Search

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012., This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections., Cataloged from student-submitted PDF version of thesis., Includes bibliographical references (p. 100-105)., In the following thesis, I describe the investigation of two problems related to the organization and structural analysis of visual information: perceptual grouping and silhouette analysis and representation. For the problem of perceptual grouping, an intuitive model framework was developed which operates on raw images and locates relevant groupings utilizing a higher dimensional space that contains not only the two spatial dimensions of the image but one or more dimension corresponding to relevant image features such as luminance, hue, or orientation. A psychophysical experiment was run to measure how human visual observers perform perceptual grouping across a variety of spatial scales and luminance differences. These results were compared with the predictions of our grouping model, and the model was able to capture much of the grouping behavior of the human subjects. A second experiment was run in which the perception of groups was disrupted by the presence of noise or shifts in brightness. Though the experiments showed only small effects resulting from these disruptions on the behavior of human subjects, the model was still able to successfully capture much of the image-to-image variability. For the question of silhouette representation and analysis, I suggest that human silhouette representation may be inextricably tied to 3D interpretation of 2D shapes. To support this, I propose a novel algorithm for 2D silhouette inflation called Puffball, which closely matches human intuition for a variety of simple shapes and can be run on almost any input. Using this algorithm, a new model of human part segmentation was derived using 2D-to-3D inflation; this model was evaluated against human-generated part segmentations and two competing part segmentation algorithms. Across a variety of different analyses, Puffball part segmentation performed as well or better than its competitors, suggesting a potential role for 2D-to-3D inflation in the segmentation of silhouette parts., by Nathaniel R. Twarog., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012., This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections., Cataloged from student-submitted PDF version of thesis., Includes bibliographical references (p. 107-116)., Some of the biggest achievements in our lives are made even before we learn to tie our shoes. Within a few years of life, we master a language, acquire cultural norms, and develop naïve, yet rich, abstract, coherent theories about how the world works. How do young learners achieve such a feat? The goal of my thesis is to lay the groundwork for a unified account of a rational inference mechanism that underlies this remarkable human faculty to learn so much, so fast, from so little. The first study (Chapter 2) provides evidence that 16-month-old infants can use co-variation information among agents and objects to infer the cause of their failed actions; depending on their attribution, infants either approached another agent or another object. The second study (Chapter 3) shows that 15-month-old infants consider both the sample and the sampling process to rationally generalize properties of novel objects in the absence of behavioral cues. The results are consistent with the quantitative predictions of a Bayesian model, and suggest that infants' inferences are graded with respect to the probability of the sample. Finally, the third study (Chapter 4) shows that older children make sophisticated inferences about properties of agents; children evaluated an informant based on information he provided, and such evaluations affected how children learned from that informant. These studies provide evidence for rational, probabilistic, domain-general inference mechanisms in preverbal infants, and demonstrate how young learners seamlessly integrate data from different sources in ways that affect their exploration, generalization, and evaluation of both the physical and the social world., by Hyowon Gweon., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012., This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections., Cataloged from student-submitted PDF version of thesis. Page 125 blank., Includes bibliographical references., The integration of anatomical, functional, and developmental approaches in cognitive neuroscience is essential for generating mechanistic explanations of brain function. In this thesis, I first establish a proof-of-principle that neuroanatomical connectivity, as measured with diffusion weighted imaging (DWI), can be used to calculate connectional fingerprints that are sufficient to delineate fine anatomical distinctions in the human brain (Chapter 2). Next, I describe the maturation of structural connectivity patterns by applying these connectional fingerprints to over a hundred participants ranging from five to thirty years of age, and show that these connectional patterns have different developmental trajectories (Chapter 3). I then illustrate how anatomical connections may shape (or in turn be shaped by) function and behavior, within the framework of reading ability and describe how white matter tract integrity may predict future acquisition of reading ability in children (Chapter 4). I conclude by summarizing how these experiments offer testable hypotheses of the maturation of structure and function. Studying the complex interplay between structure, function, and development will get us closer to understanding both the constraints present at birth, and the effect of experience, on the biological mechanisms underlying brain function., by Zeynep Mevhibe Saygin., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012., This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections., Cataloged from student-submitted PDF version of thesis., Includes bibliographical references (p. 100-105)., In the following thesis, I describe the investigation of two problems related to the organization and structural analysis of visual information: perceptual grouping and silhouette analysis and representation. For the problem of perceptual grouping, an intuitive model framework was developed which operates on raw images and locates relevant groupings utilizing a higher dimensional space that contains not only the two spatial dimensions of the image but one or more dimension corresponding to relevant image features such as luminance, hue, or orientation. A psychophysical experiment was run to measure how human visual observers perform perceptual grouping across a variety of spatial scales and luminance differences. These results were compared with the predictions of our grouping model, and the model was able to capture much of the grouping behavior of the human subjects. A second experiment was run in which the perception of groups was disrupted by the presence of noise or shifts in brightness. Though the experiments showed only small effects resulting from these disruptions on the behavior of human subjects, the model was still able to successfully capture much of the image-to-image variability. For the question of silhouette representation and analysis, I suggest that human silhouette representation may be inextricably tied to 3D interpretation of 2D shapes. To support this, I propose a novel algorithm for 2D silhouette inflation called Puffball, which closely matches human intuition for a variety of simple shapes and can be run on almost any input. Using this algorithm, a new model of human part segmentation was derived using 2D-to-3D inflation; this model was evaluated against human-generated part segmentations and two competing part segmentation algorithms. Across a variety of different analyses, Puffball part segmentation performed as well or better than its competitors, suggesting a potential role for 2D-to-3D inflation in the segmentation of silhouette parts., by Nathaniel R. Twarog., Ph.D.

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012., Cataloged from PDF version of thesis., Includes bibliographical references (p. 37-42)., Chronic stress has been linked to variation in gene regulation in the hippocampus (HIP) among other areas. These lead to cytoskeletal and volumetric rearrangements in various nuclei of the central nervous system and are thought to contribute to several stress-sensitive disorders. One such gene that has been shown to be downregulated in HIP in response to stress is somatotropin, colloquially known as growth hormone (GH). These experiments were conducted to develop a novel assay for examination of working memory in rats and explore the nature of stress-induced impairment of hippocampal function and determine whether infusion of a modified herpes simplex virus (HSV) carrying the recombinant rodent growth hormone (GH) would be sufficient to restore normal hippocampal function. After 21 days of chronic immobilization stress (CIS), animals received bilateral infusions into the dorsal HIP of 2[mu]l HSV carrying either GH with green florescent protein (GFP) or GFP only. On the second day following the infusion, the animals received trace conditioning, a HIP-dependent task, with five tone-shock pairings of a 16 second tone followed by a 30 second trace interval terminating with a 1 second 0.85 milliamp footshock. An inter-trial interval of 3 minutes was used to separate the tone-shock pairings. The following day the animals were tested for fear to the context and for fear to the tone in a novel context, measured by amount of time the animal spent freezing. Using this criterion, animals that had undergone stress that received the control vector were less likely to freeze when presented with the tone, indicating an impairment of hippocampal function. Viral-mediated overexpression of GH in the dorsal HIP was able to reverse the CIS-related impairment in hippocampal function. ELISA was used to verify the expression of GH from the infused vector. These experiments may yield future directions of investigation for stress-based disorders., by Christopher M. Saenz., S.M.

Thesis (S.M. and S.B.)--Massachusetts Institute of Technology, Dept. of Political Science; and, (S.B.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2011., Cataloged from PDF version of thesis., Includes bibliographical references (p. 81-86)., State failure is becoming increasingly prevalent across the globe, creating human suffering, black markets, lost economic opportunities, and safe havens for militant actors. It is imperative that the international community find a way to combat state failure. This study investigates the effects of irregular leadership transitions on state failure recovery. Irregular leadership transitions occur when the executive of a state comes to power through unconstitutional means. Regular leaders are more likely than irregular leaders to have personal experience as a ruler, beneficial domestic and international ties, and familiarity among the population. Irregular transitions may damage bureaucracies, damaging government functionality and halting development projects that had already been underway. Regular leaders benefit from a legacy that was likely able to pass spoils onto an elite group. This elite group is likely to resist relative losses to power more than lower status groups would fight to gain power because of the cognitive principles of risk aversion, and the sensitivity to status inherent to social identity theory. Regular leaders also have traditional legitimacy, while irregular leaders are more likely to have to gain legitimacy. State failure and failure recovery are overdetermined, so it is impossible to be able to confidently determine the direction of causal flow. Every determinant of failure is related to every other, and it is difficult to separate their effects. The role of leadership regularity is therefore investigated as a proxy that can predict variation on the rate of failure recovery. The quantitative analysis consisted of multi and bivariate regressions investigating the effects of leadership regularity on failure duration, as well as the relative explanatory power held by several factors associated with leadership regularity. Robustness checks were performed using Bayesian statistics, and survival analyses. Irregular leadership transitions were found, by Laila A. Wahedi., S.B., S.M.and S.B.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012., "June 2012." Cataloged from PDF version of thesis., Includes bibliographical references., Parvalbumin-containing (PV+) neurons and somatostatin-containing (SOM+) neurons are two key cortical inhibitory cell classes that are poised to play distinct computational roles in cortical circuits: PV+ neurons form synapses on the perisomatic region near the spike initiation zone of target cells, while SOM+ neurons form synapses on distal dendrites. The goals of this thesis are to better understand the functional roles of these two cell types with four major lines of questioning. 1) When and how do PV+ and SOM+ neurons respond to visual stimuli? 2) How do inhibitory neurons obtain their response selectivity? 3) How do PV+ and SOM+ neurons affect the responses of their targets? and 4) What are the targets of PV+ and SOM+ neurons? We used Cre-lox recombination to introduce either fluorescent protein or channelrhodopsin to PV+ or SOM+ neurons, targeting these cells for two-photon targeted physiological recording and morphological reconstruction, or selectively stimulating the population of PV+ or SOM+ neurons or stimulating single PV+ or SOM+ neurons. We find diverse response properties within both groups, suggesting that further functional subclasses of PV+ and SOM+ neurons may exist. Furthermore, orientation selectivity was strongly correlated to dendritic length in PV+ neurons, whose orientation preferences matched the preferences of neighboring cells, implying that inhibitory neurons may obtain selectivity by spatially limiting their sampling of the local network. When we stimulated PV+ and SOM+ neurons, we found that they perform distinct inhibitory operations on their targets: PV+ neurons divide responses while SOM+ neurons subtract. Even single PV+ and SOM+ neurons were capable of suppressing responses of other cells in the local network, but their functional targeting was sparse and followed different rules of wiring: PV+ neurons functionally suppressed a higher percentage of cells that shared their own tuning, while SOM+ neurons seemed to target other neuron, by Caroline A. Runyan., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012., Cataloged from PDF version of thesis., Includes bibliographical references (p. 127-139)., This thesis proposes a computational framework for understanding human Theory of Mind (ToM): our conception of others' mental states, how they relate to the world, and how they cause behavior. Humans use ToM to predict others' actions, given their mental states, but also to do the reverse: attribute mental states - beliefs, desires, intentions, knowledge, goals, preferences, emotions, and other thoughts - to explain others' behavior. The goal of this thesis is to provide a formal account of the knowledge and mechanisms that support these judgments. The thesis will argue for three central claims about human ToM. First, ToM is constructed around probabilistic, causal models of how agents' beliefs, desires and goals interact with their situation and perspective (which can differ from our own) to produce behavior. Second, the core content of ToM can be formalized using context-specific models of approximately rational planning, such as Markov decision processes (MDPs), partially observable MDPs (POMDPs), and Markov games. ToM reasoning will be formalized as rational probabilistic inference over these models of intentional (inter)action, termed Bayesian Theory of Mind (BToM). Third, hypotheses about the structure and content of ToM can be tested through a combination of computational modeling and behavioral experiments. An experimental paradigm for eliciting fine-grained ToM judgments will be proposed, based on comparing human inferences about the mental states and behavior of agents moving within simple two-dimensional scenarios with the inferences predicted by computational models. Three sets of experiments will be presented, investigating models of human goal inference (Chapter 2), joint belief-desire inference (Chapter 3), and inference of interactively-defined goals, such as chasing and fleeing (Chapter 4). BToM, as well as a selection of prominent alternative proposals from the social perception literature will be evaluated by their quantitative fit to behavioral d, by Chris L. Baker., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012., Cataloged from PDF version of thesis., Includes bibliographical references (p. 81-93)., Developmental dyslexia is a neurological condition that specifically impairs the development of expert reading ability. Phonological processing deficits -- impaired representation of, or access to, the abstract units of spoken language -- have been implicated as the principal source of reading difficulties in dyslexia, independent of other cognitive factors. However, the source of these phonological impairments remains unknown: What mechanisms preclude development of the robust phonological representations critical for reading development? Experiments with phonological processing in dyslexia typically employ metalinguistic tasks that require explicit knowledge about phonological structure, failing to distinguish between access to representations and the representations themselves. Here I report a series of experiments that elucidate the nature of phonological impairments in dyslexia by examining the implicit processing of phonetic variability. Phonetic variability affects language processing at the interface between perceiving the physical speech signal and mapping it onto stored linguistic representations. This approach is well-suited to interrogate the integrity of phonological processing in dyslexia and to provide insight into how phonological representations may come to be impaired in this disorder. In Experiment 1, individuals with dyslexia demonstrated profoundly reduced ability to learn to use phonetic consistency in talker identification, thus reifying the status of phonological representations themselves as fundamentally impaired in this disorder. In Experiment 2, functional magnetic resonance imaging (fMRI) adaptation revealed reduced neural sensitivity to phonetic consistency during speech perception in individuals with dyslexia, indicating impaired rapid, implicit learning of phonetic-phonological consistency. The neural mechanisms that support such learning may be a specific instance of general brain mechanisms for adapting to stimulus consistency. In E, by Tyler K. Perrachione., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012., Cataloged from PDF version of thesis., Includes bibliographical references., According to the World Health Organization, neuropsychiatric diseases account for approximately one third of years lost to disability. Yet, despite this huge disease burden, there is a lack of new treatments under development: approved treatments all essentially target the same target(s), if the target itself is known. There is now considerable evidence for a common set of heritable risk for psychiatric disorders including schizophrenia, bipolar disorder, as well as autism. Many of these risk alleles affect genes implicated in neuronal development with known roles at an early stage; these genes would have an effect on the individual before the onset of overt symptoms or diagnosis. Furthermore, many of the genes identified are known to participate in established pathways that are relevant for neuronal development and function. It is important then to address the causality between these signaling pathways that are important for neurodevelopment, and the risk of developing neuropsychiatric disorder. The work presented in this thesis represents two projects that aim to work toward this goal. The first project pertains to the mechanisms of transcriptional repression by DISC1 on ATF4-mediated gene transcription. The second project presents some initial steps towards uncovering the role of BCL9 in neuronal development., by Takahiro Soda., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012., Cataloged from PDF version of thesis., Includes bibliographical references., The over-arching hypothesis that drives my work is that neural dynamics, fluctuating on millisecond to second time scales, powerfully impact perception. In this thesis, I employ correlative electrophysiological recording methods and causal optogenetic control of neural circuits to systematically test the importance of dynamics in the expression of pre-stimulus oscillations on perception. Specifically, I test the prediction that alpha oscillations expressed in a given sensory representation within a neocortical map predict diminished sensory capability in that region of sensory space, while gamma oscillations predict enhanced capacity. My model system throughout is primary somatosensory neocortex and tactile perception: I combine studies from human and mouse to benefit from the relative merits of each preparation. Several prior studies support this more generally stated view of oscillatory dynamics -- alpha predicting diminished and gamma predicting enhanced perceptual capacity. However, there is significant disagreement on even this broad assumption. Leading researchers have argued that alpha in fact predicts enhanced detection of tactile stimuli (e.g., Nicolelis and Fanselow, 2002). Further, there remains significant discord over whether gamma oscillations predict enhanced ability and, even if they do so, whether their expression is a causal contributor to this increased capacity or whether gamma is an epiphenomenal by-product of other beneficial shifts in neural dynamics. My thesis directly addresses these basic questions as to the predictive value of these oscillations, and favors the view that alpha and gamma are in general predictive of perception as stated. Further, I provide unique causal data showing that, under the conditions of our experiments, entrainment of a realistic and local gamma oscillation in neocortex can enhance stimulus detection. I also address important questions as to the independence of different frequency bands expressed in pre-stimulus os, by Dominique L. Pritchett., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2011., Cataloged from PDF version of thesis., Includes bibliographical references., Dopamine (DA) containing neurons project throughout the brain. DA has been implicated in mediating brain disorders such as Schizophrenia, Parkinson's disease, Huntington's disease and drug addiction. The role of DA in working memory and procedural learning is also well established. DA is a ubiquitous neurotransmitter that affects much of the brain, but very little is known how dopamine functions in hippocampal dependent learning. It was only until recently that dopamine-containing neurons were found to project to the hippocampus. Even less understood are the expression patterns of DA receptors within the hippocampus and this is underlined by the inability of distinguishing the dopamine 1 receptor family (D1 and 5 receptors (D1/D5Rs)). Given the interaction of the D1 family with similar G-protein coupled receptors it has been assumed that these two receptors function in an analogous fashion. Additionally, the specific expressional pattern of each receptor lacks clarity due to non-specific binding by molecular probes. Moreover, D1 and D5 pharmacological and global KO studies cannot and have not functionally delineated D1Rs from D5Rs and global KOs of the D1Rs or D5Rs are not specific to the hippocampus, thus compensatory mechanisms likely ameliorate most physiological and behavioral deficits. Still, the aforementioned studies do point to the D1 family in modulating hippocampal synaptic plasticity, learning and memory consolidation. In order to characterize D1Rs distinctly from D5Rs we have generated three strains of conditional mutant mice (D1 KO, D5 KO, D1/5 KO). I present data that shows distinct expression patterns within the hippocampus, the importance of D1 Rs and D5Rs in modulating hippocampal plasticity, and hippocampal dependent learning. These data highlight distinct functional roles of D1Rs and D5Rs in hippocampal function., by Joshua Sariñana Jr., Ph.D.

Thesis (S.M. and S.B.)--Massachusetts Institute of Technology, Dept. of Political Science; and, (S.B.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2011., Cataloged from PDF version of thesis., Includes bibliographical references (p. 81-86)., State failure is becoming increasingly prevalent across the globe, creating human suffering, black markets, lost economic opportunities, and safe havens for militant actors. It is imperative that the international community find a way to combat state failure. This study investigates the effects of irregular leadership transitions on state failure recovery. Irregular leadership transitions occur when the executive of a state comes to power through unconstitutional means. Regular leaders are more likely than irregular leaders to have personal experience as a ruler, beneficial domestic and international ties, and familiarity among the population. Irregular transitions may damage bureaucracies, damaging government functionality and halting development projects that had already been underway. Regular leaders benefit from a legacy that was likely able to pass spoils onto an elite group. This elite group is likely to resist relative losses to power more than lower status groups would fight to gain power because of the cognitive principles of risk aversion, and the sensitivity to status inherent to social identity theory. Regular leaders also have traditional legitimacy, while irregular leaders are more likely to have to gain legitimacy. State failure and failure recovery are overdetermined, so it is impossible to be able to confidently determine the direction of causal flow. Every determinant of failure is related to every other, and it is difficult to separate their effects. The role of leadership regularity is therefore investigated as a proxy that can predict variation on the rate of failure recovery. The quantitative analysis consisted of multi and bivariate regressions investigating the effects of leadership regularity on failure duration, as well as the relative explanatory power held by several factors associated with leadership regularity. Robustness checks were performed using Bayesian statistics, and survival analyses. Irregular leadership transitions were found, by Laila A. Wahedi., S.B., S.M.and S.B.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, September 2011., Cataloged from PDF version of thesis. "September 2011.", Includes bibliographical references (p. 125-156)., Parkinson's disease (PD) is an age-related degenerative disease of the brain, characterized by motor, cognitive, and psychiatric symptoms. Neurologists and neuroscientists now understand that several symptoms of the disease, including hallucinations and impulse control behaviors, stem from the dopaminergic medications used to control the motor aspects of PD. Not all patients experience these nonmotor symptoms and tools that can predict a priori which patients are likely to have an adverse response to medication do not exist. This thesis begins to fill this gap by elucidating the mechanisms underlying the adverse effects of dopaminergic medications. Converging evidence from animals and humans shows that individual differences in particular genes that affect the dopamine system may alter the response of PD patients to dopaminergic medication. We examined the hypothesis that patients taking dopamine replacement therapy who carry candidate alleles that increase dopamine signaling experience a dopamine overdose, causing unwanted psychiatric symptoms., by Paymon Ashourian., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2011., Cataloged from PDF version of thesis., Includes bibliographical references., Dopamine (DA) containing neurons project throughout the brain. DA has been implicated in mediating brain disorders such as Schizophrenia, Parkinson's disease, Huntington's disease and drug addiction. The role of DA in working memory and procedural learning is also well established. DA is a ubiquitous neurotransmitter that affects much of the brain, but very little is known how dopamine functions in hippocampal dependent learning. It was only until recently that dopamine-containing neurons were found to project to the hippocampus. Even less understood are the expression patterns of DA receptors within the hippocampus and this is underlined by the inability of distinguishing the dopamine 1 receptor family (D1 and 5 receptors (D1/D5Rs)). Given the interaction of the D1 family with similar G-protein coupled receptors it has been assumed that these two receptors function in an analogous fashion. Additionally, the specific expressional pattern of each receptor lacks clarity due to non-specific binding by molecular probes. Moreover, D1 and D5 pharmacological and global KO studies cannot and have not functionally delineated D1Rs from D5Rs and global KOs of the D1Rs or D5Rs are not specific to the hippocampus, thus compensatory mechanisms likely ameliorate most physiological and behavioral deficits. Still, the aforementioned studies do point to the D1 family in modulating hippocampal synaptic plasticity, learning and memory consolidation. In order to characterize D1Rs distinctly from D5Rs we have generated three strains of conditional mutant mice (D1 KO, D5 KO, D1/5 KO). I present data that shows distinct expression patterns within the hippocampus, the importance of D1 Rs and D5Rs in modulating hippocampal plasticity, and hippocampal dependent learning. These data highlight distinct functional roles of D1Rs and D5Rs in hippocampal function., by Joshua Sariñana Jr., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2011., Cataloged from PDF version of thesis., Includes bibliographical references (p. 121-130)., The visual system is a dynamic entity whose response properties depend on context and experience. In this thesis, I examine how the brain changes as we learn to see - what changes occur during the onset of recognition, in the mature visual system on the one hand, and in a developmentally nascent one, on the other? Working with normal adults, I focus on the processes that underlie the interpretation of images as meaningful entities. This interpretation is greatly facilitated by prior information about a stimulus. What are the neural sites that exhibit experience dependent changes? Using multivariate decoding techniques, I find pervasive evidence of such changes throughout the visual system. Critically, cortical regions previously implicated in such learning are not the same loci as sites of increased information. Examining the temporal mechanisms of recognition, I identify the perceptual state transitions corresponding to the onset of meaning in an observed image. Furthermore, decoding techniques reveal the flow of information during this 'eureka moment.' I find feedback processing when a degraded image is first meaningfully interpreted, and then a rapid transition into feed-forward processing for more coherent images. Complementing the studies with mature subjects, my work with developmentally nascent observers explores the genesis of visual interpretation. What neural changes accompany the earliest stages of visual learning? I show that children treated for congenital blindness exhibit significant cortical re-organization after sight onset, in contrast to the classical notion of a critical period for visual plasticity. The specific kind of reorganization suggests that visual experience enhances information coding efficiency in visual cortex. Additionally, I present evidence of rapid development of functionally specialized cortical regions. Overall, the thesis presents two complementary perspectives on the genesis of visual meaning. The results help advance our unde, by Scott Gorlin., Ph.D.

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012., Cataloged from PDF version of thesis., Includes bibliographical references (p. 37-42)., Chronic stress has been linked to variation in gene regulation in the hippocampus (HIP) among other areas. These lead to cytoskeletal and volumetric rearrangements in various nuclei of the central nervous system and are thought to contribute to several stress-sensitive disorders. One such gene that has been shown to be downregulated in HIP in response to stress is somatotropin, colloquially known as growth hormone (GH). These experiments were conducted to develop a novel assay for examination of working memory in rats and explore the nature of stress-induced impairment of hippocampal function and determine whether infusion of a modified herpes simplex virus (HSV) carrying the recombinant rodent growth hormone (GH) would be sufficient to restore normal hippocampal function. After 21 days of chronic immobilization stress (CIS), animals received bilateral infusions into the dorsal HIP of 2[mu]l HSV carrying either GH with green florescent protein (GFP) or GFP only. On the second day following the infusion, the animals received trace conditioning, a HIP-dependent task, with five tone-shock pairings of a 16 second tone followed by a 30 second trace interval terminating with a 1 second 0.85 milliamp footshock. An inter-trial interval of 3 minutes was used to separate the tone-shock pairings. The following day the animals were tested for fear to the context and for fear to the tone in a novel context, measured by amount of time the animal spent freezing. Using this criterion, animals that had undergone stress that received the control vector were less likely to freeze when presented with the tone, indicating an impairment of hippocampal function. Viral-mediated overexpression of GH in the dorsal HIP was able to reverse the CIS-related impairment in hippocampal function. ELISA was used to verify the expression of GH from the infused vector. These experiments may yield future directions of investigation for stress-based disorders., by Christopher M. Saenz., S.M.

Thesis (S.M. and S.B.)--Massachusetts Institute of Technology, Dept. of Political Science; and, (S.B.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2011., Cataloged from PDF version of thesis., Includes bibliographical references (p. 81-86)., State failure is becoming increasingly prevalent across the globe, creating human suffering, black markets, lost economic opportunities, and safe havens for militant actors. It is imperative that the international community find a way to combat state failure. This study investigates the effects of irregular leadership transitions on state failure recovery. Irregular leadership transitions occur when the executive of a state comes to power through unconstitutional means. Regular leaders are more likely than irregular leaders to have personal experience as a ruler, beneficial domestic and international ties, and familiarity among the population. Irregular transitions may damage bureaucracies, damaging government functionality and halting development projects that had already been underway. Regular leaders benefit from a legacy that was likely able to pass spoils onto an elite group. This elite group is likely to resist relative losses to power more than lower status groups would fight to gain power because of the cognitive principles of risk aversion, and the sensitivity to status inherent to social identity theory. Regular leaders also have traditional legitimacy, while irregular leaders are more likely to have to gain legitimacy. State failure and failure recovery are overdetermined, so it is impossible to be able to confidently determine the direction of causal flow. Every determinant of failure is related to every other, and it is difficult to separate their effects. The role of leadership regularity is therefore investigated as a proxy that can predict variation on the rate of failure recovery. The quantitative analysis consisted of multi and bivariate regressions investigating the effects of leadership regularity on failure duration, as well as the relative explanatory power held by several factors associated with leadership regularity. Robustness checks were performed using Bayesian statistics, and survival analyses. Irregular leadership transitions were found, by Laila A. Wahedi., S.B., S.M.and S.B.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, September 2011., Cataloged from PDF version of thesis. "September 2011.", Includes bibliographical references (p. 125-156)., Parkinson's disease (PD) is an age-related degenerative disease of the brain, characterized by motor, cognitive, and psychiatric symptoms. Neurologists and neuroscientists now understand that several symptoms of the disease, including hallucinations and impulse control behaviors, stem from the dopaminergic medications used to control the motor aspects of PD. Not all patients experience these nonmotor symptoms and tools that can predict a priori which patients are likely to have an adverse response to medication do not exist. This thesis begins to fill this gap by elucidating the mechanisms underlying the adverse effects of dopaminergic medications. Converging evidence from animals and humans shows that individual differences in particular genes that affect the dopamine system may alter the response of PD patients to dopaminergic medication. We examined the hypothesis that patients taking dopamine replacement therapy who carry candidate alleles that increase dopamine signaling experience a dopamine overdose, causing unwanted psychiatric symptoms., by Paymon Ashourian., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2011., Cataloged from PDF version of thesis., Includes bibliographical references (p. 179-191)., This thesis develops the hypothesis that key aspects of learning and development can be understood as rational statistical inferences over a compositionally structured representation system, a language of thought (LOT) (Fodor, 1975). In this setup, learners have access to a set of primitive functions and learning consists of composing these functions in order to created structured representations of complex concepts. We present an inductive statistical model over these representations that formalizes an optimal Bayesian trade-off between representational complexity and fit to the observed data. This approach is first applied to the case of number-word acquisition, for which statistical learning with a LOT can explain key developmental patterns and resolve philosophically troublesome aspects of previous developmental theories. Second, we show how these same formal tools can be applied to children's acquisition of quantifiers. The model explains how children may achieve adult competence with quantifiers' literal meanings and presuppositions, and predicts several of the most-studied errors children make while learning these words. Finally, we model adult patterns of generalization in a massive concept-learning experiment. These results provide evidence for LOT models over other approaches and provide quantitative evaluation of different particular LOTs., by Steven Thomas Piantadosi., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012., Cataloged from PDF version of thesis., Includes bibliographical references (p. 127-139)., This thesis proposes a computational framework for understanding human Theory of Mind (ToM): our conception of others' mental states, how they relate to the world, and how they cause behavior. Humans use ToM to predict others' actions, given their mental states, but also to do the reverse: attribute mental states - beliefs, desires, intentions, knowledge, goals, preferences, emotions, and other thoughts - to explain others' behavior. The goal of this thesis is to provide a formal account of the knowledge and mechanisms that support these judgments. The thesis will argue for three central claims about human ToM. First, ToM is constructed around probabilistic, causal models of how agents' beliefs, desires and goals interact with their situation and perspective (which can differ from our own) to produce behavior. Second, the core content of ToM can be formalized using context-specific models of approximately rational planning, such as Markov decision processes (MDPs), partially observable MDPs (POMDPs), and Markov games. ToM reasoning will be formalized as rational probabilistic inference over these models of intentional (inter)action, termed Bayesian Theory of Mind (BToM). Third, hypotheses about the structure and content of ToM can be tested through a combination of computational modeling and behavioral experiments. An experimental paradigm for eliciting fine-grained ToM judgments will be proposed, based on comparing human inferences about the mental states and behavior of agents moving within simple two-dimensional scenarios with the inferences predicted by computational models. Three sets of experiments will be presented, investigating models of human goal inference (Chapter 2), joint belief-desire inference (Chapter 3), and inference of interactively-defined goals, such as chasing and fleeing (Chapter 4). BToM, as well as a selection of prominent alternative proposals from the social perception literature will be evaluated by their quantitative fit to behavioral d, by Chris L. Baker., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012., Cataloged from PDF version of thesis., Includes bibliographical references., The over-arching hypothesis that drives my work is that neural dynamics, fluctuating on millisecond to second time scales, powerfully impact perception. In this thesis, I employ correlative electrophysiological recording methods and causal optogenetic control of neural circuits to systematically test the importance of dynamics in the expression of pre-stimulus oscillations on perception. Specifically, I test the prediction that alpha oscillations expressed in a given sensory representation within a neocortical map predict diminished sensory capability in that region of sensory space, while gamma oscillations predict enhanced capacity. My model system throughout is primary somatosensory neocortex and tactile perception: I combine studies from human and mouse to benefit from the relative merits of each preparation. Several prior studies support this more generally stated view of oscillatory dynamics -- alpha predicting diminished and gamma predicting enhanced perceptual capacity. However, there is significant disagreement on even this broad assumption. Leading researchers have argued that alpha in fact predicts enhanced detection of tactile stimuli (e.g., Nicolelis and Fanselow, 2002). Further, there remains significant discord over whether gamma oscillations predict enhanced ability and, even if they do so, whether their expression is a causal contributor to this increased capacity or whether gamma is an epiphenomenal by-product of other beneficial shifts in neural dynamics. My thesis directly addresses these basic questions as to the predictive value of these oscillations, and favors the view that alpha and gamma are in general predictive of perception as stated. Further, I provide unique causal data showing that, under the conditions of our experiments, entrainment of a realistic and local gamma oscillation in neocortex can enhance stimulus detection. I also address important questions as to the independence of different frequency bands expressed in pre-stimulus os, by Dominique L. Pritchett., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012., This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections., Cataloged from student-submitted PDF version of thesis., Includes bibliographical references (p. 191-197)., Faces are an important class of visual stimuli, and are thought to be processed differently from objects by the human visual system. Going beyond the false dichotomy of same versus different processing, it is more important to understand how exactly faces are processed similarly or differently from objects. However, even by itself, face processing is poorly understood. Various aspects of face processing, such as holistic, configural, and face-space processing, are investigated in relative isolation, and the relationships between these are unclear. Furthermore, face processing is characteristically affected by various stimulus transformations such as inversion, contrast reversal and spatial frequency filtering, but how or why is unclear. Most importantly, we do not understand even the basic mechanisms of face processing. We hypothesize that what makes face processing distinctive is the existence of large, coarse face templates. We test our hypothesis by modifying an existing model of object processing to utilize such templates, and find that our model can account for many face-related phenomena. Using small, fine face templates as a control, we find that our model displays object-like processing characteristics instead. Overall, we believe that we may have made the first steps towards achieving a unified account of face processing. In addition, results from our control suggest that face and object processing share fundamental computational mechanisms. Coupled with recent advances in brain recording techniques, our results mean that face recognition could form the "tip of the spear" for attacking and solving the problem of visual recognition., by Cheston Y.-C. Tan., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012., Cataloged from PDF version of thesis., Includes bibliographical references., According to the World Health Organization, neuropsychiatric diseases account for approximately one third of years lost to disability. Yet, despite this huge disease burden, there is a lack of new treatments under development: approved treatments all essentially target the same target(s), if the target itself is known. There is now considerable evidence for a common set of heritable risk for psychiatric disorders including schizophrenia, bipolar disorder, as well as autism. Many of these risk alleles affect genes implicated in neuronal development with known roles at an early stage; these genes would have an effect on the individual before the onset of overt symptoms or diagnosis. Furthermore, many of the genes identified are known to participate in established pathways that are relevant for neuronal development and function. It is important then to address the causality between these signaling pathways that are important for neurodevelopment, and the risk of developing neuropsychiatric disorder. The work presented in this thesis represents two projects that aim to work toward this goal. The first project pertains to the mechanisms of transcriptional repression by DISC1 on ATF4-mediated gene transcription. The second project presents some initial steps towards uncovering the role of BCL9 in neuronal development., by Takahiro Soda., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012., "June 2012." Cataloged from PDF version of thesis., Includes bibliographical references., Parvalbumin-containing (PV+) neurons and somatostatin-containing (SOM+) neurons are two key cortical inhibitory cell classes that are poised to play distinct computational roles in cortical circuits: PV+ neurons form synapses on the perisomatic region near the spike initiation zone of target cells, while SOM+ neurons form synapses on distal dendrites. The goals of this thesis are to better understand the functional roles of these two cell types with four major lines of questioning. 1) When and how do PV+ and SOM+ neurons respond to visual stimuli? 2) How do inhibitory neurons obtain their response selectivity? 3) How do PV+ and SOM+ neurons affect the responses of their targets? and 4) What are the targets of PV+ and SOM+ neurons? We used Cre-lox recombination to introduce either fluorescent protein or channelrhodopsin to PV+ or SOM+ neurons, targeting these cells for two-photon targeted physiological recording and morphological reconstruction, or selectively stimulating the population of PV+ or SOM+ neurons or stimulating single PV+ or SOM+ neurons. We find diverse response properties within both groups, suggesting that further functional subclasses of PV+ and SOM+ neurons may exist. Furthermore, orientation selectivity was strongly correlated to dendritic length in PV+ neurons, whose orientation preferences matched the preferences of neighboring cells, implying that inhibitory neurons may obtain selectivity by spatially limiting their sampling of the local network. When we stimulated PV+ and SOM+ neurons, we found that they perform distinct inhibitory operations on their targets: PV+ neurons divide responses while SOM+ neurons subtract. Even single PV+ and SOM+ neurons were capable of suppressing responses of other cells in the local network, but their functional targeting was sparse and followed different rules of wiring: PV+ neurons functionally suppressed a higher percentage of cells that shared their own tuning, while SOM+ neurons seemed to target other neuron, by Caroline A. Runyan., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012., Cataloged from PDF version of thesis., Includes bibliographical references (p. 81-93)., Developmental dyslexia is a neurological condition that specifically impairs the development of expert reading ability. Phonological processing deficits -- impaired representation of, or access to, the abstract units of spoken language -- have been implicated as the principal source of reading difficulties in dyslexia, independent of other cognitive factors. However, the source of these phonological impairments remains unknown: What mechanisms preclude development of the robust phonological representations critical for reading development? Experiments with phonological processing in dyslexia typically employ metalinguistic tasks that require explicit knowledge about phonological structure, failing to distinguish between access to representations and the representations themselves. Here I report a series of experiments that elucidate the nature of phonological impairments in dyslexia by examining the implicit processing of phonetic variability. Phonetic variability affects language processing at the interface between perceiving the physical speech signal and mapping it onto stored linguistic representations. This approach is well-suited to interrogate the integrity of phonological processing in dyslexia and to provide insight into how phonological representations may come to be impaired in this disorder. In Experiment 1, individuals with dyslexia demonstrated profoundly reduced ability to learn to use phonetic consistency in talker identification, thus reifying the status of phonological representations themselves as fundamentally impaired in this disorder. In Experiment 2, functional magnetic resonance imaging (fMRI) adaptation revealed reduced neural sensitivity to phonetic consistency during speech perception in individuals with dyslexia, indicating impaired rapid, implicit learning of phonetic-phonological consistency. The neural mechanisms that support such learning may be a specific instance of general brain mechanisms for adapting to stimulus consistency. In E, by Tyler K. Perrachione., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012., This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections., Cataloged from student-submitted PDF version of thesis., Includes bibliographical references (p. 191-197)., Faces are an important class of visual stimuli, and are thought to be processed differently from objects by the human visual system. Going beyond the false dichotomy of same versus different processing, it is more important to understand how exactly faces are processed similarly or differently from objects. However, even by itself, face processing is poorly understood. Various aspects of face processing, such as holistic, configural, and face-space processing, are investigated in relative isolation, and the relationships between these are unclear. Furthermore, face processing is characteristically affected by various stimulus transformations such as inversion, contrast reversal and spatial frequency filtering, but how or why is unclear. Most importantly, we do not understand even the basic mechanisms of face processing. We hypothesize that what makes face processing distinctive is the existence of large, coarse face templates. We test our hypothesis by modifying an existing model of object processing to utilize such templates, and find that our model can account for many face-related phenomena. Using small, fine face templates as a control, we find that our model displays object-like processing characteristics instead. Overall, we believe that we may have made the first steps towards achieving a unified account of face processing. In addition, results from our control suggest that face and object processing share fundamental computational mechanisms. Coupled with recent advances in brain recording techniques, our results mean that face recognition could form the "tip of the spear" for attacking and solving the problem of visual recognition., by Cheston Y.-C. Tan., Ph.D.

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012., Cataloged from PDF version of thesis., Includes bibliographical references (p. 117-122)., This thesis aims to elucidate shared mechanisms between retrieval in sentence processing and memory retrieval processes in nonlinguistic domains using an individual differences approach. Prior research in individual differences in sentence processing has provided conflicting evidence as to whether the same memory mechanisms operate in linguistic processing, potentially a quite specialized cognitive domain, and in other, more general areas of cognition (Just & Carpenter, 1992; Caplan & Waters, 1999). This question has been primarily addressed from the point of view of capacity-based theories of working memory (Baddeley, 1986). Under these theories, verbal working memory is either comprised of multiple components including separate components for syntactic and non-syntactic verbal processing, or is dependent on a unitary pool of resources shared across all verbal domains. However, recent memory research has suggested that the capacity-theory architecture may be incorrect. Instead of a three-part memory system composed of focal attention, working memory, and long-term memory, a better model of the memory system may be bipartite, comprising focal attention and long-term memory. In the bipartite theory, working memory is viewed as a set of mechanisms mediating between these two stores, and accurately describes empirical data (McElree, 2006). If the latter hypothesis is correct, then it follows that the bipartite system underlying sentence processing should rely on the same set of working memory mechanisms as in general memory processes. In particular, a number of empirical studies have shown that both general memory and sentence processing are subject to interference from contextually-relevant intervening elements. Such interference is thought to occur at retrieval (as opposed to encoding) both for general memory tasks (e.g., retrieving items from a list) and in sentence processing (e.g., retrieving elements in long-distance syntactic dependencies). However, no systemati, by Melissa L. Troyer., S.M.

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012., Cataloged from PDF version of thesis., Includes bibliographical references (p. 37-42)., Chronic stress has been linked to variation in gene regulation in the hippocampus (HIP) among other areas. These lead to cytoskeletal and volumetric rearrangements in various nuclei of the central nervous system and are thought to contribute to several stress-sensitive disorders. One such gene that has been shown to be downregulated in HIP in response to stress is somatotropin, colloquially known as growth hormone (GH). These experiments were conducted to develop a novel assay for examination of working memory in rats and explore the nature of stress-induced impairment of hippocampal function and determine whether infusion of a modified herpes simplex virus (HSV) carrying the recombinant rodent growth hormone (GH) would be sufficient to restore normal hippocampal function. After 21 days of chronic immobilization stress (CIS), animals received bilateral infusions into the dorsal HIP of 2[mu]l HSV carrying either GH with green florescent protein (GFP) or GFP only. On the second day following the infusion, the animals received trace conditioning, a HIP-dependent task, with five tone-shock pairings of a 16 second tone followed by a 30 second trace interval terminating with a 1 second 0.85 milliamp footshock. An inter-trial interval of 3 minutes was used to separate the tone-shock pairings. The following day the animals were tested for fear to the context and for fear to the tone in a novel context, measured by amount of time the animal spent freezing. Using this criterion, animals that had undergone stress that received the control vector were less likely to freeze when presented with the tone, indicating an impairment of hippocampal function. Viral-mediated overexpression of GH in the dorsal HIP was able to reverse the CIS-related impairment in hippocampal function. ELISA was used to verify the expression of GH from the infused vector. These experiments may yield future directions of investigation for stress-based disorders., by Christopher M. Saenz., S.M.

Thesis (S.M. and S.B.)--Massachusetts Institute of Technology, Dept. of Political Science; and, (S.B.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2011., Cataloged from PDF version of thesis., Includes bibliographical references (p. 81-86)., State failure is becoming increasingly prevalent across the globe, creating human suffering, black markets, lost economic opportunities, and safe havens for militant actors. It is imperative that the international community find a way to combat state failure. This study investigates the effects of irregular leadership transitions on state failure recovery. Irregular leadership transitions occur when the executive of a state comes to power through unconstitutional means. Regular leaders are more likely than irregular leaders to have personal experience as a ruler, beneficial domestic and international ties, and familiarity among the population. Irregular transitions may damage bureaucracies, damaging government functionality and halting development projects that had already been underway. Regular leaders benefit from a legacy that was likely able to pass spoils onto an elite group. This elite group is likely to resist relative losses to power more than lower status groups would fight to gain power because of the cognitive principles of risk aversion, and the sensitivity to status inherent to social identity theory. Regular leaders also have traditional legitimacy, while irregular leaders are more likely to have to gain legitimacy. State failure and failure recovery are overdetermined, so it is impossible to be able to confidently determine the direction of causal flow. Every determinant of failure is related to every other, and it is difficult to separate their effects. The role of leadership regularity is therefore investigated as a proxy that can predict variation on the rate of failure recovery. The quantitative analysis consisted of multi and bivariate regressions investigating the effects of leadership regularity on failure duration, as well as the relative explanatory power held by several factors associated with leadership regularity. Robustness checks were performed using Bayesian statistics, and survival analyses. Irregular leadership transitions were found, by Laila A. Wahedi., S.B., S.M.and S.B.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2010., Cataloged from PDF version of thesis., Includes bibliographical references (p. 297-205)., This thesis introduces EMRE, an expectation-based model of referring expressions. EMRE is proposed as a model of non-syntactic dependencies - in particular, discourse-level semantic dependencies that bridge sentence gaps. These include but are not limited to anaphora (references to noun phrases in previous sentences) and coherence predicates such as causality, temporal ordering and resemblance -- two domains that have typically been treated as entirely distinct aspects of language. EMRE is a computational-level model, and is agnostic about any particular algorithms, cognitive faculties, or neurological substrates that might be applied to the problem of semantic reference. Instead, it describes reference as a computational problem framed in terms of expectation and inference, and describes a solution to the problem based on rational top-down expectations about the likely targets of referring expressions, and on bottom-up feature-based matching that occurs when a referring expression is encountered. EMRE is used to derive novel empirical predictions about how people will construe particular discourse constructions involving NP anaphora and coherence predicates. These predictions are tested in controlled behavioral experiments, in which participants read and answer questions about short texts. The results of these experiments are shown to be consistent with a model of reference as an expectation-based computational structure with different underlying rules than those governing syntactic processing., by John Kræmer., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, February 2011., This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections., Cataloged from student-submitted PDF version of thesis., Includes bibliographical references., Inhibitory interneurons are thought to play a crucial role in several features of neocortical processing, including dynamics on the timescale of milliseconds. Their anatomical and physiological characteristics are diverse, suggesting that different types regulate distinct aspects of neocortical dynamics. Interneurons expressing parvalbumin (PV) and somatostatin (SOM) form two non-overlapping populations. Here, I describe computational, correlational (neurophysiological) and causal (optogenetic) studies testing the role of PV and SOM neurons in dynamic regulation of sensory processing. First, by combining extra- and intracellular recordings with optogenetic and sensory stimulation and pharmacology, we have shown that PV cells play a key role in the generation of neocortical gamma oscillations, confirming the predictions of prior theoretical and correlative studies. Following this experimental study, we used a biophysically plausible model, simulating thousands of neurons, to explore mechanisms by which these gamma oscillations shape sensory responses, and how such transformations impact signal relay to downstream neocortical areas. We found that the local increase in spike synchrony of sensory-driven responses, which occurs without decreasing spike rate, can be explained by pre- and post-stimulus inhibition acting on pyramidal and PV cells. This transformation led to increased activity downstream, constituting an increase in gain between the two regions. This putative benefit of PV-mediated inhibition for signal transmission is only realized if the strength and timing of inhibition in the downstream area is matched to the upstream source. Second, we tested the hypothesis that SOM cells impact a distinct form of dynamics, sensory adaptation, using intracellular recordings, optogenetics and sensory stimulation. In resting neocortex, we found that SOM cell activation generated inhibition in pyramidal neurons that matched that seen in in-vitro studies. Optical SOM cell a, by Ulf Knoblich., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2010., Cataloged from PDF version of thesis., Includes bibliographical references., Ecologically relevant search typically requires making rapid and strategic eye movements in complex, cluttered environments. Attention allocation is known to be influenced by low level image features, visual scene context, and top down task constraints. Scene specific context develops when observers repeatedly search the same environment (e.g. one's workplace or home) and this often leads to faster search performance. How does prior experience influence the deployment of eye movements when searching a familiar scene? One challenge lies in distinguishing between the roles of scene specific experience and general scene knowledge. Chapter 1 investigates eye guidance in novel scenes by comparing how well several models of search guidance predict fixation locations, and establishes a benchmark for inter-observer fixation agreement. Chapters 2 and 3 explore spatial and temporal characteristics of eye guidance from scene specific location priors. Chapter 2 describes comparative map analysis, a novel technique for analyzing spatial patterns in eye movement data, and reveals that past history influences fixation selection in three search experiments. In Chapter 3, two experiments use a response-deadline approach to investigate the time course of memory-based search guidance. Altogether, these results describe how using long-term memory of scene specific representations can effectively guide the eyes to informative regions when searching a familiar scene., by Barbara Hidalgo-Sotelo., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2011., Cataloged from PDF version of thesis., Includes bibliographical references (p. 190-212)., Declarative memory requires the integration and association of multiple input streams within the medial temporal lobe. Understanding the role each neuronal circuit and projection plays in learning and memory is essential to understanding how declarative and episodic-like memories are formed. This work here addresses the role of the medial entorhinal cortex layer III (MEC-III) to CA1 projections in episodic-like memory formation and recall. This circuit is addressed with a triple transgenic mouse which allows for the expression of tetanus toxin, an enzyme that disrupts synaptic vesicle fusion, specifically in MEC-III neurons. Utilizing this triple transgenic mouse model, which allows for the specific and reversible ablation of synaptic transmission only in medial entorhinal cortex layer III excitatory neurons, the function of this pathway in various learning and memory tasks is tested. Synaptic output from the medial entorhinal cortex layer III neurons is necessary for acquisition, but not recall of tone and contextual fear memories in trace fear conditioning, and not in delay conditioning. This is the first demonstration that acquisition and recall of the same memory engram do not require the exact same anatomy. Additionally, this pathway is necessary for performance in a delayed nonmatch-to-place working memory task, in which the animal must utilize memory from the previous trial to successfully complete the following trial. Both the trace and working memory paradigm require the integration of information across a delay, which we propose is supported by known persistent activity in entorhinal neurons. CAl receives input from both entorhinal layer III and CA3. We show that synaptic transmission from CA3 is not required for tone fear memory in the trace paradigm and not required for working memory in the same delayed nonmatch-to-place paradigm, further isolating the necessity for MEC-III inputs in both of these behaviors. Functional MEC-III synaptic transmission is a, by Alexander Jay Rivest., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2011., Cataloged from PDF version of thesis., Includes bibliographical references (p. 399-407)., This work serves as the first comprehensive investigation into typically developing children's acquisition of subject-to-subject (StS) raising. In particular, it asks how English-speaking children come to comprehend a StS raised sentence like (1) versus its semantically equivalent unraised counterpart (2), and how the presence of an experiencer-phrase affects interpretation (3): (1) John[subscript i] seems [t[subscript i] to be dancing]. (2) It seems that John is dancing. (3) John[subscript i] seems to Mary [t[subscript i] to be dancing]. The acquisition of StS raising is of particular bearing given renewed interest in the acquisition of verbal passives, which share syntactic traits with StS raising and which have been argued to develop late under genetic guidance. Using sentence-picture matching and truth-value judgment experiments, the following comprehension results obtain: e Unraised sentences are acquired early, with most three-year-old children demonstrating mastery. - Sentences involving StS raising over an experiencer (ROE) are delayed until around age seven, with many children incorrectly interpreting them as involving raising-to-object (RtO) syntax. e Sentences involving StS raising with no experiencer (RNE) are likewise delayed until around age seven, with many children incorrectly interpreting them as involving either subject control or copular syntax. - Subject control sentences are acquired early, by at least age three. - The delayed acquisition of StS raising (ROE and RNE) appears to be developmentally linked with the delayed acquisition of verbal passives. The noted delay in comprehension of StS raising occurs despite the fact that StS raising sentences are found to be relatively common in child-directed speech. These data serve to rule out several grammatical acquisition accounts in the literature that have attempted to capture children's delayed comprehension of verbal passives (e.g. External Argument Requirement Hypothesis, Canonical Alignment Hyp, by Christopher K. Hirsch., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2011., This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections., Cataloged from student-submitted PDF version of thesis., Includes bibliographical references (p. 254-302)., The ease with which we recognize visual objects belies the computational difficulty of this feat. Despite the concerted efforts of both biological and computer vision research communities over the last forty years, human-level visual recognition remains an unsolved problem. The impact of a robust yet inexpensive solution would dramatically change computer science and neuroscience, unleashing a host of innovative applications in our modern society. In this thesis, we identify two operational barriers that have obstructed progress towards finding a solution { namely the lack of clear indicators and operational definitions of success, and the currently limited exploration of the staggeringly large hypothesis space of biologically- inspired solutions. To break down these barriers, we first establish new neuroscience-motivated baselines and new suites of fully-controlled benchmarks for object and face recognition. We also compare and contrast a variety of high-level visual systems, both artificial (state-of-the- art computer vision) and biological (humans). Then, we propose a simple high-throughput approach to undertake a systematic exploration of the biologically-inspired model class. By leveraging recent advances in massively parallel computing, we show that it is possible to generate a multitude of candidate models, screen them for desirable properties and discover robust solutions. Finally, we validate the scalability of our approach by showing its potential on large-scale real-world" applications. Taken together, this thesis represents a humble attempt towards an integrated approach to the problem of brain-inspired object recognition { spanning the engineering, specification, evaluation, and application of an interesting set of biologically-inspired ideas, driven and enabled by massively parallel technology. Even relatively early instantiations of this approach yield algorithms that achieve state-of-the-art performance in object recognition tasks and can generalize, by Nicolas Pinto., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2010., Cataloged from PDF version of thesis., Includes bibliographical references., This thesis is a collection of manuscripts addressing connectivity of neural circuits in cultured hippocampal neurons. These studies begin with an investigation of dopaminergic modulation of excitatory synapses in small circuits of neurons grown on glial micro islands. We found that dopamine transiently depressed excitatory synaptic transmission. Scaling up to larger circuits of neurons proved more challenging, since finding connected pairs became combinatorially more improbable. The discovery and use of light-activatable ion channel channel rhodopsin-2 (ChR2) promised to revolutionize the way in which we could map connectivity in vitro. We successfully delivered the gene for ChR2 in hippocampal cultures using recombinant adeno-associated virus and characterized the spatial resolution, as well as the reliability of stimulating action potentials. However, there were limitations to this technique that would render circuit maps ambiguous and incomplete. More recently, the engineering of rabies virus (RV) as a neural circuit tracer has produced an exciting method whereby viral infection can be targeted to a population of neurons and spread of the virus restricted to monosynaptically connected neurons. We further investigated potential mechanisms for previous observations which claim that RV spread is restricted to synaptically connected neurons by manipulating neural activity and synaptic vesicle release. We found that RV spread increased for blockade of synaptic vesicle exocytosis and for blockade of neural activity. The underlying premise for pursuing these methods to elucidate connectivity is that the computational power of the brain comes from changeable, malleable connectivity and that to test network models of computation in a biological brain, we must map the connectivity between individual neurons. This thesis builds a framework for experiments designed to bridge the gap between computational learning theories and networks of live neurons., by Jennifer Lynn Wang., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, February 2011., This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections., Cataloged from student-submitted PDF version of thesis., Includes bibliographical references., Inhibitory interneurons are thought to play a crucial role in several features of neocortical processing, including dynamics on the timescale of milliseconds. Their anatomical and physiological characteristics are diverse, suggesting that different types regulate distinct aspects of neocortical dynamics. Interneurons expressing parvalbumin (PV) and somatostatin (SOM) form two non-overlapping populations. Here, I describe computational, correlational (neurophysiological) and causal (optogenetic) studies testing the role of PV and SOM neurons in dynamic regulation of sensory processing. First, by combining extra- and intracellular recordings with optogenetic and sensory stimulation and pharmacology, we have shown that PV cells play a key role in the generation of neocortical gamma oscillations, confirming the predictions of prior theoretical and correlative studies. Following this experimental study, we used a biophysically plausible model, simulating thousands of neurons, to explore mechanisms by which these gamma oscillations shape sensory responses, and how such transformations impact signal relay to downstream neocortical areas. We found that the local increase in spike synchrony of sensory-driven responses, which occurs without decreasing spike rate, can be explained by pre- and post-stimulus inhibition acting on pyramidal and PV cells. This transformation led to increased activity downstream, constituting an increase in gain between the two regions. This putative benefit of PV-mediated inhibition for signal transmission is only realized if the strength and timing of inhibition in the downstream area is matched to the upstream source. Second, we tested the hypothesis that SOM cells impact a distinct form of dynamics, sensory adaptation, using intracellular recordings, optogenetics and sensory stimulation. In resting neocortex, we found that SOM cell activation generated inhibition in pyramidal neurons that matched that seen in in-vitro studies. Optical SOM cell a, by Ulf Knoblich., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2010., Cataloged from PDF version of thesis., Includes bibliographical references (p. 117-126)., Bayesian Decision Theory describes optimal methods for combining sparse, noisy data with prior knowledge to build models of an uncertain world and to use those models to plan actions and make novel decisions. Bayesian computational models correctly predict aspects of human behavior in cognitive domains ranging from perception to motor control and language. However the predictive success of Bayesian models of cognition has highlighted long-standing challenges in bridging the computational and process levels of cognition. First, the computations required for exact Bayesian inference are incommensurate with the limited resources available to cognition (e.g., computational speed; and memory). Second, Bayesian models describe computations but not the processes that carry out these computations and fail to accurately predict human behavior under conditions of cognitive load or deficits. I suggest a resolution to both challenges: The mind approximates Bayesian inference by sampling. Experiments across a wide range of cognition demonstrate Monte-Carlo-like behavior by human observers; moreover, models of cognition based on specific Monte Carlo algorithms can describe previously elusive cognitive phenomena such as perceptual bistability and probability matching. When sampling algorithms are treated as process models of human cognition, the computational and process levels can be modeled jointly to shed light on new and old cognitive phenomena.., by Edward Vul., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2010., Cataloged from PDF version of thesis., Includes bibliographical references (p. 201-211)., An infant reaches out for her new toy, struggling day after day to simply grasp her fingers around it. A few years later, she hits a tennis serve, perfect in the timing of its intricately choreographed movements. How does a young brain learn to use the muscles it controls, to properly coordinate motor gestures into complex behavioral sequences? To a surprising extent, for many advanced vertebrate behaviors this knowledge is neither innately programmed nor acquired via deterministic developmental rules, but must be learned through trial-and-error exploration. This thesis is an investigation of the neural mechanisms that underlie the production and maturation of one exploratory behavior - the babbling, or subsong, of a juvenile zebra finch. Using lesions and inactivations of brain areas in the song system, I identified neural circuits involved in the production of subsong. Remarkably, subsong did not require the high vocal center (HVC) - a premotor structure long known as the key region for controlling singing in adult birds - but did require the lateral magnocellular nucleus of the nidopallium (LMAN) - the output region of basal ganglia-forebrain circuitry previously considered a modulatory area. Recordings in LMAN during subsong revealed premotor activity related to the vocal output on a fast timescale. These results show, for the first time, the existence of a specialized circuit for driving exploratory motor control, distinct from the one that produces the adult behavior. The existence of two neural pathways for singing has raised the question of how motor control is transferred from one pathway to another and, in particular, how the control of song timing develops in these pathways. I found that early singing can be decomposed into mechanistically distinct "modes" of syllable and silent gap timing - randomly-timed modes that are LMAN-dependent and developmentally-acquired, consistently-timed modes that are HVCdependent. Combining acoustic analysis with respirator, by Dmitriy Aronov., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2010., Cataloged from PDF version of thesis., Includes bibliographical references., Ecologically relevant search typically requires making rapid and strategic eye movements in complex, cluttered environments. Attention allocation is known to be influenced by low level image features, visual scene context, and top down task constraints. Scene specific context develops when observers repeatedly search the same environment (e.g. one's workplace or home) and this often leads to faster search performance. How does prior experience influence the deployment of eye movements when searching a familiar scene? One challenge lies in distinguishing between the roles of scene specific experience and general scene knowledge. Chapter 1 investigates eye guidance in novel scenes by comparing how well several models of search guidance predict fixation locations, and establishes a benchmark for inter-observer fixation agreement. Chapters 2 and 3 explore spatial and temporal characteristics of eye guidance from scene specific location priors. Chapter 2 describes comparative map analysis, a novel technique for analyzing spatial patterns in eye movement data, and reveals that past history influences fixation selection in three search experiments. In Chapter 3, two experiments use a response-deadline approach to investigate the time course of memory-based search guidance. Altogether, these results describe how using long-term memory of scene specific representations can effectively guide the eyes to informative regions when searching a familiar scene., by Barbara Hidalgo-Sotelo., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2010., This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections., Cataloged from student-submitted PDF version of thesis., Includes bibliographical references., One of the great puzzles of vision science is how, over the course of development, the complex visual array comprising many regions of different colors and luminances is transformed into a sophisticated and meaningful constellation of objects. Gestaltists describe some of the rules that seem to govern a mature parsing of the visual scene, but where do these rules come from? Are they innate--endowed by evolution, or do they come somehow from visual experience? The answer to this question is usually confounded in infant studies as the timelines of maturation and experience are inextricably linked. Here, we describe studies with a special population of late--onset vision patients, which suggest a distinction between those capabilities available innately and those which are crafted via learning from the visual environment. We conclude with a hypothesis, based on these findings and other evidence, that early-available common fate motion cues provide a level of perceptual organization which forms the basis for the learning of subsequent cues., by Yuri Ostrovsky., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2011., Cataloged from PDF version of thesis., Includes bibliographical references., The field of neuroscience has the potential to address profound questions including explaining how neural activity enables complex behaviors and conscious experience. However, currently the field is a long way from understanding these issues, and progress has been slow. One of the main problems holding back the pace of discovery is that it is still unclear how to interpret neural activity once it has been recorded. This lack of understanding has led to many different data analysis methods, which makes it difficult to evaluate the validity and importance of many reported results. If a clearer understanding of how to interpret neural data existed, it should be much easier to answer other questions about how the brain functions. In this thesis I describe how to use a data analysis method called 'neural population decoding' to analyze data in a way that is potentially more relevant for understanding neural information processing. By applying this method in novel ways to data from several vision experiments, I am able to make several new discoveries, including the fact that abstract category information is coded in the inferior temporal cortex (ITC) and prefrontal cortex (PFC) by dynamic patterns of neural activity, and that when a monkey attends to an object in a cluttered display, the pattern of ITC activity returns to a state that is similar to when the attended object is presented alone. These findings are not only interesting for insights that they give into the content and coding of information in high level visual areas, but they also demonstrate the benefits of using neural population decoding to analyze data. Thus, the methods developed in this thesis should enable more rapid progress toward an algorithmic level understanding of vision and information processing in other neural systems., by Ethan M. Meyers., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2011., Cataloged from PDF version of thesis., Includes bibliographical references., Astrocytes play an important role in regulating neuronal activity and local brain states, in part by serving as intermediaries between neurons and vasculature. We postulate that neurons and astrocytes are sensitive to biophysical conditions in their local environment, in addition to their participation in traditional signaling networks with other neurons. Mechanically sensitive astrocytic endfeet ensheathe cerebral blood vessels, which change size in order to regulate blood flow. We found that changes in local biophysical state caused by mechanical perturbations exerted through blood vessels can depolarize astrocytes and some neurons in slice. To test the hemoneural hypothesis in vivo, we developed a means of inducing dilation using the SUR2B receptor agonist pinacidil, which is specific to vascular smooth muscle. It was important to ascertain that pinacidil had no direct effect on astrocytes or neurons, and we confirmed this in whole cell recordings in cortical slices. We then used two-photon imaging to visualize astrocytic calcium dynamics in vivo while manipulating vasodilation in vivo. Pinacidil caused a 10-20% dilation in most vessels, a degree of dilation of similar magnitude to those naturally evoked by persistent sensory stimulation (e.g. in fMRI studies). We found that increases in pial arteriole diameter could occasionally evoke traveling calcium waves in astrocytes. We also saw consistently slow increases (which took tens of seconds to onset, and persisted for minutes) in astrocytic calcium levels at both endfeet and soma in cortical layer 1, corresponding to vessel dilation. When vessels partially reconstricted due to pinacidil washout, calcium levels also showed a relative decrease. At short time scales (from 0.5 - 5 seconds) we saw strong correlations (>0.5) between small fluctuations in astrocytic calcium levels (1-3%) and vessel diameter (1-3%). Fluctuations in vessel diameter predicted similar fluctuations in astrocytic calcium, as often and as stro, by Rosa Cao., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2010., Cataloged from PDF version of thesis., Includes bibliographical references., Most neurons are born during the embryonic period to become the building blocks for a variety of brain circuits. However, two brain regions only start to assemble during the postnatal period. Both brain areas, olfactory bulb and dentate gyrus, mainly accommodate the integration of new neurons during the postnatal period, and continuously receive new neurons throughout animals' life. In this thesis, I used the rat olfactory bulb (OB) as a model system to address two important issues regarding the integration and plasticity of new neurons generated during the postnatal period. The first feature of postnatal neurogenesis is that when new neurons arrive and integrate into an adult OB, only half of neurons can ultimately survive. However, what form of activity pattern determines the survival of new neurons remains unclear. Using NaChBac sodium channels to selectively alter the intrinsic excitability of new neurons in vivo, this manipulation reveals that neuronal survival critically depends on the level of membrane depolarization. Once neurons integrate and survive in the brain circuits, neurons have the capability of monitoring their activity level and adaptively maintain their membrane excitability within the operational range. How they achieve the long-term stability of membrane excitability remains unclear. By altering the resting membrane potential of individual neurons in vivo, OB granule neurons are found to use a subthreshold parameter, resting membrane potential, to guide the compensatory changes of intrinsic ion channels and synaptic receptors. In summary, studies from this thesis have revealed the cellular mechanisms underlying neuronal survival in an in vivo brain circuit. I also uncover a novel form of homeostatic computation by which granule neurons preferentially use the subthreshold membrane potential response rather than spiking rates as a set point., by Chia-Wei Lin., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2009., "June 2009." Cataloged from PDF version of thesis., Includes bibliographical references., Unlike the human brain, which produces few neurons in adulthood, the brains of songbirds continue to produce new neurons throughout life. The function of these new neurons is not know, although it has been suggested that they endow the avian brain with a remarkable regenerative capacity that does not exist in mammals. It has also been proposed that the addition of new neurons in adulthood underlies behavioral plasticity, such as song learning. A better understanding of the cellular mechanisms that control the addition of new neurons to the postnatal brain may help clarify its biological function. This thesis is an investigation of the cell biology of postnatal neurogenesis in the songbird forebrain, with special emphasis on the High Vocal Center. Neuronal progenitors in the juvenile zebra finch brain were identified by fate mapping using engineered retroviruses. Multiple populations of neural progenitors appear to exist in the juvenile zebra finch brain, and each produces different types of neurons. At least three cell types appear to be added to the postnatal finch brain. Homology between neurogenesis in the postnatal finch and embryonic mammalian forebrain was also assessed. To characterize the mechanism of cell addition, videos were made, documenting the migration and integration of new neurons into the High Vocal Center. Neural progenitors were labeled using retroviruses, carrying the gene for the green fluorescent protein, allowing new neurons to be observed in the intact brain, with a powerful infrared laser. By replacing a small hole in the skull with a piece of optical glass, one could observe labeled neurons periodically over many days as they were born until they wired up to the existing circuitry. New neurons engaged in a previously undescribed form of migration. Further study of this form of neuron migration as well as other aspects of postnatal neurogenesis may lead to the development of strategies for replacing neurons in the human brain lost to death, by Benjamin Barnett Scott., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2010., Cataloged from PDF version of thesis., Includes bibliographical references (p. 109-122)., How do children learn their first words? Do they do it by gradually accumulating information about the co-occurrence of words and their referents over time, or are words learned via quick social inferences linking what speakers are looking at, pointing to, and talking about? Both of these conceptions of early word learning are supported by empirical data. This thesis presents a computational and theoretical framework for unifying these two different ideas by suggesting that early word learning can best be described as a process of joint inferences about speakers' referential intentions and the meanings of words. Chapter 1 describes previous empirical and computational research on "statistical learning"--the ability of learners to use distributional patterns in their language input to learn about the elements and structure of language-and argues that capturing this abifity requires models of learning that describe inferences over structured representations, not just simple statistics. Chapter 2 argues that social signals of speakers' intentions, even eye-gaze and pointing, are at best noisy markers of reference and that in order to take advantage of these signals fully, learners must integrate information across time. Chapter 3 describes the kinds of inferences that learners can make by assuming that speakers are informative with respect to their intended meaning, introducing and testing a formalization of how Grice's pragmatic maxims can be used for word learning. Chapter 4 presents a model of cross-situational intentional word learning that both learns words and infers speakers' referential intentions from labeled corpus data., by Michael C. Frank., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2010., Cataloged from PDF version of thesis., Includes bibliographical references., This thesis is a collection of manuscripts addressing connectivity of neural circuits in cultured hippocampal neurons. These studies begin with an investigation of dopaminergic modulation of excitatory synapses in small circuits of neurons grown on glial micro islands. We found that dopamine transiently depressed excitatory synaptic transmission. Scaling up to larger circuits of neurons proved more challenging, since finding connected pairs became combinatorially more improbable. The discovery and use of light-activatable ion channel channel rhodopsin-2 (ChR2) promised to revolutionize the way in which we could map connectivity in vitro. We successfully delivered the gene for ChR2 in hippocampal cultures using recombinant adeno-associated virus and characterized the spatial resolution, as well as the reliability of stimulating action potentials. However, there were limitations to this technique that would render circuit maps ambiguous and incomplete. More recently, the engineering of rabies virus (RV) as a neural circuit tracer has produced an exciting method whereby viral infection can be targeted to a population of neurons and spread of the virus restricted to monosynaptically connected neurons. We further investigated potential mechanisms for previous observations which claim that RV spread is restricted to synaptically connected neurons by manipulating neural activity and synaptic vesicle release. We found that RV spread increased for blockade of synaptic vesicle exocytosis and for blockade of neural activity. The underlying premise for pursuing these methods to elucidate connectivity is that the computational power of the brain comes from changeable, malleable connectivity and that to test network models of computation in a biological brain, we must map the connectivity between individual neurons. This thesis builds a framework for experiments designed to bridge the gap between computational learning theories and networks of live neurons., by Jennifer Lynn Wang., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, February 2011., Cataloged from PDF version of thesis., Includes bibliographical references (p. 97-102)., Successful interaction with the external world requires choosing appropriate actions in the context of available choices. Such decisions require the evaluation of the reward magnitude, or value, associated with each potential action. Delineating the neural circuits involved in this process remains an important goal in systems neuroscience. However, little is known about the neural circuits that compute, or represent, low level primary reward signals. We have combined quantitative psychophysical measures of subjective reward magnitude elicited by rewarding electrical brain stimulation, fMRI as a readout of whole-brain neural activity, and local inactivation of brain structures, to identify the neural representation of subjective reward magnitude. We find that multiple brain regions are activated by rewarding brain stimulation, but only two brain regions, the nucleus accumbens and the central and basolateral nucleus of the amygdala, exhibit patterns of activity levels that track the reward magnitude measured psychophysically, suggesting a role in the neural representation of reward magnitude. Furthermore, pharmacological silencing of the ventral tegmental area (VTA) disrupts reward-tracking behavior and increases stimulus-dependent activity in the nucleus accumbens and amygdala. Together these data suggest that ascending and descending pathways combine to produce a signal that ultimately guides behavior and is subject to modulation by VTA inputs., by Ana Marcia Fiallos., Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2011., This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections., Cataloged from student-submitted PDF version of thesis., Includes bibliographical references (p. 254-302)., The ease with which we recognize visual objects belies the computational difficulty of this feat. Despite the concerted efforts of both biological and computer vision research communities over the last forty years, human-level visual recognition remains an unsolved problem. The impact of a robust yet inexpensive solution would dramatically change computer science and neuroscience, unleashing a host of innovative applications in our modern society. In this thesis, we identify two operational barriers that have obstructed progress towards finding a solution { namely the lack of clear indicators and operational definitions of success, and the currently limited exploration of the staggeringly large hypothesis space of biologically- inspired solutions. To break down these barriers, we first establish new neuroscience-motivated baselines and new suites of fully-controlled benchmarks for object and face recognition. We also compare and contrast a variety of high-level visual systems, both artificial (state-of-the- art computer vision) and biological (humans). Then, we propose a simple high-throughput approach to undertake a systematic exploration of the biologically-inspired model class. By leveraging recent advances in massively parallel computing, we show that it is possible to generate a multitude of candidate models, screen them for desirable properties and discover robust solutions. Finally, we validate the scalability of our approach by showing its potential on large-scale real-world" applications. Taken together, this thesis represents a humble attempt towards an integrated approach to the problem of brain-inspired object recognition { spanning the engineering, specification, evaluation, and application of an interesting set of biologically-inspired ideas, driven and enabled by massively parallel technology. Even relatively early instantiations of this approach yield algorithms that achieve state-of-the-art performance in object recognition tasks and can generalize, by Nicolas Pinto., Ph.D.