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Combined effects of methamphetamine and zolpidem on performance and mood during simulated night shift work.

Individuals who work irregular or rotating shifts often use stimulants and sedatives to offset shift-change-related mood and performance decrements. During this simulated shift work study the acute effects of the stimulant, methamphetamine were examined, and the effects of the hypnotic, zolpidem, and the combination were assessed during the shift after drug administration. Eight volunteers completed this 21-day, within-participant, residential laboratory study during which they received a single oral methamphetamine dose (0 or 10 mg) 1 h after waking, i.e., before task performance, and a single oral zolpidem dose (0 or 10 mg) 1 h before bedtime under 2 shift conditions: day shift and night shift. When participants received placebo at both dosing times, performance on some psychomotor tasks (e.g., the digit-symbol substitution task) and on some measures of mood (e.g., ratings of "Energetic") were disrupted during the night shift, relative to the day shift. Methamphetamine alone eliminated virtually all shift-related disruptions, while zolpidem alone and the drug combination produced few effects. These data indicate that shift changes produce performance impairments and mood alterations that are improved by a single low to moderate dose of methamphetamine. Zolpidem, given alone or in combination with methamphetamine, did not alleviate most shift-change mood and performance effects.

Adult↗

Electrophysiological evidence for right frontal lobe dominance in spatial visuomotor learning.

Slow negative potential shifts were recorded together with the error made in motor performance when two different groups of 14 students tracked visual stimuli with their right hand. Various visuomotor tasks were compared. A tracking task (T) in which subjects had to track the stimulus directly, showed no decrease of error in motor performance during the experiment. In a distorted tracking task (DT) a continuous horizontal distortion of the visual feedback had to be compensated. The additional demands of this task required visuomotor learning. Another learning condition was a mirrored-tracking task (horizontally inverted tracking, hIT), i.e. an elementary function, such as the concept of changing left and right was interposed between perception and action. In addition, subjects performed a no-tracking control task (NT) in which they started the visual stimulus without tracking it. A slow negative potential shift was associated with the visuomotor performance (TP: tracking potential). In the learning tasks (DT and hIT) this negativity was significantly enhanced over the anterior midline and in hIT frontally and precentrally over both hemispheres. Comparing hIT and T for every subject, the enhancement of the tracking potential in hIT was correlated with the success in motor learning in frontomedial and bilaterally in frontolateral recordings (r = 0.81-0.88). However, comparing DT and T, such a correlation was only found in frontomedial and right frontolateral electrodes (r = 0.5-0.61), but not at the left frontolateral electrode. These experiments are consistent with previous findings and give further neurophysiological evidence for frontal lobe activity in visuomotor learning. The hemispherical asymmetry is discussed in respect to hemispherical specialization (right frontal lobe dominance in spatial visuomotor learning).

Contingent Negative Variation↗

Systemic sulpiride in young adult volunteers simulates the profile of cognitive deficits in Parkinson's disease.

RATIONALE: The mesotelencephalic dopamine system has been implicated in cognitive processes dependent on an intact prefrontal cortex. Most previous research in humans has focused on dopaminergic agonists and their effects on tasks of working memory. OBJECTIVES: The present study was designed to investigate the cognitive and subjective effects of two doses (200 mg and 400 mg) of the dopaminergic D(2) receptor antagonist, sulpiride on a broad range of well-validated neuropsychological tasks in a group of 34 young healthy male volunteers. METHODS: Cognitive tasks were administered to subjects after ingestion of either drug or placebo within a double-blind, placebo-controlled, cross-over design. The cognitive tests included tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and were designed to assess visuospatial recognition memory, planning ability, working memory, strategy learning, sustained attention and attentional set-shifting. In addition, the National Adult Reading Test (NART) was used to assess verbal IQ, and visual analogue scales to assess subjective effects of the drug. RESULTS: Subjects on sulpiride were impaired on the tasks of spatial recognition, spatial working memory (sequence generation), planning (one-touch Tower of London) and attentional set-shifting. Only the spatial working memory task demonstrated a dose dependent effect. The impairments were not due to generalised sedative or motoric influences of sulpiride. CONCLUSIONS: All of the tasks impaired following sulpiride are known to be sensitive to frontal lobe damage and the precise pattern of deficits seen is consistent with the anatomical distribution of central dopamine receptors. The results are discussed with particular reference to their close simulation of the impairments seen in idiopathic Parkinson's disease.

Adult↗

Multiple components of lateral posterior parietal activation associated with cognitive set shifting.

Posterior parietal activation has commonly been observed in previous neuroimaging studies in association with flexible shifting of cognitive set. However, it is not clear whether the parietal activation reflects cognitive processes intrinsic to the shifting itself or other confounding factors such as spatial attention. To address this issue, the Wisconsin Card Sorting Task (WCST) was modified such that spatial components were eliminated from the sensory and motor aspects of the task. Moreover, a visual instruction of a next dimension was introduced to eliminate cognitive processes related to trial and error identification of a next rule, and a control null-instruction was also introduced to eliminate perceptual/oddball effects of the instruction cue. Localizer scans using a visually guided saccade task were also conducted to identify eye movement/spatial attention-related areas. Activity related to set shifting with trial and error was revealed in the lateral parts of the intraparietal regions, while activity related to eye movements/spatial attention was revealed in the medial parts of the intraparietal regions, confirming little spatial contribution to the modified WCST as indexed by the double dissociation. The lateral intraparietal activity was bilateral, but when the instructed shifting was contrasted with the null-instructed shifting to purify the shift-related activity further, the left intraparietal activation was significantly greater than that in the right hemisphere. These results reveal the left hemisphere dominance of purified shifting-related activity in the lateral posterior parietal cortex that may cooperate with the lateral prefrontal cortex whose left hemisphere dominance has already been reported.

Adult↗

Ergonomics in the design and evaluation of a system for "postal video letter coding".

In co-operation with the German Central Post Office for Technological Development, the authors designed and investigated the task of and workplace for "Postal video-letter-coding". Experiments including measures of performance, errors, heart rate, arrhythmia, EMG's, and EOG's were used to experiment with variations in the design of displays, codes, keyboards, shifts and rest pauses. As a result of this work the following recommendations have been made by the authors and accepted by the authorities: An optimal display configuration has been developed with two vertically arranged tv displays. Coding-rules are to be simplified by modifications of the postcode. The usual flat keyboard has been replaced by an inclined and angular keyboard. Night-shifts must be avoided because of the tedious nature of the task. A work-rest-schedule of 50 min work and 10 min rest is proposed. In 1978 the complete work-system-design will be introduced in the standard postal service.

Journal Article↗

Amygdala reactivity predicts automatic negative evaluations for facial emotions.

The amygdala is a key structure in a limbic circuit involved in the rapid and unconscious processing of facial emotions. In the present study, the role of the amygdala in automatic, involuntary appraisal processes, which are believed to be a crucial component of emotion processing, was investigated in 23 healthy subjects. Amygdala activity was recorded in response to masked displays of angry, sad, and happy facial expressions using functional magnetic resonance imaging (fMRI). In a subsequent experiment, the subjects performed a masked affective priming task that characterizes automatic emotion processing by investigating the biasing effect of subliminally presented emotional faces on evaluative ratings to subsequently presented neutral stimuli. In the affective priming task, significant valence-congruent evaluation manipulation was observed. Subjects rated neutral targets more positively if they were primed by happy faces. Significant correlations were found between amygdala responses to masked negative facial expressions and negative evaluation shifts elicited by the corresponding emotion quality in the affective priming task. Spontaneous amygdala reactivity to facial emotions appears to be a determinant of automatic negative evaluative response tendencies. This finding might shed some light on how amygdala hyperresponsivity contributes to negative cognitive biases commonly observed in affective disorders.

Adult↗

Dissociating executive functions of the prefrontal cortex.

An analysis is provided of three distinct paradigms that have been used to study executive functions of the prefrontal cortex involving planning, self-ordered memory or attentional set-shifting. Psychological and anatomical dissociations are sought from the perspective of studies of patients with frontal lobe lesions, functional neuroimaging, psychometric studies in normal volunteers and experimental studies in non-human primates. Particular attention is paid to attempts to dissociate mnemonic from other executive capacities. Thus, patients with frontal damage are shown to have deficits in their (1) use of strategies to improve performance in a spatial working memory task and (2) capacity to make an extra-dimensional shift due to a high-order failure of inhibition in an attentional set-shifting paradigm. These results are discussed in terms of anatomical and neuropharmacological dissociations of different aspects of executive function within the prefrontal cortex shown in monkeys.

Animals↗

Mechanisms of cognitive set flexibility in Parkinson's disease.

Previous research on cognitive set shifting in patients with Parkinson's disease has often been confounded by concept formation, rule learning, working memory and/or general slowing of cognitive processes. To circumvent this problem, the present study used the task-set switching procedure in which good performance was independent of rule learning, and in which working memory load was reduced by explicitly cueing the task switches. Our results provide strong evidence for a specific cognitive set shifting deficit in patients with mild Parkinson's disease in a non-learning context, which also cannot be explained by general slowing of cognitive processes. Moreover, the deficit was robust in a small sample of patients at the earliest stages of the disease. Finally, the impairment in task-set switching was only apparent when competing information was present, i.e. when the load on selection mechanisms was increased.

Cognition↗

Functional specificity of superior parietal mediation of spatial shifting.

Using event-related functional magnetic resonance imaging (fMRI) we determined how brain activity changes when an attended target shifts its location. In the main experiment, a white square could appear at 10 possible eccentricities along the horizontal meridian. It remained on the screen for a variable period of time and then changed location. At any time the stimulus could dim briefly. Subjects had to press a button when the stimulus dimmed. In order to perform this task attention had to be locked onto the target and shift with it. Half of the runs were performed overtly and half covertly. The event of interest consisted of the shift in the location of the attentional target. The state of maintained attention occurring in between the shifts constituted the baseline. The superior parietal gyrus was activated bilaterally in response to attentional shifts. No other area showed a significant response to shifting. On the left side the amplitude of the superior parietal response correlated positively with the distance of the shift. On the right side a significant correlation was present only for overt shifts. In a separate experiment we compared the maintaining of attention at a single spatial location to passive fixation: the frontal eye fields, anterior cingulate, right dorsolateral prefrontal cortex, and inferior parietal lobule were significantly activated, indicating that the absence of a shift-related response in these areas in the main experiment was due to the fact that they were equally activated by maintaining and shifting attention. The response to spatial shifts and the correlation with the distance between the original and the new location points to a specific role of the superior parietal gyrus in shifting the locus of spatial attention.

Adult↗

Manual response preparation and saccade programming are linked to attention shifts: ERP evidence for covert attentional orienting and spatially specific modulations of visual processing.

The premotor theory of attention claims that attentional shifts are triggered during response programming, regardless of which response modality is involved. To investigate this claim, event-related brain potentials (ERPs) were recorded while participants covertly prepared a left or right response, as indicated by a precue presented at the beginning of each trial. Cues signalled a left or right eye movement in the saccade task, and a left or right manual response in the manual task. The cued response had to be executed or withheld following the presentation of a Go/Nogo stimulus. Although there were systematic differences between ERPs triggered during covert manual and saccade preparation, lateralised ERP components sensitive to the direction of a cued response were very similar for both tasks, and also similar to the components previously found during cued shifts of endogenous spatial attention. This is consistent with the claim that the control of attention and of covert response preparation are closely linked. N1 components triggered by task-irrelevant visual probes presented during the covert response preparation interval were enhanced when these probes were presented close to cued response hand in the manual task, and at the saccade target location in the saccade task. This demonstrates that both manual and saccade preparation result in spatially specific modulations of visual processing, in line with the predictions of the premotor theory.

Adolescent↗

Semantic encoding deficits in a case of traumatic amnesia.

A 33-year-old patient was studied neuropsychologically 19 years after sustaining severe head trauma. A recent CT scan showed lesions in the left frontal and right temporal regions. Performance on standard memory tests, both verbal and visuospatial, was extremely poor, although other intellectual functioning was relatively spared. The patient showed some interesting deficits in semantic processing. In a depth of processing task there was no advantage for words where semantic encoding had been induced. Neither was there any release from proactive interference after shifts in semantic categories. Deficits were also observed in short-term memory distractor tasks as well as in cueing tasks. These findings suggest that the cognitive deficits commonly observed in Korsakoff's disease can also be present in other amnesic disorders and may in part be related to cortical and especially frontal lobe atrophy.

Adult↗

Interval timing performance in temporal lobe epilepsy: differences between patients with left and right hemisphere foci.

This experiment examined interval timing performance on a temporal reproduction procedure and a temporal discrimination (interval bisection) procedure in 19 patients with temporal lobe epilepsy (ten with a left-hemisphere focus [LTE group] and nine with a right- hemisphere focus [RTE group]), and 14 normal control subjects. In the temporal reproduction task, subjects were required to reproduce the durations of visual stimuli (0.5, 1, 2, 4, 8 s). In the temporal discrimination task, subjects were required to classify the visual stimuli as either 'short' or 'long'. Following exposure to the two standard durations (1 and 2 s), 'probe' trials were introduced in which the stimulus was presented for durations intermediate between the two standard durations. Psychophysical functions were derived from both timing tasks for each individual subject, as well as for the group mean data. The results showed that, compared to the normal subjects, the RTE group's timing ability was significantly compromized, as reflected by larger Weber fractions in both timing tasks. The LTE group's Weber fractions did not differ significantly from those of the control group; however they showed a leftward shift (i.e. a shorter bisection point) of the psychophysical function under the temporal discrimination task. The results suggest that the right and left hemispheres may play different roles in regulating interval timing performance.

Adult↗

Color appearance of surfaces viewed through fog.

How do the colors of surfaces seen through fog depend on the chromatic properties of the fog? Prior work (e.g. Chen and D'Zmura, 1998 Perception 27 595-608) shows that the colors of surfaces seen through a transparent filter can be described by a convergence model. The convergence model takes into account color shift and change in contrast. Whether the convergence model can also be applied to fog was tested experimentally with an asymmetric matching task. In computer graphic simulation, observers adjusted the color of a surface seen through fog in order to match the color of a surface seen in the absence of fog. The convergence model fits the data well. The results suggest that the color constancy revealed in this task with fog is described best by a model that takes into account both shift in color and change in contrast.

Color Perception↗

Indexical and symbolic referencing: what role do they play in children's success on theory of mind tasks?

Numerous measures have been employed in the last 17 years to assess theory of mind (ToM). The literature reports marked variability in the age at which children succeed on these measures. To account for this variability, researchers have provided explanations ranging from cognitive shifts and voids to the inability to understand the language of the tasks or to social/pragmatic considerations, all of which tell us little if anything about the internal mechanism underlying ToM. The main purpose of this paper is to provide a comprehensive theoretical account of children's success and the discrepancies found across different ToM tasks. We test the hypothesis that children's understanding of ToM is sensitive to the basic elements of language, that is, to whether the language is indexical or symbolic. Support for this account was found in the analysis of selected test protocols in four published studies of ToM, and new data collected from 53 children (4--6 years) which showed that a higher percentage of children succeeded on tasks with a high ratio of indexical to symbolic references than on tasks with a high ratio of symbolic to indexical references. There was also a main effect of age with older children succeeding at higher rates on both tasks than younger children. Our findings suggest that indexical representation can afford ToM understanding in 4-year-olds, but is not sufficient for a more mature ToM. The latter requires symbolic representation that was demonstrated by the majority of 5--6-year-olds.

Child↗

A shift of attention may be necessary, but it is not sufficient, for the generation of the Simon effect.

The Simon effect is the performance advantage for spatially corresponding, compared to non-corresponding, target-response ensembles when the location of the target is task irrelevant. In four experiments, we tested the predictions of the attention-shift account of the Simon effect. In all experiments, subject made choice responses with respect to the identity of a central target that followed a spatially non-informative peripheral precue. The first experiment showed a Simon effect away from the precue when the precue was a go/no-go signal: responses to spatially non-corresponding precue-response pairs were faster than responses to spatially corresponding precue-response pairs. The results of the second experiment suggested that this "reverse" Simon effect was not due to inhibition. In the third experiment, a secondary working memory task required the encoding, and later recall, of "oddball" precues. Although the Simon effect was absent, larger Simon effects towards the precue (i.e., responses were faster to spatially corresponding, compared to non-corresponding, precue-response ensembles) were correlated with poorer performance on the memory task. In the last experiment, the identity of completely non-informative precues was congruent, incongruent, or unrelated to the identity of the target. With precues that were unrelated to the identity of the target, there was a Simon effect towards the precues. Conversely, the Simon effect occurred away from the precue when the identity of the precue was related to that of the target. The findings suggest that a shift of attention alone is not sufficient to produce the Simon effect. Rather, the shift of attention must originate from an intentionally defined object. The results are discussed within a framework that integrates the attention-shift and referential-coding hypotheses.

Analysis of Variance↗

4 T-fMRI study of nonspatial shifting of selective attention: cerebellar and parietal contributions.

Regional blood oxygenation in the cerebellum and posterior cerebral cortices was monitored with functional magnetic resonance imaging (fMRI) at four Tesla while 16 normal subjects performed three tasks with identical visual stimulation: fixation; attention focused upon either stimulus shape or color and sustained during blocks of trials (sustained attention); and rapid, serial shifts in attention between stimulus shape or color within blocks of trials (shifting attention). The stimuli were displayed centrally for 100 ms followed by a central fixation mark for 900 ms. Each stimulus was either a circle or a square displayed in either red or green. Attention shifting required switching between color and shape information after each target detection and occurred on average once every three seconds. Subjects pressed a response key upon detecting the target; reaction time and response accuracy were recorded. Two protocols for T2*-weighted echo-planar imaging were optimized, one with a surface coil for the cerebellum alone and the other with a volume coil for imaging both cerebellum and posterior brain structures (parietal, occipital, and part of temporal cortices). Because fMRI of the cerebellum is particularly susceptible to cardiac and respiratory fluctuations, novel techniques were applied to isolate brain activation signals from physiological noise. Functional activation maps were generated for contrasts of 1) sustained attention to color minus fixation; 2) sustained attention to shape minus fixation; and 3) shifting attention minus sustained attention (to color and shape; i.e., summed across blocks of trials). Consistent with the ease of these tasks, subjects performed with >80% accuracy during both sustained attention and shifting attention. Analysis of variance did not show significant differences in false alarms or true hits across either attentional condition. A subgroup of subjects whose performance data were recorded during ten minutes of continuous practice did not show significant changes over time. Both contrasts between the conditions of sustained attention to color or to shape as compared with the fixation condition showed significant bilateral activation in occipital and inferior temporal regions (Brodmann areas 18, 19, and 37). The anterior medial cerebellum was also significantly activated ipsilateral to the finger used for responding. The principal comparison of interest, the contrast between the condition of shifting attention and the condition of sustained attention produced significant and reproducible activation: lateral cerebellar hemisphere (ansiform lobule: Crus I Anterior and Crus I Posterior; left Crus I Posterior); cerebellar folium; posterior superior parietal lobule (R and L); and cuneus and precuneus (R and L).

Adult↗

Attention and stimulus characteristics determine the locus of motor-sequence encoding. A PET study.

PET revealed the effects of stimulus characteristics on the neural substrate of motor learning. Right-handed subjects performed a serial reaction time task with colour-coded stimuli to eliminate the potential for learned eye-movements. The task was performed with the right hand under two different conditions. In one condition, subjects simultaneously performed a distractor task. Although they did show behavioural evidence of learning, they were not explicitly aware of the stimulus-response sequence. In the second condition, there was no distractor task, and seven out of the 11 subjects then became explicitly aware of the stimulus sequence. Metabolic correlates of learning were distinct in the two conditions. When learning was implicit under dual-task conditions, learning-related changes were observed in left motor and supplementary motor cortex as well as in the putamen. These regions are similar to those observed in a previous study in which the stimuli were cued by spatial position. Under single-task conditions, metabolic changes were found in the right prefrontal cortex and premotor cortex, as well as in the temporal lobe. A similar shift to the right hemisphere was observed in the spatial study during single-task learning. However, explicit learning of the task with colour stimuli activated more ventral regions. The areas supporting motor-sequence learning are contingent on both stimulus properties and attentional constraints.

Adult↗

[Cognitive set depends on the involvement of the ventral and dorsal visual systems].

Healthy adults were examined in three series of experiments with formation of an unconscious visual set: 1) the set was formed by repeated presentation of pairs of unequal circles (control); 2) an additional task of recognition of words/pseudowords was introduced into the context of the set-forming trials; 3) in the task additionally introduced, a subject had to spatially localize a certain target letter in a letter matrix. Scores of stability of the visual set to circles were compared. Coherence of the cortical electric activity in the alpha band was analyzed. We revealed a significant decrease in stability (rigidity) of the nonverbal visual set in the series with the additional task of spatial localization of the target stimulus. On the contrary, the set rigidity increased in the series with additional recognition of the verbal stimulus. EEG coherence patterns and behavioral data suggest that successful cognitive performance that demands dynamic situation-dependent shifts of unconscious sets takes place under conditions of alternation of tasks involving, predominantly, either the ventral ("what?") or dorsal ("where?") visual streams and, respectively, anterior or posterior systems of selective attention.

Adult↗