Thesis (Ph. D.)--University of Missouri-Columbia, 1999. / Typescript. Vita. Includes bibliographical references (leaves 103-110). Also available on the Internet.

The present study translated the major theories of obesity into physiological terms, then tested for the ways these theories might find physiological expression. Theoretical positions included the psychoanalytic perspective, emphasizing intrapsychic processes; psychosomatic perspective, emphasizing food as an anxiolytic agent; and Schachterian perspective, emphasizing heightened sensitivity to external stimuli. Additionally, two classificatory distinctions, age at onset of obesity and extent of dietary restraint, were examined. The later distinction suggested that Schachterian findings on obese behavior were due not to obesity, but to a dieting life style.

The overarching purpose of this work is to investigate the effect of pupil-linked arousal systems and heart rate-linked arousal systems on behavior and the use of pupil dynamics as an index for adaptive behavior. These arousal systems are correlated with behavior states which have modulatory effects on perception and neural coding and are therefore integral in carrying out complex behaviors, such as decision-making. Additionally, cholinergic transmission is proposed to be critical for adaptive behavior via its modulation of thalamic neurons. While the first two chapters focus on the behavior output and the non-invasive ways to index arousal and behavior, the third aim attempts to investigate the neural circuits that underlie arousal’s effect on adaptive behavior by studying the pattern of cholinergic axons between brainstem nuclei and the thalamus, opening avenues for future investigation of their mechanistic impact on adaptive behavior. For characterization of the influence of arousal indexed by pupil dynamics and heartbeat dynamics, we simultaneously recorded electrocardiogram (ECG) and pupil size in head-fixed rats performing tactile discrimination tasks. We found both heartbeat dynamics and pupil size co-varied with behavioral outcomes, indicating behavior was dependent upon arousal indexed by both physiological signals. The potential difference between the effects of pupil-linked arousal and heart-rate linked arousal on behavior were estimated by constructing a Bayesian decoder predicting animals’ behavior from both signals prior to stimulus presentation. The decoder performed significantly better when using both physiological signals as inputs, suggesting both arousal systems, pupil-linked and heart rate-linked are not completely redundant. Additionally, the pupil size-based decoder failed to correctly predict animals’ behavior on a substantial portion of trials correctly predicted by the heart rate-based decoder, furthermore suggesting that both arousal systems exert different influences on animals’ behavior (Y.Liu, S. Narasimhan, B.J.Schriver, & Q.Wang, 2021). For characterization of how adaptive behavior in response to changing sensory environments depends on pupil-linked arousal, we recorded pupil size and behavioral output simultaneously during a similar tactile Go/No-Go discrimination task while systematically varying the statistics of the sensory environment. For each session, the probability of the presence of reward linked-stimuli (S+/Go) was randomly set at 80%, 50% or 20%. Animals adapted their behavioral responses and the task evoked pupil responses were bigger when the probability of S+ was lower. Impulsive licking (pre-stimulus response) decreased as the probability of S+ was lower. Animals became more liberal as the probability of S+ increased, in line with signal detection theory, indexed by a decrease in the decision criterion. We additionally found that reaction time decreased as the probability of S+ increased. A hierarchical drift diffusion model (HDDM) was used to model the decision-making process in these paradigms. We found the drift rate to monotonically vary with task difficulty. Animals performed sub-optimally to adaptively change their action in response to changes in the sensory environment and this adaptive adjustment in decision-making was indexed by their pupil dynamics. For studying the pattern of cholinergic axons between brainstem nuclei and the thalamus, we used two different AAV-retrograde constructs with two different reporters (mCherry and GFP) injected in the left and right hemisphere of the ventral-posterior-medial (VPM) thalamic nucleus of recombinant ChAT-cre mice. In agreement with previous studies done with conventional tracing methods, labelled projecting cells were traced to the LDT and PPN in the brainstem. Labelled cells were found in a clustered area of the LDT, suggesting a topographic distribution of the projections between the LDT and the VPM. A larger quantity of labelled cells was found in the PPN than the LDT. Additionally, bilateral injections with double reporters enabled us to find that a majority of cells project from the brainstem to the VPM project ipsilaterally while still displaying lateralization. This work provides methods and tools for future investigation of the functional impact of these projections between LDT, PPN and the VPM.

Resting State functional Magnetic Resonance Imaging (rs-fMRI) has revealed brain-wide correlation patterns throughout the human brain, interpreted as Functional Connectivity. Dynamic Functional Connectivity (DFC) has recently expanded on this technique via sliding window correlation analysis, revealing moment-to-moment changes in functional connectivity across an imaging session. However, the meaning of these transitions in terms of neural activity and behavior are not well understood.In this work, I utilized Dynamic Functional Connectivity analytical techniques in conjunction with Wide Field Optical Mapping (WFOM) in the awake, freely behaving mouse. I hypothesized that neural and hemodynamic activity observed with WFOM would exhibit similar transitions between functional connectivity states as reported by fMRI DFC studies. I also explored whether changes in functional connectivity would correspond to changes in behavior. Simultaneous neural and hemodynamic activity was collected using WFOM from five freely behaving head-fixed Thy1-jRGECO1a mice. Behavioral metrics of movement, whisking and pupillometry were acquired simultaneously. Raw neuroimaging data were dimensionally reduced to representative time courses across the dorsal surface of the cortex for each subject utilizing a semi-supervised clustering technique. Functional Connectivity analysis revealed rich spatiotemporal structures within neural and hemodynamic activity, which were consistent across imaging sessions and subjects. I observed broad changes in Functional Connectivity metrics during rest, locomotion, and transitional epochs between the two by directly comparing windows captured during these epochs. It was also observed that Functional Connectivity metrics immediately following locomotion offset could be distinguished from periods of sustained rest. Similar to human fMRI studies, a distinct increase in bilateral connectivity of anterior lateral prefrontal cortex was observed, which became significantly less synchronized with posterior brain regions during sustained periods of rest. I next used an unsupervised clustering technique on the same data to test if these properties could be observed in an indirect manner. This approach has been previously used in numerous human fMRI studies, and contextualized this work to human fMRI studies. A sliding window was used to calculate moment-to-moment Functional Connectivity maps across each imaging session. These dynamic correlation maps were clustered into multiple states, which could then be used to calculate the most representative state for any given epoch. Unsupervised clustering revealed strikingly similar dynamic states to our previous observations. These dynamic states also exhibited independent distributions of behavioral activity both in neural and hemodynamic models, leading us to conclude that there is not only a meaningful link between Functional Connectivity in neural and hemodynamic activity, but that behavioral shifts largely drive these changes. My findings provide strong evidence that Dynamic Functional Connectivity has neural origins, and hemodynamic responses are able to depict correlation patterns that tracks rapid changes in behavior and internal brain states such as the level of arousal or alertness. Future studies are necessary to further investigate this speculation, but this offers an excellent framework to better understand the rich, dynamic properties of brain activity.

Alcohol consumption on college campuses is a major public health concern, particularly among emerging adults. Extant literature has identified trauma exposure and posttraumatic stress as robust risk factors for problematic alcohol use. However, the mechanisms underlying this association are less well-studied. Research indicates that bodily arousal is a fundamental feature of trauma exposure and posits that internal stimuli (e.g., heart pounding) at the time of trauma may manifest into conditioned cues that can trigger posttraumatic responding and related symptomatology, including alcohol use. However, past work supporting these assertions have used paradigms purposefully designed to evoke memories of the trauma, making it difficult to conclude whether the subsequent alcohol craving was due more to the explicit memory cue or the associated bodily arousal. The current study examined whether an implicit, trauma-relevant cue of bodily arousal (via hyperventilation) – independent of any explicit memory cue – would elicit increased desire to drink among 80 (Mage = 20.34; 63.8% female) trauma-exposed, emerging adult students. Results found no statistically significant difference in change in alcohol craving between the hyperventilation and control tasks. However, exploratory analyses indicated that trauma type (i.e., interpersonal/non-interpersonal) may moderate this relationship; more specifically, individuals reporting interpersonal trauma as their most traumatic event evidenced a significantly greater increase in desire to drink following hyperventilation compared to the non-interpersonal index trauma group. Generally, results suggest that bodily arousal, without an explicit trauma reminder, is not a specific and/or powerful enough trauma-relevant cue to reliably influence alcohol cravings across all trauma exposed emerging adult students. Suggestions for future directions to help in identifying at-risk subgroups, as well as methodological and procedural improvements, are discussed.