Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2015. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 212-230). / Memories thread and unify our overall sense of being. With the accumulation of our knowledge about how memories are formed, consolidated, retrieved, and updated, neuroscience has reached a point where brain cells active during these discrete mnemonic processes can be identified and manipulated at rapid timescales. Here, I begin with historical studies that lead to the modem memory engram theory. Then, I present our recent advances in memory research that combine transgenic and optogenetic approaches to reveal underlying neuronal substrates sufficient for activating mnemonic processes. Our studies' conclusions are threefold: (1) we provide proof of principle evidence demonstrating that learning-related neural changes can be isolated at the level of single cells, and that these cells can then be tagged for subsequent manipulation; (2) a defined subset of hippocampus cells are sufficient to elicit the neuronal and behavioral expression of memory recall, as well as sufficient to modify existing positive and negative memories; (3) and finally, artificially activated memories can be leveraged to acutely and chronically suppress psychiatric disease-related states. We propose that hippocampus cells that show activity-dependent changes during learning construct a cellular basis for contextual memory engrams and that directly activating these endogenous neuronal processes may be an effective means to correct maladaptive behaviors. / by Steve Ramirez. / Ph. D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 1991. / Includes bibliographical references. / by Margaret M. Keane. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2008. / Includes bibliographical references. / A new treatment tested in laboratory animals increases synaptic membrane and cholinergic neurotransmission. This treatment involves giving three compounds; DHA, a phosphatide precursor; choline, another phosphatide precursor present in the rodents' diets but not varied in this study; and UMP, a precursor of CTP, the rate-limiting compound in Kennedy Cycle production of phosphatides. Their administration increases the quantities of phosphatides, the major constituent of neuronal membrane, per brain cell, as well as specific synaptic proteins, the number of dendritic spines; and the expression of genes related to hippocampal glutamatergic neurotransmission. Since such membrane is the predominant component of synapses, the treatment might also ameliorate the loss of synapses occurring in the brains of Alzheimer's patients. My study involves assessing the behavioral effects of the treatment in individual rats or gerbils subsequently shown to manifest its neurochemical effects (i.e., increased phosphatides). My present findings show that the treatment improves performance on various tests of memory function. The largest improvements in memory function and increases in phosphatide levels are observed when DHA, choline, and UMP are consumed in combination. / by Sarah Holguin. / Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2015. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 133-142). / The trained enhancement of working memory and visual attention has both theoretical implications for understanding the architectures of cognition, as well as practical implications for education and clinical treatment. In particular, transfer of training from one task to another may reveal shared psychological processes or neural systems across domains of cognition. In three experiments presented here, participants underwent a month of intensive training on either a complex working memory task or a visual attention task. Although participants made substantial gains on the trained tasks, that training did not yield transfer to untrained tasks measuring fluid intelligence, reading comprehension, or processing speed (Experiment 1). Brain imaging conducted before and after training revealed that increased working memory performance was accompanied by decreases of functional activation within anatomically circumscribed regions of frontal and parietal cortex as well as more wide-spread increases in frontoparietal functional connectivity (Experiment 2). Visual attention training using adaptively adjusted speeds on a multiple object tracking task revealed sizeable gains on the task itself, and those gains enabled the tracking of an increased number of items at a constant speed. This transfer from speed to quantity suggests that a common process underlies tracking speed and tracking capacity in visual attention (Experiment 3). / by Todd Wesley Thompson. / 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. 177-195). / How much visual information can we hold in mind at once? A large body of research has attempted to quantify the capacity of visual working memory by focusing on how many individual objects or visual features can be actively maintained in memory. This thesis presents a novel theoretical framework for understanding working memory capacity, suggesting that our memory representations are complex and structured even for simple visual displays, and formalizing such structured representations is necessary to understand the architecture and capacity of visual working memory. Chapter 1 reviews previous empirical research on visual working memory capacity, and argues that an understanding of memory capacity requires moving beyond quantifying how many items people can remember and instead focusing on the content of our memory representations. Chapter 2 argues for structured memory representations by demonstrating that we encode a summary of all of the items on a display in addition to information about particular items, and use both item and summary information to complete working memory tasks. Chapter 3 describes a computational model that formalizes the roles of perceptual organization and the encoding of summary statistics in visual working memory, and provides a way to quantify capacity even in the presence of richer, more structured memory representations. This formal framework predicts how well observers will be able to remember individual working memory displays, rather than focusing on average performance across many displays. Chapter 4 uses information theory to examine visual working memory through the framework of compression, and demonstrates that introducing regularities between items allows us to encode more colors in visual working memory. Thus, working memory capacity needs to be understood by taking into account learned knowledge, rather than simply focusing on the number of items to be remembered. Together, this research suggests that visual working memory capacity is best characterized by structured representations where prior knowledge influences how much can be stored and displays are encoded at multiple levels of abstraction. / by Timothy F. Brady. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 1997. / Includes bibliographical references (p. 139-143). / by Robert S. Thau. / 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, 1997. / Includes bibliographical references (leaves 176-170). / by M. Claudia Uller. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 1990. / Includes bibliographical references (leaves 128-133). / by M. Karen Wynn. / 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.