Past studies of focal brain lesions, such as those arising from stroke or traumatic brain injury, focused on determining how specific behavioral deficits are related to the properties of the damaged tissue in a localization of function approach However, considerable evidence now suggests that focal lesions also affect the physiology of remote regions of the brain. Here, we investigate a novel view that the widespread consequences of a lesion may partly be predicted by large-scale network interactions of the damaged region. Specifically, some regions (connectors) have strong interactions across many different networks while other regions (system hubs) have strong interactions mainly within their own network. We hypothesize that these designations will predict the extent of impairments seen after brain lesions, providing important clinical and scientific insight into these system-levl effects. This hypothesis will be tested through two aims.
Aim 1 examines the relationship between damage to connectors and hubs on behavioral performance across a number of domains in lesion patients.
Aim 2 uses functional Magnetic Resonance Imaging to examine network interactions in these lesion patients' brains and healthy controls.
This aim will examine interactions within pre-specified brain systems and whether system organization is itself altered by brain damage. Neural simulations will also be used to help interpret the findings. Preliminary evidence suggests that damage to connectors, but not to hubs, has pronounced impact on behavior across many different domains and network interactions in many different systems. We propose establishing this pattern in a large patient group with lesions to diverse locations to examine the generality of the preliminary findings and eliminate a number of potential alternative explanations for these effects. By examining disruptions after lesions, this research will shed light on the mechanisms by which networks are maintained in the healthy human brain and how regions with different network properties may contribute to behavior. Furthermore, these findings will provide important new insight into behavioral and brain deficits caused by lesions, improving the ability of clinicians to make prognoses for lesion patients and revealing new avenues to target for rehabilitation. The research aspects of this proposal will be complemented by a strong training regime for the applicant in (1) novel processing methods, (2) neuropsychological characterization of clinical populations, and (3) innovative network analysis techniques. These areas will allow the applicant to create a more sophisticated and multifaceted depiction of how brain networks contribute to function. The proposed research and training regime, in combination with the premier resources available in the Petersen lab at Washington University in St Louis, will position the applicant well for her future goal of becoming a independent investigator in the field, specializing in brain network physiology and it's connection to complex functions.
Brain damage (from stroke, traumatic brain injury, etc.) is extremely common and many individuals survive the initial incident, living the rest of their lives with significant impairments (e.g., in the US stroke alone is the 6th most common cause of disability, with 500 out of every 100,000 individuals living with disabilities). Although advance have been made in relating behavioral deficits to information directly encoded in the disrupted region, lesions can also be associated with diffuse behavioral and widespread neural changes. In this proposal we will use novel network analysis methods to examine how brain damage influences behavior and brain network interactions across many systems, providing an account of why localized brain damage can have widespread consequences on physiology and function - findings that may have important ramifications in the clinical prognosis of lesion patients and development of rehabilitation strategies.
| Gratton, Caterina; Laumann, Timothy O; Nielsen, Ashley N et al. (2018) Functional Brain Networks Are Dominated by Stable Group and Individual Factors, Not Cognitive or Daily Variation. Neuron 98:439-452.e5 |
| Gratton, Caterina; Sun, Haoxin; Petersen, Steven E (2018) Control networks and hubs. Psychophysiology 55: |
| Gratton, C; Neta, M; Sun, H et al. (2017) Distinct Stages of Moment-to-Moment Processing in the Cinguloopercular and Frontoparietal Networks. Cereb Cortex 27:2403-2417 |
| Gratton, Caterina; Laumann, Timothy O; Gordon, Evan M et al. (2016) Evidence for Two Independent Factors that Modify Brain Networks to Meet Task Goals. Cell Rep 17:1276-1288 |
