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Effects of developmental exposure to methyl mercury on spatial and temporal visual function in monkeys.

Detailed characterization of several aspects of visual function was made in two groups of monkeys exposed developmentally to methyl mercury. One group of monkeys (Macaca fascicularis) was dosed from birth onward with 50 micrograms/kg/day of mercury as methyl mercury. Another group was exposed in utero by dosing the mother with 10, 25, or 50 micrograms/kg/day of mercury as methyl mercury, and postnatally until 4.0-4.5 years of age with the same dose the mother had received. Spatial and temporal visual function was tested in both groups. Spatial visual deficits observed in the group dosed beginning postnatally were reported previously (Rice and Gilbert, 1982, Science, 216, 759-761). Monkeys exposed in utero plus postnatally exhibited impaired high- and low-luminance spatial vision. They also exhibited deficits in low-frequency high-luminance temporal vision, while low-luminance temporal vision was superior to that of control monkeys. Monkeys in which exposure began at birth displayed superior low-luminance temporal vision, while high-luminance temporal vision was not impaired. These effects were observed in the absence of constriction of visual fields. These data suggest that the pattern of visual deficits produced by developmental exposure to methyl mercury may be different from that in the adult, and that the developing visual system may be able to remodel as a result of early insult by a neurotoxic agent.

Animals↗

Visual cortical receptive fields in monkey and cat: spatial and temporal phase transfer function.

The response amplitude of simple cortical cells to spatiotemporal sine-wave patterns has been thoroughly documented in both cat and monkey. However, comparable measurements of response phase are not available even though phase measurements are essential for estimating the complete transfer function of a cell, and thus its spatiotemporal receptive field. This report describes a simple procedure for measuring both the amplitude and the phase transfer functions of striate cells. This technique was applied to 15 monkey and 27 cat simple cells. The spatiotemporal phase response functions were found to be adequately described by linear equations in four parameters. Both the amplitude and phase responses were found to satisfy several strong constraints implied by the class of linear quadrature models proposed recently in theories of biological motion sensitivity. Because the data satisfied these constraints, it was possible to determine four important receptive field properties from the phase data: the spatial symmetry, the temporal symmetry, the response latency, and the spatial position. The receptive fields were found to have a wide range of spatial symmetries, but a more narrow range of temporal symmetries. Spatiotemporal receptive fields reconstructed from complete transfer functions are used to illustrate some of the differences between direction selective and nondirection selective cells. Finally, the effects of linear and nonlinear mechanisms on amplitude, phase, and direction selective responses are considered.

Animals↗

Acute effects of d-amphetamine in a monkey operant behavioral test battery.

The acute effects of d-amphetamine were assessed using a battery of complex food-reinforced operant tasks that included responding in delayed matching-to-sample (DMTS, n = 6), conditioned position responding (CPR, n = 7), progressive ratio (PR, n = 8), temporal response differentiation (TRD, n = 4), and incremental repeated acquisition (IRA, n = 9) tasks. Performance in these tasks is thought to depend upon specific brain functions such as short-term memory and attention (DMTS), color and position discrimination (CPR), motivation to work for food (PR), time perception (TRD), and learning (IRA). d-Amphetamine sulfate (0.01-1.0 mg/kg IV), given 15-min pression produced significant dose-dependent decreases in the number of reinforcers obtained in each task. Response accuracy was significantly decreased at doses of 0.3 and 1.0 mg/kg for TRD and at 1.0 mg/kg for CPR when compared to saline injections. Accuracy was not consistently affected in the DMTS or IRA tasks. Response rates decreased or response latencies increased significantly at doses of 0.3 and 1.0 mg/kg in the PR and DMTS tasks. A dose of 0.1 mg/kg for the IRA and TRD tasks, 0.3 mg/kg for DMTS and 1.0 mg/kg for the CPR tasks significantly decreased percent task completed. Thus, the relative sensitivities of these tasks for detecting d-amphetamine behavioral effects were IRA = TRD greater than PR = DMTS greater than CPR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Acute effects of chlorpromazine in a monkey operant behavioral test battery.

The effects of acute chlorpromazine treatment were assessed using a complex operant test battery (OTB) containing five tasks thought to depend upon processes associated with short-term memory and attention [delayed-matching-to-sample (DMTS)], color and position discrimination [conditioned position responding (CPR)], motivation [progressive ratio (PR)], time perception [temporal response differentiation (TRD)], and learning [incremental repeated acquisition (IRA)]. Adult male rhesus monkeys were tested 15 min after IV injection of saline or chlorpromazine (0.010, 0.030, 0.100, or 0.175 mg/kg). Behavioral endpoints measured included percent task completed, response rate or latency, and response accuracy. The order of task sensitivity to disruption by chlorpromazine was TRD = PR = IRA = DMTS = CPR in which sensitivity was defined as a significant alteration in any aspect of task performance. Chlorpromazine slowed response rates in all tasks except TRD but did decrease accuracy in that task. These effects were similar to those noted in previous studies of acute chlorpromazine treatment. Specific motoric effects suggested decreased task initiation at doses that left general motor ability intact. This finding is similar to that noted in parkinsonism caused by chronic chlorpromazine treatment.

Animals↗

Identification of language-impaired children on the basis of rapid perception and production skills.

Discriminant function analysis was used to determine whether performance on temporal perception and production tasks alone could correctly classify children as language-impaired or normal. The analysis identified six variables, all of which assessed temporal perceptual and production abilities, which taken in combination correctly classified 98% of participating subjects. None of these variables assess the higher-level linguistic abilities (semantic, syntactic, pragmatic) that have classically been considered to be deficient in language-impaired children, or have been used to diagnose them clinically.

Aphasia↗

Laterality patterns in young fluent readers.

Neuropsychological profiles of kindergarten children who were reading fluently with understanding were compared with those of both chronological age controls and reading level controls. Finger tapping, dichotic listening, and nonverbal intersensory tasks succeeded in differentiating the two kindergarten groups, but not the kindergarten readers and the older reading level controls. Correlations among the measures were significant only for the young fluent readers, with greater bilaterality of both fine motor and linguistic functions being associated with better intersensory skills, indicating qualitative differences in central nervous system organization. Neuropsychological predisposition to early acquisition of reading is suggested.

Auditory Perception↗

Nonlinguistic auditory capabilities in aphasia.

Nonlinguistic auditory capabilities were assessed through psychophysical tests in 11 left-CVA aphasic, four right-CVA nonaphasic, and eight normal male subjects selected from the same age group. The tests included frequency discrimination, gap detection, gap discrimination, frequency sweep discrimination, assessment of the magnitude of the frequency uncertainty effect in the detectability of tones in noise, and assessment of frequency selectivity through simultaneous masked thresholds. Results of these tests were compared to measures of auditory comprehension obtained from the Boston Diagnostic Aphasia Examination, the Porch Index of Communicative Ability, and the Token Test. Nonlinguistic auditory performance of the three subject groups differed significantly from each other. For the left-CVA subjects, frequency sweep discrimination, frequency discrimination, and the frequency uncertainty effect in tone-in-noise detection were the best predictors of verbal auditory comprehension. The right-CVA subjects displayed marked deficits with regard to all pitch-related tests. The findings stress the importance of considering the presence of nonlinguistic auditory dysfunctions when evaluating linguistic auditory capabilities in aphasia.

Adult↗

Comparative characteristics of unit activity in the prefrontal and parietal areas during delayed performance in monkeys.

Neuronal mechanisms of prefrontal and parietal areas were compared in 3 monkeys during delayed performance. Spatioselective neurons were found in both areas in question. In the prefrontal cortex, they constitute 28% of all units sampled and in the parietal cortex they account for 21%. For the prefrontal area, spatial selectivity was particularly great during the delay (8%), and in the parietal area during the cue display (9%). During the delay, however, spatioselective parietal neurons accounted for 4% of all units sampled, i.e. their number was half that in the prefrontal area. The prefrontal cortex appears to play a major role in short-term memory proper, whereas the parietal area is more involved in assessing spatial relationships of emerging sensory stimuli. Spatioselective neurons of both areas were heterogeneous in their functions. Activity of some (11% in the prefrontal and 10% in the parietal area) was related only to the cue location. Activity of others (13% in the prefrontal cortex and 8% in the parietal cortex) was moreover coupled with the forthcoming movement. With lengthening of the delay, units related to the established temporal stereotype and some labile units which quickly rearranged to a new temporal task were recorded. Thus association area neurons reflect two concurrent processes linked with spatial and temporal memories. During cue displays, it is not only their spatial location that is described, but also a future motor act with its temporal and spatial properties programmed.

Animals↗

The pattern electroretinogram in Parkinson's disease reveals lack of retinal spatial tuning.

Spatio-temporal visual abnormalities, involving processing of medium coarse stimuli, are known to occur in Parkinson's disease (PD). While these deficits have been related to retinal dopaminergic deficiency, previous ERG studies in PD patients have provided conflicting results, probably due to differences in stimulus conditions. The influence of pattern element size (spatial frequency, SF) on the pattern electroretinogram (PERG) in PD has not been systematically studied. We recorded steady-state PERG to sinusoidal gratings of 50% contrast, counterphase modulated at 7.5 Hz with a series of SFs ranging from 0.5 to 6.9 c/deg in 20 PD patients and 20 healthy volunteers, subdivided in 10 "young" and 10 "age-matched" (AM) subjects. The PERG was analyzed by means of Fast Fourier Transform and the amplitude and the phase of the second harmonic response (15 Hz) were taken into account. We evaluated the medium-to-low SF amplitude ratio and termed it "PERG tuning ratio" (TR). The results indicate that aging affects all the studied SF, but the pattern of age-related loss differs from that observed in PD. Compared to AM subjects, PD patients show a specific deficit at medium SF, with a distorted PERG SF response function. Consequently, all PD patients show an attenuated PERG TR and 17 of them (85%) have an inverted TR. A significant TR decrease is correlated with the clinical stage of PD. There is a marked TR difference between patients receiving and not receiving L-DOPA. We conclude that stimulus SF is a crucial variable of the PERG in PD. PERG measurements and the derived PERG TR may provide a simple tool to evaluate retinal dopaminergic mechanisms and could contribute to the clinical assessment and monitoring of dopaminergic therapy in PD.

Aged↗

Experience-dependent maturation of the spatial and temporal characteristics of the cell receptive fields in the kitten visual cortex.

The development of contrast sensitivity to spatial and temporal frequencies was studied in the visual cortex of 6-week-old kittens reared from birth in three conditions: normal, dark-reared (DR) and dark-reared after 6 h of visual experience. Receptive fields of cells recorded in area 17 were quantitatively analysed using drifting sine-wave gratings. Compared to the low values obtained in the DR kittens, we observed after 6 h of visual experience: (1) an adult-like detection of higher spatial frequencies, (2) an increase of contrast sensitivity at low temporal frequencies; (3) a shift of the cell optimum towards 3 Hz, all values close to the normal ones. Unlike the spatial frequency selectivity, contrast sensitivity and detection of higher temporal frequencies continue to develop with age and visual experience.

Animals↗

Drugs and homicide: a theory.

In this paper we report our experience with 24 cases in which there was a homicide or homicides committed in association with use of large amounts of psychoactive drugs. Many, if not most of these homicides, would not have occurred without drug effects, for frequently there was evidence of grossly illogical thinking in close temporal association with use of intoxicants and in many cases there was no previous history of violence, no evidence of premeditation, no plan to avoid arrest and little or no discernible motivation. Usually there were multiple losses or other severe stress in the lives of the persons committing the homicide in the months preceding the crime. The stress increase was accompanied by increased and extraordinary intake of psychoactive substances. We theorize that high doses of psychoactive drugs impaired severely the brain systems upon which the mental functions of reality testing and judgment depend. Drug induced impairment of reality testing and judgment is frequently uncritically equated with hallucinations, disorientation, changes in time perception or other drug induced mental phenomena. Impairment of reality testing and judgment are basic criteria for linking drug effects with the behavior of homicide in the cases reviewed.

Adult↗

Physiological and psychophysical correlates of temporal processes in hearing.

Discharges of auditory nerve fibers are synchronized to stimulus frequencies below 4-5 kHz. The phase-locking phenomenon has been studied in considerable detail in several animal species. Although strikingly close correspondences exist between phase-locking behavior in animals and human perceptual performance on certain tasks, there is still no clear evidence that the human brain actually bases perceptual decisions on temporally encoded frequency information. The alternative to temporal coding is rate-place coding, in which frequency is assigned on the basis of peaks in cochlear excitation patterns. This paper reviews pertinent physiological, psychophysical and modeling data in three classes of experiment whose results are explanable in terms of both rate-place and temporal processing of neural responses. The experiments deal with the pitch of complex tones, vowel identification, and pure-tone frequency discrimination. The data described here suggest that temporal models of frequency coding compete well with and in some cases offer a more parsimonious explanation of perceptual performance than rate-place codes do, particularly at low and middle frequencies. A potentially important implication of the analyses conducted here is that humans may not code frequency information in synchronized activity as well as other species. The data suggest that within limits the human ear is capable of using either temporal and rate-place frequency codes, and that the specific code employed by the perceptual processor is task-dependent.

Animals↗

An in-depth analysis of lead effects in a delayed spatial alternation task: assessment of mnemonic effects, side bias, and proactive interference.

This study examined the effects of chronic postweaning lead (Pb) exposure in Long-Evans rats on a series of spatial alternation tasks. All tasks were administered in automated testing chambers, with a nosepoke as the critical response. While neither Pb-exposed group (median blood lead levels: 19 and 39 micrograms/dl, respectively) was impaired in learning the alternation rule, both groups performed more poorly than controls on the alternation task with variable intertrial delays (0, 10, 20, and 40 s). The deficit was constant across delays, arguing against memory dysfunction. Analyses of the responses on individual trials shed further light on the impaired and spared processes in the Pb-exposed rats. First, these analyses revealed stronger side biases in the higher exposure group. One interpretation is that these animals experienced impatience when the longer delays were included, making it more difficult for them to inhibit a prepotent response to a preferred side. In contrast, these trial-by-trial analyses revealed that several other factors-retention interval, semantic proactive interference, and temporal discriminability-exerted similar effects on performance in the control and lead-exposed animals. The use of logistic regression for these trial-by-trial analyses provided a means of simultaneously assessing the influence of several variables on performance, a significant advantage when there is confounding or interactions between variables.

Animals↗

Modulation of motor activity by cutaneous input: inhibition of the magnetic motor evoked potential by digital electrical stimulation.

We examined the inhibitory effect of a brief train of digital (D2) electrical stimuli at 4 times perception threshold on transcranial magnetic motor evoked potentials (MEPs) recorded from abductor pollicis brevis (APB) and flexor carpi radialis (FCR) muscles ipsilateral to the side of D2 stimulation. We compared this to the inhibitory effect of ipsilateral D2 stimulation on averaged rectified EMG recorded at 10% maximum voluntary contraction and on F-responses and H-reflexes recorded from these same muscles. We also compared MEPs recorded following D2 stimulation just above perception threshold to MEPs following higher intensity D2 stimulation. As well, we assessed the effect of preceding D2 stimulation on MEPs recorded from a relaxed versus tonically contracted hand muscle. D2 stimulation elicited a triphasic response of modest MEP facilitation followed by inhibition and further facilitation. The duration and onset of MEP inhibition correlated with those of the initial period of rectified EMG inhibition, however, the magnitude of MEP inhibition was generally less than the magnitude of EMG inhibition, consistent with a greater inhibitory effect of digital afferents on smaller motor neurons. MEPs were not facilitated during the rebound of EMG activity (the E2 period) that usually followed the initial period of EMG inhibition (I1 period). The behavior of H-reflexes and F-responses following ipsilateral D2 stimulation suggested that inhibition of both EMG and MEPs is not mediated via presynaptic inhibition of Ia afferents, and that inhibition is augmented by descending rather than segmental input to spinal motor neurons. Tonic contraction of the target muscle during D2 stimulation decreased the inhibitory effect of the preceding digital stimulus possibly due to recruitment of larger spinal motor neurons less likely to be inhibited by cutaneous input.

Adult↗

Neural correlates of temporal-order judgments versus those of spatial-location: deactivation of hippocampus may facilitate spatial performance.

The retrieval of temporal-order versus spatial-location information was investigated using fMRI. The primary finding in the hippocampus proper, seen in region of interest analyses, was an increase in BOLD signal intensity for temporal retrieval, and a decrease in signal intensity for spatial retrieval, relative to baseline. The negative BOLD signal change with spatial memory processing, while unexpected, is consistent with the recent fMRI literature indicating decreased BOLD can be associated with neuronal activation, and it is argued that the deactivation observed here may facilitate spatial performance. Spatial-location judgments also yielded a stronger (positive) response in the right midfrontal gyrus, while temporal-order judgments (autobiographic condition only) showed greater activity in the left superior temporal gyrus, suggesting greater working memory demands and greater semantization for each judgment type, respectively. Finally, all conditions activated the left midfrontal gyrus, although autobiographic memories showed additional activity in the medial frontal gyrus.

Adult↗