Mechanisms Of Attention-deficit Hyperactivity Disorder Research Articles

Face processing in ADHD: A review of the N170 event-related potential.

Attention-deficit hyperactivity disorder (ADHD) is associated with deficits in social functioning, including peer difficulties and poor relationship quality. Little is known, however, about the integrity of foundational sociocognitive abilities that support interpersonal interactions in ADHD. Face processing-a fundamental component of social cognition-has been a popular topic of recent investigations in this area. Researchers have attempted to delineate face processing mechanisms in ADHD to elucidate social deficits often seen in the disorder. Investigating the N170 event-related potential, a neural marker of face processing, has been a popular approach in this endeavour. Here, we present two accounts that offer competing views of how social deficits might arise in those with ADHD. Next, we systematically review and synthesise the literature on the N170 in ADHD to identify whether atypicalities in sociocognitive domains like face processing occur in this patient population. Gaps in the literature are identified and concrete solutions are offered to improve future research in this area. We end by discussing immediate implications for treatment approaches designed to address widely observed social deficits in individuals with ADHD. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Delineating early developmental pathways to ADHD: Setting an international research agenda.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent, impairing, and highly heritable condition typically diagnosed in middle childhood. However, it is now recognized that symptoms emerge much earlier in development. Research focused on understanding-using multiple units of analysis-the cascade of early-life (i.e., prenatal-infant-toddler) developmental changes that will later emerge as ADHD has the potential to transform early identification, prevention, and intervention. To this end, we introduce the recently established Early ADHD Consortium, an international network of investigators engaged in prospective, longitudinal studies of risk for ADHD beginning early in life, conducted within a developmental framework, and which incorporate multimethod approaches. This network seeks to harmonize measures and methodological approaches to increase the potential for data sharing and subsequent impact. This perspective paper highlights the importance of investigating pre-diagnostic markers of ADHD, and potential models and mechanisms of ADHD risk and development, with the long-term objective of facilitating development of preemptive interventions that will minimize the impact of ADHD symptoms on everyday functioning and maximize health and developmental outcomes. We selectively describe key challenges and questions for this field related to theoretical models and developmental mechanisms in ADHD and recommend next steps for the science, including methodological, measurement, and study design considerations. We then describe potential implications for preemptive intervention development. We conclude by considering other issues including ethical concerns and the critical value of incorporating stakeholder input. It is hoped that this perspective puts forth a research agenda that will enhance collaborative efforts and accelerate progress in understanding developmental mechanisms and the early ADHD phenotype, with implications for early intervention enhancement of healthy development for infants, young children, and their families.

Reinforcement and Compensatory Mechanisms in Attention-Deficit Hyperactivity Disorder: A Systematic Review of Case-Control Studies.

Attention-deficit hyperactivity disorder (ADHD) is a neuropsychological disorder that causes inattentiveness, hyperactivity, and impulsiveness in patients. Ventral striatal hypo-responsiveness, orbitofrontal cortex, and dopaminergic status in the brain are related to the pathogenesis of ADHD. Reinforcement tasks by monetary incentive delay (MID) was shown to produce more responsiveness in patients. In this study, we reviewed how reinforcement interventions and compensatory mechanisms affect the behavior of ADHD patients. This systematic review was undertaken as per the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, and PubMed database was used for literature search.The quality appraisal was completed using the Newcastle-Ottawa scale, and nine case-control studies were included in this systematic review. A total of 976 participants were included, with 493 cases and 330 controls. The studies included discuss reinforcement, attention networks, and compensatory mechanisms. Our review concludes that reinforcement improves responsiveness to gain and loss of rewards in ADHD patients. Reward processing is selectively associated with the salience network. While ADHD, predominantly the inattentive type, is insensitive to stimuli, ADHD combined type and controls showed similar responsiveness. The right visual cortex may also be related to compensatory mechanisms in ADHD. As we only included case-control studies from the last eight years, in the English language, we might have missed some relevant studies related to this research. Because the included studies have a relatively small sample size, we recommend future studies to explore larger cohorts of patients to improve the reliability of findings pertinent to this field.

Non-coding structural variation differentially impacts attention-deficit hyperactivity disorder (ADHD) gene networks in African American vs Caucasian children

Previous studies of attention-deficit hyperactivity disorder (ADHD) have suggested that structural variants (SVs) play an important role but these were mainly studied in subjects of European ancestry and focused on coding regions. In this study, we sought to address the role of SVs in non-European populations and outside of coding regions. To that end, we generated whole genome sequence (WGS) data on 875 individuals, including 205 ADHD cases and 670 non-ADHD controls. The ADHD cases included 116 African Americans (AA) and 89 of European Ancestry (EA) with SVs in comparison with 408 AA and 262 controls, respectively. Multiple SVs and target genes that associated with ADHD from previous studies were identified or replicated, and novel recurrent ADHD-associated SV loci were discovered. We identified clustering of non-coding SVs around neuroactive ligand-receptor interaction pathways, which are involved in neuronal brain function, and highly relevant to ADHD pathogenesis and regulation of gene expression related to specific ADHD phenotypes. There was little overlap (around 6%) in the genes impacted by SVs between AA and EA. These results suggest that SVs within non-coding regions may play an important role in ADHD development and that WGS could be a powerful discovery tool for studying the molecular mechanisms of ADHD

Elevated neutrophil-to-lymphocyte ratio in children and adolescents with attention-deficit/hyperactivity disorder

Objective Inflammation is reported to play a substantial role in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). Neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) are inexpensive and potentially interesting biomarkers of inflammation. In this cross-sectional and retrospective study, we investigated the relationship between NLR, PLR and ADHD. Methods This study consisted of 100 children and adolescents with ADHD (85 of those receiving psychopharmacological treatment), and 99 physically and mentally healthy children. Results The mean NLR and PLR were significantly higher in patients than in controls. There was no significant difference between patients who received psychopharmacological treatment for ADHD and patient that did not with regard to NLR and PLR. No associations were found between NLR and PLR and ADHD symptom severity. The significance of NLR is not influenced by medication use, age and sex. Conclusions Our findings suggest that NLR and PLR may be inflammation biomarkers in children and adolescents with ADHD. Moreover, the significance of NLR is not influenced by medication use, age and sex. Prospective studies that address alterations in NLR and PLR and other pro-inflammatory cytokines following ADHD treatment may provide additional information about the inflammatory mechanisms in ADHD. Key points The mean NLR and PLR were significantly higher in patients than in controls. The significance of NLR is not influenced by medication use, age and sex. No associations were found between NLR and PLR and ADHD symptom severity. Prospective studies that address alterations in NLR and PLR and other pro-inflammatory cytokines following psychopharmacological treatment of ADHD may provide additional information about the inflammatory mechanisms in ADHD

Habit Expression and Disruption as a Function of Attention-Deficit/Hyperactivity Disorder Symptomology.

Attention-deficit/hyperactivity disorder (ADHD) is associated with neurobehavioral reward system dysfunctions that pose debilitating impairments in adaptive decision-making. A candidate mechanism for such anomalies in ADHD may be a compromise in the control of motivated behaviors. Thus, demonstrating and restoring potential motivational control irregularities may serve significant clinical benefit. The motivational control of action guides goal-directed behaviors that are driven by outcome value, and habits that are inflexibly cue-triggered. We examined whether ADHD symptomology within the general population is linked to habitual control, and whether a motivation-based manipulation can break well-learned habits. We obtained symptom severity scores from 106 participants and administered a Go/NoGo task that capitalizes on familiar, well-learned associations (green-Go and red-NoGo) to demonstrate outcome-insensitivity when compared to newly learned Go/NoGo associations. We tested for outcome-insensitive habits by changing the Go and NoGo contingencies, such that Go signals became NoGo signals and vice versa. We found that generally, participants responded less accurately when green and red stimuli were mapped to color-response contingencies that were incongruent with daily experiences, whereas novel Go/NoGo stimuli evoked similar accuracy regardless of color-response mappings. Thus, our Go/NoGo task successfully elicited outcome-insensitive habits (i.e., persistent responses to familiar stimuli without regard for consequences); however, this effect was independent of ADHD symptomology. Nevertheless, we found an association between hyperactivity and congruent Go response latency, suggesting heightened pre-potency to perform habitual Go actions as hyperactivity increases. To examine habit disruption, participants returned to the lab and underwent the familiar version of the Go/NoGo task, but were given mid-experiment performance tracking information and a monetary incentive prior to contingency change. We found that this motivational boost via dual feedback prevented the incongruency-related accuracy impairment, effectively breaking the habit, albeit independent of ADHD symptomology. Our findings present only a modest link between ADHD symptomology and motivational control, which may be due to compensatory mechanisms in ADHD driving goal-directed control, or our task’s potential insensitivity to individual differences in ADHD symptomology. Further investigations may be crucial for determining whether ADHD is related to motivational impairments.

A data mining and item response mixture modeling method to retrospectively measure Diagnostic and Statistical Manual of Mental Disorders-5 attention deficit hyperactivity disorder in the 1970 British Cohort Study.

To facilitate future outcome studies, we aimed to develop a robust and replicable method for estimating a categorical and dimensional measure of Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) attention deficit hyperactivity disorder (ADHD) in the 1970 British Cohort Study (BCS70). Following a data mining framework, we mapped DSM-5 ADHD symptoms to age 10 BCS70 data (N=11,426) and derived a 16-item scale (α=0.85). Mapping was validated by an expert panel. A categorical subgroup was derived (n=594, 5.2%), and a zero-inflated item response theory (IRT) mixture model fitted to estimate a dimensional measure. Subgroup composition was comparable with other ADHD samples. Relative risk ratios (ADHD/not ADHD) included boys=1.38, unemployed fathers=2.07, below average reading=2.58, and depressed parent=3.73. Our estimated measures correlated with two derived reference scales: Strengths and Difficulties Questionnaire hyperactivity (r=0.74) and a Rutter/Conners-based scale (r=0.81), supporting construct validity. IRT model items (symptoms) had moderate to high discrimination (0.90-2.81) and provided maximum information at average to moderate theta levels of ADHD (0.5-1.75). We extended previous work to identify ADHD in BCS70, derived scales from existing data, modeled ADHD items with IRT, and adjusted for a zero-inflated distribution. Psychometric properties were promising, and this work will enable future studies of causal mechanisms in ADHD.

Heterogeneity in development of aspects of working memory predicts longitudinal attention deficit hyperactivity disorder symptom change.

The current study uses an accelerated longitudinal design and latent trajectory growth mixture models in a sample of children ages 7-13 years carefully characterized as with (n = 437) and without (n = 297) ADHD to (a) identify heterogeneous developmental trajectories for response inhibition, visual spatial working memory maintenance, and delayed reward discounting and (b) to assess the relationships between these cognitive trajectories and ADHD symptom change. Best-fitting models indicated multiple trajectory classes in both the ADHD and typically developing samples, as well as distinct relationships between each cognitive process and ADHD symptom change. Developmental change in response inhibition and delayed reward discounting were unrelated to ADHD symptom change, while individual differences in the rate of visual spatial working memory maintenance improvement predicted symptom remission in ADHD. Characterizing heterogeneity in cognitive development will be crucial for clarifying mechanisms of symptom persistence and recovery. Results here suggest working memory maintenance may be uniquely related to ADHD symptom improvement. (PsycINFO Database Record

Abnormal patterns of functional connectivity between right temporal parietal junction and whole brain in children with attention deficit hyperactivity disorder

Objective To investigate the pathophysiological distinction of the functional connectivity between right temporal parietal junction(rTPJ) and whole brain in children with attention-deficit/hyperactivity disorder(ADHD) on resting-state functional magnetic resonance imaging(fMRI)and explore the neurological mechanisms of ADHD at the point of functional connectivity. Methods Resting-state functional magnetic resonance imaging scans were obtained in 30 children with ADHD from The Third Affiliated Hospital of Soochow University and another 33 with age and gender matched controls from a normal primary school over the same period, and then, blood oxygenation level dependent(BOLD) signal was acquired to calculate the functional connectivity of rTPJ with other brain regions.Significant differences of connectivity intra-class and between groups were analyzed.Also, the correlation between the connectivity strength and the ADHD rating scales were tested. Results The pattern of functional connectivity of the rTPJ for the ADHD group was similar to that of the normal control group.Compared with the normal controls, the left superior temporal gyrus(MNI coordinates -33, 6, 48), the right anterior cingulate cortex(MNI coordinates 6, 39, -3), the right inferior parietal lobule(MNI coordinates 42, -33, 30), the left medial frontal gyrus(MNI coordinates -3, 63, -18) in children with ADHD showed an increased resting-state functional connectivity with the whole brain, while the right middle temporal gyrus(MNI coordinates 57, -33, -12), the right cingulate gyrus(MNI coordinates 18, -21, 36) showed a decreased resting-state functional connectivity with the whole brain.The average connection strength between the rTPJ and the whole brain showed positive correlation with the ADHD scores, while in normal controls, it showed negative. The connection strength between the rTPJ and those 6 brain areas with significant statistical difference was relevant to the ADHD scores, but they had no statistical significance. Conclusion The functional connection abnormalities between the rTPJ and the whole brain in children with ADHD may be relevant to the clinical symptom of attention-deficit. Key words: Attention-deficit/hyperactivity disorder; Resting state; Functional magnetic resonance imaging; Right temporal parietal junction

Intensity of functional connection between bilateral hemispheres of children with attention-deficit hyperactivity disorder by functional magnetic resonance imaging

To explore the neural mechanisms of attention-deficit hyperactivity disorder (ADHD) through analyzing the intensity of functional connection between bilateral hemispheres of children with ADHD by resting-state functional magnetic resonance imaging (rs-fMRI). The approach of voxel-mirrored homotopic connectivity (VMHC) was employed to analyze 31 school-age and 31 ADHD children by rs-fMRI scans. Positively activated brain regions were visualized when comparing ADHD and normal children, suggesting that ADHD children's VMHC scores were higher in bilateral frontal lobe (t = 5.81), bilateral occipital lobe (t = 5.82) and bilateral cerebellar posterior lobe (t = 6.17). Statistically significant differences existed between two groups (FDR correction, Q<0.01). The increased intensity of functional connection between bilateral prefrontal lobes in children with ADHD reflects attention disorder and leads to a decline of working memory . The strengthening of bilateral occipital lobes slows down memory process. And the increased intensity of cerebellar connections may damage neural circuits and aggravate ADHD symptoms.

Effect of treadmill exercise on social interaction and tyrosine hydroxylase expression in the attention-deficit/ hyperactivity disorder rats.

Attention-deficit/hyperactivity disorder (ADHD) involves clinically heterogeneous dysfunctions of sustained attention, with behavioral hyper-activity and impulsivity. The exact underlying mechanisms of ADHD are not known, however, impairment of dopaminergic system in the nigrostriatal pathway was suggested as the one of the possible mechanisms of ADHD. Tyrosine hydroxylase (TH) is the rate-limiting enzyme that is involved in the synthesis of dopamine. Spontaneous hypertensive rats have been used as the animal model for ADHD. Physical exercise is known to restore the brain functions disrupted by several neurode-generative and psychiatric disorders. In the present study, we investigated whether treadmill exercise exerts therapeutic effect on ADHD. Social interaction test for the evaluation of impulsivity was performed using spontaneous hypertensive rats. TH expressions in the substantia nigra and striatum were evaluated by immunohistochemistry. In the present results, the rats of ADHD model showed hyper-social behaviors. TH expressions in the substantia nigra and striatum were decreased in the rats of ADHD model. Treadmill exercise alleviated hyper-social behaviors in the ADHD rats. TH expressions of ADHD rats were also enhanced by treadmill exercise. Here in this study, we showed that treadmill exercise effectively alleviates the ADHD-induced symptoms through enhancing of TH expression in the brain.

The Physiology of BDNF and Its Relationship with ADHD.

Brain-derived neurotrophic factor (BDNF) is a major neurotrophin in the central nervous system that plays a critical role in the physiological brain functions via its two independent receptors: tropomyosin-related kinase B (TrkB) and p75, especially in the neurodevelopment. Disrupting of BDNF and its downstream signals has been found in many neuropsychological diseases, including attention-deficit hyperactivity disorder (ADHD), a common mental disorder which is prevalent in childhood. Understanding the physiological functions of BDNF during neural development and its potential relationship with ADHD will help us to elucidate the possible mechanisms of ADHD and to develop therapeutic approaches for this disease. In this review, we summarized the important literatures for the physiological functions of BDNF in the neurodevelopment. We also performed an association study on the functional genetic variation of BDNF and ADHD by a case-control study in the Chinese mainland population and revealed the potential correlation between BDNF and ADHD which needs further research to confirm.

Lag in maturation of the brain's intrinsic functional architecture in attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood, and there is great interest in understanding its neurobiological basis. A prominent neurodevelopmental hypothesis proposes that ADHD involves a lag in brain maturation. Previous work has found support for this hypothesis, but examinations have been limited to structural features of the brain (e.g., gray matter volume or cortical thickness). More recently, a growing body of work demonstrates that the brain is functionally organized into a number of large-scale networks, and the connections within and between these networks exhibit characteristic patterns of maturation. In this study, we investigated whether individuals with ADHD (age 7.2-21.8 y) exhibit a lag in maturation of the brain's developing functional architecture. Using connectomic methods applied to a large, multisite dataset of resting state scans, we quantified the effect of maturation and the effect of ADHD at more than 400,000 connections throughout the cortex. We found significant and specific maturational lag in connections within default mode network (DMN) and in DMN interconnections with two task positive networks (TPNs): frontoparietal network and ventral attention network. In particular, lag was observed within the midline core of the DMN, as well as in DMN connections with right lateralized prefrontal regions (in frontoparietal network) and anterior insula (in ventral attention network). Current models of the pathophysiology of attention dysfunction in ADHD emphasize altered DMN-TPN interactions. Our finding of maturational lag specifically in connections within and between these networks suggests a developmental etiology for the deficits proposed in these models.

A bimodal neurophysiological study of motor control in attention-deficit hyperactivity disorder: a step towards core mechanisms?

Knowledge about the core neural mechanisms of attention-deficit hyperactivity disorder, a pathophysiologically heterogeneous psychiatric disorder starting in childhood, is still limited. Progress may be achieved by combining different methods and levels of investigation. In the present study, we investigated neural mechanisms of motor control in 19 children with attention-deficit hyperactivity disorder (aged 9-14 years) and 21 age-matched typically developing children by relating neural markers of attention and response control (using event-related potentials) and measures of motor excitability/inhibition (evoked by transcranial magnetic stimulation). Thus, an interplay of processes at a subsecond scale could be studied. Using a monetary incentives-based cued Go/No-Go task, parameters that are well-known to be reduced in attention-deficit hyperactivity disorder were analysed: event-related potential components P3 (following cue stimuli; in Go and No-Go trials) and contingent negative variation as well as the transcranial magnetic stimulation-based short-interval intracortical inhibition measured at different latencies in Go and No-Go trials. For patient and control groups, different associations were obtained between performance, event-related potential and transcranial magnetic stimulation measures. In children with attention-deficit hyperactivity disorder, the P3 amplitude in Go trials was not correlated with reaction time measures but with short-interval intracortical inhibition at rest (r=0.56, P=0.01). In No-Go trials, P3 and short-interval intracortical inhibition after inhibiting the response (at 500 ms post-stimulus) were correlated in these children only (r=0.62; P=0.008). A classification rate of 90% was achieved when using short-interval intracortical inhibition (measured shortly before the occurrence of a Go or No-Go stimulus) and the amplitude of the P3 in cue trials as input features in a linear discriminant analysis. Findings indicate deviant neural implementation of motor control in children with attention-deficit hyperactivity disorder reflecting compensatory cognitive mechanisms as a result of a basal motor cortical inhibitory deficit (reduced activation of inhibitory intracortical interneurons). Both deviant inhibitory and attentional processes, which are not related to each other, seem to be characteristic for attention-deficit hyperactivity disorder at the neural level in motor control tasks. The underlying neural mechanisms, which are probably not restricted to the motor cortex and the posterior attention network, may play a key role in the pathophysiology of this child psychiatric disorder. The high classification rate can further be interpreted as a step towards the development of neural markers. In summary, the bimodal neurophysiological concept may contribute to developing an integrative framework for attention-deficit hyperactivity disorder.

Electroencephalographic Alpha Reactivity on Opening the Eyes in Children With Attention-Deficit Hyperactivity Disorder

The quantification of differences in alpha electroencephalograph (EEG) activity between the eyes-closed and eyes-open resting conditions could be used as a measure of resting state arousal. The objective of this study was to evaluate the contribution of EEG alpha reactivity on opening the eyes, to the neurophysiology of children with attention-deficit hyperactivity disorder (ADHD). Thirty-eight children with ADHD were assessed using quantitative EEG (qEEG) analysis of absolute band power at rest, with eyes open and closed. Alpha reactivity index was calculated on opening the eyes, defined from the relationship between the absolute powers in the respective bands in the periods with the eyes open and closed. EEG data of 38 sex- and age-matched controls, with no neurological or psychiatric problems, were collected for comparison. There was a significant reduction in absolute alpha power at all electrodes for both ADHD and control groups with eyes open, indicating an increase in the arousal level. However, the alpha reactivity index was greater, corresponding to less reactivity, in the frontal regions of the children with ADHD (P < .01). Such a finding suggests alterations in arousal mechanisms in ADHD. This research suggests that alpha reactivity on opening the eyes, allied with other variables from the qEEG, may improve diagnostic accuracy in ADHD.

Time Perception: Modality and Duration Effects in Attention-Deficit/Hyperactivity Disorder (ADHD)

Time perception performance was systematically investigated in adolescents with and without attention-deficit/hyperactivity disorder (ADHD). Specifically, the effects of manipulating modality (auditory and visual) and length of duration (200 and 1000 ms) were examined. Forty-six adolescents with ADHD and 44 controls were administered four duration discrimination tasks and two control tasks, and a set of standardized measures. Participants with ADHD had higher thresholds than controls on all of the duration discrimination tasks, with the largest effect size obtained on the visual 1000 ms duration discrimination task. No group differences were observed on the control tasks. Visual-spatial memory was found to be a significant predictor of visual and auditory duration discrimination at longer intervals (1000 ms) in the ADHD sample, whereas auditory verbal working memory predicted auditory discrimination at longer intervals (1000 ms) in the control sample. These group differences suggest impairments in basic timing mechanisms in ADHD.

Resting EEG theta activity predicts cognitive performance in attention-deficit hyperactivity disorder

Quantitative electroencephalography has contributed significantly to elucidating the neurobiologic mechanisms of attention-deficit hyperactivity disorder. The most consistent and robust electroencephalographic disturbance in attention-deficit hyperactivity disorder has been abnormally increased theta band during resting conditions. Separate research using attention-demanding tests has elucidated cognitive disturbances that differentiate attention-deficit hyperactivity disorder. This study attempts to integrate electroencephalographic and neuropsychological indices to determine whether cognitive performance is specifically related to increased theta. Theta activity was recorded during a resting condition for 46 children/adolescents with attention-deficit hyperactivity disorder and their sex- and age-matched control subjects. Accuracy and reaction time during an auditory oddball and a visual continuous performance test were then recorded. Compared with control subjects, the attention-deficit hyperactivity disorder group manifested significantly increased (primarily left) frontal theta. Furthermore, the attention-deficit hyperactivity disorder group scored significantly delayed reaction time and decreased accuracy in both tasks. Correlation analysis revealed a significant relationship between frontal (primarily left) theta and oddball accuracy for the attention-deficit hyperactivity disorder group compared with a significant relationship between posterior (primarily right) theta and reaction time in the continuous performance test for the control group. These results indicate that spatial neurophysiologic deficits in attention-deficit hyperactivity disorder may be related to disturbances in signal detection. This observation has important implications for the role of trait-like biologic deficits in attention-deficit hyperactivity disorder predicting performance in information processing.