ADHD patients fail to maintain task goals in face of subliminally and consciously induced cognitive conflicts.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) patients have been reported to display deficits in action control processes. While it is known that subliminally and consciously induced conflicts interact and conjointly modulate action control in healthy subjects, this has never been investigated for ADHD. METHOD: We investigated the (potential) interaction of subliminally and consciously triggered response conflicts in children with ADHD and matched healthy controls using neuropsychological methods (event-related potentials; ERPs) to identify the involved cognitive sub-processes. RESULTS: Unlike healthy controls, ADHD patients showed no interaction of subliminally and consciously triggered response conflicts. Instead, they only showed additive effects as their behavioural performance (accuracy) was equally impaired by each conflict and they showed no signs of task-goal shielding even in cases of low conflict load. Of note, this difference between ADHD and controls was not rooted in early bottom-up attentional stimulus processing as reflected by the P1 and N1 ERPs. Instead, ADHD showed either no or reversed modulations of conflict-related processes and response selection as reflected by the N2 and P3 ERPs. CONCLUSION: There are fundamental differences in the architecture of cognitive control which might be of use for future diagnostic procedures. Unlike healthy controls, ADHD patients do not seem to be endowed with a threshold which allows them to maintain high behavioural performance in the face of low conflict load. ADHD patients seem to lack sufficient top-down attentional resources to maintain correct response selection in the face of conflicts by shielding the response selection process from response tendencies evoked by any kind of distractor.

Immunomodulatory treatments and cognition in MS.

Cognitive impairments occur frequently and early in multiple sclerosis (MS) and contribute significantly to a reduced quality of life of patients with MS. Executive functions (EFs) play a pivotal role for the behavioral adaption to the environment and are also crucial for compensatory processes of cognitive impairments. Disease-modifying drugs (DMDs) are effective in reducing the frequency of relapses and slow the disease progression in MS. The effects of DMDs on cognitive impairments were reviewed with a special focus on EFs. Most studies show some beneficial effects of DMDs on cognition in MS, but the evidence for effects on EFs is sparse. Additionally, most studies suffer from methodological issues, small sample sizes and learning effects. We discuss that EFs may constitute a viable cognitive endpoint for cognitive impairments in MS, which could foster the early detection of subtle cognitive changes in MS.

Effects of multisensory integration processes on response inhibition in adolescent autism spectrum disorder.

BACKGROUND: In everyday life it is often required to integrate multisensory input to successfully conduct response inhibition (RI) and thus major executive control processes. Both RI and multisensory processes have been suggested to be altered in autism spectrum disorder (ASD). It is, however, unclear which neurophysiological processes relate to changes in RI in ASD and in how far these processes are affected by possible multisensory integration deficits in ASD. METHOD: Combining high-density EEG recordings with source localization analyses, we examined a group of adolescent ASD patients (n = 20) and healthy controls (n = 20) using a novel RI task. RESULTS: Compared to controls, RI processes are generally compromised in adolescent ASD. This aggravation of RI processes is modulated by the content of multisensory information. The neurophysiological data suggest that deficits in ASD emerge in attentional selection and resource allocation processes related to occipito-parietal and middle frontal regions. Most importantly, conflict monitoring subprocesses during RI were specifically modulated by content of multisensory information in the superior frontal gyrus. CONCLUSIONS: RI processes are overstrained in adolescent ASD, especially when conflicting multisensory information has to be integrated to perform RI. It seems that the content of multisensory input is important to consider in ASD and its effects on cognitive control processes.

Specific cognitive-neurophysiological processes predict impulsivity in the childhood attention-deficit/hyperactivity disorder combined subtype.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neuropsychiatric disorders in childhood. Besides inattention and hyperactivity, impulsivity is the third core symptom leading to diverse and serious problems. However, the neuronal mechanisms underlying impulsivity in ADHD are still not fully understood. This is all the more the case when patients with the ADHD combined subtype (ADHD-C) are considered who are characterized by both symptoms of inattention and hyperactivity/impulsivity. METHOD: Combining high-density electroencephalography (EEG) recordings with source localization analyses, we examined what information processing stages are dysfunctional in ADHD-C (n = 20) compared with controls (n = 18). RESULTS: Patients with ADHD-C made more impulsive errors in a Go/No-go task than healthy controls. Neurophysiologically, different subprocesses from perceptual gating to attentional selection, resource allocation and response selection processes are altered in this patient group. Perceptual gating, stimulus-driven attention selection and resource allocation processes were more pronounced in ADHD-C, are related to activation differences in parieto-occipital networks and suggest attentional filtering deficits. However, only response selection processes, associated with medial prefrontal networks, predicted impulsive errors in ADHD-C. CONCLUSIONS: Although the clinical picture of ADHD-C is complex and a multitude of processing steps are altered, only a subset of processes seems to directly modulate impulsive behaviour. The present findings improve the understanding of mechanisms underlying impulsivity in patients with ADHD-C and might help to refine treatment algorithms focusing on impulsivity.

Associations between the tumor necrosis factor alpha gene (-308G→A) and event-related potential indices of attention and mental rotation.

The tumor necrosis factor alpha (TNF-α) is a cytokine that exerts neuroprotective and neurodegenerative effects. While some research suggests enhancing effects of the TNF-α gene (TNF-α -308G→A) on cognitive function, further research is needed to clarify the association between the TNF-α gene and specific areas of cognitive performance including their neurophysiological correlates. In this study we examine association of the TNF-α -308G→A single nucleotide polymorphism (rs1800629) with attention and mental rotation performance in an event-related potential (ERP) study in healthy participants (n=67). The results show that carriers of the -308 A allele display elevated attentional processes (i.e. a stronger N1) as compared to the GG genotype group. Mental rotation performance varied across genotypes when demands on mental rotation were high. Here, carriers of the -308 A allele performed better than the GG genotype group. This is paralleled by the neurophysiological data showing genotype-dependent variations in parietal positivities only under the condition of high demands on mental rotation. The finding of enhanced attentional and mental rotation performance in A allele carriers supports recent findings that the A allele of this single nucleotide polymorphism (SNP) enhances cognitive performance on a general measure of cognitive processing speed.

ERP indices for response inhibition are related to anxiety-related personality traits.

Anxiety is often associated with impaired cognitive control and avoidance behaviour. The aim of this study was to investigate the effect of anxiety-related personality traits, such as anxiety sensitivity and trait anxiety, on event-related potentials of response inhibition in a standard Go/Nogo-paradigm. We focused on the Nogo-N2 and Nogo-P3 components, which probably represent different sub-processes of response inhibition. The Nogo-N2 was mainly influenced by trait anxiety, while it was slightly affected by anxiety sensitivity. In contrast, the Nogo-P3 was significantly associated with anxiety sensitivity, but was less affected by trait anxiety. Thus, anxious subjects seem to maintain a higher level of cognitive control to prepare and to monitor the outcome of their actions, which is differentially reflected in Nogo-N2 and Nogo-P3 potentials. Our results show that anxiety-related personality traits modulate electrophysiological responses related to cognitive control processes and should be taken into consideration in studies investigating response inhibition.

Association between genetic variants of the metabotropic glutamate receptor 3 (GRM3) and cognitive set shifting in healthy individuals.

Set-shifting and maintenance are complex cognitive processes, which are often impaired in schizophrenia. The genetic basis of these processes is poorly understood. We aimed to investigate the association between genetic variants of the metabotropic glutamate receptor 3 (GRM3) and cognitive set-shifting in healthy individuals. The relationship between 14 selected single nucleotide polymorphisms (SNPs) of the GRM3 gene and cognitive set-shifting as measured by perseverative errors using the modified card sorting test (MCST) was analysed in a sample of N = 98 young healthy individuals (mean age in years: 22.7 +/- 0.19). Results show that SNP rs17676277 is related to the performance on the MCST. Subjects with the TT genotype showed significantly less perseverative errors as compared with the AA (P = 0.025) and AT (P = 0.0005) and combined AA/AT genotypes (P = 0.0005). Haplotype analyses suggest the involvement of various SNPs of the GRM3 gene in perseverative error processing in a dominant model of inheritance. The findings strongly suggest that the genetic variation (rs17676277 and three haplotypes) in the metabotropic GRM3 is related to cognitive set-shifting in healthy individuals independent of working memory. However, because of a relatively small sample size for a genetic association study, the present results are tentative and require replication.

Paradoxical association of the brain-derived-neurotrophic-factor val66met genotype with response inhibition.

Response inhibition is a basic executive function which is dysfunctional in various basal ganglia diseases. The brain-derived-neurotrophic-factor (BDNF) plays an important pathophysiological role in these diseases. In the current study we examined the functional relevance of the BDNF val66met polymorphism for response inhibition processes in 57 healthy human subjects using event-related potentials (ERPs), i.e. the Nogo-N2 and Nogo-P3, which likely reflect different aspects of inhibition. Our results support the pre-motor inhibition theory of the Nogo-N2. We show that the BDNF val66met polymorphism selectively modulates the Nogo-N2. Response inhibition was better in the val/met-met/met group, since this group committed fewer false alarms, and their Nogo-N2 was larger, compared to the val/val group. This is the first study showing that met alleles of the BDNF val66met polymorphism confer an advantage for a specific cognitive function. We propose a neuronal model how this advantage gets manifest on a neuronal level.

Error processing in normal aging and in basal ganglia disorders.

Recently it has been shown that effects of aging and pathologically induced changes of basal ganglia structures may have quite similar effects on cognitive functions mediated by the medial prefrontal cortex. The question appears, if this pattern may be assignable to other cognitive functions that are mediated via the basal ganglia and medial prefrontal brain areas. Error processing is a component of executive functions that also depends on these areas and especially on the anterior cingulate cortex (ACC). Hence we ask, if error processing functions are differentially modulated by normal aging and basal ganglia diseases. Error processing mechanisms in these groups were investigated using a cognitive event-related potential (ERP), the error negativity. Enrolling an extended sample of young and elderly controls, as well as patients with Parkinson's and Huntington's disease, we show that modulations of error processing differ between aging, different basal ganglia diseases. Despite that the examined basal ganglia disorder groups (Parkinson's and Huntington's disease) differ in their age they show similar modulations in error processing, suggesting that aging effects are overridden by pathogenic effects. The study shows that it may be valuable to compare aging not only to different forms of basal ganglia disorders in order to gain knowledge about age- and disease-related mechanisms and the effects of these on cognitive functions. Diseases of the basal ganglia may impact error processing above and beyond the effects of normal aging. Although many aging, Parkinson's disease and Huntington's disease studies on error processing functions have already been published, this study ties together several related observations across all of these groups in one experiment.