Faculty Bibliography

At high and ultra-high magnetic field strengths, understanding interactions between tissues and the electromagnetic fields generated by radiofrequency coils becomes crucial for safe and effective coil design as well as for insight into limits of performance. In this work, we present a rigorous electrodynamic modeling framework, using dyadic Green's functions, to derive the electromagnetic field in homogeneous spherical and cylindrical samples resulting from arbitrary surface currents in the presence or absence of a surrounding radiofrequency shield. We show how to calculate ideal current patterns that result in the highest possible signal-to-noise ratio (ultimate intrinsic signal-to-noise ratio) or the lowest possible radiofrequency power deposition (ultimate intrinsic specific absorption rate) compatible with electrodynamic principles. We identify familiar coil designs within optimal current patterns at low to moderate field strength, thereby establishing and explaining graphically the near-optimality of traditional surface and volume quadrature designs. We also document the emergence of less familiar patterns, e.g., involving substantial electric- as well as magnetic-dipole contributions, at high field strength. Performance comparisons with particular coil array configurations demonstrate that optimal performance may be approached with finite arrays if ideal current patterns are used as a guide for coil design. Magn Reson Med, 2011. (c) 2011 Wiley Periodicals, Inc

We present high-resolution anatomical imaging of the cervical spinal cord in healthy volunteers at the ultrahigh field of 7 T with a prototype four-channel radiofrequency coil array, in comparison with 3-T imaging of the same subjects. Signal-to-noise ratios at both field strengths were estimated using the rigorous Kellman method. Spinal cord cross-sectional area measurements were performed, including whole-cord measurements at both fields and gray matter segmentation at 7 T. The 7-T array coil showed reduced sagittal coverage, comparable axial coverage and the expected significantly higher signal-to-noise ratio compared with equivalent 3-T protocols. In the cervical spinal cord, the signal-to-noise ratio was found by the Kellman method to be higher by a factor of 3.5 with the 7-T coil than with standard 3-T coils. Cervical spine imaging in healthy volunteers at 7 T revealed not only detailed white/gray matter differentiation, but also structures not visualized at lower fields, such as denticulate ligaments, nerve roots and rostral-caudal blood vessels. Whole-cord cross-sectional area measurements showed good agreement at both field strengths. The measurable gray/white matter cross-sectional areas at 7 T were found to be comparable with reports from histology. These pilot data demonstrate the use of higher signal-to-noise ratios at the ultrahigh field of 7 T for significant improvement in anatomical resolution of the cervical spinal cord, allowing the visualization of structures not seen at lower field strength, particularly for axial imaging

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.

RATIONALE: Although high anxiety is commonly associated with drug addiction, its causal role in this disorder is unclear. OBJECTIVES: In light of strong evidence for dissociable neural mechanisms underlying heroin and cocaine addiction, the present study investigated whether high anxiety predicts the propensity of rats to lose control over intravenous cocaine or heroin self-administration. METHODS: Sixty-four rats were assessed for anxiety in the elevated plus-maze, prior to extended access to intravenous cocaine or heroin self-administration. RESULTS: High-anxious rats, identified in the lower quartile of the population, showed a greater escalation of cocaine, but not heroin, self-administration compared with low-anxious rats selected in the upper quartile of the population. Anxiety scores were also positively correlated with the extent of escalation of cocaine self-administration. CONCLUSIONS: The present data suggest that high anxiety predisposes rats to lose control over cocaine-but not heroin-intake. High anxiety may therefore be a vulnerability trait for the escalation of stimulant but not opiate self-administration.

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.

The sentinel lymph node is the initial site of metastasis. Downregulation of antitumor immunity has a role in nodal progression. Our objective was to investigate the relationship between immune modulation and sentinel lymph node positivity, correlating it with outcome in melanoma patients. Lymph node/primary tissues from melanoma patients prospectively accrued and followed at New York University Medical Center were evaluated for the presence of regulatory T cells (Foxp3(+)) and dendritic cells (conventional: CD11c(+), mature: CD86(+)) using immunohistochemistry. Primary melanoma immune cell profiles from sentinel lymph node-positive/-negative patients were compared. Logistic regression models inclusive of standard-of-care/immunological primary tumor characteristics were constructed to predict the risk of sentinel lymph node positivity. Immunological responses in the positive sentinel lymph node were also compared with those in the negative non-sentinel node from the same nodal basin and matched negative sentinel lymph node. Decreased immune response was defined as increased regulatory T cells or decreased dendritic cells. Associations between the expression of these immune modulators, clinicopathological variables, and clinical outcome were evaluated using univariate/multivariate analyses. Primary tumor conventional dendritic cells and regression were protective against sentinel lymph node metastasis (odds ratio=0.714, 0.067; P=0.0099, 0.0816, respectively). Antitumor immunity was downregulated in the positive sentinel lymph node with an increase in regulatory T cells compared with the negative non-sentinel node from the same nodal basin (P=0.0005) and matched negative sentinel lymph node (P=0.0002). The positive sentinel lymph node also had decreased numbers of conventional dendritic cells compared with the negative sentinel lymph node (P<0.0001). Adding sentinel lymph node regulatory T cell expression improved the discriminative power of a recurrence risk assessment model using clinical stage. Primary tumor regression was associated with prolonged disease-free (P=0.025) and melanoma-specific (P=0.014) survival. Our results support an assessment of local immune profiles in both the primary tumor and sentinel lymph node to help guide therapeutic decisions.

BACKGROUND: While 20% of schizophrenia patients worldwide speak tonal languages (e.g. Mandarin), studies are limited to Western-language patients. Western-language patients show tonal deficits that are related to impaired emotional processing of speech. However, language processing is minimally affected. In contrast, in Mandarin, syllables are voiced in one of four tones, with word meaning varying accordingly. We hypothesized that Mandarin-speaking schizophrenia patients would show impairments in underlying basic auditory processing that, unlike in Western groups, would relate to deficits in word recognition and social outcomes.MethodAltogether, 22 Mandarin-speaking schizophrenia patients and 44 matched healthy participants were recruited from New York City. The auditory tasks were: (1) tone matching; (2) distorted tunes; (3) Chinese word discrimination; (4) Chinese word identification. Social outcomes were measured by marital status, employment and most recent employment status. RESULTS: Patients showed deficits in tone-matching, distorted tunes, word discrimination and word identification versus controls (all p<0.0001). Impairments in tone-matching across groups correlated with both word identification (p<0.0001) and discrimination (p<0.0001). On social outcomes, tonally impaired patients had 'lower-status' jobs overall when compared with tonally intact patients (p<0.005) and controls (p<0.0001). CONCLUSIONS: Our study is the first to investigate an interaction between neuropsychology and language among Mandarin-speaking schizophrenia patients. As predicted, patients were highly impaired in both tone and auditory word processing, with these two measures significantly correlated. Tonally impaired patients showed significantly worse employment-status function than tonally intact patients, suggesting a link between sensory impairment and employment status outcome. While neuropsychological deficits appear similar cross-culturally, their consequences may be language- and culture-dependent

Kidney stones composed predominantly (50% or more) of calcium phosphate constitute up to 10% of all stones and 15%-20% of calcium stones, 80% of which are composed of calcium oxalate. Calcium phosphate is a minor component of up to 30% of calcium oxalate stones as well. The cause of calcium phosphate stones is often obscure but most often related to a high urine pH. Some patients with calcium phosphate stones may have incomplete renal tubular acidosis. Others have distal renal tubular acidosis characterized by hyperchloremic acidosis, hypocitraturia, and high urine pH. The use of carbonic anhydrase inhibitors such as acetazolamide, topiramate, and zonisamide leads to a similar picture. Treatment options to specifically prevent calcium phosphate stone recurrence have not been tested in clinical trials. Increases in urine volume and restriction of sodium intake to limit calcium excretion are important. Citrate supplementation is probably effective, although the concomitant increase in urine pH may increase calcium phosphate supersaturation and partially offset the inhibition of crystallization resulting from the increased urine citrate excretion and the alkali-associated reduction in urine calcium excretion. Thiazides lower urine calcium excretion and may help ensure the safety of citrate supplementation.