Working memory gating in obesity: Insights from a case-control fMRI study.

Computational models and neurophysiological data propose that a 'gating mechanism' coordinates distractor-resistant maintenance and flexible updating of working memory contents: While maintenance of information is mainly implemented in the prefrontal cortex, updating of information is signaled by phasic increases in dopamine in the striatum. Previous literature demonstrates structural and functional alterations in these brain areas, as well as differential dopamine transmission among individuals with obesity, suggesting potential impairments in these processes. To test this hypothesis, we conducted an observational case-control fMRI study, dividing participants into groups with and without obesity based on their BMI. We probed maintenance and updating of working memory contents using a modified delayed match to sample task and investigated the effects of SNPs related to the dopaminergic system. While the task elicited the anticipated brain responses, our findings revealed no evidence for group differences in these two processes, neither at the neural level nor behaviorally. However, depending on Taq1A genotype, which affects dopamine receptor density in the striatum, participants with obesity performed worse on the task. In conclusion, this study does not support the existence of overall obesity-related differences in working memory gating. Instead, we propose that potentially subtle alterations may manifest specifically in individuals with a 'vulnerable' genotype.

Effects of cholinesterase inhibition on attention and working memory in Lewy body dementias.

Cholinesterase inhibitors are frequently used to treat cognitive symptoms in Lewy body dementias (Parkinson's disease dementia and dementia with Lewy bodies). However, the selectivity of their effects remains unclear. In a novel rivastigmine withdrawal design, Parkinson's disease dementia and dementia with Lewy bodies patients were tested twice: once when taking rivastigmine as usual and once when they had missed one dose. In each session, they performed a suite of tasks (sustained attention, simple short-term recall, distractor resistance and manipulating the focus of attention) that allowed us to investigate the cognitive mechanisms through which rivastigmine affects attentional control. Consistent with previous literature, rivastigmine withdrawal significantly impaired attentional efficacy (quicker response latencies without a change in accuracy). However, it had no effects on cognitive control as assessed by the ability to withhold a response (inhibitory control). Worse short-term memory performance was also observed when patients were OFF rivastigmine, but these effects were delay and load independent, likely due to impaired visual attention. In contrast to previous studies that have examined the effects of dopamine withdrawal, cognitively complex tasks requiring control over the contents of working memory (ignoring, updating or shifting the focus of attention) were not significantly impaired by rivastigmine withdrawal. Cumulatively, these data support that the conclusion that cholinesterase inhibition has relatively specific and circumscribed-rather than global-effects on attention that may also affect performance on simple short-term memory tasks, but not when cognitive control over working memory is required. The results also indicate that the withdrawal of a single dose of rivastigmine is sufficient to reveal these impairments, demonstrating that cholinergic withdrawal can be an informative clinical as well as an investigative tool.

Foraging behaviour affects nest architecture in a cross-species comparison of ant nests.

Animals construct and inhabit nests that can exhibit dramatic intra- and interspecific variation due to differences in behaviour, the biotic and abiotic environment, and evolutionary history. In ants, variation in nest architecture reflects both differences in ecology and in the collective behaviour of the colonies that live in the nests. Each component of the nest (such as depth, and the number, size and connectivity of chambers) reflects selective pressures for different functions, or structural constraints that are imposed by the environment or evolutionary history. To determine potential drivers of nest structure variation in subterranean nests, we performed a meta-analysis of measures of published ant nests to compare different structural elements within and across species. We complemented this survey with 42 nest casts of two closely related species. We quantified nest features that can potentially impact ant foraging behaviour and examined whether phylogeny or foraging strategy are better explanatory variables for the variation we observed. We found that foraging strategy better explained nest features than evolutionary history. Our work reveals the importance of ecology in shaping nest structure and provides an important foundation for future investigations into the selective pressures that have shaped ant nest architecture. This article is part of the theme issue 'The evolutionary ecology of nests: a cross-taxon approach'.

Self-reported intake of high-fat and high-sugar diet is not associated with cognitive stability and flexibility in healthy men.

Animal studies indicate that a high-fat/high-sugar diet (HFS) can change dopamine signal transmission in the brain, which could promote maladaptive behavior and decision-making. Such diet-induced changes may also explain observed alterations in the dopamine system in human obesity. Genetic variants that modulate dopamine transmission have been proposed to render some individuals more prone to potential effects of HFS. The objective of this study was to investigate the association of HFS with dopamine-dependent cognition in humans and how genetic variations might modulate this potential association. Using a questionnaire assessing the self-reported consumption of high-fat/high-sugar foods, we investigated the association with diet by recruiting healthy young men that fall into the lower or upper end of that questionnaire (low fat/sugar group: LFS, n = 45; high fat/sugar group: HFS, n = 41) and explored the interaction of fat and sugar consumption with COMT Val158Met and Taq1A genotype. During functional magnetic resonance imaging (fMRI) scanning, male participants performed a working memory (WM) task that probes distractor-resistance and updating of WM representations. Logistic and linear regression models revealed no significant difference in WM performance between the two diet groups, nor an interaction with COMT Val158Met or Taq1A genotype. Neural activation in task-related brain areas also did not differ between diet groups. Independent of diet group, higher BMI was associated with lower overall accuracy on the WM task. This cross-sectional study does not provide evidence for diet-related differences in WM stability and flexibility in men, nor for a predisposition of COMT Val158Met or Taq1A genotype to the hypothesized detrimental effects of an HFS diet. Previously reported associations of BMI with WM seem to be independent of HFS intake in our male study sample.

Mechanisms underlying corruption of working memory in Parkinson's disease.

Working memory (WM) impairments are reported to occur in patients with Parkinson's disease (PD). However, the mechanisms are unclear. Here, we investigate several putative factors that might drive poor performance, by examining the precision of recall, the order in which items are recalled and whether memories are corrupted by random guessing (attentional lapses). We used two separate tasks that examined the quality of WM recall under different loads and retention periods, as well as a traditional digit span test. Firstly, on a simple measure of WM recall, where patients were asked to reproduce the orientation of a centrally presented arrow, overall recall was not significantly impaired. However, there was some evidence for increased guessing (attentional lapses). On a new analogue version of the Corsi-span task, where participants had to reproduce on a touchscreen the exact spatial pattern of presented stimuli in the order and locations in which they appeared, there was a reduction in the precision of spatial WM at higher loads. This deficit was due to misremembering item order. At the highest load, there was reduced recall precision, whereas increased guessing was only observed at intermediate set sizes. Finally, PD patients had impaired backward, but not forward, digit spans. Overall, these results reveal the task- and load-dependent nature of WM deficits in PD. On simple low-load tasks, attentional lapses predominate, whereas at higher loads, in the spatial domain, the corruption of mnemonic information-both order item and precision-emerge as the main driver of impairment.

Preliminary evidence that caffeine improves attention in multiple sclerosis.

There are no licensed drugs to boost cognitive performance in multiple sclerosis (MS). Here, we provide preliminary evidence that caffeine can improve attention in people with MS. Participants were tested on three different metrics of attentional functioning [choice reaction times, Stroop performance and a Rapid Serial Visual Presentation (RSVP) task] repeated across four sessions (baseline, one week after caffeine abstention and two sessions on days 8 and 9 where participants were pseudorandomized to receive counterbalanced caffeine or decaffeinated products). The administration of caffeine, compared to decaffeinated substances, was found to selectively reduce the 'attentional blink' in MS patients. There was no evidence that caffeine administration significantly affected performance on the Stroop or choice reaction time tasks. However, in contrast to other metrics of attention used in this study, there was evidence that Stroop performance declined on day 7 compared to day 1, an effect perhaps due to caffeine withdrawal. Cumulatively, these results suggest that caffeine can act as a cognitive enhancer in MS but may only benefit patients under situations of high attentional demand (RSVP dual task). Interestingly, there may be long-term positive effects of caffeine on cognition in MS that are only exposed following sustained abstinence periods.

Harvester ant nest architecture is more strongly affected by intrinsic than extrinsic factors.

Behavior is shaped by genes, environment, and evolutionary history in different ways. Nest architecture is an extended phenotype that results from the interaction between the behavior of animals and their environment. Nests built by ants are extended phenotypes that differ in structure among species and among colonies within a species, but the source of these differences remains an open question. To investigate the impact of colony identity (genetics), evolutionary history (species), and the environment on nest architecture, we compared how two species of harvester ants, Pogonomyrmex californicus and Veromessor andrei, construct their nests under different environmental conditions. For each species, we allowed workers from four colonies to excavate nests in environments that differed in temperature and humidity for seven days. We then created casts of each nest to compare nest structures among colonies, between species, and across environmental conditions. We found differences in nest structure among colonies of the same species and between species. Interestingly, however, environmental conditions did not have a strong influence on nest structure in either species. Our results suggest that extended phenotypes are shaped more strongly by internal factors, such as genes and evolutionary history, and are less plastic in response to the abiotic environment, like many physical and physiological phenotypes.

Caffeine and attentional control: improved and impaired performance in healthy older adults and Parkinson's disease according to task demands.

INTRODUCTION: Caffeine is frequently consumed to boost goal-directed attention. These procognitive effects may occur due to the adenosine-mediated enhancement of monoamines, such as dopamine, after caffeine administration. As such, caffeine's beneficial effects may be altered in conditions such as Parkinson's disease (PD). However, whether caffeine improves cognition, and at what cost, has not been experimentally established in patients with neurodegenerative disease. METHODS: Single-dose trials to probe cognitive effects of caffeine are often confounded by short-term caffeine abstinence which conflates caffeine's effects with treatment of withdrawal. Using a placebo controlled, blinded, randomised trial design, we assessed the effect of 100 mg of caffeine across well-established tasks (Choice reaction time, Stroop Task and Rapid Serial Visual Presentation Task; RSVP) that probe different aspects of attention in PD patients (n = 24) and controls (n = 44). Critically, participants withdrew from caffeine for a week prior to testing to eliminate the possibility that withdrawal reversal explained any cognitive benefit. RESULTS: Caffeine administration was found to reduce the overall number of errors in patients and controls on the Stroop (p = .018, η2p = .086) and Choice reaction time (p < . 0001, η2p = .588) tasks, but there was no specific effect of caffeine on ignoring irrelevant information in the Stroop task. On the RSVP task, caffeine improved dual item accuracy (p = .037) but impaired single item accuracy (p = .044). Across all tasks, there was little evidence that caffeine has different effects in PD participants and controls. CONCLUSION: When removing withdrawal effects as a factor, we demonstrate caffeine has beneficial effects on selective attention but is a double-edge sword for visual temporal attention and would need careful targeting to be clinically useful.

Modularity and connectivity of nest structure scale with colony size.

Large body sizes have evolved structures to facilitate resource transport. Like unitary organisms, social insect colonies must transport information and resources. Colonies with more individuals may experience transport challenges similar to large-bodied organisms. In ant colonies, transport occurs in the nest, which may consist of structures that facilitate movement. We examine three attributes of nests that might have evolved to mitigate transport challenges related to colony size: (1) subdivision-nests of species with large colonies are more subdivided to reduce crowd viscosity; (2) branching-nest tunnels increase branching in species with large colonies to reduce travel distances; and (3) shortcuts-nests of species with large colonies have cross-linking tunnels to connect distant parts of the nest and create alternative routes. We test these hypotheses by comparing nest structures of species with different colony sizes in phylogenetically controlled meta-analyses. Our findings support the hypothesis that nest subdivision and branching evolved to mitigate transport challenges related to colony size. Nests of species with large colonies contain more chambers and branching tunnels. The similarity in how ant nests and bodies of unitary organisms have evolved in response to increasing size suggests common solutions across taxa and levels of biological organization.

The benefits of being big and diverse: early colony survival in harvester ants.

In sessile organisms such as plants and benthic invertebrates, founding propagules typically suffer extremely high rates of mortality due to both extrinsic and intrinsic factors. Many social insect species share similarities with these groups, but factors influencing early colony survival are relatively unstudied. We used a field experiment to measure the importance of environmental quality relative to intrinsic colony properties in the harvester ant, Pogonomyrmex occidentalis, by monitoring the survival of 584 experimental colonies. We measured survival of transplanted colonies over four months in each of three years (2014-2016) at a site in western Colorado. Colony survival was primarily determined by colony features. Multiple mating by the queen and larger colony size at the time of transplant increased survival, but queen size, maternal lineage and the composition of plant species in the vicinity of the colony did not. Food supplementation increased survival significantly when natural food was scarce, but was not consistently beneficial, in contrast to predictions. Our results emphasize the general importance of rapid growth and early attainment of large size in the survival of sessile species. However, attributes specific to ants that are a consequence of their sociality also strongly affected survival. Colonies with multiply-mated queens were more likely to survive over a wide range of circumstances, highlighting the importance of this trait even at the early stages of colony life.

T2 heterogeneity as an in vivo marker of microstructural integrity in medial temporal lobe subfields in ageing and mild cognitive impairment.

A better understanding of early brain changes that precede loss of independence in diseases like Alzheimer's disease (AD) is critical for development of disease-modifying therapies. Quantitative MRI, such as T2 relaxometry, can identify microstructural changes relevant to early stages of pathology. Recent evidence suggests heterogeneity of T2 may be a more informative MRI measure of early pathology than absolute T2. Here we test whether T2 markers of brain integrity precede the volume changes we know are present in established AD and whether such changes are most marked in medial temporal lobe (MTL) subfields known to be most affected early in AD. We show that T2 heterogeneity was greater in people with mild cognitive impairment (MCI; n = 49) compared to healthy older controls (n = 99) in all MTL subfields, but this increase was greatest in MTL cortices, and smallest in dentate gyrus. This reflects the spatio-temporal progression of neurodegeneration in AD. T2 heterogeneity in CA1-3 and entorhinal cortex and volume of entorhinal cortex showed some ability to predict cognitive decline, where absolute T2 could not, however further studies are required to verify this result. Increases in T2 heterogeneity in MTL cortices may reflect localised pathological change and may present as one of the earliest detectible brain changes prior to atrophy. Finally, we describe a mechanism by which memory, as measured by accuracy and reaction time on a paired associate learning task, deteriorates with age. Age-related memory deficits were explained in part by lower subfield volumes, which in turn were directly associated with greater T2 heterogeneity. We propose that tissue with high T2 heterogeneity represents extant tissue at risk of permanent damage but with the potential for therapeutic rescue. This has implications for early detection of neurodegenerative diseases and the study of brain-behaviour relationships.

Impact of processing demands at encoding, maintenance and retrieval in visual working memory.

There has been surprisingly little examination of how recall performance is affected by processing demands induced by retrieval cues, how manipulations at encoding interact with processing demands during maintenance or due to the retrieval cue, and how these are affected with aging. Here, we investigate these relationships by examining the fidelity of working memory recall across two delayed reproduction tasks with a continuous measure of report across the adult lifespan. Participants were asked to remember and subsequently reproduce from memory the identity and location of a probed item from the encoding display. In Experiment 1, we examined the effect of filtering irrelevant information at encoding and the impact of filtering distracting information at retrieval simultaneously. In Experiment 2, we tested how ignoring distracting information during maintenance or updating current contents with new information during this period affects recall. The results reveal that manipulating processing requirements induced by retrieval cues (by altering the nature of the retrieval foil) had a significant impact on memory recall: the presence of two previously viewed features from the encoding display in the retrieval foil led to a decrease in identification accuracy. Although irrelevant information can be filtered out well at encoding, both ignoring irrelevant information and updating the contents of memory during the maintenance delay had a detrimental effect on recall. These effects were similar across the lifespan, but older individuals were particularly affected by manipulations of processing demands at encoding as well as increasing set size of information to be retained in memory. Finally, analyses revealed that there were no systematic relationships between filtering performance at encoding, maintenance and retrieval suggesting that these processing demands are independent of each other. Rather than filtering being a single, monolithic entity, the data suggest that it is better accounted for as distinctly dissociable cognitive processes that engage and articulate with different phases of working memory.

Reduced decision bias and more rational decision making following ventromedial prefrontal cortex damage.

Human decisions are susceptible to biases, but establishing causal roles of brain areas has proved to be difficult. Here we studied decision biases in 17 people with unilateral medial prefrontal cortex damage and a rare patient with bilateral ventromedial prefrontal cortex (vmPFC) lesions. Participants learned to choose which of two options was most likely to win, and then bet money on the outcome. Thus, good performance required not only selecting the best option, but also the amount to bet. Healthy people were biased by their previous bet, as well as by the unchosen option's value. Unilateral medial prefrontal lesions reduced these biases, leading to more rational decisions. Bilateral vmPFC lesions resulted in more strategic betting, again with less bias from the previous trial, paradoxically improving performance overall. Together, the results suggest that vmPFC normally imposes contextual biases, which in healthy people may actually be suboptimal in some situations.

A new toolbox to distinguish the sources of spatial memory error.

Studying the sources of errors in memory recall has proven invaluable for understanding the mechanisms of working memory (WM). While one-dimensional memory features (e.g., color, orientation) can be analyzed using existing mixture modeling toolboxes to separate the influence of imprecision, guessing, and misbinding (the tendency to confuse features that belong to different memoranda), such toolboxes are not currently available for two-dimensional spatial WM tasks. Here we present a method to isolate sources of spatial error in tasks where participants have to report the spatial location of an item in memory, using two-dimensional mixture models. The method recovers simulated parameters well and is robust to the influence of response distributions and biases, as well as number of nontargets and trials. To demonstrate the model, we fit data from a complex spatial WM task and show the recovered parameters correspond well with previous spatial WM findings and with recovered parameters on a one-dimensional analogue of this task, suggesting convergent validity for this two-dimensional modeling approach. Because the extra dimension allows greater separation of memoranda and responses, spatial tasks turn out to be much better for separating misbinding from imprecision and guessing than one-dimensional tasks. Code for these models is freely available in the MemToolbox2D package and is integrated to work with the commonly used MATLAB package MemToolbox.

Changes in six domains of cognitive function with reproductive and chronological ageing and sex hormones: a longitudinal study in 2411 UK mid-life women.

BACKGROUND: There may be changes in cognitive function in women going through the menopause. The current evidence remains unclear, however, whether these changes occur over and above those of general ageing. We aimed to evaluate the potential impact of the menopause (assessed by reproductive age and hormone levels) on cognitive function in women in mid-life accounting for the underlying effects of ageing. METHODS: The study was based on the follow up of women originally enrolled in pregnancy in a birth cohort when resident in the South West of England, UK between 1991 and 1992. Using up to three repeated measurements in 2411 women (mean age 51 at first assessment), we modelled changes in six cognitive function domains: immediate and delayed verbal episodic memory, working memory, processing speed, verbal intelligence and verbal fluency. The exposures of interest were reproductive age measured as years relative to the final menstrual period (FMP), chronological age and reproductive hormones (follicle-stimulating hormone (FSH), luteinizing hormone (LH) and anti-Müllerian hormone (AMH)). RESULTS: Processing speed (- 0.21 (95% CI - 0.36 to - 0.06) standard deviation (SD) difference per 10 years since FMP), immediate verbal episodic memory (- 0.15 (95% CI - 0.35 to 0.06)) and delayed verbal episodic memory (- 0.17 (95% CI - 0.37 to 0.03)) declined with reproductive age. Reproductive hormones were not robustly associated with processing speed, but FSH and LH were both negatively associated with immediate (- 0.08 (95% CI - 0.13 to - 0.02) SD difference per SD difference in hormone level) and delayed verbal episodic memory (- 0.08 (95% CI - 0.13 to - 0.03)). There was little consistent evidence of cognitive function declining with menopause in other cognitive domains. CONCLUSIONS: Of the cognitive domains tested only verbal episodic memory declined both in relation to age since the menopause and in conjunction with the reproductive hormones that reflect the menopause. This decline was independent of normal ageing and suggests that the menopause is associated with a mild impact on this specific domain of cognitive function.

Short-term memory advantage for brief durations in human APOE ε4 carriers.

The Apolipoprotein-E (APOE) ε4 gene allele, the highest known genetic risk factor for Alzheimer's disease, has paradoxically been well preserved in the human population. One possible explanation offered by evolutionary biology for survival of deleterious genes is antagonistic pleiotropy. This theory proposes that such genetic variants might confer an advantage, even earlier in life when humans are also reproductively fit. The results of some small-cohort studies have raised the possibility of such a pleiotropic effect for the ε4 allele in short-term memory (STM) but the findings have been inconsistent. Here, we tested STM performance in a large cohort of individuals (N = 1277); nine hundred and fifty-nine of which included carrier and non-carriers of the APOE ε4 gene, those at highest risk of developing Alzheimer's disease. We first confirm that this task is sensitive to subtle deterioration in memory performance across ageing. Importantly, individuals carrying the APOE ε4 gene actually exhibited a significant memory advantage across all ages, specifically for brief retention periods but crucially not for longer durations. Together, these findings present the strongest evidence to date for a gene having an antagonistic pleiotropy effect on human cognitive function across a wide age range, and hence provide an explanation for the survival of the APOE ε4 allele in the gene pool.

Dopamine Modulates Dynamic Decision-Making during Foraging.

The mesolimbic dopaminergic system exerts a crucial influence on incentive processing. However, the contribution of dopamine in dynamic, ecological situations where reward rates vary, and decisions evolve over time, remains unclear. In such circumstances, current (foreground) reward accrual needs to be compared continuously with potential rewards that could be obtained by traveling elsewhere (background reward rate), to determine the opportunity cost of staying versus leaving. We hypothesized that dopamine specifically modulates the influence of background, but not foreground, reward information when making a dynamic comparison of these variables for optimal behavior. On a novel foraging task based on an ecological account of animal behavior (marginal value theorem), human participants of either sex decided when to leave locations in situations where foreground rewards depleted at different rates, either in rich or poor environments with high or low background reward rates. In line with theoretical accounts, people's decisions to move from current locations were independently modulated by changes in both foreground and background reward rates. Pharmacological manipulation of dopamine D2 receptor activity using the agonist cabergoline significantly affected decisions to move on, specifically modulating the effect of background reward rates. In particular, when on cabergoline, people left patches in poor environments much earlier. These results demonstrate a role of dopamine in signaling the opportunity cost of rewards, not value per se. Using this ecologically derived framework, we uncover a specific mechanism by which D2 dopamine receptor activity modulates decision-making when foreground and background reward rates are dynamically compared.SIGNIFICANCE STATEMENT Many decisions, across economic, political, and social spheres, involve choices to "leave". Such decisions depend on a continuous comparison of a current location's value, with that of other locations you could move on to. However, how the brain makes such decisions is poorly understood. Here, we developed a computerized task, based around theories of how animals make decisions to move on when foraging for food. Healthy human participants had to decide when to leave collecting financial rewards in a location, and travel to collect rewards elsewhere. Using a pharmacological manipulation, we show that the activity of dopamine in the brain modulates decisions to move on, with people valuing other locations differently depending on their dopaminergic state.

Hemispheric Asymmetry of Globus Pallidus Relates to Alpha Modulation in Reward-Related Attentional Tasks.

Whereas subcortical structures such as the basal ganglia have been widely explored in relation to motor control, recent evidence suggests that their mechanisms extend to the domain of attentional switching. We here investigated the subcortical involvement in reward related top-down control of visual alpha-band oscillations (8-13 Hz), which have been consistently linked to mechanisms supporting the allocation of visuospatial attention. Given that items associated with contextual saliency (e.g., monetary reward or loss) attract attention, it is not surprising that the acquired salience of visual items further modulates. The executive networks controlling such reward-dependent modulations of oscillatory brain activity have yet to be fully elucidated. Although such networks have been explored in terms of corticocortical interactions, subcortical regions are likely to be involved. To uncover this, we combined MRI and MEG data from 17 male and 11 female participants, investigating whether derived measures of subcortical structural asymmetries predict interhemispheric modulation of alpha power during a spatial attention task. We show that volumetric hemispheric lateralization of globus pallidus (GP) and thalamus (Th) explains individual hemispheric biases in the ability to modulate posterior alpha power. Importantly, for the GP, this effect became stronger when the value saliency parings in the task increased. Our findings suggest that the GP and Th in humans are part of a subcortical executive control network, differentially involved in modulating posterior alpha activity in the presence of saliency. Further investigation aimed at uncovering the interaction between subcortical and neocortical attentional networks would provide useful insight in future studies.SIGNIFICANCE STATEMENT Whereas the involvement of subcortical regions into higher level cognitive processing, such as attention and reward attribution, has been already indicated in previous studies, little is known about its relationship with the functional oscillatory underpinnings of said processes. In particular, interhemispheric modulation of alpha band (8-13 Hz) oscillations, as recorded with magnetoencephalography, has been previously shown to vary as a function of salience (i.e., monetary reward/loss) in a spatial attention task. We here provide novel insights into the link between subcortical and cortical control of visual attention. Using the same reward-related spatial attention paradigm, we show that the volumetric lateralization of subcortical structures (specifically globus pallidus and thalamus) explains individual biases in the modulation of visual alpha activity.

Dopamine D2 receptor stimulation modulates the balance between ignoring and updating according to baseline working memory ability.

BACKGROUND: Working memory (WM) deficits in neuropsychiatric disorders have often been attributed to altered dopaminergic signalling. Specifically, D2 receptor stimulation is thought to affect the ease with which items can be gated into and out of WM. In addition, this effect has been hypothesised to vary according to baseline WM ability, a putative index of dopamine synthesis levels. Moreover, whether D2 stimulation affects WM vicariously through modulating relatively WM-free cognitive control processes has not been explored. AIMS: We examined the effect of administering a dopamine agonist on the ability to ignore or update information in WM. METHOD: A single dose of cabergoline (1 mg) was administered to healthy older adult humans in a within-subject, double-blind, placebo-controlled study. In addition, we obtained measures of baseline WM ability and relatively WM-free cognitive control (overcoming response conflict). RESULTS: Consistent with predictions, baseline WM ability significantly modulated the effect that drug administration had on the proficiency of ignoring and updating. High-WM individuals were relatively better at ignoring compared to updating after drug administration. Whereas the opposite occurred in low-WM individuals. Although the ability to overcome response conflict was not affected by cabergoline, a negative relationship between the effect the drug had on response conflict performance and ignoring was observed. Thus, both response conflict and ignoring are coupled to dopaminergic stimulation levels. CONCLUSIONS: Cumulatively, these results provide evidence that dopamine affects subcomponents of cognitive control in a diverse, antagonistic fashion and that the direction of these effects is dependent upon baseline WM.