Faculty Bibliography

The hypothesis that Attention-Deficit/Hyperactivity Disorder (ADHD) reflects a primary inhibitory executive function deficit has spurred a substantial literature. However, empirical findings and methodological issues challenge the etiologic primacy of inhibitory and executive deficits in ADHD. Based on accumulating evidence of increased intra-individual variability in ADHD, we reconsider executive dysfunction in light of distinctions between 'hot' and 'cool' executive function measures. We propose an integrative model that incorporates new neuroanatomical findings and emphasizes the interactions between parallel processing pathways as potential loci for dysfunction. Such a reconceptualization provides a means to transcend the limits of current models of executive dysfunction in ADHD and suggests a plan for future research on cognition grounded in neurophysiological and developmental considerations

Molecular mechanisms underlying tauopathy remain undetermined. In the current study, single cell gene expression profiling was coupled with custom-designed cDNA array analysis to evaluate tau expression and other cytoskeletal elements within individual neuronal populations in patients with no cognitive impairment (NCI), mild cognitive impairment (MCI), and Alzheimer's disease (AD). Results revealed a shift in the ratio of three-repeat tau (3Rtau) to four-repeat tau (4Rtau) mRNAs within individual human cholinergic basal forebrain (CBF) neurons within nucleus basalis (NB) and CA1 hippocampal neurons during the progression of AD, but not during normal aging. A shift in 3Rtau to 4Rtau may precipitate a cascade of events in the selective vulnerability of neurons, ultimately leading to frank neurofibrillary tangle (NFT) formation in tauopathies including AD.

BACKGROUND AND PURPOSE: Clinical MR imaging scanners now offer many choices of hardware configurations that were not available in the first 25 years of their existence. Our goal was to assess the influence of coil technology, magnetic field strength, and echo time (TE) on the sensitivity, reflected by the signal intensity-to-noise-ratio (SNR) and reproducibility of proton MR spectroscopy (1H-MR spectroscopy). MATERIAL AND METHODS: The SNR, the intersubject reproducibility, and the intrasubject reproducibility of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) levels were compared at the common TEs of 30, 144, and 288 ms, by using 1H-MR spectroscopy in 6 volunteers at (1) 3T with a single-element quadrature (SEQ); (2) 1.5T with SEQ; and (3) 1.5T with a 12-channel phased-array (PA) head coil. RESULTS: In terms of sensitivity, the best SNR for all metabolites was obtained at the shortest TE (30 ms). It was comparable between the 3 and 1.5T with the PA, but approximately 35% better than the 1.5T with SEQ. This SNR difference declined <25% at TE of 144 ms and to equity among all imagers at TE of 288 ms. Reproducibility, reflected in the coefficient of variation (CV), was best for NAA at TE of 288 ms, 15%-50% better than at TE of 30 ms in either gray (GM) or white matter (WM). The CV for Cr was best, at TE of 288 ms for GM, but its WM results were independent of TE. Metabolite level reproducibility did not depend on coil technology or magnetic field strength. CONCLUSIONS: For the same coil type, the SNR of all major metabolites was approximately 35% better at 3T than at 1.5T. This advantage, however, was offset at 1.5T with a PA coil, making it a cost-effective upgrade for existing scanners. Surprisingly and counterintuitively, despite the lowest SNR, the best reproducibility was obtained at the longest TE (288 ms), regardless of field or coil

PURPOSE: The aim of this study was to review and describe techniques for the reconstruction of large, complex perioral defects after resection of oral squamous cell carcinoma with emphasis on cosmetic and functional outcome. PATIENTS AND METHODS: A review of techniques and selected case presentations using different flap designs for the reconstruction of large perioral defects following resection of squamous cell carcinoma was performed. The Bernard and Karapandzic flaps were used for large lower lip defects. A Zisser flap technique was used to reconstruct a large commissure defect. RESULTS: All reconstructed patients had acceptable functional results and healed without complication. The large lower lip defects were easily closed with the Bernard and Karapandzic flaps. The commissure defect was reconstructed using the Zisser technique. While cosmesis was acceptable in all cases, the commissure was the most difficult region to reconstruct with a favorable appearance. There were no flap failures. The Karapandzic flap led to greater rounding of the commissure area and the composite resection resulted in a lack of lower lip support that was improved with prosthesis. Function was noted to be excellent in the Bernard and Karapandzic flaps, with the patients able to purse lips and blow up balloon-type devices. CONCLUSION: The Bernard, Karapandzic, and Zisser flaps provide a predictable method to reconstruct large perioral defects following resection for oral cancer. Subsequent fabrication of a prosthesis can aid in lip support for the resected area

We studied ocular asymmetries and orienting responses induced by angular rotation in rabbits with binocular video recordings. Slow phase velocities were significantly larger in the eye moving temporonasally than nasotemporally. The eyes also converged and pitched down during rotation, which increased and refocused binocular overlap in the visual fields. Eye position also shifted into the slow phase direction. Vergence and pitch outlasted the induced nystagmus, suggesting that they were generated by a separate vestibulo-oculomotor subsystem(s). Thus, mechanisms in the rabbit increase compensatory eye velocity in the eye that leads into the direction of rotation and enhance binocular vision

Dyskinesia is the most troublesome side effect in long-term treatment of both Parkinson's disease (PD) and schizophrenia. The 5-HT1A agonist and D3/D4 ligand sarizotan [Bartoszyk, G.D., van Amsterdam, C., Greiner, H.E., Rautenberg, W., Russ, H., Seyfried, C.A., 2004. Sarizotan, a serotonin 5-HT1A receptor agonist and dopamine receptor ligand. 1. Neurochemical profile. J. Neural Transm. 111, 113-126.] is in clinical development for the treatment of PD-associated dyskinesia. Because 5-HT1A agonists are known to counteract antipsychotic-induced motor side effects, sarizotan was investigated for its effects in two rat models of tardive dyskinesia (TD). The acute administration of sarizotan (0.17-13.5 mg/kg i.p.) reduced episodes of SKF 38393-induced repetitive jaw movements (RJM) in rats with a maximal effect at 1.5 mg/kg. In a chronic study, sarizotan (0.04-9 mg/kg/day), administered in the drinking water for 7 weeks during withdrawal from chronic haloperidol treatment (1.5 mg/kg/day), dose-dependently reversed haloperidol-induced RJM, significant at the doses of 1.5 and 9 mg/kg. Agonism at 5-HT1A receptors may be mediating the inhibitory effect of sarizotan on RJM in rat models of tardive dyskinesia

Galactocerebroside (GalC) and sulfatide are abundant myelin lipids. In mice incapable of synthesizing these lipids, myelin is thin and regionally unstable and exhibits several subtle structural abnormalities. Although galactolipid-null mice have been beneficial in the analysis of galactolipid function, it has not been possible to differentiate between the functions of GalC and sulfatide with these mice alone. In the present work, we have analyzed a murine model that forms normal levels of GalC but is incapable of synthesizing sulfatide. By comparing a plethora of morphological features between the galactolipid-null and the sulfatide-null mice, we have begun to differentiate between the specific functions of these closely related lipids. The most striking difference between these two mutants is the reduction of myelin developmental abnormalities (e.g., redundant and uncompacted myelin sheaths) in young adult sulfatide-null mice as compared with the galactolipid-null animals. Although sulfatide appears to play a limited role in myelin development, this lipid is essential for myelin maintenance, as the prevalence of redundant, uncompacted, and degenerating myelin sheaths as well as deteriorating nodal/paranodal structure is increased significantly in aged sulfatide-null mice as compared with littermate wildtype mice. Finally, we show that the role played by sulfatide in CNS maintenance is not limited to the myelin sheath, as axonal caliber and circularity are normal in young adult mutant mice but are significantly altered in aged sulfatide-null animals.

We present a detailed theoretical framework for statistical descriptions of neuronal networks and derive (1+1)-dimensional kinetic equations, without introducing any new parameters, directly from conductance-based integrate-and-fire neuronal networks. We describe the details of derivation of our kinetic equation, proceeding from the simplest case of one excitatory neuron, to coupled networks of purely excitatory neurons, to coupled networks consisting of both excitatory and inhibitory neurons. The dimension reduction in our theory is achieved via novel moment closures. We also describe the limiting forms of our kinetic theory in various limits, such as the limit of mean-driven dynamics and the limit of infinitely fast conductances. We establish accuracy of our kinetic theory by comparing its prediction with the full simulations of the original point-neuron networks. We emphasize that our kinetic theory is dynamically accurate, i.e., it captures very well the instantaneous statistical proper-ties of neuronal networks under time-inhomogeneous inputs