Faculty Bibliography

Here analytical and simulation results are presented characterizing the recoding arising when overlapping patterns of sensor input impinge on an array of model neurons with branched thresholded dendritic trees. Thus, the neural units employed are intended to capture the integrative behavior of pyramidal cells that sustain isolated Na(+) or NMDA spikes in their branches. Given a defined set of sensor vectors, equations were derived for the probability of firing of both branches and neurons and for the expected overlap between the neural firing patterns triggered by two afferent patterns of given overlap. Thus, both the sparseness of the neural representation and the orthogonalization of overlapping vectors were computed. Simulations were then performed with an array of 1000 neurons comprising 30,000 branches to verify the analytical results and confirm their applicability to systems (which include any practicable artificial system) in which the combinatorically possible branches and neurons are severely subsampled. A means of readout and a measure of discrimination performance were provided so that the accuracy of discrimination among overlapping sensor vectors could be optimized as a function of neuron structure parameters. Good performance required both orthogonalization of the afferent patterns, so that discrimination was accurate and free of interference, and maintenance of a minimum level of neural activity, so that some neurons fired in response to each sensor pattern. It is shown that the discrimination performance achieved by arrays of neurons with branched dendritic trees could not be reached with single-compartment units, regardless of how many of the latter are used. The analytical results furnish a benchmark against which to measure further enhancements in the performance of subsequent simulated systems incorporating local neural mechanisms which, while often less amenable to closed-form analysis, are ubiquitous in biological neural circuitry

OBJECTIVES: Since the advent of cochlear implants, age at implantation has declined as investigators report greater benefit the younger a child is implanted. Infants younger than 12 mos currently are excluded from Food and Drug Administration clinical trials, but have been implanted with Food and Drug Administration-approved devices. With a chance that an infant without profound hearing loss could be implanted because of the limitations of the diagnostic measures used with this population and the potential for additional anesthetic risks to infants younger than 1-yr-old, it is prudent to evaluate benefit in the youngest cochlear implant recipients. The goals of this research were to investigate whether significant gains are made by children implanted before 1-yr-old relative to those implanted at later ages, while controlling for potential covariates, and whether there is behavioral evidence for sensitive periods in spoken language development. It was expected that children implanted before age 1 yr would have more advanced spoken language skills than children implanted at later ages; there would be a negative relationship between age at implantation and rate of spoken language development, allowing for an examination of the effects of sensitive periods in spoken language development; and these trends would remain despite accounting for participant characteristics and experiences that might influence spoken language outcomes. DESIGN: Ninety-six children with congenital profound sensorineural hearing loss bilaterally and no additional identified disabilities who were implanted before the age of 4 yrs were stratified into four groups based on age at implantation. Children's spoken language development was followed for at least 2 yrs after device activation. Spoken language scores and rate of development were evaluated along with four covariates (unaided pure-tone average, communication mode, gender, and estimated family income) as a function of age at implantation. RESULTS: In general, the developmental trajectories of children implanted earlier were significantly better than those of children implanted later. However, the advantage of implanting children before 1-yr old versus waiting until the child was between 1 and 2 yrs was small and only was evident in receptive language development, not expressive language or word recognition development. Age at implantation did not significantly influence the rate of the word recognition development, but did influence the rate of both receptive and expressive language acquisition: children implanted earlier in life had faster rates of spoken language acquisition than children implanted later in life. CONCLUSIONS: Although in general earlier cochlear implantation led to better outcomes, there were few differences in outcome between the small sample of six children implanted before 12 mos of age and those implanted at 13 to 24 mos. Significant performance differences remained among the other age groups despite accounting for potential confounds. Further, oral language development progressed faster in children implanted earlier rather than later in of life (up to age 4 yrs), whereas the rate of open-set speech recognition development was similar. Together, the results suggest that there is a sensitive period for spoken language during the first 4 yrs of life, but not necessarily for word recognition development during the same period

Anatomical knowledge of the structures to be targeted and of the circuitry involved is crucial in stereotactic functional neurosurgery. The present study was undertaken in the context of surgical treatment of motor disorders such as essential tremor (ET) and Parkinson's disease (PD) to precisely determine the course and three-dimensional stereotactic localisation of the cerebellothalamic and pallidothalamic tracts in the human brain. The course of the fibre tracts to the thalamus was traced in the subthalamic region using multiple staining procedures and their entrance into the thalamus determined according to our atlas of the human thalamus and basal ganglia [Morel (2007) Stereotactic atlas of the human thalamus and basal ganglia. Informa Healthcare Inc., New York]. Stereotactic three-dimensional coordinates were determined by sectioning thalamic and basal ganglia blocks parallel to stereotactic planes and, in two cases, by correlation with magnetic resonance images (MRI) from the same brains prior to sectioning. The major contributions of this study are to provide: (1) evidence that the bulks of the cerebellothalamic and pallidothalamic tracts are clearly separated up to their thalamic entrance, (2) stereotactic maps of the two tracts in the subthalamic region, (3) the possibility to discriminate between different subthalamic fibre tracts on the basis of immunohistochemical stainings, (4) correlations of histologically identified fibre tracts with high-resolution MRI, and (5) evaluation of the interindividual variability of the fibre systems in the subthalamic region. This study should provide an important basis for accurate stereotactic neurosurgical targeting of the subthalamic region in motor disorders such as PD and ET

The predominance of dopamine (DA) receptors at extrasynaptic vs. synaptic sites implies that DA signaling is by diffusion-based volume transmission. In this review, we compare characteristics that regulate extracellular DA behavior in substantia nigra pars compacta (SNc) and striatum, including regional differences in structure (a 40% greater extracellular volume fraction in SNc vs. striatum) and in dynamic DA uptake (a 200-fold greater DA uptake rate in striatum vs. SNc). Furthermore, we test the assumption of diffusion-based volume transmission for SNc and striatum by modeling dynamic DA behavior after quantal release using region-specific parameters for diffusion and uptake at 37 degrees C. Our model shows that DA uptake does not affect peak DA concentration within 1 mum of a release site in either SNc or striatum because of the slow kinetics of DATs vs. diffusion. Rather, diffusion and dilution are the dominant factors governing DA concentration after quantal release. In SNc, limited DAT efficacy is reflected in a lack of influence of uptake on either amplitude or time course of DA transients after quantal release up to 10 mum from a release site. In striatum, the lack of effect of the DAT within 1 mum of a release site means that perisynaptic DATs do not 'gate' synaptic spillover. This contrasts with the conventional view of DA synapses, in which DATs efficiently recycle DA by re-uptake into the releasing axon terminal. However, the model also shows that a primary effect of striatal uptake is to curtail DA lifetime after release. In both SNc and striatum, effective DA radius after quantal release is ~2 mum for activation of low-affinity DA receptors and 7-8 mum for high-affinity receptors; the corresponding spheres of influence would encompass tens to thousands of synapses. Thus, the primary mode of intercellular communication by DA, regardless of region, is volume transmission

We analyze the potential efficiency of laser beam projection onto a remote object in atmosphere with incoherent and coherent phase-locked conformal-beam director systems composed of an adaptive array of fiber collimators. Adaptive optics compensation of turbulence-induced phase aberrations in these systems is performed at each fiber collimator. Our analysis is based on a derived expression for the atmospheric-averaged value of the mean square residual phase error as well as direct numerical simulations. Operation of both conformal-beam projection systems is compared for various adaptive system configurations characterized by the number of fiber collimators, the adaptive compensation resolution, and atmospheric turbulence conditions

Abnormal protein deposits are a common feature of many human diseases including Alzheimer's disease. In Alzheimer's disease, the appearance of tangles, composed of the microtubule associated protein tau, correlates with both cell death and symptom severity. However, are tau filaments simply markers of disease progression, or are they directly responsible for cell death? Due to conflicting findings from cell and animal models, it remains controversial whether tau polymers or smaller pre-fibrillar aggregates or tau monomers are the toxic species. Indeed, if monomeric or oligomeric species are mediators of disease, formation of larger tau filaments may prove beneficial to affected cells. This review will examine the findings regarding the toxicity of various tau species

There are a limited number of methods available to quantify the extracellular diffusion of macromolecules in an anisotropic brain region, e.g., an area containing numerous aligned fibers where diffusion is faster along the fibers than across. We applied the integrative optical imaging method to measure diffusion of the fluorophore Alexa Fluor 488 (molecular weight (MW) 547) and fluorophore-labeled flexible random-coil dextran polymers (dex3, MW 3000; dex75, MW 75,000; dex282, MW 282,000; dex525, MW 525,000) in the extracellular space (ECS) of the anisotropic molecular layer of the isolated turtle cerebellum. For all molecules, two-dimensional images acquired an elliptical shape with major and minor axes oriented along and across, respectively, the unmyelinated parallel fibers. The effective diffusion coefficients, D*(major) and D*(minor), decreased with molecular size. The diffusion anisotropy ratio (DAR = D*(major)/D*(minor)) increased for Alexa Fluor 488 through dex75 but then unexpectedly reached a plateau. We argue that dex282 and dex525 approach the ECS width and deform to diffuse. In support of this concept, scaling theory shows the diffusion behavior of dex282 and dex525 to be consistent with transition to a reptation regime, and estimates the average ECS width at approximately 31 nm. These findings have implications for the interstitial transport of molecules and drugs, and for modeling neurotransmitter diffusion during ectopic release and spillover

OBJECTIVE: The objective of our study was to retrospectively compare the degree of pelvic organ prolapse shown on dynamic true fast imaging with steady-state precession (FISP) versus HASTE sequences in symptomatic patients. MATERIALS AND METHODS: Fifty-nine women (mean age, 57 years) with suspected pelvic floor dysfunction underwent MRI using both a sagittal true FISP sequence, acquired continuously during rest alternating with the Valsalva maneuver, and a sagittal HASTE sequence, acquired sequentially at rest and at maximal strain. Data sets were evaluated in random order by two radiologists in consensus using the pubococcygeal line (PCL) as a reference. Measurement of prolapse was based on a numeric grading system indicating severity as follows: no prolapse, 0; mild, 1; moderate, 2; or severe, 3. A comparison between sequences on a per-patient basis was performed using a Wilcoxon's analysis with p < 0.05 considered significant. RESULTS: Overall, 66.1% (39/59) of patients had more severe prolapse (>or= 1 degrees ) based on dynamic true FISP images, with 28.8% (17/59) of the cases of prolapse seen exclusively on true FISP images. Only 20.3% (12/59) of patients had greater degrees of prolapse on HASTE images than on true FISP images, with 10.2% (6/59) of the cases seen exclusively on HASTE images. A statistically significant increase in the severity of cystoceles (p < 0.01) and urethral hypermobility (p < 0.01)-with a trend toward more severe urethroceles (p < 0.07), vaginal prolapse (p < 0.09), and rectal descent (p < 0.06)-was shown on true FISP images. CONCLUSION: Overall, greater degrees of organ prolapse in all three compartments were found with a dynamic true FISP sequence compared with a sequential HASTE sequence. Near real-time continuous imaging with a dynamic true FISP sequence should be included in MR protocols to evaluate pelvic floor dysfunction in addition to dynamic multiplanar HASTE sequences

Image denoising methods are often designed to minimize mean-squared error (MSE) within the subbands of a multiscale decomposition. However, most high-quality denoising results have been obtained with overcomplete representations, for which minimization of MSE in the subband domain does not guarantee optimal MSE performance in the image domain. We prove that, despite this suboptimality, the expected image-domain MSE resulting from applying estimators to subbands that are made redundant through spatial replication of basis functions (e.g., cycle spinning) is always less than or equal to that resulting from applying the same estimators to the original nonredundant representation. In addition, we show that it is possible to further exploit overcompleteness by jointly optimizing the subband estimators for image-domain MSE. We develop an extended version of Stein's unbiased risk estimate (SURE) that allows us to perform this optimization adaptively, for each observed noisy image. We demonstrate this methodology using a new class of estimator formed from linear combinations of localized 'bump' functions that are applied either pointwise or on local neighborhoods of subband coefficients. We show through simulations that the performance of these estimators applied to overcomplete subbands and optimized for image-domain MSE is substantially better than that obtained when they are optimized within each subband. This performance is, in turn, substantially better than that obtained when they are optimized for use on a nonredundant representation

Impulsive acts and decisions are a part of everyday normal behavior. However, in its pathological forms, impulsivity can be a debilitating disorder often associated with a number of neuropsychiatric disorders, including attention-deficit hyperactivity disorder (ADHD). This article reviews recent progress in our understanding of the neurobiology of impulsivity using examples from recent investigations in experimental animals. Evidence is reviewed from several well-established paradigms with putative utility in assessing distinct forms of impulsive behavior in rodents, including the 5-choice serial reaction time (5CSRT) task and the delay discounting paradigm. We discuss, in particular, recent psychopharmacological and in-vivo neurochemical data in task-performing rats showing functional heterogeneity of the forebrain dopamine (DA), noradrenaline (NA), serotonin (5-HT) and acetylcholine (ACh) systems and identify how these systems normally function to facilitate flexible goal-directed behavior in situations that tax basic attentional functions and inhibitory response control mechanisms. We also discuss future research needs in terms of understanding the functional diversity of different sub-regions of prefrontal cortex (PFC) and how these systems normally interact with the striatum and main nuclei of origin of DA and NA neurons. Finally, we argue in line with others that animal paradigms are unlikely to model all aspects of complex psychiatric conditions such as ADHD but components of such syndromes may be amenable to investigation using sophisticated animal models based on highly-defined psychiatric endophenotypes.