EEG, EMG, and single cell activity were examined under states of animal hypnosis, sleep, and wakefulness. Rabbits and chickens were repetitively hypnotized to determine whether animal hypnosis was caused by a fear reaction. Differential susceptibility of chickens and rabbits to animal hypnosis suggests that more than a "paralysis of terror" is involved in causing this state. There was a difference in theta frequency in records from moving and still animals, and a 13-18 Hz component appeared on many records during synchronized and desynchronized sleep. A large number of cells fired with respect to certain EEG conditions rather than to a behavioural state. EEG and single cell activity obtained during early hypnosis were very similar to those appearing in an animal that was sitting alert. / Thesis / Doctor of Philosophy (PhD)

Due to the presumed associations of dopamine (DA) receptor supersensitivity phenomena in both long-term neuroleptic-treated tardive dyskinetic rats and neonatal 6-hydroxydopamine (n6-OHDA)-lesioned rats, we studied the influence of haloperidol on n6-OHDA-lesioned rats. At 3 days after birth rats received 6-OHDA-HBr (200 $\mu$g, bilateral intracerebroventricularly; desipramine pretreatment, 20 mg/kg, 1h) or vehicle. Two months later haloperidol (1.5/kg/day $\times$ 2 days/week for 4 weeks, then 1.5 mg/kg/day, every day for 10 months) was added to the drinking water. Spontaneous oral activity of intact and n6-OHDA-lesioned rats receiving haloperidol was reached and maintained at significantly higher levels after 15 weeks of haloperidol treatment. Haloperidol treatment produced greater oral activity in n6-OHDA-lesioned rats as compared to intact rats. At 11 months there were 35.8 $\pm$ 4.9 vs. 18.4 $\pm$ 2.1 oral movements in lesioned vs. intact rats receiving haloperidol. This high level of spontaneous oral activity was not attenuated by scopolamine and persisted in the lesioned rats for at least 8 months after haloperidol withdrawal. Reverse transcription polymerase chain reaction (RT-PCR) analysis of alternatively-spliced isoforms of DA D$\sb2$ (D$\sb{\rm 2S}$ and D$\sb{\rm 2L}$) receptors showed that D$\sb{\rm 2L}$ receptor mRNA levels of intact and n6-OHDA-lesioned rats receiving haloperidol were significantly elevated after 11 months of treatment and returned to normal level 8 months after haloperidol withdrawal. Similarly, the B$\sb{\rm max}$ for $\rm\lbrack\sp3 H\rbrack$raclopride binding to striatal homogenates was significantly increased in intact and nG-OHDA lesioned rats receiving chronic haloperidol. The B$\sb{\rm max}$ was at the control level after 8 months of haloperidol cessation. D$\sb{\rm 2L}$ and 5-HT$\sb{\rm 2C}$ receptor mRNA levels were not altered by chronic haloperidol treatment. The effects of assorted receptor-specific drugs on oral activity were tested in our rats to study possible mechanisms underlying the regulation of oral activity. The findings of this study demonstrate that alterations at mRNA and receptor levels of DA D$\sb2$ receptors are not critical for maintaining persisting enhanced oral dyskinesias after long-term haloperidol treatment. The long-lasting stable high frequency of oral dyskinesias after haloperidol withdrawal in these rats provides a means for testing agents that have the potential to attenuate dyskinetic oral activity.

Repetitive stimulation of motor nerves causes an increase in the number of packets of transmitter ("quanta") that can be released in the ensuing period. This represents a type of conditioning, in which synaptic transmission may be enhanced by prior activity. Despite many studies of this phenomenon, there have been no investigations of the quantal mechanisms underlying these events, due to the rapid changes in transmitter output and the short time periods involved. To examine this problem, a method was developed in which estimates of the quantal release parameters could be obtained over very brief periods (3 s). Conventional microelectrode techniques were used to record miniature endplate potentials (MEPPs) from isolated frog (Rana pipiens) cutaneous pectoris muscles, before and after repetitive (40 sec at 80 Hz) nerve stimulation. Estimates were obtained of m (number of quanta released), n (number of functional release sites), p (mean probability of release) and var$\rm\sb{s}$p (spatial variance in p) using a method that employs counts of MEPPs per unit time. Fluctuations in the estimates were reduced using a moving bin technique (bin size = 3 s, $\Delta$bin = 1 s). Muscle contraction was prevented using low Ca$\sp{2+},$ high Mg$\sp{2+}$ Ringer or normal Ringer to which $\mu$-conotoxin GIIIA was added. These studies showed that: (1) the post-stimulation increase in transmitter release was dependent on stimulation frequency and not on the total number of stimulus impulses. When the total number of pulses was kept constant, the high frequency pattern produced a higher level of transmitter release than did the lower frequency patterns; (2) augmentation and potentiation were present in both low Ca$\sp{2+},$ high Mg$\sp{2+}$ and normal Ringer solutions, but potentiation, m, n, p and var$\rm\sb{s}$p were greater in normal Ringer solution than in low Ca$\sp{2+},$ high Mg$\sp{2+}$ solution. In low Ca$\sp{2+},$ high Mg$\sp{2+}$ solution, there was a larger decrease in n compared to p; (3) hypertonicity (addition of 100 mM sucrose) produced a marked increase in both basal and stimulation-induced values of m, n, and p. By contrast, there was a marked increase in the stimulation-induced but not the basal values of var$\rm\sb{s}$p; (4) hypertonicity produced a decrease in augmentation but had no effect on potentiation; (5) augmentation and potentiation appeared to involve mitochondrial uptake and efflux of cytoplasmic Ca$\sp{2+}.$ Tetraphenylphosphonium (which blocks mitochondrial Ca$\sp{2+}$ efflux and uptake) decreased augmentation and potentiation in low Ca$\sp{2+},$ high Mg$\sp{2+}$ solutions but increased potentiation in the same solution made hypertonic with 100 mM sucrose; (6) the overall findings suggest that this new method may be useful for investigating the subcellular dynamics of transmitter release following nerve stimulation.

Typescript (photocopy). / Digitized by Kansas Correctional Industries

Background: 'Neuromarketing' is a term that has often been used in the media in recent years. These public discussions have generally centered around potential ethical aspects and the public fear of negative consequences for society in general, and consumers in particular. However, positive contributions to the scientific discourse from developing a biological model that tries to explain context-situated human behavior such as consumption have often been neglected. We argue for a differentiated terminology, naming commercial applications of neuroscientific methods 'neuromarketing' and scientific ones 'consumer neuroscience'. While marketing scholars have eagerly integrated neuroscientific evidence into their theoretical framework, neurology has only recently started to draw its attention to the results of consumer neuroscience. Discussion: In this paper we address key research topics of consumer neuroscience that we think are of interest for neurologists; namely the reward system, trust and ethical issues. We argue that there are overlapping research topics in neurology and consumer neuroscience where both sides can profit from collaboration. Further, neurologists joining the public discussion of ethical issues surrounding neuromarketing and consumer neuroscience could contribute standards and experience gained in clinical research. Summary: We identify the following areas where consumer neuroscience could contribute to the field of neurology: First, studies using game paradigms could help to gain further insights into the underlying pathophysiology of pathological gambling in Parkinson's disease, frontotemporal dementia, epilepsy, and Huntington's disease. Second, we identify compulsive buying as a common interest in neurology and consumer neuroscience. Paradigms commonly used in consumer neuroscience could be applied to patients suffering from Parkinson's disease and frontotemporal dementia to advance knowledge of this important behavioral symptom. Third, trust research in the medical context lacks empirical behavioral and neuroscientific evidence. Neurologists entering this field of research could profit from the extensive knowledge of the biological foundation of trust that scientists in economically-orientated neurosciences have gained. Fourth, neurologists could contribute significantly to the ethical debate about invasive methods in neuromarketing and consumer neuroscience. Further, neurologists should investigate biological and behavioral reactions of neurological patients to marketing and advertising measures, as they could show special consumer vulnerability and be subject to target marketing. (authors' abstract)

Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) by overexpression of the transcription factors OCT4, SOX2, KLF4, and c-Myc holds great promise for the development of personalized cell replacement therapies. In an attempt to minimize the risk of chromosomal disruption and to simplify reprogramming, several studies demonstrated that a reduced set of reprogramming factors is sufficient to generate iPSC. We recently showed that a reduction of reprogramming factors in murine cells not only reduces reprogramming efficiency but also may worsen subsequent differentiation. To prove whether this is also true for human cells, we compared the efficiency of neuronal differentiation of iPSC generated from fetal human neural stem cells with either one (OCT4; hiPSC1F-NSC) or two (OCT4, KLF4; hiPSC2F-NSC) reprogramming factors with iPSC produced from human fibroblasts using three (hiPSC3F-FIB) or four reprogramming factors (hiPSC4F-FIB). After four weeks of coculture with PA6 stromal cells, neuronal differentiation of hiPSC1F-NSC and hiPSC2F-NSC was as efficient as iPSC3F-FIB or iPSC4F-FIB. We conclude that a reduction of reprogramming factors in human cells does reduce reprogramming efficiency but does not alter subsequent differentiation into neural lineages. This is of importance for the development of future application of iPSC in cell replacement therapies.

<p>Syftet med denna uppsats är att beskriva hur skillnaderna i det pedagogiska och det medicinska perspektivet konstrueras i kurslitteraturen för blivande lärare och läkare, samt hur barn med uppmärksamhetsstörningar konstrueras i litteraturen. Metoden i denna studie baseras på textanalys. Resultatet visar att olika diskurser speglas i kurslitteraturen för respektive utbildning och att barn med uppmärksamhetsstörningar därmed beskrivs på skilda sätt. Kurslitteraturen för läkarstudenter presenterar avvikelse utifrån det som anses normalt och avvikelse som begrepp har där en central roll. Kurslitteraturen för lärarstudenter presenterar olikheter som en utmaning vilka bör ligga till grund för positiv utveckling hos eleven.  Slutsatsen är att barn med neuropsykiatriska störningar/barn i behov av särskilt stöd beskrivs utifrån olika diskurser och att kurslitteraturen för respektive utbildning förespråkar olika behandlingar för dessa barn. Läkaren nämns nästan enbart i den pedagogiska litteraturen i samband med en diagnos, eller i de samband där specialpedagogens utveckling genom samverkan med olika professioner nämns. Den medicinska litteraturen beskriver sällan lärarens roll utan detta sker enbart i ett fåtal fall, däremot benämns skolmiljön som ett område där avvikande beteende kan definieras.                 </p> / <p> </p><p>The purpose of this essay is to describe how differences in the educational and medical perspective are constructed in the literature for future teachers and doctors, and also how children with attention disorders are constructed in this literature. A text analysis was based on books from medical training program and teacher training program. The results show that different discourses are reflected in the literature and that children with attention disorders hence are described in different ways. The course literature for medical students present deviation from what is considered normal, and deviation as a concept has a central role consistently through the literature. The course literature for teacher students presents differences as a challenge which should be the basis for positive development of the student. The conclusion is that children with neuropsychiatric disorders/ children with special needs are described by various discourses and that the course literature for medical students and teacher students advocate different treatments for these children. The medical doctor is almost only referred in the educational literature when associated with a diagnosis. The medical literature rarely describes the role of the teacher, this happens only in a few cases, however the school environment is more frequently mentioned as an area in which deviant behavior can be defined.</p>

Section A reviews and critically evaluates the empirical literature on psychosocial interventions for multiple sclerosis (MS), the determinants of adjustment to MS, and the theoretical frameworks to account for these. Further, a conceptual and empirical review of the literature on narrative therapy is provided and an argument advanced for the utility of narrative therapy in facilitating adjustment to MS. Possible areas for further research are outlined. Section B describes a feasibility study which aimed to begin to test a theoretical argument for the application of group narrative therapy to facilitate psychosocial adjustment to MS, and to ascertain the feasibility of a larger scale randomised controlled trial. Fourteen MS patients received 8 weekly sessions of group narrative therapy delivered at two sites in England. Quality of life, coping processes, and illness representations were assessed at two time points prior to the intervention and immediately after the intervention, and analysed using Wilcoxon Matched-Pairs tests. Additional qualitative measures were taken and analysed using content analysis. The feasibility of a larger scale study was, in part, assessed by means of semi-structured interviews with health professionals involved in the study, and analysed using thematic analysis. Although none of the findings reached statistical significance upon correcting for multiple comparisons, positive trends were revealed for the mental health component of quality of life, confrontive coping, and the consequences component of illness representations. With respect to the feasibility of this study, several issues pertaining to recruitment and data collection emerged from the data that can inform future research. Taken together, the results of this pilot study are promising and warrant further investigation using a sufficiently large sample. Section C provides a reflection on the skills and abilities developed and learning needs identified whilst undertaking the research. It further offers a critical reflection on the study‟s methodology and the potential implications for clinical practice. Further potential lines of enquiry are outlined.

No description available.

Background: Idiopathic inflammatory myopathies (IIM) constitute a heterogeneous group of diseases with severe consequences for the life of affected patients. Dermatomyositis, polymyositis and inclusion body myositis (IBM) are the classical representatives of this group. The treatments given today often have limited effects, and are taken at the cost of side effects. Major obstacles in the search for more effective treatments are; (1) an incomplete understanding of the disease mechanisms, (2) difficulties to delineate homogeneous disease groups for clinical studies and (3) the sometimes challenging task to diagnose these diseases. Aims: We addressed a number of “loose ends” in the areas of pathogenesis, classification and diagnosis; mechanisms of muscle fiber degeneration in IIM, with a focus of programmed cell death (apoptosis) and invasion of muscle  fibers by inflammatory cells (partial invasion); protecting and mediating factors present in muscle; the association of other diseases with IIM, in particular celiac disease ; the evaluation of two classification systems and laboratory methods for increased diagnostic performance. The studies: We included 106 patients, diagnosed at the Neuromuscular unit in Linköping, Sweden, with pathological muscle findings consistent with IIM. The incidence in the county of Östergötland (during 5 years) was 7.3 per million/year (3 patients each year). Of 88 patients with confirmed IIM 4 (4.5 %) had celiac disease, 33 (38%) had an associated systemic inflammatory disease and 5 (5.7 %) had a malignancy. Ninety-nine patients were included for a comparison of two classification systems using criteria of the European Neuromuscle Centre (Amato/ENMC), and the widely used Bohan and Peter classification, both with the addition of IBM according to Griggs et al. Using the Amato/ENMC criteria the most prevalent diagnostic group after IBM (30%) was nonspecific myositis (23%), followed by polymyositis (20%) and dermatomyositis 17%). A substantial number of patients meeting Bohan and Peter (or Griggs) criteria were excluded by Amato/ENMC criteria, most (21/23) due to lack of detectable muscle weakness. Extended muscle sectioning increased the sensitivity of a muscle biopsy by 15 % and the specificity by 22%, and showed an overlap between disease groups. Muscle biopsies from patients with IIM and controls were used to investigate pathological findings considered specific for disease groups, and for the presence of programmed cell death (apoptosis) and disease protecting and mediating factors in muscle. The presence of apoptotic muscle fiber nuclei was detected in muscle with partial invasion (however not in the invaded fibers) in the presence of granzyme B and CD8+ cytotoxic T cells. The major apoptosis inhibiting protein Bcl-2 was shown to be constitutionally expressed in healthy muscle but weakened in IIM. Conclusion: We present apoptosis as a possible disease mechanism in parallel with partial invasion of fibers. Furthermore, partial invasion may not be a suitable distinguishing feature in the pathogenesis, or for classification and diagnosis of IIM. We also introduce the anti-apoptotic Bcl-2 as a possible relevant muscle fiber protecting factor. A more extensive pathological work-up improves classification and diagnosis of IIM. The proposed Amato/ENMC creates a substantial portion of patients with non-specific or unclassified myositis. Associated diseases are common in IIM, and also include celiac disease.