Research Program
“The essence of a normally functioning brain is proper connectivity.” This statement inspired and drove our activities in the CRC 936. Since its launch in 2011, the CRC has effectively promoted a paradigm shift in how we view the brain. In the decade before, concepts of brain function had still largely been based on the notion of local processing and specialization of brain areas. This had resulted from lesion studies, from neuroimaging studies addressing focal activation and from cell physiology and molecular biology, both typically addressing local phenomena at the level of single cells. What had critically been lacking in many domains was an appropriate understanding of the networks that provide the causal link between genetic factors and cellular processes on the one hand, and behavioral and cognitive phenomena on the other. Awareness had been increasing in the neuroscience community that such networks, at a genuine intermediate level of description, needed to be characterized with respect to their connectivity, structure-function relationships and, in particular, their emergent spatiotemporal dynamics in order to advance the understanding of the mechanisms underlying cognition and behavior.
Our overarching hypothesis has been that the crucial determinant of cognition and behavior is neuronal network interaction and not local processing. Perception and action emerge from multi-site communication, reflected in dynamic spatiotemporal coordination of brain activities across multiple sites. The mapping between these functions and their neural substrate is not trivial because the brain is able to dynamically generate and configure a plurality of functional networks even without major changes in structural connections. We advanced the hypothesis that it is the ability for dynamic configuration of functional connectivity that underlies the information processing capabilities of the brain. We assumed that this view would also have strong implications for a better understanding of neurological and psychiatric disorders involving malfunction in distributed networks. Examples of disorders with network malfunctions include schizophrenia, depression, chronic pain, autism, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, or stroke. We conjectured that understanding the spatiotemporal dynamics of distributed networks in these disorders may provide a key to understanding their pathophysiology.
Already during the first funding period, the projects of the CRC made substantial contributions to the testing of these key hypotheses. We implemented a research program for the combined analysis of structural (connectomic) and functional or effective connectivity as well as the evaluation of multisite communication across different temporal and spatial scales. Over the three funding periods, the research program of the CRC evolved continuously. In the first funding phase, we focused on multimodal network analysis, complemented already by substantial modeling activities. In the second funding phase we could enrich analytical approaches with perturbation and intervention techniques (brain stimulation, optogenetics) in order to better probe for causal relations and options of network modulation. In the second funding period, we also benefitted from specific sub-networks that we had identified before and could study them in unprecedented depth while, at the same time, elaborating on whole-brain network models. The third funding period enabled us to consolidate many of the emerging new cross-links and activities. We combined the study of structural and functional connectivity at different temporal and spatial scales with a strong emphasis on network function and on behavioral relevance of network dynamics.
The CRC had defined three key goals for its research program on the processing and dynamics in distributed networks: (1) We set out to characterize multi-site neuronal communication that underlies cognitive functions in the healthy brain; (2) we aimed at studying changes of multi-site interactions during development, plasticity and learning; and (3) we aimed to investigate alterations of multi-site communication in brain disorders including stroke, Parkinson’s disease (PD) and schizophrenia. These key goals mapped directly onto the three thematic areas of the CRC: A. Multi-site communication as a basis of cognition; B. Multi-site interactions during development, plasticity and learning; C. Altered multi-site communication in brain disorders. The conceptual structure with these three thematic areas proved highly successful and was continued throughout the entire lifetime of the CRC. The thematic areas represented the key perspectives within the overall topic and integrated closely related projects.
A key aspect of the research program was that all projects used multi-site methodologies for imaging or recording of neuronal activity. The application of multi-site measurement approaches and appropriate analysis tools was among the criteria that projects had to match for being included in the CRC. The CRC successfully applied a complementary set of state-of-the-art approaches for: (i) the study of multi-site communication, including EEG, MEG, fMRI, DTI, multi-site-microelectrode recordings; (ii) the modulation of multi-site communication, like deep brain stimulation (DBS), multi-site TMS, transcranial alternating current stimulation (tACS), optogenetic modulation, pharmacological modulation and behavioral training; and (iii) the advanced analysis of multi-site communication, including techniques for distributed source modeling, game-theoretical and graph-theoretical algorithms, measures of structural and functional connectivity and computational modeling. This combination of technologies and expertises has allowed us to investigate neuronal interactions at different spatial scales, ranging from local microcircuits to large-scale interactions between different brain regions. In addition, the modulation approaches have enabled us to perturb and entrain network nodes and edges, in adult systems and during development.
With respect to the brain networks studied, there was substantial convergence between projects that investigated multisensory (A2, A3, B11), frontoparietal (A3, A7, C1, C2, C5, C6, C7), hippocampal-frontal (B5, B10, C7), prefrontal-motor (A7, C1, C8) and cortico-subcortical (A5, A6, A7, B8, C1, C8) networks. The modeling projects A1, C9 and Z3 carried out whole-brain investigations on connectivity.
