Dedifferentiation Does Not Account for Hyperconnectivity after Traumatic Brain Injury

Abstract

ObjectiveChanges in functional network connectivity following traumatic brain injury (TBI) have received increasing attention in recent neuroimaging literature. This study sought to understand how disrupted systems adapt to injury during resting and goal-directed brain states. Hyperconnectivity has been a common finding, and dedifferentiation (or loss of segregation of networks) is one possible explanation for this finding. We hypothesized that individuals with TBI would show dedifferentiation of networks (as noted in other clinical populations) and these effects would be associated with cognitive dysfunction.MethodsGraph theory was implemented to examine functional connectivity during periods of task and rest in 19 individuals with moderate/severe TBI and 14 healthy controls (HCs). Using a functional brain atlas derived from 83 functional imaging studies, graph theory was used to examine network dynamics and determine whether dedifferentiation accounts for changes in connectivity. Regions of interest were assigned to one of three groups: task-positive, default mode, or other networks. Relationships between these metrics were then compared with performance on neuropsychological tests.ResultsHyperconnectivity in TBI was most commonly observed as increased within-network connectivity. Network strengths within networks that showed differences between TBI and HCs were correlated with performance on five neuropsychological tests typically sensitive to deficits commonly reported in TBI. Hyperconnectivity within the default mode network (DMN) during task was associated with better performance on Digit Span Backward, a measure of working memory [R2(18) = 0.28, p = 0.02]. In other words, increased differentiation of networks during task was associated with better working memory. Hyperconnectivity within the task-positive network during rest was not associated with behavior. Negative correlation weights were not associated with behavior.ConclusionThe primary hypothesis that hyperconnectivity occurs through dedifferentiation was not supported. Instead, enhanced connectivity post injury was observed within network. Results suggest that the relationship between increased connectivity and cognitive functioning may be both state (rest or task) and network dependent. High-cost network hubs were identical for both rest and task, and cost was negatively associated with performance on measures of psychomotor speed and set-shifting.

Diminished neural network dynamics after moderate and severe traumatic brain injury

“…First, like most all studies in this literature, TBI is a heterogeneous disorder and ideally we would have a sample size that permitted subgroups for analysis. While the current data demonstrated the within subject reliability of network dynamics and the sample size here is comparable to prior graph theory analysis examining static networks after moderate and severe TBI [ 4 , 6 , 7 , 68 ], the sample size for this study does preclude direct examination of the reliability of these findings with respect to the groups (e.g., split-half reliability). For this reason, replication of the current findings is needed in a separate group of individuals with moderate and severe TBI with focus on the primary findings: 1) network dynamic loss (i.e., reduced state transitions), 2) occurrence of rare states not evident in the healthy adults in this sample.…”

Diminished neural network dynamics in amnestic mild cognitive impairment

“…With respect to the meaning of the enhanced response observed in state 3, increased regional brain response commonly observed during goal directed behavior in neurological disorders, and even during normal aging, has been historically interpreted as neural compensation (Hillary et al, 2006; Dennis & Cabeza, 2008) or scaffolding (Park et al, 2009). More recently, this finding has been extended to studies of network dynamics (Bernier et al, 2017; Medaglia et al, 2017). Based upon this explanation, the posterior connectivity loss observed in the MCI literature would be bolstered by greater anterior connectivity representing enhanced support via cognitive control (Hillary et al, 2006).…”

Disrupted functional network connectivity predicts cognitive impairment after acute mild traumatic brain injury

“…Meanwhile, our previous study used GCA to analyze the causal connections in the acute mTBI patients and demonstrated significantly increased connectivity from the left ACC to the left MFG 34 . For mTBI patients, Benier et al and Sharp et al hypothesized that such hyperconnectivity patterns in the DMN could be related to dysfunction in working memory and attention switching during cognitive demand 35,36 . MFG connectivity appeared to be associated with the degree of language deficit, a finding supported by the notion of increased use of MFG neural resources as a compensation for impaired neural cognitive function.…”