Chronology and Chronicity of Altered Resting-State Functional Connectivity after Traumatic Brain Injury

Abstract

Whereas traumatic brain injury (TBI) results in widespread disruption of neural networks, changes in regional resting-state functional connectivity patterns after insult remain unclear. Specifically, little is known about the chronology of emergent connectivity alterations and whether they persist after a critical recovery window. We used resting-state functional magnetic resonance imaging and seed-voxel correlational analyses in both cross-sectional and longitudinal designs to probe intrinsic connectivity patterns involving the posterior cingulate cortex (PCC) and hippocampi, regions shown to be important in the default mode network (DMN) and vulnerable to neuropathology. A total of 22 participants in the chronic stage of moderateto-severe TBI and 18 healthy controls were included for cross-sectional study. Longitudinal analyses included 13 individuals in the TBI group for whom data approximately 3 months after injury (subacute) were available. Overall, results indicated dissociable connectivity trajectories of the PCC and hippocampi during recovery from TBI, with PCC alterations characterized by early hypersynchrony with the anterior DMN that is gradually reduced, and hippocampal changes marked by increasing synchrony with proximal cortex and subcortex. The PCC also showed increasing antiphase synchrony with posterior attentional regions, and the hippocampi showed decreasing antiphase synchrony with frontal attentional regions. Antiphase synchrony of the hippocampus and dorsolateral prefrontal cortex at the subacute stage of TBI was positively associated with attentional performance on neuropsychological tests at both the subacute and chronic stages. Our findings highlight the heterogeneity of regional whole-brain connectivity changes after TBI, and suggest that residual connectivity alterations exist in the clinically stable phase of TBI. Parallels between the chronicity of the observed effects and findings in neurodegenerative disease are discussed in the context of potential long-term outcomes of TBI.

Altered functional connectivity in children with mild to moderate TBI relates to motor control

“…Many rs-fMRI studies have focused on the default mode, or task negative, network (DMN), a well-characterized network which is active during self-reflective thought but suppressed during attentionally-demanding tasks (4). In adults with TBI, rs-fMRI has revealed altered DMN IC throughout recovery (5-7). Additionally, a recent study of adolescents symptomatic from sports-related concussion identified altered IC within the DMN in even this population (8).…”

Longitudinal recovery of local neuronal activity and consciousness level in acquired brain injury

“…The present investigation represents the first longitudinal study to evaluate local neuronal activity restoration in ABI patients. Previous longitudinal fMRI studies in ABI patients have been focused on functional connectivity changes [Falletta Caravasso et al, ; Hillary et al, ; Nakamura et al, ; Venkatesan et al, ]. Nakamura and colleagues showed that functional connectivity strength throughout the whole brain longitudinally decreased in 6 ABI patients, with only one scan from control subjects [Nakamura et al, ].…”

“…The findings from previous longitudinal fMRI studies in ABI patients have been inconsistent [Falletta Caravasso et al, ; Hillary et al, ; Nakamura et al, ; Venkatesan et al, ], and conclusions have been limited, possibly due to the absence of longitudinal data from matched control subjects [Falletta Caravasso et al, ; Nakamura et al, ; Venkatesan et al, ]. Thus, it is important to systematically investigate the potential roles of brain functional activity in tracking the recovery of consciousness level in ABI patients in a relatively large ABI sample with matched healthy controls.…”

Brain structural connectivity distinguishes patients at risk for cognitive decline after carotid interventions

“…Anatomic and physiologic brain organization, referred to as the connectome [DeFelipe, ; Sporns et al, ] have been used to distinguish healthy controls from patients with schizophrenia, traumatic brain injury, Alzheimer's disease or depression [Peng et al, ; Prasad et al, ; van den Heuvel et al, ; Venkatesan et al, ]. However, it is not known if brain connectivity patterns present prior to injury can predict post‐injury pathological clinical outcomes .…”