Exploring Variations in Functional Connectivity of the Resting State Default Mode Network in Mild Traumatic Brain Injury

Background: There is a significant number of military personnel with a history of mild traumatic brain injury (mTBI) who suffer from comorbid posttraumatic stress symptoms (PTS). Although there is evidence of disruptions of the default mode network (DMN) associated with PTS and mTBI, previous studies have only studied static connectivity while ignoring temporal variability of connectivity. Objective: To assess DMN disrupted or dysregulated neurocircuitry, cognitive functioning, and psychological health of active-duty military with mTBI and PTS. Method: U.S. Army soldiers with PTS (n = 14), mTBI + PTS (n = 25), and healthy controls (n = 21) voluntarily completed a cognitive and symptom battery. In addition, participants had magnetic resonance imaging (MRI) to assess both static functional connectivity (SFC) and variance of dynamic functional connectivity (vDFC) of the DMN. Results: Both the PTS and mTBI + PTS groups had significant symptoms, but only the comorbid group had significant decrements in cognitive functioning. Both groups showed less stable and disrupted neural signatures of the DMN, mainly constituting the cingulate-frontal-temporal-parietal attention network. Specifically, the PTS group showed a combination of both reduced contralateral strength and reduced unilateral variability of frontal- cingulate- temporal connectivities, as well as increased variability of frontal- parietal connectivities. The mTBI + PTS group had fewer abnormal connectives than the PTS group, all of which included reduced strength of frontal- temporal regions and reduced variability frontal- cingulate- temporal regions. Greater SFC and vDFC connectivity of the left dorsolateral prefrontal cortex (dlPFC) ↔ precuneus was associated with higher cognitive scores and lower symptom scores. Conclusions: Findings suggest that individuals with PTS and mTBI + PTS have a propensity for accentuated generation of thoughts, feelings, sensations, and/or images while in a resting state. Compared with controls, only the PTS group was associated with accentuated variability of the frontal- parietal attention network. While there were no significant differences in DMN connectivity strength between the mTBI + PTS and PTS groups, variability of connectivity was able to distinguish them.

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Disruption of periaqueductal grey-default mode network functional connectivity predicts persistent post-traumatic headache in mild traumatic brain injury

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-318886 ◽

2018 ◽

Vol 90 (3) ◽

pp. 326-332 ◽

Cited By ~ 12

Author(s):

Xuan Niu ◽

Lijun Bai ◽

Yingxiang Sun ◽

Shan Wang ◽

Jieli Cao ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Functional Connectivity ◽

Healthy Volunteers ◽

Mild Traumatic Brain Injury ◽

Default Mode Network ◽

Physical Symptoms ◽

Periaqueductal Grey ◽

Default Mode ◽

Post Traumatic

ObjectivePost-traumatic headache (PTH) is one of the most frequent and persistent physical symptoms following mild traumatic brain injury (mTBI) and develop in more than 50% of this population. This study aimed to investigate the periaqueductal grey (PAG)-seeded functional connectivity (FC) in patients with mTBI with acute post-traumatic headache (APTH) and further examine whether the FC can be used as a neural biomarker to identify patients developing chronic pain 3 months postinjury.Methods70 patients with mTBI underwent neuropsychological measurements and MRI scans within 7 days postinjury and 56 (80%) of patients were followed up at 3 months. 46 healthy controls completed the same protocol on recruitment to the study. PAG-seeded resting-state FC analysis was measured in 54 patients with mTBI with APTH, in comparison with 46 healthy volunteers.ResultsThe mTBI+APTH group presented significantly reduced PAG-seeded FC within the default mode network (DMN), compared with healthy volunteers group. The connectivity strength can also predict patients’ complaints on the impact of headache on their lives. Crucially, the initial FC strength between the PAG-right precuneus as well as the PAG-right inferior parietal lobule became the important predictor to identify patients with mTBI developing persistent PTH 3 months postinjury.ConclusionsPatients with mTBI+APTH exhibited significant PAG-related FC differences mainly within the DMN. These regions extended beyond traditional pain processing areas and may reflect the diminished top-down attention regulation of pain perception through antinociceptive descending modulation network. The disrupted PAG-DMN FC may be used as an early imaging biomarker to identify patients at risk of developing persistent PTH.

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Longitudinal Resting State Functional Connectivity Predicts Clinical Outcome in Mild Traumatic Brain Injury

Journal of Neurotrauma ◽

10.1089/neu.2018.5739 ◽

2019 ◽

Vol 36 (5) ◽

pp. 650-660 ◽

Cited By ~ 11

Author(s):

Radhika Madhavan ◽

Suresh E. Joel ◽

Rakesh Mullick ◽

Taylor Cogsil ◽

Sumit N. Niogi ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Functional Connectivity ◽

Clinical Outcome ◽

Mild Traumatic Brain Injury ◽

Resting State ◽

Resting State Functional Connectivity

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Resting-state functional connectivity as a biomarker of aggression in mild traumatic brain injury

Neuroreport ◽

10.1097/wnr.0000000000001127 ◽

2018 ◽

Vol 29 (16) ◽

pp. 1413-1417 ◽

Cited By ~ 1

Author(s):

Natalie S. Dailey ◽

Ryan Smith ◽

John R. Vanuk ◽

Adam C. Raikes ◽

William D.S. Killgore

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Functional Connectivity ◽

Mild Traumatic Brain Injury ◽

Resting State ◽

Resting State Functional Connectivity

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Resting State Functional Connectivity is Directly Related to Clinical Presentation of Mild Traumatic Brain Injury

Neurology ◽

10.1212/01.wnl.0000581088.06830.74 ◽

2019 ◽

Vol 93 (14 Supplement 1) ◽

pp. S26.2-S27

Author(s):

Teena Shetty ◽

Joseph Nguyen ◽

Esther Kim ◽

George Skulikidis ◽

Matthew Garvey ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

White Matter ◽

Functional Connectivity ◽

Mild Traumatic Brain Injury ◽

Resting State ◽

Symptom Severity ◽

Grey Matter ◽

Clinical Presentation ◽

Severity Scores

ObjectiveTo determine the utility of fractional amplitude of low frequency fluctuations (fALFF) during resting state fMRI (rs-fMRI) as an advanced neuroimaging biomarker for Mild Traumatic Brain Injury (mTBI).BackgroundmTBI is defined by a constellation of functional rather than structural deficits. As a measure of functional connectivity, fALFF has been implicated in long-term outcomes post-mTBI. It is unclear however, how longitudinal changes in fALFF may relate to the clinical presentation of mTBI.Design/Methods111 patients and 32 controls (15–50 years old) were enrolled acutely after mTBI and followed with up to 4 standardized serial assessments. Patients were enrolled at either Encounter 1 (E1), within 72 hours, or Encounter 2 (E2), 5–10 days post-injury, and returned for Encounter 3 (E3) at 15–29 days and Encounter 4 (E4) at 83–97 days. Each encounter included a clinical exam, neuropsychological assessment, as well as rs-fMRI imaging. fALFF was analyzed independently in 14 functional networks and, in grey and white matter as a function of symptom severity. Symptom severity scores (SSS) ranged from 0–132 as defined by the SCAT2 symptom evaluation.ResultsIn mTBI patients, fALFF scores across 5 functional brain networks (language, sensorimotor, visuospatial, higher-order visual, and posterior salience) differed between mTBI patients with low versus high SSS (SSS <5 and >30, respectively). Overall, greater SSS were indexed by reduced connectivity (p < 0.03, Bonferroni corrected). Further analysis also identified corresponding network pairs which were most predictive of increased SSS. White matter fALFF was not correlated with symptom severity, however, decreased grey matter fALFF was significantly correlated with greater SSS (r = −0.25, p = 0.002).ConclusionsGrey matter fALFF was correlated with mTBI symptom burden suggesting that patterns of neural connectivity relate directly to the clinical presentation of mTBI. Furthermore, differences in functional network connectivity as a function of SSS may reflect which networks are implicated in recovery of mTBI.

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Network disruption following mild traumatic brain injury: clinical and experimental research implications

Journal of Neurophysiology ◽

10.1152/jn.00913.2017 ◽

2018 ◽

Vol 119 (5) ◽

pp. 1592-1594

Author(s):

Casey Swick ◽

Tiffany Andersen ◽

Ana-Mercedes Flores

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mild Traumatic Brain Injury ◽

Experimental Research ◽

Default Mode Network ◽

Default Mode ◽

Postconcussive Symptoms ◽

Neural Underpinnings ◽

Network Disruption ◽

Insight Into

Illuminating the pathophysiological mechanisms that underlie persistent postconcussive symptoms following mild traumatic brain injury (mTBI) is a growing area of study. Alhourani et al. ( J Neurophysiol 116: 1840–1847, 2016) added to this emerging body of literature with their study examining default mode network disruption in mTBI using magnetoencephalography. The findings provided enhanced insight into the neural underpinnings of mTBI, which can be applied to future clinical and experimental research in this area.

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Diffuse disconnectivity in traumatic brain injury: a resting state fMRI and DTI study

Translational Neuroscience ◽

10.2478/s13380-012-0003-3 ◽

2012 ◽

Vol 3 (1) ◽

Cited By ~ 23

Author(s):

Cheuk Tang ◽

Emily Eaves ◽

Kristen Dams-O’Connor ◽

Lap Ho ◽

Eric Leung ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

White Matter ◽

Default Mode Network ◽

Resting State ◽

Axonal Injury ◽

White Matter Integrity ◽

White Matter Tracts ◽

Imaging Protocol ◽

Default Mode

AbstractDiffuse axonal injury is a common pathological consequence of Traumatic Brain Injury (TBI). Diffusion Tensor Imaging is an ideal technique to study white matter integrity using the Fractional Anisotropy (FA) index which is a measure of axonal integrity and coherence. There have been several reports showing reduced FA in individuals with TBI, which suggest demyelination or reduced fiber density in white matter tracts secondary to injury. Individuals with TBI are usually diagnosed with cognitive deficits such as reduced attention span, memory and executive function. In this study we sought to investigate correlations between brain functional networks, white matter integrity, and TBI severity in individuals with TBI ranging from mild to severe. A resting state functional magnetic resonance imaging protocol was used to study the default mode network in subjects at rest. FA values were decreased throughout all white matter tracts in the mild to severe TBI subjects. FA values were also negatively correlated with TBI injury severity ratings. The default mode network showed several brain regions in which connectivity measures were higher among individuals with TBI relative to control subjects. These findings suggest that, subsequent to TBI, the brain may undergo adaptation responses at the cellular level to compensate for functional impairment due to axonal injury.

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