This study examined the correlation between covert attention and basal temperature change during menstrual cycle phase in 22 adult females. Previous work showing beneficial effects of estrogen on working memory led us to hypothesize that attentional function would be facilitated at the apparent time of ovulation. Menstrual phase was determined through questionnaires and objective measurements of basal body temperature spikes over a one month period. The Cued Target Detection (CTD) task was used to assess visuospatial attentional performance at three times during the menstrual cycle. The mean reaction times to visual targets were measured as a function of menstrual cycle phase, cue type and target location. As predicted, the onset of ovulation showed decreased reaction times and a significant increase in the cue validity effect on the days immediately preceding and following ovulation. The magnitude of the attention validity effect was negatively correlated with the basal temperature rise. Women lacking basal temperature shifts failed to show these changes. Results support the conclusion that the natural fluctuations of body temperature, and possibly reproductive hormones, during the menstrual cycle may enhance the attentional component of cognitive performance.
Advances in cellular neuroscience in the past decade now allow us to specify key neuronal operations underlying the selection and exclusion of information. Our goals are to use these data to identify the structure and function of the major reflexive and voluntary components of attention, understand how they are modulated by other structures, and work in an integrated fashion. In this chapter, we document recent advances from our lab and others that offer some insights into the mechanisms underlying reflexive attention and its interaction with voluntary attention. We also interpret new data on attention deficits in light of these advances. Four objectives motivate our studies. First, we seek to understand attention in its
simplest form, reflexive covert orienting. We practice the comparative approach, using the Posner covert target detection (CTD) task and attention network task (ANT) to study the orienting of rodents and primates (e.g., Marrocco & Davidson, 1998). There are two behavioral components to reflexive attention, orienting and alerting, and we find that an improved CTD task best assesses both components (Witte, Villareal and Marrocco, 1996). Second, we use pharmacological means to uncover the neurotransmitters that mediate the components of reflexive attention. Third, we localize the structures controlling reflexive attention through the use of local drug infusion and electrical microstimulation. Fourth, we seek to understand attention deficits in humans and animal models within the framework of normal, reflexive attention. It should be appreciated that this chapter is highly selective and not a general summary of the field. Interested readers should refer to several comprehensive reviews (Colby and Goldberg, 1999; Parasuraman,
1998)
Rationale: The link between attention and brain cholinergic neurotransmission is widely accepted. Human chronic tobacco smokers maintain high levels of nicotine in plasma and body tissues and show enhanced attentional orienting and other attentional tasks. Objective: We wished to test whether abstinence from smoking caused levels of the nicotine metabolite cotinine to decline and attentional enhancement to be reduced in a correlated manner. Methods. The levels of salivary cotinine and behavioral performance on a cued target detection task were measured in chronic, adult tobacco smokers over a 5 day abstinence period. Control groups assessed over the same time period include nonsmokers, smokers that did not abstain from tobacco, and smokers that abstained for 4 days and smoked on the last day. Results. In all groups with tobacco exposure, the levels of cotinine declined steadily with time after abstinence, reaching near zero levels at day 5. During this period, reaction times declined as well for all groups, due in part to task practice effects. In contrast, the validity effect, which indexes attentional allocation, increased with abstinence and was inversely related to cotinine levels in groups exposed to tobacco. Conclusions: We conclude that 1) nicotine abstinence increases the attentional validity effect, and 2) this increases is indexed by salivary cotinine, and 3) that control levels of attentional performance are achieved after 3 to 4 days of tobacco abstinence.
Arousal is a physiological and behavioral response to external or internal events (threat, pain, reward, etc). The arousal response can be divided into three categories based on the duration of response: short term alerting, long term vigilance, and longer term arousal. Each category represents an interplay of mechanisms in the peripheral and central nervous systems. Arousal is a result of the release of modulatory neurotransmitters that control target structures e.g., brain, internal organs) that contain a large variety of receptors. While all of the arousal neurotransmitters can induce EEG arousal, they play different roles in behavioral arousal. The noradrenergic system mediates alertness to sensory events and regulates the vigilant state of the organism. The cholinergic system increases behavioral and cognitive arousal, thereby facilitating attention and the encoding of information. The dopaminergic system facilitates the execution of appropriate behavioral responses to external and internal events. The serotonergic system facilitates the acquisition of rewarding stimuli such as food and maintains adequate activation of mood. Histamine's function is less clear, but like acetylcholine, it regulates cortical and subcortical excitability.
Rationale: Nicotine is known to facilitate attentional processing but its role in processing spatial and nonspatial cues is not well established in rodents. Objective: These experiments test the hypothesis that nicotine facilitates the orienting of attention in space but has no effect on nonspatial cues and that the benefits are blocked by the nicotinic antagonist mecamylamine. Methods: Eight male rats were trained to insert their noses in an opening, which triggered the presentation of cue and target lights in a modified covert orienting task. Four types of trials were presented: valid cues (cue and target lights on the same side of the nose hole), invalid cues (cue and targets on opposite sides), double cues (both cue lights illuminated, target on either side), and no cue (cue lights omitted, targets on either side). The reaction time required to withdraw the nose from the fixation hole (RT) and the time for the rat to move to the feeder (MT) were measured. Results: Nicotine decreased all RTs in a dose-dependent manner, but significantly lowered the invalid cue RTs and the validity effect (invalid - valid cue RT). Mecamylamine slowed RTs in a dose-dependent fashion and reduced the validity effect by significantly slowing the valid cue RTs. With mixtures of a fixed strength of nicotine and an increasing dose mecamylamine, RTs showed nicotine-like effects at low doses and mecamylamine-like effects at high doses. Neither of these drugs had a major effect on non-orienting trials (double and no cue RTs, and the alerting effect (no cue RTs - double cue RTs). Conclusions: Taken together with recent work in humans and non-human primates, these results suggest that the nicotinic cholinergic modulation of visual covert orienting is conserved across species despite different ecological niches.
The posterior parietal cortex (PPC) is implicated in the control of visuospatial orienting, including both overt saccadic eye movements and covert shifts of attention (i.e., attention to a location other than at visual fixation). Some studies have suggested that the attentional system is part of the premotor processing in the brain, while others suggest they are separate. Here, we test how the PPC controls covert attention shifts in the absence of executed eye movements. Electrical microstimulation was applied to the right PPC while monkeys performed a spatial, cued target detection task in which they were not allowed to move their gaze. At high currents, contralateral saccades were evoked. With currents below the thresholds for eliciting saccades, microstimulation produced purely attentional shifts, as indexed by changes in reaction time to visually cued targets. Our results indicate that such microstimulation can move covert attention in the absence of any overt movements of the eyes or limbs. This provides direct evidence that the PPC may be a site of visuospatial attentional modulation to peripheral visual stimuli.
A symposium was convened to discuss recent developments in the assessment of attention and the effects of drugs and toxic chemicals on attention at the 17th annual meeting of the Behavioral Toxicology and Teratology Society on May 1, 1999, in Research Triangle Park, NC. Speakers addressed issues including the methodology of assessing cognitive function, the neurobiology of specific aspects of attention, the dual roles of attention as a target of intoxication and as a mediating variable in the development of addiction to psychoactive drugs, the changes in attention that accompany neuropsychological disorders of schizophrenia, senile dementia of the Alzheimer type, and attention deficit hyperactivity disorder, and potential therapies for these disorders. This article provides an overview of the objectives of the symposium, followed by summaries of each of the talks given.P>
Head-related transfer functions (HRTFs) are direction-specific acoustic filters formed by the head, the pinnae, and the ear canals. They can be used to assess acoustical cues available for sound localization and to construct virtual auditory environments. We measured the HRTFs of three anesthetized Rhesus monkeys (Macaca mulatta) from 591 locations in the frontal hemisphere ranging from -90 (left) to 90 (right) in azimuth and -60 (down) to 90 (up) in elevation for frequencies between 0.5 and 22.5 kHz. Acoustic validation of the HRTFs shows good agreement between free-field and virtual sound sources. Monaural spectra exhibit deep notches at frequencies above 9 kHz, providing putative cues for elevation discrimination. Interaural level differences (ILDs) and interaural time differences (ITDs) generally vary monotonically with azimuth between 0.5-8 kHz, suggesting that these two cues can be used to discriminate azimuthal position. Comparison with subsets of HRTFs from squirrel monkeys (Saimiri sciureus) shows good agreement. Comparison with human HRTFs from the frontal hemisphere demonstrates overall similarity in the patterns of ILD and ITD, suggesting that the Rhesus monkey is a good acoustic model for these two sound localization cues in humans. Finally, the measured ITDs in the horizontal plane agree well between -40 and 40 in azimuth with those calculated from a spherical head model with a radius of 52 mm, one-half the interaural distance of the monkey.
Data collected from rat frontal cortical neurons have shown a surprising change in electrical power levels at frequencies surrounding 245 Hz following local injections of the neurotransmitters noradrenaline and glutamate. The power spectrum does not change anywhere else op to 1000 Hz. This effect does not appear to be related to the firing rates of individual neurons, nor their overall power spectal densities.
There is accumulating evidence to suggest that cholinergic neurotransmission may play an important role in visuospatial attention but the brain sites at which acetylcholine modulates attention are not well understood. The present work tested the hypothesis that the cholinergic influences within the intraparietal cortex are necessary for normal attentional shifting (covert orienting) in non-human primates. Two rhesus monkeys were trained to perform a visual, cued target detection task for liquid reinforcement. The animals pressed a lever to produce a visual display in which a central fixation point was flanked by two circles. Shortly after fixation was established, one of the circles brightened (cue) and a target appeared subsequently within one of the circles. Detection was signaled by a manual response and the reaction time to the appearance of the target was recorded. Four types of trials were presented. For valid cue trials, the cue and target were at the same spatial location; for invalid cues, cue and target were in opposite hemifields; for double cues, both cues were brightened but the target appeared in either the left or right circle; in no-cue trials, the cue was omitted. We localized the intraparietal region by recording attention-related, cellular activity with intracerebral microelectrodes. Among visually responsive cells in this area, valid cues presented to the receptive fields of visual neurons enhanced the responses to target stimuli in about half the cells and inhibited those responses in the remainder. In addition, some cells showed longer response latencies to invalid cues than to valid cues. We then infused scopolamine into attention-related activity sites and assessed its effect on performance. Scopolamine produced a dose-dependent increase in reaction times and decrease in performance accuracy that lasted more than 1 hr. Neither vehicle injections in the same locations nor scopolamine outside the physiologically defined area produced any significant change in behavior. Under our conditions of measurement, we conclude that activity mediated by muscarinic cholinergic receptors within the intraparietal cortex is necessary for normal covert orienting.
Abstract
Recent evidence suggests that arousal during the waking state may be regulated by multiple, interdependent, neurotransmitter systems that originate in the brainstem or hypothalamus and project to subcortical and cortical sites. We discuss efforts to determine the mechanisms by which these systems exert their effects and the roles they play in the control of arousal.
Abstract
Experiments were conducted to elucidate the role of the noradrenergic neurotransmitter system in arousal and the orienting of attention. Rhesus monkeys were trained to perform a peripherally-cued, covert orienting task [Posner, 1980 #148] for juice reward, and behavioral reaction times (RTs) were measured to visual stimuli. Parenteral injections of drugs that selectively altered the levels of norepinephrine (NE) were compared in their affects on the task with control sessions in which the animals were given injections of normal saline. To alter brain levels of NE, the alpha-2 adrenergic agonists clonidine or guanfacine were given in separate sessions. We assessed the effects of the drugs on 1) overall error rates 2) the difference in RTs between validly vs. invalidly cued trials (validity effect), and 3) the difference in RTs between neutral vs. no-cue trials (alerting effect). Changes in norepinephrine levels produced by clonidine and to a lesser extent guanfacine significantly decreased the alerting effect but did not change the validity effect, suggesting that NE is normally involved in maintaining sensory readiness to external cues but not in the shifting of the attentional focus.
Abstract
The strengths and weaknesses of neurochemical (neuropharmacologic, excitotoxic lesioning) methods in the study of attention are evaluated. Because attention is labile, the need for simple, well-controlled attentional and mnemonic paradigms is stressed. The most frequent approaches are 1) systemic alteration of neurotransmitter function with receptor specific drugs, and 2) neurochemically specific excitotoxic lesions. Results from these approaches have provided ample evidence that norepinephrine and acetylcholine play key roles in purely attentionaltasks and tasks with attentional components that are largely free of concomitant changes in arousal or perceptual processing. These transmitters facilitate attention shifting, the utilization of cues, and the maintenance of attention during arousing environmental conditions.
Experiments were conducted to elucidate the role of the cholinergic neurotransmitter system in arousal and the orienting of attention. Monkeys and humans were trained to fixate a visual stimulus and respond to the onset of visual targets presented in the peripheral visual field. The target location was validly forecast by a flashed visual cue in 80% of the trials and invalidly forecast in the remaining trials. Reaction times (RTs) to the detection of the target were recorded. Systemic injections of cholinergic agonists and antagonists in monkeys provided some evidence that the cholinergic system modulates attentional orienting in both a general and a specific manner. RTs for all trials were uniformly decreased compared to controls, indicating general behavioral stimulation. In addition, RTs for invalid trials were specifically altered by nicotine injections (reduced validity effect). No effect was seen for trials that required no spatial orienting. The validity effect was also reduced in human chronic tobacco smokers but not in controls or non-smokers after smoking a single cigarette. Interestingly, performance was not changed by smoking in the centrally cued version of the task, indicating that the nicotinic cholinergic system may play a greater role in the modulating the more automatic sensory orienting involved in the peripherally cued version of the task than in the more cognitively controlled orienting necessary for orienting after central cues.
Arousal is the ability to mobilize metabolic energy to meet environmental or internal demands on behavior. As such, it is an organismal property that is found throughout the animal kingdom, including those species with very rudimentary nervous systems. For example, in jellyfish, arousal may be produced by the diffusion of activating substances within the body wall that increase metabolic activity. In insects, activating substances may be generally mobilized within ganglia and released onto specific target structures from single neurons. In marine mollusks, repeated application of a noxious stimulus to the skin causes a withdrawal response that grows in magnitude over time. Though termed sensitization, it is associated with global changes in metabolism and is probably the precursor to the arousal response in higher organisms. The anatomy and physiology of arousal is similar among primitive vertebrates and highly complex mammals.
A symposium was convened to discuss recent developments in the assessment of attention and the effects of drugs and toxic chemicals on attention at the 1 7th annual meeting of the Behavioral Toxicology Society on May 1, 1999, in Research Triangle Park, NC. Speakers addressed issues including the methodology of assessing cognitive function, the neurobiology of specific aspects of attention, the dual roles of attention as a target of intoxication and as a mediating variable in the development of addiction to psychoactive drugs, the changes in attention that accompany neuropsychological disorders of schizophrenia, senile dementia of the Alzheimer type and attention deficit hyperactivity disorder, and potential therapies for these disorders. This article provides an overview of the objectives of the symposium, followed by summaries of each of the talks given.
The cholinergic agonist nicotine facilitates visuospatial attention shifting, but the role of muscarinic cholinergic drugs in this behavior is unclear. In order to establish the generality of cholinergic action in attention shifting, we administered the muscarinic antagonist scopolamine to two rhesus monkeys trained to perform a cued target detection (Posner) task. In this task, monkeys signaled the detection of a peripheral visual target by releasing a switch and their reaction times were measured. The location of the target's appearance was preceded by a cue that was either valid (target and cue in the same spatial location), invalid (target and cue to opposite hemifields), spatially uninformative (cues in both hemifields, target to one hemifield), or omitted altogether. Scopolamine produced a dose-dependent increase in all reaction times and a decrease in accuracy. The slowing was most prominent for valid cues in either visual field. However, slowing did not occur in trials whose cues lacked spatial information, or in tasks in which attention was directed to events at the fixation point, whether or not peripheral distractors were present. These results provide additional support for the hypothesis that acetylcholine plays a key role in reflexive attention shifting to peripheral visual targets.
Data collected from rat frontal cortical neurons has shown a surprising change in power levels at frequencies surrounding 245 Hz following local injections of the neurotransmitters noradrenaline and glutamate. The power spectrum does not change anywhere else up to 1000 Hz. This effect does not appear to be related to the firing rate of individual neurons, nor the overall power spectral densities.
The behavioral capacities of the rhesus monkey for several sensory and cognitive tasks appear quite similar to those of humans. To evaluate the monkey's attentional capacities, we have compared monkey and human performance on a visuospatial attentional task, the cued target detection (CTD) paradigm. Animals were trained to fixate a small spot of light while a cue and a subsequent target, are flashed in the visual periphery. In valid trials, the cue and target appeared in the same spatial location; in insalid trials, the cue and target appeared in the opposite location; in double trials, two cues were presented and the target appeared in one of their locations; in no-cue trials, the cue was omitted and the target appeared in one location. In addition, we varied cognitive control over the task initiation by making the trial onset either self-paced or computer- paced. Reaction times (RTs) to target presentation, response accuracy, and frequency of aborted trials were measured for all subjects. No significant species differences were found for the patterns of RTs for different trial types or for attentional dynamics, as indexed by the decreases in RT with increasing cue-target intenal. However, humans and non-human primates reacted differently to changes in cognitive control. Humans shows significant increases in no-cue trial RTs in the auto-paced task compared to the self-paced, but no differences in overall RT between tasks; monkeys showed a significant faster overall RT for the self-paced than the computer-paced task, but no difference between no-cue RTs. The performance differences between species may be related to the training history of the animals or to known anatomical differences in cortical organization, especially in the parietal lobe.
Previous studies of the cortical input to the mammalian dorsal lateral gemculate nucleus (LGN) have identified a number of possible fullctions for the corticogeniculate pathway, including alteration of LGN spatial frequency selectivity and facilitation of both binocular inleractions and orientation selectivity. These changes may be due to either a tonic or a phasic cortical facilitation or both. The temporal diiterences between each of these inputs suggests that their impact on LGN cell temporal tuning should be unique. To test this hypothesis, we reversibly blocked the visual cortex (Vl) and measured the effects on several indices of the temporal properties of LGN cells, including peak frequency, bandwidth, and response phase. Macaque monkeys were anesthetized and paralyzed during single cell recording from the LGN while area Vl was cryogenically deactivated. Single-cell responses were visually evoked with drifting, luminance-modulated, sine-wave gratings and discrete-Fourier analyzed. Cortical cooling produced statistically significant increases or decreases in response amplitude in 64% of cells recorded. In most cases, alterations in response amplitude occurred for stimuli that varied in spatial as well as temporal frequency. For those cells influenced by changes in stimulus temporal frequency, the majority showed changes over a broad range of frequencies. A minority of cells showed changes in either peak temporal tuning or temporal frequency bandwidth. Response phase angles for all temporal frequencies tested were unaffected by cortical cooling. Overall, these results suggest that the cortical input may alter the temporal response properties of LGN cells, perhaps by tonic, but not exclusively excitatory, corticofugal influences.
Recent technological advances have led to an increased emphasis on understanding how separate anatomical systems interact to carry out basic computational functions associated with sensorimotor selection and control. In the first section of this paper we review evidence for three anatomical networks involved in selective attention. We then describe a simple neural network model that we have used to simulate aspects of the interaction between anterior and posterior attention networks 'finally, we focus upon the computational role of the brain's catecholamine neurotransmitter systems, and speculate on whether these systems may implement certain computational devices utilized within our neural network model.