Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 1999. / Includes bibliographical references (p. 193-199). / The ability to individuate entities (i.e. conceptualize one entity as distinct from two) and trace their identity (i.e. judge that an entity is the same one as an entity encountered before) is a fundamental component of the human mind and is critical to proper name reference (i.e. a proper name, like lvfax, refers to a unique individual, namely Max). Philosophers have proposed that sortals-concepts which refer to kinds of individuals-support these abilities (Gupta, 1980; Hirsch, 1982; Macnamara, 1986; Wiggins, 1967, 1980). However, while adults may well have sortal concepts and learn proper names for individuals, it is an open question whether children do so also. Proponents of the Continuity hypothesis (e.g. Macnamara, 1982; Pinker, 1984) argue that children and adults have fundamentally the same conceptual resources, whereas proponents of the Discontinuity hypothesis (e.g. Piaget, 1954; Quine, 1960, 1969) argue that child.en and adults have qualitatively different conceptual systems. In this thesis, evidence is reviewed that very young infants have at least one sortal, physical object, which suggests that infants have the conceptual structure needed to support representations of kinds and individuals. Experiments probing infant understanding of the concept, person, suggest that infants have the ability to reason about the action and appearance of others, but data presented in the thesis falls short of providing conclusive evidence that infants under a year are able to individuate people. Evidence is presented that by age three, children represent unique individuals and interpret proper names in an adult like manner as referring to unique individuals. This rules out a discontinuity alternative, namely that preschoolers represent proper names as referring to highly similar objects or to restricted subkinds. Evidence is also presented that children as young as two years are like adults in being willing to accept a range of individuals as nameable if given information which highlights the named objects' importance, such as the attribution of mental states to the object. Together these findings provide support for the continuity hypothesis and suggest a number of avenues of research into children's understanding of kinds, individuals, and their names. / by Christina M. Sorrentino. / Ph.D.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 1990. / Includes bibliographical references (leaves 52-53). / by Jacob Feldman. / M.S.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2018. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 125-129). / In this thesis, I develop and explore two novel models of how humans might be able to acquire high-level conceputal knowledge by performing probabilistic inference over a language of thought (Fodor 1975) - a space of symbolic and compositional mental representations sufficiently expressive to capture the meanings of human thoughts and utterances. These models and their associated learning algorithms are motivated by an attempt to provide an understanding of the algorithmic principles that might underlie a child's ability to search the haystack of sentences in her language of thought to find the needle that corresponds to any specific concept. The first model takes advantage of the compositionality inherent to LOT representations, framing concept acquisition as program induction in a functional programming language; the Exploration- Compression algorithm this model motivates iteratively builds a library of useful program fragments that, when composed, restructures the search space, making more useful programs shorter and easier to find. The second model, the Infinite Knowledge Base Model (IKM), frames concept learning as probabilistic inference over the space of relational knowledge bases; the algorithm I develop for learning in this model frames this inference problem as a state-space search over abductive proofs of the learner's observed data. This framing allows us to take advantage of powerful techniques from the heuristic search and classical planning literature to guide the learner. In the final part of this thesis, I explore the behavior of the IKM on several case studies of intuitive theories from the concept learning literature, and I discuss evidence for and against it with respect to other approaches to LOT models. / by Eyal Dechter. / 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 strongly as the reverse, suggesting feedback regulation between vascular diameter and astrocytic calcium activation levels. / by Rosa Cao. / Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, June, 2019 / Cataloged from the PDF version of thesis. / Includes bibliographical references (pages 179-192). / General anesthesia (GA) reversibly induces unconsciousness. It is arguably the most powerful brain state manipulation that clinicians and researchers can reliably perform. However, the mechanisms underlying GA at the neural systems level are underexplored and largely not understood. To link neural dynamics to the loss of consciousness, we measured spiking activity and local field potentials (LFPs) from multiple cortical and thalamic regions while monkeys were pharmacologically rendered unconscious. In Chapter 2, we examine effects of the GABAergic anesthetic propofol across prefrontal cortices (PFC), parietal cortex, temporal cortex, and the mediodorsal and intralaminar thalamic nuclei. Propofol decreased brain-wide spiking and high-frequency LFPs (e.g. gamma, 30- 80Hz) while producing prominent slow cortical oscillations (0-4 Hz). These slow rhythms were incoherent across PFC yet synchronized in frontoparietal networks. Electrical stimulation of the central thalamus immediately and continuously reversed the neurophysiological effects of propofol and awakened the anesthetized monkeys. Thus, we interpret GABAergic anesthetics to produce unconsciousness via fragmented network dynamics facilitated by subcortical arousal pathway inhibition. In Chapter 3, we explore an alternative unconscious state mediated by the anti-glutamatergic anesthetic ketamine. Ketamine substantially increased spiking and gamma rhythms while eliminating beta (13- 25 Hz) power and coherence across the cortical areas studied in Chapter 2. In anesthesia, slow waves interrupted high-frequency activity globally and PFC uniquely entrained central thalamic LFPs. Seemingly, ketamine harnesses an excitatory mechanism to disrupt conscious processing, overwhelming cortex with disordered spiking activity and binding thalamo-prefrontal flexibility. In Chapter 4, we describe our model for closed-loop control of GA in monkeys. We established and implemented a pharmacokinetic-pharmacodynamic paradigm within an optimal control framework that automatically titrated propofol using an LFP-derived GA biomarker. Together, this collection of work demonstrates the distinct network mechanisms that can drive GA and the systems-level approach to enhanced control of conscious states. / by Jacob A. Donoghue. / Ph. D. / Ph.D. Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences

Thesis: Ph. D. in Neuroscience, Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, June, 2019 / Cataloged from the PDF version of thesis. "June 2019"--Hand written on title page. / Includes bibliographical references. / With ease, we recognize a friend's voice in a crowd, or pick out the first violin in a concerto. But the effortlessness of everyday perception masks its computational challenge. Perception does not occur in the eyes and ears - indeed, nearly half of primate cortex is dedicated to it. While much is known about peripheral auditory processing, auditory cortex remains poorly understood. This thesis addresses basic questions about the functional and computational organization of human auditory cortex through three studies. In the first study we show that a hierarchical neural network model optimized to recognize speech and music does so at human levels, exhibits a similar pattern of behavioral errors, and predicts cortical responses, as measured with fMRI. The multi-task optimization procedure we introduce produces separate music and speech pathways after a shared front end, potentially recapitulating aspects of auditory cortical functional organization. Within the model, different layers best predict primary and non-primary voxels, revealing a hierarchical organization in human auditory cortex. We then seek to characterize the representational transformations that occur across stages of the putative cortical hierarchy, probing for one candidate: invariance to realworld background noise. To measure invariance, we correlate voxel responses to natural sounds with and without real-world background noise. Non-primary responses are substantially more noise-invariant than primary responses. These results illustrate a representational consequence of the potential hierarchical organization of the auditory system. Lastly, we explore of the generality of deep neural networks as models of human hearing by simulating many psychophysical and fMRI experiments on the above-described neural network model. The results provide an extensive comparison of the performance characteristics and internal representations of a deep neural network with those of humans. We observe many similarities that suggest that the model replicates a broad variety of aspects of auditory perception. However, we also find discrepancies that suggest targets for future modeling efforts. / by Alexander James Eaton Kell. / Ph. D. in Neuroscience / Ph.D.inNeuroscience Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences

Thesis: Ph. D. in Neuroscience, Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, June, 2019 / Cataloged from the PDF version of thesis. Vita. / Includes bibliographical references (pages 143-153). / Sensory experiences in daily life modulates corresponding primary sensory cortices and eventually alter our behavior in a befitting manner. One of the most impactful sensory modules is vision. Primary visual cortex (V1) in mammals is particularly malleable during a juvenile critical period, but this plasticity lasts even in adulthood. A representative form of visual cortical plasticity is ocular dominance (OD) plasticity following temporary monocular deprivation (MD). Here, we used a mouse model of amblyopia and revealed that juvenile OD plasticity, which manifests as depression of response to the deprived eye, requires expression of an immediate early gene, Arc. Also, the juvenile OD shift requires the activity of N-methyl-D-aspartate (NMDA) receptors in layer 4 excitatory principal neurons in V1. Another simple but powerful phenomenon of an adult form of visual cortical plasticity is stimulus-selective response potentiation (SRP). SRP is induced simply through experience to the same gratings visual stimulus over days, resulting in potentiation of visually-evoked potentials (VEPs) in layer 4 of V1. Due to the lack of studies regarding the cellular and network activity changes coincident with the induction of SRP, we have used calcium indicator expressing mice to visualize cellular activity across days of SRP training. Using two-photon calcium imaging, we found that there is indeed no significant net change in the population of active neurons during presentation of the familiar (trained) visual stimulus. Follow-up endoscopic calcium imaging revealed that rather, there is a significant reduction of somatic calcium responses selectively for the familiar visual stimulus on the test day following 5 days of SRP induction. Interestingly, the cellular calcium response to the first presentation of the familiar visual stimulus in each block was substantially similar to the response to those of a novel, yet unseen visual stimulus. However, calcium responses to the familiar visual stimulus dramatically decreased as stimulation was repeated in each presentation block within, and across days of SRP training, whereas the response to the novel visual stimulus on the test day was maintained. The findings that short-latency VEP responses are potentiated, while the slower responses revealed by calcium imaging are depressed suggest that feedback inhibition in V1 is strongly recruited by visual recognition of familiar stimulus. A number of previous studies have suggested that deficits in experience-dependent sensory cortical plasticity and perceptual learning are associated with neuropsychiatric disorders such as autism spectrum disorder (ASD), Rett syndrome and schizophrenia. Our results, therefore, may contribute to our understanding of the underlying mechanisms of these disorders and may help inform ways of intervention and treatments. / by Taekeun Kim. / Ph. D. in Neuroscience / Ph.D.inNeuroscience Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, June, 2019 / Cataloged from the PDF version of thesis. / Includes bibliographical references. / Color is a fundamental aspect of visual experience that confers a myriad of behavioral advantages: finding objects in cluttered scenes, recognizing familiar objects, and gleaning information about the material composition and state of objects (e.g. the edibility of fruit) and agents in the world (e.g. health or emotional status). As famously pointed out by Marr (1980), a full understanding of perception requires an analysis of the computations performed, the algorithms that carry out those computations, and the implementation of those algorithms in the physical hardware of the brain. This thesis employs psychophysical methods and functional imaging to tackle questions about human color vision at all three levels: what it is used for, how we solve the classic problem of color constancy, and how our color processing machinery is functionally organized in the brain. Chapter 1 provides a brief survey of the background to these questions. Chapter 2 describes functional MRI studies in humans that find both segregation and convergence of the processing of color and shape in the brain, as well as evidence for the homology of the color system between humans and macaques. Chapter 3 uses psychophysics and a recently discovered ambiguous color stimulus ('#theDress') to investigate the cues and assumptions used by the human visual system to constrain the classic ill-posed problem of inferring the intrinsic reflectance of an object by discounting the spectral properties of the illuminant. Specifically, these studies find evidence that color constancy is mediated by sensory, perceptual, and cognitive factors (i.e., low-level features, inferences about 3D scene geometry, prior knowledge, and attention), and provide the first evidence that human skin is a sufficient cue to infer the illuminant and bring about color constant percepts. Chapter 4 uses psychophysics to evaluate the impact of memory on the color appearance of familiar objects and faces. The study finds a novel perceptual illusion that reveals the role of memory for face color in perceptual experience and social communication, sheds light on the selective pressures for the evolution of trichromatic vision in primates, and demonstrates the powerful ability of cognition to influence perception. Taken together, these studies provide clues about the perceptual and neural mechanisms underlying our rich experience of a colorful world. / by Rosa Lafer-Sousa. / Ph. D. / Ph.D. Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, June, 2019 / Cataloged from the PDF version of thesis. Page 123 blank. / Includes bibliographical references (pages 115-122). / Changes in gamma activity (30-90 Hz) have been observed in humans and animal-models of Alzheimer's disease (AD). Examining the relationship between gamma oscillations and disease pathology is a significant problem in neuroscience. Recent work using a non-invasive light flicker at 40 Hz, termed Gamma ENtrainment Using Sensory stimulus, or 'GENUS', was shown to impact pathology in the visual cortex of AD-mouse models. However, it is not known whether other sensory modalities at 40 Hz can change pathology in higher order brain regions, or affect cognition, in AD-like animal models. In this thesis, I combine in vivo electrophysiology, biochemical and imaging techniques, and behavioral assays to understand the effects of multi-sensory gamma stimulation in AD-like animals. I first show that auditory tone stimulation at 40 Hz (auditory GENUS) can drive gamma frequency neural activity in auditory cortex (AC) and hippocampal CA1. I then demonstrate that seven days of auditory GENUS results in improved spatial and recognition memory and reduced amyloid load in AC and hippocampus of 5XFAD mice. These changes in activation responses were evident in microglia, astrocytes, and vasculature. Additionally, auditory GENUS reduced phosphorylated tau in the tau P301S model. Finally, I demonstrate that combined auditory and visual GENUS, but not either alone, decreases amyloid and produces a microglial-clustering response in the medial prefrontal cortex. Whole brain analysis using SHIELD processing revealed widespread reduction of amyloid plaques throughout neocortex after multi-sensory GENUS. These findings suggest that GENUS can be achieved through multiple sensory modalities with wide-ranging effects across multiple brain areas to improve cognitive function. / by Anthony J. Martorell. / Ph. D. / Ph.D. Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, June, 2019 / Cataloged from the PDF version of thesis. / Includes bibliographical references (pages 186-208). / Schizophrenia is a psychiatric disorder characterized by multiple clusters of symptoms including positive symptoms, such as hallucinations and delusions, negative symptoms, such as decreased motivation and flattened affect, and cognitive symptoms, such as memory impairment and impaired executive function. Currently available antipsychotics mitigate some symptoms of schizophrenia, particularly the positive symptoms, but there is no preventive treatment nor cure after schizophrenia develops. Efforts to generate more effective antipsychotics are made particularly challenging by the fact that the therapeutic effect of currently prescribed antipsychotics is not well understood and the cell type(s) and brain circuits crucial for beneficial effects have not been conclusively identified. Here we show that chronic antipsychotic administration enhances glutamatergic function in the ventral striatum through translational alterations and increased synaptic function. Cell type-specific mRNA profiling on spiny projection neurons (SPNs) of the direct (dSPNs) and indirect (iSPNs) pathways following chronic antipsychotic administration revealed cell type-specific molecular alterations indicating increases in components of the glutamatergic postsynaptic density. Subsequent functional experiments demonstrated the presence of calcium-permeable AMPARs and increased mEPSC frequency following chronic administration of one especially effective antipsychotic, clozapine. Furthermore, we find that striatal astrocytes also respond to chronic antipsychotic treatment with translational alterations promoting synaptogenesis. Together, these data have identified a core molecular signature of increased glutamatergic transmission in the striatum induced by chronic antipsychotic treatment. This work provides evidence that effective antipsychotics address a lack of glutamatergic drive into the striatum in cases of schizophrenia. Additionally, it suggests that drug development efforts seeking improved antipsychotics may benefit by finding compounds that feature an increased glutamatergic drive into the striatum as a core function. / by Amanda Vernon. / Ph. D. / Ph.D. Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences