Connectomics

Principles of wiring of the human connectome

A central theme of the work in my group is to find natural rules that govern the efficient organisation of brain networks. I hypothesise the existence of basic ‘principles of wiring’ that define the topological organization of the human connectome, and study how these principles are associated to brain function and brain disfunction in several neurological and psychiatric disorders.

We particularly like to examine the role of central connected hubs in nervous systems (one of the believed ‘principles of wiring’) and how they form a central rich-club core in the human brain. We examine the brain’s rich club in relationship to genetics, to behaviour, to brain dynamics, in relationship to various brain disorders, and during human brain evolution.

A major focus of our research is on linking brain networks to other fields of neuroscience: These include

• imaging-genetics, in which we link aspects of genetics (e.g. candidate genes, GWAS, gene-expression) to brain connectivity, in health, disease and development. This with the goal to elucidate the genetic underpinnings of the hypothesised ‘principles of wiring’
• cross-disorder connectomics, in which we examine relationships of connectome alterations across different brain disorders
• multi-scale connectomics, in which we link micro- and macroscale features of neural connectivity in health, disease and brain development
• comparative connectomics, in which we aim to bridge connectome properties across different species and search for commonalities and differences in connectome organization between species.

Oh, and of course(!), we have great joy in linking and bridging these different topics as much as possible….

A major research interest of our group is also to develop new methods for MRI connectome research and to explore the usability of AI (e.g. deep learning, classification, data analytics) approaches to medical data, combining all sorts of data including genetics, imaging, questionnaires and multiple other (brain) traits to search for new biomarkers for disease.

I am a handling associate editor for Human Brain Mapping, Network Neuroscience and a member of the Editorial Board of Neuroimage. I am actively involved in several connectome workshops at international conferences and international summerschools on brain network analysis.

More about our work (including movies, data downloads, publications, internship positions) can also be found at www.dutchconnectomelab.nl .

Central publications of the lab

Romme I, de Reus MA, Kahn RS, van den Heuvel MP (2016). Cortical gene expression and macroscale connectome disconnectivity in schizophrenia. Biological Psychiatry. Epub ahead of print. This paper was the first in which we linked cortical gene expression profiles to macroscale connectivity patters in context of schizophrenia. We identified overlapping patterns of gene expression and disconnectivity and hypothesized new risk-genes for schizophrenia.

Van den Heuvel MP, Scholtens LH, de Reus MA, Kahn RS. (2016). Associated Microscale Spine Density and Macroscale Connectivity Disruptions in Schizophrenia. Biological Psychiatry. In this paper we linked cortical microscale neuronal changes in schizophrenia to macroscale changes in connectivity as observed by means of MRI.

Van den Heuvel MP, Bullmore ET, Sporns O. (2016). Comparative Connectomics. Trends in Cognitive Neurosciences. This paper introduces the field of comparative connectomics, with the aim to explore commonalities and differences in wiring structure across species.

Schmidt R, de Reus MA, Scholtens LH, van den Berg LH, van den Heuvel MP (2015). Simulating disease propagation across white matter connectome reveals anatomical substrate for neuropathology staging in amyotrophic lateral sclerosis. Neuroimage. In this study we combined cortical patterns of TDP43 load with macroscale connectivity providing system level evidence for pathology spread in ALS.

Scholtens LH, Schmidt R, de Reus MA, van den Heuvel MP (2014). Linking macroscale graph analytical organization to microscale neuroarchitectonics in the macaque connectome. Journal of Neuroscience. In this paper we examined the link between neuronal organization and macroscale connectome organization in the macaque cortex.

Van den Heuvel MP, Sporns O (2013). Network hubs in the human brain (2013). Trends in Cogn Sciences. Dec;17(12):683-96. This review discusses the existence of macroscale hub organization in human and animal nervous systems and the implication of this type of organization for disease.

Van den Heuvel MP, Sporns O, Collin G, Scheeuwe T, Mandl RCW, Cahn W, Goni J, Hulshoff Pol HE, Kahn RS (2013). Abnormal rich-club organization and functional brain dynamics in schizophrenia. JAMA Psychiatry/Archives of General Psychiatry. In this paper we showed that affected rich club organization may play an important role in the aetiology of schizophrenia.

Van den Heuvel MP, Kahn RS, Goni J, Sporns O (2013). A high-cost, high-capacity backbone of brain communication. Proc Nat Acad Sci. We studied rich club organization of the human connectome and its effect on efficient communication.

Van den Heuvel MP & Sporns O. Rich-club organization of the human connectome (2011). Journal of Neuroscience. This paper introduced the concept of rich club organization in the human brain.

Van den Heuvel MP & Hulshoff Pol. Exploring the human brain network (2010). European Neuropsychopharmacology. A review on functional MRI brain networks and the application of brain network neuroscience to health and_disease.