Objectives: Executive function deficits are major impairments in adults with attention deficit/hyperactivity disorder (ADHD). Previous studies have shown that the insula is involved in cognitive and executive functions. However, the insula is highly heterogeneous in function, and few studies have focused on functional networks which related to specific insular subregions in adults with ADHD. We explored the functional networks of the insular subregions (anterior insula [AI], mid insula [MI], and posterior insula [PI]). Furthermore, their correlations with self-ratings of ecological executive functions, including inhibition, shifting, and working memory were investigated. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data in 28 adults with ADHD and 30 matched healthy controls (HCs) were analyzed. The seed-based resting-state functional connectivity (RSFC) of the insular subregions were evaluated. We also investigated their associations with the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) inhibition, working memory, and shifting factor scores. Results: Compared with HCs, adults with ADHD showed altered RSFC of the AI, with the precuneus, precentral gyrus, and inferior temporal gyrus extended to the middle temporal gyrus, lingual gyrus and superior occipital gyrus, respectively. There were no significant differences in RSFC of the MI and PI between the two groups. Within the HC group, working memory scores were associated with the RSFC of AI with precuneus and temporal gyrus. However, there was no correlation between these variables in the ADHD group. Conclusion: The study evaluated RSFC patterns of the insular subregions in adults with ADHD for the first time. Altered RSFC of the anterior insula which is a crucial region of salience network (SN) and part of regions in default mode network (DMN), were detected in adults with ADHD in both results with and without global signal regression (GSR), suggesting that disrupted SN-DMN functional connectivity may be involved in EF impairments in adults with ADHD, especially with respect to working memory. Deficits of the anterior insula which is involved in salient stimuli allocation, might be associated with the pathophysiology of ADHD. The inconsistent results of MI and PI between analyses with and without GSR need further exploration.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder in children, usually categorized as three subtypes, predominant inattention (ADHD-I), predominant hyperactivity-impulsivity (ADHD-HI), and a combined subtype (ADHD-C). Yet, common and unique abnormalities of electroencephalogram (EEG) across different subtypes remain poorly understood. Here, we leveraged microstate characteristics and power features to investigate temporal and frequency abnormalities in ADHD and its subtypes using high-density EEG on 161 participants (54 ADHD-Is and 53 ADHD-Cs and 54 healthy controls). Four EEG microstates were identified. The coverage of salience network (state C) were decreased in ADHD compared to HC (p = 1.46e-3), while the duration and contribution of frontal–parietal network (state D) were increased (p = 1.57e-3; p = 1.26e-4). Frequency power analysis also indicated that higher delta power in the fronto-central area (p = 6.75e-4) and higher power of theta/beta ratio in the bilateral fronto-temporal area (p = 3.05e-3) were observed in ADHD. By contrast, remarkable subtype differences were found primarily on the visual network (state B), of which ADHD-C have higher occurrence and coverage than ADHD-I (p = 9.35e-5; p = 1.51e-8), suggesting that children with ADHD-C might exhibit impulsivity of opening their eyes in an eye-closed experiment, leading to hyper-activated visual network. Moreover, the top discriminative features selected from support vector machine model with recursive feature elimination (SVM-RFE) well replicated the above results, which achieved an accuracy of 72.7% and 73.8% separately in classifying ADHD and two subtypes. To conclude, this study highlights EEG microstate dynamics and frequency features may serve as sensitive measurements to detect the subtle differences in ADHD and its subtypes, providing a new window for better diagnosis of ADHD.

Attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood, with a shift of symptoms including less hyperactivity/impulsivity and more co-morbidity of affective disorders in ADHD_adult. Many studies have questioned the stability in diagnosing of ADHD from childhood to adulthood, and the shared and distinct aberrant functional connectivities (FCs) between ADHD_child and ADHD_adult remain unidentified. We aim to explore shared and distinct FC patterns in ADHD_child and ADHD_adult, and further investigated the cross-cohort predictability using the identified FCs. After investigating the ADHD-discriminative FCs from healthy controls (HCs) in both child (34 ADHD_child, 28 HCs) and adult (112 ADHD_adult,77 HCs) cohorts, we identified both shared and distinct aberrant FC patterns between cohorts and their association with clinical symptoms. Moreover, the cross-cohort predictability using the identified FCs were tested. The ADHD-HC classification accuracies were 84.4% and 81.0% for children and male adults, respectively. The ADHD-discriminative FCs shared in children and adults lie in the intra-network within default mode network (DMN) and the inter-network between DMN and ventral attention network, positively correlated with total scores of ADHD symptoms. Particularly, inter-network FC between somatomotor network and dorsal attention network was uniquely impaired in ADHD_child, positively correlated with hyperactivity index; whereas the aberrant inter-network FC between DMN and limbic network exhibited more adult-specific ADHD dysfunction. And their cross-cohort predictions were 70.4% and 75.6% between each other. This work provided imaging evidence for symptomatic changes and pathophysiological continuity in ADHD from childhood to adulthood, suggesting that FCs may serve as potential biomarkers for ADHD diagnosis.

Working memory impairment is a typical cognitive abnormality in patients with attention-deficit/hyperactivity disorder (ADHD) and is closely related to attention. Exploring the interaction between working memory and attention in patients with ADHD is of great significance for studying the pathological mechanism of this disease. In this study, electrophysiological markers of attention, posterior contralateral N2 (N2pc), and working memory, contralateral delay activity (CDA), were used to explore the relationship between these two cognitive abilities in patients with ADHD. EEG data were collected from adults with ADHD and age-, sex-, and IQ-matched normal controls while performing a classical visuospatial working memory task that consisted of low-load and high-load memory conditions. In different memory load conditions, the memory array elicited a smaller N2pc (220-260 ms) and a smaller CDA (400-800 ms) in adults with ADHD than in normal controls. Further analysis revealed that the reduced CDA amplitude could be significantly predicted by the earlier and reduced N2pc amplitude in adults with ADHD. Moreover, when the number of memory items increased, the increase in N2pc highly predicted the increases in CDA. Our findings illustrate the relationship between spatial working memory and attention ability in ADHD adults from the neurophysiological aspect that reduced working memory is closely related to insufficient attention ability and provide a potential physiological basis for the pathological mechanism of ADHD.

Objective: This study evaluated the functional networks of amygdala subregions (basolateral [BLA], centromedial [CMA], and superficial amygdala [SFA]) in ADHD and their association with emotional lability (EL) symptoms. Method: Resting-state functional connectivity (RSFC) of amygdala subregions and their correlations with EL scores were evaluated in 35 drug-naïve boys with ADHD and 30 age-matched healthy controls (HC). Results: Compared with HC, altered RSFC were detected differently for each amygdala subregion in ADHD: altered RSFC of BLA with the thalamus and vermis; aberrant RSFC of CMA with the superior temporal gyrus/pole and insula, precuneus and cerebellum; reduced RSFC of SFA with dorsal frontoparietal cortices. Within ADHD, higher EL scores were associated with reduced negative RSFC of SFA with the dorsolateral prefrontal cortex and inferior parietal lobe. Conclusion: Diffuse alterations of amygdala subregion-based networks are associated with ADHD, and the weaker SFA–frontoparietal networks might be involved in the hypothesized top–down effortful regulation of emotion.