Homeostatic structural plasticity can account for topology changes following deafferentation and focal stroke.

Markus Butz,Arjen Van Ooyen,Ines D Steenbuck

doi:10.3389/fnana.2014.00115

Abstract

After brain lesions caused by tumors or stroke, or after lasting loss of input (deafferentation), inter- and intra-regional brain networks respond with complex changes in topology. Not only areas directly affected by the lesion but also regions remote from the lesion may alter their connectivity—a phenomenon known as diaschisis. Changes in network topology after brain lesions can lead to cognitive decline and increasing functional disability. However, the principles governing changes in network topology are poorly understood. Here, we investigated whether homeostatic structural plasticity can account for changes in network topology after deafferentation and brain lesions. Homeostatic structural plasticity postulates that neurons aim to maintain a desired level of electrical activity by deleting synapses when neuronal activity is too high and by providing new synaptic contacts when activity is too low. Using our Model of Structural Plasticity, we explored how local changes in connectivity induced by a focal loss of input affected global network topology. In accordance with experimental and clinical data, we found that after partial deafferentation, the network as a whole became more random, although it maintained its small-world topology, while deafferentated neurons increased their betweenness centrality as they rewired and returned to the homeostatic range of activity. Furthermore, deafferentated neurons increased their global but decreased their local efficiency and got longer tailed degree distributions, indicating the emergence of hub neurons. Together, our results suggest that homeostatic structural plasticity may be an important driving force for lesion-induced network reorganization and that the increase in betweenness centrality of deafferentated areas may hold as a biomarker for brain repair.

Highlights

Repair of brain networks following lesions, stroke or neurodegeneration goes along with massive rewiring of connections
Our results suggest that homeostatic structural plasticity may be an important driving force for lesion-induced network reorganization and that the increase in betweenness centrality of deafferentated areas may hold as a biomarker for brain repair
We developed a novel computational model, called Model of Structural Plasticity (MSP) (Butz and van Ooyen, 2013; Butz et al, 2014), in which neurons create new dendritic spines and axonal boutons when neuronal activity is below a homeostatic set-point, and delete spines and boutons when activity is above the set-point

Summary

Introduction

Repair of brain networks following lesions, stroke or neurodegeneration goes along with massive rewiring of connections. An important aspect of network rewiring is diaschisis (von Monakov, 1914; Andrews, 1991), the phenomenon that brain regions not directly affected by the primary lesion but deafferentated by the lesion change their connectivity Extending this early concept of diaschisis, recent studies analysing neuroimaging data (e.g., from stroke patients) using graph theoretical methods have revealed complex changes in global network topology after brain lesions (Honey and Sporns, 2008; Alstott et al, 2009; Carter et al, 2012; van Meer et al, 2012; Rehme and Grefkes, 2013). Changes in topology after brain damage have mostly been reported for inter-area connectivity (Wang et al, 2010), but both global inter-area connectivity and local intra-area connectivity rewire after lesions (Murphy and Corbett, 2009; Winship and Murphy, 2009)

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