Functional MRI of mild traumatic brain injury (mTBI): progress and perspectives from the first decade of studies

McDonald, Brenna C.; Saykin, Andrew J.; McAllister, Thomas W.

doi:10.1007/s11682-012-9173-4

Cited by 144 publications

(93 citation statements)

References 53 publications

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“…1,3,6 Standard clinical neuroimaging sequences (computed tomography [CT] scans; T1 and T2-weighted images), however, are typically negative for the majority of patients, leading to a proliferation of studies that have attempted to define objective biomarkers of mTBI. 7 There has been great interest in using functional magnetic resonance imaging (fMRI) to study mTBI given the ability to perform in vivo measurements of neuronal function during demanding cognitive tasks 8 as well as during passive mental activity. [9][10][11] Previous fMRI studies have reported a mixed pattern of both hypoand hyperactivation during the semi-acute stage of mTBI, as well as no observable group differences.…”

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confidence: 99%

Investigating the Properties of the Hemodynamic Response Function after Mild Traumatic Brain Injury

Mayer

Toulouse

Klimaj

et al. 2014

Journal of Neurotrauma

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Although several functional magnetic resonance imaging (fMRI) studies have been conducted in human models of mild traumatic brain injury (mTBI), to date no studies have explicitly examined how injury may differentially affect both the positive phase of the hemodynamic response function (HRF) as well as the post-stimulus undershoot (PSU). Animal models suggest that the acute and semi-acute stages of mTBI are associated with significant disruptions in metabolism and to the microvasculature, both of which could impact on the HRF. Therefore, fMRI data were collected on a cohort of 30 semi-acute patients with mTBI (16 males; 27.83 -9.97 years old; 13.00 -2.18 years of education) and 30 carefully matched healthy controls (HC; 16 males; 27.17 -10.08 years old; 13.37 -2.31 years of education) during a simple sensory-motor task. Patients reported increased cognitive, somatic, and emotional symptoms relative to controls, although no group differences were detected on traditional neuropsychological examination. There were also no differences between patients with mTBI and controls on fMRI data using standard analytic techniques, although mTBI exhibited a greater volume of activation during the task qualitatively. A significant Group · Time interaction was observed in the right supramarginal gyrus, bilateral primary and secondary visual cortex, and the right parahippocampal gyrus. The interaction was the result of an earlier time-to-peak and positive magnitude shift throughout the estimated HRF in patients with mTBI relative to HC. This difference in HRF shape combined with the greater volume of activated tissue may be indicative of a potential compensatory mechanism to injury. The current study demonstrates that direct examination and modeling of HRF characteristics beyond magnitude may provide additional information about underlying neuropathology that is not available with more standard fMRI analyses.

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confidence: 99%

Investigating the Properties of the Hemodynamic Response Function after Mild Traumatic Brain Injury

Mayer

Toulouse

Klimaj

et al. 2014

Journal of Neurotrauma

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“…Functional MRI and ERPs have been found to be among the most sensitive of these techniques (for recent reviews see Gosselin and colleagues 25 and McDonald and colleagues 37 ). One advantage of these approaches is that they allow the measurement of brain function during the performance of a cognitive task.…”

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confidence: 99%

Evaluating the cognitive consequences of mild traumatic brain injury and concussion by using electrophysiology

Gosselin

Bottari

Chen

et al. 2012

FOC

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Object Mild traumatic brain injury (MTBI), often referred to as concussion when it occurs in sports, produces persistent cognitive problems in at least 15% of patients. Unfortunately, conventional neuropsychological tests usually yield results within normal limits in this population. The main objective of this event-related potential (ERP) study was to understand brain functioning during the performance of a working memory (WM) task in patients who have sustained an MTBI, mostly due to motor vehicle accident or sports concussion. This study also aimed for a better understanding of the association between brain functioning as measured with ERP, behavioral performance on the WM task, postconcussion symptoms, type of injury (that is, sports concussion vs other types), and time since the injury. Methods Forty-four patients with MTBI (7.6 ± 8.4 months postinjury) were tested on a visual WM task with simultaneous recording of ERP, and were compared with 40 control volunteers who were their equivalent for age and sex. Amplitude and latency of frontal (N200 and N350) and parietal (P200 and P300) ERP waves were measured and were compared between groups. Correlation analyses were also performed between ERP characteristics, clinical variables, and behavioral performance. Results A significant group difference was found for behavioral performance on the WM task, in which the MTBI group had a lower percentage of correct answers than the control group (p < 0.05). The patients with MTBI also had smaller amplitudes of both frontal N350 and parietal P300 ERP components when compared with control volunteers (p < 0.05). No changes were found for latency of ERP components. Smaller ERP amplitudes were associated with slower reaction times and worse accuracy on the WM task among patients with MTBI (p < 0.05). Types of injury (that is, sports concussion vs other mechanisms) were not associated with different ERP characteristics. Conclusions Abnormal ERP results are observed in patients after MTBI or sports concussion, even for those in the nonacute stage after their injury. Current standard clinical evaluations most often fail to detect cerebral dysfunction after MTBI, even when patients or athletes report symptoms. Clinicians should be aware that patients with MTBI, including sports concussion, probably have underlying mild but persistent cerebral dysfunctions that require further investigation.

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“…An initial 69 PCS patients underwent the fNCI protocol and z-scores were calculated for each FR in each fNCI exam. In previous task-related fMRI studies of PCS, distinct patterns of either hyperactivation [25][26][27][28][29][30][31][32] or hypoactivation [26,[33][34][35][36][37][38][39][40] have been reliably observed, depending on the cognitive task employed and the cortical…”

Section: Biomarker Candidate Searchmentioning

confidence: 99%

Discovery of Therapy-targeting Biomarkers for Post-Concussion Syndrome using Functional Neurocognitive Imaging

Epps¹,

Allen²

2018

Brain Disord Ther

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Background: Post-concussion syndrome (PCS) occurs in a significant percentage of concussion patients. Functional MRI reveals irregular blood-oxygen level dependent signals in PCS patients. PCS biomarkers with functional predictive values have yet to be discovered and validated. Therefore, this study describes five PCS biomarkers and includes a description of their therapeutic application.Methods: A neurocognitive imaging protocol was developed and a group of healthy control patients was used to generate a normative reference atlas. Biomarker candidate search was performed using an initial sample of PCS patients. Sample validation was applied to each biomarker using a new sample of PCS patients to assess sensitivities/ specificities. A multivariate base rate analysis was performed using 132 new patients and a base rate cutoff matrix was constructed. An example of the biomarker's therapeutic application in a PCS patient is described. Results:The five functional biomarkers included: Frontal Attentional System hypoactivation, Subcortical System hypoactivation, Visual System hyperactivation, Verbal System hypoactivation, and Frontal/Parietal System hyperactivation. Individual biomarker sensitivities and specificities are reported. Collectively, using the base rate cutoff matrix, a threshold using 3/5 biomarkers below the 10 th percentile as the cutoff resulted in a suitable sensitivity (88%) and specificity (99%). The uses of these biomarkers were crucial in guiding the successful treatment of Patient A. Conclusion:We report the discovery of five functional PCS biomarkers. We show an example of the therapeutic application of the five biomarkers in the successful treatment of PCS. These neuroimaging biomarkers serve to advance diagnostic capabilities and subsequent PCS rehabilitation efforts.

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Functional MRI of mild traumatic brain injury (mTBI): progress and perspectives from the first decade of studies

Cited by 144 publications

References 53 publications

Investigating the Properties of the Hemodynamic Response Function after Mild Traumatic Brain Injury

Investigating the Properties of the Hemodynamic Response Function after Mild Traumatic Brain Injury

Evaluating the cognitive consequences of mild traumatic brain injury and concussion by using electrophysiology

Discovery of Therapy-targeting Biomarkers for Post-Concussion Syndrome using Functional Neurocognitive Imaging

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