Encoding of Depth in Parietal Reach Region (PRR)
Rajan Bhattacharyya, Richard Andersen

Technological developments in the past decade have accelerated the pace of research in brain computer interfaces. Multiple research groups across the country are pursuing this area of research as a possible solution to spinal cord injury. The Andersen lab at Caltech specializes in studying brain areas in the parietal cortex, which is associated with vision and motor planning, and in particular the Parietal Reach Region (PRR) which encodes the plan for the next intended reach movement, which is markedly different than the approach taken by other research groups which are using the motor cortex as the source of control signal. The Cortical Prosthetic Project at the Andersen lab has multiple research areas, including the development of an implantable chip to read signals from the parietal cortex, development of computational models for the neural signals involved, development of an online decoding algorithm for the intended movements, and finally the implementation of the real time control of a robotic arm through a brain computer interface.

This project seeks to investigate the encoding of depth by PRR neurons by carrying out experiments that in essence characterize the system. The first experiment will involve training non-human primates to maintain fixed eye positions while reaching to targets at various locations in three dimensional space. The second experiment will have the primates vary eye positions, however maintain fixed reach locations. Subsequently, we will investigate the neural mechanism by which PRR neurons encode the intended three dimensional reach location and develop a computational model to simulate the process. Lastly, we will augment the online decoding algorithm that is under development to decode PRR signals from implanted arrays in non human primates to control a robotic arm in real time to make reaches to locations in three dimensional space. (full report)

Reward Expectancy in Dorsomedial Frontal Cortex
of the Macaque Monkey
M. Campos, B. Breznen, and R. A. Andersen

We recorded neural activity from the dorsomedial frontal cortex of two macaque monkeys during the performance of memory guided and object based saccade tasks. Target locations in both tasks were identical, and event defined intervals could be readily compared across tasks. In about 75% of the recorded neurons we observed a burst of activity during the interval following the instructed saccade in both tasks. The majority (65%) of these neurons also showed a shift in the onset time of this burst from one task to the other. The burst occurred immediately after the target-acquiring saccade in the object based task, but with a ~250ms delay in the memory guided task. The timing of the burst corresponded to the appearance of the visual feedback that indicated to the monkey that he successfully completed the task. Furthermore, in successful trials the burst terminated with the delivery of the reward, but in error trials, in which the monkey attempted the proper saccade but was not rewarded, the burst was sustained for up to 2 seconds. We interpret these results to mean that the burst activity in these cells reflects an expectation of a reward, and that it persists until the reward is obtained.

Decoding Neuroprosthetic Control Signals from Human Parietal Cortex
Daniel Rizzuto, Richard Andersen

Recent work in macaques has shown that different areas of posterior parietal cortex are specialized for planning hand and eye movements (1; 2), and that it is possible to use recordings from these areas to predict the direction of the planned movement (3). Preliminary studies from our group have taken the first step toward identifying the human homologue of the macaque parietal reach region (PRR), which is responsible for planning hand movements (4). However, it is still unknown if neural activity in human PRR exhibits the same spectral characteristics as that in the macaque. To address this question we are working with human participants who have chronically implanted electrodes placed on the surface of cortex and within deep brain regions, often in partial cortex. Recording taken from these participants while they execute delayed reaches allow us to acquire high signal-to-noise intracranial EEG (iEEG) activity from cortical areas during motor planning. Analysis of this neural activity is aimed at determining which properties of the signal can be used to decode and predict planned movement.

Additionally, in order for human PRR to serve as a substrate for neuroprosthetic control signals it must be resistant to pathological reorganization after cortico-spinal tract (CST) injury, an issue which is still a matter of debate. To address this, we have begun using fMRI to examine differences in motor planning activity in quadriplegic patients compared to normal participants. This comparison will allow us to see to what degree the activity in these areas degenerates after CST injury. The results of these studies will provide an assessment of the feasibility of using PRR recordings in patients with CST injury to control a prosthetic device.(full report)

Robotics Facilitation in Spinal Learning
Lance Cai, Andy Fong, Joel Burdick and V. Reggie Edgerton

Each year, 11,000 Americans suffer spinal cord injury. Victims of severe spinal cord injury may suffer symptoms as severe as paraplegia, quadriplegia, and death. Currently we have no means of restoring locomotor function to patients who have suffered severe neural tissue damage resulting from spinal cord injury. While ideal treatments for such injuries involve regenerating the damaged tissues or developing compensatory neural connections, these options are not yet feasible. For patients who have lost the ability to walk, however, promising studies indicate that properly conducted, systematic motor training may help them walk again. (full report)

Neuromechanical Design and Active Sensory Systems in Animals
Malcolm Maciver, Joel Burdick

The field of neuroethology has made tremendous progress in understanding the sensory processing that subserve natural behaviors. Much work remains, however, in obtaining an equally detailed and quantitative understanding of how the mechanics of animals subserve natural behaviors, and in particular, how sensory abilities complement an animal’s mechanical control and locomotory needs and characteristics. In addition to its basic science import, these issues have relevance to engineers seeking to emulate some of key advantages of animal neuromechanical design, such as high maneuverability, and high levels of sensory integration for executing behaviors under changing and uncertain conditions. In this work we study how motion and sensing are integrated in the weakly electric fish. (full report)

Control Algorithm for Movable Neuro-Probes
Zoran Nenadic

Abstract. The process of extracellular recording from animals cortex is rarely automated. Moreover, such a procedure requires a constant human supervision and could be very time consuming. Here we propose a new algorithm that automatically controls the position of a recording electrode, while maintaining a certain level of signal quality. (full report)

Fly Flight Simulator to Study Visual and Rotational Stimuli
John Bender, Michael Dickinson, Pietro Perona

The fly flight arena was designed (not by me!) to explore the connections between the different sensory modalities that fruit flies use to control their flight. The fly is glued to a metal post mounted in the center of a cylindrical arena. The walls of this cylinder are made out of 11,340 LEDs which are controlled in real time by a computer. (Flies have poor spatial resolution, estimated at 5°, but very fast temporal resolution - around 200 Hz. Human vision has spatial resolution of about 1/30th degree and temporal resolution around 20 Hz.) (full report)

Modular Electronics for Rapid Development of Behavioral Stimuli
Michael Reiser, Michael Dickinson

Whereas flies use many sensory modalities, most of the behaviors we casually observe are dominated by visual control. For this reason, presenting controlled visual environment to tethered flies continues to be a powerful experimental paradigm. Most experiments have been done in simple arenas, either patterns attached to a rotating drum, or in recent years, using cylinders covered with LEDs. Conventional display technologies (LCDs, CRTs, etc.) can not be used as stimuli for insect experiments, because their refresh rates are typically several times slower than the flicker fusion rate of insect visual systems. LEDs are used because they can be rapidly refreshed, which is necessary to maintain the illusion of motion. We have designed modular panels of 64 LEDs each, which can be snapped together to ‘tile’ an experimental environment with controllable displays. The panels are individually addressed and communicated with via a rapid serial interface. The panels have been designed to be extremely bright (with the added flexibility of individual pixel programmable brightness control), allowing experimentation over a broad range of behaviorally relevant stimuli conditions. The panels are controlled via a microprocessor controller which, for most experiments, will not require a computer in the loop, significantly reducing the infrastructure necessary for experiments. This technology allows an experimenter to build a visual arena with a customized geometry in a matter of hours.
(full report)

Vision as a Compensatory Mechanism for Disturbance Rejection in Upwind Flight
Michael Reiser, Michael Dickinson, Sean Humbert, Richard Murray

For several decades the visuo-motor control system of flies has been extensively studied. However, recent results have cast new light on many long standing assumptions about the operation of the flight control system. In this project we seek to demonstrate that through a faithful model of the fly's behavior, it is possible to provide some context within which controlled behavioral assays can be interpreted. (full report)

A Biosphere for Studying Neural Circuits of Drosophila melanogaster
Jasper Simon, Michael Dickinson

Research Proposal. Observation rather than experimentation dominates the study of animal behavior, a limit to our understanding. We require the ability to study behavior while aspects of an animal's environment can be controlled. To meet this goal, I plan a biosphere in which I can control various parameters to recapitulate the pertinent aspects of an animal's natural environment.

Seasonal change and undesirable habitats force animals to assess local resources and decide between to stay or to move somewhere potentially more desirable. Cues from both the environment and an animal's current internal state influence such decisions. What mechanisms underlie the ability to integrate and process these cues? Is movement directed simply by cue saliency? Or do animals carry out some rudimentary cost-benefit analysis?

Within a neuroethological context, resource leaving in the fruit fly Drosophila melanogaster provides a useful model to study such elementary decision making. With the molecular tools available in Drosophila, I propose to study the neural circuits involved in this process.

Neurogenetic Dissection of Resource Choice in the Fruit Fly Drosophila melanogaster
Jasper Simon, Michael Dickinson

Abstract. I propose to study the neurogenetic mechanisms that underlie resource choice in the fruit fly Drosophila melanogaster. Specifically, how do genes regulate the decision to leave resources? In natural environments the distribution and abundance of resources vary over space and time—quite scarce during certain times in the life of a fly. Thus, it seems flies would stay indefinitely on an established resource, but casual observation proves this false. At various times scales: moment-to-moment, over the course of a day, or throughout a lifetime, flies leave resources. What external and internal cues influence the probability to leave? How do these cues interact? Moreover, this behavior initiates dispersal and has implications for the animal’s life history. Within a neuroethologcal context, resource leaving in flies provides a useful model to study elementary decision-making in a simple nervous system. I aim to characterize, identify, and define the relative contribution of external sensory cues, internal state cues, and their interactions in the determination of resource choice. Using molecular and population genetic approaches, I will attempt to identify the neuronal circuits and genes that participate in the regulation of resource choice.

The Stochastic Nature of Single Neurons
Kamran Diba, Christof Koch

Our labs have been very active in furthering our understanding of the biophysical noise in neocortical pyramidal cells. The Hebrew University group traveled to California in March, and Dr. Kamran Diba traveled twice to Jerusalem in April and August to discuss and advance our collaborative research. Theoretically, we have strengthened our understanding of the role of ion channels and synaptic vesicular release in determining the voltage noise fluctuations. Experimentally, we made more measurements under varied pharmacological conditions. We also developed a method for quantifying instrumental noise, and we began measuring the input impedance of the cell with zap currents. We presented a poster at the Society for Neuroscience meeting in November. We are presently working to understand some of the low-frequency noise features that we recently uncovered. (full report)

Line Source Approximation Predicts Extra-Cellular Voltage for CA1 Neurons Recorded In Vivo
Carl Gold, Christof Koch, Darrell Henze, Gyorgy Buzsaki

Abstract. The Line Source Approximation (LSA) is a mathematical method for calculating the extracellular field from a 3-D distribution of membrane current sources. We investigate the use of the LSA combined with detailed compartmental modeling, including a model of the electrodes used, to predict the extracellular voltage waveform shape and magnitude resulting from the spiking activity of individual neurons. This provides an estimate of the maximal distance at which a neuron could be detected by an extracellular electrode. In order to tune the model we compare simultaneous intracellular and extracellular recordings of CA1 neurons recorded in vivo with model predictions for the same cells reconstructed and simulated. The approximate electrode position is estimated from the histologically determined track. We overcome the uncertainty regarding the values of biophysical parameters, such as the extra-cellular conductivity and the membrane Na+ conductance, by comparing the model and experimental results for numerous samples of the same class of neuron. Based upon comparisons with experimental data, we conclude that the compartmental model can accurately simulate the in vivo intracellular action potential and the LSA model can accurately simulate the extracellular fields of individual spiking neurons.

The Involvement of the Anterior Cingulate Cortex in Novelty
Han C.J., Anderson D.J., & Koch, C.

The activation of the anterior cingulate cortex was previously shown to correlate with novelty detection. However, whether the anterior cingulate cortex is necessary to novelty detection is unclear. We set up a novelty object paradigm in mice. Mice were brought to the testing room in their home cage. A group of mice received a novel object (a corning 15 ml tube), a group received the same procedure including lifting the cage lid but not the object, and a group received nothing. We showed that the novel object readily induces the exploratory behaviors of the mouse directed towards the novel object, and cage lid lifting induces general exploratory behaviors. The sum of time that the group receiving the novel object and the group receiving the lid lifting spend in exploratory behaviors are equal, but the exploratory behaviors in the group that received the novel object are mostly directly to the object. c-fos mRNA was used as a surrogate marker to detect neuronal activation by in situ hybridization on brains from each group. Animals from each of the three groups were sacrificed 30 minutes after the first exposure of the stimulus. We discovered that there are more c-fos positive cells in the anterior cingulate cortex of the brain that received the novel object, compared with the other two groups. To answer the question whether the anterior cingulate cortex is necessary for novelty detection, a group of mice received excitotoxic lesions of the anterior cingulate cortex and another group received sham surgery. Behavioral experiments and analyses are being conducted to determine whether the lesions to the anterior cingulate cortex cause any exploratory behavioral changes directed to the novel object.

Inter-stimulus Distance Effects in Visual Search
Lavanya Reddy, Rufin VanRullen, Christof Koch

Abstract. In a previous study, we showed that the attentional requirements of a task, as revealed by the dual-task paradigm, do not necessarily determine whether visual search will be parallel or serial. For example, natural scene categorization can be performed "preattentively" in a dual-task situation (i.e., a single scene containing animals can be discriminated from non-animal scenes even while attention is occupied elsewhere), and yet visual search for an animal scene among a number of non-animal scenes is a serial process. We interpreted these findings as follows: a task can be performed preattentively if there exist specific neuronal populations selective to the target and distractor categories, independent of the level of processing involved (from V1 to IT); when such selectivities exist, visual search is parallel only if the receptive fields of the relevant neurons do not significantly overlap. When receptive fields are too large, target and distractors compete within the same field and search is serial. It follows that search performance should improve if target and distractors can be separated enough to prevent them from falling into the same receptive field. We tested this prediction and found that for preattentive tasks that usually result in serial visual search (e.g., color-orientation conjunction discrimination, upright vs. inverted face discrimination), search performance improved as inter-stimulus distance was increased. For preattentive parallel tasks (color discrimination, orientation discrimination), the effect of increasing inter-stimulus distance was negligible. These results support the idea that for preattentive tasks, competition within the relevant receptive fields can affect visual search performance.

Trace and Delay Fear Conditioning and its Dependence on Awareness in Humans
Tsuchia, N., Koch, C

Previous studies of associative learning implicate higher-level cognitive processes in some forms of classical conditioning. An ongoing debate is concerned with the extent to which attention and awareness are necessary for trace but not delay eye blink conditioning (Clark, R.E. & Squire, L.R. (1998) Science 280, 77-81; Lovibond, P.F. & Shanks, D. (2002) J. Exp. Psychol. Anim. Behav. Process 28, 38-42]. In trace conditioning, a short interval is interposed between the termination of the conditioned stimulus CS and the onset of the unconditioned stimulus US. In delay conditioning, the CS and US overlap. We investigate the extent to which human classical fear conditioning depends on working memory and attention. (full report)