Faculty Bibliography

The hybrid nature of optoacoustic imaging might impose limitations on concurrent placement of optical and ultrasonic detection components, especially in high resolution microscopic applications that require dense arrangements and miniaturization of components. This hinders optimal deployment of the optical excitation and ultrasonic detection paths, leading to reduction of imaging speed and spatial resolution performance. We suggest a compact coaxial design for optoacoustic microscopy that allows optimizing both the light illumination and ultrasonic detection parameters of the imaging system. System performance is showcased in phantoms and in vivo imaging of microvasculature, achieving real time operation in two dimensions and penetration of 6 mm into optically dense human tissues.

The medial superior olive (MSO) is a key auditory brainstem structure that receives binaural inputs and is implicated in processing interaural time disparities used for sound localization. The deaf white cat, a proven model of congenital deafness, was used to examine how deafness and cochlear implantation affected the synaptic organization at this binaural center in the ascending auditory pathway. The patterns of axosomatic and axodendritic organization were determined for principal neurons from the MSO of hearing, deaf, and deaf cats with cochlear implants. The nature of the synapses was evaluated through electron microscopy, ultrastructure analysis of the synaptic vesicles, and immunohistochemistry. The results show that the proportion of inhibitory axosomatic terminals was significantly smaller in deaf animals when compared with hearing animals. However, after a period of electrical stimulation via cochlear implants the proportion of inhibitory inputs resembled that of hearing animals. Additionally, the excitatory axodendritic boutons of hearing cats were found to be significantly larger than those of deaf cats. Boutons of stimulated cats were significantly larger than the boutons in deaf cats, although not as large as in the hearing cats, indicating a partial recovery of excitatory inputs to MSO dendrites after stimulation. These results exemplify dynamic plasticity in the auditory brainstem and reveal that electrical stimulation through cochlear implants has a restorative effect on synaptic organization in the MSO.

The P300 is a known ERP component assessing stimulus value, including the value of a monetary reward. In parallel, the incentive value of reinforcers relies on the pFC, a major cortical projection region of the mesocortical reward pathway. Here we show a significant positive correlation between P300 response to money (vs. no money) with pFC gray matter volume in the OFC, ACC, and dorsolateral and ventrolateral pFC in healthy control subjects. In contrast, individuals with cocaine use disorders showed compromises in both P300 sensitivity to money and pFC gray matter volume in the ventrolateral pFC and OFC and their interdependence. These results document for the first time the importance of gray matter structural integrity of subregions of pFC to the reward-modulated P300 response

Rats were trained in a 2-alternative odor choice task to discriminate between a 10-component odor mixture and the same mixture with one component removed and replaced with 1 of 3 concentrations of a different monomolecular odor (contaminant). All stimuli were presented within a training session, thus the rat essentially had to learn to discriminate the 10-component mixture from "not" the 10-component mixture. Rats performed most poorly discriminating the complete mixture from the mixture with one component removed and no contaminant added. As the concentration of the contaminant increased from 10 ppm to a concentration equal to the other components (100 ppm), discrimination improved linearly. In analyses of individual differences, rats that spent more time in the sampling port (sampling and making a decision) were more accurate than rats that spent less time. Together, these results emphasize the balance between perceptual stability and perceptual discrimination expressed by the olfactory system dealing with dynamic mixtures and the robust effects of contamination on those processes. In addition, they provide further support that modification of sampling/decision time is a strategy used by rats to deal with difficult discriminations of complex odors.

Tubulocystic renal cell carcinoma (TC-RCC) is a rare, typically unilateral renal tumor. We report the first case of bilateral multifocal TC-RCC associated with end-stage renal disease with cytogenetic, immunohistochemical, and ultrastructural studies. A 62-year-old man with type 2 diabetes, hypertension, and end-stage renal disease on hemodialysis had bilateral complex renal masses smaller than 3.0 cm in greatest dimension found incidentally. Follow-up imaging studies demonstrated slowly enlarging masses. The patient underwent bilateral laparoscopic radical nephrectomy. Grossly, both kidneys had multifocal, unencapsulated, sharply demarcated, gray, spongy cystic lesions (0.3-2.5 cm) in cortex and medulla. The lesions contained clear serous fluid. Microscopically, the background kidneys showed end-stage changes with glomerulosclerosis and atrophic tubules. The well-delineated cystic lesions are composed of tightly packed tubules and cysts, separated by bland fibrous stroma. The lining cells are single-layer, flattened, cuboidal to columnar, with abundant eosinophilic cytoplasm, large round to oval nuclei, and prominent nucleoli. Hobnail cells are common. No desmoplastic reaction or cellular ovarian-like stroma is present. No solid growth or papilla is seen in either kidney. Immunohistochemically, the tumor cells showed diffuse and strong positivity for AMACR, AE1/AE3, CK8/18, CD10, and PAX2; focally strong positivity for CK7, EMA, vimentin, and 34BE12; and negativity for p63 and CK20. TC-RCC was diagnosed. Fuhrman nuclear grade was 2 to 3. Pathologic stage was pT1 on both kidneys. Fluorescence in situ hybridization shows gain of chromosome 7 and chromosome 17. Transmission electronic microscopy showed 2 types of epithelial cells: type I cells reminiscent of proximal tubular cells and lining the tubules and type II cells reminiscent of distal tubular cells lining the cysts. The patient was disease-free 3 years after radiologic detection and 12 months after bilateral nephrectomy. Our studies suggest TC-RCC is closely related to papillary RCC. This tumor appears to be low-grade with no metastasis

Karoly Schaffer (1864-1939) was a Hungarian neurologist who distinguished himself through original discoveries in human neuropathology. At the beginning of his scientific carrier, he described the cellular and fiber structure of the hippocampus, earning him a high reputation in neuroscience. Schaffer (1892) described the so-called "collateral fiber system" that connects the CA3 and CA1 regions of the hippocampus, known today as Schaffer collaterals. To decipher the history of this well-known eponym, we review Schaffer's original German publication and follow the impact of his research in the contemporary literature. (c) 2012 Wiley Periodicals Inc.

Neuronal control with high temporal precision is possible with optogenetics, yet currently-available methods do not enable to independently control multiple locations in the brains of freely-moving animals. Here, we describe a diode-probe system that allows real-time and location-specific control of neuronal activity at multiple sites. Manipulation of neuronal activity in arbitrary spatiotemporal patterns is achieved by means of an optoelectronic array, manufactured by attaching multiple diode-fiber assemblies to high-density silicon probes or wire tetrodes, and implanted into the brains of animals that are expressing light-responsive opsins. Each diode can be controlled separately, allowing localized light stimulation of neuronal activators and silencers in any temporal configuration and concurrent recording of the stimulated neurons. Because the only connections to the animals are via a highly flexible wire cable, unimpeded behavior is allowed for circuit monitoring and multi-site perturbations in the intact brain. The capacity of the system to generate unique neural activity patterns facilitates multi-site manipulation of neural circuits in a closed-loop manner and opens the door to addressing novel questions.

In previous studies of a genetic isolate, we identified significant linkage of attention deficit hyperactivity disorder (ADHD) to 4q, 5q, 8q, 11q and 17p. The existence of unique large size families linked to multiple regions, and the fact that these families came from an isolated population, we hypothesized that two-locus interaction contributions to ADHD were plausible. Several analytical models converged to show significant interaction between 4q and 11q (P<1 x 10(-8)) and 11q and 17p (P<1 x 10(-6)). As we have identified that common variants of the LPHN3 gene were responsible for the 4q linkage signal, we focused on 4q-11q interaction to determine that single-nucleotide polymorphisms (SNPs) harbored in the LPHN3 gene interact with SNPs spanning the 11q region that contains DRD2 and NCAM1 genes, to double the risk of developing ADHD. This interaction not only explains genetic effects much better than taking each of these loci effects by separated but also differences in brain metabolism as depicted by proton magnetic resonance spectroscopy data and pharmacogenetic response to stimulant medication. These findings not only add information about how high order genetic interactions might be implicated in conferring susceptibility to develop ADHD but also show that future studies of the effects of genetic interactions on ADHD clinical information will help to shape predictive models of individual outcome.

Objectives.- Autism has been hypothesized to reflect neuronal disconnection. Several recent reports implicate the abnormalities of the white matter connectivity in autism. We aimed to focus on evaluating hemispheric asymmetry in autism spectrum disorders (ASD) using a Diffusion Tensor Imaging (DTI). Methods.- We examined the difference of white matter integrity between left and right hemispheres using the DTI in Korean boys with high functioning ASD and age and sex matched healthy controls. Results.- We found that the asymmetry of FA values between left and right hemispheres in inferior longitudinal fasciculus and inferior fronto-occipital fasciculus were significantly decreased in ASD group compared to controls. It mainly was due to reduced FA value of left hemisphere in ASD. Conclusions.- Our findings suggested that the ASD might have atypical hemispheric asymmetry of white matter integrity assessed with DTI. These findings will help on understanding of more advanced neurobiological basis underlying ASD