Dissertations / Theses on the topic 'Brain damage – Complications – Treatment'

The current work explores the therapeutic potential of experiential treatments for enhancing functional recovery and anatomical change after early brain damage. Normal rats and rats with perinatal cortical lesions (P2 or P7) were exposed to one of the following treatments: complex housing as juveniles, complex housing as adults, prenatal tactile stimulation, postnatal tactile stimulation, or postnatal handling (removal from the nest with no additional stimulaion). Behavior was assessed in adulthood the Morris water task and the Whishaw reaching task. There were sex differences in the details of the effect of experience on both behavioral recovery and brain morphology. For both sexes treatments initiated prior to or immediately after brain injury were most effective in improving functional outcome. This was correlated with changes in dendritic arborization and Acetylcholinesterase staining. The results suggest that behavioral treatments can be used to stimulate functional recovery after early brain injury.
v, [14], 208 leaves : ill. ; 28 cm.

Haemostasis is an important aspect in neurosurgical operations for the achievement of good outcome. Bipolar coagulation is an extensively used haemostatic technique in modern neurosurgery but it may also cause iatrogenic brain trauma due to thermal injury. Published studies on coagulation-induced brain injury on a histological level are, however, limited. The present study aimed at investigating the extent of inflammatory and glial responses caused by different settings of bipolar coagulation using an animal model. It also investigated whether and how pre-operative treatment with dexamethasone or progesterone, both known to have neuro-protective effects, would modulate gliosis and macrophage infiltration induced by bipolar coagulation. The study consisted of two parts. The first part investigated the astrocytic and macrophage responses after bipolar coagulation at different power settings. 45 Sprague-Dawley rats received craniotomy, followed by bipolar coagulation at different power output settings (mock operation as control, 20W and 40W) over the rat cortex for a standardized duration of two seconds. On day 3, day 7 and day 28, brain sections were assessed by immunohistochemical staining for GFAP (astrocytes) and ED1 (macrophages). Quantification of outcome by random field cell counting under light microscopy was performed. The second part of the study used another 45 male Sprague-Dawley rats, divided into three treatment groups: Group 1 received the vehicle agents only (Control); Group 2 received progesterone 20mg/kg; Group 3 received dexamethasone 1 mg/kg. All treatments were given intraperitoneally two hours before craniotomy. The animals received bipolar coagulation at 40W for a standardized duration of two seconds. On day 1, 3 and 7, brain sections were assessed by immunohistochemical staining for GFAP and ED1. Quantification of outcome by random field cell counting under light microscopy was performed. T2-weighted magnetic resonance imaging for the animals on day 3 was also performed. The results showed that bipolar coagulation was associated with significant glial and inflammatory responses that correlated with power output. Progesterone and dexamethasone were both effective in reducing the glial hypertrophy and macrophage infiltration associated with bipolar coagulation. Dexamethasone had an additional advantage of reducing brain oedema and cavity formation. The findings suggested that progesterone and dexamethasone could be further explored as potential protective and/or remedial agents for bipolar coagulation-induced brain trauma sustained during neurosurgical procedures.
published_or_final_version
Surgery
Master
Master of Research in Medicine

As a result of medical advancement and cultural patterns of Western society, traumatic head injury is increasingly a problem for the injured, their families, medical and social services professionals, and the community at large. Head trauma is remarkable because of the complex nature of the residual disabilities which include long lasting cognitive and emotional problems, social isolation, and family disruption. The purpose of this study was to re-examine the phenomenon of recovery after mild to moderate head injury using an ethnographic research approach. The data were based on the experiences of 21 disabled and their families in the community setting. The disabled represented a range of stages of recovery and severity of disability. The data was collected using three field work strategies: extensive semi-structured interviews, participant observation, and non-academic document review. After collection the data was subjected to thematic and content analysis, that resulted in the selection of themes that characterized the experiences for the head injured and their families. The themes for the head injured informants were: dead days, loneliness, and forgetting. The family members' experiences were represented in the themes: responsibility, vulnerability, tough love, gender differences, and reactions to the experience. Next the data were interpreted using five theoretical concepts from cultural anthropology: liminality, personhood, social labelling, sick role and double bind. In addition, the reflexive influence of the investigator on the research process was addressed. The trustworthiness of the ethnography was assessed in terms of credibility, transferability, dependability and confirmability. Several variables were found to be important to the long term outcome of head injury. These variables were: family directed therapy, double bind communication patterns, and lifelong recovery. Two other factors were found to be critical for the recovery of the head injured. These were economic disincentives to the return to employment and the importance of the social and family environment. In the final section the research and policy implications of the study were discussed in relation to management and service provisions.

This study examined the relationship between executive and psychosocial functioning in 45 children and adolescents age 6 to 17 years who had been treated for a brain tumor. Executive functioning deficits can profoundly impact an adult's ability to function successfully in life. The purpose of the study was to evaluate the potential impact of executive functioning deficits on the day-to-day functioning in a pediatric population. The domains of executive functioning assessed included cognitive flexibility, conceptual thinking, sustained attention, and response inhibition. Psychosocial functioning was assessed using both parent and child report. Several significant relationships were found for adolescents ages 15 and older, with effect sizes ranging from medium to large. In particular, cognitive flexibility and conceptual thinking were significantly related to parent report of depression and adaptive functioning. Fewer significant relationships with smaller effect sizes were found for younger children. The results may reflect the developmental emergence of executive functioning abilities and late effects of executive functioning deficits upon psychosocial functioning. The correlational design of this study precludes definitive statements regarding the temporal nature of the relationship. Additional research, including longitudinal research and replicatory studies, will be needed to further investigate the developmental consequences of executive functioning impairment.

Thesis (M.A.)--Miami University, Dept. of Speech Pathology and Audiology, 2003.
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Neurocognitive and symptom profiles of concussed and nonconcussed adult provincial rugby union players were investigated over one rugby season, including early season (baseline), intermittent postconcussion, and end of season testing. In a non-equivalent quasi-experimental design, nonconcussed (n = 54) and concussed (n = 17) rugby groups were compared with demographically equivalent noncontact sport controls (n = 37, and n = 17, respectively). Measures included the ImPACT cognitive and symptom composites, and the WMS-III Visual Reproduction and Verbal Paired Associates subtests. The independent and dependent comparative analyses in respect of both nonconcussed and concussed groups, provided cross-validation of poorer acute and/or chronic neuropsychological outcomes for the rugby groups on the ImPACT Reaction Time, Visual Motor Speed, Impulse Control and Symptom composites, and the WMS-III Verbal Paired Associates. The finding of significantly poorer scores on Verbal Paired Associates up to 24 days post concussion for the rugby players versus controls, was longer than the 7 – 10 day recovery period frequently cited in the literature. The overall implication of the study is that even in a group with high cognitive reserve such as these provincial level athletes, there may be prolonged acute recovery, as well as permanent deleterious neuropsychological consequences of cumulative concussive injury in association with a sport such as rugby. Accordingly, the move towards careful individualised postconcussion monitoring of neurocognitive functioning is endorsed, including early identification of any significant permanent reductions in cognitive reserve. Sensitivity of the ImPACT test might be enhanced via inclusion of a verbal associate learning task.

The study investigated the long-term neuropsychological effects of repetitive mild traumatic brain injury (MTBI) due to participation in a contact sport amongst South African final year male high school athletes (N=189). The sample was divided by sports affiliation (Contact n = 115; Non-Contact n = 74) and concussion history (2+ Concussion n = 43; 0 Concussion n = 108). Comparative subgroups were statistically equivalent for age, education and estimated IQ (P > 0.05), with the Contact sport groups having markedly higher incidences of concussion than controls (p < 0.000). Measures included the ImPACT Verbal and Visual Memory, Visuomotor Speed and Reaction Time Composites, Digit Symbol Substitution and Digit Symbol Incidental Recall (immediate and delayed), the ImPACT Symptom Scale and a Post-concussion Symptom (PCS) questionnaire. Independent t-tests on cognitive measures at pre-and post-season revealed a predominant trend of Contact and 2+ Concussion groups performing worse, although only ImPACT Reaction Time at pre-season reached significance (p = 0.014). PCS comparisons revealed an overwhelming tendency of enhanced symptoms for Contact and 2+ Concussion groups with total scores being significantly different in most instances at pre-and post-season. Fatigue and aggression were the symptoms most pervasively high for the Contact and 2+ Concussion groups. Dependent t-test analyses at pre- versus post-season, revealed significant practice effects for the Contact group, not in evidence for controls on ImPACT Visual Motor Speed and Digit Symbol Incidental Recall-Delayed. Overall the results imply the possible presence of lingering neurocognitive and symptomatic concussion sequelae amongst South African final year high school participants of a contact sport. The indications gain potency when understood against the background of (i) Brain Reserve Capacity threshold theory, and (ii) the known risk of Type II error in group MTBI research, that might result in under-emphasis of subtle effects and miscalculation of cost-benefit risks. Clinical implications, and the need for prospective case-based research to ratify the results of this predominantly cross-sectional study, are discussed.

This study investigates the cumulative effects of concussive and subconcussive mild head injury on the cognitive functioning of schoolboy rugby players. A comprehensive battery of neuropsychological tests and a self-report postconcussive questionnaire were administered to top level schoolboy rugby players (n=47), and a non-contact sport control group of top level schoolboy hockey players (n=34). Group comparisons of the percentage of individuals with cognitive deficit were carried out between i) the schoolboy rugby and the schoolboy hockey players, ii) the rugby forward and the rugby backline players; iii) the rugby forward and the schoolboy hockey players and, iv) the rugby backline and the schoolboy hockey players. Results on the neuropsychological test battery did not provide any substantial evidence of a higher level of neuropsychological impairment in the rugby players relative to the control group, or in the rugby forward players relative to the rugby backline players. Results obtained on the postconcussive symptom questionnaire provided tentative indications that the rugby players do report a greater frequency of postconcussive symptomatology. The symptoms most frequently reported were being easily angered, memory problems, clumsy speech and sleep difficulties. It was hypothesized that the absence of cognitive impairment in the schoolboy rugby players compared with that noted for professional players was due to their younger age, relatively high IQ and education level and a less intensive level of physical participation in the sport, and hence less accumulated exposure to the game, thereby decreasing their exposure to mild head injuries. From a theoretical perspective, these pre-existing conditions were considered to act as protective factors against reductions in brain reserve capacity and concomitant susceptibility to the onset of neuropsychological dysfunction.

This study investigated the cumulative effect of mild head injuries on rugby players. A comprehensive battery of neuropsychological tests was administered and subjects completed a self-report postconcussive symptom questionnaire. Data were collected for the two rugby groups, Springbok rugby players (n = 26) and Under 21 rugby players (n = 19), and for the control group, national hockey players (n = 21). Group comparisons of the percentage of individuals with deficit or self-reported symptomatology were made between: (i) the contact sport groups and the control group; (ii) the forwards and the backs within each rugby group and the rugby forwards and the control group; and (iii) the Springbok and Under 21 rugby players. Broadly speaking, comparative results on the neuropsychological tests and the self-reported postconcussive symptoms clearly distinguished between contact sport players and non-contact sport players and indicated the presence of diffuse brain damage in the contact sport players. There was also clear evidence of positional variation within the rugby groups, with the forwards (more full contact positions) most susceptible to impairment. Neuropsychological test results revealed deficit in information processing speed, attention and concentration, mental flexibility, visual memory and verbal new learning. The most significant neuropsychiatric complaints were reported in the areas of memory, social contact, sensitivity to noise, lowered frustration tolerance, anxiety and worry, and depression. The most sensitive neuropsychological test used in the present study was the Digit Symbol Substitution test. This test clearly distinguished contact sport players from non-contact sport players, and forwards from backs.

Traumatic brain injury (TBI) incidence rates are increasing among the U.S. population and represent substantial acute and chronic care costs. A confounding factor in TBI treatment is the incidence rates of concomitant mental health disorders including depression, anxiety, and posttraumatic stress disorder (PTSD). Clinical data establish that the prevalence of any of these 3 diagnoses complicates the treatment of TBI regardless of whether the diagnosis was pre-existing or occurred because of the TBI, such that prognosis and recovery are negatively impacted. Despite this evidence, psychological assessment is not a first line step in the approach to TBI. The purpose of this research was to assess the prevalence of psychological screening among TBI patients for depression, anxiety, and PTSD to enable conclusions about the current standard of care in TBI management. Meta-analysis of peer reviewed journals on TBI management was used to determine if there was considerable evidence to support that depression, anxiety, and PTSD were being addressed as the standard of care in TBI management. Mean analysis of literature search results established that there was not considerable evidence to support a conclusion that depression, anxiety, and PTSD assessment were standard of care in TBI management. Among the recommendations resulting from this finding were for additional studies on TBI points of care to determine how mental health is currently being managed among TBI patients, and for a change in current TBI treatment protocols to incorporate mental health assessment as part of overall TBI management. If these, and the remaining recommendations, were implemented, it was affirmed that these would have a positive social impact resulting in improved patient outcomes, decreased healthcare costs, and better healthcare delivery for TBI patients.

A study was conducted on the self-reported symptoms of Mild Traumatic Brain Injury sustained in Rugby Union at the pre- and post-season stages. A full sample of 30 rugby players at Rhodes University was compared to 27 non-contact sport controls. A reduced sample of 20 rugby players and 9 control participants provided improved control for education and IQ and was compared. Measures included the WAIS-III Vocabulary and Picture Completion Sub-tests to estimate IQ level, the symptom checklist on a widely used computer-based program (ImPACT), and a paper and pencil self-report 31-Item Post-Concussion Symptom Questionnaire. Independent and Dependent T-Test comparisons were conducted on the full and reduced samples. The symptoms reported by the rugby group appeared to be more pronounced on both the ImPACT Symptom Scale and the 31-Item Post-Concussion Symptom Questionnaire when compared to the control group at both the pre-and post-season stages. It was concluded that the rugby players demonstrated evidence to support the hypothesis of having sustained more previous concussions and reporting more symptoms at the pre-season stage when compared to comtrol participants. No prevalent changes for either the rugby or control groups were seen in dependent comparisons from pre-to post-season.

The study sought to determine whether there is evidence for the presence of residual (chronic) deleterious effects on cognition due to repetitive mild traumatic brain injury in top team university level rugby players, using ImPACT 3.0, Trail Making Test (TMT) and Digit Span. The initial sample of 48 participants was divided into groups; Rugby (n = 30) and Controls (n = 18), Rugby Forwards (n = 14) and Rugby Backs (n = 16). A reduced sample (N = 31) comprised of Rugby (n = 20) and Controls (n = 11), Rugby Forwards (n = 9) and Rugby Backs (n = 11). Comparative subgroups were equivalent for estimated IQ but not for age and educational level in the full sample; in the reduced sample there was equivalence for all three variables of age, education and estimated IQ. All cognitive test measures were subjected to independent t-test analyses between groups at the pre- and post-season, and dependent t-test analyses for Rugby and Controls at pre- versus post-season. Overall, the results implicated the presence of deleterious effects of concussive events on Rugby players in the areas of speed of information processing, working memory and impulse control. Significant practice effects were found on the TMT and Digit Span for controls, but not on ImPACT 3.0, supporting the use of this computer-based programme in the sports management context.

[Truncated abstract] Controlled and automatic processing are broad categories, and how best to measure these constructs and their impact on functioning after mild traumatic brain injury (TBI) remains uncertain. The purpose of this thesis was to examine automatic and controlled processing aspects of attention after mild TBI using the Paced Auditory Serial Addition Task (PASAT) and event-related potentials (ERPs). The PASAT is one of the most frequently used tests to evaluate attentional functioning. It has been demonstrated to be a measure sensitive to both acute and longer-term effects of mild TBI, presumably due to demands for rapid processing and executive attentional control. ERPs provide a noninvasive neurophysiological index of sensory processing and cognitive functions and have demonstrated sensitivity to even minor cognitive dysfunction. The parameters provided by this functional technique may be those most likely to distinguish individuals with mild TBI from controls. Initially, it was hypothesized that successful novice PASAT performance requires the engagement of executive attention to establish novel controlled information processing strategies. Ten individuals who had suffered a mild TBI an average of 15.20 months previously were therefore expected to demonstrate processing abnormalities on the PASAT, relative to 10 healthy matched controls. Although the mild TBI group reported significant intensification of subjective symptoms since their injury, compared to controls, the mild TBI group provided a similar amount of correct PASAT responses. ... In the first experiment a visual search task consisting of an automatic detection and a controlled search condition was developed. In the second experiment the search task was performed concurrently with the PASAT task in a dual-task paradigm. In the mild TBI group, prior failure to establish more efficient forms of information processing with practice was found to significantly interfere with simultaneous performance of the PASAT task and the attention demanding condition of the search task. The pattern of impaired performance was considered to reflect a reduction in processing resources rather than a deficit in resource allocation. Dual-task performance in the control group was not associated with a large interference effect. In general, the results of this thesis suggest that individuals with mild TBI are impaired in their ability to progress from the stage of effortful controlled information processing to a stage of more efficient, automatic processing, and thus suffer a subtle attentional deficit. Following mild TBI, performance levels equivalent to controls may only be achieved with an abnormal expenditure of cognitive effort. As a result of the neuropathologic consequences of injury, individuals who have sustained a mild TBI are less able to benefit from practice, experience difficulty coping with simultaneous performance of secondary task, and are susceptible to distressing subjective symptomatology.

Kardijalni biomarkeri u predviđanju operativnog rizika kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore Evaluacija rezultata u kardiohirurgiji podrazumeva praćenje ishoda operativnog lečenja u određenom vremenskom periodu. Najčešće je to interval od 30 dana od datuma intervencije. Najčešći kriterijumi za praćenje su stopa mortaliteta i morbiditeta, dužina boravka u jedinici intenzivnog lečenja, ukupna dužina hospitalizacije i troškovi lečenja. Stratifikacija rizika podrazumeva da se bolesnici mogu podeliti u grupe u zavisnosti od broja i važnosti preoperativno utvrđenih faktora rizika, odnosno da se pre operacije može predvideti ishod hirurške intervencije kod svakog od njih pojedinačno. U Evropi je, u periodu između 1995. i 1999. godine, na osnovu multicentrične studije u 8 evropskih zemalja i 128 kardiohirurških centara u kojima je operisano 19.030 odraslih bolesnika, kreiran EvroSKOR - EuroSCORE (European System for Cardiac Operative Risk Evaluation) model za stratifikaciju rizika u kardiohirurgiji. Međutim, neminovne promene i napredak u operativnom lečenju doveli su do toga da je neophodno ažurirati postojeći sistem stratifikacije. Tako je 2012. godine u rutinsku upotrebu uveden novi sistem Euroscore II. Na Klinici za kardiohirurgiju Instituta za kardiovaskularne bolesti Vojvodine (IKVBV), EuroSCORE model uveden je u rutinsku upotrebu od početka 2001. godine. Analizom rezultata, posle dvogodišnje primene, pokazalo se da je model bio precizan, odnosno da nije postojala značajna razlika između očekivanog (3,7%) i stvarnog mortaliteta (3,47%). U poslednjih nekoliko godina, kod bolesnika kojima sledi kardiohirurška intervencija, u smislu razmatranja njihove prediktivne vrednosti, sve više pažnje se poklanja kardijalnim biomarkerima. Najznačajniji biomarkeri u kardiovaskularnoj medicini su: Troponin, Kreatin kinaza MB izoenzim (CKMB), N-terminalni pro B-tip natriuretski peptid (NT-proBNP), C-reaktivni protein (CRP), Laktat dehidrogenaza (LDH), Mokraćna kiselina (Acidum uricum). Ciljevi ovog rada su bili da se kreira model za predviđanje preoperativnog rizika kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore na osnovu preoperativnih vrednosti određenih biomarkera i da se kreira novi model sa kombinacijom prethodnog modela i već postojećeg modela EuroSCORE II. Ispitana su 704 bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcione frakcije manje ili jednake 50%. Bolesnici su operisani na Institutu za kardiovaskularne bolesti Vojvodine, od 20. januara 2014. do 20. aprila 2016. Kod bolesnika su urađene tri vrste operacija: revaskularizacija miokarda-koronarna hirurgija, hirurgija stečenih srčanih mana - valvularna hirurgija i kombinovane operacije. Od biohemijskih analiza, 24 sata pre operacije, urađene su sledeće analize: troponin I, kreatin kinaza, kreatin kinaza MB izoenzim, masena kreatin kinaza, laktat dehidrogenaza, C-reaktivni protein, NT-proBNP i mokraćna kiselina. Praćen je postoperativni mortalitet, postoperativni infarkt miokarda i postoperativni cerebrovaskularni incident i njihova povezanost sa preoperativnim vrednostima nabrojanih biomarkera. U studiju su bili uključeni svi bolesnici sa stečenim bolestima srca, stariji od 18 godina, kod kojih je ejekciona frakcija leve komore bila manja ili jednaka 50% i kod kojih su izvršene sledeće vrste operacija: revaskularizacija miokarda - koronarna hirurgija, hirurgija stečenih srčanih mana - valvularna hirurgija i kombinovane operacije - koronarna i valvularna hirurgija. Rezultati su pokazali da je postoperativni mortalitet bio 3,13%, da je postoperativni infarkt miokarda imalo 7,95% a postoperativni cerebrovaskularni incident 9,23% od ukupnog broja ispitanika. 1. Povezanost vrednosti biomarkera sa postoperativnim infarktom miokarda kod bolesnika sa oslabljenom ejekcionom frakcijom leve komore: povišene preoperativne vrednosti troponina I su bile povezane sa postoperativnim infarktom miokarda. Povezanost preoperativnih vrednosti biomarkera sa postoperativnim cerebrovaskularnim incidentom kod bolesnika sa oslabljenom ejekcionom frakcijom leve komore: povišene preoperativne vrednosti troponina I i CRP-a su bile povezane sa postoperativnim cerebrovaskularnim incidentom. 2. Analiziran je uticaj preoperativnog nivoa svih biomarkera, pojedinačno, na značajne neželjene kardijalne i cerebrovaskularne događaje - Major Adverse Cardiac and Cerebrovascular Events (MACCE) kao ishod posle operacije na srcu, kod bolesnika sa oslabljenom ejekcionom frakcijom leve komore. Dobijeni su sledeći rezultati: Preoperativna vrednost nivoa troponina I veća od 0,01μg/L i MACCE bili su povezani. Povećane preoperativne vrednosti nivoa C-reaktivnog proteina (CRP) i postoperativni MACCE bili su povezani. Povećane preoperativne vrednosti nivoa laktat dehidrogenaze (LDH) i MACCE bili su povezani. Zaključci ove teze su: 1. Nezavisni prediktor postoperativnog infarkta miokarda i značajnih neželjenih kardijalnih i cerebrovaskularnih događaja, kod kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcionom frakcijom manjom ili jednakom 50%, jeste povišena preoperativna vrednost troponina I. 2.Vrednost preoperativnog troponina I je slab marker za predviđanje postoperativnog infarkta miokarda i značajnih neželjenih kardijalnih i cerebrovaskularnih događaja, kod kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcionom frakcijom manjom ili jednakom 50%. 3. Na pojavu postoperativnog cerebrovaskularnog incidenta, kod kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcionom frakcijom manjom ili jednakom 50%, ne utiče nijedna od ispitivanih varijabli. 4. Nezavisni prediktori postoperativnog mortaliteta kod kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcionom frakcijom manjom ili jednakom 50%, na osnovu kojih je moguće kreirati prediktivni Model su godine starosti i povišene preoperativne vrednosti NT-proBNP. 5. Kreirani Model je dobar marker za predikciju ishoda posle operacije na srcu, kod kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcionom frakcijom manjom ili jednakom 50%. 6. Povišena preoperativna vrednost NT- proBNP može da bude dobar marker u predikciji smrtnog ishoda posle operacije na srcu kod bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcionom frakcijom manjom ili jednakom 50%. 7. Model EuroSCORE II se pokazao kao slabiji marker za predikciju ishoda posle operacije na srcu kod kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcionom frakcijom manjom ili jednakom 50%. 8. Testiranjem kreiranog modela, podelom na manje rizične i više rizične bolesnike, u odnosu na visinu ejekcione frakcije leve komore, pokazalo se da je model dobar marker za predviđanje smrtnog ishoda posle operacije na srcu, u obe grupe.
Cardiac surgery operative risk assessment in patients with imapired systolic left ventricular function using cardial biomarkers Evaluation of results in cardiac surgery involves monitoring the outcomes of operative treatment in a given time period. Typically, this interval includes 30 days from the date of operation. The most common criteria used for monitoring are the rate of mortality and morbidity, length of stay in the intensive care unit, the total length of hospitalization and medical costs. Risk stratification means that patients can be divided into groups depending on the number and importance of preoperatively identified risk factors, and that the outcome of surgery for each of the patients can be predicted preoperatively. In Europe, in the period of 1995-1999 on the basis of a multi-center study in 8 European countries and 128 cardiac centers in which 19,030 adult patients were operated on, EuroSCORE (European System for Cardiac Operative Risk Evaluation) model for risk stratification in cardiac surgery was developed. However, the inevitable changes and progress in the surgical treatment rendered the EuroSCORE model obsolete warranting updated system. It was in 2012 when a new system EuroSCORE II was introduced into practice At the Clinic for Cardiac Surgery of the Institute of Cardiovascular Diseases, EuroSCORE model was introduced in routine clinical use since the beginning of 2001. By analyzing the results, two years after application, it was shown that the model was accurate, and that there was no significant difference between the expected (3.7%) and the actual mortality (3.47%) In recent years, in patients who are candidates for cardiac surgery, more attention is paid to cardiac biomarkers in terms of evaluating their predictive power. The most significant biomarkers in cardiovascular medicine are: Troponin, creatine kinase MB isoenzyme (CKMB), N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), Lactate dehydrogenase (LDH), and uric acid (Uric uricum). The objectives of this study were to create a model to predict preoperative risk for cardiac surgery patients with impaired systolic left ventricular function on the basis of preoperative levels of certain biomarkers and to create a new model with a combination of the previous model and already existing EuroSCORE II model. The study included 704 patients with impaired systolic left ventricular function, ejection fraction less than or equal to 50%. All patients underwent cardiac surgery at the Institute of Cardiovascular Diseases, from January 20th 2014 until 20th April 2016. Patients were submitted to three types of operations: revascularization - coronary surgery, surgery of acquired heart defects - valvular surgery and combined operations. Following biochemical analyses were performed 24 hours prior to surgery: troponin I, creatine kinase, creatine kinase MB isoenzyme, mass creatine kinase, lactate dehydrogenase, C-reactive protein, NT-proBNP and uric acid. Postoperative mortality, postoperative onset of myocardial infarction and occurence of cerebrovascular accident and their correlation with preoperative values of listed biomarkers were registered. The study included all patients with acquired heart disease, older than 18 years, with the left ventricular ejection fraction less than or equal to 50% who were submitted to the following types of operations: revascularization - coronary surgery, surgery of acquired heart diseases - valvular surgery and combined operations - coronary and valvular surgery. The results showed that the postoperative mortality was 3.13%, new onset of postoperative myocardial infarction was detected in 7.95% of the patients and postoperative cerebrovascular accident developed in 9.23% of patients. Correlation of preoperative biomarkers values with postoperative myocardial infarction in patients with impaired left ventricular ejection fraction - elevated preoperative troponin I were associated with postoperative myocardial infarction. Correlation of preoperative biomarkers values with postoperative cerebrovascular incident occurence in patients with impaired left ventricular ejection fraction - elevated preoperative troponin I and CRP were associated with postoperative cerebrovascular incident. The influence of preoperative levels of all biomarkers, separetly, on the rate of significant adverse cardiac and cerebrovascular events - Major Adverse Cardiac and Cerebrovascular Events (MACCE) as the heart surgery outcome, in patients with impaired left ventricular ejection fraction. The following results were obtained: Increased preoperative levels of C-reactive protein (CRP) and postoperative MACCE were related. Increased preoperative levels of lactate dehydrogenase (LDH) and MACCE were related. The conclusions of this thesis are: 1. Independent predictor of postoperative myocardial infarction onset and significant adverse cardiac and cerebrovascular events in cardiac surgery patients with impaired systolic left ventricular function (ejection fraction less than or equal to 50%) is elevated preoperative value of troponin I. 2. Preoperative Troponin I value was poor marker for predicting postoperative myocardial infarction and significant adverse cardiac and cerebrovascular events in cardiac surgery patients with impaired systolic left ventricular function (ejection fraction less than or equal to 50%). 3. None of the studied variables showed influence on the postoperative cerebrovascular accident occurence, in cardiac surgery patients with impaired systolic left ventricular function (ejection fraction less than or equal to 50%). 4. Independent predictors of postoperative mortality in cardiac surgery patients with impaired systolic left ventricular function (ejection fraction less than or equal to 50%), that could be used to create a predictive model are: age and elevated preoperative value of NT-proBNP. 5. Developed model showed satisfactory results for predicting outcome after heart surgery in cardiac surgery patients with impaired systolic left ventricular function (ejection fraction less than or equal to 50%). 6. Elevated preoperative value of NT-proBNP may be a good marker for mortality prediction after the cardiac surgery in patients with impaired systolic left ventricular function (ejection fraction less than or equal to 50%). 7. EuroSCORE II model showed poor performance when predicting outcomes after cardiac surgery in patients with impaired systolic left ventricular function (ejection fraction less than or equal to 50%). 8. Validation of the newly-created model, considering low and medium risk patients, based on the value of left ventricular ejection fraction, showed that the model is a good marker for the mortality prediction in both groups.

While the cognitive disturbances that frequently follow severe TBI are relatively well understood, the ways in which these affect the psychosocial functioning of people with TBI are yet to be determined and have thus received little attention in treatment research. Growing evidence indicates that that a significant proportion of individuals with TBI demonstrate deficits in the perception of affective information from the face, voice, bodily movement and posture. As accurate evaluation of emotion in others is critical for the successful negotiation of social interactions, effective treatments are necessary. Until recently, however, there have been no rehabilitation efforts in this area with TBI groups. The present research aims to redress this absence. The literature on emotion perception deficits in TBI is examined, and a theoretical rationale for intervention is presented. Several lines of research are reviewed which suggest that rehabilitation targeting such deficits is tenable. These include research on emotion perception remediation with other cognitively impaired populations, findings from cognitive neuroscience suggesting the potential for neuronal restoration after brain damage, and the successful applications of remediation techniques, in particular errorless learning and self-instruction, for treating other cognitive deficits in a range of neurological disorders and TBI. Discussion of this research is followed by a description of two randomised controlled trials aimed at improving emotion perception in individuals with TBI. The findings are discussed with reference to useful theoretical models of rehabilitation, learning and emotion perception. Suggestions for future directions of research are outlined together with relevant design issues.

碩士
國立成功大學
藥理學研究所
100
The synthetic glucocorticoid dexamethasone (DEX) is frequently used to prevent or lessen the morbidity of chronic lung disease (CLD) by facilitating surfactant synthesis in pulmonary alveolus in premature infants. Typically, high doses of DEX are administered for several weeks, notably during a period of life that is critical for the development of the infant brain. Therefore, growing concern has arisen for the long-term safety of this therapy on the brain development of the child. Although DEX treatment is a powerful way for the prevention and management of CLD, but preterm infants are still under the risk of encountering hypoxic-ischemic stress. Based on our cDNA microarray data, we have found that DEX administration during neonatal development may alter the expression pattern of several genes associated with neurotrophic and neuroprotective functions. Thus, the objective is to evaluate the impact of neonatal DEX treatment on hypoxic-ischemic brain damage and characterize the possible underlying mechanisms. Using a schedule of tapering doses of DEX similar to that used in premature infants, we demonstrate that neonatal DEX treatment exacerbates hypoxic-ischemic brain damage in the immature rats through a glucocorticoid receptor-mediated mechanism. The influence of neonatal DEX treatment on hypoxic-ischemic brain damage was correlated with a decrease in glutamate reuptake. Furthermore, neonatal DEX treatment decreased the expression of GLT-1 and GLAST mRNA and protein in the cerebral cortex. The expression level of the NMDA receptor subunits NR2A and NR2B was not significantly altered by neonatal DEX treatment. By using promoter luciferase assay, we identified that the decrease of GLT-1 transcriptional activity after DEX treatment was associated to the GLT-1 promoter region form -956 to -306. Pretreatment with ceftriaxone effectively increased the expression of GLT-1 protein and rescued exacerbated hypoxic-ischemic brain damage by neonatal DEX treatment. In conclusion, these results suggest that neonatal DEX treatment before an episode of hypoxic-ischemia actually enhances the brain injury through an enhanced glutamate-mediated excitotoxicity.

Traumatic brain injury (TBI) is the signature injury of the ongoing military conflicts in the Middle East and Afghanistan, largely due to the use of improvised explosive devices (IEDs), which have affected soldiers and civilians alike. Blast-induced TBI (bTBI) biomechanics are complex and multiphasic. While research has clearly demonstrated the negative effects of penetrative (secondary blast) and inertia-driven (tertiary blast) injury, the effect of shock wave loading (primary blast) on the brain remains unclear. Combined primary-tertiary blast exposure in vivo has been reported previously to alter brain function, specifically hippocampal function; however, it is extremely difficult to deliver primary blast exposure in isolation with an in vivo injury model. The research presented in this thesis utilized a custom-designed in vitro blast injury model to deliver military-relevant shock wave exposures, in isolation, to organotypic hippocampal slice cultures (OHSCs). To contextualize blast-induced pathobiology with previous TBI studies, the first goal of this thesis was to experimentally characterize the deformation profile induced in OHSCs with our blast injury model. Using stereoscopic, high-speed cameras and digital image correlation to calculate strain, we found that our blast model induced low strain magnitudes (<9%) but at high strain rates (25-86s-1), which aligned closely with associated computational simulations of our model. The second aim was to determine if primary blast was capable of altering hippocampal electrophysiological function. We exposed OHSCs to a range of shock intensities and found, using a micro-electrode array system, that long-term potentiation (LTP), a measure of synaptic plasticity, was very sensitive to primary blast exposure; a threshold for disruption of LTP was found between 9 and 39 kPa•ms impulse. Alternative measures of basal electrophysiology were less sensitive than LTP. Blast exposure significantly reduced LTP between 1 and 24 hours post-injury, and this deficit persisted through 6 days post-injury. Depending on shock intensity, LTP spontaneously recovered 10 days post-injury. The third aim was to explore the cellular mechanisms for blast-induced LTP deficits. Using a chemical LTP induction protocol, blast exposure altered key proteins necessary for the induction of LTP by 24 hours post-injury including, postsynaptic density protein-95 (PSD-95), a major scaffolding protein that organizes the postsynaptic density (PSD), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptor 1 (AMPA-GluR1), and stargazin, an auxiliary GluR1 protein that binds AMPA-GluR1 to PSD-95. Modulation of the cyclic adenosine monophosphate (cAMP) pathway reversed the observed effects of blast on LTP. We theorized that blast-induced disruption of PSD-95 prevented translocation, and subsequent phosphorylation, of GluR1-containing AMPARs to the postsynaptic membrane, which, in turn, prevented potentiation. The final aim was to investigate the efficacy of phosphodiesterase-4 (PDE4) inhibitors, which block degradation of cAMP, as a therapeutic strategy. When delivered immediately following primary blast injury, multiple PDE4 inhibitors proved efficacious in restoring LTP measured 24 hours post-injury. Roflumilast, a Food and Drug Administration-approved PDE4 inhibitor, was effective when delivered at a clinically relevant concentration (1nM) and at a delayed time point (up to 6 hours). Roflumilast reversed blast-induced changes in expression/phosphorylation of the key LTP protein targets. We hypothesized that maintenance of PSD-95 drove the observed therapeutic effect. Greater work is necessary to determine how blast exposure degrades PSD-95 and how roflumilast prevented these detrimental effects. This thesis has shown that primary blast exposure can negatively alter neurological function, as well as protein expression and phosphorylation. These studies expand the understanding of primary blast injury mechanisms, provide computational models with important tissue-level tolerance criteria, inform protective equipment design, inform clinical care guidelines for bTBI, and present a promising therapeutic candidate for further clinical investigation.

初級運動皮質直接負責運動控制。大量關於帕金森式癥(PD)的有效治療手段的研究已經證明，初級運動皮質在病理情況下的功能改變，直接與患者運動障礙相關。本論文的研究重點在於探索初級運動皮質在深部腦刺激治療帕金森氏症的運動障礙的過程中發揮的作用及其與運動學習功能障礙的聯繫。
丘腦底核深部腦刺激(STN-DBS) 已被廣泛應用於治療帕金森式症。雖然該項治療手段能顯著地改善患者的運動功能障礙，但其確切的治療機制仍未明確。理論上來說，丘腦底核深部腦刺激能夠直接啟動丘腦底核內部和其周圍很大範圍的神經組織，包括丘腦底核內部本身的神經元胞體，以及與其相連接的輸入輸出核團的神經元軸突。在丘腦底核眾多輸入核團之中，一個重要的神經輸入來自於初級運動皮質(MI)第五層的離皮質神經元(CxFn)，電刺激引起的逆行皮質啟動作用被提出，用於解釋丘腦底核深部腦刺激的治療機制。
為了研究逆行皮質啟動效應究竟如何在丘腦底核深部腦刺激的過程之中帶來治療效果，我們採用多通道神經電生理信號記錄系統在自由活動的單側帕金森大鼠的初級運動皮質進行鋒電位元和局部場電位元信號的記錄。實驗結果證明，當對丘腦底核進行高頻電刺激，在運動皮質第五層的離皮質神經元能成功記錄到保持固定延時的逆行鋒電位。由於增加刺激頻率會引起逆行鋒電位被成功記錄到的百分比下降，因此當深部腦刺激的頻率選擇在125Hz時，逆行鋒電位的放電頻率達到最高，而此刺激頻率正好與行為學實驗中帶來最佳治療效果的刺激頻率一致。於此同時，逆行皮質啟動作用還伴隨著初級運動皮質離皮質神經元的自發放電頻率增加、同步性爆發式放電減少等電生理信號特點。場電位分析的結果進一步表明，丘腦底核深部腦刺激減弱了病理情況下出現的beta波頻譜能量增高以及鋒電位-場電位相干性增強。更重要的是，我們發現只有逆行鋒電位被成功誘發，離皮質神經元的發放電機率才能被調節。這點有力地表明由電刺激隨機誘發的逆行鋒電位傳導至初級運動皮質，直接幹預並抑制了離皮質神經元在病理情況下的同步性爆發式放電活動，從而緩解了帕金森氏症的運動障礙。
另外，初級運動皮質並不僅僅是一個靜態的運動控制中樞，更為重要的功能在於它參與著與運動學習和運動記憶相關的動態資訊編碼。帕金森氏症患者普遍存在皮質可塑性減弱以及運動技能學習障礙。由於初級運動皮質分層結構的存在，層內神經元之間的突觸連接為神經可塑性提供了很好的結構基礎。因此，我們在初級運動皮質誘發在體長時程增強(LTP)，旨在研究與運動技能學習相關的皮質神經可塑性的動態變化過程，以及探索中腦多巴胺能投射系統對皮質神經可塑性的影響。
一方面，我們採用間斷性高頻刺激誘發在體長時程增強，證實六羥多巴損毀後皮質的長時程增強水準顯著下降。另一方面，我們設計前肢抓食的行為學範式用來評價動物在運動技能學習的不同階段皮質可塑性發生的動態變化。實驗結果表明，直接損毀皮質的多巴胺能輸入，模型組大鼠與假實驗組大鼠的行為表現在初期的技能獲取階段並無明顯差異，而只在後期的技能鞏固階段模型組大鼠表現出技能鞏固障礙。更為有趣的是，兩組行為學變化趨勢與各自的在體長時程增強的變化趨勢有很高的一致性。本研究表明多巴胺對初級運動皮質的支配在運動記憶的鞏固過程中起著關鍵作用。在帕金森氏症的病理情況下，多巴胺耗竭將影響皮質的突觸可塑性，從而造成帕金森患者在運動技能的鞏固階段表現出障礙。
The primary motor cortex (MI) controls movement directly, but is an under-investigated brain region in the pathogenesis and treatment of Parkinsonian motor disability, when compared with the basal ganglia circuitry. In this study, the roles of MI in underlying the therapeutic action of surgical deep brain stimulation and motor learning impairment were investigated.
Deep brain stimulation of the subthalamic nucleus (STN-DBS) is now a recognized therapeutic option for Parkinson’s disease (PD). Although this surgical strategy provides behavioral benefits remarkably, its exact mechanism is still a matter of controversy. In principle, STN-DBS can directly activate a wide range of neuronal elements within the STN and surrounding areas. As the corticofugal neurons (CxFn) in the layer V motor cortex provide a major input to the STN, we hypothesized that the stimulation evoked antidromic cortical activation is involved in the therapeutic mechanism of STN-DBS. In the first series of experiments, we performed simultaneous recordings of multi-unit neuronal activities and local field potentials (LFPs) in MI in freely moving hemi-parkinsonian rats. By identifying stimulation evoked antidromic spike, which occurred at a fixed, short latency, CxFn located in the layer V MI were identified. Increasing stimulation frequency also increased failure rate of activation, resulting in a peak frequency of stochastic antidromic spikes at 125Hz STN-DBS, which was correlated with the optimal therapeutic efficacy observed in behavioral tests. Meanwhile, this antidromic effect was accompanied by the rectification of pathological neuronal activities including increased spontaneous firing rate, reduced burst discharge and synchrony among the CxFn. Field potential analysis revealed that STN-DBS alleviated the dominance of pathological beta band oscillation and spike-field coherence in the MI. More importantly, it was found that the firing probability of CxFn could only be modified following the occurrence of antidromic spikes, suggesting that direct interference of stochastic antidromic spikes with pathological neuronal activities underlies the beneficial effect of STN-DBS.
The MI is not simply a static motor control structure. It also contains a dynamic substrate that participates in motor learning or stores motor memory. In PD patients, loss of cortical plasticity and impaired motor learning is a common feature. As the intrinsic horizontal neuronal connections in MI are a strong candidate of cellular correlate for activity-dependent plasticity, in the second series of experiments, we developed in vivo long-term potentiation (LTP) technique in the MI to investigate the dynamics of cortical plasticity during motor skill learning and the role of the innervation by mesocortical dopamine input. Local depletion of dopamine in the primary motor cortex resulted in reduced performance in the forelimb reaching for food learning task. Although the performance of the PD rats in the initial learning phase was comparable to that of the sham-operated group, as training continued, these animals exhibited deficit in consolidating the motor skill. These deficits closely paralleled the impairment in training-enhanced synaptic connections in layer V neurons, and the in vivo LTP of evoked field excitatory postsynaptic potentials induced by intermittent high frequency stimulation. In addition, progressive recruitment of task-specific neurons was suppressed. Our study therefore revealed that dopamine depletion confined to the MI could lead to impairment in cortical synaptic plasticity which may preferentially affect the consolidation, but not the acquisition, of motor skills. These findings shed light on the cellular mechanisms of motor skill learning and could explain the decreased ability of PD patients in learning new motor skills.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Li, Qian.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2013.
Includes bibliographical references (leaves 168-190).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstracts also in Chinese.
CHAPTER 1 --- p.1
General Introduction --- p.1
Chapter 1.1 --- Anatomical organization of the basal ganglia --- p.1
Chapter 1.1.1 --- Overview of the basal ganglia circuit --- p.1
Chapter 1.1.2 --- Cortico-basal ganglia-cortical circuit --- p.1
Chapter 1.1.2.1 --- Direct and indirect pathway --- p.2
Chapter 1.1.2.2 --- Hyperdirect pathway --- p.2
Chapter 1.1.2.3 --- The midbrain dopamine system --- p.2
Chapter 1.2 --- Striatum --- p.3
Chapter 1.2.1 --- Cell types in the striatum. --- p.3
Chapter 1.2.2 --- The Cortico-striatal system --- p.4
Chapter 1.3 --- Subthalamic Nucleus --- p.5
Chapter 1.3.1 --- Neuronal property of the STN. --- p.5
Chapter 1.3.2 --- Electrophysiological property of the STN --- p.6
Chapter 1.3.3 --- Cortico-subthalamic system --- p.7
Chapter 1.3.4 --- Functional significance of the cortico-subthalamic and corticostriatal system. --- p.8
Chapter 1.4 --- Parkinson’s disease --- p.9
Chapter 1.4.1 --- Pathogenesis of PD --- p.9
Chapter 1.4.2 --- Genetic risk factors of PD --- p.10
Chapter 1.4.3 --- Progressive motor symptoms of PD --- p.11
Chapter 1.4.4 --- Non-motor symptoms of PD --- p.13
Chapter 1.4.5 --- Pathological neuronal rhythms in the basal ganglia of PD. --- p.16
Chapter 1.5 --- Experimental studies of PD. --- p.18
Chapter 1.5.1 --- Animal modeling of PD. --- p.18
Chapter 1.5.2 --- Motor deficits evaluation in rodent models of PD --- p.21
Chapter 1.5.3 --- Non-motor symptoms evaluation in experimental models of PD --- p.24
Chapter 1.6 --- Deep Brain Stimulation --- p.27
Chapter 1.6.1 --- DBS in alleviating Parkinsonian motor symptoms --- p.28
Chapter 1.6.2 --- DBS in alleviating Parkinsonian non-motor symptoms --- p.29
Chapter 1.6.3 --- Investigation of the STN-DBS mechanism. --- p.31
Chapter 1.6.3.1 --- Local inhibitory effect within the STN --- p.32
Chapter 1.6.3.2 --- Excitatory effect at output nuclei --- p.33
Chapter 1.6.3.3 --- The de-coupling of soma and axons at system level --- p.34
Chapter 1.6.3.4 --- Effects of DBS on abnormal rate or pattern --- p.35
Chapter 1.6.3.5 --- Antidromic propagation of DBS effect towards cortex --- p.37
Chapter 1.7 --- Objective --- p.38
Chapter 1.8 --- Figures --- p.41
CHAPTER 2 --- p.47
General Methods --- p.47
Chapter 2.1 --- Animals --- p.47
Chapter 2.2 --- Stereotaxic surgery --- p.47
Chapter 2.2.1 --- Preoperative preparation --- p.47
Chapter 2.2.2 --- Anesthesia and craniotomy --- p.48
Chapter 2.2.3 --- Induction of hemi-Parkinsonian rat model --- p.48
Chapter 2.2.4 --- Electrode implantation techniques. --- p.49
Chapter 2.3 --- Behavioral assessment. --- p.50
Chapter 2.3.1 --- Apomorphine-induced contralateral rotation. --- p.50
Chapter 2.3.2 --- Open field test --- p.50
Chapter 2.4 --- STN-DBS protocol --- p.50
Chapter 2.5 --- Electrophysiological data acquisition --- p.51
Chapter 2.6 --- Data analysis --- p.52
Chapter 2.6.1 --- Statistical analysis of behavioral data --- p.52
Chapter 2.6.2 --- Electrophysiological data --- p.52
Chapter 2.6.2.1 --- Stimulation artifact removal --- p.52
Chapter 2.6.2.2 --- Multi-unit spike sorting --- p.53
Chapter 2.6.2.3 --- Electrophysiological identification of pyramidal neuron and interneuron. --- p.54
Chapter 2.6.2.4 --- Identification of antidromic cortical activation --- p.54
Chapter 2.6.2.5 --- Discharge pattern classification --- p.54
Chapter 2.6.2.6 --- Synchrony level evaluation --- p.55
Chapter 2.6.2.7 --- Oscillatory rhythm characterization --- p.55
Chapter 2.6.2.8 --- Coherence Level Measurement --- p.56
Chapter 2.7 --- Histological verification --- p.56
Chapter 2.8 --- Figures --- p.58
CHAPTER 3 --- p.60
Alleviation of Parkinsonian Motor Symptoms during Deep Brain Stimulation in Hemi-Parkinsonian Rats --- p.60
Chapter 3.1 --- Introduction --- p.60
Chapter 3.2 --- Materials & Methods --- p.61
Chapter 3.2.1 --- Animals --- p.61
Chapter 3.2.2 --- Chemicals --- p.61
Chapter 3.2.3 --- Equipment --- p.61
Chapter 3.3 --- Results --- p.62
Chapter 3.3.1 --- Time course of the Apomorphine induced rotation behavior --- p.62
Chapter 3.3.2 --- Dose-dependence of the Apomorphine induced rotation --- p.62
Chapter 3.3.3 --- Acute behavioral response to STN-DBS. --- p.63
Chapter 3.3.4 --- The dependence of STN-DBS effect on stimulation paradigm. --- p.64
Chapter 3.3.5 --- Acute effects of STN-DBS on APO induced rotation. --- p.64
Chapter 3.3.6 --- Long-term effects of STN-DBS on APO induced rotation --- p.64
Chapter 3.3.7 --- Histological confirmation of the stimulation electrodes localization --- p.65
Chapter 3.3.8 --- Loss of DA neurons in the SNc --- p.65
Chapter 3.3.9 --- Reductions of the DA axon terminals in the striatum --- p.65
Chapter 3.3.10 --- Chronic STN-DBS failed to rescue nigrostsriatal and striatal DA --- p.66
Chapter 3.4 --- Discussion --- p.66
Chapter 3.4.1 --- Neurotoxic mechanism of 6-OHDA --- p.66
Chapter 3.4.2 --- Time course of dopamine degeneration induced by 6-OHDA --- p.66
Chapter 3.4.3 --- Failure in observing worsened motor symptoms during low frequency STN-DBS. --- p.67
Chapter 3.4.4 --- Experimental DBS based on rat model: does it mimic human case? --- p.67
Chapter 3.4.5 --- Technical issues about STN-DBS --- p.69
Chapter 3.5 --- Figures --- p.72
CHAPTER 4 --- p.82
Direct involvement of the Corticofugal Neurons in Motor Cortex during Therapeutic Deep Brain Stimulation --- p.82
Chapter 4.1 --- Introduction --- p.82
Chapter 4.2 --- Materials --- p.83
Chapter 4.2.1 --- Animals --- p.83
Chapter 4.2.2 --- Chemicals --- p.83
Chapter 4.2.3 --- Equipment --- p.83
Chapter 4.3 --- Results --- p.84
Chapter 4.3.1 --- Identification of CxFn based on antidromic effect --- p.84
Chapter 4.3.2 --- Antidromic spikes frequency correlates with therapeutic effect of STN-DBS. --- p.84
Chapter 4.3.3 --- Pathological changes of neuronal firing rate in MI --- p.85
Chapter 4.3.4 --- Only high frequency STN-DBS normalizes neuronal firing rate in MI --- p.86
Chapter 4.3.5 --- Pathological changes of neuronal discharge pattern in MI --- p.88
Chapter 4.3.6 --- Pathological synchrony of MI neuronal population, especially during burst discharge --- p.89
Chapter 4.3.7 --- High frequency STN-DBS successfully suppresses synchronized burst discharge in MI --- p.89
Chapter 4.3.8 --- Pathological β-band oscillatory activity in MI-LFPs induced by 6-OHDA lesion --- p.90
Chapter 4.3.9 --- High frequency STN-DBS alleviates the β-band oscillation in MI-LFPs --- p.90
Chapter 4.3.10 --- Synchronized bursting discharge correlates with oscillatory activity --- p.91
Chapter 4.3.11 --- Pathological increased spike-LFP coherence level induced by 6-OHDA lesion --- p.92
Chapter 4.3.12 --- High frequency STN-DBS modulated the spike-LFP coherence properties --- p.92
Chapter 4.3.13 --- Antidromic spikes directly modulate the firing probability of CxFn --- p.93
Chapter 4.3.14 --- Antidromic spikes modulate the firing probability of INs and non-CxFn nearby. --- p.94
Chapter 4.3.15 --- The efficiency of antidromic cortical modulation depends on DBS frequency --- p.94
Chapter 4.3.16 --- Orthodromic vs. antidromic effect: which one is responsible for the beneficial effect of DBS? --- p.95
Chapter 4.3.17 --- Histology --- p.96
Chapter 4.4 --- Discussion --- p.96
Chapter 4.4.1 --- Origin of pathogenic rhythm in basal ganglia circuit --- p.96
Chapter 4.4.2 --- Suppression of oscillatory synchronization equals to therapeutic effects of DBS? --- p.97
Chapter 4.4.3 --- Beneficial effect of DBS corresponds to the topographic distribution of cortico-subthalamic projection. --- p.98
Chapter 4.4.4 --- What is the reason for a stochastic pattern of antidromic activation effect? --- p.99
Chapter 4.4.5 --- Desynchronization of pathological oscillatory rhythm by antidromic activation --- p.100
Chapter 4.4.6 --- Antidromic vs. orthodromic: which is the cause of the beneficial effects of DBS? --- p.101
Chapter 4.4.7 --- Wide propagation of antidromic effect by cortical horizontal circuits --- p.102
Chapter 4.4.8 --- Significance of antidromic cortical activation in during STN-DBS --- p.102
Chapter 4.4.9 --- Implication of antidromic activation effect on pathogenesis and treatment of PD --- p.104
Chapter 4.5 --- Figures --- p.105
CHAPTER 5 --- p.132
Impaired Synaptic Plasticity in the Primary Motor Cortex after Dopamine Depletion: Potential Role in Motor Memory Consolidation --- p.132
Chapter 5.1 --- Introduction --- p.132
Chapter 5.1.1 --- Characteristics of motor learning --- p.132
Chapter 5.1.2 --- Motor learning related cortical plasticity. --- p.133
Chapter 5.1.3 --- Dopaminergic signals in the primary motor cortex --- p.134
Chapter 5.1.4 --- Impaired cortical plasticity in PD --- p.135
Chapter 5.1.5 --- Objective --- p.136
Chapter 5.2 --- Materials --- p.136
Chapter 5.2.1 --- Animals --- p.136
Chapter 5.2.2 --- Chemicals --- p.136
Chapter 5.2.3 --- Equipment --- p.136
Chapter 5.3 --- Methods --- p.136
Chapter 5.3.1 --- Functional mapping of the forelimb territory in MI --- p.136
Chapter 5.3.2 --- Stereotaxic surgery --- p.137
Chapter 5.3.3 --- Forelimb-reaching Task. --- p.137
Chapter 5.3.4 --- In-vivo LTP Induction. --- p.138
Chapter 5.4 --- Results --- p.139
Chapter 5.4.1 --- Functional mapping of rat forelimb territory. --- p.139
Chapter 5.4.2 --- Morphologies of evoked field potential response --- p.139
Chapter 5.4.3 --- LTP of the early, monosynaptic plasticity within horizontal layer V MI --- p.140
Chapter 5.4.4 --- LTP of the late, polysynaptic plasticity within horizontal layer V MI --- p.140
Chapter 5.4.5 --- Impaired synaptic plasticity in MI after dopamine depletion --- p.140
Chapter 5.4.6 --- Learning curve of forelimb-reaching task --- p.140
Chapter 5.4.7 --- Physiologically enhanced cortical plasticity during motor learning --- p.141
Chapter 5.4.8 --- Dynamic modulation of cortical neuronal activities during motor skill learning. --- p.142
Chapter 5.4.9 --- Statistical analysis of ‘task related’ neuron’s modulation pattern. --- p.143
Chapter 5.4.10 --- Loss of dopamine modulation in the MI --- p.144
Chapter 5.5 --- Discussion --- p.144
Chapter 5.5.1 --- Distinguishing between monosynaptic and polysynaptic transmission --- p.144
Chapter 5.5.2 --- Artificially vs physiologically induced cortical plasticity. --- p.145
Chapter 5.5.3 --- Cortical synaptic plasticity interprets motor learning dynamics --- p.146
Chapter 5.5.4 --- Balance between neuronal recruitment and withdrawal in the consolidation stage --- p.147
Chapter 5.5.5 --- Dopamine’s involvement in mediating the cortical synaptic plasticity. --- p.148
Chapter 5.6 --- Figures --- p.150
Conclusion --- p.162
Abbreviations --- p.165
References --- p.168

The single subject alternating treatment design experiment reported here compared the effectiveness of pencil-and-paper versus computerized communication treatment for neurologically impaired adults. Five stroke patients receiving outpatient speech/language treatment (ages 51-72) served as subjects. One subject completed the experiment as designed and clearly supported the hypothesis that a higher number of correct responses would be produced using the computer generated exercises than the pencil-and-paper version. Two subjects were unable to demonstrate improvement using the experimental treatment program and the other two subjects were unable to master keyboarding skills necessary to use the computer effectively. However, four out of five subjects preferred using the computer even though it did not result in improved performance. Details of specific subjects' performance, and benefits and cautions regarding computer use are discussed. Results suggest that adequate receptive language skills favor effective computer use while impulsivity and visual spatial deficits may be expected to interfere. Careful matching of treatment task to the individual is important; if the task is too easy or too difficult potential benefit of computer use may be masked. The study also supports the finding that computer use is a highly motivating treatment technique for some patients and may be of benefit even if improved task performance does not result. Suggestions for further research include comparison of computerized versus non-computerized treatment for a greater variety of tasks, careful task analysis of currently available software, examination of techniques for training the mechanics of computer use, examination of specific subject characteristics which correlate with successful use of the computer, and determination of which aspect of computer use, specific feedback or improved motivation, is responsible for improved performance.
Graduation date: 1992