Spatial frequency response functions obtained from cat visual evoked potentials

Visual evoked potentials (VEPs) were obtained from the surface of teh cat visual cortex in response to contrast reversing sinusoidal gratings. Gratings of different spatial frequency were presented either separately, using signal averaging to increase the signal-to-noise ratio, or as a spatial frequency sweep, in which spatial frequency was sequentially increased every 5 sec during a 40 sec trial (3.99 Hz) or every 3 sec during a 24 sec trial (6.65 Hz). The second harmonic amplitude- and phase-spatial frequency functions derived from averaging or from sweep trials were similar, indicating that the swept stimulus method can be used to provide a rapid and reliable measure of the VEP-spatial frequency function. Intravenous administration of physostigmine, an acetylcholinesterase inhibitor, evoked a spatial frequency-dependent change in VEP amplitude. At 3.99 Hz, responses to low spatial frequencies were enhanced to a greater extent than were responses to high spatial frequency stimuli. At 6.65 Hz, responses to mid-range spatial frequencies were enhanced to a greater extent than were responses to low and high spatial frequency stimuli. VEP phase at both 3.99 and 6.65 Hz was advanced to a greater degree at the higher spatial frequencies. These results indicate that the swept spatial frequency method may be useful in studying spatial frequency-dependent pharmacological effects on the VEP and support the possibility that pharmacological disruption of the cholinergic visual system can produce such changes.     

Depression of the cat cortical visual evoked potential by soman

The effects of intravenous administration of the anticholinesterase agent soman (pinacolyl methylphosphonofluoridate, 3-15 micrograms/kg) on the visual evoked potential (VEP) were examined in cats using phase-reversed sine wave grating stimuli of different spatial frequencies and contrasts. Doses of 5-7 micrograms/kg caused a depression of the VEP across all spatial frequencies in an abrupt, non-graded fashion. Studies in which contrast was varied showed that VEP depression resulted primarily from a decrease in the system gain rather than a change in the contrast sensitivity, and that response depression increased with increasing contrast. The dominant changes in gain revealed by these studies are consistent with a modulation of potassium conductance in the cell membrane which previous studies have shown to be dependent on a cholinergic mechanism.     

Multivariate vectorial analysis of the visual evoked response

Principal component analysis of a set of V.E.R.s yields vectorial representations of the responses in a diagram of a reduced dimensionality. In a vectorial diagram the responses can be resolved into components, associated with the aspects of the stimulus modulation and the state of the visual system. The appearance of a scotopic and a photopic component is demonstrated. In another experiment small modulations of luminance and color evoked the responses. The distorting effect of a type of non-linearity of the visual system, that is latency variation of the responses and the components, is discussed and demonstrated.     

Nonlinear analysis of the human visual evoked response

Using time-domain correlation techniques, the first- and second-order Wiener kernels have been calculated for the system mediating the human visual evoked response. The first-order kernels indicate the linear element is a resonant one, with a natural frequency near 20 Hz, and a memory of approximately 250 ms. The transport delay associated with this element is approximately 56 ms. The second-order kernels indicate a quadratic nonlinear element with a memory less than 20 ms. The analytic form of this element can be approximated by a parabola shifted to the right of the origin. A close correspondance between the spectrum of the first-order kernel and the spectrum of the main diagonal of the second-order kernel suggests the nonlinear element preceeds the linear one. Tests of reproducibility on the first-order kernel and the main diagonal of the second-order kernel suggest they are reliable describing functions for the system mediating the human visual evoked response.     

Recovery of the acetylcholinesterase activity in a monolayer culture of chick myoblasts after irreversible inhibition by an organophosphorus inhibitor

The recovery of the acetylcholine esterase (AChE) activity after the irreversible inhibition with an organophosphorus inhibitor B-156 was studied in a developing monolayer culture of chick myoblasts. The culture was obtained from muscles of posterior limbs of the 11 day old chick embryos. The AChE activity was estimated by the modified Ellman method from the moment of inoculation to the stage of spontaneous contractions of muscle fibres. After the B-156 treatment the AChE activity of muscle cells decreased, then started to increase and the maximum recovery of activity, below the initial level, was attained within roughly 2 days after the treatment. The AChE activity in the treated culture somewhat decreased thereafter. The lower the inhibitor concentration, i.e. the lower the value of the initial AChE inhibition, the higher the starting rate and degree of recovery of the AChE activity. The results obtained suggest that, unlike the multilayer culture of muscle tissue at later stages of differentiation no compensatory enhancement of AChE biosynthesis after irreversible inhibition of this enzyme by an organophosphorus inhibitor is observed in the monolayer culture of chick myoblasts at the early stages of myogenesis.     

Temporal correlations in modulated evoked responses in the visual cortical cells of the cat

We analysed evoked responses recorded from 97 cells in the visual cortex of 4 adult cats and 8 kittens, stimulated by a drifting sinusoidal grating. A Fourier analysis of the responses allowed us to select 30 cells showing a clear modulating response (relative modulation index > 1). The 162 records from these selected cells were scanned to detect precise temporal correlations in the form of replicating triplets and associated ghost doublets. Temporal correlations of this nature were observed in these cells. They are about 10 times more abundant in adult cats than in kittens, and mostly observed in infragranular cortical layer cells. The possible role of these precise temporal patterns in information processing in the brain is examined, as well as the relation between this type of temporal correlation with coherent oscillations and principal components waveforms.     

Recovery cycles of mass evoked potentials of different levels of the visual system following electrical stimulation of the optic nerve

Recovery cycles of mass evoked potentials of the optic tract, lateral geniculate body, optic radiation, and primary projection area of the visual cortex were investigated in amytal-anesthetized cats following electrical stimulation of the optic nerve (in some experiments, optic radiation) by paired short stimuli of supraliminal intensity. The recovery of the amplitude and time characteristics of all components of the mass responses to a testing stimulus applied to the nerve at different intervals after an identical conditioning stimulus was studied. The responses of all portions of the visual system (except the retina) were recorded simultaneously, which made it possible to compare the changes of their reactivity arising after the first stimulus under rigorously identical conditions. It was shown that at the upper levels of the visual system the exaltation phase of the recovery cycle and the depression phase following it become increasingly more pronounced and protracted. Depression is especially pronounced in the visual cortex, which maximally affects the recovery of the late components of the mass response. Under the experimental conditions the processes of successive inhibition in the cortex were more pronounced than at the lower levels. There are grounds to assume that the depression of the cortical responses is partially due to pre- and partially postsynaptic inhibition.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 2, No. 3, pp. 251–259, May–June, 1970.     

Pre-stimulus spectral EEG patterns and the visual evoked response

The relationship between the latencies and amplitudes of the N1 and P2 components of the visual evoked potential (VEP) and the psychophysiological state of the brain immediately preceding the time of the stimulus has been investigated in 7 male subjects. Power spectral measures in the delta, theta, alpha and beta bands of the 1 sec pre-stimulus EEG were used to assess the brain state, and low intensity flashes, delivered randomly between 2 and 6 whole seconds, were used as the stimuli. Trials were ranked separately according to the relative amounts of pre-stimulus power in each EEG band and were partitioned into groups by an equal pre-stimulus spectral power criterion. Averaged EPs were computed from these groups and multiple regression analysis was used to relate pre-stimulus spectral power values to EP features. Five of the 7 subjects displayed consistent increases in N1-P2 amplitude as a function of increasing pre-stimulus relative alpha power. The between-subjects effect of pre-stimulus EEG on N1 latency was small, but was moderate for P2 latency (both significant). Both N1 and P2 latency were found to decrease with increasing amounts of pre-stimulus relative delta and theta power.     

(p-Amidinophenyl)methanesulfonyl fluoride, an irreversible inhibitor of serine proteases

p-(Amidinophenyl)methanesulfonyl fluoride (p-APMSF) has been synthesized and shown to be a specific, irreversible inhibitor of the class of plasma serine proteases which demonstrate substrate specificity for the positively charged side chains of the amino acid lysine or arginine. In equimolar concentration, this compound causes immediate and complete irreversible inhibition of bovine trypsin and human thrombin. A 5-10-fold molar excess of reagent over enzyme is required to achieve complete irreversible inhibition of bovine Factor Xa, human plasmin, human C1-r, and human C1-s. the Ki of p-APMSF for all of the above-mentioned proteases is between 1 and 2 microM. In contrast, p-APMSF in large molar excess does not inactivate chymotrypsin or acetylcholinesterase. The unique reactivity of p-APMSF has been further shown in comparison with the related compound p-nitrophenyl (p-amidinophenyl)methanesulfonate which is an active-site titrant for thrombin but reacts poorly with Factor Xa, C1-r, and C1-s and is not hydrolyzed by bovine trypsin or human plasmin. Similarly, (p-amidinophenyl)methanesulfonate has a Ki of 30 microM for thrombin but is a poor inhibitor of trypsin, Factor Xa, C1-r, C1-s, and plasmin. Studies with bovine trypsin have demonstrated that the inhibitory activity of p-APMSF is the result of its interaction with the diisopropyl fluorophosphate reactive site. The unique reactivity of this inhibitor classifies it as one of the most effective active site directed reagents for this class of serine proteases. Collectively, these results suggest that the primary substrate binding site of these enzymes, which share a high degree of structural homology, do in fact significantly differ from each other in their ability to interact with low molecular weight inhibitors and synthetic substrates.     

D,L-alpha-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, induces differentiation in MEL cells

In the present study, the effect of D,L-alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), on Friend's murine erythroleukemia (MEL) cell differentiation is investigated. DFMO was able to induce differentiation of MEL cells in culture as determined by haemoglobin (Hb) content and percentage of cells synthesizing Hb detected by benzidine staining. DFMO at a concentration of 2 mM resulted in about 70% benzidine-positive cells on the fifth day. There was a time-dependent increase in the percentage of benzidine-positive cells starting from day three. However, only a 24 h presence of DFMO in the medium was required to induce differentiation suggesting that DFMO switches on a pathway during this period leading to terminal differentiation of MEL cells. DFMO induced differentiation of MEL cells was sensitive to dexamethasone and 5-bromo-2'-deoxyuridine.     

Lithium effects on the somatosensory cortical evoked response in the rat and cat

The early positive cortical evoked potential to somatosensory stimuli is regularly increased in amplitude in patients receiving lithium carbonate treatment. This may reflect a unique neurochemical effect of lithium since similar changes have not been observed in humans following other drugs. To investigate this finding, cortical evoked potentials to peripheral somatosensory stimulation were obtained in rats and cats with implanted epidural electrodes. In rats, increasing doses of oral lithium chloride, up to 5 meq/kg/d which approached the LD 50, produced no reliable change in the early positive evoked response amplitude. In cats, an increased amplitude of the early positive-negative cortical potential was observed in every instance and the serum lithium levels were within the range used clinically in humans. The increased cortical evoked response amplitude in cats did not directly correlate with serum lithium levels but was delayed 1 to 5 days after serum lithium levels reached their peak. The findings in cats are similar to the human studies. The negative results observed in rats may reflect important species differences regarding lithium.     

Localization of areas of the cat visual cortex giving an invariant response to changes in pattern size

Regions of the visual cortex forming a code invariant to the transformation of pattern size were investigated by the averaged evoked potentials method. The response was assessed by amplitude of the negative wave, whose peak latency was 130±20 msec. A set of strips of light forming a grating was used as the stimulus. The gratings differed from each other in the number of strips or in area. With an increase in stimulus area, the response in area 17 increased, but the responses were identical to gratings of equal area but different orientation of the strips. In area 7 (middle part of the suprasylvian gyrus) response size was unchanged with an increase in area of the grating, whereas an increase in the number of orientations of the strips forming the grating led to an increased response. Since response magnitude is independent of the area of the grating, it is postulated that responses to pattern size invariant to transformation are located in area 7.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 5, No. 2, pp. 115–121, March–April, 1973.