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.

A simple technique for remote scanning of the focal plane in temporal focusing multiphoton microscopy is demonstrated both theoretically and experimentally. A new on-axis light propagation optical setup design enables this scanning, which was considered not feasible in previous studies. The focal plane is axially displaced by the movement of a remote optical device, consisting of a double prism grating, and optionally a cylindrical lens. The displacement is linear, and its slope is inversely proportional to the square of the optical system's magnification.

The method of patterned photoactivation is a natural fit for the study of neuronal dendritic integration. Photoactivatable molecules that influence a wide range of extracellular and intracellular neurophysiological functions are available. The choice of photosensitive molecules depends on the research question and will influence the design of the experimental apparatus. An acousto-optical deflector (AOD)-based system can be used for rapid ultraviolet (UV) photolysis in arbitrary spatial and temporal patterns. This protocol describes how to prepare caged neurotransmitter compound solutions for use in this system and discusses options for introducing caged compounds into an experimental preparation.

Brain-machine interfaces (BMIs) rely on decoding neuronal activity from a large number of electrodes. The implantation procedures, however, do not guarantee that all recorded units encode task-relevant information: selection of task-relevant neurons is critical to performance but is typically performed based on heuristics. Here, we describe an algorithm for decoding/classification of volitional actions from multiple spike trains, which automatically selects the relevant neurons. The method is based on sparse decomposition of the high-dimensional neuronal feature space, projecting it onto a low-dimensional space of codes serving as unique class labels. The new method is tested against a range of existing methods using simulations and recordings of the activity of 1592 neurons in 23 neurosurgical patients who performed motor or speech tasks. The parameter estimation algorithm is orders of magnitude faster than existing methods and achieves significantly higher accuracies for both simulations and human data, rendering sparse decoding highly attractive for BMIs.

There are two views on vertebrate retinogenesis: a deterministic model dependent on fixed lineages and a stochastic model in which choices of division modes and cell fates cannot be predicted. In this issue of Neuron, He et al. (2012) address this question in zebrafish using live imaging and mathematical modeling.

The compound eye of Drosophila melanogaster consists of about 750 ommatidia (unit eyes). Each ommatidium is composed of about 20 cells, including lens-secreting cone cells, pigment cells, a bristle cell and eight photoreceptors (PRs) R1-R8. The PRs have specialized microvillar structures, the rhabdomeres, which contain light-sensitive pigments, the Rhodopsins (Rhs). The rhabdomeres of six PRs (R1-R6) form a trapezoid and contain Rh1. The rhabdomeres of R7 and R8 are positioned in tandem in the center of the trapezoid and share the same path of light. R7 and R8 PRs stochastically express different combinations of Rhs in two main subtypes: In the 'p' subtype, Rh3 in pR7s is coupled with Rh5 in pR8s, whereas in the 'y' subtype, Rh4 in yR7s is associated with Rh6 in yR8s. Early specification of PRs and development of ommatidia begins in the larval eye-antennal imaginal disc, a monolayer of epithelial cells. A wave of differentiation sweeps across the disc and initiates the assembly of undifferentiated cells into ommatidia. The 'founder cell' R8 is specified first and recruits R1-6 and then R7. Subsequently, during pupal development, PR differentiation leads to extensive morphological changes, including rhabdomere formation, synaptogenesis and eventually rh expression. In this protocol, we describe methods for retinal dissections and immunohistochemistry at three defined periods of retina development, which can be applied to address a variety of questions concerning retinal formation and developmental pathways. Here, we use these methods to visualize the stepwise PR differentiation at the single-cell level in whole mount larval, midpupal and adult retinas (Figure 1).

Knowledge of the long-term course of childhood Attention Deficit Hyperactivity Disorder (ADHD) is limited by the lack of longitudinal studies that extend beyond the third decade. Information about the later adult status of children with ADHD, one of the most common disorders of childhood, is important since the disorder is widely reported to persist through adulthood. Findings from a prospective 30 year longitudinal study addresses the extended course of ADHD. We report on the functional and psychiatric outcome of 135 males at mean age 41, diagnosed with ADHD at mean age of 8 (range, 6-12 years), and 136 non-ADHD males matched for age and SES, interviewed blindly by trained clinicians. As expected, ADHD at follow-up was significantly elevated in probands (P < 0.001). When the number of ADHD criteria is reduced, as recommended for ADHD in adults, rates rise in both groups. Other disorders significantly more prevalent in probands were:antisocial personality disorder (APD), drug (non-alcohol) disorders, and nicotine dependence. Childhood ADHD was not associated with elevated rates of mood or anxiety disorders in adulthood. Findings pertaining to other functional domains also will be presented. The extended clinical course of ADHD appears diagnostically specific, consisting of ADHD, APD and drug (non-alcohol) use disorders, supporting the validity of the ADHD diagnosis

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

Because multiple symptoms associated with "sickness behavior" have a negative impact on functional status and quality of life, increased information on the mechanisms that underlie inter-individual variability in this symptom experience is needed. The purposes of this study were to determine: if distinct classes of individuals could be identified based on their experience with pain, fatigue, sleep disturbance, and depression; if these classes differed on demographic and clinical characteristics; and if variations in pro- and anti- inflammatory cytokine genes were associated with latent class membership. Self-report measures of pain, fatigue, sleep disturbance, and depression were completed by 168 oncology outpatients and 85 family caregivers (FCs). Using latent class profile analysis (LCPA), three relatively distinct classes were identified: those who reported low depression and low pain (83%), those who reported high depression and low pain (4.7%), and those who reported high levels of all four symptoms (12.3%). The minor allele of IL4 rs2243248 was associated with membership in the "All high" class along with younger age, being White, being a patient (versus a FC), having a lower functional status score, and having a higher number of comorbid conditions. Findings suggest that LPCA can be used to differentiate distinct phenotypes based on a symptom cluster associated with sickness behavior. Identification of distinct phenotypes provides new evidence for the role of IL4 in the modulation of a sickness behavior symptom cluster in oncology patients and their FCs.