Altersabhängige Veränderungen des EEGs in Kindheit und Adoleszenz

Der vorliegende Mantelteil bildet einen Rahmen für drei empirische Arbeiten, die sich mit altersabhängigen Veränderungen des Elektroenzephalogramms (= EEG) in Kindheit und Adoleszenz beschäftigen. In der Einleitung wird Hirnentwicklung als gemeinsamer Hintergrund der Arbeiten vorgestellt. Im Theorieteil wird das EEG als Methode zur Erfassung von Hirnentwicklung bei Kindern und Jugendlichen dargestellt. Abschließend werden dann frühere Befunde in diesem Bereich skizziert und eigene Hypothesen abgeleitet. Nach einer kurzen Beschreibung des Designs, der Stichprobe und des allgemeinen Vorgehens bei der Erfassung und Auswertung der Daten im Methodenteil werden im Diskussionsteil eigene Befunde zusammengefasst und im Hinblick auf eine mögliche Bedeutung für ein Verständnis normaler und pathologischer Entwicklung erörtert. Ausgangspunkt der vorliegenden Promotion ist ein Artikel zu frequenzspezifischen Veränderungen der hirnelektrischen Ruheaktivität über das Schulalter (Arbeit I), in den Erkenntnisse der Diplomarbeit des Autors wesentlich verfeinert eingingen. Die auf diesem Weg beschriebene hirnelektrische Aktivität wurde dann in einem weiteren Manuskript im Hinblick auf altersabhängige Veränderungen ihrer räumlichen Synchronisierung analysiert (Arbeit II). Daraus ergibt sich eine umfassende Beschreibung des Ruhe-EEGs in Kindheit und Adoleszenz. Über Veränderungen des Ruhe-EEGs hinaus wurden in Arbeit III altersabhängige Veränderungen ereigniskorrelierter Potentiale beschrieben. Das hierfür herangezogene P3-Paradigma wird im Folgenden als neurophysiologisches Korrelat höherer Aufmerksamkeits- und Gedächtnisprozesse betrachtet. Gegenwärtig wird eine Reorganisation des Ruhe-EEGs in Folge von Informationsverarbeitungsprozessen als eine mögliche Grundlage ereigniskorrelierter Potentiale diskutiert. Dieser Zusammenhang unterstreicht die Bedeutung einer gemeinsamen Untersuchung von Ruhe-Aktivität und ereigniskorrelierter Aktivität für ein Verständnis der markanten kognitiven Fortschritte in der Kindheit und Adoleszenz

Intraindividual variability in inhibitory function in adults with ADHD - an ex-Gaussian approach

OBJECTIVE: Attention deficit disorder (ADHD) is commonly associated with inhibitory dysfunction contributing to typical behavioral symptoms like impulsivity or hyperactivity. However, some studies analyzing intraindividual variability (IIV) of reaction times in children with ADHD (cADHD) question a predominance of inhibitory deficits. IIV is a measure of the stability of information processing and provides evidence that longer reaction times (RT) in inhibitory tasks in cADHD are due to only a few prolonged responses which may indicate deficits in sustained attention rather than inhibitory dysfunction. We wanted to find out, whether a slowing in inhibitory functioning in adults with ADHD (aADHD) is due to isolated slow responses. METHODS: Computing classical RT measures (mean RT, SD), ex-Gaussian parameters of IIV (which allow a better separation of reaction time (mu), variability (sigma) and abnormally slow responses (tau) than classical measures) as well as errors of omission and commission, we examined response inhibition in a well-established GoNogo task in a sample of aADHD subjects without medication and healthy controls matched for age, gender and education. RESULTS: We did not find higher numbers of commission errors in aADHD, while the number of omissions was significantly increased compared with controls. In contrast to increased mean RT, the distributional parameter mu did not document a significant slowing in aADHD. However, subjects with aADHD were characterized by increased IIV throughout the entire RT distribution as indicated by the parameters sigma and tau as well as the SD of reaction time. Moreover, we found a significant correlation between tau and the number of omission errors. CONCLUSIONS: Our findings question a primacy of inhibitory deficits in aADHD and provide evidence for attentional dysfunction. The present findings may have theoretical implications for etiological models of ADHD as well as more practical implications for neuropsychological testing in aADHD

Attentional Lapses of Adults with Attention Deficit Hyperactivity Disorder in Tasks of Sustained Attention

Adults with attention deficit hyperactivity disorder (ADHD) show attentional dysfunction such as distractibility and mind-wandering, especially in lengthy tasks. However, fundamentals of dysfunction are ambiguous and relationships of neuropsychological test parameters with self-report measures of ADHD symptoms are marginal. We hypothesize that basic deficits in sustaining attention explain more complex attentional dysfunction in persons with ADHD and relate to ADHD symptoms. Attentional function was analyzed by computing ex-Gaussian parameters for 3 time Blocks in a 20 min test of sustained alertness. Changes in performance across these blocks were analyzed by comparing adult persons with ADHD (n = 24) with healthy matched controls (n = 24) and correlated with neuropsychological measures of selective and divided attention as well as self-report measures of ADHD symptoms. We found a significantly steeper increase in the number of slow responses (ex-Gaussian parameter τ) in persons with ADHD with time on task in basic sustained alertness. They also performed significantly worse in tasks of sustained selective and divided attention. However, after controlling for an increase in τ during the alertness task, significant differences between groups disappeared for divided and partly selective attention. Increases in τ in the sustained alertness task correlated significantly with self-report measures of ADHD symptoms. Our results provide evidence that very basic deficits in sustaining attention in adults with ADHD are related to infrequent slow responses (=attentional lapses), with changes over time being relevant for more complex attentional function and experienced ADHD symptoms in everyday life

Frequency of intraindividual RTs with fitted ex-Gaussian probability functions exemplary for a control (left) and an ADHD (right) subject.

<p>NOTE: Please keep in mind that RTs in ADHD encompass a broader range (200</p

Distribution of age for both adult controls and adult ADHD.

<p>Distribution of age for both adult controls and adult ADHD.</p

Exemplary distribution of RT and relation of Mean, SD and the number of slow responses.

<p><b>NOTE</b>: Dotted grey arrows illustrate a rightward shift of mean RT and an increase of the SD of RT as a consequence of an increasing number of slow responses forming the right tail of the distribution.</p

Age-adjusted high-dose chemotherapy followed by autologous stem cell transplantation or conventional chemotherapy with R-MP as first-line treatment in elderly primary CNS lymphoma patients – the randomized phase III PRIMA-CNS trial

Abstract Background Older primary central nervous system lymphoma (PCNSL) patients have an inferior prognosis compared to younger patients because available evidence on best treatment is scarce and treatment delivery is challenging due to comorbidities and reduced performance status. High-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) after high-dose methotrexate (MTX)-based immuno-chemotherapy has become an increasingly used treatment approach in eligible elderly PCNSL patients with promising feasibility and efficacy, but has not been compared with conventional chemotherapy approaches. In addition, eligibility for HCT-ASCT in elderly PCNSL is not well defined. Geriatric assessment (GA) may be helpful in selecting patients for the best individual treatment choice, but no standardized GA exists to date. A randomized controlled trial, incorporating a GA and comparing age-adapted HCT-ASCT treatment with conventional chemotherapy is needed. Methods This open-label, multicenter, randomized phase III trial with two parallel arms will recruit 310 patients with newly diagnosed PCNSL > 65 years of age in 40 centers in Germany and Austria. The primary objective is to demonstrate that intensified chemotherapy followed by consolidating HCT-ASCT is superior to conventional chemotherapy with rituximab, MTX, procarbazine (R-MP) followed by maintenance with procarbazine in terms of progression free survival (PFS). Secondary endpoints include overall survival (OS), event free survival (EFS), (neuro-)toxicity and quality of life (QoL). GA will be conducted at specific time points during the course of the study. All patients will be treated with a pre-phase rituximab-MTX (R-MTX) cycle followed by re-assessment of transplant eligibility. Patients judged transplant eligible will be randomized (1:1). Patients in arm A will be treated with 3 cycles of R-MP followed by maintenance therapy with procarbazine for 6 months. Patients in arm B will be treated with 2 cycles of MARTA (R-MTX/AraC) followed by busulfan- and thiotepa-based HCT-ASCT. Discussion The best treatment strategy for elderly PCNSL patients remains unknown. Treatments range from palliative to curative but more toxic therapies, and there is no standardized measure to select patients for the right treatment. This randomized controlled trial will create evidence for the best treatment strategy with the focus on developing a standardized GA to help define eligibility for an intensive treatment approach. Trial registration German clinical trials registry DRKS00024085 registered March 29, 2023