The Research Group Resilient Networks

For most brain disorders, the progression of pathological changes at the molecular and cellular level poorly correlates with their phenotypic presentation. There are many examples for which behavioral functionality is maintained even following drastic regional neural loss. Here, we put forward the concept that neural networks undergo fundamental changes very early in neurodegenerative, neuro-immunological as well as psychiatric disorders in a disease-transcending manner, even in regions not yet affected by the underlying molecular and cellular pathophysiology. These early changes are often maladaptive and associated with hyperactive neurons, which marks the starting point for activity-dependent neurodegeneration (Arnoux et al, Rosales et al, Ellwardt et al). We propose that networks undergo plastic changes not necessarily aiming at optimizing the phenotypic outcome, but by systems dynamics governed in a selfish, stability retaining manner. These states can be formalized as self-balancing attractors, based on systems-theoretical framework (please see the Initiative for Systems Analysis in Neuroscience). We propose that these early neural network changes are a distinct (patho-)physiological entity which offers new therapeutic targets for preventing the manifestation of disease and fostering resilience (please see Learning Resilience project).

At this early stage short-term application of mediators can rebalance the network to achieve a physiological state and to counterbalance maladaptation early, preventing or delaying activity-depending neurodegeneration (Arnoux et al). For a translationally relevant neuromodulation, we will explore circuit-wide, long-lasting disinhibitory effect of sub-ablative dose stereotactic radiosurgery to focal brain targets for durable rebalancing of neuronal networks (Zaer et al 2021, 2021, 2022). Not the least, these network states are highly dependent on the internal brain state. We investigate functional brain states – such as the slow wave state and the persistent state – in various conditions of vigilance (Stroh et al Neuron, Schwalm et al 2017, Aedo Jury et al 2020).

For assessing and manipulating primarily cortico-thalamic network states, we implement all optical and optomagnetic multi-modal imaging approaches in rodents (Fu et al, Backhaus et al), such as 2-photon Ca2+ imaging, optic-fiber-based Ca2+ recordings (Schmid et al 2016), single cell optogenetics (Fois et al 2014), and functional MRI. We e.g. combine optical recordings of slow oscillations with simultaneous fMRI, to attain the brain-wide fMRI signature of neuronal signals-of-interest slow oscillations (Cleppien et al)(please see the Mainz Animal Imaging Center). We also enhance the temporal resolution of fMRI by implementing fast line-scanning methods. These pipelines are also translationally applicable in human EEG-fMRI recordings (Ilhan et al).