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Concussion Research papers from USA

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1. Neurosurg Focus. 2012 Dec;33(6):E9: 1-7. doi: 10.3171/2012.10.FOCUS12282.
Magnetoencephalographic virtual recording: a novel diagnostic tool for

Tormenti M(1), Krieger D, Puccio AM, McNeil MR, Schneider W, Okonkwo DO.
Author information:

(1)Department of Neurological Surgery, University of Pittsburgh, Pennsylvania, USA.

OBJECT: Heightened recognition of the prevalence and significance of head injury
in sports and in combat veterans has brought increased attention to the
physiological and behavioral consequences of concussion. Current clinical
practice is in part dependent on patient self-report as the basis for medical
decisions and treatment. Magnetoencephalography (MEG) shows promise in the
assessment of the pathophysiological derangements in concussion. The authors have
developed a novel MEG-based neuroimaging strategy to provide objective,
noninvasive, diagnostic information in neurological disorders. In the current
study the authors demonstrate a novel task protocol and then assess MEG virtual
recordings obtained during task performance as a diagnostic tool for concussion.

METHODS: Ten individuals (5 control volunteers and 5 patients with a history of
concussion) were enrolled in this pilot study. All participants underwent an MEG
evaluation during performance of a language/spatial task. Each individual
produced 960 responses to 320 sentence stimuli; 0.3 sec of MEG data from each
word presentation and each response were analyzed: the data from each participant
were classified using a rule constructed from the data obtained from the other 9

RESULTS: Analysis of response times showed significant differences (p < 10(-4))
between concussed and normal groups, demonstrating the sensitivity of the task.
The MEG measures enabled the correct classification of 8 of 10 individuals as
concussed versus nonconcussed (p = 0.055). Analysis of single-trial data
classified 70% of trials correctly (p < 10(-10)). Concussed patients showed
increased activation in the occipitoparietal and temporal regions during

CONCLUSIONS: These pilot findings are the first evidence of the utility of MEG
virtual recording in diagnosing concussion. With further refinements, MEG virtual
recordings may represent a noninvasive test to diagnose concussion and monitor
its resolution.

PMID: 23199432  [PubMed - indexed for MEDLINE]

2. Neuroimage. 2011 Apr 1;55(3):1189-99. doi: 10.1016/j.neuroimage.2010.12.046. Epub
2010 Dec 29.

Principles of recovery from traumatic brain injury: reorganization of functional

Castellanos NP(1), Leyva I, Buldú JM, Bajo R, Paúl N, Cuesta P, Ordóñez VE,
Pascua CL, Boccaletti S, Maestú F, del-Pozo F.

Author information:
(1)Cognitive and Computational Neuroscience Laboratory, Centre for Biomedical
Technology, Technical University of Madrid and Complutense University of Madrid,

Recovery after brain injury is an excellent platform to study the mechanism
underlying brain plasticity, the reorganization of networks. Do complex network
measures capture the physiological and cognitive alterations that occurred after
a traumatic brain injury and its recovery? Patients as well as control subjects
underwent resting-state MEG recording following injury and after
neurorehabilitation. Next, network measures such as network strength, path
length, efficiency, clustering and energetic cost were calculated. We show that
these parameters restore, in many cases, to control ones after recovery,
specifically in delta and alpha bands, and we design a model that gives some
hints about how the functional networks modify their weights in the recovery
process. Positive correlations between complex network measures and some of the
general index of the WAIS-III test were found: changes in delta-based path-length
and those in Performance IQ score, and alpha-based normalized global efficiency
and Perceptual Organization Index. These results indicate that: 1) the principle
of recovery depends on the spectral band, 2) the structure of the functional
networks evolves in parallel to brain recovery with correlations with
neuropsychological scales, and 3) energetic cost reveals an optimal principle of

Copyright © 2010 Elsevier Inc. All rights reserved.
PMID: 21195199  [PubMed - indexed for MEDLINE]

3. J Neurotrauma. 2013 Oct 15;30(20):1702-9. doi: 10.1089/neu.2012.2679. Epub 2013
Aug 31.

Complexity analysis of resting state magnetoencephalography activity in traumatic
brain injury patients.

Luo Q(1), Xu D, Roskos T, Stout J, Kull L, Cheng X, Whitson D, Boomgarden E,
Gfeller J, Bucholz RD.

Author information:
(1)1 Department of Neurosurgery, Saint Louis University School of Medicine, Saint
Louis University , St. Louis, Missouri.

Diagnosis of mild traumatic brain injuries (TBIs) has been difficult because of
the absence of obvious focal brain lesions, using conventional computed
tomography (CT) or magnetic resonance imaging (MRI) scans, in a large percentage
of TBIs. One useful measure that can characterize potential tissue and neural
network damage objectively is Lempel-Ziv complexity (LZC) applied to
magnetoencephalography (MEG) signals. LZC is a model-independent estimator of
system complexity that estimates the number of different patterns in a sequence.

We hypothesized that because of the potential network damage, TBIs would show a
reduced level of complexity in regions that are impaired. We included 18 healthy
controls and 18 military veterans with TBI in the study. Resting state MEG data
were acquired, and the LZCs were analyzed across the whole brain. Our results
indicated reduced complexity in multiple brain areas in TBI patients relative to
the healthy controls. In addition, we detected several neuropsychological
measures associated with motor responses, visual perception, and memory,
correlated with LZC, which likely explains some of the cognitive deficits in TBI

PMCID: PMC3796321 [Available on 2014/10/15]
PMID: 23692211  [PubMed - in process]

4. J Neurosurg. 2013 Jun;118(6):1306-16. doi: 10.3171/2013.3.JNS12398. Epub 2013 Apr

Resting state magnetoencephalography functional connectivity in traumatic brain

Tarapore PE(1), Findlay AM, Lahue SC, Lee H, Honma SM, Mizuiri D, Luks TL, Manley
GT, Nagarajan SS, Mukherjee P.

Author information:

(1)Department of Neurological Surgery, University of California, San Francisco,
California 94107-0946, USA.

Comment in
    J Neurosurg. 2013 Jun;118(6):1304-5; discussion 1305.

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.

PMID: 23600939  [PubMed - indexed for MEDLINE]

5. J Neurotrauma. 2009 Aug;26(8):1213-26. doi: 10.1089/neu.2008.0672.
Integrated imaging approach with MEG and DTI to detect mild traumatic brain
injury in military and civilian patients.

Huang MX(1), Theilmann RJ, Robb A, Angeles A, Nichols S, Drake A, D'Andrea J,
Levy M, Holland M, Song T, Ge S, Hwang E, Yoo K, Cui L, Baker DG, Trauner D,
Coimbra R, Lee RR.

Author information:

(1)Research, Radiology, Rehabilitation, and Psychiatry Services, VA San Diego
Healthcare System, San Diego, California, USA.

Traumatic brain injury (TBI) is a leading cause of sustained impairment in
military and civilian populations. However, mild (and some moderate) TBI can be
difficult to diagnose due to lack of obvious external injuries and because the
injuries are often not visible on conventional acute MRI or CT. Injured brain
tissues in TBI patients generate pathological low-frequency neuronal magnetic
signal (delta waves 1-4 Hz) that can be measured and localized by
magnetoencephalography (MEG). We hypothesize that abnormal MEG delta waves
originate from gray matter neurons that experience de-afferentation due to axonal
injury to the underlying white matter fiber tracts, which is manifested on
diffusion tensor imaging (DTI) as reduced fractional anisotropy. The present
study used a neuroimaging approach integrating findings of magnetoencephalography
(MEG) and diffusion tensor imaging (DTI), evaluating their utility in diagnosing
mild TBI in 10 subjects in whom conventional CT and MRI showed no visible lesions
in 9.

The results show: (1) the integrated approach with MEG and DTI is more
sensitive than conventional CT and MRI in detecting subtle neuronal injury in
mild TBI; (2) MEG slow waves in mild TBI patients originate from cortical gray
matter areas that experience de-afferentation due to axonal injuries in the white
matter fibers with reduced fractional anisotropy; (3) findings from the
integrated imaging approach are consistent with post-concussive symptoms; (4) in
some cases, abnormal MEG delta waves were observed in subjects without obvious
DTI abnormality, indicating that MEG may be more sensitive than DTI in diagnosing
mild TBI.

PMID: 19385722  [PubMed - indexed for MEDLINE]

6. J Head Trauma Rehabil. 2007 May-Jun;22(3):141-55.
Objective documentation of traumatic brain injury subsequent to mild head trauma:
multimodal brain imaging with MEG, SPECT, and MRI.

Lewine JD(1), Davis JT, Bigler ED, Thoma R, Hill D, Funke M, Sloan JH, Hall S,
Orrison WW.

Author information:

(1)Department of Radiology, the University of Utah School of Medicine, Salt Lake
City, Utah, USA.

OBJECTIVE: To determine to what extent magnetic resonance imaging (MRI), single
photon emission computed tomography (SPECT), and magnetoencephalography (MEG) can
provide objective evidence of brain injury in adult patients with persistent (>1
year) postconcussive symptoms following mild blunt head trauma.

DESIGN: A retrospective and blind review of imaging data with respect to the
presence of specific somatic, psychiatric, and cognitive complaints.

SETTING/PARTICIPANTS: Thirty complete data sets (with MRI, SPECT, MEG, and
neuropsychological testing results) were collected between 1994 and 2000 from the
MEG programs at the Albuquerque VAMC and the University of Utah.

MAIN OUTCOME MEASURES: MRI data were evaluated for focal and diffuse structural
abnormalities, SPECT data for regions of hypoperfusion, and resting MEG data for
abnormal dipolar slow wave activity (DSWA) and epileptiform transients.

RESULTS: Structural MRI was abnormal for 4 patients. SPECT showed regions of
hypoperfusion in 12 patients, while MEG showed abnormal activity in 19 patients.
None of the imaging methods produced findings statistically associated with
postconcussive psychiatric symptoms. A significant association was found between
basal ganglia hypoperfusion and postconcussive headaches. For patients with
cognitive complaints, abnormalities were more likely to be detected by MEG (86%)
than either SPECT (40%) or MRI (18%) (P<.01). MEG also revealed significant
(P<.01) associations between temporal lobe DSWA and memory problems, parietal
DSWA and attention problems, and frontal DSWA and problems in executive function.

CONCLUSIONS: Functional brain imaging data collected in a resting state can
provide objective evidence of brain injury in mild blunt head trauma patients
with persistent postconcussive somatic and/or cognitive symptoms. MEG proved to
be particularly informative for patients with cognitive symptoms.

PMID: 17510590  [PubMed - indexed for MEDLINE]


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