Characterising resting-state functional connectivity in a large sample of adults with ADHD

AbstractAttention-deficit/hyperactivity disorder (ADHD) is a common childhood psychiatric disorder that often persists into adulthood. While several studies have identified altered functional connectivity in brain networks during rest in children with ADHD, few studies have been performed on adults with ADHD. Existing studies have generally investigated small samples. We therefore investigated aberrant functional connectivity in a large sample of adult patients with childhood-onset ADHD, using a data-driven, whole-brain approach. Adults with a clinical ADHD diagnosis (N=99) and healthy, adult comparison subjects (N=113) underwent a 9-minute resting-state fMRI session in a 1.5T MRI scanner. After elaborate preprocessing including a thorough head-motion correction procedure, group independent component analysis (ICA) was applied from which we identified six networks of interest: cerebellum, executive control, left and right frontoparietal and two default-mode networks. Participant-level network maps were obtained using dual-regression and tested for differences between patients with ADHD and controls using permutation testing. Patients showed significantly stronger connectivity in the anterior cingulate gyrus of the executive control network. Trends were also observed for stronger connectivity in the cerebellum network in ADHD patients compared to controls. However, there was considerable overlap in connectivity values between patients and controls, leading to relatively low effect sizes despite the large sample size. These effect sizes were slightly larger when testing for correlations between hyperactivity/impulsivity symptoms and connectivity strength in the executive control and cerebellum networks. This study provides important insights for studies on the neurobiology of adult ADHD; it shows that resting-state functional connectivity differences between adult patients and controls exist, but have smaller effect sizes than existing literature suggested

Diminished modulation of preparatory sensorimotor mu rhythm predicts attention-deficit hyperactivity disorder severity

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is characterized by problems in regulating attention and in suppressing disruptive motor activity, i.e. hyperactivity and impulsivity. We recently found evidence that aberrant distribution of posterior α band oscillations (8–12 Hz) is associated with attentional problems in ADHD. The sensorimotor cortex also produces strong 8–12 Hz band oscillations, namely the μ rhythm, and is thought to have a similar inhibitory function. Here, we now investigate whether problems in distributing α band oscillations in ADHD generalize to the μ rhythm in the sensorimotor domain.MethodIn a group of adult ADHD (n = 17) and healthy control subjects (n = 18; aged 21–40 years) oscillatory brain activity was recorded using magnetoencephalography during a visuo-spatial attention task. Subjects had to anticipate a target with unpredictable timing and respond by pressing a button.ResultsPreparing a motor response, the ADHD group failed to increase hemispheric μ lateralization with relatively higher μ power in sensorimotor regions not engaged in the task, as the controls did (F1,33 = 8.70, p = 0.006). Moreover, the ADHD group pre-response μ lateralization not only correlated positively with accuracy (rs = 0.64, p = 0.0052) and negatively with intra-individual reaction time variability (rs = −0.52, p = 0.033), but it also correlated negatively with the score on an ADHD rating scale (rs = −0.53, p = 0.028).ConclusionsWe suggest that ADHD is associated with an inability to sufficiently inhibit task-irrelevant sensorimotor areas by means of modulating μ oscillatory activity. This could explain disruptive motor activity in ADHD. These results provide further evidence that impaired modulation of α band oscillations is involved in the pathogenesis of ADHD.</jats:sec

Disturbed corpus callosum microstructure in the presence of normal volume characterizes patients with adult ADHD

Background: Microstructural changes and volume reductions in the corpus callosum (CC) are implicated in childhood ADHD. There are however indications that, in adulthood ADHD, reduced white matter integrity is persistent whereas CC volume normalizes. Our goal was to investigate this in a relatively large adult ADHD sample. In addition to commonly used fractional anisotropy (FA) and mean diffusivity (MD), we calculated parallel (axial diffusion; AD) and perpendicular (radial diffusion; RD) diffusivities to white matter tracts which may offer additional information regarding tissue microstructure. Methods: White matter integrity and volume of the CC were investigated in 87 adult ADHD patients and 98 matched controls. We used diffusion tensor imaging in conjunction with tract-based spatial statistics to examine FA, MD, AD and RD within the genu, body and splenium of the CC. Volumetrics of the CC and its subdivisions were determined using FreeSurfer software. Results: The body of the CC showed lower FA (p = .005) and higher MD (p = .019) and RD (p = .008) values in ADHD patients, compared to controls. Volume of the CC did not differ between the groups (p = .633). Conclusions: Our findings show that callosal volume becomes normal while disturbed white matter integrity of the CC is persistent in adult ADHD. Abnormalities in the body of the CC, the subdivision that contains the commissural fibers connecting the somatosensory, auditory and motor areas may play an important role in the pathophysiology of ADHD

Enlarged striatal volume in adults with ADHD carrying the 9-6 haplotype of the dopamine transporter gene DAT1

The dopamine transporter gene, DAT1 (SLC6A3), has been studied extensively as a candidate gene for attention-deficit/hyperactivity disorder (ADHD). Different alleles of variable number of tandem repeats (VNTRs) in this gene have been associated with childhood ADHD (10/10 genotype and haplotype 10-6) and adult ADHD (haplotype 9-6). This suggests a differential association depending on age, and a role of DAT1 in modulating the ADHD phenotype over the lifespan. The DAT1 gene may mediate susceptibility to ADHD through effects on striatal volumes, where it is most highly expressed. In an attempt to clarify its mode of action, we examined the effect of three DAT1 alleles (10/10 genotype, and the haplotypes 10-6 and 9-6) on bilateral striatal volumes (nucleus accumbens, caudate nucleus, and putamen) derived from structural magnetic resonance imaging scans using automated tissue segmentation. Analyses were performed separately in three cohorts with cross-sectional MRI data, a childhood/adolescent sample (NeuroIMAGE, 301 patients with ADHD and 186 healthy participants) and two adult samples (IMpACT, 118 patients with ADHD and 111 healthy participants; BIG, 1718 healthy participants). Regression analyses revealed that in the IMpACT cohort, and not in the other cohorts, carriers of the DAT1 adult ADHD risk haplotype 9-6 had 5.9 % larger striatum volume relative to participants not carrying this haplotype. This effect varied by diagnostic status, with the risk haplotype affecting striatal volumes only in patients with ADHD. An explorative analysis in the cohorts combined (N = 2434) showed a significant gene-by-diagnosis-by-age interaction suggesting that carriership of the 9-6 haplotype predisposes to a slower age-related decay of striatal volume specific to the patient group. This study emphasizes the need of a lifespan approach in genetic studies of ADHD

Shared and disorder-specific task-positive and default mode network dysfunctions during sustained attention in paediatric Attention-Deficit/Hyperactivity Disorder and obsessive/compulsive disorder

Patients with Attention-Deficit/Hyperactivity Disorder (ADHD) and obsessive/compulsive disorder (OCD) share problems with sustained attention, and are proposed to share deficits in switching between default mode and task positive networks. The aim of this study was to investigate shared and disorder-specific brain activation abnormalities during sustained attention in the two disorders. Twenty boys with ADHD, 20 boys with OCD and 20 age-matched healthy controls aged between 12 and 18 years completed a functional magnetic resonance imaging (fMRI) version of a parametrically modulated sustained attention task with a progressively increasing sustained attention load. Performance and brain activation were compared between groups. Only ADHD patients were impaired in performance. Group by sustained attention load interaction effects showed that OCD patients had disorder-specific middle anterior cingulate underactivation relative to controls and ADHD patients, while ADHD patients showed disorder-specific underactivation in left dorsolateral prefrontal cortex/dorsal inferior frontal gyrus (IFG). ADHD and OCD patients shared left insula/ventral IFG underactivation and increased activation in posterior default mode network relative to controls, but had disorder-specific overactivation in anterior default mode regions, in dorsal anterior cingulate for ADHD and in anterior ventromedial prefrontal cortex for OCD. In sum, ADHD and OCD patients showed mostly disorder-specific patterns of brain abnormalities in both task positive salience/ventral attention networks with lateral frontal deficits in ADHD and middle ACC deficits in OCD, as well as in their deactivation patterns in medial frontal DMN regions. The findings suggest that attention performance in the two disorders is underpinned by disorder-specific activation patterns

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders

Het nemen van beslissingen door volwassenen met ADHD:Een systematisch literatuuronderzoek

Personen met aandachtstekortstoornis met hyperactiviteit (ADHD) hebben een grotere kans om minder goede (levens)beslissingen te nemen en om risicovolle activiteiten te ondernemen dan personen zonder ADHD. Mogelijk komt dit doordat de kenmerken van ADHD van invloed zijn op het besluitvormingsproces. Hoewel beslissingsproblematiek reeds uitgebreid is onderzocht bij kinderen en adolescenten met ADHD, is er nog relatief weinig bekend over de besluitvorming van volwassenen met ADHD. Om die reden was het doel van dit literatuuronderzoek de aard en omvang van eventuele tekorten in het besluitvormingsproces van volwassenen met ADHD vast te stellen. Hiertoe is de bestaande literatuur, waarin de prestatie van volwassenen met ADHD op beslissingstaken werd vergeleken met de prestatie van een gezonde controlegroep, systematisch doorzocht, waartoe de databases PsycINFO, MEDLINE en PubMed zijn geraadpleegd. In totaal werden er 31 studies geïncludeerd. In de meerderheid van de studies (i.e. 55 %) weken de prestaties van volwassenen met ADHD af op een of meer van de gebruikte beslissingstaken in vergelijking met de controlegroep(en). Dit literatuuronderzoek levert daarmee voorzichtig bewijs voor het bestaan van verschillen in het besluitvormingsproces tussen gezonde individuen en volwassenen met ADHD. De grote inconsistentie in de bevindingen wordt deels verklaard door de verscheidenheid aan domeinen van besluitvorming die werden onderzocht, de comorbide stoornissen van de participanten en het medicatiegebruik in de ADHD-groepen. Het literatuuronderzoek besluit met een bespreking van de implicaties die de bevindingen hebben voor theorieën over de onderliggende mechanismen van ADHD