Functional Limitations Persist After Mild Sports-Related Traumatic Brain Injury.

According to this study.

Prefrontal Cortex Activity During Gait in People With Persistent Symptoms After Concussion.

BACKGROUND: Concussions result in transient symptoms stemming from a cortical metabolic energy crisis. Though this metabolic energy crisis typically resolves in a month, symptoms can persist for years. The symptomatic period is associated with gait dysfunction, the cortical underpinnings of which are poorly understood. Quantifying prefrontal cortex (PFC) activity during gait may provide insight into post-concussion gait dysfunction. The purpose of this study was to explore the effects of persisting concussion symptoms on PFC activity during gait. We hypothesized that adults with persisting concussion symptoms would have greater PFC activity during gait than controls. Within the concussed group, we hypothesized that worse symptoms would relate to increased PFC activity during gait, and that increased PFC activity would relate to worse gait characteristics. METHODS: The Neurobehavior Symptom Inventory (NSI) characterized concussion symptoms. Functional near-infrared spectroscopy quantified PFC activity (relative concentration changes of oxygenated hemoglobin [HbO2]) in 14 people with a concussion and 25 controls. Gait was assessed using six inertial sensors in the concussion group. RESULTS: Average NSI total score was 26.4 (13.2). HbO2 was significantly higher (P = .007) for the concussed group (0.058 [0.108]) compared to the control group (-0.016 [0.057]). Within the concussion group, HbO2 correlated with NSI total symptom score (ρ = .62; P = .02), sagittal range of motion (r = .79; P = .001), and stride time variability (r = -.54; P = .046). CONCLUSION: These data suggest PFC activity relates to symptom severity and some gait characteristics in people with persistent concussion symptoms. Identifying the neurophysiological underpinnings to gait deficits post-concussion expands our knowledge of motor behavior deficits in people with persistent concussion symptoms.

Applicability of machine learning technique in the screening of patients with mild traumatic brain injury.

Even though the demand of head computed tomography (CT) in patients with mild traumatic brain injury (TBI) has progressively increased worldwide, only a small number of individuals have intracranial lesions that require neurosurgical intervention. As such, this study aims to evaluate the applicability of a machine learning (ML) technique in the screening of patients with mild TBI in the Regional University Hospital of Maringá, Paraná state, Brazil. This is an observational, descriptive, cross-sectional, and retrospective study using ML technique to develop a protocol that predicts which patients with an initial diagnosis of mild TBI should be recommended for a head CT. Among the tested models, he linear extreme gradient boosting was the best algorithm, with the highest sensitivity (0.70 ± 0.06). Our predictive model can assist in the screening of mild TBI patients, assisting health professionals to manage the resource utilization, and improve the quality and safety of patient care.

Immediate induction of varicosities by transverse compression but not uniaxial stretch in axon mechanosensation.

Uniaxial stretch is believed to drive diffuse axonal injury (DAI) in mild traumatic brain injury (mTBI). Axonal varicosities are enlarged structures along axonal shafts and represent a hallmark feature of DAI. Here we report that axonal varicosities initiate in vivo immediately after head impact and are mainly induced by transverse compression but not uniaxial stretch. Vertical and lateral impacts to the mouse head induced axonal varicosities in distinct brain regions before any changes of microglial markers. Varicosities preferentially formed along axons perpendicular to impact direction. In cultured neurons, whereas 50% uniaxial strain was needed to rapidly induce axonal varicosities in a nanowrinkled stretch assay, physiologically-relevant transverse compression effectively induced axonal varicosities in a fluid puffing assay and can generate large but nonuniform deformation simulated by finite element analysis. Therefore, impact strength and direction may determine the threshold and spatial pattern of axonal varicosity initiation, respectively, partially resulting from intrinsic properties of axon mechanosensation.

A role of Na+, K+ -ATPase in spatial memory deficits and inflammatory/oxidative stress after recurrent concussion in adolescent rats.

Sports-related concussions are particularly common during adolescence, and there is insufficient knowledge about how recurrent concussions in this phase of life alter the metabolism of essential structures for memory in adulthood. In this sense, our experimental data revealed that seven recurrent concussions (RC) in 35-day-old rats decreased short-term and long-term memory in the object recognition test (ORT) 30 days after injury. The RC protocol did not alter motor and anxious behavior and the immunoreactivity of brain-derived neurotrophic factor (BDNF) in the cerebral cortex. Recurrent concussions induced the inflammatory/oxidative stress characterized here by increased glial fibrillary acidic protein (GFAP), interleukin 1ß (IL 1ß), 4-hydroxynonenal (4 HNE), protein carbonyl immunoreactivity, and 2',7'-dichlorofluorescein diacetate oxidation (DCFH) levels and lower total antioxidant capacity (TAC). Inhibited Na+,K+-ATPase activity (specifically isoform α2/3) followed by Km (Michaelis-Menten constant) for increased ATP levels and decreased immunodetection of alpha subunit of this enzyme, suggesting that cognitive impairment after RC is caused by the inability of surviving neurons to maintain ionic gradients in selected targets to inflammatory/oxidative damage, such as Na,K-ATPase activity.

Structural changes in retina (Retinal nerve fiber layer) following mild traumatic brain injury and its association with development of visual field defects.

BACKGROUND: Mild traumatic brain injury (mTBI)is the most common form of traumatic brain injury accounting for 70-80% of all brain injuries annually. There is increasing evidence that long lasting morphological and functional consequence can be present in visual system following mTBI. Among all the visual manifestation, awareness of Visual field defects is important because it may compromise the social, personal or professional life of any individual. Retinal structural changes such as thinning of Retinal nerve fiber layer (RFNL)captured using optical coherence tomography have emerged as a possible biomarker in many neurological diseases however very little is known in cases with mTBI OBJECTIVE: (I) To demonstrate the structural changes/morphological changes in retina if any following mTBI. (II) Whether the structural changes in retina have any association with the development of Visual field deficits leading to Visual function impairment following mTBI (III) Clinical relevance of structural changes in retina as a possible biomarker for visual function impairment due to visual field deficits. MATERIALS AND METHODS: Our study included 60 patients with mTBI who fulfilled the inclusion criteria. All patients underwent a detailed ophthalmic evaluation with special focus on temporal recording of Retinal nerve layer thickness using SD- Optical Coherence Tomography and Visual field (Visual field Index) by Humphrey Automated Field Analyser. RESULTS: 30% of eyes had significant thinning of RFNL (> 30% of the base line thickness) at 6 months following mTBI. Visual function impairment due to visual field deficits (VFI < 80%) at 6 months was seen in 40% of the eyes. The structural changes and visual function impairment peaked at 6 months' post injury. A strong Association was noted between RFNL thinning and manifestation of Visual field deficits (VFI < 80%) leading to visual function impairment (P < 0.001). The Correlation Co-efficient between thinning of RFNL and Visual field deficits had a positive correlation(p < 0.001). CONCLUSION: This novel study has demonstrated that visual functional impairment due to Visual field deficits is a real possibility following mTBI. Monitoring of retinal parameter such as thinning of Retinal nerve fiber layer, using Optical coherence tomography, can be a biomarker for early detection or development of visual field defects in mTBI.

Vestibular-Evoked Myogenic Potential Outcomes Associated with Pediatric Sports-Related Concussion.

OBJECTIVES/HYPOTHESIS: To 1) characterize vestibular-evoked myogenic potential responses in children and young adults with sports-related concussion (SRC) histories as compared with a normal healthy control group, and 2) correlate VEMP characteristics to SRC/sport history outcomes. STUDY DESIGN: Prospective cohort study. METHODS: Seventy-six children and young adults with and without a history of SRC received cervical and ocular VEMP testing using a 500 Hz tone burst air conduction stimuli. VEMP response parameters (response rates, peak latencies, and peak-to-peak amplitudes) were assessed. Other clinical vestibular measures were performed. In the SRC group, sport history outcomes including number of SRC sustained over a lifetime, years of playing contact sports, and length of time playing contact sports were collected via in-person questionnaire. RESULTS: Children and young adults with SRC had significantly reduced oVEMP responses and peak-to-peak amplitudes and greater amplitude response asymmetries between left and right ear. There was no effect of group on cVEMP findings. A greater frequency of SRCs sustained throughout a lifetime, a greater number of contact sports played, and a longer duration of playing a contact sport correlated with significantly poorer VEMP response characteristics. CONCLUSIONS: Our results suggest that SRC and repeated subclinical head impact events have an effect on oVEMP outcomes. SRC may affect the utricle, superior vestibular nerve, and/or brainstem-mediated vestibular-ocular-reflex pathway. The prevalence of post-concussion-related dizziness is becoming increasingly common in a pediatric-otology clinic, thus performing VEMP testing in youth post-SRC provides an objective, noninvasive, and cost-effective method for monitoring the effects of sports-related impact on the vestibular system and related neural pathways. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:436-442, 2022.

Use of Mayer wave activity to demonstrate aberrant cardiovascular autonomic control following sports concussion injury.

Dysregulation of cardiovascular autonomic control is gaining recognition as a prevailing consequence of concussion injury. Characterizing the presence of autonomic dysfunction in concussed persons is inconsistent and conventional metrics of autonomic function cannot differentiate the presence/absence of injury. Mayer wave (MW) activity originates through baroreflex adjustments to blood pressure (BP) oscillations that appear in the low-frequency (LF: 0.04-0.15 Hz) band of the BP and heart rate (HR) power spectrum after a fast Fourier transform. We prospectively explored MW activity (∼0.1 Hz) in 19 concussed and 19 noninjured athletes for 5 min while seated at rest within 48 h and 1 week of injury. MW activity was derived from the LF band of continuous digital electrocardiogram and beat-to-beat BP signals (LFHR, LF-SBP, MWHR, and MW-SBP, respectively); a proportion between MWBP and MWHR was computed (cMW). At 48 h, the concussion group had a significantly lower MWBP and cMW than controls; these differences were gone by 1 week. MWHR, LFHR, and LF-SBP were not different between groups at either visit. Attenuated sympathetic vasomotor tone was present and the central autonomic mechanisms regulating MW activity to the heart and peripheral vasculature became transiently discordant early after concussion with apparent resolution by 1 week.

Acute Physical and Mental Activity Influence on Concussion Recovery.

INTRODUCTION: Physical activity (PA) and mental activity (MA) postconcussion has received renewed attention to improve concussion management; however, most protocols start after several days and do not assess the acute window. Therefore, the purpose of this study was to assess PA and MA in the first 48 h postconcussion on the time to symptom-free status and return to play. METHODS: We recruited 78 NCAA Division I athletes (male, 51.3%; age, 19.6 ± 1.4 yr; height, 173.7 ± 11.5 cm; weight, 80.1 ± 23.2 kg) who were diagnosed with a sports-related concussion. Participants completed a 0-5 PA and MA scale daily until fully cleared for return to participation (mean, 15.1 ± 6.9 d). A quadratic model regression assessed PA and MA over the first 2 d (acute) postconcussion on to time to symptom-free status and return to play. RESULTS: The overall model was significant for both time to symptom free (r2 = 0.27, P = 0.004) and return to play (r2 = 0.23, P = 0.019). Reported PA was the only significant predictor for time to symptom-free (P = 0.002) and return-to-participation (P = 0.006) day. Reported MA was not associated either outcome. CONCLUSIONS: The primary finding of this study was that mild to moderate PA acutely postconcussion was associated with reduced time to symptom free and return to participation as opposed to either lower or higher levels of PA. Conversely, acute MA was not associated with recovery outcomes. These results further elucidate the role of postconcussion PA.

Cerebral blood flow is associated with matrix metalloproteinase levels during the early symptomatic phase of concussion.

Concussion is associated with disrupted cerebral blood flow (CBF), although there appears to be substantial inter-individual variability in CBF response. At present, the mechanisms of variable CBF response remain incompletely understood, but one potential contributor is matrix metalloproteinase (MMP) expression. In more severe forms of acquired brain injury, MMP up-regulation contributes to CBF impairments via increased blood-brain barrier permeability. A similar relationship is hypothesized for concussion, where recently concussed individuals with higher MMP levels have lower CBF. To test this hypothesis, 35 concussed athletes were assessed longitudinally at early symptomatic injury (median: 5 days post-injury) and at medical clearance (median: 24 days post-injury), along with 71 athletic controls. For all athletes, plasma MMPs were measured and arterial spin labelling was used to measure CBF. Consistent with our hypothesis, higher concentrations of MMP-2 and MMP-3 were correlated with lower global CBF. The correlations between MMPs and global CBF were also significantly diminished for concussed athletes at medical clearance and for athletic controls. These results indicate an inverse relationship between plasma MMP levels and CBF that is specific to the symptomatic phase of concussion. Analyses of regional CBF further showed that correlations with MMP levels exhibited some spatial specificity, with greatest effects in occipital, parietal and temporal lobes. These findings provide new insights into the mechanisms of post-concussion cerebrovascular dysfunction.

Sex differences in acute and long-term brain recovery after concussion.

Concussion is associated with acute disturbances in brain function and behavior, with potential long-term effects on brain health. However, it is presently unclear whether there are sex differences in acute and long-term brain recovery. In this study, magnetic resonance imaging (MRI) was used to scan 61 participants with sport-related concussion (30 male, 31 female) longitudinally at acute injury, medical clearance to return to play (RTP), and 1-year post-RTP. A large cohort of 167 controls (80 male, 87 female) was also imaged. Each MRI session assessed cerebral blood flow (CBF), along with white matter fractional anisotropy (FA) and mean diffusivity (MD). For concussed athletes, the parameters were converted to difference scores relative to matched control subgroups, and partial least squares modeled the main and sex-specific effects of concussion. Although male and female athletes did not differ in acute symptoms or time to RTP , all MRI measures showed significant sex differences during recovery. Males had greater reductions in occipital-parietal CBF (mean difference and 95%CI: 9.97 ml/100 g/min, [4.84, 15.12] ml/100 g/min, z = 3.73) and increases in callosal MD (9.07 × 10-5 , [-14.14, -3.60] × 10-5 , z = -3.46), with greatest effects at 1-year post-RTP. In contrast, females had greater reductions in FA of the corona radiata (16.50 × 10-3 , [-22.38, -11.08] × 10-3 , z = -5.60), with greatest effects at RTP. These findings provide new insights into how the brain recovers after a concussion, showing sex differences in both the acute and chronic phases of injury.

Auditory evoked brain potentials as markers of chronic effects of mild traumatic brain injury in mid-life.

OBJECTIVE: Auditory event-related potential (ERP) correlates of pre-dementia in late-life may also be sensitive to chronic effects of mild traumatic brain injury (mTBI) in mid-life. In addition to mTBI history, other clinical factors may also influence ERP measures of brain function. This study's objective was to evaluate the relationship between mTBI history, auditory ERP metrics, and common comorbidities. METHODS: ERPs elicited during an auditory target detection task, psychological symptoms, and hearing sensitivity were collected in 152 combat-exposed veterans and service members, as part of a prospective observational cohort study. Participants, with an average age of 43.6 years, were grouped according to positive (n = 110) or negative (n = 42) mTBI history. Positive histories were subcategorized into repetitive mTBI (3 + ) (n = 40) or non-repetitive (1-2) (n = 70). RESULTS: Positive history of mTBI was associated with reduced N200 amplitude to targets and novel distractors. In participants with repetitive mTBI compared to non-repetitive and no mTBI, P50 was larger in response to nontargets and N100 was smaller in response to nontargets and targets. Changes in N200 were mediated by depression and anxiety symptoms and hearing loss, with no evidence of a supplementary direct mTBI pathway. CONCLUSIONS: Auditory brain function differed between the positive and negative mTBI groups, especially for repetitive injury, which implicated more basic, early auditory processing than did any mTBI exposure. Symptoms of internalizing psychopathology (depression and anxiety) and hearing loss are implicated in mTBI's diminished brain responses to behaviorally relevant and novel stimuli. SIGNIFICANCE: A mid-life neurologic vulnerability conferred by mTBI, particularly repetitive mTBI, may be detectable using auditory brain potentials, and so auditory ERPs are a target for study of dementia risk in this population.

Arcuate Fasciculus Subsegment Impairments Distinctly Associated with Memory and Language Deficits in Acute Mild Traumatic Brain Injury Patients.

In acute mild traumatic brain injury (mTBI), the injury-related axonal swelling leads to white matter fiber bundle impairments, closely related to the memory and language deficits commonly shown in the patients. The arcuate fasciculus (AF) plays a central role in verbal learning and language function but could be functionally heterogeneous along the fiber tract. In this study, 25 patients with acute mTBI (<48 h after trauma) and 33 age- and sex-matched healthy controls (HCs) were included. Impaired verbal memory and language functions were shown in the patient group compared with the HCs. Combined diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) were applied to investigate the altered diffusion measure profiles of the AF tracts and the associated functional features. The fractional anisotropy (FA) in the right AF temporal subsegment of the mTBI group was negatively associated with the patient verbal memory function, whereas a positive correlation was found in the HC group. On the other hand, the correlation between the FA in the right AF frontal subsegment and the language function in HCs diminished in the patient group. Moreover, the functional connectivity between the inferior frontal gyrus and the middle occipital gyrus decreased, and its correlation with language function in HCs was absent in the patients with mTBI. Our work provides new insights into the understanding of the structural and functional heterogeneity of the AF tracts as well as the distinct associations of its subsegment impairments with verbal memory and language function deficits in patients with acute mTBI.

Longitudinal auditory pathophysiology following mild blast-induced trauma.

Blast-induced hearing difficulties affect thousands of veterans and civilians. The long-term impact of even a mild blast exposure on the central auditory system is hypothesized to contribute to lasting behavioral complaints associated with mild blast traumatic brain injury (bTBI). Although recovery from mild blast has been studied separately over brief or long time windows, few, if any, studies have investigated recovery longitudinally over short-term and longer-term (months) time windows. Specifically, many peripheral measures of auditory function either recover or exhibit subclinical deficits, masking deficits in processing complex, real-world stimuli that may recover differently. Thus, examining the acute time course and pattern of neurophysiological impairment using appropriate stimuli is critical to better understanding and intervening in bTBI-induced auditory system impairments. Here, we compared auditory brainstem response, middle-latency auditory-evoked potentials, and envelope following responses. Stimuli were clicks, tone pips, amplitude-modulated tones in quiet and in noise, and speech-like stimuli (iterated rippled noise pitch contours) in adult male rats subjected to mild blast and sham exposure over the course of 2 mo. We found that blast animals demonstrated drastic threshold increases and auditory transmission deficits immediately after blast exposure, followed by substantial recovery during the window of 7-14 days postblast, although with some deficits remaining even after 2 mo. Challenging conditions and speech-like stimuli can better elucidate mild bTBI-induced auditory deficit during this period. Our results suggest multiphasic recovery and therefore potentially different time windows for treatment, and deficits can be best observed using a small battery of sound stimuli.NEW & NOTEWORTHY Few studies on blast-induced hearing deficits go beyond simple sounds and sparsely track postexposure. Therefore, the recovery arc for potential therapies and real-world listening is poorly understood. Evidence suggested multiple recovery phases over 2 mo postexposure. Hearing thresholds largely recovered within 14 days and partially explained recovery. However, midlatency responses, responses to amplitude modulation in noise, and speech-like pitch sweeps exhibited extended changes, implying persistent central auditory deficits and the importance of subclinical threshold shifts.

Concussion history in rugby union players is associated with depressed cerebrovascular reactivity and cognition.

Recurrent contact and concussion in rugby union remains a significant public health concern given the potential increased risk of neurodegeneration in later life. This study determined to what extent prior-recurrent contact impacts molecular-hemodynamic biomarkers underpinning cognition in current professional rugby union players with a history of concussion. Measurements were performed in 20 professional rugby union players with an average of 16 (interquartile range [IQR] 13-19) years playing history reporting 3 (IQR 1-4) concussions. They were compared to 17 sex-age-physical activity-and education-matched non-contact controls with no prior history of self-reported concussion. Venous blood was assayed directly for the ascorbate free radical (A•- electron paramagnetic resonance spectroscopy) nitric oxide metabolites (NO reductive ozone-based chemiluminescence) and select biomarkers of neurovascular unit integrity (NVU chemiluminescence/ELISA). Middle cerebral artery blood flow velocity (MCAv doppler ultrasound) was employed to determine basal perfusion and cerebrovascular reactivity (CVR) to hyper/hypocapnia ( CVR CO 2 Hyper / Hypo ). Cognition was assessed by neuropsychometric testing. Elevated systemic oxidative-nitrosative stress was confirmed in the players through increased A•- (p < 0.001) and suppression of NO bioavailability (p < 0.001). This was accompanied by a lower CVR range ( CVR CO 2 Range ; p = 0.045) elevation in neurofilament light-chain (p = 0.010) and frontotemporal impairments in immediate-memory (p = 0.001) delayed-recall (p = 0.048) and fine-motor coordination (p < 0.001). Accelerated cognitive decline subsequent to prior-recurrent contact and concussion history is associated with a free radical-mediated suppression of CVR and neuronal injury providing important mechanistic insight that may help better inform clinical management.

Altered Attention Network in Paratroopers Exposed to Repetitive Subconcussion: Evidence Based on Behavioral and Event-Related Potential Results.

Cognitive impairment caused by repetitive subconcussion has received increasing attention in recent years. Although the dysfunction of attention has been confirmed by neuropsychological research using scales, there is no event-related potentials (ERPs) research. The Attention Network Test (ANT) has been widely used to evaluate the three separate components of attention processing (alerting, orienting, and executive control). Twenty-seven paratroopers exposed to repetitive subconcussion (subconcussion group) and 25 matched healthy control participants (HCs group) were enrolled, and all of them performed the ANT test while continuous scalp electroencephalography data were recorded. On the behavioral performance level, the subconcussion group showed a slower task response, with an especially significant slower reaction time in alerting. Concerning ERP results, reduction amplitudes of cue-N1 in the alerting network were observed, indicating that this group was less able to make efficient use of cues and maintain an alerting state for incoming information. For the orienting network, no difference in N1 amplitude was observed between the two groups. Moreover, there was a reduced P3 amplitude in the executive control network in the subconcussion group compared with the HCs group, suggesting a dysfunction of attentional resource allocation and inhibition control in the former group. This study is, to our knowledge, the first analysis of the altered attention network caused by repetitive subconcussion from the perspectives of behavioral and neuropsychology levels. These preliminary results revealed the possible damage of the alerting and executive control networks and provided a reference for further research on subconcussion cognitive impairment.

Concussion/Mild Traumatic Brain Injury (TBI) Induces Brain Insulin Resistance: A Positron Emission Tomography (PET) Scanning Study.

Brain injury/concussion is a growing epidemic throughout the world. Although evidence supports association between traumatic brain injury (TBI) and disturbance in brain glucose metabolism, the underlying molecular mechanisms are not well established. Previously, we reported the release of cellular prion protein (PrPc) from the brain to circulation following TBI. The PrPc level was also found to be decreased in insulin-resistant rat brains. In the present study, we investigated the molecular link between PrPc and brain insulin resistance in a single and repeated mild TBI-induced mouse model. Mild TBI was induced in mice by dropping a weight (~95 g at 1 m high) on the right side of the head. The procedure was performed once and thrice (once daily) for single (SI) and repeated induction (RI), respectively. Micro PET/CT imaging revealed that RI mice showed significant reduction in cortical, hippocampal and cerebellum glucose uptake compared to SI and control. Mice that received RI also showed significant motor and cognitive deficits. In co-immunoprecipitation, the interaction between PrPc, flotillin and Cbl-associated protein (CAP) observed in the control mice brains was disrupted by RI. Lipid raft isolation showed decreased levels of PrPc, flotillin and CAP in the RI mice brains. Based on observation, it is clear that PrPc has an interaction with CAP and the dislodgment of PrPc from cell membranes may lead to brain insulin resistance in a mild TBI mouse model. The present study generated a new insight into the pathogenesis of brain injury, which may result in the development of novel therapy.

Visual Dysfunction after Repetitive Mild Traumatic Brain Injury in a Mouse Model and Ramifications on Behavioral Metrics.

Mild traumatic brain injury (mTBI) is a major cause of morbidity and mortality with a poorly understood pathophysiology. Animal models have been increasingly utilized to better understand mTBI and recent research has identified visual deficits in these models that correspond to human literature. While visual impairment is being further characterized within TBI, the implications of impaired vision on behavioral tasks commonly utilized in animal models has not been well described thus far. Visual deficits may well confound behavioral tests that are believed to be isolated to cognitive functioning such as learning and memory. We utilized a mouse model of repetitive mTBI (rmTBI) to further characterize visual deficits using an optomotor task, electroretinogram, and visually evoked potential, and located likely areas of damage to the visual pathway. Mice were tested on multiple behavioral metrics, including a touchscreen conditional learning task to better identify the contribution of visual dysfunction to behavioral alterations. We found that rmTBI caused visual dysfunction resulting from damage distal to the retina that likely involves pathology within the optic nerve. Moreover, loss of vision led to poorer performance of rmTBI animals on classic behavioral tests such as the Morris water maze that would otherwise be attributed solely to learning and memory deficits. The touchscreen conditional learning task was able to differentiate rmTBI induced learning and memory dysfunction from visual impairment and is a valuable tool for elucidating subtle changes resulting from TBI.

Noninvasive magnetic resonance imaging techniques in mild traumatic brain injury research and diagnosis.

Mild traumatic brain injury (mTBI), frequently referred to as concussion, is one of the most common neurological disorders. The underlying neural mechanisms of functional disturbances in the brains of concussed individuals remain elusive. Novel forms of brain imaging have been developed to assess patients postconcussion, including functional magnetic resonance imaging (fMRI), susceptibility-weighted imaging (SWI), diffusion MRI (dMRI), and perfusion MRI [arterial spin labeling (ASL)], but results have been mixed with a more common utilization in the research environment and a slower integration into the clinical setting. In this review, the benefits and drawbacks of the methods are described: fMRI is an effective method in the diagnosis of concussion but it is expensive and time-consuming making it difficult for regular use in everyday practice; SWI allows detection of microhemorrhages in acute and chronic phases of concussion; dMRI is primarily used for the detection of white matter abnormalities, especially axonal injury, specific for mTBI; and ASL is an alternative to the BOLD method with its ability to track cerebral blood flow alterations. Thus, the absence of a universal diagnostic neuroimaging method suggests a need for the adoption of a multimodal approach to the neuroimaging of mTBI. Taken together, these methods, with their underlying functional and structural features, can contribute from different angles to a deeper understanding of mTBI mechanisms such that a comprehensive diagnosis of mTBI becomes feasible for the clinician.