Long latency components of the visually evoked potential in man: effects of aging.

Visual stimuli were used to elicit event related potential (ERPs) from frontal, central, and parietal midline scalp of ten right-handed male subjects in each of five groups (mean ages 28, 47, 63, 72, and 79 years). Stimuli consisted of 35 mm slides in three categories: 80% background; 10% target; and 10% colorful novel slides. Amplitude and latency of four ERP components, N1, P2, N2 and P3 were examined with three-way analysis of variance. Significant differences were found among age groups, stimulus categories and scalp locations. Although ERP component amplitudes were minimally affected by age, two waves, N2 and P3, showed reliable age-related changes in latency with latencies of both being prolonged in older subjects. Advancing age was associated with an acceleration of P3 slowing. Latency increased from 0.8 msec per year between ages 28 and 63 to 1.6 msec per year between ages 63 and 79. An effort was made to relate these results to a neurophysiological model involving the possible neural mechanisms of the P3 component.

Memory-For-Designs Test: comparison of performance of young and old adults.

Administered the Graham-Kendall MFD test to 80 normal male Ss, who ranged in age from 21 to 90 years. While no significant decline in performance occurred in Ss to age 50, the older groups, 40 Ss 60 years and older, differed significantly in error scores from Ss 50 years and younger, p < .001. As older Ss were given complete neurological examinations and visual acuity was evaluated carefully, the results suggest that decline in MFD performance after the age of 60 is sufficient to suggest caution in the use of the test by present interpretation for the evaluation of brain damage in the older patient.

Temporal effects of hemodialysis on measures of neural efficiency.

The short-term effects of hemodialysis on the integrity of the central nervous system (CNS) were examined. Evoked potentials (EP) and performance on five neuropsychologic tests were obtained from six patients undergoing maintenance hemodialysis. Measurements were taken 1, 24, 42, and 66b hours following dialysis. A highly consistent relationship between time since dialysis and EP latency was found. EP latencies tended to decrease during the 1-hour and the 24-hour recording sessions (compared to predialysis recordings), the shortest latencies typically occurring during the 24-hour period, then increasing steadily during the 42-hour and 66-hour intervals. EP amplitude was largest 1 hour after dialysis, then decreased progressively with time since dialysis. Performance on two tests of visual-motor speed and accuracy was best 24 hours after dialysis. The results indicate that there are consistent and measurable changes in the responsivity of the CNS which are related to time since dialysis.

Naloxone-induced electrographic seizures in the primate.

Electrographic seizure activity was recorded shortly following naxolone injections in artificially ventilated, methadone-treated stump-tailed macaques. Plasma-methadone concentrations prior to seizure activity were many times higher than those that have produced respiratory depression and death in nonventilated monkeys. The duration of seizure activity was clearly related to the dose of naloxone. Naloxone was without epileptogenic properties in animals that had not been pretreated with methadone. The results suggest that methadone and naloxone have additive epileptogenic properties when high blood levels of methadone are achieved in the artificially ventilated primate. Naloxone was devoid of antagonistic properties with respect to opiate-induced electroencephalographic spiking activity.

Visual evoked potentials in monkeys.

Visual evoked potentials (VEPs) were recorded from 2 cortical sites in stump-tailed macaques. VEPs recorded from striate cortex were basically consistent between animals (especially at low light intensity), remained remarkably stable over time, and compared favorably to VEPs reported by other investigators. We concluded that the VEP recorded from the striate cortex of day-active monkeys consists of 5 major peaks within the first 250 msec. The potentials recorded from post-central gyrus were simpler and more individualized and did not show intensity-related latency changes or increases in inter-subject variability. However, amplitudes of potentials recorded from both electrode placements increased with light intensity apparently reflecting the amplitude of individual potentials rather than the variability of these potentials from which the average VEPs were derived.

Methadone-induced changes in the visual evoked response recorded from multiple sites in the cat brain.

Visual evoked responses (VERs) and EEG were recorded following the i.p. administration of five doses of methadone (0.5--4 mg/kg) to 12 adult cats, which were implanted with cortical and subcortical electrodes. Additional cats, subjected to the same drug regimen, were used to evaluate plasma methadone concentrations. Doses of methadone that produced plasma concentrations between 80 and 190 ng/ml differentially affected VERs recorded from cortical and subcortical sites. Of the subcortical structures evaluated, the limbic system, specifically the hippocampus, was the most sensitive to the effects of the drug. These effects appeared to be primarily depressant. Responses recorded from the reticular formation and centromedian were affected only by the highest dose of methadone, while VERs recorded from cortical sites were reliably altered following the two highest doses and appeared to reflect both excitation and depression. Behavioral changes, however, were clearly evidenced in some cats at lower doses of methadone. Therefore, the data suggest (1) that those structures evaluated electrophysiologically did not reflect the full force of the drug's action as evidenced by its effect on behavior, (2) that cortical and subcortical recording sites have differential sensitivities, and (3) that one clearly defined, principal size of action of methadone is absent in the cat.

Ontogeny of the visual evoked response in the stump-tailed macaque.

Visual evoked responses (VER's) of stump-tailed macaques were studied from birth to 80 weeks in an attempt to establish the utility of this species as a model of human neurophysiological development. Although human subjects and monkeys share a unique complexity of the VER at birth, the postnatal development of their VER's does not appear to follow a parallel sequence. The relatively dynamic nature of the VER during the 1st few weeks in a monkey's life may limit the usefulness of this species as a model of human development. The rapid changes in the VER of the developing monkey and the observation that these changes continue beyond 2 years of age should be considered in studies of the VER in which repeated measures are obtained over a prolonged period of time.

Sustained ingestion of methadone and the sleep of monkeys.

Methadone HCl was administered daily to four stump-tailed macaques. The animals' sleep was periodically examined throughtout a year of methadone maintenance and, in two animals, during eight months of withdrawal. REM sleep was substantially decreased by methadone treatment and gradually returned to predrug values over a 6- to 8-month period of maintenance. Measures of non-REM sleep and awakenings showed similar disruption with no return to predrug values. These changes were not correlated with alterations in plasma-methadone concentrations. REM sleep rebound occurred temporarily upon drug withdrawal in two animals, but no consistent sleep disruption was apparent during the subsequent eight months. Contrary to some suggestions, therefore, tolerance to the sleep-disruptive effects of the drug may be specific and incomplete, and extended REM rebound upon withdrawal is not a universal response.

Visual and somatosensory evoked potentials characteristics of patients undergoing hemodialysis and kidney transplantation.

The effects of prolonged hemodialysis and kidney transplantation on visual and somatosensory evoked potentials and EEG frequency were assessed. Significant changes were found in both amplitude and latency characteristics of evoked potentials recorded from eight hemodialysis patients. Their evoked potentials tended to be of longer latency and larger amplitude when compared to responses of an age-matched control group. This was true for visual and somatosensory responses recorded from several scalp locations. A correlational analysis revealed no consistent relationship between blood chemistries and evoked potential characteristics. EEG power spectral analysis showed that the dominant frequency of five of the eight dialysis patients was in the 8-10 c/sec range. Two other patients demonstrated EEG frequencies which were scattered across the 3-12 c/sec range while for another subject the dominant frequency was 7-8 c/sec. The evoked potential latencies and amplitudes of patients with successful kidney transplant tended to return to the normal range and their predominant EEG frequency increased to around 10 c/sec. A depression of function in those neural systems underlying the visual and somatosensory modalities, along with a reduction in the cortical suppression of afferent stimulation normally exerted by the thalamic reticular system and the basal ganglia were postulated to account for the reported findings.

Life span changes in the averaged evoked responses of Down's syndrome and nonretarded persons.

Visual, auditory, and somatosensory evoked responses were recorded from six age groups of Down's syndrome persons and age and sex-matched nonretarded individuals ranging in age from 5 to 62 years and assigned to groups on the basis of observable signs of development and aging. Results indicated that, regardless of stimulus modality, the amplitude of late wave components was dramatically larger for Down's syndrome than for the nonretarded subjects. Where obvious amplitude reduction occurred with maturation and aging among nonretarded subjects, amplitude changes were generally absent among Down's syndrome subjects. The findings for Down's syndrome persons were discussed in terms of deficits in central inhibition and abnormalities in neuronal excitability to different levels of stimulus intensity.

Neuropsychological correlates of chronic alcoholism and aging.

Independent investigations of alcoholism and aging have demonstrated significant parallels between the two phenomena suggesting the possibility of "premature aging" as a result of alcoholism. To test this hypothesis a cross-sectional design was utilized with three groups of 20 male subjects: young normal (mean age 31 years), young alcoholics (mean age 33 years), and elderly normal (mean age 71 years). Eleven objective measures, selected from a battery of sensory and perceptual motor tests routinely used to evaluate cerebral dysfunction in hospitalized patients, were compared for the three groups. The results indicated a definite general decline in neuropsychological functioning with aging and suggested a similar trend with alcoholism. The tendency seen with alcoholism was least apparent with regard to fundamental sensory-motor functions and the perceptual functions of vision and audition and most apparent with regard to short term memory and abstract reasoning, i.e., higher mental processes. The results provided support for the hypothesis that chronic alcoholism causes premature aging of neuropsychological functions and possibly the brain.

WAIS performance in young normal, young alcoholic, and elderly normal groups: an evaluation of organicity and mental aging indices.

Investigated the effects of alcoholism and advanced age on Wechsler Adult Intelligence Scale (WAIS) performance and tested the validity of indices of "organicity" and "mental aging" derived from WAIS scores. The WAIS was administered to three groups of 20 males each: young normal (mean age 31 years), young alcoholic (mean age 33 years), and elderly normal (mean age 71 years. In terms of scaled scores, the young normal group was generally superior to the other groups on Verbal and Performance subtests, and the alcoholic and elderly groups resembled each other more on the Verbal than the Performance subtests. In view of an almost 40-year difference in age between the young alcoholic and the elderly normal Ss, similarities in pattern of performance provided some evidence for the hypothesis of "premature aging" in alcholics.

Visual evoked response and behavioral correlates of plasma methadone concentrations in cats.

Twelve cats were implanted with cortical and depth electrodes. After they recovered from the operation, visual evoked responses (VERs) were recorded at 20 min following saline and methadone (0.5, 1, 2, 3, 4 mg/kg) administered IP in a semi-random order to each cat. Four other cats were similarly drugged and plasma was obtained for radioimmunoassay of methadone content. At the three lowest dose levels behavioral excitation and salivation were evident in some cats, while their VER configuration remained essentially unaltered and plasma methadone was barely measurable. Following the 3 and 4 mg/kg doses plasma methadone concentration increased dramatically, behavioral excitation and salivation were evident in most cats and VERs were reliably altered. The VER alterations, consisting of amplitude attenuation and a decrease in some latencies, were restricted to secondary VER components occurring between 50 and 100 msec despite the animals' extreme behavioral excitation. These results suggest that the reticular formation is not a principal site of the drug's effect.

Sudden toxicity of methadone in monkeys: behavioral and electrophysiological evidence.

A sudden and potentially lethal toxic reaction to a previously well-tolerated maintenance dose of methadone occurred in 4 of 6 monkeys. The reaction was characterized by gross behavioral and respiratory depression and a marked attenuation of both early and late components of the visual evoked response with an increase in most latencies. The nature of the evoked response alteration suggests a widespread central nervous system depressant effect of the drug during toxicity. Concomitant with the toxic reactions were dramatic increases in plasma methadone concentrations. Therefore the observed changes in sensitivity to methadone would appear to be the consequence of a sudden shift in pharmacokinetics resulting in toxic plasma concentrations.

Endemic eastern equine encephalomyelitis in Florida: a twenty-year analysis, 1955-1974.

Research and surveillance programs relating to the circulation of eastern equine encephalomyelitis (EEE) virus in Florida between 1955 and 1974 are summarized. All available data suggest that EEE virus is 1) endemic in many Florida fresh water swamps and waterways, 2) active in a continuous cycle throughout the year with a peak between May and August, and 3) circulating in Culiseta melanura. It has been isolated also from eight other mosquito species.