Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2007. / Includes bibliographical references (p. 118-130). / Perceptual systems are specialized for transducing and interpreting information from the environment. But perceptual systems can also be used for processing information that arises from other sources, such as mental imagery and cued associations. Here we ask how a particular sensory property, visual motion, is represented when it is not directly perceived but only imagined or inferred from other cues. In a series of experiments, a motion adaptation paradigm is used to assess directional properties of the responses to mental imagery of motion and viewing photographs that depict motion. The results show that both imagining motion and inferring motion from pictures can cause direction-specific adaptation of perceptual motion mechanisms, thus producing a motion aftereffect when a subsequent real motion stimulus is viewed. The transfer of adaptation from implied and imagined motion to real motion indicates that shared mechanisms are used for the perception, inference and imagination of visual motion. / by Jonathan Winawer. / Ph.D.

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2002. / Includes bibliographical references. / The ability to group stimuli into meaningful categories is a fundamental cognitive process though little is known its neuronal basis. To address this issue, we trained monkeys to perform a categorization task in which they classified visual stimuli into well defined categories that were separated by a "category-boundary". We recorded from neurons in the prefrontal (PFC) and inferior temporal (ITC) cortices during task performance. This allowed the neuronal representation of category membership and stimulus shape to be independently examined. In the first experiment, monkeys were trained to classify the set of morphed stimuli into two categories, "cats" and "dogs". Recordings from the PFC of two monkeys revealed a large population of categorically tuned neurons. Their activity made sharp distinctions between categories, even for stimuli that were visually similar but from different classes. Likewise, these neurons responded similarly to stimuli from the same category even if they were visually dissimilar from one another. In the second experiment, one of the monkeys used in the first experiment was retrained to classify the same stimuli into three new categories. PFC recordings collected after the monkeys were retrained revealed that the population of neurons reflected the three new categories but not the previous (now irrelevant) two categories. In the third experiment, we recorded from neurons in the ITC while a monkey performed the two-category "cat" vs. "dog" task. There were several differences between ITC and PFC neuronal properties. Firstly, a greater proportion of ITC neurons were only stimulus selective but not category tuned. / (cont.) Secondly, while many PFC neurons displayed category tuning that persisted into the memory delay, such tuning in the ITC was primarily observed during stimulus presentation. Thirdly, whereas many PFC neurons reflected the monkeys' decisions about whether a stimulus indicated a behavioral response, most ITC neurons conveyed information about the visual stimuli only, and not about the monkey's task-related decisions. In conclusion, our results suggest that neurons in the PFC and ITC can convey information about the category of visual stimuli. The differences in neuronal responses between the ITC and PFC support the hypothesis that the ITC plays an important role in object recognition and visual learning while the PFC is more involved in cognitive functions related to executive control. / by David J. Freedman. / 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 also necessary for pattern-completion contextual recall in the pre-exposure contextual fear conditioning paradigm. Contrary to previous literature, the MEC-II to CAl pathway is not necessary for consolidation of spatial memories and anatomical tracings using this mouse line demonstrate that the MEC-III projects to CA1 and not CA3. The MEC-II pathway however, does project via two pathways to the same target in CA1, the perforant and alvear pathways. The alvear pathway has not been reported before in mice. Recent advances in mouse genetic tools have allowed for circuit studies of the medial temporal lobe. We have used these tools and elucidated some of the specific circuits involved with temporal and working memory. / by Alexander Jay Rivest. / 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. / The nature of habits, their formation, expression, and underlying causes have been pondered for centuries. Early definitions, still in use today, posited that habits are actions associated with outcomes that, when repeated, become stimulus-response associations that can be performed automatically, or without the reinforcement of a rewarding stimulus. A prominent theory of what drives the process is reinforcement learning (RL). This definition and underlying theory may be inadequate to describe the complicated series of actions that we form and express as habits in every day life. We designed a task that would test the limits of RL by providing a nearly infinite number of action choices and no clear association with reward. We recorded using ~100 chronically implanted independently moveable electrodes from the frontal eye fields (FEF), prefrontal cortex (PFC), and caudate nucleus (CN) simultaneously as naïve monkeys performed a free-viewing scan task. Neural recordings began on the first day of this task where a random dot on a grid of targets was chosen to be baited with reward on every trial and the monkeys were free to look around until they captured the baited target. We found that monkeys formed selfguided and uninstructed sequences of eye movements that gradually evolved over months of task performance and did not appear to be driven by overall reward or cost measures. Only on a much smaller, trial-by-trial, time scale were we able to detect the RL forces at work and that the monkeys were minimizing cost on an extremely local level. We also found that neural units in the FEF showed standard single direction and non-standard multiple direction tuning very early in task acquisition. We also found a disproportionately high number of units whose tuning directions were selective for those eye movement combinations that were members of the monkeys' habitual sequences. This suggested that the FEF very rapidly adapts to the task at hand and the neural representation becomes biased towards those sequences that are repeated. Together these findings lay the foundation to understand natural habit formation and the neural mechanisms that underlie it. / by Theresa M. Desrochers. / Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2014. / 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 (pages 151-179). / Social life depends on understanding other people's behavior: why they do the things they do, and what they are likely to do next. These actions are just observable consequences of an unobservable, internal causal structure: the person's intentions, beliefs, and goals. A cornerstone of the human capacity for social cognition is the ability to reason about these invisible causes; having a "theory of mind". A remarkable body of evidence has demonstrated that social cognition reliably and selectively recruits a specific group of brain regions. Yet, we have little insight into how these neural substrates function at a computational level. This thesis lays the groundwork to address that question, both empirically and theoretically, first by demonstrating that functional neuroimaging can find behaviorally relevant features of mental state representation within the cortical regions that support social cognition, and second by proposing a theoretical framework to interpret activity in these brain regions. In Chapter 1, I review the literature of the last 15 years, and argue that a key next step in understanding the neural basis of social cognition is characterizing the neural representations and computations supported by "social" brain regions. In Chapter 2, I demonstrate in four experiments that functional neuroimaging can be used to find neural representations of distinct features of mental states. Specifically, I show that multivoxel pattern analysis (MVPA) can detect features of mental state representations (e.g., intent), and that these neural patterns are behaviorally relevant, including in autism spectrum disorders. In Chapter 3, I demonstrate that these brain regions contain explicit, abstract representations of another feature of others' mental states: perceptual source. I find that these representations persist in the face of drastic changes in developmental history (congenital blindness), providing evidence that these representations emerge even in the absence of relevant first-person experience. In Chapter 4, I demonstrate that these cortical regions contain representations of epistemic and emotional features of others' beliefs, and that these features are represented along continuous, abstract dimensions. Finally, in Chapter 5, I extend a model from vision and neuroeconomics - predictive coding - and explore its application to the neural basis of social cognition. Together, this work provides a key next step to understanding the neural basis of theory of mind, by demonstrating that it is possible to find abstract, behaviorally relevant features of mental state inferences inside cortical regions that support social cognition, and taking a first step in characterizing their content and format. / by Jorie Koster-Hale. / Ph. D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 1996. / Includes bibliographical references (leaves 129-131). / by Janine Dale Mendola. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2004. / Includes bibliographical references (p. 155-160). / One of the fundamental issues in cognitive science is the problem of grounding concepts in the perceptual world. In this thesis, I present a computational theory for how spatial relations are grounded in the perceptual world. Three constraints are critical to this theory: abstractness, groundedness and flexibility all of which need to be satisfied in order to explain the structure of spatial concepts. I then show how a formal framework, based on the mathematical notions of category theory can be used to model the grounding problem. The key computational ideas are that of minimal mapping and derivations. A minimal mapping of two categories, A and B, is the "smallest' category, C, that contains A and B. A derivation is a sequence of categories that follow a minimal mapping rule. Derivations and minimal mappings are used to model three domains - the semantics of prepositions, the structure of a toy "Jigsaw World" and the semantics of generic terms and quantifiers. In each case, I show how the computational theory gives rise to insights that are not available upon a purely empirical analysis. In particular, the derivational account shows the importance of stable, non-accidental features and of multiple scales in spatial cognition. / by Rajesh Kasturirangan. / Ph.D.

Thesis: Ph. D. in Neuroscience, Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2017. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 113-119). / While the mechanisms preserving genomic integrity are well defined in proliferating cells, corresponding pathways in postmitotic neurons remain poorly understood. In this report, I characterize the functions of two lysine deacetylases, SIRT1 and HDAC1, in the neuronal response to DNA double strand breaks (DSBs). Both SIRT1 and HDAC1 were previously shown to promote neuronal survival in a mouse model of neurodegeneration in which the appearance of DSBs precedes other neurotoxic symptoms. Here I show for the first time the recruitment of both SIRT1 and HDAC1 to sites of DNA DSBs in neurons, where they work cooperatively to coordinate DSB signaling and DNA repair. SIRT1 physically binds HDAC1 and this interaction is strengthened upon DNA damage. I demonstrate that SIRT1 deacetylates HDAC1 at a critical lysine residue, K432, and stimulates its enzymatic activity. Moreover, HDAC1 mutants that mimic a constitutively acetylated state render neurons more susceptible to DNA damaging agents, and pharmacological SIRT1 activators that promote HDAC1 deacetylation also mitigate neuronal loss in a mouse model of neurodegeneration. I propose that the interaction between SIRT1 and HDAC1 constitutes an essential step in the DNA damage response that could be exploited to enhance neuronal survival in various neurodegenerative diseases. / by Matthew Milnes Dobbin. / Ph. D. in Neuroscience

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 1999. / Includes bibliographical references (leaves 73-75). / by Ranxiao Wang. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2001. / Includes bibliographical references. / Relative motion information is required for solving many complex visual tasks, such as depth perception by motion parallax and motion-induced figure/ground segmentation. However, little is known about the neural substrate for relative motion. To explore the neural mechanisms underlying relative motion, we recorded single unit responses to relative motion in macaque VI and V2. We found that a substantial portion of V1 (62.2%) and V2 (70%) neurons respond to relative motion inputs. These neurons usually show V-shaped tuning curves to relative motion, with minimum response at zero relative motion. They respond predominantly to relative motion rather than to absolute motion. The relative ratio of target velocity to background velocity, rather than the absolute amplitude of either target/background velocity or the difference of the two determines neural responses. In area VI, relative-motion-defined boundaries matching a cell's preferred orientation evoke excitatory responses in a relative motion sensitive neuron. However, the responses are not strong enough to make such a neuron selective to the orientation of the relative-motion-defined boundaries. Relative motion sensitive neurons may participate in segregating objects from a moving background as well as preprocessing complex motion patterns. / (cont.) Utilizing a new random-dot stereogram, we tested further if these relative motion sensitive neurons contribute to the processing of motion parallax, as suggested by Nakayama and Loomis (1974). Several factors, i.e., the symmetric V shaped tuning to relative motion, the lack of neurons tuned to the degree of differential motion and the lack of correlation between disparity and relative motion tuning, indicate that those neurons are unlikely to process motion parallax directly. To summarize, we confirm the existence of relative motion sensitive neurons in macaque VI and V2. Although these neurons are not directly involved in processing motion parallax, they facilitate other motion processing such as figure/ground segmentation and motion discontinuity detection. / by An Cao. / Ph.D.