Impairments in attention are commonly seen in individuals with traumatic brain injury (TBI). While attention assessment measurements have been developed rigorously and utilized frequently in cognitive neurorehabilitation, there is a paucity of auditory attention assessment instruments that are ecologically valid and that assess different subtypes of attention. Yet, deficits in auditory attention can severely limit everyday functioning, negatively impact work and personal relationships and compromise personal safety. The purpose of this study was to develop and to investigate the psychometric properties of a Music-based Attention Assessment (MAA) instrument. The MAA is a multiple choice, melodic contour identification test, designed to assess three different types of auditory attention, including sustained attention, selective attention, and divided attention. The MAA was piloted with patients with TBI (n = 15) and healthy adults (n = 30) separately to evaluate preliminary psychometric properties. Both pilot studies reported that the MAA possessed a very high reliability and appropriate item properties. However, the MAA was revised due to a ceiling effect on mean test scores in the healthy adult group. The revised version of the MAA was administered to healthy adults (n = 165) as well as TBI patients (n= 22) to investigate construct validity, item properties, test reliability, and difference in MAA performance between groups. Here, psychometric validation of the revised version of the MAA is described, and the obtained results reported. Exploratory factor analysis identified five-factor constructs, supporting the different types of attention that underlie the test items of the revised version of the MAA. The factors identified were Sustained-Short, Sustained-Med to Long, Selective-Noise, Selective & Divided, and Divided-Long. After item elimination, the finalized 45-item MAA in relation to the identified five-factor constructs provided evidence of high internal consistencies as computed by split-half reliability coefficients (r = .836) and Cronbach’s alpha (α = .940), indicating homogeneity of test items within each of the five subtest as well as for the total test. As predicted, significant differences were found between the healthy adult and TBI patient samples across the exploratively obtained five-factor constructs of the revised version of the MAA. The MAA performance was significantly better in the healthy adult group than in the TBI patient group, except on the Sustained Attention–Short Subtest, indicating pervasive attention impairments in patients with TBI. The finding also suggests that a basic level of sustained attention to deal with a small amount of auditory information during a limited time might be intact for the patients with TBI who have a moderate to severe level of brain injury. The aggregate findings suggest that the MAA is a valid and reliable measure that provides diagnostic information in regards to the three types of auditory attention deficits frequently observed in patients with TBI. The use of melodic contours in attention assessment is discussed along with limitations of the study and suggestions for future research. The MAA, when used in conjunction with attention assessment instruments in different sensory modalities, would provide a greater level of precision in the attention assessment of patients with TBI, resulting in more symptom specific and individualized rehabilitation and treatment.

Although it is well established that persons with traumatic brain injury (TBI) experience word retrieval difficulties, the underlying cause of these deficits is not known. Difficulties with word retrieval have negative social implications as they can impact on the ability to converse with others. The overarching goal of this dissertation was to determine the underlying cause of problems with word retrieval after TBI. To test word retrieval in this dissertation, participants were given a series of word fluency tasks and the speed of word generation was measured. In addition to measuring interresponse times, procedures used by Rohrer, Wixted, Salmon and Butters (1995) were also followed. This involved the calculation of parameter estimates to investigate whether slowed retrieval or degraded semantic stores were responsible for the patients� word retrieval difficulties. One parameter (N) was a measure of the total number of retrievable words and the second parameter (tau) was an estimate of mean latency. Study 1 was designed to trial the procedure and equipment adopted throughout this dissertation to analyse speech. University students were presented with categories on a computer screen and asked to generate as many exemplars as possible in 60 seconds. A PowerLab Chart sound system was used to measure the time that each word was generated. The results of Study 1 showed that the methodology of previous research could be replicated using the PowerLab Chart sound system. In Study 2, persons with postconcussion syndrome (PCS) and matched controls were given two word fluency tasks. Results showed that on both tasks patients recalled fewer words, had longer pauses between words, and took significantly longer to generate their first word than controls. Also, patients had a significantly reduced N relative to controls, but there was no difference in tau between patients and controls. Given that the participants had not finished responding and that parameter estimates require responses to be exhausted, Study 3 was designed to replicate the findings of Study 2 using an extended recall period. In Study 3, patients with PCS and matched controls completed a series of word fluency tasks and were given extended periods of time to generate words. Results showed that the patients obtained significantly fewer words on two of the tasks, but no evidence of slowed retrieval was found. There was also no difference in the estimates of N and tau between patients and controls. As the patients in Study 3 sustained more minor injuries than those in Study 2, Study 4 tested patients with severe TBI. In Study 4, patients with severe TBI and matched controls were given a series of word fluency tasks. Results showed that the patients generated fewer words and experienced slowed retrieval. Again, there was no difference in the estimates of N and tau between patients and controls. The results of Study 4 confirmed the hypothesis that slowed word retrieval is a consequence of TBI. Taken together, the results of this dissertation show that an underlying slowness of processing is the primary cause of problems with word retrieval in persons with TBI.

Doctor of Philosphy (PhD) / Agitation following traumatic brain injury (TBI) is characterised by a heightened state of activity with disorganised information processing that interferes with learning and achieving functional goals. This thesis outlines a series of studies across four research phases, investigating how occupational performance of adults with TBI is affected by agitated behaviour and information processing difficulties. Clinicians report the presence of agitation interferes with engagement in therapy and achievement of rehabilitation goals. Research Phase One used a retrospective chart review of 80 adults with severe TBI to identify a high incidence of agitated behaviour during inpatient TBI rehabilitation. Agitated behaviour was associated with lengthier rehabilitation admission, prolonged duration of post-traumatic amnesia (PTA), and poor cognitive functioning at discharge. The association between agitation and poor cognition persisted for at least two years after discharge, highlighting the significant impact of agitated behaviour on people’s ability to relearn cognitive skills for daily function. These initial research findings directed subsequent research phases, in which an information processing model was adopted to examine application of cognitive strategies during occupational performance. An emerging occupational therapy assessment, The Perceive, Recall, Plan and Perform (PRPP) System of Task Analysis, was selected as the primary method for evaluating how application of cognitive strategies during occupational performance is affected in agitated patients. Clinical utility of this measure was established in a case study of an adult demonstrating severely agitated behaviour during inpatient TBI rehabilitation, followed by examination of instrument reliability and validity with ten experienced occupational therapists and five adults with agitated behaviour following brain injury. The PRPP System of Task Analysis emerged as a valid and reliable method for determining strategy application deficits during occupational performance of adults with agitated behaviour, in acute stages of TBI rehabilitation. Consistent patterns of processing deficits were related to the Perceive and Recall Quadrants of the PRPP System. The assessment tool forms part of a dynamic, interactive assessment and intervention system. The PRPP System of Intervention was evaluated in the final research phase, using an experimental single case design with replication across eight adults. The effectiveness of PRPP Intervention was examined in comparison to conventional occupational therapy in an ABAB design. Efficacy of the PRPP Intervention was demonstrated, with patients applying significantly more information processing strategies to occupational performance tasks during PRPP Intervention than during conventional occupational therapy sessions. Agitated behaviour concurrently reduced over the period of the study. Relationships between information processing and agitated behaviour are hypothesised.

Doctor of Philosphy (PhD) / Agitation following traumatic brain injury (TBI) is characterised by a heightened state of activity with disorganised information processing that interferes with learning and achieving functional goals. This thesis outlines a series of studies across four research phases, investigating how occupational performance of adults with TBI is affected by agitated behaviour and information processing difficulties. Clinicians report the presence of agitation interferes with engagement in therapy and achievement of rehabilitation goals. Research Phase One used a retrospective chart review of 80 adults with severe TBI to identify a high incidence of agitated behaviour during inpatient TBI rehabilitation. Agitated behaviour was associated with lengthier rehabilitation admission, prolonged duration of post-traumatic amnesia (PTA), and poor cognitive functioning at discharge. The association between agitation and poor cognition persisted for at least two years after discharge, highlighting the significant impact of agitated behaviour on people’s ability to relearn cognitive skills for daily function. These initial research findings directed subsequent research phases, in which an information processing model was adopted to examine application of cognitive strategies during occupational performance. An emerging occupational therapy assessment, The Perceive, Recall, Plan and Perform (PRPP) System of Task Analysis, was selected as the primary method for evaluating how application of cognitive strategies during occupational performance is affected in agitated patients. Clinical utility of this measure was established in a case study of an adult demonstrating severely agitated behaviour during inpatient TBI rehabilitation, followed by examination of instrument reliability and validity with ten experienced occupational therapists and five adults with agitated behaviour following brain injury. The PRPP System of Task Analysis emerged as a valid and reliable method for determining strategy application deficits during occupational performance of adults with agitated behaviour, in acute stages of TBI rehabilitation. Consistent patterns of processing deficits were related to the Perceive and Recall Quadrants of the PRPP System. The assessment tool forms part of a dynamic, interactive assessment and intervention system. The PRPP System of Intervention was evaluated in the final research phase, using an experimental single case design with replication across eight adults. The effectiveness of PRPP Intervention was examined in comparison to conventional occupational therapy in an ABAB design. Efficacy of the PRPP Intervention was demonstrated, with patients applying significantly more information processing strategies to occupational performance tasks during PRPP Intervention than during conventional occupational therapy sessions. Agitated behaviour concurrently reduced over the period of the study. Relationships between information processing and agitated behaviour are hypothesised.

Thesis (M.A.)--Miami University, Dept. of Speech Pathology and Audiology, 2004. / Title from first page of PDF document. Includes bibliographical references (p. 54-59).

Traumatic Brain Injury (TBI) accounts for 1,000,000 hospital admissions in the European Union every year and is the leading cause of death in individuals under 45 years of age in both Europe and the United States. This thesis examines the consequences to both the brain and lung following TBI using the lateral fluid percussion injury (FPI) in an in-vivo murine model. In the murine FPI model, alongside cerebral inflammation (associated with neuronal damage and the infiltration of inflammatory cells), there is significant neutrophil accumulation within the pulmonary interstitium 6 and 24 hours after TBI. This was associated with pulmonary haemorrhage and increased vascular permeability. In an attempt to reduce pulmonary injury, 17-DMAG, an HSP90 inhibitor, was applied but proved to be nonprotective. Since patients with TBI show increased susceptibility to bacterial infection, microaspiration and ventilator-induced lung injury, a double-hit model was established whereby mice first received the head injury and then received a lung injury. This demonstrated worse lung injury following intra-tracheal administration of hydrochloric acid after TBI. Depleting neutrophils with an anti-LY-6G depleting antibody improved outcome in this model, indicating increased susceptibility to damage was neutrophil dependent. To test whether neutrophil accumulation within the pulmonary interstitium was specifically related to brain injury, lung tissue following other distant organ injury such as renal ischemia-reperfusion injury (IRI) and renal transplantation were assessed. Significant pulmonary interstitial neutrophil accumulation was seen following both models and was associated with significant pulmonary haemorrhage. Inducing HSP70 activity with an HSP90 inhibitor was shown to be protective by reducing the degree of pulmonary haemorrhage in these models. In an attempt to identify the mechanisms behind neutrophil accumulation in TBI, renal IRI and renal transplantation, ICAM-1 (CD54), a marker of the reverse transmigration of neutrophils was investigated. No differences in ICAM-1 expression were seen following TBI, indicating that another mechanism must be responsible. This mechanism is the focus of on going work within the laboratory. Hypoxia is believed to contribute towards the development of secondary brain injury however little is known regarding its direct contribution. Working alongside chemists at the University of Edinburgh, a number of novel fluorescent hypoxia probes were designed and tested, but none proved to be able to detect hypoxia in-vitro. In conclusion, this thesis has demonstrated that following mild TBI, the lungs are “primed” with a massive interstitial neutrophil influx and that a subsequent micro aspiration of acid induces exaggerated lung injury. The mechanism by which this occurs is the focus of on-going investigation. Pulmonary sequestration of neutrophils is also a predominant feature of other distant organ injuries.

Hypertonic saline (HS) is an accepted treatment for traumatic brain injury (TBI). However, the behavioral and cognitive consequences following HS administration have not thoroughly been examined. Recent preclinical evidence has suggested that nicotinamide (NAM) is beneficial for recovery of function following TBI. The first study compared the behavioral and cognitive consequences of HS and NAM as competitive therapeutic agents for the treatment of TBI. Following controlled cortical impact (CCI), bolus administrations of NAM (500 mg/kg), 7.5% HS, or 0.9% saline vehicle (1.0 mL/kg) were given at 2, 24, and 48 hrs post-CCI. Behavioral results revealed that animals treated with NAM and HS showed significant improvements in beam walk and locomotor placing compared to the Vehicle group. The Morris water maze (MWM) retrograde amnesia test was conducted on day 12 post-CCI and showed that all groups had significant retention of memory compared to injured, Vehicle-treated animals. Working memory was also assessed on days 18-20 using the MWM. The NAM and Vehicle groups quickly acquired the task; however, HS animals showed no acquisition of this task. Histological examinations revealed that the HS-treated animals lost significantly more cortical tissue than either the NAM or Vehicle-treated animals. HS-treated animals showed a greater loss of hippocampal tissue compared to the other groups. In general, NAM showed a faster rate of recovery than HS without this associated tissue loss. Study 1 suggested that future research into HS should include drug injection time course studies. Multiple injections may be responsible for the notable tissue damage. Therefore, it is possible that fewer injections will result in comparable behavioral recovery and less tissue damage that was observed. Due to the detrimental effects of 7.5% HS on cognition and hippocampal tissue following multiple administration in study 1, the proposed second study sought to study the behavioral and cognitive effects of HS using either single or multiple injection regime. The proposed study entailed a lengthier testing schedule than in study 1 and included the same histological examination to compare the different dosages. Additionally, edema formation was measured 24 hours following each drug endpoint in order to delineate the possible underlying mechanism of the observed deficits. In Study 2, HS tended to improve function on motor, sensorimotor and neurological tasks. Although this was a trend on all tests, animals treated with a single administration of HS overall performed better on all tasks compared to those receiving double or multiple injections. In the retrograde amnesia test, although not significant, the Sham, HS-2, and HS-24 animals showed improvement; whereas, the Vehicle and HS-48 animals showed no improvement in performance. This could possibly be linked to the additional hippocampal tissue loss that was noted in the HS-48 animals. In the working memory paradigm, the HS-2 and Vehicle groups had longer latencies to reach the platform than did the Sham group. However, after the first testing day, there were no significant differences between any of the groups. All animals treated with HS performed at the same rate and their performance either stayed the same over the three day testing period or became worse. It appears these animals were unable to learn and improve in the new memory acquisition task which is comparable to the results found in study 1. In study 1, there were again no observed hippocampal volume differences between the Sham and Vehicle-treated animals. However, there was extensive hippocampal tissue damage observed in all of the HS groups. Furthermore, animals treated with a single administration of HS had less hippocampal loss than those with double or multiple doses. Those animals receiving more than one dose of HS lost significantly more hippocampal tissue than the Vehicle group. The results of study 2 are comparable, and support, the results of study 1. Both studies support the strengths and weakness of HS therapy following TBI. Although there are potential benefits of HS therapy, there are also detrimental risks involved. Cognitive and structural damage could possible occur if the dosage amounts are not closely studied and monitored. Although the use of HS may be beneficial to reduce ICP following TBI, it appears that the use of HS may also lead to direct or indirect tissue loss possibly by chronic cellular dehydration. Stronger or more delineated effects may be noticed using higher doses or concentrations of HS in future studies. However, due to the nature of these results, caution should be advised with the use of all therapeutic usage of HS until further detailed studies are conducted.

While participation in youth sports bolster a myriad of health benefits, it can also pose a risk to the athlete's health from the increasing prevalence of repetitive mild traumatic brain injuries (TBI), often referred to as concussions. The adverse effects from repeated traumatic blows give a combination of acute symptoms, which may potentially develop into long-term complications. There is little known about the epidemiology of concussions, and thus the development of an animal model would help enhance our understanding of this potentially debilitating injury. An appropriate animal model should mimic the conditions of how concussions occur, in that there is not an invasive method to induce the injury and follows the same biomechanics. In our adolescent repetitive mild TBI model, we utilized a free-falling weight to deliver the traumatic blow to anesthetized mice that allowed free head rotation after impact. The injured group received one hit daily over the course of three days. The mice then underwent several behavioral tests to analyze the cognitive deficits, and the pathology of the tissue was analyzed via silver, Hematoxylin and Eosin (H&E), and Fluoro Jade-B staining. The injured mice developed both short- and long-term memory and spatial learning deficits, symptoms commonly found in concussed athletes, but failed to show deficits in anxiety and depression tests. The Fluoro Jade-B, silver and H&E staining resulted in negative signals for cell death. This study properly demonstrates repetitive mild TBIs in an adolescent mice model.

Traumatic brain injury (TBI) is a major health problem affecting the adult and pediatric population. Scientists and clinicians are working diligently to discover possible therapeutics for the treatment of TBI. Two possible treatments to deal with TBI include sleep and the administration of progesterone. Yet, there are conflicting results from studies regarding the efficacy of either treatment. Sleep appears to reduce neuroinflammation and reduce axonal damage in the brain following TBI. Sleep deprivation, however, may have neuroprotective effects after TBI. Progesterone has also been shown to have neuroprotective effects following TBI. But, there are no sufficient data from animal studies to determine if progesterone is an effective therapeutic. More research studies will have to be conducted to further understand the role of sleep and progesterone in alleviating TBI.

The pathophysiology of traumatic brain injury (TBI) includes perturbations to energy metabolism. Improving our understanding of cerebral energy metabolism will lead to strategies that improve clinical outcomes. For the studies in my thesis I used microdialysis to deliver carbon-13 labelled substrates to the human brain. I combined this with nuclear magnetic resonance (NMR) spectroscopy of interstitial fluid sampled from the brain to interrogate glucose, lactate and tricarboxylic acid (TCA) cycle metabolism. Study I: I defined the optimal parameters for quantitative proton and carbon-13 NMR of cerebral microdialysates. Study II: I measured baseline microdialysate metabolite concentrations for brain and muscle and investigated the influence of muscle activity and cerebral catheter placement in grey or white matter on metabolite concentrations. Study III: I used 1,2-13C2 glucose to measure glycolysis and pentose phosphate pathway activity. Glycolysis is the dominant lactate-producing pathway but the pentose phosphate pathway also contributes and is increased in some TBI patients. Study IV: I used arterio-venous gradients to measure glucose and lactate delivery to the brain. There are periods after injury when lactate is imported from the circulation despite relatively high brain lactate levels suggesting up-regulation of lactate transport. Study V: I followed the metabolism of 3-13C lactate and demonstrated that lactate is metabolised by the TCA cycle. This occurs in both normal and injured brain but not in muscle. Study VI: I used 2,3-13C2 succinate to investigate the role of the TCA cycle in producing metabolites that are exported into the interstitium. The TCA cycle is found to be a source of lactate. Succinate delivered to the brain improves redox and enhances glutamate uptake into cells. The implications of the findings in my thesis on existing knowledge of cerebral metabolism are discussed. Strategies that might potentiate cerebral metabolism and improve clinical outcomes are suggested.