Richard T. Marrocco

Effects of altering brain cholinergic activity on covert orienting of attention: comparison of monkey and human performance

Abstract Experiments were conducted to elucidate the role of the cholinergic neurotransmitter system in arousal and the orienting of attention to peripheral targets. Rhesus monkeys and humans fixated a visual stimulus and responded to the onset of visual targets presented randomly in two visual field locations. The target was preceded by a valid cue (cue and target at the same location), an invalid cue (cue and target to opposite locations), a double cue (cues to both spatial locations, target to one), or, the cue was omitted (no-cue, target to either location). Reaction times (RTs) to the onset of the target were recorded. For monkeys, systemic injections of nicotine (0.003–0.012 mg/kg) or atropine (0.001–0.01 mg/kg), but not saline control injections, reduced mean RTs for all trials, indicating general behavioral stimulation. In addition, nicotine significantly reduced RTs for invalid trials but had little additional effect on those for valid, double, or no-cue trials. Virtually identical effects were observed for human chronic tobacco smokers in performing the same task following cigarette smoking. Injections of atropine in monkeys had no effect on RTs for valid or invalid trials but significantly slowed RTs in double-cue trials that did not require the orienting of attention. These results suggest that in both species, the nicotinic cholinergic system may play a role in automatic sensory orienting. In addition, the muscarinic system may play a role in alerting to visual stimuli in monkeys.

Alteration of brain noradrenergic activity in rhesus monkeys affects the alerting component of covert orienting.

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 for juice reward, and their manual reaction times (RTs) to visual stimuli were measured. The effects of parenteral injections of the α-2 adrenergic agonists clonidine and guanfacine, and normal saline were compared on the covert task. We assessed 1) overall error rates, 2) the difference in RTs between validly and invalidly cued trials (validity effect), 3) the difference in RTs between neutral and no-cue trials (alerting effect), 4) target location (visual field), and 5) cue-target interval. Changes in noradrenaline levels produced by clonidine (and to a lesser extent guanfacine) significantly decreased the alerting effect, and lowered RTs to stimuli in the left visual field, but did not change the validity effect, suggesting that noradrenaline is involved in maintaining non-spatial, sensory readiness to external cues but not in the shifting of the attentional focus.

Normal attention orienting but abnormal stimulus alerting and conflict effect in combined subtype of ADHD.

Recent pharmacological studies in animals and neuroimaging studies in normal humans suggest that the spatial and nonspatial cues in tasks measuring reflexive attention may be modulated by different neurotransmitter systems. The efficiency with which attention is oriented to explicit spatial cues may be altered by manipulating levels of brain acetylcholine, whereas reactions to nonspatial cues may be influenced by altering brain noradrenaline levels but not acetylcholine levels. In humans, however, previous attention studies have implicated dopamine when either explicit or implicit cueing is used. Some of the differences between animal and human work may be due to inadequate testing of nonspatial cues. To remedy this, we tested adult humans with ADHD that were primarily inattentive (ADHD/I) or combined inattentive/hyperactive (ADHD/C) and controls with the Attention Network Task that assesses both reflexive and voluntary attention and explicitly tests nonspatial cueing. Our results showed that spatial orienting in both subtypes was no different than controls. However, ADHD/C but not ADHD/I subjects had significantly slowed response times to nonspatial cues and cues with spatial conflict. Stimulant medication in a subset of ADHD/C subjects reduced these deficits to control levels. Based on these results, we conclude that ADHD/C subjects orient the focus of their attention normally but are impaired in their reactions both to abrupt visual cues and those that contain conflicting spatial cues.

Scopolamine slows the orienting of attention in primates to cued visual targets

Abstract 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.

Cholinergic modulation of covert attention in the rat.

Abstract Rationale: Nicotine is known to facilitate attentional processing, but its role in processing spatial and non-spatial cues is not well established in rodents. Objective: These experiments tested the hypothesis that nicotine facilitates the orienting of attention in space but has no effect on non-spatial 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 of 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.

Head-related transfer functions of the Rhesus monkey

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 degrees (left) to 90 degrees (right) in azimuth and -60 degrees (down) to 90 degrees (up) in elevation for frequencies between 0.5 and 15 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 and 8 kHz, suggesting that these two cues can be used to discriminate azimuthal position. Comparison with published subsets of HRTFs from squirrel monkeys (Saimiri sciureus) shows good agreement. Comparison with published 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 degrees and 40 degrees in azimuth with those calculated from a spherical head model with a radius of 52 mm, one-half the interaural distance of the monkey.

Attention as a target of intoxication:: Insights and methods from studies of drug abuse

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 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.

1994 Special Issue: Networks of anatomical areas controlling visuospatial attention

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 brains catecholamine neurotransmitter systems, and speculate on whether these systems may implement certain computational devices utilized within our neural network model.

Visual orienting and alerting in rhesus monkeys: comparison with humans

The behavioral capacities of the rhesus monkey for several sensory and cognitive tasks appear quite similar to those of humans. To evaluate the monkeys 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 invalid 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 interval. 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.

The influence of the visual cortex on the spatiotemporal response properties of lateral geniculate nucleus cells

Previous studies of the cortical input to the mammalian dorsal lateral geniculate nucleus (LGN) have identified a number of possible functions for the corticogeniculate pathway, including alteration of LGN spatial frequency selectivity and facilitation of both binocular interactions and orientation selectivity. These changes may be due to either a tonic or a phasic cortical facilitation or both. The temporal differences 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 (VI) 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 VI 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.