Test-retest reliability and practice effects of a rapid screen of mild traumatic brain injury

Test-retest reliabilities and practice affects of measures from the Rapid Screen of Concussion (RSC), in addition to the Digit Symbol Substitution Test (Digit Symbol), were examined. Twenty five male participants were tested three times; each testing session scheduled a week apart. The test-retest reliability estimates for most measures were reasonably good, ranging from .79 to .97. An exception was the delayed word recall test, which has had a reliability estimate of .66 for the first retest, and .59 for the second retest. Practice effects were evident from Times 1 to 2 on the sentence comprehension and delayed recall subtests of the RSC, Digit Symbol and a composite score. There was also a practice effect of the same magnitude found from Time 2 to Time 3 on Digit Symbol, delayed recall and the composite score. Statistics on measures for both the first and second retest intervals, with associated practice affects, are presented to enable the calculation of reliable change indices (RCI). The RCI may be used to assess any improvement in cognitive functioning after mild Traumatic Brain Injury.

The acute effects of mild traumatic brain injury on finger tapping with and without word repetition

This study aimed to investigate the acute effects of mild Traumatic Brain Injury (mTBI) on the performance of a finger tapping and word repetition dual task in order to determine working memory impairment in mTBI Sixty-four (50 male, 14 female) right-handed cases of mTBI and 26 (18 male and 8 female) right-handed cases of orthopaedic injuries were tested within 24 hours of injury. Patients with mTBI completed fewer correct taps in 10 seconds than patients with orthopaedic injuries, and female mTBI cases repeated fewer words. The size of the dual task decrement did not vary between groups. When added to a test battery including the Rapid Screen of Concussion (RSC; Comerford, Geffen, May, Medland T Geffen, 2002) and the Digit Symbol Substitution Test,finger tapping speed accounted for 1% of between groups variance and did not improve classification rates of male participants. While the addition of tapping rate did not improve the sensitivity and specificity of the RSC and DSST to mTBI in males, univariate analysis of motor performance in females indicated. that dual task performance might be diagnostic. An increase in female sample Size is warranted. These results confirm the view that there is a generalized slowing of processing ability following mTBI.

Mechanisms of axon guidance in the developing nervous system

The human brain assembles an incredible network of over a billion neurons. Understanding how these connections form during development in order for the brain to function properly is a fundamental question in biology. Much of this wiring takes place during embryonic development. Neurons are generated in the ventricular zone, migrate out, and begin to differentiate. However, neurons are often born in locations some distance from the target cells with which they will ultimately form connections. To form connections, neurons project long axons tipped with a specialized sensing device called a growth cone. The growing axons interact directly with molecules within the environment through which they grow. In order to find their targets, axonal growth cones use guidance molecules that can either attract or repel them. Understanding what these guidance cues are, where they are expressed, and how the growth cone is able to transduce their signal in a directionally specific manner is essential to understanding how the functional brain is constructed. In this chapter, we review what is known about the mechanisms involved in axonal guidance. We discuss how the growth cone is able to sense and respond to its environment and how it is guided by pioneering cells and axons. As examples, we discuss current models for the development of the spinal cord, the cerebral cortex, and the visual and olfactory systems. (c) 2005, Elsevier Inc.

Patterns of neuronal activation in the rat brain and spinal cord in response to increasing durations of restraint stress

By most accounts the psychological stressor restraint produces a distinct pattern of neuronal activation in the brain. However, some evidence is incongruous with this pattern, leading us to propose that the restraint- induced pattern in the central nervous system might depend on the duration of restraint used. We therefore determined the pattern of neuronal activation ( as indicated by the presence of Fos protein) seen in the paraventricular nucleus (PVN), bed nucleus of the stria terminalis, amygdala, locus coeruleus, nucleus tractus solitarius (NTS), ventrolateral medulla (VLM) and thoracic spinal cord of the rat in response to 0, 15, 30 or 60 min periods of restraint. We found that although a number of cell groups displayed a linear increase in activity with increasing durations of restraint ( e. g. hypothalamic corticotrophin-releasing factor (CRF) cells, medial amygdala neurons and sympathetic preganglionic neurons of the thoracic spinal cord), a number of cell groups did not. For example, in the central amygdala restraint produced both a decrease in CRF cell activity and an increase in non-CRF cell activity. In the locus coeruleus, noradrenergic neurons did not display Fos in response to 15 min of restraint, but were significantly activated by 30 or 60 min restraint. After 30 or 60 min restraint a greater degree of activation of more rostral A1 noradrenergic neurons was observed compared with the pattern of A1 noradrenergic neurons in response to 15 min restraint. The results of this study demonstrate that restraint stress duration determines the amount and the pattern of neuronal activation seen in response to this psychological stressor.

Adoption of a sedation scoring system and sedation guideline in an intensive care unit

Aim. The paper presents a study assessing the rate of adoption of a sedation scoring system and sedation guideline. Background. Clinical practice guidelines including sedation guidelines have been shown to improve patient outcomes by standardizing care. In particular sedation guidelines have been shown to be beneficial for intensive care patients by reducing the duration of ventilation. Despite the acceptance that clinical practice guidelines are beneficial, adoption rates are rarely measured. Adoption data may reveal other factors which contribute to improved outcomes. Therefore, the usefulness of the guideline may be more appropriately assessed by collecting adoption data. Method. A quasi-experimental pre-intervention and postintervention quality improvement design was used. Adoption was operationalized as documentation of sedation score every 4 hours and use of the sedation and analgesic medications suggested in the guideline. Adoption data were collected from patients' charts on a random day of the month; all patients in the intensive care unit on that day were assigned an adoption category. Sedation scoring system adoption data were collected before implementation of a sedation guideline, which was implemented using an intensive information-giving strategy, and guideline adoption data were fed back to bedside nurses. After implementation of the guideline, adoption data were collected for both the sedation scoring system and the guideline. The data were collected in the years 2002-2004. Findings. The sedation scoring system was not used extensively in the pre-intervention phase of the study; however, this improved in the postintervention phase. The findings suggest that the sedation guideline was gradually adopted following implementation in the postintervention phase of the study. Field notes taken during the implementation of the sedation scoring system and the guideline reveal widespread acceptance of both. Conclusion. Measurement of adoption is a complex process. Appropriate operationalization contributes to greater accuracy. Further investigation is warranted to establish the intensity and extent of implementation required to positively affect patient outcomes.

The development of self-awareness and relationship to emotional functioning during early community reintegration after traumatic brain injury

Impaired self-awareness may affect clients' emotional status, engagement in rehabilitation and community reintegration following traumatic brain injury (TBI). The study aimed to investigate the relationship between self-awareness, emotional distress and community integration in adults with TBI during the transition from hospital to the community. Thirty-four rehabilitation clients with TBI were assessed in the week before and 2 months after discharge home. Measures of self-awareness and emotional functioning were administered predischarge and repeated at follow-up along with a measure of community integration. Nonparametric tests were used to compare levels of self-awareness and emotional distress pre- and postdischarge, their interrelationships and association with community integration. Self-awareness significantly increased following discharge, and a trend towards increased depression was found. There were no consistent relationships found between level of self-awareness, emotional functioning, and community integration. The development of self-awareness in the immediate postdischarge phase suggests this is an important time for clinical interventions targeting compensation strategies and adjustment to disability.

Treating dysarthria following traumatic brain injury: Investigating the benefits of commencing treatment during post-traumatic amnesia in two participants

Primary objective: The aims of this preliminary study were to explore the suitability for and benefits of commencing dysarthria treatment for people with traumatic brain injury (TBI) while in post-traumatic amnesia ( PTA). It was hypothesized that behaviours in PTA don't preclude participation and dysarthria characteristics would improve post-treatment. Research design: A series of comprehensive case analyses. Methods and procedures: Two participants with severe TBI received dysarthria treatment focused on motor speech deficits until emergence from PTA. A checklist of neurobehavioural sequelae of TBI was rated during therapy and perceptual and motor speech assessments were administered before and after therapy. Main outcomes and results: Results revealed that certain behaviours affected the quality of therapy but didn't preclude the provision of therapy. Treatment resulted in physiological improvements in some speech sub-systems for both participants, with varying functional speech outcomes. Conclusions: These findings suggest that dysarthria treatment can begin and provide short-term benefits to speech production during the late stages of PTA post-TBI.

EphA4 regulates central nervous system vascular formation

Molecules involved in axon guidance have recently also been shown to play a role in blood vessel guidance. To examine whether axon guidance molecules, such as the EphA4 receptor tyrosine kinase, might also play a role in development of the central nervous system (CNS) vasculature and repair following CNS injury, we examined wild-type and EphA4 null mutant (-/-) mice. EphA4-/- mice exhibited an abnormal CNS vascular structure in both the cerebral cortex and the spinal cord, with disorganized branching and a 30% smaller diameter. During development, EphA4 was expressed on endothelial cells. This pattern of expression was not maintained in the adult. After spinal cord injury in wild-type mice, expression of EphA4 was markedly up-regulated on activated astrocytes, many of which were tightly associated with blood vessels. In EphA4-/- spinal cord following injury, astrocytes were not as tightly associated with blood vessels as the wild-type astrocytes. In uninjured EphA4-/- mice, the blood-brain barrier (BBB) appeared normal, but it showed prolonged leakage following spinal cord injury. These results support a role for EphA4 in CNS vascular formation and guidance during development and an additional role in BBB repair.

An Internet-based telerehabilitation system for the assessment of motor speech disorders: A pilot study

Purpose: This pilot study explored the feasibility and effectiveness of an Internet-based telerehabilitation application for the assessment of motor speech disorders in adults with acquired neurological impairment. Method: Using a counterbalanced, repeated measures research design, 2 speech-language pathologists assessed 19 speakers with dysarthria on a battery of perceptual assessments. The assessments included a 19-item version of the Frenchay Dysarthria Assessment (FDA; P. Enderby, 1983), the Assessment of Intelligibility of Dysarthric Speech (K. M. Yorkston & D. R. Beukelman, 1981), perceptual analysis of a speech sample, and an overall rating of severity of the dysarthria. One assessment was conducted in the traditional face-to-face manner, whereas the other assessment was conducted using an online, custom-built telerehabilitation application. This application enabled real-time videoconferencing at 128 kb/s and the transfer of store-and-forward audio and video data between the speaker and speech-language pathologist sites. The assessment methods were compared using the J.M.Bland and D.G.Altman (1986, 1999) limits-of-agreement method and percentage level of agreement between the 2 methods. Results: Measurements of severity of dysarthria, percentage intelligibility in sentences, and most perceptual ratings made in the telerehabilitation environment were found to fall within the clinically acceptable criteria. However, several ratings on the FDA were not comparable between the environments, and explanations for these results were explored. Conclusions: The online assessment of motor speech disorders using an Internet-based telerehabilitation system is feasible. This study suggests that with additional refinement of the technology and assessment protocols, reliable assessment of motor speech disorders over the Internet is possible. Future research methods are outlined.

Brain morphology in large pelagic fishes: A comparison between sharks and teleosts

A quantitative comparison was made of both relative brain size (encephalization) and the relative development of five brain area of pelagic sharks and teleosts. Two integration areas (the telencephalon and the corpus cerebellum) and three sensory brain areas (the olfactory bulbs, optic tectum and octavolateralis area, which receive primary projections from the olfactory epithelium, eye and octavolateralis senses, respectively), in four species of pelagic shark and six species of pelagic teleost were investigated. The relative proportions of the three sensory brain areas were assessed as a proportion of the total 'sensory brain', while the two integration areas were assessed relative to the sensory brain. The allometric analysis of relative brain size revealed that pelagic sharks had larger brains than pelagic teleosts. The volume of the telencephalon was significantly larger in the sharks, while the corpus cerebellum was also larger and more heavily foliated in these animals. There were also significant differences in the relative development of the sensory brain areas between the two groups, with the sharks having larger olfactory bulbs and octavolateralis areas, whilst the teleosts had larger optic tecta. Cluster analysis performed on the sensory brain areas data confirmed the differences in the composition of the sensory brain in sharks and teleosts and indicated that these two groups of pelagic fishes had evolved different sensory strategies to cope with the demands of life in the open ocean.

Comparative gene expression in brain regions of human alcoholics

The mesocorticolimbic system is the reward centre of the brain and the major target for drugs of abuse including alcohol. Neuroadaptive changes in this region are thought to underlie the process of tolerance and dependence. Recently, several research groups have searched for alcohol-responsive genes using high-throughput microarrays and well-characterized human post-mortem material. Comparison of data from these studies of cortical regions highlights the differences in experimental approach and selection of cases. However, alcohol-responsive gene sets associated with transcription, oxidative stress and energy production were common to these studies. In marked contrast, alcohol-responsive genes in the nucleus accumbens and the ventral tegmental area are primarily associated with changes in neurotransmission and signal transduction. These data support the concept that, within cortical regions, changes in gene expression are associated with alcoholism-related pathology. In the dopaminergic tract of the mesocorticolimbic system, alcohol-responsive gene sets suggest long-term neuroplastic changes in synaptic transmission.

Emergency department assessment of mild traumatic brain injury and prediction of post-concussion symptoms at one month post injury

Mild traumatic brain injury (mTBI) is a common injury and a significant proportion of those affected report chronic symptoms. This study investigated prediction of post-concussion symptoms using an Emergency Department (ED) assessment that examined neuropsychological and balance deficits and pain severity of 29 concussed individuals. Thirty participants with minor orthopedic injuries and 30 ED visitors were recruited as control subjects. Concussed and orthopedically injured participants were followed up by telephone at one month to assess symptom severity. In the ED, concussed subjects performed worse on some neuropsychological tests and had impaired balance compared to controls. They also reported significantly more post-concussive symptoms at follow-up. Neurocognitive impairment, pain and balance deficits were all significantly correlated with severity of post-concussion symptoms. The findings suggest that a combination of variables assessable in the ED may be useful in predicting which individuals will suffer persistent post-concussion problems.

Expression and role of complex carbohydrates in axon guidance in the olfactory system

Primary sensory neurons in the vertebrate olfactory systems are characterised by the differential expression of distinct cell surface carbohydrates. We show here that the histo-blood groups Sda (or CT1 antigen) and H are expressed by primary sensory neurons in the olfactory system, while the blood group A carbohydrate is expressed by a subset of vomeronasal neurons only in the developing accessory olfactory system. We have used both loss-of-function and gain-of-function approaches to manipulate expression of these carbohydrates in the olfactory system. In null mutant mice lacking the alpha(1,2)fucosyltransferase FUT1, the blood group H and A carbohydrates were not expressed in the olfactory systems which caused delayed development of the nerve fibre and glomerular layers in the main olfactory bulb. In contrast, ubiquitous expression of blood group A on olfactory axons in gain-of-function transgenic mice perturbed the ability of vomeronasal axons to terminate in the accessory olfactory bulb and affected the selective targeting of axons in the main olfactory bulb. During regeneration following bulbectomy, vomeronasal axons were unable to effectively sort out from the main olfactory axons when blood group A was misexpressed. These results provide in vivo evidence for a role of specific cell surface carbohydrates during development and regeneration of the olfactory nerve pathways.

Imaging, anatomical, and molecular analysis of callosal formation in the developing human fetal brain

A complex set of axonal guidance mechanisms are utilized by axons to locate and innervate their targets. In the developing mouse forebrain, we previously described several midline glial populations as well as various guidance molecules that regulate the formation of the corpus callosum. Since agenesis of the corpus callosum is associated with over 50 different human congenital syndromes, we wanted to investigate whether these same mechanisms also operate during human callosal development. Here we analyze midline glial and commissural development in human fetal brains ranging from 13 to 20 weeks of gestation using both diffusion tensor magnetic resonance imaging and immunohistochemistry. Through our combined radiological and histological studies, we demonstrate the morphological development of multiple forebrain commissures/decussations, including the corpus callosum, anterior commissure, hippocampal commissure, and the optic chiasm. Histological analyses demonstrated that all the midline glial populations previously described in mouse, as well as structures analogous to the subcallosal sling and cingulate pioneering axons, that mediate callosal axon guidance in mouse, are also present during human brain development. Finally, by Northern blot analysis, we have identified that molecules involved in mouse callosal development, including Slit, Robo, Netrin1, DCC, Nfia, Emx1, and GAP-43, are all expressed in human fetal brain. These data suggest that similar mechanisms and molecules required for midline commissure formation operate during both mouse and human brain development. Thus, the mouse is an excellent model system for studying normal and pathological commissural formation in human brain development. (c) 2006 Wiley-Liss, Inc.