Disruptions in Resting State Functional Connectivity and Cerebral Blood Flow in Mild Traumatic Brain Injury Patients

Abstract

Mild traumatic brain injury (mTBI) is often occult to conventional imaging techniques. However, there is growing evidence that mTBI patients who lack evidence of structural intracranial injury may develop post-concussive syndrome (PCS). We investigated longitudinal alterations in resting state functional connectivity (rs-FC) in brain networks in a population of 28 patients compared to 28 matched control participants. Rs-FC and cerebral blood flow (CBF) within the nodes of the Default Mode Network (DMN) and Task Positive Network (TPN) were assessed at three time points including acute, sub-acute, and chronic stages following mTBI. Participants received the Automated Neuropsychological Assessment Metrics (ANAM) to assess cognitive performance. Main findings indicate that despite normalized cognitive performance, chronic mTBI patients demonstrate increased rs-FC between the DMN and regions associated with the salience network (SN) and TPN compared to the control populations, as well as reduced strength of rs-FC within the DMN at the acute stage of injury. In addition, chronic mTBI patients demonstrate an imbalance in the ratio of CBF between nodes of the DMN and TPN. Furthermore, preliminary exploratory analysis suggests that compared to those without chronic PCS, patients with chronic PCS reveal an imbalance in the ratio of CBF between the DMN nodes and TPN nodes across multiple stages of recovery. Findings suggest that the altered network perfusion with the associated changes in rs-FC may be a possible predictor of which mTBI patients will develop chronic PCS.

Small world properties changes in mild traumatic brain injury

“…The normalized characteristic path length to random network was higher in spinal cord injury patients than in controls, suggested reduced normalized global efficiency as well . The disruption of the global efficiency (and, therefore, disturbance of the global integration of networks) agreed with a recent study which reported that MTBI patients with chronic PCSs revealed an imbalance in the ratio of cerebral blood flow between the default mode nodes and task positive nodes across multiple stages of recovery . Consistent abnormal thalamo‐cortical connectivity and decreased activity had been found from recent studies in our group, partially due to the center relay station role of the thalamus in contrast to other sub‐cortical regions such as caudate, which was found not to be functionally disrupted in patients in our data.…”

Altered segregation between task-positive and task-negative regions in mild traumatic brain injury

“…Specifically, the reduced segregation at the chronic stage of injury was linked to increased communication between networks in response to escalating task difficulty in mTBI patients. These results extend previous findings suggesting an imbalance in the communication between DMN and task-positive networks in mTBI patients during resting-state conditions [Mayer et al, 2011; Sours et al, 2013; Sours et al, 2015] demonstrating that this imbalance is present, if not exaggerated, during effortful task execution. Finally, our results reveal that changes in network interactions persist into the chronic stage of injury, highlighting the need of further longitudinal research to adequately map the neural recovery of mTBI patients.…”

“…Reductions in functional connectivity have been reported in mTBI patients within the DMN [Iraji et al, 2014; Johnson et al, 2012; Mayer et al, 2011; Zhou et al, 2012] and within the task-positive network [Mayer et al, 2011; Shumskaya et al, 2012]. However, increased functional connectivity between the DMN and task-positive regions during resting conditions has also been observed at various stages following head injury [Mayer et al, 2011; Sours et al, 2013; Sours et al, 2015]; see [Mayer et al, 2015] for a comprehensive review of current literature). The latter findings suggest an imbalance in the communication during resting conditions between the internally directed, task-negative regions, and the externally directed task-positive regions following TBI.…”

“…Here, we sought to investigate changes in large-scale brain networks following mTBI while addressing the problems noted above. Guided by our previous work showing alterations in between-network connectivity during resting state conditions [Sours et al, 2013; Sours et al, 2015], as well as the diffuse and heterogeneous nature of injury, we hypothesized that, relative to controls, participants with mTBI would exhibit decreased segregation between DMN and task-positive networks – i.e., reduced network antagonism – in the context of effortful task execution. Our central goal was to characterize changes in between -network segregation in chronic mTBI patients as a function of cognitive demands during a working memory task.…”

Orbitofrontal cortical thinning and aggression in mild traumatic brain injury patients

“…Further, the groups were not matched for aggressive behavior; a future study comparing aggression- onance spectroscopy could also be used to study between group differences in neurotransmitters and metabolites in the OFC and associated regions (Cady et al, 1996;Kierans et al, 2014;Sivak et al, 2014). Another modality that would be useful is functional connectivity, which measures the correlation of neural activity in different brain regions (Nathan et al, 2015;Raichle et al, 2001;Sours et al, 2015). Using resting state functional connectivity, the impact of the OFC on aggression could be studied by observing changes in functional connectivity between the OFC and functionally and structurally connected regions such as the amygdala, the dorsolateral prefrontal cortex, the thalamus, the striatum, and primary sensory areas (Barbas, 2007;Cavada et al, 2000;Elliott et al, 2000;Bonelli & Cummings, 2007).…”