Faculty Bibliography

This study examines the source of direction-dependent errors in movement extent made by human subjects in a reaching task. As in the preceding study, subjects were to move a cursor on a digitizing tablet to targets displayed on a computer monitor. Movements were made without concurrent visual feedback of cursor position, but movement paths were displayed on the monitor after the completion of each movement. We first examined horizontal hand movements made at waist level with the upper arm in a vertical orientation. Targets were located at five distances and two directions (30 degrees and 150 degrees) from one of two initial positions. Trajectory shapes were stereotyped, and movements to more distant targets had larger accelerations and velocities. Comparison of movements in the two directions showed that in the 30 degrees direction responses were hypermetric, accelerations and velocities were larger, and movement times were shorter. Since movements in the 30 degrees direction required less motion of the upper arm than movements in the 150 degrees direction, we hypothesized that the differences in accuracy and acceleration reflected a failure to take into account the difference in total limb inertia in the two directions. To test this hypothesis we simulated the initial accelerations of a two-segment limb moving in the horizontal plane with the hand at shoulder level when a constant force was applied at the hand in each of 24 directions. We compared these simulated accelerations to ones produced by our subjects with their arms in the same position when they aimed movements to targets in the 24 directions and at equal distances from an initial position. The magnitudes of both simulated and actual accelerations were greatest in the two directions perpendicular to the forearm, where inertial resistance is least, and lowest for movements directed along the axis of the forearm. In all subjects, the directional variation in peak acceleration was similar to that predicted by the model and shifted in the same way when the initial position of the hand was displaced. The pattern of direction-dependent variations in initial acceleration did not depend on the speed of movement. It was also unchanged when subjects aimed their movements toward targets presented within the workspace on the tablet instead of on the computer monitor. These findings indicate that, in programming the magnitude of the initial force that will accelerate the hand, subjects do not fully compensate for direction dependent differences in inertial resistance.(ABSTRACT TRUNCATED AT 400 WORDS)

We studied acute and chronic effects of levo-acetyl-carnitine (LAC) on event-related potentials (ERPs) in 3 monkeys trained in a 'go'/'no-go' visual 'oddball' discrimination task. The stimuli were 2.5 cpd sinusoidal gratings differing in their respective orientation only (0 degrees or 45 degrees). Each monkey was trained to release a lever during a prespecified time window. Target stimulus presentation probabilities were between 0.25 and 0.5. ERPs had comparable mean latencies and amplitudes in all monkeys. Primary evoked potentials recorded to either the target or non-target stimulus did not change significantly as a result of LAC treatment. On the other hand, P300 latency decreased following LAC administration, with a maximum occurring in 15-20 min. The major effects of LAC were consistent within each animal and for all three of them

Using a visual 'oddball' paradigm we studied ERPs in monkeys trained in a 'go' 'no-go' discrimination task. The stimuli were 2.5 cpd sinusoidal gratings differing only in orientation (0 degrees or 25 degrees). Monkeys released a lever during 1 of 2 response windows (RW), 480-1762 or 740-1672 msec, following target stimulus onset. Target stimulus presentation probabilities were 1.0, 0.5 and 0.3. The primary evoked potentials recorded to either the target or non-target stimulus were similar in all monkeys. P3 signals progressively emerged in the monkeys only to the target stimulus. P3 recorded at Cz, P3, and P4 had similar mean latencies and amplitudes. Eye movements showed no relationship to P3 potentials. Neither the primary visual potentials nor P3 changed significantly as a function of RW. P3 amplitude was inversely related to target probability. When the target stimulus was presented 100% of the time (P = 1.0) P3 disappeared over 4-5 blocks of trials, while the primary evoked potentials remained consistent

We have studied the relationship between N70 and P100 of the pattern visual evoked potential in 98 patients with multiple sclerosis and in 59 controls. In patients with multiple sclerosis, P100 was either absent or had prolonged latency in 121 eyes (61.7%), while N70 was absent or prolonged in 97 eyes (49.5%). The total number of eyes with either N70 and/or P100 abnormalities was 137 (69.9%). Eighty eyes (40.8%) had abnormal latency of both P100 and N70, while 41 eyes showed P100 delays without corresponding N70 changes. Seventeen eyes had abnormal N70, but normal P100 latency. N70 and P100 appear to be more often absent in the definite rather than in the possible multiple sclerosis group. These data show that N70 and P100 can be independently affected in patients with MS

Acetyl-levo-carnitine (ALC) protects against 1-methyl, 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in the nonhuman primate. ALC pretreated monkeys do not show signs of parkinsonism or electroretinographic changes typical of dopaminergic deficiency when given MPTP. In addition, pilot neurochemical and morphological data confirm a partial protection effect. While MAO-B inhibitors, like L-Deprenyl, are thought to protect dopaminergic neurons from MPTP-induced cell death by preventing the conversion of MPTP to its toxic metabolite MPP+, ALC is not known to have MAO-B affinity. Converging evidence suggests that ALC may affect directly mitochondrial respiration, which is known to be the target of MPP+ and affected in human neurodegenerative diseases, including Parkinson's disease. The results of this study point to new therapeutic avenues for the treatment of these nosologic entities

Median nerve somatosensory evoked potentials (SEP) were recorded in 7 Cynomolgus monkeys, before and after the administration of N-Methyl 1,4 Phenyl 1,2,3,6 tetrahydropiridine (MPTP), a neurotoxin which induces a parkinsonian syndrome in primates. Following MPTP administration, the amplitude of the negative component recorded at 15 ms over the frontal derivations (N15) decreased by 70% or more. This amplitude reduction was not modified by administration of dopamine precursors. These findings shed light on recent findings in human parkinsonian patients

This paper reports the results of recordings and maps of event-related potentials (ERPs) obtained in normal subjects, patients with Alzheimer's disease (AD), progressive supranuclear palsy, confusional states, and in subjects with homonymous hemianopsia. ERPs were recorded from 19 scalp electrode derivations using both visual and acoustic paradigms. In normal subjects, the topographical distribution of all ERP components is described in detail. In 45% of AD patients, ERPs were normal; in 35%, although present, ERP components were delayed, while in the other 20% the N2 and P3 peaks could not be recorded. In patients with progressive supranuclear palsy, the normal ERP sequence was not identified. Our findings in normals and in hemianopic patients suggest that the early modulation of stimulus-related potentials could be located in primary associative areas, and that N2, P3a, P3b, SW should have different origins

In previous studies, we showed that in the monkey, systemically administered N-methyl, 4-phenyl, 1-2-3-6 tetrahydropyridine (MPTP) produces a chronic parkinsonian syndrome accompanied by spatial frequency-dependent abnormalities in both the pattern electroretinogram and visual evoked potential. We describe the effect of intravitreally administered 6-hydroxydopamine (6-OH-DA) on the pattern electroretinogram and pattern visual evoked potential of 3 aphakic monkeys. Because of the aphake condition, several complexities of intravitreal injection of 6-OH-DA could be avoided. Nevertheless, following 6-OH-DA treatment, both the phase and the amplitude of pattern electroretinogram and pattern visual evoked potential became abnormal. This abnormality was most pronounced for the higher spatial frequencies (2.5 and 3.5 cycles per degree), whereas lower spatial frequencies (0.5 and 1.2 cycles per degree) were less impaired. The effects of systemically administered MPTP on pattern electroretinogram and pattern visual evoked potential are similar to the effects of intravitreal injections of 6-OH-DA, suggesting that a retinal catecholaminergic system plays an important role in pattern vision of primates