MEG coherence imaging in dyslexia: Activation of working memory pathways

The aims of this dissertation are to 1) review the genetic, neurodevelopmental, structural, and functional brain imaging studies that are the foundations of our understanding of dyslexia and 2) investigate the pattern of activation and functional connectivity of neuronal networks critical in working memory in dyslexics by means of magnetoenchephalographic (MEG) coherence imaging. Dyslexics showed an early onset of activation in the precentral gyrus and the superior frontal gyrus, which differed from controls where activation was initiated in posterior cortical regions (supramarginal gyrus and superior temporal gyrus). Further, dyslexics showed lower normalized amplitudes of activation in the right superior temporal gyrus and right middle temporal gyrus than controls during a spatial working memory (SWM) task. In contrast, during a verbal working memory (VWM) task, dyslexics showed lower normalized amplitudes in the right insular cortex and right superior temporal gyrus and higher, likely compensatory, activation in the right fusiform gyrus, left parahippocampal gyrus, and left precentral gyrus. Dyslexics performing a SWM task showed significantly reduced MEG coherence and lower 1) right frontal connectivity, 2) right fronto-temporal connectivity, 3) left and right frontal connectivity, 4) left temporal and right frontal connectivity, and 5) left occipital and right frontal connectivity. MEG coherence by frequency band showed lower mean coherences in dyslexics than in controls at each frequency range and when the bands were combined during the SWM task. In contrast, during the VWM task, dyslexics showed a higher coherence in the low frequency range (1-15 Hz) and lower coherence in the high gamma frequency range (30-45 Hz) than controls. Logistic regression of the coherence by group membership was significant, with an overall predictive success of 84.4% (88.9% for controls and 77.8% for dyslexics). Coherence between the right lateral orbitofrontal gyrus and right middle orbitofrontal gyrus paired region substantially contributed to group membership. These findings deepen our understanding of the underlying pathophysiology of dyslexia, highlighting the importance of working memory circuits and prefrontal cortical dysregulation in this disorder. These results have far-reaching ramifications not only for prevention and early diagnosis, but also for the development of effective, evidence-based treatments and interventions

Hydrophobic Residues of the D 2 Dopamine Receptor Are Important for Binding and Signal Transduction

Dopamine receptors belong to the seven transmembrane helix-containing, G protein-coupled receptor superfamily. Mutagenesis studies suggest that dopamine and its analogues interact with aspartate-114 in helix 3 and two helix 5 serines (194 and 197) of the D 2 receptor. In addition to these amino acids, hydrophobic residues within the receptor core may be important not only for binding but also for receptor activation. Described is a site-directed mutagenesis investigation into the roles of these hydrophobic residues in the long isoform of the human D 2 receptor. Replacement of helix 6 phenylalanines (389 or 390) with alanines resulted in disrupted binding to several agonists and antagonists and impaired inhibition of adenylyl cyclase activity. Replacement of the helix 5 phenylalanine-198 with an alanine selectively disrupted [ 3 H]N-0437 binding, whereas the affinities for other agonists and antagonists remained unchanged. This mutant remained functionally intact when stimulated with dopamine or bromocriptine. Replacement of the helix 7 phenylalanine-411 or the helix 6 leucine-387 with alanines produced receptors that bound agonists well but were unable to inhibit adenylyl cyclase. Based on these data, two conserved helix 6 phenylalanines (389 and 390) appear to be crucial for ligand binding, and phenylalanine-411 in helix 7 and leucine-387 in helix 6 may be important for propagating conformational changes from the agonist binding site(s) to G protein coupling domain(s) of the D 2 receptor.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65921/1/j.1471-4159.1995.65052105.x.pd

Pathologic Femur Fracture through Osteoid Osteoma after Radiofrequency Ablation: Case Report and Review of the Literature.

This is a case report of a 4-year-old girl who sustained a femoral shaft fracture 2 weeks after radiofrequency ablation of an osteoid osteoma. The fracture occurred after a relatively low-energy impact, jumping off the second to last step of a staircase. The pathologic fracture was successfully treated with closed reduction and spica casting, with full return to activities. Cases have been reported in the literature of femoral shaft fractures in older patients after radiofrequency ablation, but all are farther out than 2 weeks and none in patients as young as 4 years

Convulsions may alter the specificity of kappa-opiate receptors

Morphine, a mu-opiate agonist, and ethylketazocine, a kappa-opiate agonist, produce distinct behavioral, pharmacologic, and biochemical effects. In the mouse, large doses of morphine produce convulsions that are usually lethal and that cannot be blocked by naltrexone, whereas ethylketazocine produces nonlethal clonic convulsions that can be blocked by naltrexone. Moreover, mice made tolerant to morphine failed to show cross-tolerance to ethylketazocine, suggesting that the convulsions induced by these drugs are not mediated via a common opioid mechanism. Following a series of electroconvulsive shocks, both morphine and ethylketazocine produced clonic convulsions that were not lethal and that could be blocked by naltrexone. Furthermore, electroconvulsive shock-treated animals made tolerant to morphine-induced convulsions showed cross-tolerance to ethylketazocine. These data suggest that eletroconvulsive shock may alter kappa-opioid systems in such a way as to allow mu-agonists to be functional at these sites.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26156/1/0000233.pd

Morphine responsiveness and seizure proneness

Previous research demonstrated that following amygdala kindling, animals showed a heightened sensitivity to morphine's convulsive effects and an exaggerated Straub tail response. These effects were evident to 3 months after their last convulsion and could be blocked by naloxone pretreatment. The present paper extends these findings by demonstrating that animals given metrazol or electroshock (ECS) convulsions also showed an enhanced morphine response that was blocked by naltrexone. Both metrazol- and ECS-treated animals convulsed in response to doses of morphine that produced little or no effect in control animals. In addition, it was shown that brain damage induced by electrode implantation or neocortex penetration by skull screws also increased an animal's sensitivity to morphine even in the absence of prior convulsions. This effect, however, could not be blocked by naltrexone. Finally, as opiate receptors vary with the diurnal rhythm, we determined that following amygdala kindling, animals are more sensitive to morphine's convulsive action during their dark phase when receptor number and sensitivity are highest. The results indicated that seizure proneness, whether induced by a history of prior convulsions or brain damage, increased sensitivity to morphine. This effect may be due to a change in opiate receptors only when prior convulsions have occurred.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24747/1/0000169.pd

Changes in responsiveness to mu and kappa opiates following a series of convulsions

After a series of seven electroconvulsive shocks, mice (C57BL/6J) showed a marked change in their response to opiates. Although very large doses of mu agonists induce convulsions in normal control mice, our evidence indicated that this was accomplished through nonopiate mechanisms: they could not be blocked by naltrexone and the pattern of drug potencies (codeine > morphine > levorphanol) was not consistent with an opiate response. In contrast, after electroconvulsive shock small doses of mu agonists induced convulsions that could be blocked by naltrexone and the pattern of drug potency (levorphanol > morphine > codeine) was consistent with an opiate mechanism. Kappa drugs, on the other hand, produced convulsions in both control and ECS animals, although there was an enhanced responsiveness in the latter. Furthermore, the convulsions produced by kappa drugs were blocked by naltrexone and showed stereoselectivity in both control and ECS animals. The changes in responsiveness to mu and kappa opiates cannot be explained on the basis of a general increase in seizure susceptibility, as sensitivity to the nonopiate convulsant, strychnine, was not enhanced after electroconvulsive shock. The results point to a qualitative change in response to mu agonists after electroconvulsive shock, but only a change in sensitivity to kappa agonists.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25549/1/0000091.pd

Expression of the dopamine D2 receptor gene in brain,

The cloning of the dopamine (DA) D2 receptor now permits the characterization and regulation of D2 messenger RNA (mRNA) in the brain. In this article, the authors describe their studies delineating the distribution of D2 receptor mRNA in the rodent and primate brain, and compare the distribution of message to D2 receptor binding sites. The effects of chronic DA agonist and antagonist treatment on D2 receptor mRNA are also presented, and provide insights into receptor regulation. Finally, the autoreceptor role of D2 receptors located in the midbrain is examined with a combination of 6-hydroxydopamine lesions and anatomic colocalization studies with tyrosine hydroxylase. These preclinical results provide a framework for subsequent investigation into the nature of D2 receptor gene expression in postmortem brains from patients with disorders putatively associated with dopaminergic dysfunction, especially schizophrenia. They also lay the groundwork for a more profound understanding of DA neurocircuitry by combining molecular biological and traditional anatomical techniques.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29030/1/0000062.pd

Combining spectral indices and statistics analysis to proposed a new risk of soil degradation method – application to the Cameroonians shores of lake Chad and its hinterland

International audienceIn the far northern part of Cameroon, the shores of Lake Chad are in the most exposed zone to the risks of soil degradation due to environmental conditions, more severe climatic conditions and modes of uses and exploitation of natural resources (National Action Plan to combat Desertification (PAN/LCD) 2006). It is an area marked by degradation and decline of soil fertility, unsuitable cultivation practices, high extension of barren land, erosion, runoff, and decrease of fallows, overgrazing, and pesticides pollution

Variability Between Full-Length Lateral Radiographs and Standard Short Knee Radiographs When Evaluating Posterior Tibial Slope in Revision ACL Patients

BACKGROUND: Increased posterior tibial slope (PTS) has been identified as a risk factor for failure after anterior cruciate ligament (ACL) reconstruction. Correction of PTS may improve outcomes after revision ACL reconstruction. There are conflicting reports demonstrating the measurement of the PTS on standard short knee (SSK) radiographs versus full-length lateral (FLL) radiographs including the entire tibia. PURPOSE/HYPOTHESIS: To compare PTS measurements between SSK and FLL radiographs in patients who failed primary ACL reconstruction. It was hypothesized that there would be high variability between the SSK and FLL radiographic measurements. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: The medial and lateral PTS were measured on the SSK and FLL radiographs of 33 patients with failed primary ACL reconstructions. All measurements were performed by 2 trained independent observers (A.A.M., J.S.), and inter- and intraobserver reliability were calculated using the intraclass correlation coefficient (ICC). Measurements recorded by the observer with the higher intraobserver ICC were used for comparison of the PTS on SSK versus FLL radiographs. RESULTS: Both the inter- and the intraobserver reliability values of the PTS measurements were excellent. There was a significant difference in mean PTS on the medial plateau as measured on the SSK and FLL radiographs (11.2°± 5.3° vs 12.5°± 4.6°; CONCLUSION: Results indicated that FLL and SSK radiographs are not interchangeable measurements for PTS associated with failed ACL reconstruction. Because FLL radiographs demonstrate less variability than SSK radiographs, we recommend obtaining them to evaluate these complex patients

A PSO inspired asynchronous cooperative distributed hyper-heuristic for course timetabling problems

This paper presents a novel approach for asynchronous cooperative hyper-heuristic incorporated with particle swarm optimisation which inspired by social individual behaviour of swarm intelligence, like bird flocking and fish schooling. The proposed hyper-heuristic algorithm starts with a complete solution and tries to improve the soft constraints, whilst always remaining in the feasible region of the search space. The performances of the proposed cooperative hyper-heuristics are evaluated using the standard course timetabling benchmark problem. From the experimental results, it shows that the proposed Asynchronous Cooperative Distribute Low-level heuristics (ACDLLHs) algorithm is able to find new best solutions for all five medium problem instances and shared optimal solutions for all five small instances. When coupled with two, four and six agents, the Asynchronous Cooperative Distributed Hyper-heuristic (ACDHH) algorithm is able to improve the solution quality for a large instance