EEG frequency patterns in the cat prepyriform cortex during sleep and waking.

The cellular populations in the prepyriform cortex are a primary processing station for sensory information from the olfactory bulb. These populations are also influenced from forebrain and other brain systems involved in behaviour. Recording electrodes can be precisely placed in this cortex compared to many other brain structures. This permits straddling the cortical superficial pyramidal cell layer with a bipolar recording configuration and the ability to obtain information about awake-vigilant and other state conditions from this brain structure. Methadone, a vigorously arousing drug in the cat, and a short acting barbiturate was administered to compare the differences of EEG patterns obtained during normal awake and sleep conditions. Fourier analysis was used in this study and combined with computer profiles of spectra to show time relationships of the state conditions in the cortex. Good separation of the spectra, between the major states in the cat, were observed using this technique for both natural and drug-induced changes.

Effects of ethanol on eye movements in the monkey.

Ethanol (0.25-2.0 g/kg) was administered by remotely controlled intravenous infusion to monkeys engaged in performance of a short-term memory task which required attention to and retention of visual stimuli. Eye movements were monitored and measured by recording the electrooculogram with implanted periorbital Ag/AgCl electrodes. Ethanol induced the following dose-dependent changes of ocular motility: (a) diminution of the frequency of saccades; (b) prolongation of fixation (immobility) periods, though stimulus-elicited fixations became shorter; (c) increase in saccade excursion; (d) increase in saccade duration; and (e) decrease in saccade velocity (preceded at low doses by a transient increase). These changes were correlated with an impairment of behavioral performance. The results of eye movement analysis complement the results obtained on studies of human subjects by oral administration of ethanol. The findings of the present study in the nonhuman primate are interpreted as a reflection of the deleterious effects of alcohol on the cerebral substrate of visual attention.

The principal projection pathway between the olfactory bulb and the prepyriform cortex in the cat.

The anatomy and neuroelectric properties of the lateral olfactory tract (LOT) were investigated in the cat. Electron micrographs were obtained from sampled areas across the rostro-caudal projection of the pathway. Fiber diameters were estimated and axon spectra were obtained from three regions corresponding to peduncle, mid-LOT, and caudal-LOT. The mean inside diameter for all measured axons was 1.13 +/- 0.53 microns. The greatest number was found in the peduncle (approximately 600,000 axons). Mid-LOT and caudal-LOT each contained approximately 250,000 axons. Unmyelinated processes were estimated to be more numerous than the myelinated axons. Synaptic structures were also observed in the LOT. Cross-sectional area measurements of the LOT were obtained from tissue prepared for light microscopy. The area decreased from about 0.3 to 0.2 mm2 across the projection from olfactory bulb to cortex. The anatomical data were used to predict the conduction properties of transmission over the LOT. The olfactory bulb mitral cells were stimulated electrically and conduction velocity and temporal dispersion were evaluated in the tract. The strength-duration and stimulus-response curves and the potential profile during stimulation were also obtained. The time constant for LOT axons was 0.3 msec. The stimulus-response curve was sigmoidal in shape for both presynaptic and postsynaptic responses. The relationship between input (the action potentials) and output (cortical postsynaptic potentials) was linear up to 90 times threshold. Action potentials were conducted at 20 m/sec across the pathway over the peduncle and decreased to about 10 m/sec in caudal aspects. The potential profile for action potentials decayed exponentially into the depths of the cortex whereas the synaptic potential was a surface negative dipole field. The axon spectra were convolved with the electrophysiological properties of the LOT to mathematically reconstruct action potentials. The empirically derived mono- and biphasic curves fitted reasonably well with experimentally derived data under various stimulus conditions.

Effects of ethanol on visual evoked responses in monkeys performing a memory task.

The effects of ethanol on behavior and visual evoked potentials were investigated in monkeys performing a visual short-term memory task. Ethanol induced a dose-dependent deficit in performance and a prolongation of visuo-motor reaction time. The normal patterns of ocular motility were concomitantly altered. The potentials elicited in the lateral geniculate nucleus, the striate cortex, the inferotemporal cortex, the amygdala, and the mesencephalic reticular formation by a colored stimulus used by the animal in the task were attenuated by the alcohol in dose-related manner. In contrast, potentials elicited in the striate cortex and reticular formation by a brief and diffuse flash were augmented under the influence of the substance. It is inferred that ethanol can increase the reactivity of reticular and cortical structures to undifferentiated stimuli, while at the same time interfering with the basic mechanisms of visual attention and perception.

Principal component analysis of evoked responses and the effects of alcohol on the geniculo-striate system of the monkey.

This study was designed to test the effects of alcohol on visual evoked potentials in nonhuman primates performing a cognitive task. Flash evoked potentials were recorded from monkeys involved in a delayed matching-to-sample (DMS) paradigm in which the flash served as an alerting signal before each trial. Event-related potentials were recorded from the lateral geniculate nucleus and homolateral striate cortex before, during, and after intravenous administration of saline or ethanol (0.25, 0.5, 1.0, and 2.0 g/kg). Average evoked potentials (AEPs) were computed. Residual waveforms were obtained by subtracting the predrug AEP from postdrug AEPs. A principal component analysis was employed to define the alcohol alterations on the evoked responses. In the analysis each AEP was represented by 40 time points spaced 12 msec apart. These reduced representations of the AEP were entered in the variance-covariance matrix calculations. The first five eigenvectors were computed and plotted. Alcohol produced the greatest variance in the AEPs at the two highest dose levels. So the data were grouped together into three experimental categories: saline, low-dose (0.25-0.5 g/kg) and high-dose (1.0-2.0 g/kg). A correlation template, representing each category, was computed by correlating individual eigenvectors with each sequential average composed of 10 individual evoked potentials in the 200 trials of an experimental session. Alcohol affected the state vector from the brain by loading the correlation coefficient in the opposite direction following alcohol administration in two principal components. One or two of the eigenvectors significantly (P less than 0.01) shifted in geniculate nucleus, indicating that either the nucleus or a previous station was affected by alcohol. In comparison, three or more eigenvectors from striate cortex were shifted significantly following alcohol injection. This difference may be explained by the effect of alcohol on multisynaptic brain structures, including the brain-stem reticular formation, which in turn influenced the cortex.

The ultrastructure of the sheath around chronically implanted electrodes in brain.

Insulated, bipolar stainless steel electrodes were chronically implanted in various regions of the cat brain and the long-term structural changes in the tissue surrounding the electrodes were studied by light and electron microscopy. A sheath surrounded and separated the electrode from normal grey or white matter. A layer of foreign body giant cells of variable thickness was formed adjacent to the electrode. This layer was attenuated in some places so that it was unrecognizable by light microscopy. The bulk of the sheath structure consisted of collagen fibrils, leptomeningeal cells and hypertrophied astrocytes. Areas consisting of modified leptomeningeal cells with long thin processes we designated as spongy areas. These have not been previously reported using the electron microscope. Glycogen bodies were seen in leptomeningeal cells. Astrocytes became greatly enlarged and were more numerous in and around the sheath. Oligodendrocytes contained lamellar bodies, and direct continuity was shown between a lamellar body and an adjacent myelin sheath. Myelin was seen in abnormal sites (around oligodendrocytes and neurons) and in unusual configurations. Neuronal changes near the sheath included whorls and stacks of modified endoplasmic reticulum and the presence of cytoplasmic nucleolus-like bodies. Reactive, regenerative and degenerative axons were observed. Blood vessels were more numerous in the sheath and surrounding tissue than normal. Perivascular spaces were prominent even around capillaries and often plasma cells and monocytes were in these spaces. As compared to normal tissue the extracellular space is noticeably increased. Electrodes passing through ventricles were surrounded with a sheath covered with ependymal cells. This sheath was comparable in structure to the sheath present around the electrode in other locations.

Design for a micropowered multichannel PAM/FM biotelemetry system for brain research.

A design for a 12-channel pulse amplitude-modulated/FM biotelemetry system is described. The biotelemeter mounts on an animal's head close to the electrode probes to record and transmit brain electrical data. The size of the unit is 4.5 x 6.5 x 2 cm and it weighs about 60 g. It is designed to acquire EEG and other physiological data where the requirement is to obtain bioelectrical activity without cable encumbrance or confining behavioral restrictions. The telemeter consumes about 800 muW of power and operates for approximately 3 continous days before it is necessary to exchange the utilization of complementary metal oxide semiconductor (CMOS) integrated circuits. Transmission range is typically about 10 m.

Medial reticular and perihypoglossal neurons projecting to cerebellum.

Almost 10% of neurons in the medial reticular nucleus or adjacent thereto were invaded antidromically in response to stimulation of the fastigial and interpositus nuclei. The fraction was 77/835 for the bulbar and caudal pontine levels, but 0/167 for rostral pontine levels. The mahority, 49, of the neurons projecting to the cerebellum were superficially located in the region of the perihypoglossal nucleus, but 23 were scattered through the medial reticular nucleus, being 2.5-5.0 mm below the bulbopontine dorsum. Both classes of cerebellopetal neurons had a similar range of antidromic latencies, usually from 0.8 to 2.0 ms, but some were ober 3 ms. Both classes responded to volleys from limb nerves and inputs from cutaneous mechanoreceptors, with ranges of excitatory and inhibitory latencies that were similar to those for other medial reticular neurons. It is conjectured that the axonal projection is primarily to the cerebellar cortex and that the branches to the nuclei are often slender, hence the long antidromic latencies; 31 of 59 neurons tested projected to cerebellar nuclei on both sides, often with a considerable latency differential. Rarely, there were also axonal branches projecting up the central tegmental tract. The experimental findings are in very good accord with the anatomical descriptions of Brodal and associates (4, 5, 8, 19). It is suggested that the paramedian reticular and the perihypoglossal nuclei may provide a background excitatory input to the interpositus nuclei.

Topographic studies on medial reticular nucleus.

Several distinct classes of neurons have been identified in the medial reticular nucleus of the medulla and pons and in proximity thereto. Neurons projecting down the spinal cord comprised the principal class with two subclasses according as the neurons did or did not receive monosynaptic inputs from the fastigial nuclei of the cerebellum. Two other classes were recognized accordings as they projected to the cerebellum or rostrally to the mesencephalon. Topographic planar maps giving the location of these neurons have been constructed by exploring the nucleus with series of microelectrode tracks in parasagittal or in transverse planes. The different classes of neurons were not arranged in large discrete nuclei. In part they appeared to be randomly distributed, but many colonies of one or another class of neurons could be recognized with 3-11 neurons in zones with dimensions of a millimeter or so. Because of the limitations of sampling by microelectrode tracks at spacings of 0.5 mm, single colonies might have an actual population of 100 or more. Many of the class of neurons projecting to the cerebellum were in the region of the perihypoglossal nucleus. However, almost as many were located deep in the medial reticular nucleus. None was found at the pontine level. Reticulospinal neurons with fast axonal conduction velocities tended to be located dorsally to those with slow velocities. Correlation with the findings of Ito et al. leads to the conjecture that the neurons with fast axons are excitatory, while those with slow axons are primary inhibitory neurons. There is a brief reference to the problems raised by the admixture of the various neuronal classes, there being discrete colonies immersed in a scattered arrangement of all classes.

Dispersion along fiber tracts and in the coupling between tracts and a cortical network.

Dispersion in a neuronal coritcal network was modeled using CSMP, a Continuous Systems Modeling Program. The signal dispersion over pathways was simulated by use of a serial product approximating the convolution integral. The program was written in a sufficiently general format to be applied to a variety of biological signals. Calculated signals from a fiber tract and activation of a cortical network were compared with experimental data from cats. The network consists of excitatory cells in a forward limb which send collaterals to interneurons that, once excited, feed back to inhibit the excitatory cells. The model was consistent with data from neuronal assemblies in the prepyriform cortex and fibers in the lateral olfactory tract.

Reticulospinal neurons with and without monosynaptic inputs from cerebellar nuclei.

An account is given of the responses of 557 medial reticular neurons with axons projecting down the spinal cord. All 30 experiments were on decerebrated unanesthetized cats paralyzed by Flaxedil. Recording from single neurons was by extracellular glass microelectrodes. Identification was first by location (confirmed by subsequent histology) in the medial reticular nucleus of medulla or pons, and second by antidromic activation from cord stimulation at C2 and L2 segmental levels. Axonal conduction velocities were calculated from the latency differential between L2 and C2 antidromic responses, and were usually in the range of 90-140 m/s; but about 25% were slower, ranging down to 30 m/s. Stimulation by electrodes in the ipsilateral and contralateral fastigial nuclei differentiated reticulospinal neurons into two classes according to whether they did or did not receive monosynaptic inputs, the respective populations of fully investigated neurons being 270 and 174. The fastigioreticular neurons were distinguished by a higher background frequency with mean values of 28 as against 15/s. There were also significant diffences in both the excitatory and inhibitory responses to afferent volleys from forelimb and hindlimb nerves. Comparison of the respective latency histograms showed that the responses of neurons with a fastigial input had an excess of latencies in the ranges that can be correlated with the latency histograms observed for fastigial responses. Thus, there is evidence for the effectiveness of the fastigial input and so for the pathway with monosynaptic linkage: Purkinje cells of cerebellar vermis yields fastigial neurons yields medial reticular neurons projecting down the spinal cord. Adequate stimulation of cutaneous receptors by pad taps and air-jet stimulation of hairy skin in a disppointingly small action when compared with fastigical responses. Explanations of this deficiency are suggested. Another discrpancy from the fastigial responses is that the medial reticular neurons have much wider receptive fields with little discrimination between ipsilateral and contralateral and between forelimb and hindlimb. Stimulation of the ipsilateral tegmental tract was tested on 183 reticulospinal neurons, 112 being with fastigial inputs. In about half there was a powerful monosynaptic excitation, which would identify such neurons as being on the pathway from mesencephalic and diencephalic centers to the spinal cord. There is a general discussion of transmission across successive synaptic relays, where specificity is sacrificed to integration.

Medial recticular neurons projecting Rostrally.

1. In the latter part of investigations on the medial reticular neurons, stimulation was applied to the ipsilateral tegmental tract in the upper pontine level. Of the 426 neurons in this series, 56 had rostrally projecting axons as evidenced by their antidromic responses. 2. Of these 56 neurons, 41 were activated by limb nerve stimulation, usually very strongly, and so qualify as units in the reticular activating system. Fastigial stimulation monosynaptically excited 14 of these reticular activating neurons, so providing and ascending pathway from the cerebellar vermis. 3. Axonal branching has been demonstrated by antidromic testing in four reticular neurons with ascending axons. In two there were branches to the fastigial nucleus and in two, down the spinal cord. 4. The latency histograms of the excitatory and inhibitory responses resembled those for reticular neurons with descending axons except for the poverty of inhibitory responses in neurons not receiving a fastigial projection.

Computer signal processing of long duration biotelemetric brain data.

The EEG represents brain processing under diverse physiological conditions. A complete system involving acquisition and quantitation of this important information about brain function is described. The time-domain EEG and other biological signals are obtained using a multichannel PAM/FM biotelemeter mounted on the head of the experimental animal. This data is transmitted, demodulated and recorded by electronic recording techniques. A computer-based EEG analysis system is described for acquiring the primary data and transforming it into the frequency domain using Fourier methods. The computing system is developed to semi-automatically signal process about 4 h of eight channel EEG records. Data compression by plotting in a quasi-three-dimensional spectral profile allows visual correlations of pattern features to drug manipulations, etc. The software programs are briefly described for each step in signal processing. The feasibility of the complete system approach is demonstrated using biotelemetry to acquire low voltage EEG signals without behavioral distortions or introduction of artifacts by cables.