Faculty Bibliography

PURPOSE: To report our initial experience implementing a noncontrast-enhanced electrocardiograph (ECG) gated fast spin echo magnetic resonance angiography (MRA) technique for assessment of the calf arteries. MATERIALS AND METHODS: Noncontrast MRA images of 36 clinical patients examined over a 6-month period were evaluated by two radiologists for length and degree of stenosis of arterial segments. Diagnostic confidence in the technique was also recorded. The reference standard was a consensus reading by both radiologists using the noncontrast technique combined with two gadolinium-enhanced techniques: bolus-chase and time-resolved imaging. RESULTS: For stenosis evaluation the noncontrast technique demonstrated accuracy 79.4% (1083/1364), sensitivity 85.4% (437/512), and specificity 75.8% (646/852). The sequence demonstrated high negative predictive value (92.3%, 646/700). The technique had serious artifacts leading to poor diagnostic confidence in 17 patients (47.2%). These included motion (n = 7) and artifacts specific to the sequence, including inaccurate trigger delays (n = 5), linear artifact (n = 7), and vessel blurring (n = 5). When only patients in whom there was satisfactory diagnostic confidence were considered, accuracy, sensitivity, and negative predictive value were 92.2% (661/717), 92.4% (158/171), and 97.5% (503/516), respectively. CONCLUSION: Our results indicate that when technically successful, noncontrast-enhanced MRA using ECG-gated fast spin echo can provide accurate imaging of the calf and pedal arteries. However, further development and optimization are needed to improve the robustness of the technique

Although short-term plasticity is believed to play a fundamental role in cortical computation, empirical evidence bearing on its role during behavior is scarce. Here we looked for the signature of short-term plasticity in the fine-timescale spiking relationships of a simultaneously recorded population of physiologically identified pyramidal cells and interneurons, in the medial prefrontal cortex of the rat, in a working memory task. On broader timescales, sequentially organized and transiently active neurons reliably differentiated between different trajectories of the rat in the maze. On finer timescales, putative monosynaptic interactions reflected short-term plasticity in their dynamic and predictable modulation across various aspects of the task, beyond a statistical accounting for the effect of the neurons' co-varying firing rates. Seeking potential mechanisms for such effects, we found evidence for both firing pattern-dependent facilitation and depression, as well as for a supralinear effect of presynaptic coincidence on the firing of postsynaptic targets

While nonenhanced magnetic resonance (MR) angiographic methods have been available since the earliest days of MR imaging, prolonged acquisition times and image artifacts have generally limited their use in favor of gadolinium-enhanced MR angiographic techniques. However, the combination of recent technical advances and new concerns about the safety of gadolinium-based contrast agents has spurred a resurgence of interest in methods that do not require exogenous contrast material. After a review of basic considerations in vascular imaging, the established methods for nonenhanced MR angiographic techniques, such as time of flight and phase contrast, are considered and their advantages and disadvantages are discussed. This article then focuses on new techniques that are becoming commercially available, such as electrocardiographically gated partial-Fourier fast spin-echo methods and balanced steady-state free precession imaging both with and without arterial spin labeling. Challenges facing these methods and possible solutions are considered. Since different imaging techniques rely on different mechanisms of image contrast, recommendations are offered for which strategies may work best for specific angiographic applications. Developments on the horizon include techniques that provide time-resolved imaging for assessment of flow dynamics by using nonenhanced approaches

In the last decade, multiple lines of transgenic APP overexpressing mice have been created that recapitulate certain aspects of Alzheimer's disease (AD). However, none of the previously reported transgenic APP overexpressing rat models developed AD-like beta-amyloid (Abeta) deposits, or age-related learning and memory deficits. In the present study, we have characterized a transgenic rat model overexpressing transgenes with three, familial AD mutations (two in APP and one in PS1) that were developed by Flood et al. [Flood, D.G., et al., Abeta deposition in a transgenic rat model of Alzheimer's disease. Society for Neuroscience 2003, Washington, DC, 2003]. From the age of 9 months, these rats develop Abeta deposits in both diffuse and compact forms, with the latter being closely associated with activated microglia and reactive astrocytes. Impaired long-term potentiation (LTP) was revealed by electrophysiological recordings performed on hippocampal slices from rats at 7 months of age, which is 2 months before the appearance of amyloid plaques. The deficit in LTP was accompanied by impaired spatial learning and memory in the Morris water maze, which became more pronounced in transgenic rats of 13 months of age. For Tg rats of both ages, there was a trend for cognitive impairment to correlate with total Abeta42 levels in the hippocampus. The rat model therefore recapitulates AD-like amyloid pathology and cognitive impairment. The advantage of the rat model over the available mouse models is that rats provide better opportunities for advanced studies, such as serial CSF sampling, electrophysiology, neuroimaging, cell-based transplant manipulations, and complex behavioral testing

Based on a newly developed method that combines finger position tracking and spectral analysis of the concurrent acoustic record, we studied the accuracy and variability of pitch performance in eight skilled cellists and the role of acoustic feedback in their performance. The tasks required shifting movements between pairs of notes and separated by various distances (pitch intervals) on a single string at the rate of 1 note/s. The same tasks were performed either using the bow, providing acoustic feedback, or without the bow. Overall, our subjects exhibited a high degree of accuracy in executing tasks when using the bow. When using the bow, two types of variability were observed: (1) trial-to-trial variability: in most subjects the mean fundamental frequency of a single nominal note was significantly different from trial to trial; and (2) within-trial variability. The within-trial variability includes two sub-types: (a) the pitch of a given note changed between notes within a 50-note trial; and (b) within a single note there were positional changes that we hypothesize are attempts by the performer to adjust the fundamental pitch within the note. When acoustic feedback was absent, note distributions were shifted, multimodal, and had large variability; error-correction movements within a single note also significantly decreased, indicating that the stability and precision of the motor map depends on constant re-calibration and updating by acoustic information. Our results suggest that a performer's intonation should not be viewed as a fixed entity implied by the score but as a sample from a statistical distribution.

Habituation is one of the simplest forms of memory, yet its neurobiological mechanisms remain largely unknown in mammalian systems. This review summarizes recent multidisciplinary analyses of the neurobiology of mammalian odor habituation including in vitro and in vivo synaptic physiology, sensory physiology, behavioral pharmacology, and computational modeling approaches. The findings show that a metabotropic glutamate receptor-mediated depression of afferent synapses to the olfactory cortex is necessary and perhaps sufficient to account for cortical sensory adaptation and short-term behavioral habituation. Furthermore, long-term habituation is an N-methyl-d-aspartate (NMDA) receptor-dependent process within the olfactory bulb. Thus there is both a pharmacological and anatomical distinction between short-term and long-term memory for habituation. The differential locus of change underlying short- and long-term memory leads to predictable differences in their behavioral characteristics, such as specificity

Neuroscience produces a vast amount of data from an enormous diversity of neurons. A neuronal classification system is essential to organize such data and the knowledge that is derived from them. Classification depends on the unequivocal identification of the features that distinguish one type of neuron from another. The problems inherent in this are particularly acute when studying cortical interneurons. To tackle this, we convened a representative group of researchers to agree on a set of terms to describe the anatomical, physiological and molecular features of GABAergic interneurons of the cerebral cortex. The resulting terminology might provide a stepping stone towards a future classification of these complex and heterogeneous cells. Consistent adoption will be important for the success of such an initiative, and we also encourage the active involvement of the broader scientific community in the dynamic evolution of this project