Dysfunctional modulation of default mode network activity in attention-deficit/hyperactivity disorder.

Metin, Barış; Krebs, Ruth M.; Wiersema, Jan R.; Verguts, Tom; Gasthuys, Roos; Meere, Jaap J. van der; Achten, Eric; Roeyers, Herbert; Sonuga‐Barke, Edmund

doi:10.1037/abn0000013

Cited by 63 publications

(56 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A possibly useful but under-utilized endophenotype is the brain default mode network (DMN), consisting of several brain regions of interest (ROIs) remaining active in the resting state. Brain activity in DMN may explain the etiology of AD (Metin et al 2015), and is a plausible indicator for incipient AD (Damoiseaux et al 2012; Greicius et al 2004; He et al 2009; Jones et al 2011; Balthazar et al 2014). Since there is growing evidence that genetic factors play a role in aberrant default mode connectivity (Glahn et al 2010), it will be more powerful to detect genetic variants associated with AD by taking advantage of DMN as imaging endophenotypes.…”

Section: Introductionmentioning

confidence: 99%

Imaging-wide association study: Integrating imaging endophenotypes in GWAS

Pan

2017

NeuroImage

View full text Add to dashboard Cite

A new and powerful approach, called imaging-wide association study (IWAS), is proposed to integrate imaging endophenotypes with GWAS to boost statistical power and enhance biological interpretation for GWAS discoveries. IWAS extends the promising transcriptome-wide association study (TWAS) from using gene expression endophenotypes to using imaging and other endophenotypes with a much wider range of possible applications. As illustration, we use gray-matter volumes of several brain regions of interest (ROIs) drawn from the ADNI-1 structural MRI data as imaging endophenotypes, which are then applied to the individual-level GWAS data of ADNI-GO/2 and a large meta-analyzed GWAS summary statistics dataset (based on about 74000 individuals), uncovering some novel genes significantly associated with Alzheimer’s disease (AD). We also compare the performance of IWAS with TWAS, showing much larger numbers of significant AD-associated genes discovered by IWAS, presumably due to the stronger link between brain atrophy and AD than that between gene expression of normal individuals and the risk for AD. The proposed IWAS is general and can be applied to other imaging endophenotypes, and GWAS individual-level or summary association data.

show abstract

Section: Introductionmentioning

confidence: 99%

Imaging-wide association study: Integrating imaging endophenotypes in GWAS

Pan

2017

NeuroImage

View full text Add to dashboard Cite

show abstract

“…Neurofunctionally, it is dependent on the interplay of four canonical brain networks (Menon, 2011, Metin et al, 2015). First is the “task-positive” central executive network consisting of dorsolateral prefrontal cortex (DLPFC), inferior frontal gyrus (IFG), lateral parietal, and dorsal striato-thalamic regions, which is engaged during tasks requiring the active maintenance of attention toward external stimuli, mediates goal-directed selection of stimuli and responses, and is associated with adaptive performance on sustained attention tasks (Dosenbach et al, 2007, Petersen and Posner, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Both disorders have also been linked to increased spontaneous mind-wandering (Mowlem et al, 2016, Seli et al, 2016, Seli et al, 2015), which is proposed to reflect an imbalance between task-positive and default mode networks (Christakou et al, 2013, Metin et al, 2015), and to underlie poor performance on sustained attention tasks, as attention is focused on internal thoughts, thereby limiting attention resources available for task-relevant processing (Thomson et al, 2015). Moreover, both ADHD and OCD patients self-report impaired executive attention abilities (Armstrong et al, 2011, Benatti et al, 2014, Grassi et al, 2015, Malloy-Diniz et al, 2007, Nandagopal et al, 2011, Sohn et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Shared and disorder-specific task-positive and default mode network dysfunctions during sustained attention in paediatric Attention-Deficit/Hyperactivity Disorder and obsessive/compulsive disorder

Norman

Carlisi

Christakou

et al. 2017

NeuroImage: Clinical

View full text Add to dashboard Cite

Patients with Attention-Deficit/Hyperactivity Disorder (ADHD) and obsessive/compulsive disorder (OCD) share problems with sustained attention, and are proposed to share deficits in switching between default mode and task positive networks. The aim of this study was to investigate shared and disorder-specific brain activation abnormalities during sustained attention in the two disorders. Twenty boys with ADHD, 20 boys with OCD and 20 age-matched healthy controls aged between 12 and 18 years completed a functional magnetic resonance imaging (fMRI) version of a parametrically modulated sustained attention task with a progressively increasing sustained attention load. Performance and brain activation were compared between groups. Only ADHD patients were impaired in performance. Group by sustained attention load interaction effects showed that OCD patients had disorder-specific middle anterior cingulate underactivation relative to controls and ADHD patients, while ADHD patients showed disorder-specific underactivation in left dorsolateral prefrontal cortex/dorsal inferior frontal gyrus (IFG). ADHD and OCD patients shared left insula/ventral IFG underactivation and increased activation in posterior default mode network relative to controls, but had disorder-specific overactivation in anterior default mode regions, in dorsal anterior cingulate for ADHD and in anterior ventromedial prefrontal cortex for OCD. In sum, ADHD and OCD patients showed mostly disorder-specific patterns of brain abnormalities in both task positive salience/ventral attention networks with lateral frontal deficits in ADHD and middle ACC deficits in OCD, as well as in their deactivation patterns in medial frontal DMN regions. The findings suggest that attention performance in the two disorders is underpinned by disorder-specific activation patterns.

show abstract

“…The DMN is a network of brain regions that are active when an individual is at wakeful rest, which includes inferior temporal, medial orbitofrontal, parahippocampal, precuneus, and posterior cingulate ROIs (Greicius et al 2004). Importantly, DMN activity distinguishes cognitively impaired patients such as with Alzheimer's, attention deficit hyperactivity disorder (ADHD), or bipolar disorder from healthy controls (Greicius et al 2004;Buckner et al 2008;Meda et al 2014;Metin et al 2015). The gray matter volumetric measures related to the DMN were extracted from the ADNI-1 baseline data.…”

Section: Real Data Examplementioning

confidence: 99%

“…Many other genetic studies have been conducted, identifying multiple common and rare variants, shedding light on pathogenic mechanisms of AD (Marei et al 2015;Saykin et al 2015). In particular, the APOEe4 allele (Metin et al 2015) and is a plausible indicator for incipient AD (Damoiseaux et al 2012;Greicius et al 2004;He et al 2009;Jones et al 2011;Balthazar et al 2014). Since there is growing evidence that genetic factors play a role in aberrant default mode connectivity (Glahn et al 2010), it may be substantially more powerful to detect genetic variants associated with the DMN, a set of multiple intermediate phenotypes, than with AD.…”

mentioning

confidence: 99%

Powerful and Adaptive Testing for Multi-trait and Multi-SNP Associations with GWAS and Sequencing Data

Kim¹,

Zhang²,

Pan

2016

Genetics

View full text Add to dashboard Cite

Testing for genetic association with multiple traits has become increasingly important, not only because of its potential to boost statistical power, but also for its direct relevance to applications. For example, there is accumulating evidence showing that some complex neurodegenerative and psychiatric diseases like Alzheimer's disease are due to disrupted brain networks, for which it would be natural to identify genetic variants associated with a disrupted brain network, represented as a set of multiple traits, one for each of multiple brain regions of interest. In spite of its promise, testing for multivariate trait associations is challenging: if not appropriately used, its power can be much lower than testing on each univariate trait separately (with a proper control for multiple testing). Furthermore, differing from most existing methods for single-SNP-multiple-trait associations, we consider SNP set-based association testing to decipher complicated joint effects of multiple SNPs on multiple traits. Because the power of a test critically depends on several unknown factors such as the proportions of associated SNPs and of traits, we propose a highly adaptive test at both the SNP and trait levels, giving higher weights to those likely associated SNPs and traits, to yield high power across a wide spectrum of situations. We illuminate relationships among the proposed and some existing tests, showing that the proposed test covers several existing tests as special cases. We compare the performance of the new test with that of several existing tests, using both simulated and real data. The methods were applied to structural magnetic resonance imaging data drawn from the Alzheimer's Disease Neuroimaging Initiative to identify genes associated with gray matter atrophy in the human brain default mode network (DMN). For genomewide association studies (GWAS), genes AMOTL1 on chromosome 11 and APOE on chromosome 19 were discovered by the new test to be significantly associated with the DMN. Notably, gene AMOTL1 was not detected by single SNP-based analyses. To our knowledge, AMOTL1 has not been highlighted in other Alzheimer's disease studies before, although it was indicated to be related to cognitive impairment. The proposed method is also applicable to rare variants in sequencing data and can be extended to pathway analysis.KEYWORDS adaptive association test; ADNI; default mode network; gene-based test; imaging genetics; multiple traits A LZHEIMER'S disease (AD) (MIM 104300) is the most common neurodegenerative disease, and every 67 sec, someone in the United States develops AD (Alzheimer's Association 2015a). Currently there is no cure for AD, and most cases are diagnosed in the late stage of the disease. It is projected that the number of Americans of age 65 years and older with AD will increase from 5.1 million in 2015 to 13.5 million in 2050, a growth from an estimated 11% of the U.S. senior population in 2015 to 16% in 2050, costing .$1.1 trillion in 2050 (Alzheimer's Association 2015b). To advance our...

show abstract

Dysfunctional modulation of default mode network activity in attention-deficit/hyperactivity disorder.

Cited by 63 publications

References 33 publications

Imaging-wide association study: Integrating imaging endophenotypes in GWAS

Imaging-wide association study: Integrating imaging endophenotypes in GWAS

Shared and disorder-specific task-positive and default mode network dysfunctions during sustained attention in paediatric Attention-Deficit/Hyperactivity Disorder and obsessive/compulsive disorder

Powerful and Adaptive Testing for Multi-trait and Multi-SNP Associations with GWAS and Sequencing Data

Contact Info

Product

Resources

About