Altered Functional Brain Connectivity in a Non-Clinical Sample of Young Adults with Attention-Deficit/Hyperactivity Disorder

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is characterized by symptoms of inattention and hyperactivity/impulsivity that often persist in adulthood. There is a growing consensus that ADHD is associated with abnormal function of diffuse brain networks, but such alterations remain poorly characterized. Using resting-state functional magnetic resonance imaging, we characterized multivariate (complex network measures), bivariate (network-based statistic), and univariate (regional homogeneity) properties of brain networks in a non-clinical, drug-naive sample of high-functioning young men and women with ADHD (nine males, seven females) and a group of matched healthy controls. Data from our sample allowed the isolation of intrinsic functional connectivity alterations specific to ADHD diagnosis and symptoms that are not related to developmental delays, general cognitive dysfunction, or history of medication use. Multivariate results suggested that frontal, temporal, and occipital cortices were abnormally connected locally as well as with the rest of the brain in individuals with ADHD. Results from the network-based statistic supportandextendmultivariateresultsbyisolatingtwobrainnetworkscomprisingregionsbetweenwhichinter-regionalconnectivitywassignificantly alteredintheADHDgroup;namely,afrontalamygdala-occipitalnetworkandafrontaltemporal-occipitalnetwork.Brainbehaviorcorrelationsfurther highlightedthekeyroleofalteredorbitofrontal-temporalandfrontal-amygdalaconnectivityforsymptomsofinattentionandhyperactivity/impulsivity. All univariate properties were similar between groups. Taken together, results from this study show that the diagnosis and the two main symptom dimensions of ADHD are related to altered intrinsic connectivity in orbitofrontal-temporal-occipital and fronto-amygdala-occipital networks. Accordingly, our findings highlight the importance of extending the conceptualization of ADHD beyond segregated fronto-striatal alterations.

Inter-hemispherical asymmetry in default-mode functional connectivity and BAIAP2 gene are associated with anger expression in ADHD adults

“…From a neuroimaging viewpoint, compelling evidence points to rather large-scale abnormalities in network organization in ADHD (Sergeant et al, 2006;Konrad and Eickhoff, 2010;Cao et al, 2013), affecting both functional (Cocchi et al, 2012;Colby et al, 2012;Fair et al, 2012;Tomasi and Volkow, 2012;Cao et al, 2013;Di Martino et al, 2013) and structural (Cao et al, 2013;Hong et al, 2014) connectivity. Moreover, an abnormal hemispheric asymmetry of brain structure and function was also consistently reported in ADHD (Dennis and Thompson, 2013;Shang et al, 2013;Cao et al, 2014;Hale et al, 2014Hale et al, , 2015Keune et al, 2015;Silk et al, 2015), suggesting a possible neurodevelopmental scenario for this disorder.…”

Causal connectivity abnormalities of regional homogeneity in children with attention deficit hyperactivity disorder: a rest-state fMRI study

“…reduced volume and cortical thickness in frontal, anterior cingulate cortex [1], amygdala [2], hippocampus [3], cerebellum [4,5] and occipital [6,7]) and brain function (i.e. functional connectivity alterations among frontal-occipital, temporo-occipital [8,9], and frontal-striatal circuits networks [10,11]). Recently, resting-state functional magnetic resonance imaging (R-fMRI) has attracted increasing attention for mapping large-scale neural network function and dysfunction.…”

Functional network study on the wild type and DISC1 transgenic mice

“…ReHo is an attractive method when describing the brain with emphasis on focal clusters of voxels and when there is a need to extract information using univariate analytical approaches. The application of multi-scale analysis on the human brain function show that local connectivity helps to draw more sound conclusions on disease states (Cocchi et al, 2012b;Liu et al, 2014). The neighbour-to-neighbour connections are important for us to understand brain organizations (Jiang and Zuo, 2015), hence its application on mice may fill the gap of local FC between ongoing human research and studies on mouse models of brain disorders.…”

“…For the nodal attribute, a two-sample t test was performed for each of the 152 regions. After the multiple comparison tests, an alpha level of 1/n (p<0.01) was used to declare the significance for the local properties (Lynall et al, 2010;Cocchi et al, 2012b;Liu et al, 2014).…”

“…The most widely applied methods in human rs-fMRI studies can be classified into regional or global levels for the puporse of extracting complementary information (Zang et al, 2004;Li et al, 2009;Rubinov and Sporns, 2010;Cocchi et al, 2012b;Liu et al, 2014). Hence, delineating functional brain networks of transgenic mice using analytical methods in parallel with those widely applied in human rs-fMRI research will provide useful and insightful information on abnormal FC associated with gene dysfunctions.…”