Effects of nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester on spatial and cued leaning.

An investigation was made of the effects of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on the acquisition and retention of two operantly conditioned discrimination tasks. Twenty Long-Evans rats were conditioned to approach one of two spatial locations that was either held constant across trials (spatial task) or was associated with a visual cue (illuminated lamp) that was randomly assigned to one of the locations on each trial (cued task). Rats were assigned to one of two treatment groups in which they received intraperitoneal injections of either NG-nitro-L-arginine methyl ester or saline approximately 2 h before sessions on each day of training. Analysis was made of the trial-by-trial performance in order to identify the characteristics of learning under each condition. Assessment of learning acquisition was based on the number of trials required to reach a criterion of 80% correct responses, whereas retention was assessed by the number of trials to criterion on each day after the criterion was initially reached. Analysis indicated that treatment groups did not differ significantly on acquisition or retention of either the spatial or cued task. These results indicate that inhibition of nitric oxide synthase does not interfere with the learning or retention of basic operant tasks that involve simple spatial or visual analysis. Whereas results from biochemical and physiological investigations have suggested an impact of nitric oxide synthase on behavioural function, behavioural investigations indicate a limited impact of nitric oxide synthase inhibition on learning and memory. Although these results do not discount the role of nitric oxide synthase in a hippocampal mechanism, they illustrate that behavioural analysis should be made in the context of multiple interacting neural systems. Viewed with previous behavioural research on the effects of NG-nitro-L-arginine methyl ester, these results indicate that nitric oxide synthase inhibition results in impairment of certain forms of learning whereas other forms are preserved.

Characteristics of perceptual grouping in rats.

Parametric analysis was made of the characteristics by which proximity and alignment serve as cues for perceptual grouping in rats. Rats were initially conditioned to discriminate a series of horizontal lines from vertical lines. Following training, rats were presented with test stimuli that consisted of bistable arrays of disjunct dots. A grouping cue (greater proximity, greater alignment, or both) was randomly assigned to either the horizontal or vertical orientation. The effectiveness of the cues was based on behavioral responses to the cued orientation. Results indicated that proximity served as a cue for perceptual grouping. The effectiveness of the proximity cue was less for rats than found previously in humans and, unlike humans, diminished with increased stimulus scale. Rats did not respond to alignment cues when used in isolation, although alignment facilitated grouping when used in conjunction with proximity cues. Diminished effectiveness of grouping cues likely reduces object recognition abilities, particularly for complex visual stimuli.

Time course of perceptual grouping.

An investigation was made of the time course of perceptual grouping that is based on two qualitatively different spatial relationships: proximity and alignment. An index of grouping capacity was used to assess the processing time required before a backward pattern mask interfered with grouping. Stimuli consisted of bistable arrays of disjunct dots that were followed by a mask. Grouping cues, either proximity or alignment, were randomly assigned to either the horizontal or vertical orientation, and subjects indicated whether the dots appeared grouped as a series of horizontal or vertical lines. Spatial metrics of the cues were systematically altered until they no longer served as a cue for grouping thereby determining the grouping threshold. The stimulus onset asynchrony (SOA) of the mask, relative to the test stimulus, ranged from 33.3 to 150 msec. The SOA at which grouping thresholds first became elevated identified the point at which the mask first interfered with the grouping process, thereby identifying the processing time required for grouping by the specified cue. The processing time for grouping by proximity and alignment differed significantly, requiring means of 87.6 and 118.8 msec, respectively, for processing to be completed. These measurements serve to identify the processing time necessary for spatially integrating stimulus elements into unified forms, thereby delineating temporal constraints at this stage of visual processing.

Expectancy of line segment orientation.

The question was asked whether briefly flashed line segments are easier to detect when presented at an expected, rather than an unexpected, orientation. Detection rates were measured in a two-interval forced choice (2IFC) paradigm that did not require the subject to identify the orientation of the line segment, only to detect its presence. The 2IFC paradigm was used to rule out bias or criterion effects. Subjects were led to expect lines in a particular or primary orientation by being presented lines with that orientation as cues before every trial, and by being tested with only that orientation during practice. Lines of the orthogonal, probe orientation replaced the primary on 25% of experimental trials. When the stimulus location was known in advance, lines of the primary orientation were detected more accurately than were probe lines, but when stimulus location was not known, detection rates were equal. Detection rates were also equal when subjects were informed of the probe at the end of the practice period, so that both orientations were expected; hence the subjects' expectations, not the probability of stimulus occurrence, are necessary for the effect to occur. Thus expecting a line of a particular orientation at a particular location facilities its detection.

Effects of eye position on auditory localization and neural representation of space in superior colliculus of cats.

The maps of visual and auditory space within the superior colliculus are in approximate register both with each other and with the underlying motor maps associated with orienting responses. The fact that eyes and ears can move independently poses a problem for the sensorimotor organization of these two modalities. By monitoring eye and pinna positions in alert, head-fixed cats, we showed that the accuracy of saccadic eye movements to auditory targets was little affected by eye eccentricity (range +/- 15 deg) at the onset of the sound. A possible neural basis for this behavioral compensation was suggested by recordings from superior colliculus neurons. The preferred sound directions of some neurons in the deep layers of this midbrain nucleus exhibited a shift with the direction of gaze, while in others the response throughout the auditory receptive field was either increased or decreased, suggesting that changes in eye position alter the gain of the auditory response.

Broad-band visual capacities are not selectively impaired in Alzheimer's disease.

Histological examination of the optic nerves of Alzheimer's disease (AD) patients has revealed a selective degeneration of large axon ganglion cells. This morphological abnormality raises the possibility of a selective impairment of broad-band channel visual function. To test this hypothesis, we administered visual psychophysical tests associated with either the color-opponent or the broad-band retinocortical channel to 14 AD patients and 29 elderly control subjects (ECS). In previous studies in monkeys, these tests had been sensitive to the effects of either parvocellular or magnocellular LGN lesions. In the present study, the color-opponent channel was assessed by tests of texture and color discrimination; the broad-band channel was assessed by tests of flicker and motion detection. Logistic regression analysis indicated that all tests collectively discriminated diagnostic groups at a borderline level of significance (p = 0.09). ANOVA also indicated a trend towards overall depressed function for AD patients on some capacities tested. Analyses comparing the prevalence of deficits in the AD and ECS groups showed that a significantly greater number of AD patients than ECS had deficits on texture discrimination, blue-violet discrimination, and 4.72 degrees/s motion detection. No individual subject demonstrated a selective impairment of broad-band channel function. The visual deficits in AD did not resemble those caused by lesions of magnocellular LGN in monkeys, indicating that the visual impairment in AD is not a functional reflection of damage limited to the broad-band channel.(ABSTRACT TRUNCATED AT 250 WORDS)

Auditory function in Alzheimer's disease.

The pattern of cerebral degeneration in Alzheimer's disease (AD) patients suggests that basic auditory capacities should be normal in AD, whereas progressively higher levels of auditory function should be increasingly impaired. To test this hypothesis, we administered tests of auditory capacities associated with primary auditory cortex (sound localization and perception of complex tones) and auditory association cortex (phoneme discrimination, timbre discrimination, and tonal memory) to 19 mildly to moderately demented AD patients, 21 elderly control subjects (ECS), and 14 young control subjects (YCS). The results showed significant differences between YCS and ECS on phoneme discrimination with synthetic speech and on tonal memory. The AD group differed from the ECS group on sound localization, one measure of synthetic speech discrimination, and timbre discrimination. Performance did not correlate with age, dementia severity, or duration of illness on any test condition. These findings indicate that although AD is accompanied by specific auditory deficits, the increase in neuropathologic change between primary auditory and auditory association cortices is not reflected in an increased impairment of functions that are mediated by these areas. Degraded aural language comprehension, which is characteristic of AD, likely reflects disruption of language processes, rather than dysfunction specific to auditory circuits.

Effects of multiple stimuli on ocular orientation by cats.

We investigated the characteristics of saccades made by cats in response to single and double stimuli. Stimuli were either visual, auditory, or bimodal. We initially trained cats to look toward the location of briefly presented single visual or single auditory targets that were extinguished before the initiation of eye movements. Following training, we monitored eye movements during and after the presentation of double targets, either two visual, two auditory, or bimodal, that were at disparate spatial locations. Cats made saccadic eye movements to positions that ranged between the location of the two targets. If the eye position at the start of a saccade was near the mid point of the targets, cats were less likely to initiate a saccade, and saccadic latencies were longer, compared to when starting eye position was at a distance from this location. These behavioral results are consistent with the hypothesis that the neural representations of briefly presented targets are combined and treated as a unitary, low resolution stimulus from which an orienting motor program is derived. The similarity of responses to double visual, double auditory, and bimodal stimuli suggests that a common sensorimotor mechanism applies within and between these sensory modalities.

Eye movements elicited by electrical stimulation of area PG in the monkey.

1. Eye positions of monkeys were tracked while low-current electrical stimulation was delivered to area PG of the posterior parietal cortex. Stimulation was delivered while monkeys were in darkness, while they were in a dimly illuminated room, or while they actively fixated on small lamps to receive a liquid reward. 2. Resulting eye movements fell into one of three categories, depending roughly on the area stimulated. Stimulation of caudal regions generally resulted in saccades that were of approximately equivalent amplitudes and directions. When more rostral areas were stimulated, saccades were generally produced that directed the eyes toward roughly the same position in the head. Distributed throughout all regions were sites for which elicited saccades did not fall clearly into either of these coordinate bases. Stimulation of lateral areas produced low-velocity eye movements that were directed ipsilaterally from the stimulated hemisphere. 3. Stimulation made while monkeys fixated on target lamps produced saccades with more variability and less amplitude than those produced while monkeys were in darkness. Low-velocity eye movements could only be elicited while monkeys were in darkness. 4. Craniocentric saccades typically brought the eyes to within a 10-20 degrees area, and saccades could not be produced when the initial eye position was near this area. Craniocentric saccades were always greater than 5 degrees in amplitude. 5. It is concluded that area PG is organized into at least two zones that differ in the way by which they code saccades. A caudal region codes saccades in a way similar to that found in the frontal cortex and superior colliculus of primates. A rostral region codes saccades in a craniocentric manner, although it is restricted only to gross redirection of gaze without the accuracy monkeys are capable of using in directing their eyes.

Interaction of visually guided saccades with saccades induced by electrical stimulation of the posterior parietal cortex in the monkey.

The properties of the neural code specifying the parameters of trained, visually guided saccades were examined by applying micro-stimulation of area PG in monkeys while they generated saccades to receive reward. It was hypothesized that electrical stimulation would alter the spatial pattern of cells being activated, and thereby predictably alter the characteristics of the resultant saccade. Instead, the two mechanisms of saccade generation, one initiated by electrical stimulation, the other initiated internally, were mutually exclusive, and resulted in either the cancellation of saccades, or the delay (up to 640 msec) of the visually guided saccade. Visually guided saccades accurately fixated visual targets (no longer visible at the start of saccades) whether or not the eyes were previously perturbated by the electrical stimulation. Unlike stimulation applied to the frontal eye fields or the superior colliculus, the end position of visually guided saccades cannot be modified by altering activity in area PG during saccade generation.

Dark adapted thresholds in young RCS rats.

The dark adapted thresholds of black-eyed RCS rats and cogenic controls were measured using a new psychophysical procedure that permits determination of thresholds at earlier ages than previously possible. Rats were tested longitudinally between about ages 1 and 3 months. At all ages, thresholds of RCS rats were higher than those of controls. Thresholds did not change systematically with age for either RCS rats or controls. At age 3 months, when the RCS rats' b-wave is no longer recordable, RCS thresholds are about 2.2 log units higher than those of controls.