Resting state magnetoencephalography functional connectivity in traumatic brain injury

Abstract

Object: Traumatic brain injury (TBI) is one of the leading causes of morbidity worldwide. One mechanism by which blunt head trauma may disrupt normal cognition and behavior is through alteration of functional connectivity between brain regions. In this pilot study, the authors applied a rapid automated resting state magnetoencephalography (MEG) imaging technique suitable for routine clinical use to test the hypothesis that there is decreased functional connectivity in patients with TBI compared with matched controls, even in cases of mild TBI. Furthermore, they posit that these abnormal reductions in MEG functional connectivity can be detected even in TBI patients without specific evidence of traumatic lesions on 3-T MR images. Finally, they hypothesize that the reductions of functional connectivity can improve over time across serial MEG scans during recovery from TBI.

Methods: Magnetoencephalography maps of functional connectivity in the alpha (8- to 12-Hz) band from 21 patients who sustained a TBI were compared with those from 18 age- and sex-matched controls. Regions of altered functional connectivity in each patient were detected in automated fashion through atlas-based registration to the control database. The extent of reduced functional connectivity in the patient group was tested for correlations with clinical characteristics of the injury as well as with findings on 3-T MRI. Finally, the authors compared initial connectivity maps with 2-year follow-up functional connectivity in a subgroup of 5 patients with TBI.

Results: Fourteen male and 7 female patients (17-53 years old, median 29 years) were enrolled. By Glasgow Coma Scale (GCS) criteria, 11 patients had mild, 1 had moderate, and 3 had severe TBI, and 6 had no GCS score recorded. On 3-T MRI, 16 patients had abnormal findings attributable to the trauma and 5 had findings in the normal range. As a group, the patients with TBI had significantly lower functional connectivity than controls (p < 0.01). Three of the 5 patients with normal findings on 3-T MRI showed regions of abnormally reduced MEG functional connectivity. No significant correlations were seen between extent of functional disconnection and injury severity or posttraumatic symptoms (p > 0.05). In the subgroup undergoing 2-year follow-up, the second MEG scan demonstrated a significantly lower percentage of voxels with decreased connectivity (p < 0.05) than the initial MEG scan.

Conclusions: A rapid automated resting-state MEG imaging technique demonstrates abnormally decreased functional connectivity that may persist for years after TBI, including cases classified as "mild" by GCS criteria. Disrupted MEG connectivity can be detected even in some patients with normal findings on 3-T MRI. Analysis of follow-up MEG scans in a subgroup of patients shows that, over time, the abnormally reduced connectivity can improve, suggesting neuroplasticity during the recovery from TBI. Resting state MEG deserves further investigation as a prognostic and predictive biomarker for TBI.

Figures

Fig. 1

Group comparison of 21 TBI patients versus 18 controls. Three-dimensional volumetric renderings of the MEG results coregistered to the T1-weighted structural MRI show significant reduction in functional connectivity of the patients, predominantly in the bilateral frontal and left greater than right parietotemporooccipital regions as well as the right thalamus. Increased connectivity is represented in the red→orange spectrum; decreased connectivity is depicted in the blue→white spectrum.

Fig. 2

Case 2. Three-dimensional renderings of the initial (left) and 23-month follow-up (right) MEG studies. Percentages of voxels with significantly increased and/or decreased connectivity compared with controls are listed below the montage. Image display conventions are as in Fig. 1.

Fig. 3

Case 12. Three-dimensional renderings of the initial (left) and 26-month follow-up (right) MEG studies. Percentages of voxels with significantly increased and/or decreased connectivity compared with controls are listed below the montage. Image display conventions are as in Fig. 1.

Fig. 4

Case 5. Three-dimensional renderings of the initial (A) and 31-month follow-up (B) MEG studies. C–F: Cases 7 and 3. Three-dimensional renderings of the initial and follow-up (at 21 and 30 months apart, respectively) MEG scans. Percentages of voxels with significantly increased and/or decreased connectivity compared with controls are listed below the montage. Image display conventions are as in Fig. 1.