Table 3.
FMRI and functional connectivity studies reported in chronological order
| Author | TBI participant characteristics and comparison cohort |
TBI population (all from Iraq or Afghanistan wars) |
Time post-injury | Magnet strength and vendor |
MRI parameters | fMRI task or type of FC analysis |
Summary of findings |
|---|---|---|---|---|---|---|---|
| Task-based fMRI | |||||||
| Matthews et al. 2011a |
Patients (all): 27 mTBI (27M,0F); 15 with LOC and 12 with AOC Age: LOC group: 26.9±5.6 years AOC group: 29.0±5.0 year |
Veterans | Mean years since most severe concussion LOC group: 3.2 years (SD=1.37) AOC group: 3.58 years (SD=1.31) |
3T; GE Signa EXCITE | T2* weighted echoplanar imaging, TR/TE=2000/32, FOV=230×230 mm, 64×64 matrix, 30 2.6 mm axial slices with a 1.4 mm gap. One run, 256 scans, 512 s |
Stop Signal Task Fast event-related |
No group differences in activation in the difficult trials. In easy trials, Veterans with LOC showed less activation in the VMPFC than Veterans who had AOC. Veterans with LOC also demonstrated a positive relation between brain activation in the VMPFC and somatic symptoms. |
| Matthews et al. 2011b |
Patients (all): 22 mTBI (22M,0F); including 11 with MDD and 11 without MDD Age: MDD group: 26.8 years, range=22–45 Non-MDD group: 30.3 years, range=22–47 |
Veterans | Mean years since most severe blast MDD: 2.8 (SD=1.0) Non-MDD: 3.3 (SD=1.1) |
3T; GE Signa EXCITE | T2* weighted echoplanar imaging, TR/TE=2000/32, FOV=230×230 mm, 64×64 matrix, 30 2.6 mm axial slices with a 1.4 mm gap. One run, 256 scans |
Emotional face matching task Block design |
Compared to the subjects with blast-related TBI alone, subjects with both TBI and MDD demonstrated increased activation in the amygdala bilaterally during fear processing, but decreased activation in a cognitive control region (e.g., DLPFC). |
| Scheibel et al. 2012 | 15 TBI (15M,0F) Age: 28.7±6.0 year, median=26.0 15 Veterans who were not exposed to blast and reported no TBI, including five had an orthopedic injury during deployment (14M,1F) Age: 30.9±5.6 years; median=33.0 |
Veterans and Active Duty Service Members | Mean number of days since most recent blast-related TBI 963.9 (333.2) |
3T; Philips Achieva | T2* weighted singleshot gradient-echo EPI; TR/TE=1700/30 ms; FA=73°;FOV=240 mm; 64×64 matrix; 3.75 mm thickness with 0.5 mm gap; 32 axial slices; 160 volumes. SENSE factor 2.0. 3 runs, each 244 s | Stimulus–response compatibility task Rapid-presentation, stochastic event-related |
Relative to the Veterans without mTBI, the Veterans with mTBI demonstrated increased activation in the anterior cingulate cortex, medial prefrontal cortex, and regions associated with visual attention and spatial processing. |
| Fischer et al. 2014 |
Patients: 21 MilTBI (20M,1F); Age: 28.3 ±4.6 years 21 CivTBI (Civilians with mild to moderate TBI; 19M,2F); Age: 26.2±4.8 years Control: 22 MilCon (Veterans without exposure to blast or history of TBI; 21M,1F) Age: 29.7±5.6 years 23 CivCon (Civilians with extracranial injury; 23M,0F) Age: 27.3 ±4.5 years |
Veterans | Mean months since most severe TBI MilTBI: 52.9 (17.9) CivTBI: 29.7 (16.1) |
3T; Siemens TIM Trio | Gradient-echo EPI; TR/TE=2800/29 ms; FA=80°; FOV=256; matrix=128×128; 31 4-mm thick contiguous axial slices, in-plane resolution=2×2-mm); whole-brain; 12-channel receive-only head array. 2 runs, each 736 s (263 volumes per run) |
Stop Signal Task Event-related |
During correct inhibitions, the blast mTBI group demonstrated increased activation in ACC and orbital gyrus. During incorrect inhibitions, the blast mTBI group demonstrated increased activation (relative to a military control group) in the caudate nucleus and cerebellum, whereas the civilian mTBI group demonstrated decreased activation (relative to a civilian control group). There was no effect of TBI in the performance of the task, although military groups demonstrating poorer performance than the civilians. |
| Newsome et al. 2015 |
Patients: 25 MilTBI with mild (23)to moderate (2) TBI (21 M,4F); Age: 29.6 (6.01) 25 CivTBI (Civilians with mild (23) to moderate (2) TBI; 24M, IF); Age: 27.4 (6.7) Control: 25 MilCon (Veterans without exposure to blast or history of TBI; 25M,0F) Age: 29.9 (5.5) 25 CivCon (Civilians with extracranial injury; 25M, OF) Age: 27.3 (5.8) |
Veterans | Mean months since most severe TBI MilTBI: 50.1 (18.0) CivTBI: 27.1 (15.0) |
3T; Siemens TIM Trio | Gradient-echo EPI; TR/TE=2800/29 ms; FA=80°; FOV=256; matrix=128×128; 31 4-mm thick contiguous axial slices, in-plane resolution=2×2-mm); who le-brain; 12-channel receive-only head coil 3 runs, each 585 s (209 volumes per run) | Sternberg Item Recognition Task Event-related |
All groups except the blast group demonstrated a monotonic relationship between working memory set size and activation in the right caudate during encoding. For performance, all groups demonstrated the set size effect first reported by Sternberg (1966), where reaction time increased with the number of letters to be remembered, but the blast TBI group was overall slower than all of the other groups, and their accuracy was worse. |
| Resting state | |||||||
| Vakhtin et al. 2013 |
Patients: 13 blast-only TBI (13M, OF) Age: 34.3 years, (SD=6.6) Control: 50 healthy civilian adults from Allen et al. (2011). (50M, OF) Age: 29.7 years, (SD=8.4) |
Veterans | Not provided | 3T; Siemens Trio | T2*-weighted gradient-echo EPI; TR/TE=2000/29 ms; FA=75°; FC)V=240; matrix=64 × 64; distance factor=30 %, voxel size=3.8×3.8×3.5 1 run: 5 min, 34 s (167 volumes total) |
Instructions to fixate eyes on crosshairs, relax and think of nothing in particular (eyes open) ICA to measure BOLD spatial maps, spectral power, and FC |
Relative to controls, the mTBI group demonstrated decreased activity in left inferior temporal lobe and increased activity in temporal parietal junctions bilaterally (spatial map results), increased frequency in attention, frontal, and DMN compononents (spectral results), and reduced FC in six pairs of networks (FC results). |
| Han et al. 2014 |
Patients: 63 TBI Cohort I (63M, OF) (54 in analysis) Age: 19–44 years (median=24) 40 TBI Cohort 2 (37M, 3F) (38 in analysis) Age: 19–44 years (median=23) Controls: 21 active duty military personnel with injuries other than TBI (20M, IF) (14 in analysis) Age: 19–49 (median 29) Subjects scanned twice with some drop-out. 55 datasets removed after QA. |
Active Duty Service Members |
Range and median days between injury and initial scan Cohort 1: 0–90, 14 Cohort 2: 0–30, 7 |
1.5 T; Siemens Magnetom Avanto |
TR/TE=2500/50 ms; FA=90°;FOV=25.6×25.6 cm; matrix=64×64; 30 axial slices (4.0 mm thick) covering whole cerebrum; 165 volumes. T2 *-weighted blipped EPI sequence 12-channel head coil 3 runs (each 412.5 s) |
No instructions to keep eyes open or closed or to stay awake. Graph theoretic analysis |
Decreased connectivity between modules in both TBI groups at the first scan, with a similar, but diminished pattern found at Time 2 in Cohort 1. Cohort 2 did not show the same pattern at Time 2. |
| Robinson et al. 2015 | 139 participants from TRACTS after exclusions (114M, based on 134 subjects with complete neuropsychological data) Age: 33.0±8.6 years; range = 19–62, | Active Duty Service Members and Veterans; 5 % of sample had not deployed | Months since deployment 31.9±26.2 |
3T; Siemens TIM Trio | Gradient echo EPI;TR/TE=3000/30 ms; FA=90°; 3 × 3 × 3.75 mm; 38 slices. 2 runs, 6 min per run |
Instructions to keep eyes open and stay awake Seed-based |
Proximity to blast, rather than the presence of concussion symptoms, associated with disruption to the DMN. |
| Nathan et al. 2015 | 15 TBI (15M) Age: 25.6±4 years 12 Active Duty Service Members without TBI age matched to TBI group (9M, 3F) Age: 26.4±5.8 years |
Active Duty Service Members | Days since injury 147.21±87.19 |
3T;GE | EPI, sagittal plane, TE/TR =25/2000 ms, FA=60°; FOV=240× 240mm; matrix size 64×64, 3.75×3.75×4 mm 1 run, 6 min | Instructions to keep eyes closed Dual-regression ICA |
Increased connectivity within posterior regions of the DMN and between supplementary motor area and cerebellum. |
| Spielberg et al. 2015 | 208 Veterans, 63 % of whom experienced TBI. Of the 63 % with TBI, TBI was due to blast, other military exposure, and pre-and post-deployment accidents. 52 % of sample met criteria for PTSD. |
Veterans | Not provided | 3T; Siemens TIM Trio | EPI; TR/TE=3000/30 ms,3×3×3 mm 2 runs; time per run=360 s |
Instructions to remain still with eyes open | A negative relation between re experiencing severity and local efficiency was observed, such that greater re-experiencing severity was associated with less efficient communication in a network surrounding the caudate. |
3T 3 Tesla; ACC anterior cingulate cortex; AOC Alteration of consciousness; DLPFC dorsolateral prefrontal cortex; DMN Default Mode Network; EPI echoplanar imaging; FC Functional Connectivity; ICA Independent Component Analysis; LOC Loss of consciousness; MDD Major Depressive Disorder; civCon Civilian Controls; civTBI Civilian TBI; FA flip angle; FOV field of view; milCon Military Controls; milTBI Military TBI; min minutes; mm millimeter; MRI magnetic resonance imaging; ms milliseconds; s seconds; SD standard deviation; TBI traumatic brain injury; TE echo time; TR repetition time; TRACTS Translational Research Center for TBI and Stress Disorders; VMPFC ventromedial prefrontal cortex