Network measures predict neuropsychological outcome after brain injury

Abstract

Hubs are network components that hold positions of high importance for network function. Previous research has identified hubs in human brain networks derived from neuroimaging data; however, there is little consensus on the localization of such hubs. Moreover, direct evidence regarding the role of various proposed hubs in network function (e.g., cognition) is scarce. Regions of the default mode network (DMN) have been frequently identified as "cortical hubs" of brain networks. On theoretical grounds, we have argued against some of the methods used to identify these hubs and have advocated alternative approaches that identify different regions of cortex as hubs. Our framework predicts that our proposed hub locations may play influential roles in multiple aspects of cognition, and, in contrast, that hubs identified via other methods (including salient regions in the DMN) might not exert such broad influence. Here we used a neuropsychological approach to directly test these predictions by studying long-term cognitive and behavioral outcomes in 30 patients, 19 with focal lesions to six "target" hubs identified by our approaches (high system density and participation coefficient) and 11 with focal lesions to two "control" hubs (high degree centrality). In support of our predictions, we found that damage to target locations produced severe and widespread cognitive deficits, whereas damage to control locations produced more circumscribed deficits. These findings support our interpretation of how neuroimaging-derived network measures relate to cognition and augment classic neuroanatomically based predictions about cognitive and behavioral outcomes after focal brain injury.functional connectivity | neuropsychology | fMRI | brain hubs T he careful description of circumscribed cognitive and behavioral deficits following localized brain damage has provided much of our knowledge of the functional geography of the brain. In some cases, however, relatively small, circumscribed lesions seem to have broader effects than would be predicted from their size and location. Historically, these effects sometimes have been attributed to diaschisis (i.e., effects at a distance) owing to connections between affected and unaffected brain regions. The potential importance of interactivity among brain regions is supported by recent research (1-3); for example, He et al. (4) found that visuospatial inattention after right inferior parietal lesions was best explained by the effects of those lesions on more superior parietal activity.In the broadest sense, interactive explanations of brain function can be thought of as reflecting the organization of the brain as a large-scale network. The advent of large-scale network descriptions of brain structure and function extends the possibility of richer and broader explanations of unusually severe cognitive and behavioral consequences that sometimes follow circumscribed lesions. Some large-scale network studies have focused on "hubs," a term from network science that indicates potential points of impo...

Imaging human brain networks to improve the clinical efficacy of non-invasive brain stimulation

“…However, the widespread effect of focal inhibition of M1 was constrained to patterns of connectivity involving the sensorimotor system, whereas excitatory TMS over the primary motor cortex did not significantly change connectivity within the sensorimotor system, or between this system and other systems in the brain. In general, these findings support earlier computational investigations suggesting that damage to highly interconnected regions may have more dramatic effects on brain functions (Honey and Sporns, 2008;Alstott et al, 2009;Warren et al, 2014).…”

“…As discussed previously, the impact that a local change in regional activity could have on whole brain connectivity and related brain function is A c c e p t e d M a n u s c r i p t Sale et al,18 most likely determined by the density of connections (i.e., the degree) of such regions with the rest of the brain (Alstott et al, 2009;Warren et al, 2014). The stimulation of densely connected neural hubs is therefore likely to cause widespread changes in patterns of integration across brain areas and systems.…”

“…If the peri-lesional effects of the stroke encompass a densely interconnected brain hub, rTMS over this region will likely have complex and widespread effects. Indeed, when a stroke affects a highly interconnected region, the associated cognitive deficits are more pronounced (Warren et al, 2014). Strategies to promote network-relevant reorganization should be employed in these circumstances.…”

The modular and integrative functional architecture of the human brain

“…These results are precisely what one would expect if connector nodes' function plays a role in global connectivity that maintains modularity. Moreover, patients with lesions damaging connector nodes exhibit widespread cognitive deficits, whereas damage to other brain regions (i.e., local nodes) causes specific cognitive deficits (90). Finally, connector node regions have been found to be metabolically demanding (91).…”

Strategy‐based reasoning training modulates cortical thickness and resting‐state functional connectivity in adults with chronic traumatic brain injury

“…The strength of brain activity in regions with high between‐network connectivity is proportional to the number of cognitive functions engaged in a task (Bertolero, Yeo, & D'Esposito, 2015). Furthermore, damage to these regions disrupts the brain's modular organization (Gratton, Nomura, Pérez, & D'Esposito, 2012) and yields widespread deficits in neuropsychological measures (Warren et al., 2014). Critically, long‐range and between‐network connections are also vulnerable to damage from TBI (Han et al., 2014, 2016).…”