Neurobiological models of attention-deficit/hyperactivity disorder: a brief review of the empirical evidence

Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric disorder characterized by inattention, impulsivity, and overactivity that begins in childhood. While considerable research has focused on the neurobiological substrates of this disorder, the specific nature of the brain dysfunction in ADHD has remained elusive. However, early data from pharmacological treatment studies, as well as from basic research in animals and humans, initially led several investigators to develop neurobiological models of ADHD. These models of ADHD and more recent evidence from neuropsychological, neuroimaging, neurochemical, and genetic research are briefly reviewed. While not completely consistent, the empirical data suggest that dysfunction in prefrontal-striatal neural circuits, as well as in brain stem catecholamine systems that innervate these circuits, may underlie the executive function deficits in ADHD.     

Normal executive attention but abnormal orienting attention in individuals with sluggish cognitive tempo

Background/objective: Sluggish Cognitive Tempo (SCT) is an attentional disorder characterized by the symptoms of slowness in behavior or thinking, a lack of en.ergy, difficulty initiating and sustaining effort, daydreaming, and drowsiness. The aim of the present study was to investigate the distinctive attentional characteristics of SCT as compared to Attention-Deficit/Hyperactivity Disorder (ADHD). Method: A total of 110 adults were recruited and divided into four groups: SCT+ADHD, SCT, ADHD, and healthy controls. The Revised version of Attention Networks Test was used to investigate each group’s attentional profile. Results: The results revealed that the two SCT groups (SCT+ADHD and SCT) showed a significantly weaker orienting network due to the problems of engaging and disengaging attention than the other two groups. Additionally, the two ADHD groups (SCT+ADHD and ADHD) showed a significantly weaker executive control network than the other two groups. Conclusions: The findings demonstrate an attentional distinction between the SCT and the ADHD groups with a greater dysfunction in the orienting network in the SCT group as compared to the ADHD group. Furthermore, a greater executive control dysfunction was observed in the ADHD group as compared to the SCT group.     

Attention-Deficit Hyperactivity Disorder and Event-Related Potentials: Evidence for Deficits in Allocating Attentional Resources to Relevant Stimuli

Current research on the nature of attentional deficits in attention-deficit hyperactivity disorder (ADHD) is reviewed with a focus on studies using event-related potentials (ERPs). A robust effect is the smaller amplitude of the P3 wave to both auditory and visual stimuli for individuals with ADHD than for normal controls. This effect is indicative of deficits in the allocation of attentional resources to task-relevant information. The Nd wave is also smaller for individuals with ADHD, an effect that suggests impairments in the discrimination and preferential processing of task-relevant information, rather than distractibility by irrelevant stimuli. Studies of the effects of methylphenidate on ERPs in ADHD indicate that this stimulant enhances the quality of stimulus evaluation and speeds response time. These specific effects support the view that ADHD involves deficits in energetic processes that are required for processing task-relevant stimuli.     

Attentional networks,vigilance, and distraction as a function of attention-deficit/hyperactivity disorder symptoms in an adult community sample

Attentional difficulties are a core axis in attention-deficit/hyperactivity disorder (ADHD). However, establishing a consistent and detailed pattern of these neurocognitive alterations has not been an easy endeavour. Based on a dimensional approach to ADHD, the present study aims at comprehensively characterizing three key attentional domains: the three attentional networks (alerting, orienting, and executive attention), two components of vigilance (executive and arousal vigilance), and distraction. To do so, we modified a single, fine-grained task (the ANTI-Vea) by adding irrelevant distractors. One hundred and twenty undergraduates completed three self-reports of ADHD symptoms in childhood and adulthood and performed the ANTI-Vea. Despite the low reliability of some ANTI-Vea indexes, the task worked successfully. While ADHD symptoms in childhood were related to alerting network and arousal vigilance, symptoms in adulthood were linked to executive vigilance. No association between ADHD symptom severity and executive attention and distraction was found. In general, our hypotheses about the relationships between ADHD symptoms and attentional processes were partially supported. We discuss our findings according to ADHD theories and attention measurement.     

Executive and attentional contributions to Theory of Mind deficit in attention deficit/hyperactivity disorder (ADHD)

Attention deficit/hyperactivity disorder (ADHD) in children has been associated with attentional and executive problems, but also with socioemotional difficulties possibly associated with deficits in Theory of Mind (ToM). Socioemotional problems in ADHD are associated with more negative prognoses, notably interpersonal, educational problems, and an increased risk of developing other psychiatric disorders that emphasize the need to clarify the nature of their ToM deficits. In this study, we hypothesized that ToM dysfunction in children with ADHD is largely attributable to their attentional and/or executive deficits. Thirty-one children with ADHD (8–12 years, IQ > 85) and 31 typically developing (TD) children were assessed using executive functions (inhibition, planning, and flexibility) and attentional tasks, as well as two advanced ToM tasks (Reading the Mind in the Eyes and Faux Pas) involving different levels of executive control. Children with ADHD performed more poorly than TD children in attentional, executive function, and ToM tasks. Linear regression analyses conducted in the ADHD group indicated that inhibition scores predicted performance on the “Faux Pas” task the best, while attention scores were the best for predicting performance on the Reading the Mind in the Eyes task. When controlled for inhibition and attentional variables, ToM performance in children with ADHD was actually similar to TD children. Contrarily, controlling for ToM scores did not normalize performance for inhibition and attentional tasks in children with ADHD. This unidirectional relationship suggests that deficits in the EF and attentional domains are responsible for ToM deficits in ADHD, which therefore may contribute to their socioemotional difficulties.     

Inattentive and noninattentive ADHD children: Do they constitute a unitary group?

Teacher-rated ADHD and normal control children were administered a continuous performance test (CPT), and were then further subdivided based upon the presence or absence of objectively assessed attentional deficits. In addition, children were assessed using several measures of cognitive and behavioral functioning. Attentional deficits were signficantly more prevalent among the ADHD group, but about half of the ADHD children showed no evidence of objectively assessed attentional dysfunction. Further group analyses indicated that ADHD children with objectively assessed attentional dysfunction appeared cognitively impaired, while ADHD children without objective evidence of attentional dysfunction had more conduct problems. CPT inattention was not related to the presence of cognitive impairments or conduct problems in the control group. These data must be considered preliminary because teacher ratings were the only source of diagnosis and a single measure of inattention was used. However, they suggest that two subtypes of ADHD children can be identified, one characterized by inattention and learning problems, and the other by conduct problems.The authors gratefully acknowledge the assistance of Sister Hildegard Kogler and the St. Francis DeSales School, and the parents and children who participated in this study.     

Co-occurring disorders: a possible key to visual perceptual deficits in children with developmental coordination disorder?

A study was conducted to examine how visual perceptual functioning in children with DCD may be influenced by co-occurring learning problems such as reading disabilities (RD) and/or attention deficit hyperactivity disorder (ADHD). Participants included seven groups of children: 27 children with DCD only, 11 with ADHD only, 14 with RD only, 63 with DCD and at least one other disorder (i.e., DCD + ADHD, DCD + RD, DCD + ADHD + RD), and 73 typically developing controls. Visual perceptual skills were assessed using the Test of Visual Perceptual Skills (TVPS) and the Rey Osterreith Complex Figure (ROCF; copy and delayed recall). Children with DCD and at least one other disorder were found to have impairments on the TVPS compared to children with DCD only, ADHD only, and typically developing controls, particularly on subtests assessing visual memory. On the ROCF, children with DCD and at least one other disorder scored significantly lower than children with ADHD only or RD only. Children with DCD plus one other disorder were then subdivided into three groups: DCD + ADHD, DCD + RD, and DCD + ADHD + RD and compared to children with DCD only, ADHD only, and RD only. Results indicated that children with DCD + ADHD + RD had significant impairments on the TVPS compared to children with DCD only and children with ADHD only. On the ROCF, children with DCD + ADHD + RD scored significantly lower than all of the groups, except the DCD+RD group. These findings suggest that DCD on its own is not associated with visual perceptual problems; rather, it is the presence of co-occurring disorders that is a possible key to visual perceptual deficits in children with DCD. The number of co-occurring disorders present with DCD is associated with the severity of the visual perceptual dysfunction. Deficits in visual memory skills appear to be a specific area of difficulty for children with DCD and co-occurring RD and/or ADHD.     

Latent inhibition and asymmetrical visual-spatial attention in children with ADHD.

The research was designed to determine whether the purported hemispheric asymmetries that are associated with attention deficit/hyperactivity disorder (ADHD) affect performance on a selective attention visual search task, and whether any obtained asymmetry will be modulated by methylphenidate. Two groups of children (8-15 years) with ADHD, one with methylphenidate treatment (ADHD+) and one without (ADHD+), were compared to matched controls on a two-stage visual search task. The task assessed right-left visual field asymmetries and the effects of changing a previous distractor into a target. Such a procedure, related to latent inhibition (LI; poorer performance to a previously irrelevant stimulus than to a novel one), can provide evidence for dysfunctional processing of irrelevant stimuli. All three groups exhibited the LI effect. The ADHD group, however, exhibited less LI for left- than right-side targets, an effect absent in the control and ADHD+ groups, suggesting a lateralized attentional deficit for ADHD+ that was normalized by methylphenidate.     

Latent Inhibition and Asymmetrical Visual-Spatial Attention in Children with ADHD

The research was designed to determine whether the purported hemispheric asymmetries that are associated with attention deficit/hyperactivity disorder (ADHD) affect performance on a selective attention visual search task, and whether any obtained asymmetry will be modulated by methylphenidate. Two groups of children (8–15 years) with ADHD, one with methylphenidate treatment (ADHD+) and one without (ADHD+), were compared to matched controls on a two-stage visual search task. The task assessed right–left visual field asymmetries and the effects of changing a previous distractor into a target. Such a procedure, related to latent inhibition (LI; poorer performance to a previously irrelevant stimulus than to a novel one), can provide evidence for dysfunctional processing of irrelevant stimuli. All three groups exhibited the LI effect. The ADHD group, however, exhibited less LI for left- than right-side targets, an effect absent in the control and ADHD+ groups, suggesting a lateralized attentional deficit for ADHD+ that was normalized by methylphenidate.     

Disentangling the adult attention-deficit hyperactivity disorder endophenotype: parametric measurement of attention

Attention deficit hyperactivity disorder (ADHD) persists frequently into adulthood. The decomposition of endophenotypes by means of experimental neuro-cognitive assessment has the potential to improve diagnostic assessment, evaluation of treatment response, and disentanglement of genetic and environmental influences. We assessed four parameters of attentional capacity and selectivity derived from simple psychophysical tasks (verbal report of briefly presented letter displays) and based on a "theory of visual attention." These parameters are mathematically independent, quantitative measures, and previous studies have shown that they are highly sensitive for subtle attention deficits. Potential reductions of attentional capacity, that is, of perceptual processing speed and working memory storage capacity, were assessed with a whole report paradigm. Furthermore, possible pathologies of attentional selectivity, that is, selection of task-relevant information and bias in the spatial distribution of attention, were measured with a partial report paradigm. A group of 30 unmedicated adult ADHD patients and a group of 30 demographically matched healthy controls were tested. ADHD patients showed significant reductions of working memory storage capacity of a moderate to large effect size. Perceptual processing speed, task-based, and spatial selection were unaffected. The results imply a working memory deficit as an important source of behavioral impairments. The theory of visual attention parameter working memory storage capacity might constitute a quantifiable and testable endophenotype of ADHD.     

Current concepts on the neurobiology of Attention-Deficit/Hyperactivity Disorder

Attention-Deficit/Hyperactivity Disorder (ADHD) is an early onset, clinically heterogeneous disorder of inattention, hyperactivity, and impulsivity. In contrast to the widespread acceptance of ADHD as a childhood diagnosis, Its prevalence In adults and its implications for clinical practice remain a source of controversy. Throughout the lifecycle, a key clinical feature observed in ADHD patients is comorbidity with Conduct Depressive, Bipolar, and Anxiety disorders. Family studies consistently support the assertion that ADHD runs in families. Heritability data from twin studies of ADHD attribute about 80 percent of the etiology of ADHD to genetic factors. Adoption studies of ADHD also implicate genes in its etiology. Molecular genetic data are bolstered by considerations suggesting that DRD4 and DAT genes may be relevant for ADHD. Independently of genes, prenatal exposure to nicotine and psychosocial adversity have also been identified as risk factors for ADHD. Structural and functional imaging studies consistently implicate catecholamine-rich fronto-subcortical systems in the pathophysiology of ADHD. The effectiveness of stimulants, along with animal models of hyperactivity, point to catecholamine disruption as at least one source of ADHD brain dysfunction. Although not entirely sufficient, changes in dopaminergic and noradrenergic function appear necessary for the clinical efficacy of pharmacological treatments for ADHD, providing support for the hypothesis that alteration of monoaminergic transmission in critical brain regions may be the basis for therapeutic action in ADHD.     

Developmental coordination disorder pertains to a deficit in perceptuo-motor synchronization independent of attentional capacities

We investigated from a dynamic pattern perspective to motor coordination whether the deficiency in motor coordination characterizing Developmental Coordination Disorder children pertains to a general disorder in synchronization leading to a lower stability of the performed coordination pattern, and the extent to which the trouble is linked to attentional capacities. Twenty-four DCD children without ADHD aged eight to thirteen and 60 control children were asked (1) to perform a Continuous Performance Test assessing sustained attention; (2) to flex one finger either in synchrony or in syncopation with a visual periodic signal whose frequency was increased stepwise, assessing synchronization abilities. For the attentional task, percentage of exact responses, number of errors and reaction time were recorded. For the synchronization task, we measured relative phase (i.e., the ratio between the stimulus and the response onset and the time separating two successive stimuli). DCD children were significantly more variable than controls in both conditions and the difficulty in synchronization was unrelated to attentional disorders (ANCOVA). These findings support the idea of a general synchronization disorder in DCD children underlying their poor motor coordination. Moreover, this synchronization disorder does not appear to be strictly dependent on the level of sustained attentional capacities.     

A psychophysical measure of attention deficit in children with attention-deficit/hyperactivity disorder

The authors explored the temporal mechanism of attention deficit in children with attention-deficit/hyperactivity disorder (ADHD). In rapid serial visual presentation tasks in which two targets (T-sub-1 and T-sub-2) were presented in close temporal proximity among distractors, participants tried to identify T-sub-1 and detect T-sub-2 in one (dual-task) experiment and only to detect T-sub-2 in a second control (single-task) experiment. The sensitivity of T-sub-2 detection was analyzed using signal detection theory. The attentional blink--the impairment in T-sub-2 detection following the identification of T-sub-1--was increased in magnitude and protracted in the patients. Moreover, some ADHD children appeared to have a blink largely normal in magnitude but temporally displaced toward a later time. The authors hypothesize that a slower closing of the attention gate may mediate this specific attention impairment in ADHD children.     

The interplay between executive control and motor functioning in Williams syndrome

Previous studies suggest that individuals with Williams syndrome (WS), a rare genetically based neurodevelopmental disorder, show specific weaknesses in visual attention and response inhibition within the visuospatial domain. Here we examine the extent to which impairments in attentional control extend to the visuomotor domain using a well‐validated measure of choice stepping reaction time (CSRT) in individuals with WS. We examined the interaction between executive control and visually guided stepping using a verbal fluency dual‐task or Go/NoGo paradigm during CSRT performance. Relationships between dual‐task and inhibitory stepping and behavioural inattention and hyperactivity were also examined. Our results showed clear dual‐task costs in stepping response times when performing a concurrent cognitive task in the WS group when compared to spatial and verbal ability matched typically developing controls. Although no group differences in stepping accuracy were observed between the WS and typically developing control groups, the WS group showed progressive slowing and more variable response times across the duration of the Go/NoGo task. These results suggest dysfunction in circuits involved in top‐down attentional control processes in WS. These findings provide novel evidence that core executive control deficits in WS extend to the visuomotor domain, and impact on ADHD‐related inattentive symptoms.     

Large-scale brain networks and psychopathology: a unifying triple network model

The science of large-scale brain networks offers a powerful paradigm for investigating cognitive and affective dysfunction in psychiatric and neurological disorders. This review examines recent conceptual and methodological developments which are contributing to a paradigm shift in the study of psychopathology. I summarize methods for characterizing aberrant brain networks and demonstrate how network analysis provides novel insights into dysfunctional brain architecture. Deficits in access, engagement and disengagement of large-scale neurocognitive networks are shown to play a prominent role in several disorders including schizophrenia, depression, anxiety, dementia and autism. Synthesizing recent research, I propose a triple network model of aberrant saliency mapping and cognitive dysfunction in psychopathology, emphasizing the surprising parallels that are beginning to emerge across psychiatric and neurological disorders.     

Connecting the Dots: A Review of Resting Connectivity MRI Studies in Attention-Deficit/Hyperactivity Disorder

Psychopathology is increasingly viewed from a circuit perspective in which a disorder stems not from circumscribed anomalies in discrete brain regions, but rather from impairments in distributed neural networks. This focus on neural circuitry has rendered resting state functional connectivity MRI (rs-fcMRI) an increasingly important role in the elucidation of pathophysiology including attention-deficit/hyperactivity disorder (ADHD). Unlike many other MRI techniques that focus on the properties of discrete brain regions, rs-fcMRI measures the coherence of neural activity across anatomically disparate brain regions, examining the connectivity and organization of neural circuits. In this review, we explore the methods available to investigators using rs-fcMRI techniques, including a discussion of their relative merits and limitations. We then review findings from extant rs-fcMRI studies of ADHD focusing on neural circuits implicated in the disorder, especially the default mode network, cognitive control network, and cortico-striato-thalamo-cortical loops. We conclude by suggesting future directions that may help advance subsequent rs-fcMRI research in ADHD.     

Attentional Performance in Children and Adolescents with Tic Disorder and Co-Occurring Attention-Deficit/Hyperactivity Disorder: New Insights from a 2 × 2 Factorial Design Study

The aim of the present study was to investigate the effect of both tic disorder (TD) and attention-deficit/hyperactivity disorder (ADHD) on attentional functions. N = 96 children and adolescents participated in the study, including n = 21 subjects with TD, n = 23 subjects with ADHD, n = 25 subjects with TD+ADHD, and n = 27 controls. Attentional performance was tested based on four computerized attention tasks (sustained attention, divided attention, go/nogo and set shifting). The effect of TD as well as ADHD on attentional performance was tested using a 2 × 2 factorial approach. A diagnosis of TD had no negative impact on attentional functions but was associated with improved performance in the set shifting task. By contrast, regardless of a diagnosis of TD, subjects with ADHD were found to perform worse in the sustained attention, divided attention and go/nogo task. No interaction effect between the factors TD and ADHD was revealed for any of the attention measures. Our results add to findings from other areas of research, showing that in subjects with TD and ADHD, ADHD psychopathology is often the main source of impairment, whereas a diagnosis of TD has little or no impact on neuropsychological performance in most cases and even seems to be associated with adaptive mechanisms.     

Attention, task difficulty, and ADHD

Comments on analysis of attention tasks in Attention Deficit Hyperactivity Disorder (ADHD) provided by Wilding (2005) points out that whereas many regulatory functions, including alertness or arousal, appear to be impaired in ADHD, demonstrating basic attention deficits in selection or orienting functions in the disorder has proven difficult. Yet several issues remain to be addressed in the field with regard to attentional function in ADHD. These include the need for further scrutiny of effects of perceptual load, the psychometric problem of differential task difficulty and differential deficit, relative value of complex versus simple tasks, and consideration of heterogeneity in ADHD. Heterogeneity pertains both to additional analysis of ADHD subtypes, in light of speculation that the Inattentive type may be characterized by true attention problems, and to newer analyses of potential distinct etiological groups within subtype. New analyses of attentional operations have a role to play in these future directions.     

Cultural influences on neural substrates of attentional control

Behavioral research has shown that people from Western cultural contexts perform better on tasks emphasizing independent (absolute) dimensions than on tasks emphasizing interdependent (relative) dimensions, whereas the reverse is true for people from East Asian contexts. We assessed functional magnetic resonance imaging responses during performance of simple visuospatial tasks in which participants made absolute judgments (ignoring visual context) or relative judgments (taking visual context into account). In each group, activation in frontal and parietal brain regions known to be associated with attentional control was greater during culturally nonpreferred judgments than during culturally preferred judgments. Also, within each group, activation differences in these regions correlated strongly with scores on questionnaires measuring individual differences in culture-typical identity. Thus, the cultural background of an individual and the degree to which the individual endorses cultural values moderate activation in brain networks engaged during even simple visual and attentional tasks.     

赌博障碍的认知功能缺陷及神经基础

赌博障碍是指持续且反复的赌博行为,给个人、家庭和社会都带来了严重后果,近年来受到越来越多研究者的关注。本研究总结了赌博障碍的认知功能缺陷及其神经基础,主要集中在如下四个方面：①认知扭曲、②奖赏和惩罚敏感性、③注意偏向和④决策。未来研究应多从认知神经科学角度深入探究赌博障碍的发生机制和发展过程,关注大脑结构变化及功能网络改变,并将其整合到一个统一的神经生物机制框架中,找到更加有效的干预和治疗手段。