Figure 2.

Brain networks in the healthy brain and during multiple sclerosis (MS). Brain networks are plastic structures in which multiple mechanisms are required to ensure physiological dynamics for multimodal information processing, context-dependent input integration, and learning mechanisms. In the figure, brain networks are represented as functionally interconnected brain regions. In particular, the graph is composed of round nodes representing specific neuronal ensembles belonging to different brain areas, intra-network connections and inter-networks projections. In the healthy brain, the physiological functioning of brain networks is made possible by synaptic plastic processes that allow to strengthen effective intra- and inter-network connections (bold arrows), while weakening others (not bold arrows). The shaping and refining of neuronal circuits lead to the selective activation of specific neuronal ensembles in the network (circled in red). Pathological activation of the immune system during MS is thought to affect synaptic structures and their functions. The MS brain is characterized by the loss of plastic mechanisms underlying the strengthening/weakening of intra- and inter-network connections. Moreover, the loss of neuronal connections due to axonal transection/damage (dashed arrows) and neuronal death (dashed nodes) contribute to network disconnection and low performance.