, 15–20, 20–32 Hz) to the VEPs of subjects and obtained four different components for each VEP. The first aim of this study is to improve the previous report using some methods in time-frequency domain to estimate interhemispheric delays and amplitudes in a time window. Using the improved estimates of interhemispheric delays, the second aim is to estimate the proportion of callosal fibers of different diameters that are activated by visual stimuli by comparing amplitudes of VEPs in different frequency bands. If the relation between frequency components of VEP and delays for callosal fibers of different dimension were reliable, it would give us an opportunity to deal with amplitude of bandpass-filtered VEPs in order to see approximately the proportion of these fibers activated by a certain stimulus. By using frequency-dependent shifts in time and maximizing the cross correlation of direct VEP (DVEP–VEP obtained from contralateral hemisphere)–indirect VEP (IVEP–VEP obtained from ipsilateral hemisphere) pairs in the time-frequency domain, we examined the delay not only at P100 and N160 peaks but along a meaningful time interval as well. Furthermore, by shifting back the IVEP according to the delay estimated at each time window, both the amplitudes and energies of the synchronized DVEP–IVEP pairs were compared at the chosen frequency bands. The percentages of IVEPs at each band was then examined further in conjunction with the distribution of axon diameters in the posterior pole of the CC, questioning the relation between the distributions of the axon diameters and activations at each band. We established an energy definition to express the activation in the fibers. When the energy percentages of IVEPs in theta and alpha were totaled, they were found to be between 76.2% and 81.6%, which is close to the value 74–77% for fibers of 0.4–1 m in diameter obtained from anatomical study of human CC. The sum of energy percentages in the beta1 and beta2 bands was between 20.1% and 24.2%, which probably reflects the proportion of activation of callosal fibers 1–3 m in diameter.     

Developmental wave form analysis of the neonatal flash evoked potential

A multiple regression technique was used to describe the wave form of the flash evoked potential (VEP) in 64 neonates born between 28 and 39 weeks of gestation. The successive appearance of new features in the VEP with increasing gestational age at birth was used to define 5 components, of which specimens were obtained by averaging VEPs of 18 selected infants. The VEPs of the other 46 infants were expressed as linear sums of the components, each multiplied by a weighting coefficient. The method accounted for 74 ± 11% (mean ± 1 S.D.) of the rms power of the observed VEPs and was used to demonstrate significant effects on wave form maturation from fetal growth retardation and maternal smoking in pregnancy.     

Influence of physiological changes of glycaemia on VEPs and visual ERPs

Since hypoglycemia is known to influence cognitive functions, we checked whether the physiological changes in glycemia (after fasting or exertion) can explain the rather high intra-individual variability of event-related potentials (ERPs). Besides the ERPs to "change in coherence of a moving pattern" with reaction time (RT) recording, binocular pattern reversal VEPs and motion-onset VEPs (to linear and radial motion) were also examined in 14 healthy subjects prior to and after 24-h fasting that decreased glycemia from 5.3 to 3.9 mmol/l on the average. We only found one significant change in the latencies and amplitudes of VEPs and ERPs (with no change of RT). The N160 peak in the motion-onset VEPs to radial (expansive) motion (EM-VEPs) showed a larger amplitude at lower glycemia. For evaluation of the exertion influence, we tested glycemia prior to and after 90 min long exercise -- bicycle ergometry with the load set to 2 W/kg in women and 2.5 W/kg in men (average age-related values for W170/kg index). The changes of glycemia to exertion were, however, less distinct than those to fasting. We conclude that in healthy subjects the glycemia decrease due to 24-h fasting or intensive time-limited exercise never reaches the critical value to change the VEP, ERPs and RTs.     

On the interactivity in the human visual cortex caused by specific and nonspecific inflows

Summary An interactivity (Sato, 1969) with respect not only to the interstimulus intervenal between the conditioned and test stimuli but also with respect to the time after the test stimulus was defined as a new generalized recovery function.The contour maps of the above interactivities of the cerebral evoked potentials elicited by the paired flash stimuli and by the conditioned cutaneous and test flash stimuli, respectively, were obtained in the adult human visual cortex.It was suggested to a certain degree by the autocorrelograms of background occipital EEGs and average VEPs that the more prominent VEPs are elicited, the more predominant are the alpha waves in the occipital background EEG, and vice versa. In the contour maps of the interactivity by the paired flash stimuli, cyclic changes of facilitory mountains and occlusive valleys were regular and conspicuous in the subject who exhibited predominant alpha waves in his background EEG, whereas the cyclic changes were less regular and less marked in the subject with few alpha waves in the background EEG.The cyclic changes in the former subject appeared at an interval of about 100 msec at an interstimulus interval of around 100 msec. This acts favorably in the contribution of the cyclic change in interactivity via natural stimulations to the generation of alpha waves in spontaneous EEG. The main facilitory mountains and occlusive valleys in the maps were arranged in a line parallel to the ordinate (axis of the interstimulus interval), which suggest that the conditioned flash will affect in a specific fashion each response compoment elicited via specific afferent inflows in the VEP timelocked to the test flash stimulus. On the contrary, those in the maps obtained by the conditioned cutaneous and test flash stimuli were diagonal to the abscissa (time after the test stimulus) and ordinate, and/or the peaks of facilitory mountains and bottoms of occlusive valleys tended to form a line parallel to the abscissa, which indicates that as the cutaneous somatosensory afferent inflow converges to the visual cortex nonspecific interactivities are exhibited in each component in the VEP.     

Amplitude asymmetry of hemifield pattern reversal VEPs in healthy subjects

The amplitudes of transient and steady-state visual evoked potentials (VEPs) were measured during hemifield stimulation of the left eye in 10 healthy adults. Pattern reversal of a checkerboard was produced at 4 stimulation frequencies: 1, 5, 10 and 15 Hz. The amplitudes of pattern VEPs were evaluated using the paired t test to determine significant differences between right and left hemifields. The transient VEP amplitudes from midoccipital, midparietal, ipsilateral occipital and contralateral occipital electrodes were significantly greater with right hemifield stimulation. The steady-state VEP amplitudes from the midoccipital electrode during 15 Hz stimulation were significantly greater with right hemifield stimulation. Our neurophysiological data may be compatible with neuroanatomical asymmetries of the occipital lobes in humans.     

Intermodulation components of the visual evoked potential: Responses to lateral and superimposed stimuli

Nonlinear interactions in the human visual system were studied using visual evoked potentials (VEPs). In one experiment (superimposed condition), all segments of a dartboard pattern were contrast reversed in time by a sum of two sinusoidal signals. In a second experiment (lateral condition), segments in some regions of the dartboard pattern were contrast reversed by a single sinusoid of one frequency, while segments in other (contiguous) regions of the pattern were contrast reversed by a single sinusoid of another frequency. An identical set of ten frequency pairs was used in each experiment. The frequency pairs were chosen such that the difference between frequencies in each pair was 2 Hz. Amplitudes and phases of the sum and difference frequency components of the VEP (intermodulation terms) were retrieved by Fourier analysis and served as measures of nonlinear interactions. The use of input pairs with a fixed separation in frequency enabled the estimation of the temporal characteristics of the visual pathways prior to a second linear stage. The use of superimposed and lateral conditions revealed antagonistic contributions to the VEP, possibly reflecting direct-through excitatory and lateral inhibitory pathways, respectively.Supported by grants from the U.S. National Eye Institute, the Esther A. and Joseph Klingenstein Fund, and the Harry Frank Guggenheim Foundation     

Mapped distribution of pattern reversal VEPs to central field and lateral half-field stimuli of different spatial frequencies

Visual evoked potentials (VEPs) to pattern reversal vertical bar stimuli of 3 different sizes (1, 2, 4 c/deg) were recorded from 19 scalp derivations in 50 controls. The stimuli were presented on a full-field (FF) screen of 24° visual angle, and on left and right half-fields (HF) of 12° radius. In 15 controls partial HF stimuli were presented on the central 3 and 6° and as hemiannular stimuli of 12° with occlusion of the central 3 and 6°.An antero-posterior polarity reversal of the N1-P1-N2 sequence was observed for FF VEPs. A tangential polarity reversal was observed for HF VEPs. Also with central or hemiannular stimuli polarity reversals of all VEP components were observed within the scalp.Variants of VEP distribution, absence of prominence of some of the ipsi- or contralateral VEP components were observed in 8–40% of controls.The FF and HF VEP distribution, and the variant VEP asymmetries were partly dependent on the pattern spatial frequency.     

A Window into brain development: hdEEG methods to track visual development in nonhuman primates

Electroencephalography (EEG) is widely used to study human brain activity, and is a useful tool for bridging the gap between invasive neural recording assays and behavioral data. High‐density EEG (hdEEG) methods currently used for human subjects for use with infant macaque monkeys, a species that exhibits similar visual development to humans over a shorter time course was adapted. Unlike monkeys, human subjects were difficult to study longitudinally and were not appropriate for direct within‐species comparison to neuronal data. About 27‐channel electrode caps, which allowed collection of hdEEG data from infant monkeys across development were designed. Acuity and contrast sweep VEP responses to grating stimuli was obtained and a new method for objective threshold estimation based on response signal‐to‐noise ratios at different stimulus levels was established. The developmental trajectories of VEP‐measured contrast sensitivity and acuity to previously collected behavioral and neuronal data were compared. The VEP measures showed similar rates of development to behavioral measures, both of which were slower than direct neuronal measures; VEP thresholds were higher than other measures. This is the first usage of non‐invasive technology in non‐human primates. Other means to assess neural sensitivity in infants were all invasive. Use of hdEEG with infant monkeys opens many possibilities for tracking development of vision and other functions in non‐human primates, and can expand our understanding of the relationship between neuronal activity and behavioral capabilities across various sensory and cognitive domains. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1342–1359, 2016