Linking Visual Cortical Development to Visual Perception

Defense Advanced Research Projects Agency and the Office of Naval Research (N00014-95-1-0409); National Science Foundation (IRI-97-20333); Office of Naval Research (N00014-95-1-0657

Neuromodulation for Depression: Insights Gained from Neuroimaging and Computational Models

Major depressive disorder (MDD) is a public health concern worldwide, affecting a sixth of the American population. Neuromodulation therapies have been employed to treat severe cases of treatment resistant depression. These procedures attempt to modulate activity in cortical regions that represent nodes in brain circuits believed to be involved in MDD. One challenge in neuromodulation trials has been the difficulty in quantifying outcome variability. We sought to understand the effects of neuromodulation therapies and their sources of variability while adding an objective perspective to assess clinical improvement in neuropsychiatric disorders such as depression. The goal of my dissertation was to investigate the neuronal circuitry of MDD patients who were treated using neuromodulation. Our primary measures were behavior scores and results from functional neuroimaging. The specific aims of this study were to answer three fundamental questions: 1) What is the role of stimulation parameters in patient response to chronic epidural cortical stimulation (EpCS) for MDD? 2) What functional changes result from repetitive transcranial magnetic stimulation (rTMS) for MDD? 3) How does stimulation of different targets in the depressive circuit affect antidepressive response? Our results suggest that combining neuroimaging with computational tools can increase the predictive power to determine who is likely to respond to a specific neuromodulation treatment course. We demonstrated the significance of stimulation parameters (location, polarity, duration) and the engagement of crucial nodes of the depressive circuit in order to achieve a sustained clinical improvement. Additionally, we showed that it is possible to affect deeper brain regions by targeting superficial areas that are easier to access with noninvasive modalities. The approaches highlighted in this dissertation can provide valuable insights about patients evaluated for neuromodulation for depression

Emulating long-term synaptic dynamics with memristive devices

The potential of memristive devices is often seeing in implementing neuromorphic architectures for achieving brain-like computation. However, the designing procedures do not allow for extended manipulation of the material, unlike CMOS technology, the properties of the memristive material should be harnessed in the context of such computation, under the view that biological synapses are memristors. Here we demonstrate that single solid-state TiO2 memristors can exhibit associative plasticity phenomena observed in biological cortical synapses, and are captured by a phenomenological plasticity model called triplet rule. This rule comprises of a spike-timing dependent plasticity regime and a classical hebbian associative regime, and is compatible with a large amount of electrophysiology data. Via a set of experiments with our artificial, memristive, synapses we show that, contrary to conventional uses of solid-state memory, the co-existence of field- and thermally-driven switching mechanisms that could render bipolar and/or unipolar programming modes is a salient feature for capturing long-term potentiation and depression synaptic dynamics. We further demonstrate that the non-linear accumulating nature of memristors promotes long-term potentiating or depressing memory transitions

Applications of transcranial direct current stimulation for understanding brain function

In recent years there has been an exponential rise in the number of studies employing transcranial direct current stimulation (tDCS) as a means of gaining a systems-level understanding of the cortical substrates underlying behaviour. These advances have allowed inferences to be made regarding the neural operations that shape perception, cognition, and action. Here we summarise how tDCS works, and show how research using this technique is expanding our understanding of the neural basis of cognitive and motor training. We also explain how oscillatory tDCS can elucidate the role of fluctuations in neural activity, in both frequency and phase, in perception, learning, and memory. Finally, we highlight some key methodological issues for tDCS and suggest how these can be addressed

A Neural Model of How Horizontal and Interlaminar Connections of Visual Cortex Develop into Adult Circuits that Carry Out Perceptual Grouping and Learning

A neural model suggests how horizontal and interlaminar connections in visual cortical areas Vl and V2 develop within a laminar cortical architecture and give rise to adult visual percepts. The model suggests how mechanisms that control cortical development in the infant lead to properties of adult cortical anatomy, neurophysiology, and visual perception. The model clarifies how excitatory and inhibitory connections can develop stably by maintaining a balance between excitation and inhibition. The growth of long-range excitatory horizontal connections between layer 2/3 pyramidal cells is balanced against that of short-range disynaptic interneuronal connections. The growth of excitatory on-center connections from layer 6-to-4 is balanced against that of inhibitory interneuronal off-surround connections. These balanced connections interact via intracortical and intercortical feedback to realize properties of perceptual grouping, attention, and perceptual learning in the adult, and help to explain the observed variability in the number and temporal distribution of spikes emitted by cortical neurons. The model replicates cortical point spread functions and psychophysical data on the strength of real and illusory contours. The on-center off-surround layer 6-to-4 circuit enables top-clown attentional signals from area V2 to modulate, or attentionally prime, layer 4 cells in area Vl without fully activating them. This modulatory circuit also enables adult perceptual learning within cortical area Vl and V2 to proceed in a stable way.Defense Advanced Research Projects Agency and the Office of Naval Research (N00014-95-1-0409); National Science Foundation (IRI-97-20333); Office of Naval Research (N00014-95-1-0657

The guilty brain: the utility of neuroimaging and neurostimulation studies in forensic field

Several studies have aimed to address the natural inability of humankind to detect deception and accurately discriminate lying from truth in the legal context. To date, it has been well established that telling a lie is a complex mental activity. During deception, many functions of higher cognition are involved: the decision to lie, withholding the truth, fabricating the lie, monitoring whether the receiver believes the lie, and, if necessary, adjusting the fabricated story and maintaining a consistent lie. In the previous 15 years, increasing interest in the neuroscience of deception has resulted in new possibilities to investigate and interfere with the ability to lie directly from the brain. Cognitive psychology, as well as neuroimaging and neurostimulation studies, are increasing the possibility that neuroscience will be useful for lie detection. This paper discusses the scientific validity of the literature on neuroimaging and neurostimulation regarding lie detection to understand whether scientific findings in this field have a role in the forensic setting. We considered how lie detection technology may contribute to addressing the detection of deception in the courtroom and discussed the conditions and limits in which these techniques reliably distinguish whether an individual is lying

Developmental disorders of vision

This review of developmental disorders of vision focuses on a few of the many disorders that disrupt visual development. Given the enormity of the human visual system in the primate brain and complexity of visual development, however, there are likely hundreds or thousands of potential types of disorders affecting high-level vision. The rapid progress seen in developmental dyslexia and Williams syndrome demonstrates the possibilities and difficulties inherent in researching such disorders, and the authors hope that similar progress will be made for congenital prosopagnosia and other disorders in the near future

How Does the Cerebral Cortex Work? Developement, Learning, Attention, and 3D Vision by Laminar Circuits of Visual Cortex

A key goal of behavioral and cognitive neuroscience is to link brain mechanisms to behavioral functions. The present article describes recent progress towards explaining how the visual cortex sees. Visual cortex, like many parts of perceptual and cognitive neocortex, is organized into six main layers of cells, as well as characteristic sub-lamina. Here it is proposed how these layered circuits help to realize the processes of developement, learning, perceptual grouping, attention, and 3D vision through a combination of bottom-up, horizontal, and top-down interactions. A key theme is that the mechanisms which enable developement and learning to occur in a stable way imply properties of adult behavior. These results thus begin to unify three fields: infant cortical developement, adult cortical neurophysiology and anatomy, and adult visual perception. The identified cortical mechanisms promise to generalize to explain how other perceptual and cognitive processes work.Air Force Office of Scientific Research (F49620-01-1-0397); Office of Naval Research (N00014-01-1-0624

Temporal Dynamics of Binocular Disparity Processing with Corticogeniculate Interactions

A neural model is developed to probe how corticogeniculate feedback may contribute to the dynamics of binocular vision. Feedforward and feedback interactions among retinal, lateral geniculate, and cortical simple and complex cells are used to simulate psychophysical and neurobiological data concerning the dynamics of binocular disparity processing, including correct registration of disparity in response to dynamically changing stimuli, binocular summation of weak stimuli, and fusion of anticorrelated stimuli when they are delayed, but not when they are simultaneous. The model exploits dynamic rebounds between opponent ON and OFF cells that are due to imbalances in habituative transmitter gates. It shows how corticogeniculate feedback can carry out a top-down matching process that inhibits incorrect disparity response and reduces persistence of previously correct responses to dynamically changing displays.Air Force Office of scientific Research (F49620-92-J-0499, F49620-92-J-0334, F49620-92-J-0225); Defense Advanced Research Projects Agency and the Office of Naval Research (N00014-95-1-0409, N00014-92-J-4015); Natioanl Science Foundation (IRI-97-20333); Office of Naval Research (N00014-95-0657

Synaptic mechanisms of interference in working memory

Information from preceding trials of cognitive tasks can bias performance in the current trial, a phenomenon referred to as interference. Subjects performing visual working memory tasks exhibit interference in their trial-to-trial response correlations: the recalled target location in the current trial is biased in the direction of the target presented on the previous trial. We present modeling work that (a) develops a probabilistic inference model of this history-dependent bias, and (b) links our probabilistic model to computations of a recurrent network wherein short-term facilitation accounts for the dynamics of the observed bias. Network connectivity is reshaped dynamically during each trial, providing a mechanism for generating predictions from prior trial observations. Applying timescale separation methods, we can obtain a low-dimensional description of the trial-to-trial bias based on the history of target locations. The model has response statistics whose mean is centered at the true target location across many trials, typical of such visual working memory tasks. Furthermore, we demonstrate task protocols for which the plastic model performs better than a model with static connectivity: repetitively presented targets are better retained in working memory than targets drawn from uncorrelated sequences.Comment: 28 pages, 7 figure