Current Projects

Modulation of brain networks for memory and learning by transcranial electrical brain stimulationLINK

Non-invasive transcranial direct current stimulation (tDCS) has recently received substantial attention in experimental and clinical science, because it allows modulation of human brain function without significant adverse effects. However, despite widespread and often successful use of this technique, little systematic research into the mechanisms underlying frequently observed highly variable effects of tDCS has been accomplished. Currently, this results in suboptimal use of this promising technique in experimental and clinical contexts. The overarching objective of the proposed Research Unit (RU) is to address this knowledge gap by investigating tDCS effects for the first time in a systematic, comprehensive and coordinated way, by a multidisciplinary and complementary team of leading experts in their respective fields. Due to its exceptional relevance for experimental and translational research, human learning and memory function will serve as a model to study tDCS effects across four functional domains (i.e., visual-spatial, language, motor, and executive) and across the human lifespan. Eight empirical projects (Projects P1-8; two per domain) will use comparable methods, individualized and targeted stimulation, highly controlled experimental settings, and tDCS application during concurrent functional imaging to investigate behavioral and neural mechanisms and predictors of stimulation response. Two overarching projects (P9, P10) will (1) relate the outcomes of biophysical models of individualized current flow to behavioral and neural modulations using the large, coordinated dataset acquired in the empirical projects and (2) cross-validate and improve current flow simulations by using in-vivo magnetic current density imaging measurements.Collaborative activities within the RU will be facilitated by the coordination project that is also responsible for crossproject data management and sharing by adhering to highest standards in the field. In sum, the proposed RU will generate fundamental insights into the neural mechanisms and predictors of tDCS response across the human lifespan, thereby informing theoretical concepts of the mechanisms-of-action by which current flow alters neural activity. From a methodological point of view, we will be able to optimize and validate biophysical models of current flow using an unprecedented dataset. Together, this will substantially advance future experimental and translational applications of tDCS in health and disease.

Short-term plasticity in the human brain induced by transcranial electrical stimulation and memory training: Aiming to identify changes in microstructure, metabolite levels, brain activity, and cognitive performanceLINK

Non-invasive brain stimulation (NIBS) techniques such as transcranial electrical stimulation (tES) with transcranial direct current stimulation (tDCS) as the most common approach, have been used to examine brain-behavior relationships and modulate human cognitive function. With regard to neuronal mechanisms, anodal tDCS over task-relevant brain regions is thought to increase excitability of the cortex and induce long-term potentiation (LTP)-like processes, leading to enhancement in behavioral task performance. The combination of tDCS with brain imaging techniques, either consecutively or concurrently, has allowed characterization of neural modulation on the levels of brain activity, brain connectivity and metabolite concentrations in the human brain. Synaptic and cellular processes, reflecting underlying the structural plasticity in vivo, have been assessed so far using electrophysiology and spectroscopy approaches in the human brain. Microstructural plasticity in brain gray and white matter, an important marker of learning-related plasticity in the brain, has not been assessed in the context of tDCS yet. To this end, the superordinate aim of this project is to investigate short-term structural brain plasticity on the level of microstructure and neurometabolite concentrations of tDCS-supported memory training in the human brain using multi-modal MR imaging. We will apply focal (high-definition) anodal tDCS over temporo-parietal sites during an object-location memory paradigm and acquire multi-modal MRI before and after training to assess microstructural plasticity using DTI metrics in memory-related network hubs and white matter pathways and metabolite concentrations using MRS as markers for neuronal function. The inter-dependency of microstructural and metabolic plasticity will additionally be investigated, together with the linkage of behavioral and functional network effects to individually induced electric fields estimated using computational modeling. This project will advance the comprehensive understanding of tDCS-induced plasticity and support the development of individually adjusted applications to target cognitive systems in the future.

The tACS challenge: Does 10 Hz tACS rhythmically modulate visual perception in humans? LINK

Transcranial alternating current stimulation (tACS) is a promising tool to non-invasively modulate rhythmic brain activity. Such a modulation allows interrogation of causal 158 mechanisms underlying cognition and behaviour, or treatment of related conditions. However, the field is plagued by non-reproducible results, most likely driven by a combination of underpowered studies, publication bias, and inefficient designs, which lead some to question whether tACS is effective overall. This registered report represents a large-scale multi-centre effort to address these challenges. We will conduct a tACS experiment designed to stimulate the visual cortex to rhythmically modulate visual perception. Our design includes two active control conditions for peripheral nerve stimulation of the retina and skin, and a passive control condition. A confirmatory result would reveal rhythmic (i.e. phasic) modulation of perception during visual cortex stimulation, as well as a significant difference in rhythmic modulation strength or in the preferred phase angle between tACS and the two active control conditions.

Neuromodulation through brain stimulation-assisted cognitive training in patients with post-chemotherapy subjective cognitive impairment (Neuromod-PCSCI) after breast cancer LINK

Breast cancer is the most common form of cancer in women. A considerable number of women with breast cancer who have been treated with chemotherapy subsequently develop neurological symptoms such as concentration and memory difficulties (also known as ‘chemobrain’). Currently, there are no validated therapeutic approaches available to treat these symptoms. Cognitive training holds the potential to counteract cognitive impairment. Combining cognitive training with concurrent transcranial direct current stimulation (tDCS) could enhance and maintain the effects of this training, potentially providing a new approach to treat post-chemotherapy subjective cognitive impairment (PCSCI). With this study, we aim to investigate the effects of multi-session tDCS over the left dorsolateral prefrontal cortex in combination with cognitive training on cognition and quality of life in women with PCSCI. The Neuromod-PCSCI trial is a monocentric, randomised, double-blind, placebo-controlled study. Fifty-two women with PCSCI after breast cancer therapy will receive a 3-week tDCS-assisted cognitive training with anodal tDCS over the left dorsolateral prefrontal cortex (target intervention), compared with cognitive training plus sham tDCS (control intervention). Cognitive training will consist of a letter updating task. Primary outcome will be the performance in an untrained task (n-back task) after training. In addition, feasibility, safety and tolerability, as well as quality of life and performance in additional untrained tasks will be investigated. A follow-up visit will be performed 1 month after intervention to assess possible long-term effects. In an exploratory approach, structural and functional MRI will be acquired before the intervention and at post-intervention to identify possible neural predictors for successful intervention.

Enhancing episodic memory in older adults through modulating oscillatory activities in the fronto-posterior network using transcranial alternating current stimulation

Oscillatory brain activity in the theta frequency range plays a central role in episodic memory processes. Age-related changes in frontal theta activity and fronto-posterior phase synchronization have been associated with cognitive deficits in older adults. Studies in young adults show that transcranial alternating current stimulation (tACS) is a promising method to modulate theta phase synchronization between frontal and parietal brain regions and enhance cognitive performance. This opens up the possibility of using tACS to modulate age-related changes in oscillatory brain activity and improve cognitive functions in older individuals. The goal of this project was to investigate the potential of tACS to modulate oscillatory brain activity and thereby improve episodic memory processes in older adults. First, electrophysiological correlates of sequential memory processes were compared between young and older adults to identify age-related differences and determinants of successful performance. Using magnetic resonance imaging (MRI), the functional neural networks underlying episodic memory functions were characterized. In subsequent experimental studies, we examined the effects of fronto-posterior tACS application on episodic memory performance and theta oscillations in young and older adults. Structural MRI data enabled the simulation of individual current distributions in the brain to explore dose-response relationships. Our results provide insights into the neural basis of age-related memory decline. On the electrophysiological level, differences in theta and gamma oscillations during encoding play a particularly important role. At the network level, the findings suggest that connectivity between the posterior hippocampus and other central brain structures of the memory-relevant default mode network may represent compensatory mechanisms. Furthermore, we demonstrated that theta-tACS over fronto-posterior brain structures can modulate hippocampal theta oscillations in relation to memory performance and improve episodic memory functions in older adults. Simulations of individual electric fields revealed that the induced dose depends on factors such as head volume, head circumference, and age-related atrophy, highlighting the need for individualized stimulation protocols. Overall, the results contribute to the understanding of tACS-induced effects on memory functions and their underlying mechanisms in the aging process. The insights gained will advance the development of individualized stimulation protocols to enhance cognitive function.

Brain Plasticity for Active Aging: Enhancing Sensory, Motor, and Cognitive Function by Training Interventions and Non-invasive Brain Stimulations

The project focused on the investigation of the effects of transcranial direct current stimulation (tDCS) in the human brain and its underlying mechanisms. Therefore, this non-invasive brain stimulation approach was combined in four work packages (WP) with imaging techniques (here magnetic resonance imaging, MRI), computer simulations for current flow modeling and intensive task-relevant brain activity in the form of cognitive training. AP 1 focused primarily on neurochemical and functional connectivity changes in the brain induced by brain stimulation and its modulation in aging processes. The observation of reduced GABAergic activity as well as increased network-specific connectivity in the young healthy brain confirmed previous study results. In addition, significant GABAergic modulation in a cohort of healthy older participants demonstrated intact neuronal plasticity in the elderly human brain. Computer simulations of induced current flow at the individual level provided preliminary evidence of a relationship of neuronal effects with the magnitude of the electric field generated on the cortical surface. In AP 2, tDCS was combined with a short cognitive training to investigate behavioral effects as well as their relationship with functional neuronal network integrity. Participants with superior baseline network integrity at baseline (i.e., higher functional connectivity in the memory network) showed superior baseline performance in the task. Furthermore, in addition to a positive effect of stimulation, we observed a predictive influence of this baseline network integrity on the individual benefit of stimulation. Subsequently, AP 3 pursued the goal of conducting a phase II clinical trial to investigate the effectiveness of a combined approach of brain stimulation and intensive cognitive training in healthy older participants on trained and non-trained functions, as well as their sustainability over time. Although there was no beneficial effect on the trained function, an improvement in a non-trained task was observed. This so-called transfer effect correlated with the individually induced electric field magnitude. Furthermore, we were able to detect microstructural changes in the brain that may underlie the observed plasticity changes. AP4 now investigates the feasibility and effects of combining brain stimulation with cognitive training in the home environment of healthy older participants. After in-depth instruction and practice, participants conduct the intervention independently in their homes, self-applying the stimulation, over a two-week period.

In sum, our findings – published in several peer-review publications – provide evidence for the efficacy of a combined tDCS-plus-training approach in the healthy older brain, and shed light on the underlying neural mechanisms. Our studies pave the way towards further investigation of the therapeutic potential of this approach for the prevention or delay of age-associated cognitive decline and pathological memory deficits (as seen, for instance, in Alzheimer’s disease) in humans.