Mit zunehmendem Alter verschlechtert sich die Leistungsfähigkeit des Gehirns, insbesondere die sogenannten fluiden kognitiven Funktionen wie z. B. die Aufmerksamkeit, die Konzentration oder die Informationsverarbeitungsgeschwindigkeit. Diese Funktionen sind ein Bindeglied zwischen Sensorik und Motorik und unerlässlich für komplexe Wahrnehmungsprozesse sowie die Planung und Steuerung des Verhaltens. Verschlechtern sich diese Funktionen im Alter, erhöht sich das Unfallrisiko. Deshalb untersuchte die Unfallforschung der Versicherer (UDV) gemeinsam mit dem Leibniz-Institut für Arbeitsforschung (IFADo), welche Trainingsprogramme die kognitiven Funktionen bei Menschen ab dem 65. Lebensjahr verbessern. Folgende Trainingsmaßnahmen wurden untersucht: - Kognitives Training (auf dem Papier und PC-gestützt) - Fitnesstraining (kombiniertes Kraft- und Ausdauertraining) und - Entspannungstraining (verschiedene Entspannungstechniken). Das Training fand in einem Zeitraum von vier Monaten regelmäßig zweimal wöchentlich statt. Die Trainingsgruppen wurden mit einer passiven Kontrollgruppe verglichen, die keine Intervention erhielt. Es zeigte sich, dass die stärkste Verbesserung der kognitiven Funktionen in der mentalen Trainingsgruppe zu verzeichnen war. Die Leistungsverbesserung ging mit einer deutlichen Veränderung der Hirnaktivität einher. Die Ergebnisse weisen darauf hin, dass regelmäßiges kognitives Training bestimmte kognitive Funktionen bei Senioren messbar verbessert.

Die Kapazität des Arbeitsgedächtnisses (AG) sagt die Leistungsfähigkeit in diversen anderen kognitiven Funktionen voraus. Zusätzlich werden altersbedingte Beeinträchtigungen in AG mit Defiziten in anderen kognitiven Funktionen assoziiert, was sich im hohen Alter in der Minderung der Selbständigkeit und des Leistungsniveaus in alltäglichen Aufgaben widerspiegelt. Das AG kann durch Trainingsmaßnahmen verbessert werden, und auch andere kognitive Funktionen können von AG-Training profitieren. Die Befundlage bezüglich dieser Transfereffekte deutet darauf hin, dass AG-Training auch Mechanismen zur Verbesserung der allgemeinen kognitiven Leistungsfähigkeit umfasst. Obwohl es zunehmend Hinweise für die Möglichkeit gibt, kognitive Funktionen durch AG-Training zu verbessern, sind die genauen Mechanismen von Training und Transfer noch unklar. In der vorliegenden Dissertation präsentiere ich vier Studien, in denen ich die genauen Mechanismen von AG-Training untersucht habe. Ich konnte zeigen, dass Training die Leistung in verschiedenen Tests zu exekutiven Funktionen verbessert, und dass der Transfer von Trainingseffekten statt auf die Förderung einer allgemeinen kognitiven Fähigkeit auf die Verbesserung in einem spezifischen Prozess zurückzuführen ist. Weiterhin habe ich zum ersten Mal gezeigt, dass bereits 16 Sitzungen eines AG-Trainings zu strukturellen Veränderungen in der weißen Substanz führen. Diese ließen sich in den Nervenbahnen nachweisen, die die mit AG assoziierten Hirnareale verbinden. Ich zeigte erstmals auch, dass altersbedingte Unterschiede in AG zwischen jungen und älteren Erwachsenen bereits nach 16 Trainingssitzungen ausgeglichen werden können. Die Befunde der vorliegenden Arbeit werden in Bezug auf die Flexibilität der kognitiven Funktionen und auf die Plastizität des zugrunde liegenden neuronalen Substrats diskutiert. Zusätzlich werden neue Ansichten für Modelle von Training- und Transfermechanismen vorgestellt. / Working memory (WM) is a cognitive function that is engaged in several everyday tasks. WM performance predicts performance in diverse other cognitive functions. Additionally, WM decline at old age is associated with age-related impairments in others cognitive functions, thus affecting autonomous performance of everyday tasks. It has been shown that WM can be improved with training interventions, and evidence has accumulated showing that also other cognitive functions can profit from WM training. The transfer findings indicate that WM training might enclose a mechanism to improve cognitive functions in general. Even though there exists a growing body of evidence on the possibilities to improve cognitive functions with WM training in different populations, the exact mechanisms of training and transfer have remained unclear. In the current dissertation I examine the prospects and precise mechanisms of WM training with four studies using the bi-modal dual n-back paradigm. I showed that dual n-back training improved performance in various tests tapping executive functions. I could also demonstrate that the mechanisms underlying transfer result from an improvement in a specific process tapped by the training task rather than in the boosting of a general cognitive ability. Consequently, transfer can occur to tasks if they engage the same specific process. Additionally, I provided primary evidence that only 16 sessions of WM training produces microstructural changes in white matter pathways connecting brain regions that support WM functions. I also showed for the first time that age-related differences in WM performance between young and older adults can be compensated for after only 16 training sessions. The findings of the present dissertation are discussed in relation to the flexibility of cognitive functions and the plasticity of the underlying neuronal substrate; additionally, new conceptions to models of training and transfer mechanisms are presented.

The past years have seen an incredible increase in the quality and success rates of treatments in pediatric medicine. One of the resulting major challenges refers to the management of primary or secondary residual executive function deficits in affected children. These deficits lead to problems in the ability to acquire, understand, and apply abstract and complex knowledge and to plan, direct, and control actions. Executive functions deficits are important to consider because they are highly predictive of functioning in social and academic aspects of daily life. We argue that current clinical practice does not sufficiently account for the complex cognitive processes in this population. This is because widely applied pharmacological interventions only rarely account for the complexity of the underlying neuronal mechanisms and do not fit well into possibly powerful “individualized medicine” approaches. Novel treatment approaches targeting deficits in executive functions in seriously ill children could focus on neuronal oscillations, as these have some specific relations to different aspects of executive function. Importantly, such treatment approaches can be individually tailored to the individuals’ deficits and can be transferred into home-treatment or e-health solutions. These approaches are easy-to-use, can be easily integrated into daily life, and are becoming increasingly cost-effective.

Deficits in working memory (WM) functions represent one of the main causes of limited participation in daily life and impaired recovery after brain injury. Based on promising research in clinically healthy individuals, which suggest that repetitive training may improve WM performance and other related cognitive functions, this thesis aimed at exploring the potential and limits of WM training in clinical populations. Existing research on WM training and relevant neuropsychological outcomes were examined with a special focus on individuals with acquired brain injury by means of a meta-analysis (study I). The findings indicated relevant impact of WM training on both behavioral performance and disease-related symptom reduction. To determine the primary outcome variable for the evaluation studies, the Corsi Block-Tapping Task was reviewed (study II). Due to the lack of an appropriate theory-based intervention tailored for the needs of individuals with low WM capacity, the program 'WOME' was developed (study III). Three randomized, double-blind, placebo-controlled trials were carried out to evaluate the efficacy of the new intervention and to provide valuable recommendations for its application in clinical practice (study IV, V and VI). Significant improvements in the trained tasks, moderate to large transfer effects in overall WM performance, and related benefits in daily life were demonstrated. The effects were short-termed with very limited evidence supporting transfer to other cognitive functions. In accordance with the results of the meta-analysis (study I), the number of sessions was identified as an important modulator of efficacy by comparing different training intensities and training tasks. The specific content, in contrast, seemed to be less relevant. Mediation analyses revealed that inter-individual differences influence the successful application of the intervention, in particular initial WM capacity. Implications for clinical application and WM training research are discussed.:1. Introduction 1.1. Definition of the working memory system 1.2. Functional neuroanatomy of working memory 1.3. Functional relevance of working memory 1.4. Training of working memory functions 1.5. Objectives of the current thesis 2. Experimental work 2.1. Study I: Can impaired working memory functioning be improved by training? A meta-analysis with a special focus on brain injured patients 2.2. Study II: „Was misst eigentlich die Blockspanne?“ — Der Gold-Standard im Fokus. 2.3. Study III: WOME working memory training — A new intervention for individuals with low WM capacity 2.4. Study IV: WOME: Theory-based working memory training — A placebo-controlled, double-blind evaluation in older adults 2.5. Study V: Effects of working memory training in patients with acquired brain injury: a double-blind randomized controlled trial. 2.6. Study VI: The effect of high vs. low intensity neuropsychological treatment on working memory in patients with acquired brain injury. 3. General discussion 3.1. Summary of the empirical findings 3.2. Implications for clinical practice 3.2.1. Benefits and limits of working memory training 3.2.2. The importance of training dose and its practical implementation 3.2.3. The influence of inter-individual differences on training efficacy 3.3. Implications for working memory training research 3.4. Critical comments and directions for future research 3.5. Conclusion 4. References 5. Summary 6. Zusammenfassung Appendices List of abbreviations List of Tables List of Figures Supplemental material Curriculum vitae List of publications Selbstständigkeitserklärung

The past years have seen an incredible increase in the quality and success rates of treatments in pediatric medicine. One of the resulting major challenges refers to the management of primary or secondary residual executive function deficits in affected children. These deficits lead to problems in the ability to acquire, understand, and apply abstract and complex knowledge and to plan, direct, and control actions. Executive functions deficits are important to consider because they are highly predictive of functioning in social and academic aspects of daily life. We argue that current clinical practice does not sufficiently account for the complex cognitive processes in this population. This is because widely applied pharmacological interventions only rarely account for the complexity of the underlying neuronal mechanisms and do not fit well into possibly powerful “individualized medicine” approaches. Novel treatment approaches targeting deficits in executive functions in seriously ill children could focus on neuronal oscillations, as these have some specific relations to different aspects of executive function. Importantly, such treatment approaches can be individually tailored to the individuals’ deficits and can be transferred into home-treatment or e-health solutions. These approaches are easy-to-use, can be easily integrated into daily life, and are becoming increasingly cost-effective.

Existing neurocomputational and empirical data link deficient neuromodulation of the fronto-parietal and hippocampal-striatal circuitries with aging-related increase in processing noise and declines in various cognitive functions. Specifically, the theory of aging neuronal gain control postulates that aging-related suboptimal neuromodulation may attenuate neuronal gain control, which yields computational consequences on reducing the signal-to-noise-ratio of synaptic signal transmission and hampering information processing within and between cortical networks. Intervention methods such as cognitive training and non-invasive brain stimulation, e.g., transcranial direct current stimulation (tDCS), have been considered as means to buffer cognitive functions or delay cognitive decline in old age. However, to date the reported effect sizes of immediate training gains and maintenance effects of a variety of cognitive trainings are small to moderate at best; moreover, training-related transfer effects to non-trained but closely related (i.e., near-transfer) or other (i.e., far-transfer) cognitive functions are inconsistent or lacking. Similarly, although applying different tDCS protocols to reduce aging-related cognitive impairments by inducing temporary changes in cortical excitability seem somewhat promising, evidence of effects on short- and long-term plasticity is still equivocal. In this article, we will review and critically discuss existing findings of cognitive training- and stimulation-related behavioral and neural plasticity effects in the context of cognitive aging, focusing specifically on working memory and episodic memory functions, which are subserved by the fronto-parietal and hippocampal-striatal networks, respectively. Furthermore, in line with the theory of aging neuronal gain control we will highlight that developing age-specific brain stimulation protocols and the concurrent applications of tDCS during cognitive training may potentially facilitate short- and long-term cognitive and brain plasticity in old age.

Existing neurocomputational and empirical data link deficient neuromodulation of the fronto-parietal and hippocampal-striatal circuitries with aging-related increase in processing noise and declines in various cognitive functions. Specifically, the theory of aging neuronal gain control postulates that aging-related suboptimal neuromodulation may attenuate neuronal gain control, which yields computational consequences on reducing the signal-to-noise-ratio of synaptic signal transmission and hampering information processing within and between cortical networks. Intervention methods such as cognitive training and non-invasive brain stimulation, e.g., transcranial direct current stimulation (tDCS), have been considered as means to buffer cognitive functions or delay cognitive decline in old age. However, to date the reported effect sizes of immediate training gains and maintenance effects of a variety of cognitive trainings are small to moderate at best; moreover, training-related transfer effects to non-trained but closely related (i.e., near-transfer) or other (i.e., far-transfer) cognitive functions are inconsistent or lacking. Similarly, although applying different tDCS protocols to reduce aging-related cognitive impairments by inducing temporary changes in cortical excitability seem somewhat promising, evidence of effects on short- and long-term plasticity is still equivocal. In this article, we will review and critically discuss existing findings of cognitive training- and stimulation-related behavioral and neural plasticity effects in the context of cognitive aging, focusing specifically on working memory and episodic memory functions, which are subserved by the fronto-parietal and hippocampal-striatal networks, respectively. Furthermore, in line with the theory of aging neuronal gain control we will highlight that developing age-specific brain stimulation protocols and the concurrent applications of tDCS during cognitive training may potentially facilitate short- and long-term cognitive and brain plasticity in old age.