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Item Functional organization of social-motivation brain systems during social interaction in autism spectrum disorder(2019) Moraczewski, Dustin; Redcay, Elizabeth; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The motivation to interact with others and the feeling of reward following a social interaction is integral to the development and maintenance of successful so- cial relationships. For those with autism spectrum disorder (ASD) successful social interaction is often more challenging relative to those who are neurotypical (NT) and atypical social reward processing may contribute to such deficits. However, our understanding of the relationship between brain systems associated with re- ward and higher-order social-cognitive processing during both typical and atypical development is limited. Middle childhood is an important time to examine the de- velopment of the functional relationship between these brain systems as this is a time when children’s social worlds expand in size and complexity and those with ASD often fall behind. The goal of the current dissertation is to characterize the development of the functional relationship between the ventral striatum (VS)—a hub of reward processing—and other brain regions implicated in reward and social-cognitive processing during an interactive social context in middle childhood. Using novel Bayesian multilevel modeling, Aim 1 examines VS functional connectivity within the NT group while Aim 2 examines group differences between the ASD and NT groups. Finally, given that heterogeneity is ubiquitous in both NT and ASD populations, Aim 3 takes a dimensional perspective through examining VS connectivity as a function of individual differences in autistic traits and subjective reports of social reward within the entire sample. Results suggest that participant age may be particularly important for the development of the relationship between reward and social-cognitive brain systems, such that older children of both groups exhibit greater sensitivity the absence of a social reward and to the contingency of a non-social reward. This dissertation underscores the importance of examining multidimensional heterogeneity in both NT and ASD populations.Item THE ACOUSTIC QUALITIES THAT INFLUENCE AUDITORY OBJECT AND EVENT RECOGNITION(2019) Ogg, Mattson Wallace; Slevc, L. Robert; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Throughout the course of a given day, human listeners encounter an immense variety of sounds in their environment. These are quickly transformed into mental representations of objects and events in the world, which guide more complex cognitive processes and behaviors. Through five experiments in this dissertation, I investigated the rapid formation of auditory object and event representations (i.e., shortly after sound onset) with a particular focus on understanding what acoustic information the auditory system uses to support this recognition process. The first three experiments analyzed behavioral (dissimilarity ratings in Experiment 1; duration-gated identification in Experiment 2) and neural (MEG decoding in Experiment 3) responses to a diverse array of natural sound recordings as a function of the acoustic qualities of the stimuli and their temporal development alongside participants’ concurrently developing responses. The findings from these studies highlight the importance of acoustic qualities related to noisiness, spectral envelope, spectrotemporal change over time, and change in fundamental frequency over time for sound recognition. Two additional studies further tested these results via syntheszied stimuli that explicitly manipulated these acoustic cues, interspersed among a new set of natural sounds. Findings from these acoustic manipulations as well as replications of my previous findings (with new stimuli and tasks) again revealed the importance of aperiodicity, spectral envelope, spectral variability and fundamental frequency in sound-category representations. Moreover, analyses of the synthesized stimuli suggested that aperiodicity is a particularly robust cue for some categories and that speech is difficult to characterize acoustically, at least based on this set of acoustic dimensions and synthesis approach. While the study of the perception of these acoustic cues has a long history, a fuller understanding of how these qualities contribute to natural auditory object recognition in humans has been difficult to glean. This is in part because behaviorally important categories of sound (studied together in this work) have previously been studied in isolation. By bringing these literatures together over these five experiments, this dissertation begins to outline a feature space that encapsulates many different behaviorally relevant sounds with dimensions related to aperiodicity, spectral envelope, spectral variability and fundamental frequency.Item CHARACTERIZATION OF CHRONIC MONOCULAR DEPRIVATION AND ESTROGEN ADMINISTRATION IN ADULT RODENTS(2018) Sengupta, Deepali Clare; Quinlan, Elizabeth M; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Reduced synaptic plasticity and excitatory synapse density contribute to age-related cognitive decline, and constrain recovery of function from injury in adults. A parallel reduction in circulating sex hormones in both sexes, particularly estrogens, exacerbates this decline in synaptic plasticity. Conversely, estrogen therapy in aged members of many species restores synapse density, promotes synaptic plasticity, and improves learning/memory. Importantly, acute estrogen administration can promote rapid synaptogenesis, and these new synapses can be stabilized by activity. Here I ask if estrogen treatment can promote synaptic plasticity in the primary visual cortex (V1) of aged rats. I demonstrate robust expression of estrogen receptors (ERs) in V1 of adult male and female rats, suggesting an opportunity to enhance plasticity with estrogens. I test this hypothesis following the induction of amblyopia by chronic monocular deprivation (cMD). I show that cMD reduces thalamic innervation from the deprived eye, and increases molecular markers which constrain plasticity, consistent with observations that the deficits induced by cMD are highly resistant to reversal. Surprisingly, cMD did not change markers for excitatory synapses, suggesting a homeostatic increase in synapses serving the non-deprived eye (NDE) to maintain synaptic density within an optimal range. Importantly, visually-evoked potentials (VEPs) induced by repetitive visual stimulation to the deprived eye depress more rapidly than those of the NDE, consistent with cMD inducing an increase in the probability of neurotransmitter release (Pr) at synapses in the cMD pathway. In contrast, treatment of cMD adults with a single dose of 17α estradiol significantly increased markers for excitatory synapses, and estradiol treatment followed by visual stimulation also increased markers for excitatory synapse activity. Repetitive estradiol treatments increased excitatory synapse markers, but not synaptic activity markers. Furthermore, one dose of estradiol enhanced VEP amplitude following repetitive visual stimulation, however this was observed only in response to stimulation of the NDE. As presynaptic ERs are known to increase Pr at glutamatergic synapses, this suggests that the effects of estradiol are specific to spared synapses where Pr has not been up-regulated by deprivation. Exploiting this selectivity may allow for receptive field remapping of spared inputs around a scotoma or cortical infarctItem Medial Frontal Theta Negativities (MFTN) as Predictors of Anxiety Sensitivity Treatment Response(2019) Ellis, Jessica Steward; Bernat, Edward M; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Anxiety is one of the most prevalent mental health problems around the world. Despite a number of widely available interventions, it can take weeks or months to see effects, and nearly half of individuals may not respond. In an effort to better understand response rates, a large body of evidence indicates the most consistent predictor of treatment outcomes is activity in the anterior cingulate cortex (ACC). Although activity in ACC can be measured by medial frontal theta event related potentials (ERPs) at a finer temporal resolution, these neurophysiological components have not been evaluated as predictors of treatment response. There is also a lack of research on the functional networks associated with ACC treatment prediction, despite implications for prefrontal engagement of cognitive control processes. The present study aimed to examine these gaps in the literature by using task-based electroencephalography (EEG) and medial frontal theta negativities (MFTN) as predictors of anxiety sensitivity treatment response. Using amplitude as well as functional connectivity measures (i.e., inter-channel phase synchrony), baseline MFTN (i.e., Theta-FN, Theta-N2) were assessed as predictors of treatment response at mid-treatment, 1-week post treatment, and 6 months post treatment. Subjects underwent a baseline EEG before completing three sessions of a computerized cognitive behavioral intervention. Contrary to the hypothesis, findings revealed MFTN amplitude did not predict treatment response. However, medial to lateral prefrontal theta phase synchrony demonstrated significant prediction effects, such that lower phase synchrony was associated with greater symptom improvement at mid-treatment, 1-week post treatment, and 6 months post treatment. This effect was specific to certain task conditions (i.e., gain feedback and go stimuli), as well as to the combined anxiety and depression treatment group. Results demonstrated accuracy and consistency of treatment prediction, as well as incremental validity after controlling for self-report measures. Finally, results provide additional support for a convergent medial frontal theta process, and suggest that low engagement of regulatory and proactive control mechanisms may be predictive of better response to cognitive behavioral interventions. This work represents a novel finding that may contribute to the improvement in treatment efficacy by serving as a target for future interventions and individualized treatment selection.Item NEURO-INSPIRED AUGMENTATIONS OF UNSUPERVISED DEEP NEURAL NETWORKS FOR LOW-SWAP EMBODIED ROBOTIC PERCEPTION(2017) Shamwell, Earl Jared; Perlis, Donald; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Despite the 3-4 saccades the human eye undergoes per second, humans perceive a stable, visually constant world. During a saccade, the projection of the visual world shifts on the retina and the net displacement on the retina would be identical if the entire visual world were instead shifted. However, humans are able to perceptually distinguish between these two conditions and perceive a stable world in the first condition, and amoving world in the second. Through new analysis, I show how biological mechanisms theorized to enable visual positional constancy implicitly contain rich, egocentric sensorimotor representations and with appropriate modeling and abstraction, artificial surrogates for these mechanisms can enhance the performance of robotic systems. In support of this view, I have developed a new class of neuro-inspired, unsupervised, heterogeneous, deep predictive neural networks that are approximately 5,000%-22,000% faster (depending on the network configuration) than state-of-the-art (SOA)dense approaches and with comparable performance. Each model in this new family of network architectures, dubbed LightEfference (LE) (Chapter 2), DeepEfference (DE) (Chapter 2), Multi-Hypothesis DeepEfference (MHDE) (Chapter 3), and Inertial DeepEfference (IDE) (Chapter 4) respectively, achieves its substantial runtime performance increase by leveraging the embodied nature of mobile robotics and performing early fusion of freely available heterogeneous sensor and motor/intentional information. With these architectures, I show how embedding extra-visual information meant to encode an estimate of an embodied agent’s immediate intention supports efficient computations of visual constancy and odometry and greatly increases computational efficiency compared to comparable single-modality SOA approaches.Item Construction and Utilization of Digital Brain Atlases in Larval Zebrafish(2017) Marquart, Gregory David; Herberholz, Jens; Burgess, Harold A; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Rapid escape responses are critical for predator avoidance in fish. Yet, while short-latency C-start (SLCs) circuitry is well-known (e.g., Mauthner and related cells), neurons integral to long-latency C-starts (LLCs) remain uncharacterized. In this dissertation, I identify neurons critical for LLC through the genetic and laser ablations of neurons in transgenic lines. Although transgenic lines provide powerful tools for implicating neurons in behavior, they suffer a number of limitations. Transgene expression is frequently broad, incompletely mapped, or off-target, making it difficult to accurately compare en masse or to other modalities. I addressed this by designing a UAS reporter that suppresses off-target expression through microRNA binding and building a digital atlas from hundreds of transgenic zebrafish lines. By co-imaging and registering lines with a broadly expressed structural marker, the Zebrafish Brain Browser aligns expression to within approximately one cell diameter allowing rapid and accurate comparison of expression, identification of transgenes, and prediction of genetic overlap in almost any set of cells in the larval zebrafish brain. Other modalities (e.g., neural activity and anatomic segmentation) were also incorporated from Z-Brain, another popular zebrafish brain atlas, by a novel multichannel secondary registration. Together, this work increases the fidelity, interoperability, and accessibility of brain atlases and provides a powerful platform for the dissection of neural circuits in larval zebrafish. Using these tools to design and analyze genetic ablations, I performed a 'circuit-breaking' screen to identify neurons underlying LLC behavior. Three of the screened lines reduced LLC probability by >50%. These lines labeled two shared cell clusters: one adjacent to the locus coeruleus (LC) and another in the dorsal hindbrain. Through laser ablation and optogenetic stimulation, LC-adjacent neurons were shown to be both necessary and sufficient for LLC startle. Projections of individual LC-adjacent neurons were characterized by a novel genetic intersection approach. These neurons were strikingly homogeneous, projecting bilaterally to midbrain and hindbrain structures. From this work, I hypothesize that ipsilateral hindbrain projections activate premotor neurons, while contralateral neurites subserve reciprocal inhibition. For the first time, I have identified a core component of the circuit mediating long-latency C-starts, an ethologically important behavior in zebrafish.Item INTERACTIONS BETWEEN APPETITIVE AND AVERSIVE PROCESSING DURING PERCEPTION AND ATTENTION(2017) Padmala, Srikanth; Pessoa, Luiz; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Although understanding brain mechanisms of appetitive-aversive interactions is relevant to our daily lives and has potential clinical relevance, our knowledge about these brain mechanisms is rudimentary. To address this gap in the literature, we conducted two functional MRI studies that investigated appetitive-aversive interactions during perception and attention in healthy adult human brain. In the first study, we probed how potential reward signaled by advance cues altered aversive distractor processing during a subsequent visual task. Behaviorally, the deleterious influence of aversive stimuli on task performance was reduced during the reward compared to no-reward condition. In the brain, at the task phase, paralleling the observed behavioral pattern, significant interactions were observed in the anterior insula and dorsal anterior cingulate cortex, such that responses during the negative (vs. neutral) condition were reduced during the reward compared to no-reward condition. Notably, negative distractor processing in the amygdala appeared to be independent of the reward manipulation. During the initial cue phase, we observed increased reward-related responses in the ventral striatum, which were correlated with behavioral interference scores at the subsequent task phase, revealing that participants with increased reward-related responses exhibited a greater behavioral benefit of reward in reducing the adverse effect of negative images. Furthermore, the ventral striatum exhibited stronger functional connectivity with fronto-parietal regions important for attentional control. These findings contribute to the understanding of how potential reward influences attentional control and reduces negative distractor processing in the human brain. In the second study, we investigated brain mechanisms underlying the joint processing of positive and negative emotional information during a passive viewing task. Specifically we focused on probing the pattern of appetitive-aversive interactions in brain regions sensitive to the valence and salience of emotional stimuli. In a subset of regions that were sensitive to stimulus valence, competitive interaction patterns were observed. Notably, in other valence-coding regions such as the ventro-medial prefrontal cortex no evidence for competitive interactions was detected. Conversely, in regions sensitive to salience, cooperative interaction patterns were observed. The findings of competitive and cooperative type interactions supported contextual modulation of emotional processing in the human brain.Item THE LONG-TERM IMPACT OF PREVIOUS COCAINE SELF-ADMINISTRATION ON DECISION-MAKING AND STRIATAL CIRCUITRY(2017) Burton, Amanda Claire; Roesch, Matthew R; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Current theories of addiction suggest that impaired decision-making observed in individuals that chronically abuse drugs reflects a decrease in goal-directed behaviors and an increase in habitual behaviors governed by neural representations of response-outcome and stimulus-response associations, respectively. The striatum is a critical input component to the basal ganglia, which is a complex set of subcortical brain structures involved in the selection and execution of actions. Striatal sub-regions are some of the first brain regions to be affected by drugs of abuse, yet we still do not fully understand how decision-making and neural correlates in these regions are affected by drug exposure or disruptions within the circuit. My project was designed to study behavioral and neural changes in the striatum after previous cocaine self-administration or pharmacological lesion while rats perform a complex decision-making task. I therefore implemented a cocaine self-administration or pharmacological lesion protocol and recorded from single neurons in striatal sub-regions, specifically the nucleus accumbens core (NAc) and dorsal lateral striatum (DLS), during performance of an odor-guided decision-making task in which reward contingencies often changed. This task independently manipulated value of expected reward by changing the delay to or size of reward across a series of blocks of trials. I found that previous cocaine self-administration made rats more impulsive, biasing choice behavior toward more immediate reward. After cocaine exposure, there were fewer task-responsive neurons in the NAc and in those that remained we observed diminished directional and value encoding compared to controls. Surprisingly, in the DLS I found evidence of increased response-outcome associations and no evidence of enhanced stimulus-response associations after cocaine exposure. After disrupting communication between the NAc and DLS, I found evidence of enhanced stimulus-response associations in the DLS during task performance. This suggests that cocaine exposure impacts decision-making and neural activity in the striatum that manifests in more complex ways than simply disrupting striatal circuitry as current theories of addiction suggest.Item THE ROLE OF FREQUENCY, TIMING AND LEVEL DISTORTION ON BINAURAL PROCESSING IN SIMULATIONS OF COCHLEAR IMPLANT USERS WITH SINGLE-SIDED DEAFNESS(2017) Wess, Jessica Marie; Bernstein, Joshua GW; Gordon-Salant, Sandra; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Cochlear implants are a promising new treatment option for single-sided deafness. Cochlear implants for single-sided deafness have been shown to improve speech perception in noise and aid in sound localization. However, this intervention is not as good as acoustic hearing and listeners’ exhibit large amounts of variability in hearing outcomes. These limitations may be caused by certain distortions inherent in the processing of the sound signals by the cochlear implant. This dissertation examined the role that three key cochlear implant distortions might play in limiting speech perception in noise for listeners with single-sided deafness. The first distortion examined was the frequency mismatch between the cochlear implant and the acoustic ear. The next distortion examined was the effect of timing differences between the cochlear implant and the normal hearing ear. Finally, the effect of compression on hearing speech in spatial noise was investigated. These limitations and distortions could limit binaural processing ability in those with single-sided deafness who receive a cochlear implant. The goal of this dissertation was to examine the role of cochlear-implant distortions on binaural hearing using simulations of cochlear implant processing presented to normal-hearing listeners. Normal-hearing listeners were presented with vocoder simulations of cochlear-implant processing to one ear, and unprocessed signals to the other ear. These simulations were used to examine the ability to understand binaural speech signals in noisy environments and to examine auditory object formation in simulated free-field environments. These data provided insight into how CI distortions and mapping strategies can limit binaural benefits for those with single-sided deafness. Knowledge of these limitations could lead to better programming strategies to improve binaural hearing and quality of life for those with single-sided deafness who receive a cochlear implant.Item SENSORY AND PERCEPTUAL CODES IN CORTICAL AUDITORY PROCESSING(2017) Cervantes Constantino, Francisco Israel; Simon, Jonathan Z; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)A key aspect of human auditory cognition is establishing efficient and reliable representations about the acoustic environment, especially at the level of auditory cortex. Since the inception of encoding models that relate sound to neural response, three longstanding questions remain open. First, on the apparently insurmountable problem of fundamental changes to cortical responses depending on certain categories of sound (e.g. simple tones versus environmental sound). Second, on how to integrate inner or subjective perceptual experiences into sound encoding models, given that they presuppose existing, direct physical stimulation which is sometimes missed. And third, on how does context and learning fine-tune these encoding rules, as adaptive changes to improve impoverished conditions particularly important for communication sounds. In this series, each question is addressed by analysis of mappings from sound stimuli delivered-to and/or perceived-by a listener, to large-scale cortically-sourced response time series from magnetoencephalography. It is first shown that the divergent, categorical modes of sensory coding may unify by exploring alternative acoustic representations other than the traditional spectrogram, such as temporal transient maps. Encoding models of either of artificial random tones, music, or speech stimulus classes, were substantially matched in their structure when represented from acoustic energy increases –consistent with the existence of a domain-general common baseline processing stage. Separately, the matter of the perceptual experience of sound via cortical responses is addressed via stereotyped rhythmic patterns normally entraining cortical responses with equal periodicity. Here, it is shown that under conditions of perceptual restoration, namely cases where a listener reports hearing a specific sound pattern in the midst of noise nonetheless, one may access such endogenous representations in the form of evoked cortical oscillations at the same rhythmic rate. Finally, with regards to natural speech, it is shown that extensive prior experience over repeated listening of the same sentence materials may facilitate the ability to reconstruct the original stimulus even where noise replaces it, and to also expedite normal cortical processing times in listeners. Overall, the findings demonstrate cases by which sensory and perceptual coding approaches jointly continue to expand the enquiry about listeners’ personal experience of the communication-rich soundscape.