Neuromodulation of Attention Thiele, Alexander; Bellgrove, Mark A.
Neuron (Cambridge, Mass.),
02/2018, Letnik:
97, Številka:
4
Journal Article
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Attention is critical to high-level cognition and attention deficits are a hallmark of neurologic and neuropsychiatric disorders. Although years of research indicates that distinct neuromodulators ...influence attentional control, a mechanistic account that traverses levels of analysis (cells, circuits, behavior) is missing. However, such an account is critical to guide the development of next-generation pharmacotherapies aimed at forestalling or remediating the global burden associated with disorders of attention. Here, we summarize current neuroscientific understanding of how attention affects single neurons and networks of neurons. We then review key results that have informed our understanding of how neuromodulation shapes these neuron and network properties and thereby enables the appropriate allocation of attention to relevant external or internal events. Finally, we highlight areas where we believe hypotheses can be formulated and tackled experimentally in the near future, thereby critically increasing our mechanistic understanding of how attention is implemented at the cellular and network levels.
Attention is a critical function that sculpts neuronal processing to benefit perception, decision making, and action. This review by Thiele and Bellgrove provides a state-of-the-art perspective on the contributions of different neuromodulators to the effects of attention on neuronal activity.
Inhibitory control describes the suppression of goal-irrelevant stimuli and behavioral responses. Current developmental taxonomies distinguish between Response Inhibition - the ability to suppress a ...prepotent motor response, and Attentional Inhibition - the ability to resist interference from distracting stimuli. Response Inhibition and Attentional Inhibition have exhibited moderately strong positive correlations in previous studies, suggesting they are closely related cognitive abilities. These results may reflect the use of cognitive tasks combining Stimulus-Stimulus- and Stimulus-Response-conflict as indicators of both constructs, which may have conflated their empirical association. Additionally, previous statistical modeling studies have not controlled for individual differences in Working Memory Capacity, which may account for some of the empirical overlap between Response Inhibition and Attentional Inhibition. The aim of the current study was to test a hierarchical model of inhibitory control that specifies Working Memory Capacity as a higher-order cognitive construct. Response Inhibition and Attentional Inhibition were conceptualized as lower-order cognitive mechanisms that should be empirically independent constructs apart from their shared reliance on Working Memory Capacity for active maintenance of goal-relevant representations. Measures of performance on modified stimulus-response compatibility tasks, complex memory span, and non-selective stopping tasks were obtained from 136 preadolescent children (
= 11 years, 10 months,
= 8 months). Consistent with hypotheses, results from Structural Equation Modeling demonstrated that the Response Inhibition and Attentional Inhibition factors were empirically independent constructs that exhibited partial statistical dependence on the Working Memory Capacity factor. These findings have important implications for current theories and models of inhibitory control during development.
The integration of modern neuroimaging methods with genetically informative designs and data can shed light on the molecular mechanisms underlying the structural and functional organization of the ...human connectome. Here, we review studies that have investigated the genetic basis of human brain network structure and function through three complementary frameworks: (1) the quantification of phenotypic heritability through classical twin designs; (2) the identification of specific DNA variants linked to phenotypic variation through association and related studies; and (3) the analysis of correlations between spatial variations in imaging phenotypes and gene expression profiles through the integration of neuroimaging and transcriptional atlas data. We consider the basic foundations, strengths, limitations, and discoveries associated with each approach. We present converging evidence to indicate that anatomical connectivity is under stronger genetic influence than functional connectivity and that genetic influences are not uniformly distributed throughout the brain, with phenotypic variation in certain regions and connections being under stronger genetic control than others. We also consider how the combination of imaging and genetics can be used to understand the ways in which genes may drive brain dysfunction in different clinical disorders.
Neural mechanisms of cognitive control enable us to initiate, coordinate and update behaviour. Central to successful control is the ability to suppress actions that are no longer relevant or ...required. In this article, we review the contribution of cognitive neuroscience, molecular genetics and clinical investigations to understanding how response inhibition is mediated in the human brain. In Section 1, we consider insights into the neural basis of inhibitory control from the effects of neural interference, neural dysfunction, and drug addiction. In Section 2, we explore the functional specificity of inhibitory mechanisms among a range of related processes, including response selection, working memory, and attention. In Section 3, we focus on the contribution of response inhibition to understanding flexible behaviour, including the effects of learning and individual differences. Finally, in Section 4, we propose a series of technical and conceptual objectives for future studies addressing the neural basis of inhibition.
Although the full aetiology of autism spectrum disorder (ASD) is unknown, familial and twin studies demonstrate high heritability of 60-90%, indicating a predominant role of genetics in the ...development of the disorder. The genetic architecture of ASD consists of a complex array of rare and common variants of all classes of genetic variation usually acting additively to augment individual risk. The relative contribution of heredity in ASD persists despite selective pressures against the classic autistic phenotype; a phenomenon thought to be explained, in part, by the incidence of spontaneous (or de novo) mutations. Notably, environmental exposures attributed as salient risk factors for ASD may play a causal role in the emergence of deleterious de novo variations, with several ASD-associated agents having significant mutagenic potential. To explore this hypothesis, this review article assesses published epidemiological data with evidence derived from assays of mutagenicity, both in vivo and in vitro, to determine the likely role such agents may play in augmenting the genetic liability in ASD. Broadly, these exposures were observed to elicit genomic alterations through one or a combination of: (1) direct interaction with genetic material; (2) impaired DNA repair; or (3) oxidative DNA damage. However, the direct contribution of these factors to the ASD phenotype cannot be determined without further analysis. The development of comprehensive prospective birth cohorts in combination with genome sequencing is essential to forming a causal, mechanistic account of de novo mutations in ASD that links exposure, genotypic alterations, and phenotypic consequences.
Epidemiological research links vitamin D status to various brain-related outcomes. However, few trials examine whether supplementation can improve such outcomes and none have examined effects on ...cognition. This study examined whether Vitamin D supplementation led to improvements in diverse measures of cognitive and emotional functioning, and hypothesised that supplementation would lead to improvements in these outcomes compared to placebo.
Healthy young adults were recruited to a parallel-arm, double-blind trial conducted at The University of Queensland. Participants were randomly allocated to receive Vitamin D (one capsule daily, containing 5000 IU cholecalciferol) or identical placebo capsule for six weeks. All participants and outcome assessors were blinded to group assignment. Primary outcome measures assessed at baseline and 6 weeks were working memory, response inhibition and cognitive flexibility. Secondary outcomes were: hallucination-proneness, psychotic-like experiences, and ratings of depression, anxiety and anger. 128 participants were recruited, randomised and included in primary analyses (vitamin D n = 63; placebo n = 65). Despite significant increases in vitamin D status in the active group, no significant changes were observed in working memory (F = 1.09; p = 0.30), response inhibition (F = 0.82; p = 0.37), cognitive flexibility (F = 1.37; p = 0.24) or secondary outcomes. No serious adverse effects were reported.
Our findings indicate that vitamin D supplementation does not influence cognitive or emotional functioning in healthy young adults. Future controlled trials in targeted populations of interest are required to determine whether supplementation can improve functioning in these domains. Australian and New Zealand Clinical Trials Registry; ACTRN12610000318088.
Brain network hubs are both highly connected and highly inter-connected, forming a critical communication backbone for coherent neural dynamics. The mechanisms driving this organization are poorly ...understood. Using diffusion-weighted magnetic resonance imaging in twins, we identify a major role for genes, showing that they preferentially influence connectivity strength between network hubs of the human connectome. Using transcriptomic atlas data, we show that connected hubs demonstrate tight coupling of transcriptional activity related to metabolic and cytoarchitectonic similarity. Finally, comparing over thirteen generative models of network growth, we show that purely stochastic processes cannot explain the precise wiring patterns of hubs, and that model performance can be improved by incorporating genetic constraints. Our findings indicate that genes play a strong and preferential role in shaping the functionally valuable, metabolically costly connections between connectome hubs.
Executive Function (EF) and Effortful Control (EC) have traditionally been viewed as distinct constructs related to cognition and temperament during development. More recently, EF and EC have been ...implicated in top‐down self‐regulation ‐ the goal‐directed control of cognition, emotion, and behavior. We propose that executive attention, a limited‐capacity attentional resource subserving goal‐directed cognition and behavior, is the common cognitive mechanism underlying the self‐regulatory capacities captured by EF and EC. We addressed three related questions: (a) Do behavioral ratings of EF and EC represent the same self‐regulation construct? (b) Is this self‐regulation construct explained by a common executive attention factor as measured by performance on cognitive tasks? and (c) Does the executive attention factor explain additional variance in attention deficit hyperactivity disorder (ADHD) problems to behavioral ratings of self‐regulation? Measures of performance on complex span, general intelligence, and response inhibition tasks were obtained from 136 preadolescent children (M = 11 years, 10 months, SD = 8 months), along with self‐ and parent‐reported EC, and parent‐reported EF, and ADHD problems. Results from structural equation modeling demonstrated that behavioral ratings of EF and EC measured the same self‐regulation construct. Cognitive tasks measured a common executive attention factor that significantly explained 30% of the variance in behavioral ratings of self‐regulation. Executive attention failed to significantly explain additional variance in ADHD problems beyond that explained by behavioral ratings of self‐regulation. These findings raise questions about the utility of task‐based cognitive measures in research and clinical assessment of self‐regulation and psychopathology in developmental samples.
A common executive attention construct, measured using cognitive assessments of working memory capacity, response inhibition, and general intelligence, explained 30% of the variance in behavioral ratings of self‐regulation, as measured by self‐ and parent‐reported effortful control and parent‐reported executive function. Task‐based measures of executive attention failed to explain statistically significant additional variance in the severity of parent‐reported attention deficit hyperactivity disorder problems to that explained by behavioral ratings of self‐regulation.
Objective
Understanding the unmet needs of healthcare consumers with attention‐deficit/hyperactivity disorder (ADHD) (individuals with ADHD and their caregivers) provides critical insight into gaps ...in services, education and research that require focus and funding to improve outcomes. This review examines the unmet needs of ADHD consumers from a consumer perspective.
Methods
A standardised search protocol identified peer‐reviewed studies published between December 2011 and December 2021 focusing on consumer‐identified needs relating to ADHD clinical care or research priorities.
Results
1,624 articles were screened with 23 studies that reviewed examining the needs of ADHD consumers from Europe, the U.K., Hong Kong, Iran, Australia, the U.S.A. and Canada. Consumer‐identified needs related to: treatment that goes beyond medication (12 studies); improved ADHD‐related education/training (17 studies); improved access to clinical services, carer support and financial assistance (14 studies); school accommodations/support (6 studies); and ongoing treatment efficacy research (1 study).
Conclusion
ADHD consumers have substantial unmet needs in clinical, psychosocial and research contexts. Recommendations to address these needs include: improving access to and quality of multimodal care provision; incorporating recovery principles into care provision; fostering ADHD health literacy; and increasing consumer participation in research, service development and ADHD‐related training/education.
•ADHD occurs in 5.9 % of youth and 2.5 % of adults.•Most cases of ADHD are caused by the combined effects of many genetic and environmental risks.•There are small differences in the brain between ...people with and without ADHD.•Untreated ADHD can lead to many adverse outcomes.•ADHD costs society hundreds of billions of dollars each year, worldwide.
Misconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base.
We reviewed studies with more than 2000 participants or meta-analyses from five or more studies or 2000 or more participants. We excluded meta-analyses that did not assess publication bias, except for meta-analyses of prevalence. For network meta-analyses we required comparison adjusted funnel plots. We excluded treatment studies with waiting-list or treatment as usual controls. From this literature, we extracted evidence-based assertions about the disorder.
We generated 208 empirically supported statements about ADHD. The status of the included statements as empirically supported is approved by 80 authors from 27 countries and 6 continents. The contents of the manuscript are endorsed by 366 people who have read this document and agree with its contents.
Many findings in ADHD are supported by meta-analysis. These allow for firm statements about the nature, course, outcome causes, and treatments for disorders that are useful for reducing misconceptions and stigma.
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