Valence-specific Enhancements in Visual Processing Regions Support Negative Memories:

Thesis advisor: Elizabeth A. KensingerResearch in four parts examines the effects of valence on the neural processes that support emotional memory formation and retrieval. Results show a consistent valence-specific enhancement of visuocortical engagement along the ventral visual stream and occipital cortex that supports negative memories to a greater extent than positive memories. Part I investigated the effects of valence on the interactions between trial-level physiological responses to emotional stimuli (i.e., heart rate deceleration) during encoding and subsequent memory vividness. Results showed that negative memory vividness, but not positive or neutral memory vividness, is tied to arousal-related enhancements of amygdala coupling with early visual cortex during encoding. These results suggest that co-occurring parasympathetic arousal responses and amygdala connectivity with early visual cortex during encoding influence subsequent memory vividness for negative stimuli, perhaps reflecting enhanced memory-relevant perceptual enhancements during encoding of negative stimuli. Part II examined links between individual differences in post-encoding increases is amygdala functional connectivity at rest and the degree and direction of emotional memory biases at retrieval. Results demonstrated that post-encoding increases in amygdala resting state functional connectivity with visuocortical and frontal regions predicted the degree of negative memory bias (i.e., better memory for unpleasant compared to pleasant stimuli) and positive memory bias, respectively. Further, the effect of amygdala-visuocortical post-encoding coupling on behavioral negative memory bias was completely mediated by greater retrieval-related activity for negative stimuli in visuocortical areas. These findings suggest that those individuals with a negative memory bias tend to engage visual processing regions across multiple phases of memory more than individuals with a positive memory bias. While Parts I-II examined encoding-related memory processes, Part III examined the effects of valence on true and false subjective memory vividness at the time of retrieval. The findings showed valence-specific enhancements in regions of the ventral visual stream (e.g., inferior temporal gyrus and parahippocampal cortex) support negative memory vividness to a greater extent than positive memory vividness. However, activation of the parahippocampal cortex also drove a false sense of negative memory vividness. Together, these findings suggest spatial overlap in regions that support negative true and false memory vividness. Lastly, Part IV utilized inhibitory repetitive transcranial magnetic stimulation (rTMS) to test if a portion of occipito-temporal cortex that showed consistent valence-specific effects of negative memory in Parts I-III was necessary for negative memory retrieval. Although some participants showed the hypothesized effect, there was no group-level evidence of a neuromodulatory effect of occipito-temporal cortex rTMS on negative memory retrieval. Together, the results of the current dissertation work highlight the importance of valence-based models of emotional memory and consistently implicated enhanced visuosensory engagement across multiple phases of memory. By identifying valence-specific effects of trial-level physiological arousal during encoding, post-encoding amygdala coupling during early consolidation, and similarities and differences between true and false negative memories, the present set of work has important implications for how negative and positive memories are created and remembered differently.Thesis (PhD) — Boston College, 2019.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Psychology

Opening Access to Visual Exploration of Audiovisual Digital Biomarkers: an OpenDBM Analytics Tool

Digital biomarkers (DBMs) are a growing field and increasingly tested in the therapeutic areas of psychiatric and neurodegenerative disorders. Meanwhile, isolated silos of knowledge of audiovisual DBMs use in industry, academia, and clinics hinder their widespread adoption in clinical research. How can we help these non-technical domain experts to explore audiovisual digital biomarkers? The use of open source software in biomedical research to extract patient behavior changes is growing and inspiring a shift toward accessibility to address this problem. OpenDBM integrates several popular audio and visual open source behavior extraction toolkits. We present a visual analysis tool as an extension of the growing open source software, OpenDBM, to promote the adoption of audiovisual DBMs in basic and applied research. Our tool illustrates patterns in behavioral data while supporting interactive visual analysis of any subset of derived or raw DBM variables extracted through OpenDBM.Comment: 6 pages, 2 figures, 2022 IEEE VIS Workshop - Visualization in BioMedical A

Telomere Length and the Cancer–Atherosclerosis Trade-Off

Modern humans, the longest-living terrestrial mammals, display short telomeres and repressed telomerase activity in somatic tissues compared with most short-living small mammals. The dual trait of short telomeres and repressed telomerase might render humans relatively resistant to cancer compared with short-living small mammals. However, the trade-off for cancer resistance is ostensibly increased age-related degenerative diseases, principally in the form of atherosclerosis. In this communication, we discuss (a) the genetics of human telomere length, a highly heritable complex trait that is influenced by genetic ancestry, sex, and paternal age at conception, (b) how cancer might have played a role in the evolution of telomere biology across mammals, (c) evidence that in modern humans telomere length is a determinant (rather than only a biomarker) of cancer and atherosclerosis, and (d) the potential influence of relatively recent evolutionary forces in fashioning the variation in telomere length across and within populations, and their likely lasting impact on major diseases in humans. Finally, we propose venues for future research on human telomere genetics in the context of its potential role in shaping the modern human lifespan

Smoking does not accelerate leucocyte telomere attrition:A meta-analysis of 18 longitudinal cohorts

Smoking is associated with shorter leucocyte telomere length (LTL), a biomarker of increased morbidity and reduced longevity. This association is widely interpreted as evidence that smoking causes accelerated LTL attrition in adulthood, but the evidence for this is inconsistent. We analysed the association between smoking and LTL dynamics in 18 longitudinal cohorts. The dataset included data from 12 579 adults (4678 current smokers and 7901 non-smokers) over a mean follow-up interval of 8.6 years. Meta-analysis confirmed a cross-sectional difference in LTL between smokers and non-smokers, with mean LTL 84.61 bp shorter in smokers (95% CI: 22.62 to 146.61). However, LTL attrition was only 0.51 bp yr−1 faster in smokers than in non-smokers (95% CI: −2.09 to 1.08), a difference that equates to only 1.32% of the estimated age-related loss of 38.33 bp yr−1. Assuming a linear effect of smoking, 167 years of smoking would be required to generate the observed cross-sectional difference in LTL. Therefore, the difference in LTL between smokers and non-smokers is extremely unlikely to be explained by a linear, causal effect of smoking. Selective adoption, whereby individuals with short telomeres are more likely to start smoking, needs to be considered as a more plausible explanation for the observed pattern of telomere dynamics

Functional Connectivity of the Human Paraventricular Thalamic Nucleus: Insights From High Field Functional MRI

The paraventricular thalamic nucleus (PVT) is a small but highly connected nucleus of the dorsal midline thalamus. The PVT has garnered recent attention as a context-sensitive node within the thalamocortical arousal system that modulates state-dependent motivated behaviors. Once considered related to generalized arousal responses with non-specific impacts on behavior, accumulating evidence bolsters the contemporary view that discrete midline thalamic subnuclei belong to specialized corticolimbic and corticostriatal circuits related to attention, emotions, and cognition. However, the functional connectivity patterns of the human PVT have yet to be mapped. Here, we combined high-quality, high-resolution 7T and 3T resting state MRI data from 121 young adult participants from the Human Connectome Project (HCP) and thalamic subnuclei atlas masks to investigate resting state functional connectivity of the human PVT. The 7T results demonstrated extensive positive functional connectivity with the brainstem, midbrain, ventral and dorsal medial prefrontal cortex (mPFC), anterior and posterior cingulate, ventral striatum, hippocampus, and amygdala. These connections persist upon controlling for functional connectivity of the rest of the thalamus. Whole-brain contrasts provided further evidence that, compared to three nearby midline thalamic subnuclei, functional connectivity of the PVT is strong with the hippocampus, amygdala, ventral and dorsal mPFC, and middle temporal gyrus. These findings suggest that, even during rest, the human PVT is functionally coupled with many regions known to be structurally connected to rodent and non-human primate PVT. Further, cosine similarity analysis results suggested the PVT is integrated into the default mode network (DMN), an intrinsic connectivity network associated with episodic memory and self-referential thought. The current work provides a much-needed foundation for ongoing and future work examining the functional roles of the PVT in humans

Corrigendum: Functional Connectivity of the Human Paraventricular Thalamic Nucleus: Insights From High Field Functional MRI.

[This corrects the article DOI: 10.3389/fnint.2021.662293.]