A parietal biomarker for ADHD liability: as predicted by the distributed effects perspective model of ADHD.

BACKGROUND: We previously hypothesized that poor task-directed sensory information processing should be indexed by increased weighting of right hemisphere (RH) biased attention and visuo-perceptual brain functions during task operations and have demonstrated this phenotype in ADHD across multiple studies, using multiple methodologies. However, in our recent distributed effects model of ADHD, we surmised that this phenotype is not ADHD specific, but rather more broadly reflective of any circumstance that disrupts the induction and maintenance of an emergent task-directed neural architecture. Under this view, increased weighting of RH-biased attention and visuo-perceptual brain functions is expected to generally index neurocognitive sets that are not optimized for task-directed thought and action, and when durable expressed, liability for ADHD. METHOD: The current study tested this view by examining whether previously identified rightward parietal EEG asymmetry in ADHD was associated with common ADHD characteristics and comorbidities [i.e., ADHD risk factors (RFs)]. RESULTS: Barring one exception (non-right handedness), we found that it was. Rightward parietal asymmetry (RPA) was associated with carrying the DRD4-7R risk allele, being male, having mood disorder, and having anxiety disorder. However, differences in the specific expression of RPA were observed, which are discussed in relation to possible unique mechanisms underlying ADHD liability in different ADHD RFs. CONCLUSION: Rightward parietal asymmetry appears to be a durable feature of ADHD liability, as predicted by the Distributed Effects Perspective Model of ADHD. Moreover, variability in the expression of this phenotype may shed light on different sources of ADHD liability.

Visual Network Asymmetry and Default Mode Network Function in ADHD: An fMRI Study.

BACKGROUND: A growing body of research has identified abnormal visual information processing in attention-deficit hyperactivity disorder (ADHD). In particular, slow processing speed and increased reliance on visuo-perceptual strategies have become evident. OBJECTIVE: The current study used recently developed fMRI methods to replicate and further examine abnormal rightward biased visual information processing in ADHD and to further characterize the nature of this effect; we tested its association with several large-scale distributed network systems. METHOD: We examined fMRI BOLD response during letter and location judgment tasks, and directly assessed visual network asymmetry and its association with large-scale networks using both a voxelwise and an averaged signal approach. RESULTS: Initial within-group analyses revealed a pattern of left-lateralized visual cortical activity in controls but right-lateralized visual cortical activity in ADHD children. Direct analyses of visual network asymmetry confirmed atypical rightward bias in ADHD children compared to controls. This ADHD characteristic was atypically associated with reduced activation across several extra-visual networks, including the default mode network (DMN). We also found atypical associations between DMN activation and ADHD subjects' inattentive symptoms and task performance. CONCLUSION: The current study demonstrated rightward VNA in ADHD during a simple letter discrimination task. This result adds an important novel consideration to the growing literature identifying abnormal visual processing in ADHD. We postulate that this characteristic reflects greater perceptual engagement of task-extraneous content, and that it may be a basic feature of less efficient top-down task-directed control over visual processing. We additionally argue that abnormal DMN function may contribute to this characteristic.

Abnormal Parietal Brain Function in ADHD: Replication and Extension of Previous EEG Beta Asymmetry Findings.

BACKGROUND: Abundant work indicates ADHD abnormal posterior brain structure and function, including abnormal structural and functional asymmetries and reduced corpus callosum size. However, this literature has attracted considerably less research interest than fronto-striatal findings. OBJECTIVE: To help address this imbalance, the current study replicates and extends our previous work showing abnormal parietal brain function in ADHD adults during the Conner's Continuous Performance Test (CPT). METHOD: Our previous study found that ADHD adults had increased rightward EEG beta (16-21 Hz) asymmetry in inferior parietal brain regions during the CPT (p = 0.00001), and that this metric exhibited a lack of normal correlation (i.e., observed in controls) with beta asymmetry at temporal-parietal regions. We re-tested these effects in a new ADHD sample and with both new and old samples combined. We additionally examined: (a) EEG asymmetry in multiple frequency bands, (b) unilateral effects for all asymmetry findings, and (c) the association between EEG asymmetry and a battery of cognitive tests. RESULTS: We replicated our original findings by demonstrating abnormal rightward inferior parietal beta asymmetry in adults with ADHD during the CPT, and again this metric exhibited abnormal reduced correlation to temporal-parietal beta asymmetry. Novel analyses also demonstrated a broader pattern of rightward beta and theta asymmetry across inferior, superior, and temporal-parietal brain regions, and showed that rightward parietal asymmetry in ADHD was atypically associated with multiple cognitive tests. CONCLUSION: Abnormal increased rightward parietal EEG beta asymmetry is an important feature of ADHD. We speculate that this phenotype may occur with any form of impaired capacity for top-down task-directed control over sensory encoding functions, and that it may reflect associated increase of attentional shifting and compensatory sustained/selective attention.

A distributed effects perspective of dimensionally defined psychiatric disorders: and convergent versus core deficit effects in ADHD.

The focus of psychiatric and psychological research has arguably shifted from brain damage and psychosis to more common forms of psychopathology that reflect extremes variants of otherwise normal cognitive and behavioral characteristics. Now, in addition to trying to understand overtly damaged brain-function (flat tire effects), we are also seeking to understand liabilities associated with non-optimized, but otherwise intact, cognitive and behavioral abilities (poor tuning effects). This shift has pushed us to evolve our investigational strategies to more broadly consider whole-brain integrated brain systems, as well as seek to develop more specific quantifiable indicators of impoverished brain function and behavior. This paper discusses such challenges in relation to dimensionally defined psychiatric disorders and presents a novel whole-brain integrated perspective of ADHD brain function pathology.

Characterization of the theta to beta ratio in ADHD: identifying potential sources of heterogeneity.

OBJECTIVE: The goal of this study is to characterize the theta to beta ratio (THBR) obtained from electroencephalogram (EEG) measures, in a large sample of community and clinical participants with regard to (a) ADHD diagnosis and subtypes, (b) common psychiatric comorbidities, and (c) cognitive correlates. METHOD: The sample includes 871 participants (595 youth and 276 adults) with and without ADHD. All participants underwent extensive assessment, including semistructured diagnostic interviews, cognitive testing, and EEG recording. RESULTS: The THBR did not differ significantly by ADHD status for youth but was significantly lower in adults with ADHD compared with controls. ADHD subtype and psychiatric comorbidities such as disruptive behavior disorders and depression have opposing and significant mediating effects on the THBR. CONCLUSION: The THBR is affected by several mediating factors associated with ADHD such as ADHD subtype and psychiatric comorbidity. More research is needed to understand the functional significance of the THBR in ADHD.

A Machine Learning-Based Analysis of Game Data for Attention Deficit Hyperactivity Disorder Assessment.

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is found in 9.5 percent of the U.S. population and poses lifelong challenges. Current diagnostic approaches rely on evaluation forms completed by teachers and/or parents, although they are not specifically trained to recognize cognitive disorders. The most accurate diagnosis is by a psychiatrist, often only available to children with severe symptoms. Development of a tool that is engaging and objective and aids medical providers is needed in the diagnosis of ADHD. The goal of this research is to work toward the development of such a tool. MATERIALS AND METHODS: The proposed approach takes advantage of two trends: The rapid adoption of tangible user interface devices and the popularity of interactive videogames. CogCubed Inc. (Minneapolis, MN) has created "Groundskeeper," a game on the Sifteo Cubes (Sifteo, Inc., San Francisco, CA) game system with elements that exercise skills affected by ADHD. "Groundskeeper" was evaluated for 52 patients, with and without ADHD. Gameplay data were mathematically transformed into ADHD-indicative feature variables and subjected to machine learning algorithms to develop diagnostic models to aid psychiatric clinical assessments of ADHD. The effectiveness of the developed model was evaluated against the diagnostic impressions of two licensed child/adolescent psychiatrists using semistructured interviews. RESULTS: Our predictive algorithms were highly accurate in correctly predicting diagnoses based on gameplay of "Groundskeeper." The F-measure, a measure of diagnosis accuracy, from the predictive models gave values as follows: ADHD, inattentive type, 78 percent (P>0.05); ADHD, combined type, 75 percent (P<0.05); anxiety disorders, 71%; and depressive disorders, 76%. CONCLUSIONS: This represents a promising new approach to screening tools for ADHD.

Atypical EEG beta asymmetry in adults with ADHD.

BACKGROUND: Abnormal brain laterality (ABL) is well established in ADHD. However, its clinical specificity and association to cognitive and clinical symptoms is not yet understood. Previous studies indicate increased right hemisphere (RH) contribution in both ADHD and reading impaired samples. The current study investigates whether this ABL characteristic occurs in adults with ADHD absent comorbid language impairment. METHODS: EEG beta asymmetry was compared in 35 adult ADHD subjects and 104 controls during rest and active cognition. Group differences in beta asymmetry were then further evaluated for association to linguistic and attentional abilities, as well as association to beta asymmetry measures across different brain regions. RESULTS: Adults with ADHD showed pronounced rightward beta asymmetry (p=.00001) in inferior parietal regions (P8-P7) during a continuous performance task (CPT) that could not be attributed to linguistic ability. Among ADHD subjects only, greater rightward beta asymmetry at this measure was correlated with better CPT performance. Furthermore, this measure showed a lack of normal association (i.e., observed in controls) to left-biased processing in temporal-parietal (TP8-TP7) brain regions important for higher order language functions. CONCLUSION: Adult ADHD involves abnormally increased right-biased contribution to CPT processing that could not be attributed to poor language ability. This appears to also involve abnormal recruitment of LH linguistic processing regions and represents an alternative, albeit less effective, CPT processing strategy. These findings suggest different pathophysiologic mechanisms likely underlie RH biased processing in ADHD and reading impaired samples.

ADHD familial loading and abnormal EEG alpha asymmetry in children with ADHD.

OBJECTIVE: Abnormal brain laterality (ABL) is indicated in ADHD. ADHD and brain laterality are heritable. Genetic factors contributing to lateralization of brain function may contribute to ADHD. If so, increased ADHD family loading should be associated with greater ABL. Previous studies have shown increased rightward alpha asymmetry in ADHD. We tested whether this was more pronounced in ADHD children with increased ADHD family loading. METHODS: We compared EEG alpha asymmetry at rest and during the Conner's Continuous Performance Test (CPT) in ADHD children with and without ADHD affected parents, and replicated our findings in a second larger sample. The replication study additionally stratified the parent-affected sample by parental persistent versus non-persistent ADHD status, increased spatial resolution of EEG measures, and assessed low versus high-alpha. RESULTS: Study-1: the parent-affected group showed increased rightward asymmetry across frontal and central regions and reduced rightward parietal asymmetry during an eyes closed (EC) condition, as well as increasing rightward parietal asymmetry with advancing age during the CPT. Study-2 replicated these findings and further delineated influences of low versus high-alpha, recording site, and effects of parental persistent versus non-persistent ADHD status. CONCLUSION: Increased ADHD familial loading was associated with increased rightward frontal asymmetry. In contrast, increased rightward parietal asymmetry was associated with reduced ADHD family loading. Frontal results are consistent with an ADHD endophenotype. Parietal results suggest an ADHD adaptive trait prevalent with less ADHD family loading. Age effects indicate a unique developmental course among ADHD children whose parents have non-persistent ADHD.

Mindfulness and attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a disorder characterized by attentional difficulties. Mindfulness is a receptive attention to present experience. Both ADHD and mindfulness are associated with attention and personality. This study tests whether individuals with ADHD have lower mindfulness scores than controls and, if true, whether personality contributes to these differences. One hundred and five adults (half with ADHD) were assessed for mindfulness, using the Kentucky Inventory of Mindfulness Skills, and personality, using the Tridimensional Character Inventory. Individuals with ADHD report themselves as less mindful than non-ADHD controls and more novelty-seeking, less self-directed, and more self-transcendent. Mindfulness is negatively associated with ADHD and positively associated with self-directedness and self-transcendence. Analyses of subscales of mindfulness suggest that ADHD is associated most with the "Acting in Awareness" dimension, perhaps because of shared items reflecting attentional variability. The current findings support that a large portion of variability in trait mindfulness can be explained by ADHD status and personality traits of self-directedness and self-transcendence. It further suggests that interventions that increase mindfulness might improve symptoms of ADHD and increase self-directedness and/or self-transcendence.

Atypical alpha asymmetry in adults with ADHD.

INTRODUCTION: A growing body of literature suggests atypical cerebral asymmetry and interhemispheric interaction in ADHD. A common means of assessing lateralized brain function in clinical populations has been to examine the relative proportion of EEG alpha activity (8-12 Hz) in each hemisphere (i.e., alpha asymmetry). Increased rightward alpha asymmetry has been associated with ADHD-like traits such as reduced reward responsiveness, a lack of inhibition toward aversive experience, and increased approach behaviors, and previous work has indicated increased rightward alpha asymmetry in children with ADHD. The current study explores whether increased rightward alpha asymmetry is also evident in adults with ADHD. METHOD: We assessed low (8-10 Hz) and high (10-12 Hz) alpha asymmetry in adults with ADHD (n=29) versus controls (n=62) during baseline and cognitive activation conditions for nine homologous electrode pairs along the anterior-posterior axis. RESULT: Seven results emerged (p<.05) showing increased rightward alpha asymmetry in adults with ADHD. This occurred in three specific electrode pairs across two testing conditions, and five of six results occurred in the lower alpha band. Finally, post hoc analysis indicated that increased rightward alpha asymmetry was generally associated with greater numbers of ADHD symptoms--with a possible parietal association for inattentive and a fronto-temporal association for hyperactivity symptoms. CONCLUSIONS: Increased rightward alpha asymmetry previously observed in children with ADHD appears to be a developmentally persistent feature of ADHD.

Cortical activity patterns in ADHD during arousal, activation and sustained attention.

OBJECTIVE: The goal of the present study is to test whether there are Attention-Deficit Hyperactivity Disorder (ADHD)-related differences in brain electrical activity patterns across arousal, activation and vigilance states. METHOD: The sample consists of 80 adults (38 with ADHD and 42 non-ADHD controls) who were recruited for a family study on the genetics of ADHD. Patterns of cortical activity were measured using electroencephalography (EEG) during baseline and sustained attention conditions and compared according to ADHD diagnostic status. Cortical activity was examined separately for the first, middle, and last 5-min of the sustained attention task to assess whether patterns differed over time and according to ADHD status. RESULTS: In frontal and parietal regions, patterns of activation in the alpha (8-10 Hz) range differed according to ADHD status, indicating increased cortical arousal among ADHD subjects. Beta power (13-14 and 17-18 Hz) also differed between ADHD and controls, indicating increased cortical activation is associated with ADHD. Behavioral performance on the sustained attention task did not differ significantly by diagnosis. EEG correlates of cognitive performance differed significantly ADHD diagnosis and were primarily in frontal regions. Brain activation patterns recorded during the sustained attention task suggest that the ADHD group exhibited significantly increased cortical activation at the end of the task when compared to controls. CONCLUSIONS: Adults with ADHD may have different neural organization primarily in frontal regions which results in the need for continually high levels of cortical activation to maintain sustained attention.

Rethinking a right hemisphere deficit in ADHD.

INTRODUCTION: Early observations from lesion studies suggested right hemisphere (RH) dysfunction in ADHD. However, a strictly right-lateralized deficit has not been well supported. An alternatively view suggests increased R > L asymmetry of brain function and abnormal interhemispheric interaction. If true, RH pathology in ADHD should reflect interhemispherically networked and overactivated functioning. The authors evaluated these assertions. METHOD: Four elements of lateralized brain function were measured: LH specialized, RH specialized, LH with interhemispheric processing (LH/IH), and RH with interhemispheric processing (RH/IH). Next, the authors tested their association with cognitive ability, psychiatric comorbidity, and sibling correlations in 79 children with ADHD. RESULTS: RH/IH processing was uniquely associated with other outcome measures. There were no associations for independent RH or LH function alone. CONCLUSION: Interhemispherically networked RH processing is critical in ADHD. In addition, lack of association between LH specialized processing and cognitive ability (especially for verbal cognitive tasks) supports increased RH mediation of task processing.

Mindfulness meditation training in adults and adolescents with ADHD: a feasibility study.

OBJECTIVE: ADHD is a childhood-onset psychiatric condition that often continues into adulthood. Stimulant medications are the mainstay of treatment; however, additional approaches are frequently desired. In recent years, mindfulness meditation has been proposed to improve attention, reduce stress, and improve mood. This study tests the feasibility of an 8-week mindfulness training program for adults and adolescents with ADHD. METHOD: Twenty-four adults and eight adolescents with ADHD enrolled in a feasibility study of an 8-week mindfulness training program. RESULTS: The majority of participants completed the training and reported high satisfaction with the training. Pre-post improvements in self-reported ADHD symptoms and test performance on tasks measuring attention and cognitive inhibition were noted. Improvements in anxiety and depressive symptoms were also observed. CONCLUSION: Mindfulness training is a feasible intervention in a subset of ADHD adults and adolescents and may improve behavioral and neurocognitive impairments. A controlled clinical study is warranted.

Atypical brain activation during simple & complex levels of processing in adult ADHD: an fMRI study.

OBJECTIVE: Executive dysfunction in ADHD is well supported. However, recent studies suggest that more fundamental impairments may be contributing. We assessed brain function in adults with ADHD during simple and complex forms of processing. METHOD: We used functional magnetic resonance imaging with forward and backward digit spans to investigate number repetitions and complex working memory function. If pathology is limited to higher cognitive operations, group differences should be confined to the backward condition. RESULTS: During the forward digit span, ADHD participants exhibited greater activation of LH linguistic processing areas and increased activation of right frontal and parietal cortices. During the backward digit span, they exhibited greater activation of LH linguistic processing areas and failed to activate bilateral parietal regions important for the complex executive operations. CONCLUSION: Abnormal brain function among adult ADHD participants was not limited to complex executive functions. Abnormal processing of numeric stimuli was indicated during both simple and complex cognitive operations.

Atypical brain laterality in adults with ADHD during dichotic listening for emotional intonation and words.

Few studies directly examined the nature of hemispheric specialization and interaction in ADHD. The present experiment investigated left/right brain dynamics in unmedicated right handed adults with ADHD (n = 19) and in controls (n = 19), using a dichotic listening task to assess hemispheric differences in word and emotion recognition. We also assessed how focusing attention on a single ear modulated lateralized performance and affected cross-callosal interference effects. Analysis of variance indicated that ADHD subjects showed reduced left hemisphere specialization, were better at processing emotions, and worse at processing words compared to controls. These differences were eliminated during focused attention. Finally, during presumed right hemisphere processing of linguistic stimuli, subjects with ADHD showed reduced left hemisphere interference. We concluded that ADHD subjects demonstrated greater right hemisphere and reduced left hemisphere contribution during this task relative to controls. We posit that these hemispheric differences were due to management or use of available cognitive resources rather than inherent capacity.