Inefficient cognitive control in adult ADHD: evidence from trial-by-trial Stroop test and cued task switching performance

<p>Abstract</p> <p>Background</p> <p>Contemporary neuropsychological models of ADHD implicate impaired cognitive control as contributing to disorder characteristic behavioral deficiencies and excesses; albeit to varying degrees. While the traditional view of ADHD postulates a core deficiency in cognitive control processes, alternative dual-process models emphasize the dynamic interplay of bottom-up driven factors such as activation, arousal, alerting, motivation, reward and temporal processing with top-down cognitive control. However, neuropsychological models of ADHD are child-based and have yet to undergo extensive empirical scrutiny with respect to their application to individuals with persistent symptoms in adulthood. Furthermore, few studies of adult ADHD samples have investigated two central cognitive control processes: interference control and task-set coordination. The current study employed experimental chronometric Stroop and task switching paradigms to investigate the efficiency of processes involved in interference control and task-set coordination in ADHD adults.</p> <p>Methods</p> <p>22 adults diagnosed with persistent ADHD (17 males) and 22 matched healthy control subjects performed a manual trial-by-trial Stroop color-word test and a blocked explicitly cued task switching paradigm. Performance differences between neutral and incongruent trials of the Stroop task measured interference control. Task switching paradigm manipulations allowed for measurement of transient task-set updating, sustained task-set maintenance, preparatory mechanisms and interference control. Control analyses tested for the specificity of group × condition interactions.</p> <p>Results</p> <p>Abnormal processing of task-irrelevant stimulus features was evident in ADHD group performance on both tasks. ADHD group interference effects on the task switching paradigm were found to be dependent on the time allotted to prepare for an upcoming task. Group differences in sustained task-set maintenance and transient task-set updating were also found to be dependent on experimental manipulation of task preparation processes. With the exception of Stroop task error rates, all analyses revealed generally slower and less accurate ADHD group response patterns.</p> <p>Conclusion</p> <p>The current data obtained with experimental paradigms deliver novel evidence of inefficient interference control and task-set coordination in adults with persistent ADHD. However, all group differences observed in these central cognitive control processes were found to be partially dependent on atypical ADHD group task preparation mechanisms and/or response inconsistency. These deficiences may have contributed not only to inefficient cognitive control, but also generally slower and less accurate ADHD group performance. Given the inability to dissociate these impairments with the current data, it remains inconclusive as to whether ineffecient cognitive control in the clinical sample was due to top-down failure or bottom-up engagement thereof. To clarify this issue, future neuropsychological investigations are encouraged to employ tasks with significantly more trials and direct manipulations of bottom-up mechanisms with larger samples.</p

Identification of new susceptibility loci for osteoarthritis (arcOGEN):a genome-wide association study

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Osteoarthritis is the most common form of arthritis worldwide and is a major cause of pain and disability in elderly people. The health economic burden of osteoarthritis is increasing commensurate with obesity prevalence and longevity. Osteoarthritis has a strong genetic component but the success of previous genetic studies has been restricted due to insufficient sample sizes and phenotype heterogeneity. We undertook a large genome-wide association study (GWAS) in 7410 unrelated and retrospectively and prospectively selected patients with severe osteoarthritis in the arcOGEN study, 80% of whom had undergone total joint replacement, and 11,009 unrelated controls from the UK. We replicated the most promising signals in an independent set of up to 7473 cases and 42,938 controls, from studies in Iceland, Estonia, the Netherlands, and the UK. All patients and controls were of European descent. We identified five genome-wide significant loci (binomial test p≤5·0×10(-8)) for association with osteoarthritis and three loci just below this threshold. The strongest association was on chromosome 3 with rs6976 (odds ratio 1·12 [95% CI 1·08-1·16]; p=7·24×10(-11)), which is in perfect linkage disequilibrium with rs11177. This SNP encodes a missense polymorphism within the nucleostemin-encoding gene GNL3. Levels of nucleostemin were raised in chondrocytes from patients with osteoarthritis in functional studies. Other significant loci were on chromosome 9 close to ASTN2, chromosome 6 between FILIP1 and SENP6, chromosome 12 close to KLHDC5 and PTHLH, and in another region of chromosome 12 close to CHST11. One of the signals close to genome-wide significance was within the FTO gene, which is involved in regulation of bodyweight-a strong risk factor for osteoarthritis. All risk variants were common in frequency and exerted small effects. Our findings provide insight into the genetics of arthritis and identify new pathways that might be amenable to future therapeutic intervention.Arthritis Research UK 1803

Strain analysis for the identification of hypertensive cardiac end-organ damage in the emergency department

Abstract Hypertensive emergency is a life-threatening state. End-organ damage affecting the heart accounts for up to 52% of hypertensive emergencies commonly encountered in the emergency department. Recent evidence indicates that strain echocardiography with computerized speckle-tracking is more sensitive at identifying hypertension induced changes in the left ventricle (LV) mechanical function than traditional 2-D echocardiography. We present a case demonstrating the use of emergency physician performed point-of-care strain echocardiography to identify and quantify LV mechanical dysfunction during a hypertensive crisis and to monitor improvement over 6 h