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The effects of single-dose fexofenadine, diphenhydramine, and placebo on cognitive performance in flight personnel.

BACKGROUND: Sedation and functional impairments are side effects associated with the use of first-generation antihistamines that preclude their use in aviation. Selected second-generation antihistamines do not have such side effects and have been proposed for use in aircrew. METHODS: Forty-two healthy naval aviation personnel served as subjects in this double-blind, randomized, placebo-controlled crossover study. Subjective drowsiness, cognitive performance, and vigilance were measured under three conditions: 180 mg fexofenadine (F), 50 mg diphenhydramine (D) as a positive control, or placebo (P). RESULTS: Subjects receiving F vs. D tended to have a faster mean hit reaction time (adjusted mean difference +/- SE, -10.5 +/- 6.8 ms, p = 0.127). Subjects performed faster and better with F vs. D on measures of omission errors and commission errors (p < 0.05). Variable symbol digit coding delayed recall accuracy was better for F vs. D (p = 0.023), and approached significance for shifting attention and divided attention tasks (p = 0.062 and p = 0.057, respectively). Subjects reported significantly more drowsiness (p < 0.005) with D than F. CONCLUSIONS: Diphenhydramine administration resulted in significant psychomotor decrements compared with fexofenadine, while the effects of fexofenadine were similar to placebo. These results provide additional support for the safe use of fexofenadine by aviation personnel.

Administration, Oral↗

Identification of static and dynamic postural instability following traumatic brain injury.

OBJECTIVE: Quantitative evaluation of static and dynamic aspects of postural instability as a long-term consequence of traumatic brain injury (TBI). DESIGN: Experimental two-group design. SETTING: Outpatient rehabilitation department. PATIENTS AND OTHER PARTICIPANTS: From a consecutive sample of TBI patients at least 6 months after trauma, 20 subjects were selected who complained of reduced gross motor skills but showed no sensorimotor impairments in a standard neurological examination (11 men, 9 women; mean age 36.2 +/- 10.7 years). Thirteen patients had sustained mild, 2 moderate, and 5 severe TBI. Twenty healthy controls were matched for age and gender. INTERVENTION: None. MAIN OUTCOME MEASURES: A dual-plate force platform recorded the amplitude and velocity of the center-of-pressure fluctuations in the anteroposterior (AP) and lateral (LAT) sway directions during quiet standing. Also, the speed and fluency of weight shifting using visual feedback was registered. Both balance tasks were combined with an arithmetic task, whereas quiet standing was also tested with visual deprivation. RESULTS: Compared to controls, TBI patients showed an increase of over 50% in AP and LAT sway, and a weight-shifting speed 20% lower. Dual-task interference was never significant. Visual deprivation was most detrimental for the TBI patients, particularly for LAT sway control. CONCLUSION: A long-term overall reduction in both static and dynamic control of posture can be present after TBI, even in patients without clear neurological deficits. Force-plate recordings can identify such (latent) balance problems. Visual deprivation during quiet standing appears a simple, sensitive test for postural instability related to sensory integration deficits.

Adolescent↗

Work schedule and task factors in upper-extremity fatigue.

We tested the combined effects of work schedule and task factors on upper-extremity fatigue in the laboratory during 8-h and 12-h shift schedules. Participants performed a simulated manual assembly task at three repetition rates and three torque loads and self-adjusted their work cycle duration to maintain fatigue at moderate levels. Work cycle durations decreased with increases in both load level and repetition rate. Fatigue was observed more quickly with increasing time on shifts and during night shifts compared with day shifts. Work schedule effects were most apparent at lighter workloads, with minimal differences at higher workloads. The highest fatigue levels were observed during 12-h night shifts, with similar levels reached by the end of both the week of 8-h night shifts and the week of 12-h day shifts. Overall durations were 20%-30% shorter than in previous short-term studies, which was likely a result of the more realistic work schedules used in this study. Results from this study could be applied to the design of work-rest schedules for manual tasks involving the upper extremities.

Adult↗

Sex differences in the dynamics of cue utilization and exploratory behavior.

The purpose of the present study was to investigate the effects of sex and estrous cycle on exploratory behavior, as well as the degree to which reliance on environmental cues changes with training. Fischer 344 rats were placed three times in an open field box that contained three objects (two identical bottles and a cylinder). During the initial exposure to the environment all females showed higher activity levels and explored a larger region of the environment compared to males. However, upon subsequent exposure to the same environment, these sex differences disappeared. During the third and final session, the locations of the bottle and the cylinder were switched. The estrous females and to a lesser degree male rats, responded to the relocation of objects with a renewal of exploration and activity; proestrous females did not show this response. The rats were then trained on a four-arm radial maze reference memory task. The correct arm could be located by its relation to extra-room cues, a large distal white panel, or to local inserts on the maze. Once the animals consistently chose the goal arm, a probe session was conducted to determine which cues the animals were using to solve the task. During the probe trial both the white panel and the local inserts were rotated 90 degrees clockwise and counterclockwise respectively and the animals' choice of arm recorded. During the first probe, females tended to rely on all three types of cues in solving the task. With additional training there was a shift towards predominantly using the distal visual information. In contrast, male rats did not show this shift; by the first probe session the males were predominantly using the distal visual information to solve the task. The findings indicate: (1) sex differences in the initial use of environmental cues; (2) the usage of environmental information is dynamic and changes with additional exposures to the environment. The results are related to previous findings on sex differences and estrous cycle effects, with an emphasis on the implications for hippocampal processing.

Animals↗

Patterns of stimulus- and self-induced slow brain potentials--a sign of task-specific preparation.

Does the scalp distribution of slow shifts in human brain potentials depend upon the processing demands? The question was approached applying two different paradigms. In the first study, the anticipation of haptic tasks presented to either of the hands was found to give rise to a contralateral slow negative brain potential (SP). The second study demonstrated that comparable hemisphere-specific patterns can be self-induced by means of biofeedback training. These results suggest that negative SPs (like the CNV) indicate preactivation of those brain-regions that process the expected task.

Biofeedback, Psychology↗

D1- versus D2-receptor modulation of visuospatial working memory in humans.

The effects of pergolide, a mixed D1/D2 receptor agonist, and bromocriptine, a selective D2 receptor agonist, were assessed in a visual delay task to further investigate the "dopamine link" of working memory in humans and to look for differential D1 versus D2 receptor contributions. Two groups of 32 healthy young adults (16 female) received either 0.1 mg of pergolide or 2.5 mg of bromocriptine in a placebo-controlled cross-over design. A pretreatment with domperidone, a peripherally active D2 antagonist, was performed in both groups to reduce side effects. Interindividual differences in pharmacokinetics were controlled by the time course of serum prolactin inhibition. The working memory paradigm was a visuospatial delayed matching task; the location of a randomly generated seven-point pattern had to be memorized and compared after 2, 8, or 16 sec with a second pattern that was either identical or slightly shifted within a reference frame. The task was designed with the intention to present unique stimuli at each trial and to require minimal motor demands. Practice effects between the two pharmacological test days were minimized by training sessions that preceded the tests. The paradigm showed significant error and reaction time increases with longer delays. After comparable doses, only pergolide, but not bromocriptine, facilitated visuospatial working memory performance as demonstrated by a significant drug-by-delay interaction. These findings are in accordance with the monkey literature as well as with neuroanatomical findings, and they confirm a preferential role of prefrontal D1 receptors for working memory modulation in humans.

Adult↗

Attentional capacities in children with autism: is there a general deficit in shifting focus?

Twenty-three children with autism and two control groups completed an attention battery comprising three versions of the continuous performance test (CPT), a digit cancellation task, the Wisconsin Card Sorting Test (WCST), and two novel, computerized tests of shifting attention (i.e., the Same-Different Computerized Task and the Computerized Matching Task). Children with autism could focus on a particular stimulus and sustain this focus as indicated by their performance on the digit cancellation task and the CPT. Their performance on the WCST suggested problems in some aspects of shifting attention (i.e., disengaging attention). The autism group performed as well as controls on the Same-Different Computerized Task, however, that required successive comparisons between stimuli. This implies that they could, in fact, shift their attention continuously. In addition, they did not differ from controls on the Computerized Matching Task, an analog of the WCST, suggesting that they do not have a general deficit in shifting attention.

Attention↗

The neurology of saccades and covert shifts in spatial attention: an event-related fMRI study.

Visual neglect occurs most frequently and persistently after lesions that include the right supramarginal gyrus (SMG), a part of the inferior parietal lobule. Patients with this syndrome make very few saccades to the left, and show abnormal performance on tasks in which they must covertly shift their attention to the left, suggesting that the right SMG is involved in the generation of saccades and attention shifts. Functional imaging studies of saccades and covert attention shifts in the normal brain, however, have shown weak or absent responses in both SMGs. We used event-related functional MRI to re-examine the responses to saccades and attention shifts within a single experiment, and to assess responses to left- and right-sided stimuli independently. When subjects made saccades to peripheral stimuli, the expected responses were seen in striate and prestriate cortex, the superior parietal lobules, the frontal eye fields, the supplementary motor area and the anterior insulae. In addition there was a response in the right SMG but not in the left SMG, as predicted from the clinical literature. When subjects made a covert visual assessment of the peripheral stimulus without any saccade, greater activity was seen in all of the areas in the frontoparietal network. Each area showed a bias towards contralateral stimuli, with two exceptions: the anterior insulae gave mainly ipsilateral responses, whilst the right SMG gave equal responses to right- and left-sided stimuli. These findings are discussed in the context of current theories pertaining to the clinical syndrome of neglect.

Adult↗

Methylphenidate increases selectivity of visual scanning in children referred for hyperactivity.

Visual scanning patterns were investigated in 32 children referred for symptoms of hyperactivity in a double-blind crossover comparison of methylphenidate and placebo treatments. Total errors, response latency, and visual fixations were recorded as the child scanned computer-generated visual matching-to-sample problems. Results indicated that the number of fixations on the standard stimulus in the matching task was significantly larger in the methylphenidate state. Drug treatment also resulted in a significant increase in the number of systematic comparisons between the standard and the variants in the task. However, the increased selectivity of attention to the standard stimulus was not accompanied by a reduction of total errors. It was suggested that the stimulant drug may increase attentional selectivity even when such a shift fails to produce improvement in task performance.

Association Learning↗

Nicotinic acetylcholine receptor agonist SIB-1508Y improves cognitive functioning in chronic low-dose MPTP-treated monkeys.

Monkeys that receive chronic low-dose 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) administration have difficulty performing numerous cognitive tasks. This study further examines the extent to which chronic low-dose MPTP exposure affects performance of a visual memory task [variable delayed response (VDR)] with both attentional and short-term memory components and assesses the effects of the novel neuronal nicotinic acetylcholine receptor agonist SIB-1508Y and levodopa on cognitive task performance. Before MPTP treatment, these monkeys displayed a delay-dependent decrement in performance on the VDR task and performed well on delayed matching-to-sample and visual pattern discrimination tasks. Chronic low-dose MPTP treatment caused a shift to a delay-independent pattern of responding on the VDR task, such that short-delay trials were performed as poorly as long-delay trials. There were also deficits in performing the delayed matching-to-sample task, whereas visual discrimination performance remained intact. SIB-1508Y normalized the pattern of response on the VDR task by significantly improving performance on short-delay trials and on the delayed matching-to-sample task. These effects lasted up to 24 to 48 h after SIB-1508Y administration. Neither levodopa nor nicotine significantly improved task performance. These results suggest that chronic low-dose MPTP exposure results in a cognitive disturbance that can be corrected by the nicotinic acetylcholine receptor agonist SIB-1508Y but not by levodopa. Thus, SIB-1508Y may be useful in the treatment of the cognitive deficits in Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

The effects of nicotine on spatial and non-spatial expectancies in a covert orienting task.

The present study examined how nicotine influences shifts of visuo spatial attention in casual smokers at each of three delays after smoking one cigarette: immediately, 1 h and 24 h. Informative peripheral cues were used to exogenously orient attention to the location where an increase or decrease in the size of a peripheral object was most likely to occur. One size change was more likely to occur than the other and the task was choice (expansion/contraction) reaction time. The performance decrement obtained when the target appeared at an uncued location was smallest in sessions run immediately after smoking (when nicotine levels were highest), suggesting that nicotine may increase the ease with which attention can be disengaged from a cued location. This finding confirms previous research which suggests a specific role for the basal forebrain cholinergic system in visual orienting. In contrast, nicotine was not found to affect non-spatial expectancies based on stimulus-response (expansion/contraction) probability. These findings, together with recent converging evidence, strongly support the proposition that different attentional operations are mediated by different neural subsystems.

Adult↗

Psychopathy and dual-task performance under focusing conditions.

Thirty psychopathic and 30 nonpsychopathic right-handed White male inmates (selected through R.D. Hare's, 1985b, Psychopathy Checklist) completed concurrent visual and auditory tasks under conditions focusing attention on the visual (i.e., primary) task. Performance indices tested 3 related hypotheses for cognitive deficits in psychopathic individuals: reduced attention to secondary tasks because of excess attention to immediate goals (interference), deficient shifts of attention, and reduced breadth of attention. The absence of differences in primary and secondary task accuracy contradicts the interference hypothesis. However, a trend toward deficits for psychopathic individuals responding with the right hand to primary task targets appearing after other targets, suggests poorer shifting of attention when left-hemisphere resources are engaged. Psychopathic individuals also overresponded to distractors following targets suggesting reduced attention to a peripheral dimension of two-dimensional stimuli.

Adult↗

Object-based selection: the role of attentional shifts.

The objective of this paper was to investigate under what conditions object-based effects are observed. Recently, Watson and Kramer (1999) used a divided-attention task and showed that unless top-down factors induce a bias toward selection at a higher level, object-based effects are obtained when same-object targets belong to the same uniformly connected (single-UC) region, but not when they belong to different single-UC regions grouped into a higher order object (grouped-UC regions). We refine this claim by proposing that a critical factor in determining whether or not object-based effects with grouped-UC regions are observed is the need to shift attention. The results of four experiments support this hypothesis. Stimuli and displays were similar to those used by Egly, Driver, and Rafal (1994). Subjects had to make size judgments. Using different paradigms, we obtained object-based effects when the task required shifts of attention (spatial cuing, same vs. different judgment with asynchronous target onsets), but not when attention remained either broadly distributed (same vs. different judgment with simultaneous targets) or tightly focused (response competition paradigm).

Attention↗

Supramodal and modality-specific mechanisms for stimulus-driven shifts of auditory and visual attention.

Two experiments are described in which visual and/or auditory location precues preceded visual or auditory targets. Observers were required to judge the location of the targets. Conditions were such that involuntary, stimulus-driven attention shifts were the only ones likely to occur and give rise to cueing effects. It was found that visual precues affected response time to localize both visual targets and auditory targets but auditory precues affected only the time to localize auditory targets. Moreover, when visual and auditory cues conflicted, visual cues dominated in the visual task but were dominated by auditory cues in the auditory task. These results imply that involuntary stimulus-driven attention shifts might be controlled by a modality-specific mechanism for visual tasks, whereas stimulus-driven shifts of auditory attention are controlled by a supramodal mechanism. This asymmetry in attention control is consistent with the idea that attentional dominance in a multimodal experimental task depends on the relative performance possible in the modalities involved; in this case visual localization is more precise than auditory and so auditory cues may be ineffective in cueing visual location, while visual cues are effective in both modalities.

Attention↗

Early social deprivation disrupts attentional, but not affective, shifts in rats.

This study examined the effects of early social deprivation in rats on 2 dissociable forms of inhibitory control of behavior that operate at 2 different levels of response selection: reversing the assignment of stimulus-reward associations within perceptual dimensions (affective shifts) and switching selective attention from 1 perceptual dimension to another (attentional shifts). Isolated subjects (isolates) and social controls (socials) were individually trained to spatial and nonspatial visual discrimination criteria on a radial arm maze. Whereas isolates and socials differed in neither acquisition nor reversal of both versions of the task, isolates were selectively impaired in shifting from spatial to nonspatial discrimination and vice versa. These findings demonstrate that isolation rearing selectively disrupts inhibitory control in attentional selection but leaves inhibitory control in affective processing intact.

Affect↗

Relationships between striatal dopamine denervation and frontal executive tests in Parkinson's disease.

Indirect evidence from human and monkey investigations supports the idea that impaired frontal tasks in Parkinson's disease (PD) may result from striato-frontal disruption caused by dopamine (DA) denervation of the caudate nucleus. To directly investigate this hypothesis, we used PET with 11C-S-Nomifensine (11C-S-NMF), a sensitive marker of striatal DA denervation, in 10 non-demented PD patients in whom two frontal executive tests, the object alternation (OA) and the conditional associative learning (CAL) tasks, thought to reflect mainly set-shifting/inhibition and planning, respectively, were given. In addition, the central executive function of verbal working memory was assessed with the Brown Peterson paradigm (BPP). We found a highly significant correlation between right caudate 11C-S-NMF specific binding and OA performance, less significant and reverse-direction correlations between CAL performance and putamen 11C-S-NMF binding, and no significant correlation with BPP performance. Thus, caudate DA denervation may subtend poor set-shifting/inhibition process in PD. Our results also point to distinct and complex relationships between striatal DA and specific frontal tasks.

Adult↗

Attention, learning, and memory performances and intellectual resources in Vietnam veterans: PTSD and no disorder comparisons.

Attention, learning, memory, and estimated intellectual potential were examined in 26 Vietnam veterans diagnosed with posttraumatic stress disorder (PTSD) and in 21 Vietnam veterans without mental disorders. Results revealed PTSD-associated cognitive deficits on tasks of sustained attention, working memory, initial learning, and estimated premorbid intelligence but not on measures of focus of attention, shift of attention, or memory savings. Cognitive task performances adjusted for estimated native intelligence remained negatively correlated with PTSD severity. An intellectual measure adjusted for cognitive task performances was negatively correlated with PTSD severity, even after the authors statistically controlled the level of combat exposure. Results suggested that although intellectual resources may constitute a vulnerability-protective factor for PTSD development, PTSD was associated with cognitive impairment independent of intellectual functioning.

Attention↗

Shift of laterality and compared analysis of paw performances in cats during practice of a visuomotor task.

Paw preference and performance were analyzed during early and late practice in 12 adult cats that reached toward a moving target. A strong preference for left-paw use was observed early in training. It was still present after practice despite a shift toward right-paw use. Comparing paw performance showed that the left paw was more accurate and quicker to trigger the movement during early practice, whereas after practice, it was the preferred paw (whether right or left) that triggered faster movement. The strong original left-paw bias could reflect the specialization of the right hemisphere in processing spatial information. Its weakening with practice could reflect the ability of the nonspecialized hemisphere to learn how to deal with the task.

Animals↗