Abnormal Distracter Processing in Adults with Attention-Deficit-Hyperactivity Disorder

Background: Subjects with Attention-Deficit Hyperactivity Disorder (ADHD) are overdistractible by stimuli out of the intended focus of attention. This control deficit could be due to primarily reduced attentional capacities or, e. g., to overshooting orienting to unexpected events. Here, we aimed at identifying disease-related abnormalities of novelty processing and, therefore, studied event-related potentials (ERP) to respective stimuli in adult ADHD patients compared to healthy subjects. Methods: Fifteen unmedicated subjects with ADHD and fifteen matched controls engaged in a visual oddball task (OT) under simultaneous EEG recordings. A target stimulus, upon which a motor response was required, and non-target stimuli, which did not demand a specific reaction, were presented in random order. Target and most non-target stimuli were presented repeatedly, but some non-target stimuli occurred only once (‘novels’). These unique stimuli were either ‘relative novels ’ with which a meaning could be associated, or ‘complete novels’, if no association was available. Results: In frontal recordings, a positive component with a peak latency of some 400 ms became maximal after novels. In healthy subjects, this novelty-P3 (or ‘orienting response’) was of higher magnitude after complete than after relative novels, in contrast to the patients with an undifferentially high frontal responsivity. Instead, ADHD patients tended to smaller centro-parietal P3 responses after target signals and, on a behavioural level, responded slower than controls

Functional magnetic resonance imaging (fMRI) of attention processes in presumed obligate carriers of schizophrenia: preliminary findings

<p>Abstract</p> <p>Background</p> <p>Presumed obligate carriers (POCs) are the first-degree relatives of people with schizophrenia who, although do not exhibit the disorder, are in direct lineage of it. Thus, this subpopulation of first-degree relatives could provide very important information with regard to the investigation of endophenotypes for schizophrenia that could clarify the often contradictory findings in schizophrenia high-risk populations. To date, despite the extant literature on schizophrenia endophenotypes, we are only aware of one other study that examined the neural mechanisms that underlie cognitive abnormalities in this group. The aim of this study was to investigate whether a more homogeneous group of relatives, such as POCs, have neural abnormalities that may be related to schizophrenia.</p> <p>Methods</p> <p>We used functional magnetic resonance imaging (fMRI) to collect blood oxygenated level dependent (BOLD) response data in six POCs and eight unrelated healthy controls while performing under conditions of sustained, selective and divided attention.</p> <p>Results</p> <p>The POCs indicated alterations in a widely distributed network of regions involved in attention processes, such as the prefrontal and temporal (including the parahippocampal gyrus) cortices, in addition to the anterior cingulate gyrus. More specifically, a general reduction in BOLD response was found in these areas compared to the healthy participants during attention processes.</p> <p>Conclusion</p> <p>These preliminary findings of decreased activity in POCs indicate that this more homogeneous population of unaffected relatives share similar neural abnormalities with people with schizophrenia, suggesting that reduced BOLD activity in the attention network may be an intermediate marker for schizophrenia.</p

An N-methyl-d-aspartate receptor agonist facilitates sleep-independent synaptic plasticity associated with working memory capacity enhancement

Working memory (WM) capacity improvement is impacted by sleep, and possibly by N-methyl-D-aspartate (NMDA) agonists such as D-cycloserine (DCS), which also affects procedural skill performance. However, the mechanisms behind these relationships are not well understood. In order to investigate the neural basis underlying relationships between WM skill learning and sleep, DCS, and both sleep and DCS together, we evaluated training-retest performances in the n-back task among healthy subjects who were given either a placebo or DCS before the task training, and then followed task training sessions either with wakefulness or sleep. DCS facilitated WM capacity enhancement only occurring after a period of wakefulness, rather than sleep, indicating that WM capacity enhancement is affected by a cellular heterogeneity in synaptic plasticity between time spent awake and time spent asleep. These findings may contribute to development, anti-aging processes, and rehabilitation of higher cognition

Role of Basal Ganglia Circuits in Resisting Interference by Distracters: A swLORETA Study

BACKGROUND: The selection of task-relevant information requires both the focalization of attention on the task and resistance to interference from irrelevant stimuli. Both mechanisms rely on a dorsal frontoparietal network, while focalization additionally involves a ventral frontoparietal network. The role of subcortical structures in attention is less clear, despite the fact that the striatum interacts significantly with the frontal cortex via frontostriatal loops. One means of investigating the basal ganglia's contributions to attention is to examine the features of P300 components (i.e. amplitude, latency, and generators) in patients with basal ganglia damage (such as in Parkinson's disease (PD), in which attention is often impaired). Three-stimulus oddball paradigms can be used to study distracter-elicited and target-elicited P300 subcomponents. METHODOLOGY/PRINCIPAL FINDINGS: In order to compare distracter- and target-elicited P300 components, high-density (128-channel) electroencephalograms were recorded during a three-stimulus visual oddball paradigm in 15 patients with early PD and 15 matched healthy controls. For each subject, the P300 sources were localized using standardized weighted low-resolution electromagnetic tomography (swLORETA). Comparative analyses (one-sample and two-sample t-tests) were performed using SPM5® software. The swLORETA analyses showed that PD patients displayed fewer dorsolateral prefrontal (DLPF) distracter-P300 generators but no significant differences in target-elicited P300 sources; this suggests dysfunction of the DLPF cortex when the executive frontostriatal loop is disrupted by basal ganglia damage. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the cortical attention frontoparietal networks (mainly the dorsal one) are modulated by the basal ganglia. Disruption of this network in PD impairs resistance to distracters, which results in attention disorders

Modes of Aβ toxicity in Alzheimer’s disease

Alzheimer’s disease (AD) is reaching epidemic proportions, yet a cure is not yet available. While the genetic causes of the rare familial inherited forms of AD are understood, the causes of the sporadic forms of the disease are not. Histopathologically, these two forms of AD are indistinguishable: they are characterized by amyloid-β (Aβ) peptide-containing amyloid plaques and tau-containing neurofibrillary tangles. In this review we compare AD to frontotemporal dementia (FTD), a subset of which is characterized by tau deposition in the absence of overt plaques. A host of transgenic animal AD models have been established through the expression of human proteins with pathogenic mutations previously identified in familial AD and FTD. Determining how these mutant proteins cause disease in vivo should contribute to an understanding of the causes of the more frequent sporadic forms. We discuss the insight transgenic animal models have provided into Aβ and tau toxicity, also with regards to mitochondrial function and the crucial role tau plays in mediating Aβ toxicity. We also discuss the role of miRNAs in mediating the toxic effects of the Aβ peptide

The need for harmonization and innovation of neuropsychological assessment in neurodegenerative dementias in Europe: consensus document of the Joint Program for Neurodegenerative Diseases Working Group

Cognitive, behavioural, and functional assessment is crucial in longitudinal studies of neurodegenerative dementias (NDD). Central issues, such as the definition of the study population (asymptomatic, at risk, or individuals with dementia), the detection of change/decline, and the assessment of relevant outcomes depend on quantitative measures of cognitive, behavioural, and functional status. Currently, we are far from having available reliable protocols and tools for the assessment of dementias in Europe. The main problems are the heterogeneity of the tools used across different European countries, the lack of standardisation of administration and scoring methods across centres, and the limited information available about the psychometric properties of many tests currently in widespread use. This situation makes it hard to compare results across studies carried out in different centres, thus hampering research progress, in particular towards the contribution to a “big data” common data set. We present here the results of a project funded by the Joint Program for Neurodegenerative Diseases (JPND) and by the Italian Ministry of Health. The project aimed at providing a consensus framework for the harmonisation of assessment tools to be applied to research in neurodegenerative disorders affecting cognition across Europe. A panel of European experts reviewed the current methods of neuropsychological assessment, identified pending issues, and made recommendations for the harmonisation of neuropsychological assessment of neurodegenerative dementias in Europe. A consensus was achieved on the general recommendations to be followed in developing procedures and tools for neuropsychological assessment, with the aim of harmonising tools and procedures to achieve more reliable data on the cognitive-behavioural examination. The results of this study should be considered as a first step to enhancing a common view and practise on NDD assessment across European countries