The red arrows describe couplings between areas that were more strongly connected in MS participants than controls during the working memory … In the detailed analysis of pair-wise correlations it was revealed that MS participants had stronger couplings between the right substantia nigra and the left thalamus (−10 −12 14, P = 0.003). In Figure ​Figure7A,7A, it is shown that both Inhibitors,research,lifescience,medical anterior medial and lateral aspects of the thalamus were more strongly coupled

to the right substantia nigra in MS participants than in controls. The results also showed that the left PPC was more strongly coupled to anterior parts of the left DLPFC (−20 56 36, P = 0.012, Fig. ​Fig.7B),7B), whereas it was more weakly coupled to the right caudate head (14 22 6, P = 0.037, Fig. ​Fig.7C)7C) in MS Inhibitors,research,lifescience,medical participants this website compared to controls. The couplings with different functional connectivity in MS participants and controls are visualized in the schematic diagram of the thalamo-striato-cortical network in Figure ​Figure6.6. The red arrows show that MS participants had stronger couplings within the cerebral

cortex (PPC DLPFC) and within subcortical regions (Substantia nigra Thalamus) compared to controls. The blue arrow in Figure ​Figure77 shows Inhibitors,research,lifescience,medical that MS participants had weaker couplings between the cerebral cortex and striatum (PPC Caudate). Figure 7 Images of regions of interest (ROIs) with different functional connectivity Inhibitors,research,lifescience,medical to the seed regions in MS participants. (A) The image shows stronger functional connectivity between the right substantia nigra and the left thalamus in MS participants compared … Discussion During performance of the complex working memory task, the MS participants showed increased activation in the bilateral PPC. This finding is in line with previous

studies that also found increased bilateral cortical activation in MS patients, especially in regions that are normally activated by the administered task (Chiaravalloti et al. 2005; Sweet et al. 2006; Morgen et al. 2007). Frequent findings of hyperactivation Inhibitors,research,lifescience,medical in MS patients have been interpreted as a compensatory reorganization in order to maintain normal performance (Lenzi et al. 2008; Genova et al. 2009). However, the hypothesis of compensatory brain Cell press networks in MS patients is challenged by an alternative hypothesis proposed by Hillary et al. (2006) and Hillary (2008). They argue that increased brain activation in MS patients is a response to increased cognitive demand, which in turn is associated with poorer performance. This argument is well in line with the neural efficiency hypothesis, discussed by Neubauer and Fink (2009). The results in this study support the latter theory, because the MS participants performed worse than the controls during the complex working memory task, and still showed higher activation in cortical areas when solving the administered task.