Shaun L. Cloherty

Saccadic modulation of neural responses: possible roles in saccadic suppression, enhancement, and time compression.

Humans use saccadic eye movements to make frequent gaze changes, yet the associated full-field image motion is not perceived. The theory of saccadic suppression has been proposed to account for this phenomenon, but it is not clear whether suppression originates from a retinal signal at saccade onset or from the brain before saccade onset. Perceptually, visual sensitivity is reduced before saccades and enhanced afterward. Over the same time period, the perception of time is compressed and even inverted. We explore the origins and neural basis of these effects by recording from neurons in the dorsal medial superior temporal area (MSTd) of alert macaque monkeys. Neuronal responses to flashed presentations of a textured pattern presented at random times relative to saccades exhibit a stereotypical pattern of modulation. Response amplitudes are strongly suppressed for flashes presented up to 90 ms before saccades. Immediately after the suppression, there is a period of 200–450 ms in which flashes generate enhanced response amplitudes. Our results show that (1) MSTd is not directly suppressed, rather suppression is inherited from earlier visual areas; (2) early suppression of the visual system must be of extra-retinal origin; (3) postsaccadic enhancement of neural activity occurs in MSTd; and (4) the enhanced responses have reduced latencies. As a whole, these observations reveal response properties that could account for perceptual observations relating to presaccadic suppression, postsaccadic enhancement and time compression.

Parameter-Optimized Model of Cardiovascular–Rotary Blood Pump Interactions

A lumped parameter model of human cardiovascular-implantable rotary blood pump (iRBP) interaction has been developed based on experimental data recorded in two healthy pigs with the iRBP in situ. The model includes descriptions of the left and right heart, direct ventricular interaction through the septum and pericardium, the systemic and pulmonary circulations, as well as the iRBP. A subset of parameters was optimized in a least squares sense to faithfully reproduce the experimental measurements (pressures, flows and pump variables). Our fitted model compares favorably with our experimental measurements at a range of pump operating points. Furthermore, we have also suggested the importance of various model features, such as the curvilinearity of the end systolic pressure-volume relationship, the Starling resistance, the suction resistance, the effect of respiration, as well as the influence of the pump inflow and outflow cannulae. Alterations of model parameters were done to investigate the circulatory response to rotary blood pump assistance under heart failure conditions. The present model provides a valuable tool for experiment designs, as well as a platform to aid in the development and evaluation of robust physiological pump control algorithms.

Intrinsic physiological properties of rat retinal ganglion cells with a comparative analysis

Mammalian retina contains 15-20 different retinal ganglion cell (RGC) types, each of which is responsible for encoding different aspects of the visual scene. The encoding is defined by a combination of RGC synaptic inputs, the neurotransmitter systems used, and their intrinsic physiological properties. Each cells intrinsic properties are defined by its morphology and membrane characteristics, including the complement and localization of the ion channels expressed. In this study, we examined the hypothesis that the intrinsic properties of individual RGC types are conserved among mammalian species. To do so, we measured the intrinsic properties of 16 morphologically defined rat RGC types and compared these data with cat RGC types. Our data demonstrate that in the rat different morphologically defined RGC types have distinct patterns of intrinsic properties. Variation in these properties across cell types was comparable to that found for cat RGC types. When presumed morphological homologs in rat and cat retina were compared directly, some RGC types had very similar properties. The rat A2 cell exhibited patterns of intrinsic properties nearly identical to the cat alpha cell. In contrast, rat D2 cells (ON-OFF directionally selective) had a very different pattern of intrinsic properties than the cat iota cell. Our data suggest that the intrinsic properties of RGCs with similar morphology and suspected visual function may be subject to variation due to the behavioral needs of the species.

Effects of saccades on visual processing in primate MSTd

In surveying their visual environment, primates, including humans make frequent rapid eye movements known as saccades. Saccades result in rapid motion of the retinal image and yet this motion is not perceived. We recorded saccade-related changes in neural activity in the dorsal medial superior temporal area (MSTd) of alert macaque monkeys. We show that the spontaneous activity of neurons in MSTd is modulated around the time of saccades. Some cells show considerable suppression of spontaneous activity, while most show early and significant enhancement. While this modulation of spontaneous activity is variable, the concomitant modulation of neural responses evoked by flashed visual stimuli is uniform and stereotypical - visual responses are suppressed for stimuli presented around the time of saccades and enhanced for stimuli presented afterwards. The combined modulation of spontaneous activity and evoked visual responses likely serves to reduce the detectability of peri-saccadic stimuli and promote the perceptual awareness of visual stimuli between saccades.

Noninvasive Average Flow and Differential Pressure Estimation for an Implantable Rotary Blood Pump Using Dimensional Analysis

Accurate noninvasive average flow and differential pressure estimation of implantable rotary blood pumps (IRBPs) is an important practical element for their physiological control. While most attempts at developing flow and differential pressure estimate models have involved purely empirical techniques, dimensional analysis utilizes theoretical principles of fluid mechanics that provides valuable insights into parameter relationships. Based on data obtained from a steady flow mock loop under a wide range of pump operating points and fluid viscosities, flow and differential pressure estimate models were thus obtained using dimensional analysis. The algorithm was then validated using data from two other VentrAssist IRBPs. Linear correlations between estimated and measured pump flow over a flow range of 0.5 to 8.0 L/min resulted in a slope of 0.98 (R 2 = 0.9848). The average flow error was 0.20 plusmn 0.14 L/min (mean plusmn standard deviation) and the average percentage error was 5.79%. Similarly, linear correlations between estimated and measured pump differential pressure resulted in a slope of 1.027 (R 2 = 0.997) over a pressure range of 60 to 180 mmHg. The average differential pressure error was 1.84 plusmn 1.54 mmHg and the average percentage error was 1.51%.

Optimizing the Electrical Stimulation of Retinal Ganglion Cells

Epiretinal prostheses aim to restore visual perception in the blind through electrical stimulation of surviving retinal ganglion cells (RGCs). While the effects of several waveform parameters (e.g., phase duration) on stimulation efficacy have been described, their relative influence remains unclear. Further, morphological differences between RGC classes represent a key source of variability that has not been accounted for in previous studies. Here we investigate the effect of electrical stimulus waveform parameters on activation of an anatomically homogenous RGC population and describe a technique for identifying optimal stimulus parameters to minimize the required stimulus charge. Responses of rat A2-type RGCs to a broad array of biphasic stimulation parameters, delivered via an epiretinal stimulating electrode (200 × 200 μm) were recorded using whole-cell current clamp techniques. The data demonstrate that for rectangular charge-balanced stimuli, phase duration and polarity have the largest effect on threshold current amplitude-cells were most responsive to cathodic-first pulses of short phase duration. Waveform asymmetry and increases in interphase interval further reduced thresholds. Using optimal waveform parameters, we observed a drop in stimulus efficacy with increasing stimulation frequency. This was more pronounced for large cells. Our results demonstrate that careful choice of electrical waveform parameters can significantly improve the efficacy of electrical stimulation and the efficacy of implantable neurostimulators for the retina.

Complex cell receptive fields: evidence for a hierarchical mechanism

Simple cells in the primary visual cortex have segregated ON and OFF subregions in their receptive fields, while complex cells have overlapping ON and OFF subregions. These two cell types form the extremes at each end of a continuum of receptive field types. Hubel and Wiesel in 1962 suggested a hierarchical scheme of processing whereby spatially offset simple cells drive complex cells. Simple and complex cells are often classified by their responses to moving sine wave gratings: simple cells have oscillatory responses while complex cells produce unmodulated responses. Here, using moving gratings as stimuli, we show that a significant number of cells that display low levels of response modulation at high contrasts demonstrate high levels of response modulation at low contrasts. Most often a drifting low contrast grating generates a large phasic response at the fundamental frequency of the grating (F1) and a smaller but significant phasic response that is approximately 180 deg out‐of‐phase with the F1 component. We present several models capable of capturing the effects of stimulus contrast on complex cell responses. The model that best reproduces our experimental results is a variation of the classical hierarchical model. In our model several spatially offset simple cells provide input to a complex cell, with each simple cell exhibiting a different contrast response function. At low contrasts only one of these simple cells is sufficiently excited to reveal its receptive field properties. As contrast is increased additional spatially offset simple cells with higher contrast thresholds add their responses to the overall spiking activity.

NONINVASIVE DETECTION OF SUCTION IN AN IMPLANTABLE ROTARY BLOOD PUMP USING NEURAL NETWORKS

Granting those heart failure patients who are recipients of an implantable rotary blood pump (iRBP) greater functionality in daily activities is a key long-term strategy currently being pursued by many research groups. A reliable technique for noninvasive detection of the various pumping states, most notably that of ventricular collapse or suction, is an essential component of this strategy. Presented in this study is such a technique, whereby various indicators are derived from the noninvasive pump feedback signals, and a suitable computational methodology developed to classify the pumping states of interest. Clinical telemetry data from ten implant recipients was categorized (with the aid of trans-oesophageal echocardiography) into the normal and suction states. These data are used to develop a pumping state classifier based on an artificial neural network (ANN). Nine indices, derived from the noninvasive impeller speed signal, form the inputs to this ANN classifier. During validation, the resulting ANN classifier achieved a maximum sensitivity of 98.54% (609/618 samples of 5 s in length) and specificity of 99.26% (12,123/12,213 samples) for correct detection of the suction state. The ability to detect the suction state with such a high degree of accuracy provides a critical parameter both for control strategy development, and for clinical care of the implant recipient.

A Dynamic Lumped Parameter Model of the Left Ventricular Assisted Circulation

A lumped parameter model of the cardiovascular system (CVS) and its interaction with an implantable rotary blood pump (iRBP) is presented. The CVS model consists of the heart, the systemic and the pulmonary circulations. The pump model is made up of three differential equations, i.e. the motor equation, the torque equation and the hydraulic equation. Qualitative comparison with data from ex vivo porcine experiments suggests that the model is able to simulate different physiologically significant pumping states with varying pump speed set points. The combined CVS- iRBP model is suitable for use as a tool for investigating changes in the circulatory system parameters in the presence of the pump, and for testing control algorithms.

Current Distribution During Parallel Stimulation: Implications for an Epiretinal Neuroprosthesis

A simplified mathematical model has been developed in order to better understand local current spread when multiple simultaneous current sources are used in an epiretinal neuroprosthesis. To test the model, pairs of platinum electrodes of 430 mum diameter and an intra-pair spacing of 1 mm between centers, were arranged either in-line or in parallel, in a bath of physiological saline. Each pair was separated by distances from 1 mm to 6 mm. The currents in each electrode in the bath were measured and compared with the computational model of the same arrangement. This approach allowed us to quantify return current interaction between parallel sources. As predicted, with parallel electrodes and matching currents in each electrode pair, there is no current cross-talk. However with imbalanced current sources, significant cross-talk is evident. The cross-talk decreases as a function of electrode pair separation. The implication of this work in the design of an epiretinal neuroprosthesis is discussed