Chris M. Dodds

Competition in visual working memory for control of search

Recent perspectives on selective attention posit a central role for visual working memory (VWM) in the top‐down control of attention. According to the biased‐competition model (Desimone & Duncan, 1995), active maintenance of an object in VWM gives matching (Downing, 2000) or related (Moores, Laiti, & Chelazzi, 2003) objects in the environment a competitive advantage over other objects in gaining access to limited processing resources. Participants in this study performed a visual search task while simultaneously maintaining a second item in VWM. On half of the trials, this item appeared as a distractor item in the search array. We found no evidence that this item interferes with successful selection of the search target, as measured with response time in a target detection task and accuracy in a target discrimination task. These results are consistent with two general models: One in which a representation of the current task biases the competition between items in a unitary VWM, or one in which VWM is fractionated to allow for maintenance of critical items that are not immediately relevant to the task.

Rightward shift in spatial awareness with declining alertness

Although transient neglect of contralesional space occurs following damage to either hemisphere, persistent forms are overwhelmingly associated with right hemisphere lesions. This has led to the suggestion that impairments in other right hemisphere systems--in particular those that mediate alertness--may undermine recovery. Reductions in neglect severity with stimulation, exacerbation with sedatives and the poor performance of chronic neglect patients on sustained attention tasks are consistent with this view. However, the question of whether changes in alertness exert a specific influence over spatial attention--or simply improve performance across many domains--is difficult to address using only patient studies. Here, we examine this question with individuals from the healthy adult population. On certain spatial tasks, adults show a modest but reliable leftward attentional bias. On the basis of the neglect studies, we hypothesised that this bias would diminish--or even reverse--as alertness levels declined. In the first study, participants were asked to judge the relative lengths of the left and right sections of a line when sleep deprived and when well rested. A significant rightward shift in attention was associated with sleep deprivation. A rightward shift was also observed over the course of the session. The second study replicated this time-on-task effect. The results suggest that a diminution in alertness may be sufficient to induce a rightward shift in visual attention in the healthy brain. Implications for the persistence of neglect in patients, for spatial biases in children and for normal free viewing asymmetries are discussed.

An event-related potential component sensitive to images of the human body.

One of the critical functions of vision is to provide information about other individuals. Neuroimaging experiments examining the cortical regions that analyze the appearance of other people have found partially overlapping networks that respond selectively to human faces and bodies. In event-related potential (ERP) studies, faces systematically elicit a negative component peaking 170 ms after presentation - the N170. To characterize the electrophysiological response to human bodies, we compared the ERPs elicited by faces, bodies and various control stimuli. In Experiment 1, a comparison of ERPs elicited by faces, bodies, objects and places showed that pictures of the human body (without the head) elicit a negative component peaking at 190 ms (an N190). While broadly similar to the N170, the N190 differs in both spatial distribution and amplitude from the N1 components elicited by faces, objects and scenes and peaks significantly later than the N170. The difference between N190 and N170 was further supported using topographic analyses of ERPs and source localization techniques. A unique, stable map topography was found to characterize human bodies between 130 and 230 ms. In Experiment 2, we tested the four conditions from Experiment 1, as well as intact and scrambled silhouettes and stick figures of the human body. We found that intact silhouettes and stick figures elicited significantly greater N190 amplitudes than their scrambled counterparts. Thus, the N190 generalizes to some degree to schematic depictions of the human form. Overall, our findings are consistent with intertwined, but functionally distinct, neural representations of the human face and body.

Dissociating Inhibition, Attention, and Response Control in the Frontoparietal Network Using Functional Magnetic Resonance Imaging

Evidence suggests that the right inferior frontal cortex (IFC) plays a specialized role in response inhibition. However, more recent findings indicate a broader role for this region in attentional control. Here, we used functional magnetic resonance imaging to examine the functional role of the right IFC in attention, inhibition, and response control in 2 experiments that employed novel variations of the go/no-go task. Across the 2 experiments, we observed a graded response in the right insula/IFC, whereby increasing response control demands led to an increase in activation. The results are consistent with the hypothesis that this region plays a key role in the integration of bottom-up, sensory information with top-down, response-related information to facilitate flexible, goal-directed behavior.

Methylphenidate has differential effects on blood oxygenation level-dependent signal related to cognitive subprocesses of reversal learning.

Complete understanding of the neural mechanisms by which stimulants such as methylphenidate ameliorate attention deficit hyperactivity disorder is lacking. Theories of catecholamine function predict that the neural effects of stimulant drugs will vary according to task requirements. We used event-related, pharmacological functional magnetic resonance imaging to investigate the effects of 60 mg of methylphenidate, alone and in combination with 400 mg of sulpiride, on blood oxygenation level-dependent (BOLD) signal in a group of 20 healthy participants during probabilistic reversal learning, in a placebo-controlled design. In a whole-brain analysis, methylphenidate attenuated BOLD signal in the ventral striatum during response switching after negative feedback but modulated activity in the prefrontal cortex when subjects maintained their current response set. The results show that the precise neural site of modulation by methylphenidate depends on the nature of the cognitive subprocess recruited.

Why does the gaze of others direct visual attention

Viewing another person directing his or her gaze can produce automatic shifts of covert visual attention in the same direction. This holds true even when the task‐relevant target is much more likely to occur at the uncued location. These findings, along with other evidence, have been taken to suggest that gaze represents a “special” stimulus—the foundation of a social cognition system that can make inferences about the mental states of other people. However, gaze‐driven cueing effects could simply be due to spatial compatibility between cue and target. We compared the attentional effects of gaze shifts to a face with the tongue extended laterally to the left or right. When tongue direction was a nonpredictive cue, we found cueing effects from tongues that were indistinguishable from those produced by gaze. However, in contrast to previous findings with gaze, tongue cues did not overcome a validity manipulation in which targets were four times more likely to appear at the uncued location. We conclude that simple attentional cueing effects from gaze may be better explained by spatial compatibility, and that more complex, unique features of cueing from gaze may be better indices into perceptual systems specialized for social cognition.

Neural and Behavioral Effects of a Novel Mu Opioid Receptor Antagonist in Binge-Eating Obese People

Background Binge eating is associated with obesity and has been conceptualized as “food addiction.” However, this view has received only inconsistent support in humans, and limited evidence relates key neurocircuitry to the disorder. Moreover, relatively few studies have used pharmacologic functional magnetic resonance imaging to probe the underlying basis of altered eating behaviors. Methods In a double-blind, placebo-controlled, parallel group study, we explored the effects of a potent mu-opioid receptor antagonist, GSK1521498, in obese individuals with moderate binge eating. Subjects were tested during a baseline placebo run-in period and retested after 28-days of drug (n = 21) or placebo (n = 21) treatment. Using functional magnetic resonance imaging and behavioral measures, we determined the drug’s effects on brain responses to food images and, separately, on motivation to expend energy to view comparable images. Results Compared with placebo, GSK1521498 was associated with a significant reduction in pallidum/putamen responses to pictures of high-calorie food and a reduction in motivation to view images of high-calorie food. Intriguingly, although motivational responding was reduced, subjective liking for the same images actually increased following drug treatment. Conclusions Stimulus-specific putamen/pallidal responses in obese people with binge eating are sensitive to altered mu-opioid function. This neuromodulation was accompanied by reductions in motivational responding, as measured by grip force, although subjective liking responses to the same stimuli actually increased. As well as providing evidence for a link between the opioid system and food-related behavior in binge-eating obese individuals, these results support a dissociation across measures of motivation and liking associated with food-related stimuli in these individuals.

Neuroanatomical Abnormalities and Cognitive Impairments Are Shared by Adults with Attention-Deficit/Hyperactivity Disorder and Their Unaffected First-Degree Relatives

Background Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder, yet the search for genes with a definitive role in its etiology has been elusive. Deconstructing the disorder in its endophenotypic traits, where the variance is thought to be associated with a fewer number of genes, should boost the statistical power of molecular genetic studies and clarify the pathophysiology of ADHD. In this study, we tested for neuroanatomical and cognitive endophenotypes in a group of adults with ADHD, their unaffected first-degree relatives, and typically developing control subjects. Methods Sixty participants, comprising 20 adults with ADHD, 20 unaffected first-degree relatives, and 20 typically developing control subjects matched for age and gender undertook structural magnetic resonance imaging scans. Voxel-based morphometry with DARTEL was performed to obtain regional gray and white matter volumes. General linear analyses of the volumes of brain regions, adjusting for age and total intracranial volume, were used to compare groups. Sustained attention and response inhibition were also investigated as cognitive endophenotypes. Results Neuroanatomical abnormalities in gray matter volume in the right inferior frontal gyrus and white matter volume in the caudal portion of the right inferior fronto-occipital fasciculus were shared between ADHD probands and their unaffected first-degree relatives. In addition, impairments in sustained attention were also found to be shared between ADHD patients and their relatives. Conclusions Cognitive impairments in sustained attention and neuroanatomical abnormalities in the right inferior frontal gyrus and the posterior part of right inferior fronto-occipital fasciculus are putative neurocognitive endophenotypes in adult ADHD.

The effects of the dopamine D? receptor antagonist GSK598809 on attentional bias to palatable food cues in overweight and obese subjects

The mesolimbic dopamine system plays a critical role in the reinforcing effects of rewards. Evidence from pre-clinical studies suggests that D₃ receptor antagonists may attenuate the motivational impact of rewarding cues. In this study we examined the acute effects of the D₃ receptor antagonist GSK598809 on attentional bias to rewarding food cues in overweight to obese individuals (n=26, BMI mean=32.7±3.7, range 27-40 kg/m²) who reported binge and emotional eating. We also determined whether individual differences in restrained eating style modulated the effects of GSK598809 on attentional bias. The study utilized a randomized, double-blind, placebo-controlled cross-over design with each participant tested following acute administration of placebo and GSK598809 (175 mg). Attentional bias was assessed by the visual probe task and modified Stroop task using food-related words. Overall GSK598809 had no effects on attentional bias in either the visual probe or food Stroop tasks. However, the effect of GSK598809 on both visual probe and food Stroop attentional bias scores was inversely correlated with a measure of eating restraint allowing the identification of two subpopulations, low- and high-restrained eaters. Low-restrained eaters had a significant attentional bias towards food cues in both tasks under placebo, and this was attenuated by GSK598809. In contrast, high-restrained eaters showed no attentional bias to food cues following either placebo or GSK598809. These findings suggest that excessive attentional bias to food cues generated by individual differences in eating traits can be modulated by D₃ receptor antagonists, warranting further investigation with measures of eating behaviour and weight loss.

The potent M1 receptor allosteric agonist GSK1034702 improves episodic memory in humans in the nicotine abstinence model of cognitive dysfunction

Episodic memory deficits are a core feature of neurodegenerative disorders. Muscarinic M(1) receptors play a critical role in modulating learning and memory and are highly expressed in the hippocampus. We examined the effect of GSK1034702, a potent M(1) receptor allosteric agonist, on cognitive function, and in particular episodic memory, in healthy smokers using the nicotine abstinence model of cognitive dysfunction. The study utilized a randomized, double-blind, placebo-controlled, cross-over design in which 20 male nicotine abstained smokers were tested following single doses of placebo, 4 and 8 mg GSK1034702. Compared to the baseline (nicotine on-state), nicotine abstinence showed statistical significance in reducing immediate (p=0.019) and delayed (p=0.02) recall. GSK1034702 (8 mg) significantly attenuated (i.e. improved) immediate recall (p=0.014) but not delayed recall. None of the other cognitive domains was modulated by either nicotine abstinence or GSK1034702. These findings suggest that stimulating M(1) receptor mediated neurotransmission in humans with GSK1034702 improves memory encoding potentially by modulating hippocampal function. Hence, selective M(1) receptor allosteric agonists may have therapeutic benefits in disorders of impaired learning including Alzheimers disease.