Memory In Attention-deficit/hyperactivity Disorder Research Articles

Ocular and neural genes jointly regulate the visuospatial working memory in ADHD children

ObjectiveWorking memory (WM) deficits have frequently been linked to attention deficit hyperactivity disorder (ADHD). Despite previous studies suggested its high heritability, its genetic basis, especially in ADHD, remains unclear. The current study aimed to comprehensively explore the genetic basis of visual-spatial working memory (VSWM) in ADHD using wide-ranging genetic analyses.MethodsThe current study recruited a cohort consisted of 802 ADHD individuals, all met DSM-IV ADHD diagnostic criteria. VSWM was assessed by Rey-Osterrieth complex figure test (RCFT), which is a widely used psychological test include four memory indexes: detail delayed (DD), structure delayed (SD), structure immediate (SI), detail immediate (DI). Genetic analyses were conducted at the single nucleotide polymorphism (SNP), gene, pathway, polygenic and protein network levels. Polygenic Risk Scores (PRS) were based on summary statistics of various psychiatric disorders, including ADHD, autism spectrum disorder (ASD), major depressive disorder (MDD), schizophrenia (SCZ), obsessive compulsive disorders (OCD), and substance use disorder (SUD).ResultsAnalyses at the single-marker level did not yield significant results (5E−08). However, the potential signals with P values less than E−05 and their mapped genes suggested the regulation of VSWM involved both ocular and neural system related genes, moreover, ADHD-related genes were also involved. The gene-based analysis found RAB11FIP1, whose encoded protein modulates several neurodevelopment processes and visual system, as significantly associated with DD scores (P = 1.96E−06, Padj = 0.036). Candidate pathway enrichment analyses (N = 53) found that forebrain neuron fate commitment significantly enriched in DD (P = 4.78E−04, Padj = 0.025), and dopamine transport enriched in SD (P = 5.90E-04, Padj = 0.031). We also observed a significant negative relationship between DD scores and ADHD PRS scores (P = 0.0025, Empirical P = 0.048).ConclusionsOur results emphasized the joint contribution of ocular and neural genes in regulating VSWM. The study reveals a shared genetic basis between ADHD and VSWM, with GWAS indicating the involvement of ADHD-related genes in VSWM. Additionally, the PRS analysis identifies a significant relationship between ADHD-PRS and DD scores. Overall, our findings shed light on the genetic basis of VSWM deficits in ADHD, and may have important implications for future research and clinical practice.

Activity-Based Prospective Memory in ADHD during Motor Sleep Inertia.

Prospective memory (PM) is essential in everyday life because it concerns the ability to remember to perform an intended action in the future. Individuals diagnosed with attention deficit hyperactivity disorder (ADHD) often show poor performance in PM. Because age can be confounding, we decided to test PM in ADHD patients (children and adults) and healthy controls (children and adults). We examined 22 children (four females; mean age = 8.77 ± 1.77) and 35 adults (14 females; mean age = 37.29 ± 12.23) with ADHD, in addition to 92 children (57 females; mean age = 10.13 ± 0.42) and 95 adults (57 females; mean age = 27.93 ± 14.35) as healthy controls. Each participant originally wore an actigraph around the non-dominant wrist and was requested to push the event-marker at get-up time. To assess the efficiency of PM performance, we calculated the time elapsing between the end of sleep in the morning and the pushing of the event-marker button. The results showed lower PM performance in ADHD participants, regardless of age. However, the differences between ADHD and control groups were more evident in the children group. Our data seem to confirm that PM efficiency is compromised in individuals diagnosed with ADHD regardless of age, and agree with the idea of considering the PM deficit as a neuropsychological marker of ADHD.

Neural basis of working memory in ADHD: Load versus complexity

Working memory (WM) deficits are key in attention deficit hyperactivity disorder (ADHD). Nevertheless, WM is not universally impaired in ADHD. Additionally, the neural basis for WM deficits in ADHD has not been conclusively established, with regions including the prefrontal cortex, cerebellum, and caudate being implicated. These contradictions may be related to conceptualizations of WM capacity, such as load (amount of information) versus operational-complexity (maintenance-recall or manipulation). For instance, relative to neurotypical (NT) individuals, complex WM operations could be impaired in ADHD, while simpler operations are spared. Alternatively, all operations may be impaired at higher loads. Here, we compared the impact of these two components of WM capacity: load and operational-complexity, between ADHD and NT, behaviorally and neurally. We hypothesized that the impact of WM load would be greater in ADHD, and the neural activation would be altered. Participants (age-range 12–23 years; 50 ADHD (18 females); 82 NT (41 females)) recalled three or four objects (load) in forward or backward order (operational-complexity) during functional magnetic resonance imaging scanning. The effects of diagnosis and task were compared on performance and neural engagement. Behaviorally, we found significant interactions between diagnosis and load, and between diagnosis, load, and complexity. Neurally, we found an interaction between diagnosis and load in the right striatum, and between diagnosis and complexity in the right cerebellum and left occipital gyrus. The ADHD group displayed hypo-activation compared to NT group during higher load and greater complexity. This informs mechanisms of functional problems related to WM in adolescents and young adults with ADHD (e.g., academic performance) and remedial interventions (e.g., WM-training).

The impact of SNAP25 on brain functional connectivity density and working memory in ADHD

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopment disorder. The deficit in working memory is a central cognitive impairment in ADHD. The SNAP-25 is a neurotransmitter vesicular docking protein whose MnlI polymorphism (rs3746544) is located in the 3′-untranslated region (3′-UTR) and known to be linked to ADHD, but the underlying mechanism of this polymorphism remains unclear. Using a functional connectivity density (FCD) mapping method based on resting-state functional magnetic resonance imaging in a sample of male children diagnosed with ADHD, we first investigated the correlation between SNAP-25 rs3746544 and FCD hubs. Compared with rs3746544 G-allele carriers, TT homozygous, which confers a high risk for ADHD, exhibited significantly decreased local and long-range FCD in anterior cingulate cortex, and decreased local FCD in the dorsal lateral prefrontal cortex. Moreover, both higher local and long-range FCD could predict better WM capacity. The current findings provide new insights into the underlying neural mechanisms linking SNAP-25 rs3746544 with the risk for ADHD via the endophenotype of brain functional connectivity.

Working Memory Mediates Increased Negative Affect and Suicidal Ideation in Childhood Attention-Deficit/Hyperactivity Disorder

Children with attention-deficit/hyperactivity disorder (ADHD) are at greater risk for suicidal ideation and suicide attempts compared to those without ADHD. Increased risk is at least partially attributable to a subset of children with ADHD and comorbid depression or disruptive behavior disorders; however, the early predictors and mechanisms driving increased risk are not well understood. Here, we investigate the contributions of two candidate mechanisms for increased suicidal ideation in children with ADHD: executive function and negative affect. 623 clinically well-characterized, community-recruited children classified by research criteria as ADHD (n=388) or typically-developing controls (n=253) participated. Parent-report on the Temperament in Middle Childhood Questionnaire provided a measure of negative affectivity. Children completed laboratory tasks to measure response inhibition and working memory. Suicidal ideation was evaluated by parent report during a semi-structured interview and child responses on the Children's Depression Inventory. Compared to typically developing controls, children with ADHD had higher rates of suicidal ideation, more negative affect, slower stop signal reaction times, and weaker working memory. Statistical path-model analyses confirmed the hypothesis that weaker working memory in ADHD statistically mediated increased negative affect. Weaker working memory also mediated and increased suicidal ideation in these cross sectional data. Findings were not attributable to comorbid disruptive behavioral disorders. Poor response inhibition did not reliably mediate negative affect or suicidal ideation. Impairment in working memory is an important early risk factor for suicidal ideation in children with ADHD, and may help in identifying children for prevention and early intervention efforts.

Altered frontal pole development affects self-generated spatial working memory in ADHD

BackgroundSpatial working memory (SWM) dysfunction is a feature of attention deficit hyperactivity disorder (ADHD). Previous studies suggested that behavioral performance in self-generated SWM improves through development in children with and without ADHD. Nevertheless, developmental changes in the neural underpinnings of self-generated SWM are unknown. MethodUsing near-infrared spectroscopy, hemodynamic activity in the prefrontal cortex (PFC) was measured in 30 children with ADHD (9.5±1.6years-old) and 35 TD children (9.0±1.6years-old) while they performed a self-generated SWM task. We then investigated correlations between age and behavioral performance, and between age and hemodynamic activity in the PFC for each group. ResultsBoth groups showed a negative correlation with age and number of errors [ADHD: r(28)=−0.37, p=0.040; TD: r(33)=−0.59, p<0.001], indicating that self-generated SWM improves through development. The TD group showed a positive correlation between age and oxygenated hemoglobin in the frontal pole [10ch: r(33)=0.41, p=0.013; 11ch; r(33)=0.44, p=0.008] and bilateral lateral PFC [4ch: r(33)=0.34, p=0.049; 13ch; r(33)=0.54, p=0.001], while no significant correlation was found in the ADHD group. Furthermore, regression slopes for the frontal pole significantly differed between the TD and ADHD groups [10ch: t(61)=2.35, p=0.021; 11ch: t(61)=2.05, p=0.044]. ConclusionChildren with ADHD showed abnormalities in functional maturation of the frontal pole, which plays a role in manipulating and maintaining information associated with self-generated behavior.

Neural hyperactivity related to working memory in drug-naive boys with attention deficit hyperactivity disorder

Impaired working memory is thought to be a core feature of attention deficit hyperactivity disorder (ADHD). Previous imaging studies investigating working memory in ADHD have used tasks involving different cognitive resources and ignoring the categorical judgments about objects that are essential parts of performance in visual working memory tasks, thus complicating the interpretation of their findings. In the present study, we explored differential neural activation in children and adolescents with ADHD and in healthy controls using functional magnetic resonance imaging (fMRI) with the categorical n-back task (CN-BT), which maximized demands for executive reasoning while holding memory demands constant. A total of 33 drug-naive, right-handed male ADHD without comorbidity (mean age 9.9±2.4 years) and 27 right-handed, healthy male controls (mean age 10.9±2.7 years) were recruited in the present study. Event-related fMRI was used to study differences in brain activity during the CN-BT between the two groups. The two groups did not differ in their accuracy in the CN-BT, although the ADHD patients showed significantly shorter reaction times to correct responses than did the controls. During the CN-BT, both ADHD patients and controls showed significant positive and negative activations by the correct responses, mainly in the sensory-motor pathways and the striato-cerebellum circuit. Additionally, the ADHD patients showed significantly higher activation in the bilateral globus pallidus and the right hippocampus compared with the controls. There was also a positive correlation between hyperactivation of the left globus pallidus and the reaction time to correct responses in ADHD. In contrast to controls, ADHD patients showed neural hyperactivation in the striatum and mediotemporal areas during a working memory task involving categorization. Hyperfunction in these areas might be the pathophysiological foundation of ADHD, related to the deficits of working memory and the impulsive symptoms.

Sleep Promotes Consolidation of Emotional Memory in Healthy Children but Not in Children with Attention-Deficit Hyperactivity Disorder

Fronto-limbic brain activity during sleep is believed to support the consolidation of emotional memories in healthy adults. Attention deficit-hyperactivity disorder (ADHD) is accompanied by emotional deficits coincidently caused by dysfunctional interplay of fronto-limbic circuits. This study aimed to examine the role of sleep in the consolidation of emotional memory in ADHD in the context of healthy development. 16 children with ADHD, 16 healthy children, and 20 healthy adults participated in this study. Participants completed an emotional picture recognition paradigm in sleep and wake control conditions. Each condition had an immediate (baseline) and delayed (target) retrieval session. The emotional memory bias was baseline–corrected, and groups were compared in terms of sleep-dependent memory consolidation (sleep vs. wake). We observed an increased sleep-dependent emotional memory bias in healthy children compared to children with ADHD and healthy adults. Frontal oscillatory EEG activity (slow oscillations, theta) during sleep correlated negatively with emotional memory performance in children with ADHD. When combining data of healthy children and adults, correlation coefficients were positive and differed from those in children with ADHD. Since children displayed a higher frontal EEG activity than adults these data indicate a decline in sleep-related consolidation of emotional memory in healthy development. In addition, it is suggested that deficits in sleep-related selection between emotional and non-emotional memories in ADHD exacerbate emotional problems during daytime as they are often reported in ADHD.

Cognitive variability in adults with ADHD and AS: Disentangling the roles of executive functions and social cognition

Attention-deficit/hyperactivity disorder (ADHD) and Asperger's Syndrome (AS) share a heterogeneous cognitive profile. Studies assessing executive functions (EF) and social cognition in both groups have found preserved and impaired performances. These inconsistent findings would be partially explained by the cognitive variability reported in these disorders. First, the present study explored the inter-individual variability in EF and social cognition in both patient groups. Second, we compared differential characteristics and commonalities in the cognitive profiles of EF and social cognition between ADHD, AS and control adults. We assessed 22 patients with ADHD, 23 adults with AS and 21 matched typically developing subjects using different measures of EF (working memory, cognitive flexibility and multitasking) and social cognition (theory of mind and decision-making). Group comparisons and multiple case series analyses (MCSA) were conducted. The between-group comparisons showed an EF deficit in working memory in ADHD and a theory of mind (ToM) impairment in AS. The MCSA evidenced that, compared to controls, ADHD patients had a higher inter-individual variability in EF, while individuals with AS had a more heterogeneous profile in social cognition tasks compared to both groups. Finally, the AS and ADHD groups presented higher task-related variability compared to controls and shared a common heterogeneous profile in EF. This is the first study to compare variability in EF and social cognition profiles of ADHD and AS. We propose that heterogeneity in EF performance is a link between ADHD and AS which may explain the overlap of symptomatology between both diagnoses. In addition, patients with AS seem to show a unique heterogeneous profile in ToM which may explain the low probability of finding AS symptoms in patients with ADHD.

Altered Cortico-Striatal–Thalamic Connectivity in Relation to Spatial Working Memory Capacity in Children with ADHD

Introduction: Attention deficit hyperactivity disorder (ADHD) captures a heterogeneous group of children, who are characterized by a range of cognitive and behavioral symptoms. Previous resting-state functional connectivity MRI (rs-fcMRI) studies have sought to understand the neural correlates of ADHD by comparing connectivity measurements between those with and without the disorder, focusing primarily on cortical–striatal circuits mediated by the thalamus. To integrate the multiple phenotypic features associated with ADHD and help resolve its heterogeneity, it is helpful to determine how specific circuits relate to unique cognitive domains of the ADHD syndrome. Spatial working memory has been proposed as a key mechanism in the pathophysiology of ADHD. Methods: We correlated the rs-fcMRI of five thalamic regions of interest (ROIs) with spatial span working memory scores in a sample of 67 children aged 7–11 years [ADHD and typically developing children (TDC)]. In an independent dataset, we then examined group differences in thalamo-striatal functional connectivity between 70 ADHD and 89 TDC (7–11 years) from the ADHD-200 dataset. Thalamic ROIs were created based on previous methods that utilize known thalamo-cortical loops and rs-fcMRI to identify functional boundaries in the thalamus. Results/Conclusion: Using these thalamic regions, we found atypical rs-fcMRI between specific thalamic groupings with the basal ganglia. To identify the thalamic connections that relate to spatial working memory in ADHD, only connections identified in both the correlational and comparative analyses were considered. Multiple connections between the thalamus and basal ganglia, particularly between medial and anterior dorsal thalamus and the putamen, were related to spatial working memory and also altered in ADHD. These thalamo-striatal disruptions may be one of multiple atypical neural and cognitive mechanisms that relate to the ADHD clinical phenotype.

Reduced sleep-associated consolidation of declarative memory in attention-deficit/hyperactivity disorder

Sleep supports the consolidation of declarative memory. Patients with attention-deficit/hyperactivity disorder (ADHD) are not only characterized by sleep problems but also by declarative memory deficits. Given that the consolidation of declarative memory during sleep is supported by slow oscillations, which are predominantly generated by the prefrontal cortex, and that ADHD patients display low prefrontal brain activity, we assumed that ADHD patients show reduced sleep-associated consolidation of declarative memory. The impact of sleep on the consolidation of declarative memory was examined with a picture recognition task. Twelve ADHD patients (10-16 years) and 12 healthy controls participated in two experimental conditions: in the sleep condition, learning was performed in the evening and picture recognition was tested after nocturnal sleep; in the wake condition, learning was conducted in the morning while retrieval took place after a day of wakefulness. Analyses of recognition accuracy revealed reduced sleep-associated enhancement of recognition accuracy in ADHD. While sleep-associated enhancement of recognition accuracy was correlated with slow oscillation power during non-REM sleep in healthy controls, no such correlations were observed in ADHD. These data indicate a deficit in sleep-associated consolidation of declarative memory in ADHD. Moreover, our results suggest reduced functionality of slow oscillations in sleep-associated consolidation of declarative memory in ADHD.

Distinctive brain function underlies working memory in ADHD and individuals at familial risk for schizophrenia

OBJECTIVE. To examine the specificity of potential endophenotypes for two groups of adolescents and young adults who have putative disorders of prefrontal neurodevelopment (as suggested by behavioral and neurocognitive alterations): Individuals with Attention Deficit Hyperactivity Disorder (ADHD) and persons at familial (“genetic”) risk for schizophrenia. We used a robust working memory task (the N-back) to assess brain activation in a functional neuroimaging study comparing these two groups of subjects and healthy controls.

Prefrontal oxygenation during working memory in ADHD

Objectives Deficits in working memory have been repeatedly found on a behavioural level in children with attention-deficit/hyperactivity disorder (ADHD). Functional brain imaging studies have revealed evidence for alterations in the prefrontal cortex associated with working memory. So far it remains unresolved whether object (OWM) and spatial visual working memory (SWM) are distinctly impaired in ADHD. We investigated this issue with the fist multi-channel functional near-infrared spectroscopy study of children with ADHD. Method We investigated 19 children with ADHD combined type (DSM-IV) and 19 controls matched for age (8–15 years), sex, handedness, and intelligence during a working memory task assessing OWM and SWM separately, and a control condition (CON). Prefrontal brain activity was measured by concentration changes of oxygenated haemoglobin. Results Working memory performance showed significant differences for conditions (OWM > SWM > CON), but no differences between groups. Cortical prefrontal activation was significantly higher for OWM and SWM in contrast to CON, again with no differences between groups. Conclusions We found no indication for an altered prefrontal processing during OWM and SWM tasks in ADHD children compared to controls. Reviewing the existing imaging literature on working memory in ADHD and considering the present data, we discuss possible confounding factors relevant for brain activity in previous, the current, and future investigations. Thus, it is of high importance to capture developmental trajectories, task specific discrepancies, and effects of permanent medication intake in future studies.

Predictors of two-year follow-up in children and adolescents with schizophrenia

Deficits in working memory have been repeatedly found on a behavioural level in children with attention-deficit/hyperactivity disorder (ADHD). Functional brain imaging studies have revealed evidence for alterations in the prefrontal cortex associated with working memory. So far it remains unresolved whether object (OWM) and spatial visual working memory (SWM) are distinctly impaired in ADHD. We investigated this issue with the fist multi-channel functional near-infrared spectroscopy study of children with ADHD.We investigated 19 children with ADHD combined type (DSM-IV) and 19 controls matched for age (8–15 years), sex, handedness, and intelligence during a working memory task assessing OWM and SWM separately, and a control condition (CON). Prefrontal brain activity was measured by concentration changes of oxygenated haemoglobin.Working memory performance showed significant differences for conditions (OWM > SWM > CON), but no differences between groups. Cortical prefrontal activation was significantly higher for OWM and SWM in contrast to CON, again with no differences between groups.We found no indication for an altered prefrontal processing during OWM and SWM tasks in ADHD children compared to controls. Reviewing the existing imaging literature on working memory in ADHD and considering the present data, we discuss possible confounding factors relevant for brain activity in previous, the current, and future investigations. Thus, it is of high importance to capture developmental trajectories, task specific discrepancies, and effects of permanent medication intake in future studies.