On the time-course of functional connectivity: theory of a dynamic progression of concussion effects

Abstract The current literature presents a discordant view of mild traumatic brain injury and its effects on the human brain. This dissonance has often been attributed to heterogeneities in study populations, aetiology, acuteness, experimental paradigms and/or testing modalities. To investigate the progression of mild traumatic brain injury in the human brain, the present study employed data from 93 subjects (48 healthy controls) representing both acute and chronic stages of mild traumatic brain injury. The effects of concussion across different stages of injury were measured using two metrics of functional connectivity in segments of electroencephalography time-locked to an active oddball task. Coherence and weighted phase-lag index were calculated separately for individual frequency bands (delta, theta, alpha and beta) to measure the functional connectivity between six electrode clusters distributed from frontal to parietal regions across both hemispheres. Results show an increase in functional connectivity in the acute stage after mild traumatic brain injury, contrasted with significantly reduced functional connectivity in chronic stages of injury. This finding indicates a non-linear time-dependent effect of injury. To understand this pattern of changing functional connectivity in relation to prior evidence, we propose a new model of the time-course of the effects of mild traumatic brain injury on the brain that brings together research from multiple neuroimaging modalities and unifies the various lines of evidence that at first appear to be in conflict.

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Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses

Journal of Neurotrauma ◽

10.1089/neu.2014.3610 ◽

2015 ◽

Vol 32 (14) ◽

pp. 1031-1045 ◽

Cited By ~ 62

Author(s):

Armin Iraji ◽

Randall R. Benson ◽

Robert D. Welch ◽

Brian J. O'Neil ◽

John L. Woodard ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Functional Connectivity ◽

Mild Traumatic Brain Injury ◽

Resting State ◽

Acute Stage ◽

Independent Component ◽

Resting State Functional Connectivity

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Connectome-scale assessment of structural and functional connectivity in mild traumatic brain injury at the acute stage

NeuroImage Clinical ◽

10.1016/j.nicl.2016.06.012 ◽

2016 ◽

Vol 12 ◽

pp. 100-115 ◽

Cited By ~ 12

Author(s):

Armin Iraji ◽

Hanbo Chen ◽

Natalie Wiseman ◽

Tuo Zhang ◽

Robert Welch ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Functional Connectivity ◽

Mild Traumatic Brain Injury ◽

Acute Stage ◽

Scale Assessment

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Dysfunction of cerebellum functional connectivity between default mode network and cerebellar structures in patients with mild traumatic brain injury in acute stage. rsfMRI study

Medical Visualization ◽

10.24835/1607-0763-2020-2-131-137 ◽

2020 ◽

Vol 24 (2) ◽

pp. 131-137

Author(s):

M. V. Ublinskiy ◽

N. A. Semenova ◽

A. V. Manzhurtsev ◽

P. E. Menshchikov ◽

A. N. Yakovlev ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Functional Connectivity ◽

Mild Traumatic Brain Injury ◽

Initial Step ◽

Acute Stage ◽

Control Group ◽

Healthy Children ◽

Planar Imaging ◽

Scan Time

Mild traumatic brain injury (mTBI) is the most common neurological damage in children that's why it is extremely important to identify and analyze biomarkers that can help in predicting patient's treatment and recovery in period of mTBI. Aim of this study is to verify a hypothesis that functional connectivity disturbances between intact cerebellum and DMN nodes are included in symptomatic manifestation of mTBI.Methods. 28 MR negative patients with mTBI were studied in age from 12 to 17 years (mean age – 14.7 years). The control group consisted of 23 healthy children. All MRI studies wereperformed on a Philips AchievadStream 3.0 T scanner equipped with a 32-channelPhilips dStream head coil. A 4 min rsfMRI gradient-echo echo planar imaging (EPI)sequence was acquired (TR = 3000 ms, echo time (TE) = 30 ms, 80 dynamics withdynamic scan time = 3 s). fMRI data were processed using functional connectivitytoolbox CONN.Results. No statistically significant differences in correlation strengths between control group and group of patients were detected as a result of DMN analysis. Intergroup seed-basedcorrelation ROI analysis revealed statistically significant (p < 0.05) differencein links between DMN regions and vermis (cerebellum): positive link in control group and negative link in groupof patients.Conclusions. The revealed changes in DMN neuronal connection and cerebellar regions in acute stage of mTBI patients can be an initial step of damages leading to cognitive deficit which can be developed in future.

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1171 SHORT-WAVELENGTH LIGHT THERAPY AS A WAY OF IMPROVING SLEEP, COGNITION, AND FUNCTIONAL CONNECTIVITY FOLLOWING A MILD TRAUMATIC BRAIN INJURY

SLEEP ◽

10.1093/sleepj/zsx050.1170 ◽

2017 ◽

Vol 40 (suppl_1) ◽

pp. A437-A437

Author(s):

JR Vanuk ◽

BR Shane ◽

S Bajaj ◽

M Millan ◽

M Grandner ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Functional Connectivity ◽

Mild Traumatic Brain Injury ◽

Short Wavelength ◽

Light Therapy ◽

Short Wavelength Light ◽

Wavelength Light

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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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