Abnormalities In Attention Deficit Hyperactivity Disorder Research Articles

Compressed cerebro-cerebellar functional gradients in children and adolescents with attention-deficit/hyperactivity disorder.

Both cortical and cerebellar developmental differences have been implicated in attention-deficit/hyperactivity disorder (ADHD). Recently accumulating neuroimaging studies have highlighted hierarchies as a fundamental principle of brain organization, suggesting the importance of assessing hierarchy abnormalities in ADHD. A novel gradient-based resting-state functional connectivity analysis was applied to investigate the cerebro-cerebellar disturbed hierarchy in children and adolescents with ADHD. We found that the interaction of functional gradient between diagnosis and age was concentrated in default mode network (DMN) and visual network (VN). At the same time, we also found that the opposite gradient changes of DMN and VN caused the compression of the cortical main gradient in ADHD patients, implicating the co-occurrence of both low- (visual processing) and high-order (self-related thought) cognitive dysfunction manifesting in abnormal cerebro-cerebellar organizational hierarchy in ADHD. Our study provides a neurobiological framework to better understand the co-occurrence and interaction of both low-level and high-level functional abnormalities in the cortex and cerebellum in ADHD.

Unravelling Neurodevelopment: A Comprehensive Neuroimaging Exploration of Paediatric Disorders in a Tertiary Care Setting

Background: Paediatric neurodevelopmental disorders, including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), intellectual disability (ID), and specific learning disabilities (SLD), present a growing healthcare challenge globally. This study, conducted at a tertiary care hospital in India, aims to explore the utility of neuroimaging techniques in understanding the structural and functional abnormalities associated with these disorders, considering the unique demographic and healthcare landscape of India. Methods: A multidisciplinary team collaborated in a cross-sectional observational study involving paediatric patients diagnosed with neurodevelopmental disorders. State-of-the-art magnetic resonance imaging (MRI) and functional MRI (fMRI) were employed. Participants underwent clinical assessments, and neuroimaging data were analyzed for structural and functional abnormalities. Advanced techniques such as diffusion tensor imaging (DTI) were utilized to explore microstructural changes in white matter tracts. Results: Distinct neuroimaging patterns were observed in different neurodevelopmental disorders. Structural abnormalities were prominent in ASD and ID, with nuanced variations in gray and white matter volumes. Functional connectivity abnormalities in ADHD were highlighted, emphasizing the involvement of attention and executive function networks. DTI revealed microstructural changes in white matter tracts, particularly in the prefrontal-striatal circuitry in ADHD and disruptions in interhemispheric communication in ASD. Conclusion: Our study contributes valuable insights into the neurobiological underpinnings of paediatric neurodevelopmental disorders, emphasizing the importance of neuroimaging for tailored diagnostic and therapeutic approaches.

Overactivated contextual visual perception and response to a single dose of methylphenidate in children with ADHD.

The pathogenesis of overactivated visual perception in attention-deficit hyperactivity disorder (ADHD) remains unclear, which is interpreted as a cognitive compensation. The existing studies have proposed that perceptual abnormalities in neurodevelopmental disorders are associated with dysfunction of the contextual knowledge system, which influences the development and formation of perception. We hypothesized that alterations in contextual states may also be responsible for inducing perceptual abnormalities in ADHD. Therefore, the present study evaluated the characteristics of pre-stimulus alpha and its response to a single dose of methylphenidate (MPH). A total of 135 Chinese children participated in the first study, including 70 children with ADHD (age = 10.61 ± 1.93years, female = 17) and 65 age- and sex-matched control children (age = 10.73 ± 1.93years, female = 20). The second clinical trial included 19 Chinese children with ADHD (age = 11.85 ± 1.72years, female = 4), with an identical visual spatial search task. Pre-stimulus alpha oscillations and P1 activity were significantly greater in children with ADHD than in the controls. Overactivated pre-stimulus alpha positively predicted P1. Both pre-stimulus alpha and P1 overactivation have beneficial effects on cognitive performance in children with ADHD. No intervening effect of a single dose of MPH on the compensatory activation of pre-stimulus alpha and P1 were observed. Our findings extended the perceptual activation to the contextual knowledge system, suggesting that compensatory perception in children with ADHD is more likely to be a top-down regulated cognitive operational process.

Aberrant brain dynamics and spectral power in children with ADHD and its subtypes

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

Effects of Methylphenidate on the Dopamine Transporter and Beyond.

The dopamine transporter (DAT) is the main target of methylphenidate (MPH), which remains the number one drug prescribed worldwide for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD). In addition, abnormalities of the DAT have been widely associated with ADHD. Based on clinical and preclinical studies, the direction of DAT abnormalities in ADHD are, however, still unclear. Moreover, chronic treatment of MPH has been shown to increase brain DAT expression in both animals and ADHD patients, suggesting that findings of overexpressed levels of DAT in ADHD patients are possibly attributable to the effects of long-term MPH treatment rather than the pathology of the condition itself. In this chapter, we will discuss some of the effects exerted by MPH, which are related to its actions on catecholamine protein targets and brain metabolites, together with genes and proteins mediating neuronal plasticity. For this purpose, we present data from biochemical, proton nuclear magnetic resonance spectroscopy (1H-NMR) and gene/protein expression studies. Overall, results of the studies discussed in this chapter show that MPH has a complex biological/pharmacological action well beyond the DAT.

Disorder-specific brain volumetric abnormalities in Attention-Deficit/Hyperactivity Disorder relative to Autism Spectrum Disorder.

The overlap/distinctiveness between Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) has been increasingly investigated in recent years, particularly since the DSM-5 allows the dual diagnosis of ASD and ADHD, but the underlying brain mechanisms remain unclear. Although both disorders are associated with brain volumetric abnormalities, it is necessary to unfold the shared and specific volume abnormalities that could contribute to explain the similarities and differences in the clinical and neurocognitive profiles between ADHD and ASD. In this voxel-based morphometry (VBM) study, regional grey matter volumes (GMV) were compared between 22 children with ADHD, 18 children with ASD and 17 typically developing (TD) children aged 8 to 12 years old, controlling for age and total intracranial volume. When compared to TD children or children with ASD, children with ADHD had a larger left precuneus, and a smaller right thalamus, suggesting that these brain abnormalities are specific to ADHD relative to ASD. Overall, this study contributes to the delineation of disorder-specific structural abnormalities in ADHD and ASD.

Abnormal functional network centrality in drug-naïve boys with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed neurodevelopmental disorder in childhood and is characterized by inattention, impulsivity, and hyperactivity. Observations of distributed functional abnormalities in ADHD suggest aberrant large-scale brain network connectivity. However, few studies have measured the voxel-wise network centrality of boys with ADHD, which captures the functional relationships of a given voxel within the entire connectivity matrix of the brain. Here, to examine the network patterns characterizing children with ADHD, we recruited 47 boys with ADHD and 21 matched control boys who underwent resting-state functional imaging scanning in a 3.0 T MRI unit. We measured voxel-wise network centrality, indexing local functional relationships across the entire brain connectome, termed degree centrality (DC). Then, we chose the brain regions with altered DC as seeds to examine the remote functional connectivity (FC) of brain regions. We found that boys with ADHD exhibited (1) decreased centrality in the left superior temporal gyrus (STG) and increased centrality in the left superior occipital lobe (SOL) and right inferior parietal lobe(IPL); (2) decreased FC between the STG and the putamen and thalamus, which belong to the cognitive cortico-striatal-thalamic-cortical (CSTC) loop, and increased FC between the STG and medial/superior frontal gyrus within the affective CSTC loop; and (3) decreased connectivity between the SOL and cuneus within the dorsal attention network. Our results demonstrated that patients with ADHD show a connectivity-based pathophysiological process in the cognitive and affective CSTC loops and attention network.

Structural and functional neuroimaging in attention-deficit/hyperactivity disorder.

Over the last decade, there has been a dramatic increase in the number of neuroimaging studies in attention-deficit/hyperactivity disorder (ADHD). In terms of brain structure, magnetic resonance imaging (MRI), and diffusion tensor imaging studies have evidenced differences in volume, surface-based measures (cortical thickness, surface area, and gyrification), and white matter integrity in different cerebral regions, in children and adults with ADHD compared to population norms. Abnormalities in the basal ganglia, prefrontal structures, and the corpus callosum have been the most consistently reported findings across studies. Hemodynamic (functional MRI, functional near-infrared spectroscopy, positron emission tomography, single-photon emission computed tomography) and magnetoencephalography measurements have also shown differences in neural activity during the execution of neuropsychological tasks and during rest, in widespread regions of the brain. Importantly, multimodal studies combining structural and functional methods have shown an intercorrelation between structural and functional abnormalities in ADHD. Further longitudinal studies are needed to clarify the effects of age and medication on brain structure and function in individuals with ADHD. WHAT THIS PAPER ADDS: In attention-deficit/hyperactivity disorder (ADHD), the brain is characterized by abnormal neural network interplay. Structural and functional cerebral abnormalities in ADHD are intercorrelated. Currently there is no neural biomarker that can be used in diagnosis. Longitudinal studies have shed light on the brain correlates of ADHD over the lifespan. The effects of stimulant intake on the brain correlates of ADHD remain unclear.

Multivariate Imaging Genetics Study of MRI Gray Matter Volume and SNPs Reveals Biological Pathways Correlated with Brain Structural Differences in Attention Deficit Hyperactivity Disorder

Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder affecting children, adolescents, and adults. Its etiology is not well understood, but it is increasingly believed to result from diverse pathophysiologies that affect the structure and function of specific brain circuits. Although one of the best-studied neurobiological abnormalities in ADHD is reduced fronto-striatal-cerebellar gray matter (GM) volume, its specific genetic correlates are largely unknown. In this study, T1-weighted MR images of brain structure were collected from 198 adolescents (63 ADHD-diagnosed). A multivariate parallel independent component analysis (Para-ICA) technique-identified imaging genetic relationships between regional GM volume and single nucleotide polymorphism data. Para-ICA analyses extracted 14 components from genetic data and 9 from MR data. An iterative cross-validation using randomly chosen subsamples indicated acceptable stability of these ICA solutions. A series of partial correlation analyses controlling for age, sex, and ethnicity revealed two genotype-phenotype component pairs significantly differed between ADHD and non-ADHD groups, after a Bonferroni correction for multiple comparisons. The brain phenotype component not only included structures frequently found to have abnormally low volume in previous ADHD studies but was also significantly associated with ADHD differences in symptom severity and performance on cognitive tests frequently found to be impaired in patients diagnosed with the disorder. Pathway analysis of the genotype component identified several different biological pathways linked to these structural abnormalities in ADHD. Some of these pathways implicate well-known dopaminergic neurotransmission and neurodevelopment hypothesized to be abnormal in ADHD. Other more recently implicated pathways included glutamatergic and GABA-eric physiological systems; others might reflect sources of shared liability to disturbances commonly found in ADHD, such as sleep abnormalities.

A randomized controlled clinical trial of real-time functional magnetic resonance imaging neurofeedback for adolescents with attention deficit hyperactivity disorder (ADHD)

A randomized controlled clinical trial of real-time functional magnetic resonance imaging neurofeedback for adolescents with attention deficit hyperactivity disorder (ADHD)

Mode of Anisotropy Reveals Global Diffusion Alterations in Attention-Deficit/Hyperactivity Disorder

Diffusion tensor imaging (DTI) can identify structural connectivity alterations in attention-deficit/hyperactivity disorder (ADHD). Most ADHD DTI studies have concentrated on regional differences in fractional anisotropy (FA) despite its limited sensitivity to complex white matter architecture and increasing evidence of global brain differences in ADHD. Here, we examine multiple DTI metrics in separate samples of children and adults with and without ADHD with a principal focus on global between-group differences. Two samples: adults with ADHD (n= 42) and without (n= 65) and children with ADHD (n= 82) and without (n= 80) were separately group matched for age, sex, and head motion. Five DTI metrics (FA, axial diffusivity, radial diffusivity, mean diffusivity, and mode of anisotropy) were analyzed via tract-based spatial statistics. Group analyses tested for diagnostic differences at the global (averaged across the entire white matter skeleton) and regional level for each metric. Robust global group differences in diffusion indices were found in adults, with the largest effect size for mode of anisotropy (MA; Cohen's d= 1.45). Global MA also differed significantly between groups in the pediatric sample (d= 0.68). In both samples, global MA increased classification accuracy compared to the model with clinical Conners' ADHD ratings alone. Regional diagnostic differences did not survive familywise correction for multiple comparisons. Global DTI metrics, particularly the mode of anisotropy, which is sensitive to crossing fibers, capture connectivity abnormalities in ADHD across both pediatric and adult samples. These findings highlight potential diffuse white matter microarchitecture differences in ADHD.

Neural correlates of visuospatial working memory in attention-deficit/hyperactivity disorder and healthy controls

Impaired visuospatial working memory (VSWM) is suggested to be a core neurocognitive deficit in attention-deficit/hyperactivity disorder (ADHD), yet the underlying neural activation patterns are poorly understood. Furthermore, it is unclear to what extent age and gender effects may play a role in VSWM-related brain abnormalities in ADHD. Functional magnetic resonance imaging (fMRI) data were collected from 109 individuals with ADHD (60% male) and 103 controls (53% male), aged 8–25 years, during a spatial span working memory task. VSWM-related brain activation was found in a widespread network, which was more widespread compared with N-back tasks used in the previous literature. Higher brain activation was associated with higher age and male gender. In comparison with controls, individuals with ADHD showed greater activation in the left inferior frontal gyrus (IFG) and the lateral frontal pole during memory load increase, effects explained by reduced activation on the low memory load in the IFG pars triangularis and increased activation during high load in the IFG pars opercularis. Age and gender effects did not differ between controls and individuals with ADHD. Results indicate that individuals with ADHD have difficulty in efficiently and sufficiently recruiting left inferior frontal brain regions with increasing task difficulty.

When Is EEG Indicated in Attention-Deficit/Hyperactivity Disorder?

The authors investigated the parameters for predicting epileptiform abnormalities in a group of children diagnosed with attention-deficit/hyperactivity disorder (ADHD). The sample consisted of 148 subjects aged between 6 and 13 (8.76 ± 1.26; 25.7% female) years. Subtypes of ADHD and comorbid psychiatric disorders were defined according to DSM-IV criteria. The Wechsler Intelligence Scale for Children-Revised was applied to all patients. Most of the subjects (89.2%) had wakefulness and sleep electroencephalography examinations lasting about one hour. The authors found out that the coexistence of speech sound disorder (odds ratio [OR] 3.90, 95% confidence interval [CI]: 1.61-9.48) and higher Digit Span test performance (OR 1.24, 95% CI: 1.06-1.44) predicted the presence of accompanying epileptiform abnormalities. The prevalence of epileptiform abnormalities was 26.4%, and they were frequently localized in the frontal (41%) and centrotemporal (28.2%) regions. Higher percentage of speech sound disorder co-occurrence (64%) in subjects with rolandic spikes suggests that epileptiform abnormalities associated with ADHD can be determined genetically at least in some cases. Pathophysiology of epileptiform abnormalities in ADHD might have complex genetic and maturational background.

Electroencephalographic activity before and after cognitive effort in children with attention deficit/hyperactivity disorder.

Numerous studies have detected elevated electroencephalographic (EEG) theta/beta ratio (TBR) or theta power in children with attention deficit/hyperactivity disorder (ADHD) and therefore TBR has been suggested to be a promising biomarker of ADHD. At the same time, recent theoretical models have emphasized the heterogeneity of ADHD and the notion that cognitive deficits in ADHD are not fixed but fluctuate according to contextual and state factors. Surprisingly, so far the context- or state-dependency of EEG abnormalities in ADHD has hardly been addressed. Therefore, in the current study, 3 minutes eyes closed resting EEG before and after execution of 3 n-back tasks were compared between 21 children with ADHD and 22 typically developing children. No difference between groups was found for TBR or theta power (or other frequency bands), neither before nor after task execution, indicating that enhanced TBR or theta power is not to be considered universal for the disorder. Hence, cautiousness is warranted in using these indices for diagnostic purposes in ADHD. Across groups, posterior theta power, as well as central and posterior beta power was attenuated after task execution, which was interpreted as the children experiencing a more alert state after cognitive effort. Yet, this EEG modulation was similar in both groups, providing no support for a context-or state-dependency of EEG abnormalities in ADHD. However, in light of the absence of any group differences in EEG parameters, further research is warranted.

Different Mechanisms of White Matter Abnormalities in Attention-Deficit/Hyperactivity Disorder: A Diffusion Tensor Imaging Study

Literature regarding white matter (WM) abnormalities in attention-deficit/hyperactivity disorder (ADHD) is sparse and inconsistent. In this article, we shed more light on WM microstructure in ADHD, its association with symptom count, and the familiality of WM abnormalities in ADHD. Diffusion tensor imaging (DTI) was performed in a large sample of individuals with ADHD (n = 170), their unaffected siblings (n = 80), and healthy controls (n = 107), aged 8 to 30 years. Extensive categorical as well as dimensional data regarding ADHD status and symptom count were collected. A whole-brain voxelwise approach was used to investigate associations between ADHD status and symptom count and WM microstructure, as measured by fractional anisotropy (FA) and mean diffusivity (MD). Individuals with ADHD showed decreased FA and decreased MD in several widespread, non-overlapping brain regions. In contrast, higher ADHD symptom count was consistently associated with increased FA and decreased MD in the ADHD group. Unaffected siblings resembled individuals in the ADHD group with regard to decreased FA but had MD similar to that in healthy controls. Results were not confounded by socioeconomic status, the presence of comorbidities, or a history of medication use. Our results indicate widespread disturbances in WM microstructure in ADHD, which seem to be driven by 2 different mechanisms. Decreased FA in ADHD may be due to a familial vulnerability to the disorder, whereas a second mechanism may drive the association between ADHD symptom count and both higher FA and lower MD. Such different mechanisms may play an important role in the inconsistencies found in the current literature.

Behavioural effects of monoamine reuptake inhibitors on symptomatic domains in an animal model of attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurobehavioural disorder. Several lines of evidence have implicated monoamine signalling systems, including transporters and receptors, in the pathogenesis of ADHD. We explored the heterogeneity of neural mechanisms that may possibly underlie symptomatic abnormalities in ADHD, by investigating the effects of monoamine reuptake inhibitors with differential spectrums for each monoamine transporter on ADHD-like behaviours in an animal model of ADHD, i.e. juvenile (6-week-old) male stroke-prone spontaneously hypertensive rats (SHRSP/Ezo). The impaired spontaneous alternation performance in a Y-maze task, demonstrated the inattentive features of SHRSP/Ezo, was improved by a selective DA reuptake inhibitor GBR-12909 (1 and 3mg/kg, i.p.). Desipramine (1, 3 and 10mg/kg, i.p.) and milnacipran (30mg/kg, i.p.), which possess a noradrenaline (NA) reuptake inhibitory activity, also ameliorated inattentive behaviour. Increased locomotor activity in open-field apparatus and total arm entries in a Y-maze task, which demonstrate the hyperactive features of SHRSP/Ezo, were improved by desipramine and milnacipran, but impaired by a high dose of GBR-12909 (10mg/kg, i.p.). A selective serotonin (5-HT) reuptake inhibitor fluvoxamine (10 and 30mg/kg, i.p.), did not affect inattention but significantly suppressed hyperactivity at a high dose (30mg/kg, i.p.). Moreover, a low dose of fluvoxamine (3mg/kg, i.p.) ameliorated the increased open arm spent time in an elevated plus-maze without affecting total arm entries, indicating an effect on impulsive features based on the anxiolytic characteristics of SHRSP/Ezo.These behavioural effects of monoamine reuptake inhibitors support the heterogeneity of monoaminergic systems, which are responsible for ADHD-like behaviours in SHRSP/Ezo. These findings may provide pharmacological evidence for the development of ADHD treatments that target more appropriate monoamine transporters.

Diagnostic Value of Resting Electroencephalogram in Attention-Deficit/Hyperactivity Disorder Across the Lifespan

The resting electroencephalogram (EEG) reflects development and arousal, but whether it can support clinical diagnosis of attention-deficit/hyperactivity disorder (ADHD) remains controversial. Here we examined whether theta power and theta/beta ratio are consistently elevated in ADHD and younger age as proposed. Topographic 48-channel EEG from 32 children (8-16years) and 22 adults (32-55years) with ADHD and matched healthy controls (n=30 children/21 adults) was compared. Following advanced artefact correction, resting EEG was tested for increased theta and theta/beta activity due to ADHD and due to normal immaturity. Discriminant analyses tested classification performance by ADHD and age using these EEG markers as well as EEG artefacts and deviant attentional event-related potentials (ERPs). No consistent theta or theta/beta increases were found with ADHD. Even multivariate analyses indicated only marginal EEG power increases in children with ADHD. Instead, consistent developmental theta decreases were observed, indicating that maturational lags of fewer than 3years would have been detected in children. Discriminant analysis based on proposed simple spectral resting EEG markers was successful for age but not for ADHD (81 vs. 53% accuracy). Including ERP markers and EEG artefacts improved discrimination, although not to diagnostically useful levels. The lack of consistent spectral resting EEG abnormalities in ADHD despite consistent developmental effects casts doubt upon conventional neurometric approaches towards EEG-based ADHD diagnosis, but is consistent with evidence that ADHD is a heterogeneous disorder, where the resting state is not consistently characterised by maturational lag.

Biochemical and genetic analyses of childhood attention deficit/hyperactivity disorder

Attention deficit/hyperactivity disorder (ADHD) in children is a neurobehavioral disorder characterized by inattention, hyperactivity, and/or impulsivity. The biochemical abnormalities and genetic factors play significant roles in the etiology of ADHD. These symptoms affect the behavior performance and social relationships of children in school and at home. Recently, many studies about biochemical abnormalities in ADHD have been published. Several research groups have also suggested the genetic contribution to ADHD, and attempted to identify susceptibility and candidate genes for this disorder through the genetic linkage and association studies. To date, these studies have reported substantial evidence implicating several genes (dopaminergic: DRD4, DAT1, DRD5, COMT; noradrenergic: DBH, ADRA2A; serotonergic: 5-HTT, HTR1B, HTR2A; cholinergic: CHRNA4, and central nervous system development pathway: SNAP25, BDNF) in the etiology of ADHD. Understanding the biochemistry and genetics of ADHD will allow us to provide a useful addition with other treatment procedures for ADHD.

Gray matter volume abnormalities in ADHD: voxel-based meta-analysis exploring the effects of age and stimulant medication.

Structural neuroimaging studies in attention-deficit hyperactivity disorder (ADHD) have been relatively inconsistent and have mainly been conducted with pediatric samples. Furthermore, there is evidence that stimulant medication may have an effect on brain structure. The authors conducted a meta-analysis of voxel-based morphometry studies in children and adults with ADHD and examined the potential effects of age and stimulant medication on regional gray matter volumes. The PubMed, ScienceDirect, Web of Knowledge, and Scopus databases were searched for articles published between 2001 and 2011. Manual searches were also conducted, and authors of studies were contacted for additional data. Coordinates were extracted from clusters of significant gray matter difference between ADHD patients and healthy comparison subjects. Metaregression methods were used to explore potential age and stimulant medication effects. Fourteen data sets comprising 378 patients with ADHD and 344 healthy subjects met inclusion criteria. The ADHD group had global reductions in gray matter volumes, which were robustly localized in the right lentiform nucleus and extended to the caudate nucleus. Both increasing age and percentage of patients taking stimulant medication were found to be independently associated with more normal values in this region. Patients also had slightly greater gray matter volumes in the left posterior cingulate cortex. These findings confirm that the most prominent and replicable structural abnormalities in ADHD are in the basal ganglia. They furthermore suggest that ADHD patients may progressively catch up with their developmental delay with advancing age and that use of stimulant medication may be associated with normalization of structural abnormalities in ADHD, although longitudinal studies are needed to confirm both observations.

Neurofeedback dans le trouble déficit de l’attention avec hyperactivité : de l’efficacité à la spécificité de l’effet neurophysiologique

Clinical guidelines for attention deficit/hyperactivity disorder (ADHD) recommend a multimodal treatment encompassing pharmacological medication with methylphenidate, cognitive-behavioral therapy (CBT) and family treatments. Methylphenidate is the most effective treatment, though the relatively high rate of partial responders, and the possible parental reluctance against the pharmacological treatment. Thus, it is interesting to consider new non-pharmacological therapies based, such as CBT, on the learning capacity of children to self-regulate their behavior. Neurofeedback is interesting insofar as it would allow children to acquire self-control over certain brain activity patterns to improve the regulation of their behavior in daily-life situation. Early studies on neurofeedback in ADHD are nearly 30 years old. Two training protocols were created, based on EEG abnormalities in ADHD. First training allows the modulation of EEG frequency bands: increased activity in the beta band, or decreased activity in the theta rhythm. The second allows an increase in a slow cortical potential. In both protocols, feedback of the brain activity patterns is given to children in real time as a kind of computer game, and changes that are made in the desired direction are rewarded, i.e., positively reinforced. The evidence-based level of the neurofeedback is still unclear. But, unlike other mental disorders, many studies have investigated the effect of this treatment on symptoms of ADHD. Thus, we propose to analyze the data of literature and especially recent studies. A meta-analysis and randomized controlled studies seem to confirm the efficacy and the possible place of neurofeedback in the multimodal treatment strategies of ADHD. But, if this treatment supposes to allow self-regulation of children behavior by learning the control of EEG activity, the specific mechanisms of action on brain activity remains problematic. Thus, we propose to identify methodological and neurophysiological areas for future research on this therapy involving the subject and electrophysiology in psychiatry.