Young People’s Experience of ADHD and Stimulant Medication: A Qualitative Study for the NICE Guideline

Background: The NICE ADHD Guideline Group found a lack of research evidence on young people’s experiences with stimulant medications. The present study was commissioned to help fill this gap in the evidence base and to inform the Guideline. Method: Focus groups and 1:1 interviews with 16 UK young people with ADHD. Results: Young people were positive about taking medication, feeling that it reduced their disruptive behaviour and improved their peer relationships. Young people experienced stigma but this was related more to their symptomatic behaviours than to stimulant drug medication. Conclusions: The study’s findings helped to inform the NICE guideline on ADHD by providing evidence that young people’s experiences of medication were in general more positive than negative. All NICE Guidelines involving recommendations for the treatment of young people should draw on research evidence of young people’s experiences of treatments.     

Psychometric properties of the French Version of the Social Responsiveness Scale in autism spectrum disorder with or without attention deficit hyperactivity disorder

ObjectivesThe Social Responsiveness Scale (SRS) is an instrument that is commonly used to screen for Autism Spectrum Disorder (ASD). Attention Deficit Hyperactive Disorder (ADHD) frequently occurs with ASD and both disorders share some phenotypic similarities. In the present study, we aimed to determine the psychometric properties of the French version of the Social Responsiveness Scale (SRS) and its 5 subscales (social awareness, social cognition, social communication, social motivation, and autistic mannerisms) to discriminate between children with ADHD and those with ASD (differential diagnosis) and children with ADHD from those with a dual diagnosis of ADHD and ASD (comorbid diagnosis).MethodSRS total scores and the 5 subscores of the SRS were compared between 4 groups of children: ADHD (n = 32), ASD + ADHD (n = 30), ASD (n = 31) and typical neurodevelopment (TD; n = 30) children. The discriminant validity was estimated using the Area Under the ROC Curves (AUC).ResultsSRS Social cognition (AUC = 0.73) and Autistic mannerisms (AUC = 0.70) subscores were the most discriminating for differential diagnosis of ASD and ADHD. SRS total scores (AUC = 0.70), and Social communication (AUC = 0.66) and Autistic mannerisms (AUC = 0.75) subscores were the most discriminating for comorbid diagnosis of ASD among ADHD children.ConclusionThe SRS autistic mannerisms subscore was found to be clinically relevant for both differential diagnosis of ASD and ADHD and comorbid diagnoses of ASD among ADHD children but with a modest discriminant power.     

Age-Related Changes in Attended and Unattended P3 Latency in Normal Subjects

Event-related potentials to visual attended and unattended stimuli were studied in 37 normal subjects between the ages of 19 and 91. The components of the P3 responses to rare nontarget stimuli and rare target stimuli were measured as P3a and P3b, respectively. Both the P3a and P3b latencies were significantly and positively correlated with age. The N2 finding of age-related latency prolongation was comparable to the P3a changes with age. From the standpoint of the theory of automatic and controlled processing, these results suggest that both automatic processing, as reflected by the P3a, and attentional controlled processing, as reflected by the P3b, are impaired with normal aging.     

Examining the relationships between attention deficit/hyperactivity disorder and developmental coordination disorder symptoms,and writing performance in Japanese second grade students

The purpose of this study was to explore the relationships between attention deficit/hyperactivity disorder and developmental coordination disorder symptoms and writing performance in Japanese second grade students from regular classrooms. The second grade students (N = 873) in Japanese public elementary schools participated in this study. We examined a variety of writing tasks, such as tracing, copying, handwriting (Hiragana and Katakana), and spelling (Hiragana, Katakana, and Kanji). We employed the Japanese version of the home form ADHD-rating scale (ADHD-RS) and the Japanese version of the Developmental Coordination Disorder Questionnaire (DCDQ-J) to assess the developmental characteristics of the participating children. Seven writing performance scores were submitted to a principal component analysis with a promax rotation, which yielded three composite scores (Spelling Accuracy, Tracing and Copying Accuracy, and Handwriting Fluency). A multiple regression analysis found that inattention predicted Spelling Accuracy and Handwriting Fluency and that hyperactive-impulsive predicted Handwriting Fluency. In addition, fine motor ability predicted Tracing and Copying Accuracy. The current study offered empirical evidence suggesting that developmental characteristics such as inattention and fine motor skill are related to writing difficulties in Japanese typical developing children.     

Environmental enrichment improves cognitive deficits in Spontaneously Hypertensive Rats (SHR): Relevance for Attention Deficit/Hyperactivity Disorder (ADHD)

The interaction between genes and environment seems to be relevant for the development of Attention Deficit/Hyperactivity Disorder (ADHD), one of the most prevalent childhood psychiatric diseases. The occurrence of ADHD is typically associated with poor academic performance, probably reflecting learning difficulties and/or cognitive impulsiveness. The inbred Spontaneously Hypertensive Rats (SHR) strain has often been considered as an animal model of ADHD, since they ‘naturally’ display the main ADHD symptomatology. Although pharmacological agents improve SHR's cognitive deficits, little is known about the involvement of environmental factors in SHR disabilities and to what extent ‘protective’ non-pharmacological factors may be considered as strategy for ADHD prevention. Here we investigated whether the rearing environment during neurodevelopment may counteract later cognitive deficits presented by adult SHR. Wistar (WIS) rats were also used to investigate whether the putative effects of environmental enrichment depend on a specific genetic background. The animals were reared in enriched environment (EE) or standard environment (SE) from the post-natal day 21 until 3 months of age (adulthood) and tested for cognitive and non-cognitive phenotypes. EE improved SHR's performance in open field habituation, water maze spatial reference, social and object recognition tasks, while non-cognitive traits, such as nociception and hypertension, were not affected by EE. Response of WIS rats was generally not affected by the present EE. These results show that the general low cognitive performance presented by SHR rats strongly depends on the rearing environment and they may suggest modifications of the familial environment as a putative preventive strategy to cope with ADHD.     

Sensory processing in children with Autism Spectrum Disorder: Relationship with non-verbal IQ,autism severity and Attention Deficit/Hyperactivity Disorder symptomatology

The main objective of this study was to analyze in a sample of children with ASD the relationship between sensory processing, social participation and praxis impairments and some of the child's characteristics, such as non-verbal IQ, severity of ASD symptoms and the number of ADHD symptoms (inattention and hyperactivity/impulsivity), both in the home and main-classroom environments. Participants were the parents and teachers of 41 children with ASD from 5 to 8 years old (M = 6.09). They completed the Sensory Processing Measure (SPM) to evaluate sensory processing, social participation and praxis; the Gilliam Autism Rating Scale (GARS-2) to evaluate autism severity; and a set of items (the DSM-IV-TR criteria) to evaluate the number of inattention and hyperactivity/impulsivity symptoms in the child. Non-verbal IQ – measured by the Raven's Coloured Progressive Matrices Test – did not show a relationship with any of the SPM variables. The SPM variables were significant predictors of autism severity and had similar weights in the two environments. In the case of ADHD symptoms, the SPM variables had a greater weight in the home than in the classroom environment, and they were significant predictors of both inattention and hyperactivity/impulsivity – especially inattention – only in the family context. The moderate association between inattention and auditory processing found in the main-classroom suggests the possible utility of certain measures aimed to simplify any classroom's acoustic environment.     

Effects of atomoxetine and methylphenidate on attention and impulsivity in the 5-choice serial reaction time test

Deficits in attention and response inhibition are apparent across several neurodegenerative and neuropsychiatric disorders for which current pharmacotherapy is inadequate. The 5-choice serial reaction time test (5-CSRTT), which originated from the continuous performance test (CPT) in humans, may serve as a useful translational assay for efficacy in these key behavioral domains. The selective norepinepherine reuptake inhibitor, atomoxetine, represents the first non-stimulant based drug approved for Attention Deficit Hyperactivity Disorder (ADHD) and has replaced methylphenidate (Ritalin) as the first line in pharmacotherapy for the treatment of ADHD. Methylphenidate and atomoxetine have different cortical and sub-cortical neurochemical signatures that could predict differences in cognitive and non-cognitive functions. The present experiments investigated the effects of acute methylphenidate and atomoxetine in male long Evans rats in the 5-choice serial reaction time (5CSRT) test that is hypothesized to serve as a model of vigilance and impulsivity behaviors associated with ADHD. Long Evans rats were trained to perform at 75% correct responses with fewer than 20% missed trials in the 5CSRT test (500 ms stimulus duration, 5 s inter-trial interval (ITI)). By varying the ITI (10, 7, 5, and 4 s) on drug test days, impulsivity (as defined by premature responses) was dramatically increased with a concomitant decrease in attention (percent correct). Subsequently, animals were treated with methylphenidate (2.5 and 5 mg/kg, i.p.) or atomoxetine (0.1, 0.5 and 1 mg/kg, i.p.) using this design. In Experiment 1, treatment with methylphenidate modestly improved overall attention but the highest dose of methylphenidate (5.0 mg/kg) significantly increased impulsivity. In contrast, treatment with atomoxetine induced a marked decrease in impulsivity whilst modestly improving overall attention. Interestingly, no effect was observed on measures of performance (e.g. motivation/sedation) with atomoxetine, whilst moderate hyperactivity (faster overall response latencies; magazine, correct, incorrect) was observed in the methylphenidate group. Those data suggest that the 5CSRT test can be used to differentiate stimulant and non-stimulant pharmacotherapies on measures of impulsivity.     

An electrophysiological investigation of reinforcement effects in attention deficit/hyperactivity disorder: Dissociating cue sensitivity from down-stream effects on target engagement and performance

ObjectiveNeural hypo-sensitivity to cues predicting positive reinforcement has been observed in ADHD using the Monetary Incentive Delay (MID) task. Here we report the first study using an electrophysiological analogue of this task to distinguish between (i) cue related anticipation of reinforcement and downstream effects on (ii) target engagement and (iii) performance in a clinical sample of adolescents with ADHD and controls.MethodsThirty-one controls and 32 adolescents with ADHD aged 10–16 years performed the electrophysiological (e)-MID task − in which preparatory cues signal whether a response to an upcoming target will be reinforced or not − under three conditions; positive reinforcement, negative reinforcement (response cost) and no consequence (neutral). We extracted values for both cue-related potentials known to be, both, associated with response preparation and modulated by reinforcement (Cue P3 and Cue CNV) and target-related potentials (target P3) and compared these between ADHD and controls.ResultsADHD and controls did not differ on cue-related components on neutral trials. Against expectation, adolescents with ADHD displayed Cue P3 and Cue CNV reinforcement-related enhancement (versus neutral trials) compared to controls. ADHD individuals displayed smaller target P3 amplitudes and slower and more variable performance − but effects were not modulated by reinforcement contingencies. When age, IQ and conduct problems were controlled effects were marginally significant but the pattern of results did not change.DiscussionADHD was associated with hypersensitivity to positive (and marginally negative) reinforcement reflected on components often thought to be associated with response preparation − however these did not translate into improved attention to targets. In the case of ADHD, upregulated CNV may be a specific marker of hyper-arousal rather than an enhancement of anticipatory attention to upcoming targets. Future studies should examine the effects of age, IQ and conduct problems on reinforcement sensitivity in ADHD.     

Impaired early visual response modulations to spatial information in chronic schizophrenia

Early visual processing stages have been demonstrated to be impaired in schizophrenia patients and their first-degree relatives. The amplitude and topography of the P1 component of the visual evoked potential (VEP) are both affected; the latter of which indicates alterations in active brain networks between populations. At least two issues remain unresolved. First, the specificity of this deficit (and suitability as an endophenotype) has yet to be established, with evidence for impaired P1 responses in other clinical populations. Second, it remains unknown whether schizophrenia patients exhibit intact functional modulation of the P1 VEP component; an aspect that may assist in distinguishing effects specific to schizophrenia. We applied electrical neuroimaging analyses to VEPs from chronic schizophrenia patients and healthy controls in response to variation in the parafoveal spatial extent of stimuli. Healthy controls demonstrated robust modulation of the VEP strength and topography as a function of the spatial extent of stimuli during the P1 component. By contrast, no such modulations were evident at early latencies in the responses from patients with schizophrenia. Source estimations localized these deficits to the left precuneus and medial inferior parietal cortex. These findings provide insights on potential underlying low-level impairments in schizophrenia.     

Impaired novelty P3 potentials in multiple system atrophy--correlation with orthostatic hypotension

Although neuropsychological tests demonstrate frontal lobe dysfunction in multiple system atrophy (MSA), assessment of frontal function using event-related brain potentials (ERPs) has not been sufficiently performed in MSA. The correlation between frontal lobe dysfunction and orthostatic hypotension (OH), which is known to cause frontal hypoperfusion, remains unclear. Our objectives were to assess frontal lobe dysfunction in MSA patients using ERPs and to elucidate the relevance of OH to changes in ERPs. Nine consecutive patients with MSA and nine age- and gender-matched healthy controls were compared by performance in the Wisconsin Card Sorting Test (WCST) and somatosensory ERPs to target and novel stimuli, namely, parietal maximal P3 (target P3) and fronto-central P3 (novelty P3), respectively. The correlation between novelty P3 and OH was evaluated in the MSA group. The MSA group showed a poorer performance in categories achieved (CA), total errors (TE) and perseverative errors by Nelson's (PEN) method in the WCST compared with the control group (CA and PEN: p<0.01; TE: p<0.02). Novelty and target P3s in the MSA group showed significantly prolonged latency (novelty: p<0.05; target: p<0.01) and reduced amplitude (novelty: p<0.02; target: p<0.01) compared with the control group. There was a significant negative correlation between novelty P3 latency and a drop in systolic blood pressure (r=0.76; p<0.02). Abnormalities of novelty P3 in the MSA group might reflect frontal lobe dysfunction, namely failure of attentional set-shifting, that was identified by the WCST. OH may play a role in the development of frontal lobe dysfunction in MSA.     

Reduced activation and inter-regional functional connectivity of fronto-striatal networks in adults with childhood Attention-Deficit Hyperactivity Disorder (ADHD) and persisting symptoms during tasks of motor inhibition and cognitive switching

Attention-Deficit Hyperactivity Disorder (ADHD) in children has been associated with fronto-striatal functional abnormalities during tasks of inhibitory control. In adults with ADHD, however, hardly any functional magnetic resonance imaging (fMRI) studies have investigated the neurofunctional correlates of the most compromised cognitive functions of motor response inhibition and no study has investigated cognitive flexibility. In this study we used fMRI to compare brain function and task-relevant inter-regional functional connectivity between 11 medication-naïve adults with persistent inattentive/hyperactive behaviours, followed up from childhood when they had been diagnosed with ADHD, and 14 age-matched healthy controls during a Stop and a cognitive Switch tasks. Whole-brain regression MR analyses were conducted within patients to correlate symptoms with brain activation. Despite comparable task performance, adults with childhood ADHD showed reduced activation compared to controls in bilateral inferior prefrontal cortex, caudate and thalamus during both tasks, as well as in left parietal lobe during the Switch task. Within patients, the severity of the behavioural symptoms was negatively correlated with more extensive activation of similar regions in fronto-striatal, parietal and cerebellar brain areas. In the Stop task, patients showed reduced inter-regional functional connectivity between right inferior fronto-frontal, fronto-striatal and fronto-parietal neural networks. The findings demonstrate that adults with childhood ADHD and persisting behavioural symptoms show strikingly similar patterns of fronto-striatal and parietal dysfunction to those observed in childhood ADHD during the same tasks of inhibitory control. This suggests that neuro-functional abnormalities in ADHD patients are likely to continue between childhood and early adulthood.     

To make a molehill out of a mountain: An ERP-study on cognitive reappraisal of negative pictures in children with and without ADHD

Objective

We investigated cognitive reappraisal in children with ADHD by means of the late positive potential (LPP) and self-report ratings. We expected diminished LPP modulation following reappraisal and lower self-report scores in children with ADHD.

Changes in EEG Spectrograms,Event-Related Potentials and Event-Related Desynchronization Induced by Relative Beta Training in ADHD Children

ABSTRACT

Background. During the last three decades EEG-based biofeedback (neurofeed-back) was used as an alternative treatment for reducing symptoms of ADHD. The goal of this study was to objectively assess the efficacy of biofeedback training by comparing spectrograms, ERPs and ERDs, measured before and after 20 sessions of neurotherapy in a group of ADHD children.

Method. Electroencephalogram (EEG), Event related potentials (ERPs) and event related synchronisation/desynchronisation (ERD/ERS) were recorded and computed in auditory GO/ NOGO task before and after 15–22 sessions of EEG biofeedback. Eighty-six ADHD children participated in the study. Each session consisted of 30 min of relative beta training. The patients were divided into two groups (good performers and poor performers) depending on their ability to elevate beta activity during sessions.

Results. Amplitude of late positive components of evoked potentials in response to NOGO stimuli increased, and event-related synchronisation in alpha frequency band measured at central areas decreased after the whole set of sessions of neurofeedback training in the group of good performers but did not change for the poor performers group. Evoked potential differences between post- and pre-treatment conditions for good performers were distributed over frontal-central areas, reflecting activation of frontal cortical areas associated with beta training.

Conclusion. Relative beta training with electrodes located above the frontal areas was associated with an increase of the late positive NOGO component. This activation likely indicates recovery of normal functioning of the executive system.     

Association between dopamine D4 receptor (DRD4) gene polymorphisms and novelty-elicited auditory event-related potentials in preschool children

We investigated associations of the exon III repeat and the -521 C/T polymorphisms of the DRD4 gene with novelty-elicited auditory ERP components and behavioral resistance to distraction in 57 healthy, typically developing 6-year-old children. Dopamine-related gene polymorphisms have previously been linked to processes directing focused attention. We did not find associations between the 7-repeat allele or the T.7 haplotype and the early ERP responses suggesting that DRD4 polymorphisms did not affect the detection of novelty. However, the same polymorphisms affected the late negative components (LN1 and LN2). Late negativities elicited by deviant and novel sounds have been regarded as reflecting reorientation after distraction or additional processing of new information. Children carrying the T.7 haplotype had significantly smaller LN1 and LN2 amplitudes. The presence of the T.7 haplotype also significantly enhanced behavioral resistance to distraction. We suggest that less distraction in T.7 carriers led to less reorienting activity (reflected by the LN components). We also speculate that activation of less sensitive and fewer D4 receptors (as with the T.7 haplotype) is less effective in modulating GABAergic inhibitory signaling, which in turn is reflected in smaller LN amplitudes.     

EEG event related potentials in sustained,focused and divided attention tasks: Potential biomarkers for cognitive impairment in HIV patients

ObjectivesThe objective of this study was to assess the usability of event-related-potentials (ERPs) during sustained, focused, and divided attention tasks as biomarkers for cognitive decline in HIV patients.MethodsEEG was acquired using a mobile/wireless 9-channel system in 39 persons with HIV, with well-controlled immune function and 63 healthy control participants (HCs) during three ERP tasks: sustained attention, focused attention, and divided attention.ResultsThe HIV-group evidenced smaller late positive potential (LPP) and larger P200 amplitudes across the tasks compared to the HC group. P200 amplitude was correlated (r = 0.56) with the estimated duration of infection. Both groups showed higher P200 and LPP amplitudes in response to infrequent stimuli; this effect was not significantly different between groups. In the sustained attention task, the HIV-group showed significantly slower reaction time than controls while maintaining the same level of accuracy. In the divided attention task, the HIV-group showed a trend towards faster/less accurate responses.ConclusionsHIV seropositive participants receiving anti-retroviral treatment (ART) demonstrated significantly larger P200 amplitude during three different attention tasks. This may reflect attentional deficits characterized by over-attending to non-target/distracting stimuli.SignificanceThese findings demonstrate the potential benefits of EEG-ERP metrics derived from attention tasks as neurocognitive biomarkers for HIV. This approach may reveal underlying causes of attentional deficits in HIV patients.     

注意缺陷多动障碍与智商及事件相关电位的关系

目的：研究事件相关电位(ERP)与智商(IQ)及注意缺陷多动障碍(ADHD)之间的相互关系。方法：采用肌电图诱发电位仪记录靶刺激及非靶刺激结果，结合测试智商的方法。结果：ADHD组事件相关电位靶刺激计数正确率显著低于对照组儿童；P2，P3潜伏期显著延长；NlP2峰峰值显著低于对照组；两次记录P3波重复性显著低于对照组儿童；IQ(包括总智商(FIQ)、言语智商(VIQ)、操作智商(PIQ))均显著低于对照组儿童；相关分析结果显示P2，N2，P3潜伏期与FIQ，PIQ呈显著负相关；NlP2峰峰值与FIQ，VlQ呈显著正相关。Logistic回归分析显示靶刺激计数正确率及FIQ为ADHD的显著保护因素，岛潜伏期与FIQ存在显著的交互作用。结论：ADHD患儿排除干扰的能力及认知功能显著受损。交互作用结果则显示IQ与P3潜伏期对ADHD的影响互为拮抗。提示ADHD患儿的额前区功能不成熟。     

Investigation of attention deficit hyperactivity disorder (ADHD) sub-types in children via EEG frequency domain analysis

Aim of the study: To investigate the frequency domain effects and changes in electroencephalography (EEG) signals in children diagnosed with attention deficit hyperactivity disorder (ADHD).

Patients and methods: The study contains 40 children. All children were between the ages of 7 and 12 years. Participants were classified into four groups which were ADHD (n=20), ADHD-I (ADHD-Inattentive type) (n=10), ADHD-C (ADHD-Combined type) (n=10), and control (n=20) groups. In this study, the frequency domain of EEG signals for ADHD, subtypes and control groups were analyzed and compared using Matlab software. The mean age of the ADHD children's group was 8.7 years and the control group 9.1 years.

Results: Spectral analysis of mean power (μV²) and relative-mean power (%) was carried out for four different frequency bands: delta (0--4 Hz), theta (4--8 Hz), alpha (8--13 Hz) and beta (13--32 Hz). The ADHD and subtypes of ADHD-I, and ADHD-C groups had higher average power value of delta and theta band than that of control group. However, this is not the case for alpha and beta bands. Increases in delta/beta ratio and statistical significance were found only between ADHD-I and control group, and in delta/beta, theta/delta ratio statistical significance values were found to exist between ADHD-C and control group.

Conclusion: EEG analyzes can be used as an alternative method when ADHD subgroups are identified.     

Beyond valence and magnitude: a flexible evaluative coding system in the brain

Outcome evaluation is a cognitive process that plays an important role in our daily lives. In most paradigms utilized in the field of experimental psychology, outcome valence and outcome magnitude are the two major features investigated. The classical “independent coding model” suggests that outcome valence and outcome magnitude are evaluated by separate neural mechanisms that may be mapped onto discrete event-related potential (ERP) components: feedback-related negativity (FRN) and the P3, respectively. To examine this model, we presented outcome valence and magnitude sequentially rather than simultaneously. The results reveal that when only outcome valence or magnitude is known, both the FRN and the P3 encode that outcome feature; when both aspects of outcome are known, the cognitive functions of the two components dissociate: the FRN responds to the information available in the current context, while the P3 pattern depends on outcome presentation sequence. The current study indicates that the human evaluative system, indexed in part by the FRN and the P3, is more flexible than previous theories suggested.     

Comparing the executive attention of adult females with ADHD to that of females with sensory modulation disorder (SMD) under aversive and non-aversive auditory conditions

Certain behavioral expressions of sensory modulation disorder (SMD) such as distractibility, hyperactivity, and impulsivity are often similar to those of attention deficit/hyperactivity disorder (ADHD) in pediatric and adult populations. There is also a high comorbidity rate between these two diagnoses and absence of research regarding the objective neuropsychological differentiation between them. In the present study we employed a factorial design which enabled us to: (a) systematically examine the effects of SMD and ADHD on executive attention in a sample of adult females using a Stroop-like task, and (b) measure the effect of aversive conditions (sounds) on executive attention. The experimental measures used were the Stroop-like Location – Direction Task (SLDT) to assess executive attention and the battery of aversiveness to sounds (BAS), a standardized measure of aversive sounds that was developed for this study and enabled individual customization of aversive auditory sounds. Results revealed, as expected, a specific core deficit in executive attention for the ADHD factor. In addition to that, the present study provides an important, pioneering finding of SMD impairment in a unique combination of a cognitively demanding task with aversive sounds, providing preliminary objective evidence differentiating SMD from ADHD.