Traumatic Brain Injury and Its Treatment Plan - Literature review Example

Literature Review: mTBI, white matter integrity, and Exercise School July Literature Review Introduction Numerous studies have been carried out on traumatic brain injury and its treatment plans. Although the literature covers several aspects of these studies, this review shall focus on exercise and white matter integrity. This review covers the history of traumatic brain injury, differential diagnosis of the injury and post-concussion syndrome. Furthermore,it explores the relationship between mild traumatic brain injury and aging, dementia and Alzheimer’s disease and how exercise relates to the white matter integrity in the human brain.The review shows the possibility of using exercise to treat case of mild traumatic injury. History of Traumatic Brain Injury Annually, about 235,000 people experience a traumatic brain injury that requires them to be hospitalized for treatment and monitoring (Arciniegas et al, 2005).In addition to these people who are hospitalized, there is another 1.1 million who experience a traumatic brain injury for which they are evaluated and released without hospitalization. The majority of these cases are reported to result from motor vehicle accidents, falls and assault,often in urban areas. Out of the 235,000 patients who are hospitalized with a case of mild traumatic brain injury, 50,000 do not survive (Arciniegas et al., 2005). About 5.4 million people live with chronic cases of traumatic brain injury in the US which leads to spending about $48million annually on the treatment and care of persons with TBI (Arciniegas et al, 2005). Most physicians are familiar with mild traumatic brain injurymanagement; however, despite this situation cases of mTbi are still on the rise(Arciniegas et al., 2005). This phenomenon occurs due to the difficulty in diagnosing and treating mTBIbecause the deficits are subtle and not easily recognized(Arciniegas et al., 2005). Nonetheless, most patients recover within the first year of injury (McDonald, Saykin & McAllister, 2012). Post-Concussion Syndrome Chen and colleagues (2007) define Post-Concussion Syndrome (PCS) as the lingering symptoms that follow a mild traumatic brain injury that is typically diagnosed when a person who has recently suffered head injury continues feeling three vital symptoms of concussion. These three symptoms are tiredness, headache and lightheadedness (Chen, et al., 2007).Clinical assessment of traumatic brain injury relies heavily on the presence of post-concussion symptoms as well as the duration of these symptoms (Chen, et al., 2007). The post-concussion symptoms are always subjective in nature and are not always specific to concussions, resulting in the need to validate their usefulness. Typically, acute post-concussion symptoms may include physical problems such as dizziness, headache and visual impairment (Chen, et al., 2007). Other symptoms include cognitive impairment, including attention and memory dysfunction (Chen et al., 2007). Behavioral problems like irritability, anxiety and depression are also some of the post-concussion symptoms. According to Chen et al. (2007) the development of these symptoms is predicted on a complex set of factors, including neural injury resulting from mTBI or preexisting psychiatric disorder. The response accuracy and speed of cognitive tests of the moderate PCS group is slower than that of a low PCS group (Chen, et al, 2007). Neuropsychological test performance factors can be effectively used to predict long term post-concussive symptoms as well as cognitive complaints that are normally a result of mild traumatic brain injury (Clerke et al., 2012).According to the study by Clerke et al. (2012), depression, neuroticism and anxiety are very good signs of post-concussive symptoms rather than neuropsychological test performances, which demonstrates that post-concussion symptoms can be a good sign of head injuries. Clerke and colleagues’ findings (2012) is supported by King &Kirwilliam(2011) who explore a broad spectrum of demographic, emotional and psychosocial factors to study patients with permanent post-concussion injury and reveals that that very high level of post-concussion symptoms can be a permanent feature of mild head injury. Furthermore, the quality of one’s life is also directly related to the severity of the post-concussion symptoms (King &Kirwilliam, 2011). mTBI and White Matter Integrity The relationship between white matter integrity and mTBI has been studied and well documented by various researchers (Gao& Chen, 2011).It is well known that mild traumatic brain injury leads to long term cognitive and emotional difficulties and behavioral disturbance (Gao& Chen, 2011). The lack of evidence based correlates of clinical manifestations of the disorder has hugely hampered treatment and diagnosis of mild traumatic brain injury. Unlike severe traumatic brain injury, mild brain injury does not show significant tissue lesions or cavities in the cortex. Furthermore, neuro-imaging through magnetic resonance has always produced negative results, indicating that the damage is beyond the resolution of current scanning technologies (Gao& Chen, 2011). Investigation by Gao& Chen (2011) on the morphologies of spared neurons in the cortex after mild traumatic brain injury reveals that mild TBI leads to limited tissue lesions and cell death. Moreover,mild traumatic brain injury causes widespread, significant synapse degeneration in the cortical neurons that were spared. This widespread loss, according to Gao and Chen (2011), disrupts neural circuitry leading to neurologic dysfunction.In the diagnosis, treatment and management of mild traumatic brain injury, it is typically important to detect clinically important axonal damage in cerebral white matter after traumatic brain injury (Bazarian et al., 2007). This is because it helps in understanding, diagnosis and treatment of mild traumatic brain disorder. Bazarian et al. (2007)evaluates a prospective pilot study of six subjects with isolated mild TBI and six matched orthopedic controls. In the study, all the subjects underwent DTI scanning, PCS assessment and neurobehavioral testing.The result revealed significant damage of cerebral white matter further proving that mild traumatic brain injury result in the damage of white matter. Due to the importance of knowledge of the extent of damage to whitematter that results from mild traumatic brain damage, several tools have been used to study the damage. Magnetic resonance imaging and computer topography have not sufficiently helped in assessing the damage to the white matter. According to Cubonet al. (2011), most sportsmen who experience mild traumatic brain injury experience rapid onset of short lived neurological impairment with no structural changes in the magnetic resonance imaging and computer tomography. Diffusion Axonal Injury is always under-diagnosed by the convectional imaging techniques (Ingles et al., 2005). Despite the fact that mean diffusivity and fractional anisotropy abnormalities in patients with Traumatic Brain Injury are not easy to detect they are still present in the brain. Diffusion tensor imaging has provided a solution to this problem. Diffusion tensor imaging is an objective tool that can be used to asses severity and recovery functions after a concussion. It involves assessing the white matter fiber tract integrity (Cubon et al., 2011). Diffusion tensor changes are a sign of subsequent brain damage. Qualitative comparison of fractional anisotropy and mean diffusivity suggest that with increasing level of injury severity, mean diffusivity might be more sensitive in detecting mild injury (Cubon et al., 2011). Fractional anisotropy on the other hand is more effective in capturing more severe injuries. Tract-based spatial statistics (TBSS) analysis can therefore be used to evaluate axonal injury of the white matter skeleton, effectively detecting structural changes in sport related concussions (Cubon et al., 2011). Mechanism of Brain Injury Generally, the biomechanical effects of non penetrating injury to the brain are broadly classified into two. Both are however applicable across spectrum of the injury severity (McDonald, Saykin & McAllister, 2012). The two broad classifications are the contact forces and the inertial forces. Contact force injuries occur when the brain moves inside the skull striking the inner surfaces of the skull. This movement of the brain across the ridges and bony proturbances of the frontal as well as the temporal fossae may result in injury to the temporal and frontal poles; the lateral temporal and frontal cortices. Moreover the notion of the brain due to such forces may also affect the ventral and medial cortices (McDonald, Saykin & McAllister, 2012). Inertial injuries on the other hand result from linear translation and rotational forces in the brain. These forces cause angular acceleration or deceleration in the brain that result in straining, shearing or compression of brain tissues. The effects of the high speed acceleration or deceleration within the brain are maximal in the axonal projections, blood vessels, gray matter, white matter and the corpus collassum. The effect is magnified especially when the angular accelerations and decelerations take place for a long duration of time causing more straining, compression or shearing (McDonald, Saykin & McAllister, 2012). The contact and inertial injuries lead to complex set of events in the brain both at the cellular and sub cellular level (McDonald, Saykin & McAllister, 2012).Mechanical perturbations result in significant release of a host of neurotransmitters such as glutamate and other amino excretory acids. This therefore causes influx of extracellular .which in turn leads to the release of from the intracellular stores providing sufficient ingredients to faciliatate intracellular reactions that cause cytotoxic injury and eventual cell death. TBI of any sort can result in cerebral edema and decrease in blood flow in the brain. The cranial vault is constrained in the skull and is fully filled with non compressible CFS.When TBI occurs, it leads the swelling of the edema. The swelling of the edema results in increase in ICP since there is no space for expansion in the cranial vault. This causes global cerebral dysfunction (McDonald, Saykin & McAllister, 2012). Moreover, mechanical perturbations in the brain especially in the neurons and its axons result in mechanoporation of the cell membranes of the neurons and the axons. This results in the influx of from extracellular sources leading to destruction of white matter due to cell death. Differential Diagnosis of mTBI The diagnosis of cases of moderate or severe brain injuries is normally self-evident (Giza &Hovda, 2001).Problems arise when other life threatening injuries that require immediate attention are present: in these situations, the brain injury is normally missed (Giza &Hovda, 2001). Mild traumatic brain damage is also occasionally missed due to the limited deficits associated withit. According to Giza &Hovda(2001), a detailed neurological examination is important and will help reveal any evidence of brain injury. Differential diagnosis of mild traumatic brain injury involves the use of a methodology that attempts to identify the internal problem that produces the patient’s symptoms; it rarely deals with the external causes of the mild Traumatic injury (Giza &Hovda, 2001). Diagnosis can involve brain imaging using techniques such as CAT scan, PET and MRI.To help clarify some specific deficits ofpatients, evaluation by physical, speechandoccupational therapists may be necessary (Giza &Hovda, 2001). Differential diagnosis should involve consideration of other neurologic and psychiatrical disordersin addition to symptom expectations (Giza &Hovda, 2001).Furthermore, diagnosis threats and development disorders should also be taken into consideration during the diagnosis of mild traumatic brain disorder.According to Giza &Hovda (2001), traumatic injury is a transient neurologic dysfunction that results from biomechanical force. Loss of consciousness is a clinical hallmark of mild Traumatic Brain Injury or concussion but it is not needed to make diagnosis. The symptoms that are likely to be considered in the differential diagnosis may include confusion, dizziness, disorientation, headache and visual disturbance (Giza &Hovda, 2001). Studies have also been carried out on athletes to determine the effects of concussion and to help determine the symptoms ofconcussion (Henry et al., 2010).A study conducted by Henry and colleagues (2010) indicates that diagnoses carried out on athletes show that the athletes display neurophysiological alterations as well as post-concussion symptoms like headache and sensitivity to light and noise.This study indicates how different the diagnosi s of mTbi in athletes is different from other cases of mTbi.A study on the effect of concussion on the athlete’s verbal memory, information processing speed, reaction time and visual memory reveals that concussion negatively impacts on the athlete’s verbal memory, information processing speed, reaction time and visual memory (Henry et al., 2010).Carrying out differential diagnosis of mild traumatic brain injury requires the understanding of the effect of concussion on brain metabolism. Henry et al.(2010) explore this and reveal that concussion leads to neurometabolic impairment in the prefrontal as well as the motor cortices. Physicians therefore need to keep in mind that there is usually the occurrence of cortical neurometabolic change after concussion has taken place. This assists in the diagnosis of mild traumatic brain injury (Henry et al, 2010). Similarity to Aging, Alzheimer’s Disease and Dementia Dementia is a general term used to describe loss of memory as well as other human intellectual abilities. This loss normally interferes with one’s daily life. The most common form of this sickness is known as Alzheimer’s disease and it accounts for the majority of the cases of dementia (Tremblay et al., 2013). Another term known as Mild Cognitive Impairment has also been used to refer to the form of dementia that does not interfere with daily life of an individual. The greatest known risks factor of the disease is aging: adults over 65 years compose the majority of the patients with this disease. According to Tremblay and colleagues (2013), Alzheimer’s disease normally worsens over time. In the early stage, memory loss is the main symptom, but in the later stages the patients normally experience loss of other intellectual abilities. Some patients end up having difficulty in conversations. Exercise has been used as remedy in the management of the disease. Apart from the known benefits of exercise like reduction of cardiovascular disease risks, strengthening muscles and bones, exercise has been used in the management of Alzheimer’s disease to benefit the brain (Tremblay et al., 2013). Studies have shown that those who are physically active are less likely to experience decline in mental ability, which subsequently lowers the risk of developing Alzheimer’s disease (Tremblay et al., 2013). Exercise has been used in the management of Alzheimer’s disease to help patients maintain their level of reasoning and thinking, improve memory and other cognitive skills and to delay the onset of Alzheimer’s disease (Tremblay et al., 2013). Furthermore, these exercise sessions are used to enhance and promote the flow of blood in the brain (Tremblay et al., 2013). Numerous studies have been conducted to establish the relationship between Alzheimer’s disease and mild traumatic brain injury: studies have shown that older adults who have had cases of mild traumatic brain injury are more likely to exhibit brain changes that are suggestive of Alzheimer’s disease (Jellinger, 2004; Van Den, Thornton &Vink, 2007; Tremblay et al., 2013). The association between Alzheimer’s disease and mild traumatic brain injury is complex, thus making numerous studies necessary (Tremblay et al., 2013). A study on the correlation between cognitive decline in late adulthood and sports concussions sustained in early adulthood has unveiled brain anomalies in otherwise healthy former athletes with concussion, and associated the manifestations to long term detrimental effect of sport concussions on the cognitive functions (Tremblay et a., 2013). These patterns of decline are often associated with abnormal aging (Tremblay et al, 2013). According toVan Den, Thornton and Vink (2007), traumatic brain injury is a possible predisposing factor in Alzheimer’s disease. Furthermore, despite significant discrepancies in the literature, there appears to be an increasing trend to support the belief that TBI is a potential risk factor for Alzheimer’s diseases (Van Den, Thornton &Vink, 2007). Apolipoprotein genotypes can be linked to Alzheimer’s disease but the link to Traumatic Brain Injury remains inconclusive and ambiguous (Van Den, Thornton &Vink, 2007). The view of the ambiguous link between head injury and dementia/Alzheimer‘s disease is further supported by Jellinger (2004). Although epidemiological studies and retrospective autopsy data have provided evidence that a later cognitive decline occurs after severe traumatic head injury, the relationship is still ambiguous (Jellinger, 2004). Both human post-mortem and experimental studies show apolipoprotein beta deposition after head injury, supporting the link between traumatic brain injury and dementia (Jellinger, 2004). Despite the ambiguous relationship, it can be concluded that traumatic brain injury is somehow related to dementia and is one of its environmental risk factors (Mielke et al., 2014). The most compelling substantiation that supports this ambiguous relationship is a meta-analysis of seven case control studies of raw data collected from original authors by Mielke and colleagues (Mielke et al., 2014). This analysis has reported a risk level of approximately 85% CI for head injury with a loss of awareness (Mielke et al., 2014). Furthermore, the relative risk remained significant even after adjustments for education, alcohol and history of Alzheimer’s disease (Mielke et al., 2014). Mielke et al. (2014) found out that among individuals with MCI, self-reported trauma with at least momentary loss of consciousness is associated with greater amyloid deposition. This therefore suggests that trauma may be associated with an Alzheimer’s disease related neuropathology. Therefore, head injury leads to an increase in level of proteins such as the amyloidal beta which is the same trend in the brain tissues of the people with Alzheimer’s disease (Mielke et al., 2014). Chronic Traumatic Encephalopathy Chronic Traumatic Encephalopathy is a progressive neuro-degeneration that is associated with memory disturbances, behavioral and personality change as well as speech and gait abnormalities (McKee et al., 2009). CTE has primarily been found in professional athletes that take part in sporting activities such as wrestling, ice hockey and football. In addition to professional athletes, soldiers have also been reported to suffer from this disease, particularly those who have been exposed to blasts or other forms of trauma during war or training (McKee et al., 2009). Self-abusive behavior and severe seizure are also some of the causes of CTE (McKee et al., 2009). People who suffer from this condition experience degeneration of the brain cells and the accumulation of the protein tau in the brain, which results in memory loss, depression and loss of other cognitive abilities (McKee et al., 2009). In some cases, patients with CTE tend to be aggressive towards other people. Tests such as CT scan, PTE and MRI have been used to diagnose the condition. However, some cases require neuropsychological tests to clearly understand the condition when carrying out diagnosis (McKee et al., 2009). Studies indicate that this condition occurs as a result of brain injury before the clinical signs can be seen (Norwinski et al., 2009). According to Norwinski and colleagues (2009), Chronic Traumatic Encephalopathy is a neuropathlogically distinct, slowly progressive tauopathy that is known to have environmental etiology. CTE is associated with memory disturbances, behavioral as well as personally changes. CTE is characterized by autopsy of the cerebral hemisphere, thalamus and brain stem (McKee et al., 2009).The condition has been widely seen in National Football League Players. This has prompted a lot of research on the current players and former players to understand its relationship with the game. Omulu and colleagues (2006) emphasize that there is the need for further empirical elucidation of pathology and pathological cascades of long term neurogenerativesequela of footballers. A study on professional footballers shows that the footballers who had long careers without multiple recorded concussions manifested Major Depressive Disorder in retirement (Omulu et al., 2006). These athletes exhibited neuro fibrilary tangles, neuropil threads and coronatry atherosclerotic diseases (Omulu et al., 2006). Due to rising and numerous cases of Chronic Traumatic Encephalopathy in athletes there has been increased need for more technology to aid the detection of CTE in athletes (Omulu et al., 2006). The rapid growth of computerized neuro-cognitive assessment provides an efficient and valid technology that can be used to test the long term and short-term implications of head injuries in athletes (Webb & Barth, 2003). Exercise and White Matter Integrity According to Leddy et al. (2007), patients with post-concussion symptoms are not supposed to be involved in exercise due to concerns from symptoms of flare up. However, extended rest may also lead to PCS patients experiencing deconditioning and secondary effects, including a depressive set of symptoms. Leddy and colleagues (2007) further suggest that PCS may be reduced by the patients being put under aerobic exercise. This type of exercise improves flow of blood in the brain (Leddy et al., 2007). Four hours a week of invigorating walking has been shown to stop or even reverse the shrinkage of the brain. This shrinkage is referred to as brain atrophy (Leddy et al., 2007). Brain atrophy normally starts at the age of forty. It occurs in the regions of the brain that are responsible for memory and cognition (Leddy et al., 2007). Physical exercise has been shown to increase actual neurons and the connection between neurons. The actual neurons are popularly referred to as the gray matter while the neuron connections are referred to as the white matter (Leddy et al., 2007). According to Baker et al. (2012),through the increased flow of blood to the brain, exercise triggers biochemical changes in the brain that lead to the production of new connections between neuronsas well as the production of new neurons. This is known as neuroplasticity.Apart from neuroplasticity,exercise of the brain helps to protect the newly formed neurons bathing them in a nerve growth factor. This facilitates the formation of functional connections with neurons in proximity (Leddy et al., 2007). Brain exercise has been shown to contribute to the development of white matter both to new brain cells and aging ones. Numerous animal studies have indicated that exercise has several benefits beyond brain neurogenesis (Leddy et al., 2007).Some of these benefits include an increase of neurotransmitters and angiogenesis. A meta-analysis conducted byBaker et al. (2007)showed that training increase the cognitive performance of individual between the ages of 55 and 80.This is an age group that is associated with low levels of cognitive performancedue to aging (Jellinger, 2004). Another meta-analysis demonstrates that exercise boosts cognitive performance through fitness training for adults over 65 years who suffer from cognitive impairment as a result of dementia (Jellinger, 2004). The demonstration of how physical activity can be used to enhance neurogenesis by these findings has been instrumental in the management of Parkin­son and Dementia (Jellinger, 2004).Aerobic exercise that lasts about thirty to sixty minutes per day, for three days a week has been shown to have positive impact on brain functioning and neurogenesis that leads to replacement of damaged white matter. However, it is important to ensure the exercise is not strenuousdue to the potential flare up of symptoms that may cause more health complicationsand reduce the benefits of the exercise sessions (Leddy et al., 2007). Rehabilitation program studies on cases of damage of white matter indicate that progressive exercise treatment helps in reducing symptoms by aiding the flowof blood in the brain (Bakers et al., 2012). Patientsput under an exercise regimen have reported increased cognitive performance compared to their counterparts who are not involved in training. Graded exercises have been incorporated in the management of physiological symptoms and signs of Post-ConcussionSyndrome (Bakers et al., 2012). Aerobic exercise has proved to be one major contributor in neurogenesis (Bakers et al., 2012).Mabbot et al. (2007) also explore neurocognitive outcomes of exercise in children. Their study utilizes DTI to examine exercise outcomes in children who have been treated with radiation for brain tumors. The intervention is found toincrease recovery from the side effects of radiation in brain cancer treatment in children. This increased memory suggests improved functioning of the hippocampus section of the brain where neurogenesis takes place (Mabbot et al., 2014). Exercise has also been used in cancerpatient recovery and management plans. This has been especially useful as an intervention after treatment of brain cancer by radiation(Mabbot et al., 2014). Radiation makes the brain unable to produce new brain cells, including white matter. The inability of the brain to produce new cells has therefore caused some cancer patients who are treated by radiation to lose memory and cognitive ability (Mabbot et al., 2014). According to Mabbot et al. (2007), exercise can help preventdecline in memory after radiation treatment. This is due to the subsequent increase inbloodflow in the hippocampus, an important area that aids learning, navigation of space and memory (Mabbot et al., 2014). Exercise following radiation preventsthe decline of erasable memory,which is the section of memory that is affected after radiation in cancer treatment. Afterradiation, thispart of memory becomes impaired in manypeople. Mabbot et al. indicate that aerobic exercises involved in the recovery plans for children who have undergone radiation to treat brain tumorshas been beneficial in boosting memory and cognitive abilities. The duration of these exercises and the exercise routines, however, need to be selected and planned with a lot of care to prevent further damage or injury (Mabbot et al., 2014). Limitation of current research This study shows the relationship of mTBI and the white matter .It further reveals the possibilities of using exercise to cure the effects of mTBI. Even though this has been successfully shown from studies on mTBI, the white matter and use of exercise to respond to cases of dementia, the paper does not show how exactly exercise repairs the white matter. There is need for further studies on how exactly exercise repair white matter that is destroyed as a result of cell death due to mTBI. Conclusion From the reviewed literature it is possible to see the relationship mTBI injury and the white matter. Further more the review shows how exercise can possibly be used respond to case of Mtbi. References Ann, C., McKee, M. D, Robert C., Cantu, M. D, [...] & Robert A. S. (2009). Chronic Traumatic Encephalopathy in Athletes: Progressive Tauopathy following Repetitive Head Injury. Journal of neuropathology and experimental neurology, 68(7), 709–735. Arciniegas, D. B., Anderson, C. A., Topkoff, J., & McAllister, T. W. (2005). Mild traumatic brain injury: a neuropsychiatric approach to diagnosis, evaluation, and treatment. Neuropsychiatric disease and treatment, 1(4), 311. Bazarian, J. J., Zhong, J., Blyth, B., Zhu, T., Kavcic, V., & Peterson, D. (2007). Diffusion tensor imaging detects clinically important axonal damage after mild traumatic brain injury: a pilot study. Journal of neurotrauma, 24(9), 1447-1459. Chen, J. K., Johnston, K. M., Collie, A., McCrory, P., &Ptito, A. (2007).A validation of the post-concussion symptom scale in the assessment of complex concussion using cognitive testing and functional MRI.Journal of Neurology, Neurosurgery & Psychiatry, 78(11), 1231-1238. Clarke, L. A., Genat, R. C., & Anderson, J. F. (2012). Long-term cognitive complaint and post concussive symptoms following mild traumatic brain injury: The role of cognitive and affective factors. Brain Injury, 26(3), 298-307. Cubon, V. A., Putukian, M., Boyer, C., &Dettwiler, A. (2011).A diffusion tensor imaging study on the white matter skeleton in individuals with sports-related concussion.Journal of neurotrauma, 28(2), 189-201. Gao, X., & Chen, J. (2011). Mild traumatic brain injury results in extensive neuronal degeneration in the cerebral cortex. Journal of neuropathology and experimental neurology, 70(3), 183. Giza, C. C., &Hovda, D. A. (2001).The neurometabolic cascade of concussion.Journal of Athletic Training, 36(3), 228. Henry, L. C., Tremblay, S., Leclerc, S., Khiat, A., Boulanger, Y., Ellemberg, D., &Lassonde, M. (2011). Metabolic changes in concussed American football players during the acute and chronic post-injury phases. BMC neurology, 11(1), 105. Inglese, M., Makani, S., Johnson, G., Cohen, B. A., Silver, J. A., Gonen, O., & Grossman, R. I. (2005). Diffuse axonal injury in mild traumatic brain injury: a diffusion tensor imaging study. Journal of neurosurgery, 103(2), 298-303. Jellinger, K. A. (2004). Head injury and dementia.Current opinion in neurology, 17(6), 719-723. King, N. S., &Kirwilliam, S. (2011). Permanent post-concussion symptoms after mild head injury.Brain injury, 25(5), 462-470. Kraus, M. F., Susmaras, T., Caughlin, B. P., Walker, C. J., Sweeney, J. A., & Little, D. M. (2007). White matter integrity and cognition in chronic traumatic brain injury.A diffusion tensor imaging study. Leddy, J. J., Kozlowski, K., Fung, M., Pendergast, D. R., &Willer, B. (2007).Regulatory and auto regulatory physiological dysfunction as a primary characteristic of post-concussion Mabbot, D, Timmons, B., Bartels, U., Bouffet, E., Laughlin, S., Piscione, J., Scantlebury, N., &Scheinemann, K. (2014).Exercise intervention in children treated with radiation for brain tumors. Canadian Cancer Society Research Institute. McDonald, B., Saykin, A. & McAllister, T. (2012).Functional MRI of mild traumatic brain injury (mTBI): progress and perspectives from the first decade of studies. Brain Imaging & Behavior, 6(2), 193-207. McKee, A. C., Cantu, R. C., Nowinski, C. J., Hedley-Whyte, E. T., Gavett, B. E., Budson, A. E., & Stern, R. A. (2009). Chronic traumatic encephalopathy in athletes: progressive tauopathy following repetitive head injury. Journal of neuropathology and experimental neurology, 68(7), 709. Mielke, M. M., Savica, R., Wiste, H. J., Weigand, S. D., Vemuri, P., Knopman, D. S., & Jack, C. R. (2014).Head trauma and in vivo measures of amyloid and neurodegeneration in a population-based study.Neurology, 82(1), 70-76. Omalu BI, DeKosky ST, Hamilton RL, et al. (2006). Chronic traumatic encephalopathy in a national football league player: part II. Neurosurgery.2006; 59:1086–92. Tremblay, S., De Beaumont, L., Henry, L. C., Boulanger, Y., Evans, A. C., Bourgouin, P., & Lassonde, M. (2013).Sports concussions and aging: a neuro imaging investigation. Cerebral Cortex, 23(5), 1159-1166. Van Den Heuvel, Corinna, Emma Thornton, and Robert Vink. (2007). Traumatic brain injury and Alzheimers disease: a review. Progress in brain research 161 (2007): 303-316. Webbe FM, Barth JT. Short-term and long-term outcome of athletic closed head injuries. Clinical Sports Med. 2003; 22:577–92. Read More