Maddie Cusimano, McDermott Lab

Title: Bayesian Auditory Scene Analysis

Abstact: We often experience sound as comprising multiple streams that arise from distinct sources. However, this structure is not evident in the sensory data, as there are an infinite number of causal explanations for any acoustic signal. This talk will describe a hierarchical Bayesian model of how the auditory system constructs explanations of auditory scenes in terms of sources, focusing on classic perceptual demonstrations of auditory grouping. Despite this emphasis, the model can also make reasonable inferences of source structure from recorded audio. Given the model's ability to generalize, this work provides a foundation for studying scene analysis with natural sounds.

Scarlett Barker, Tsai Lab

Title: Resilient brains: Epigenetic signatures of early life enrichment and cognitive reserve

Abstract: Experiences can have a profound impact on the health and functioning of our brains. For instance, individuals who are raised in conditions of neglect and isolation have a higher incidence of many neurological disorders, while those who are cognitively stimulated throughout life often display enhanced cognition and a delayed onset of neurodegenerative diseases. While these epidemiological findings are correlative, studies using animal models have shown that environmental manipulations alone (rather than underlying genetic differences) can give rise to biological changes that confer cognitive risk or reserve. Epigenetic mechanisms are responsible for translating environmental signals into biological changes at the molecular level. Thus, we set out to epigenetically characterize the neurons of mice that have been subjected to a range of environmental conditions early in life, ranging from isolation to a combination of cognitive, social, and physical enrichment. Using both ATAC- and RNA sequencing, we identified changes in chromatin state and basal transcription that occur as a result of environmental enrichment. Computational analysis revealed that binding sites of the MEF2 family of transcription factors are statistically enriched among the regions of chromatin that become more accessible, or functionally relevant, following environmental enrichment. Remarkably, neurons from human patients who displayed cognitive resilience in the face of Alzheimer’s pathology also showed statistical enrichment of MEF2 transcripts, potentially validating the relevance of this finding in mice. Future directions of this work aim to manipulate the activity of this transcription factor family in order to induce an enriched brain state in non-enriched animals. 

Jacob Donoghue, Miller Lab

Title: Thalamic Deep Brain Stimulation Restores Awake-like Behavior and Cortical Dynamics in Anesthetized Macaques

Abstract: A convergence of theoretical and electrophysiological findings suggests that a conscious state of wakefulness and awareness may emerge from the integration of information in finely tuned cortical networks coordinated by connections with the thalamus. The central thalamus has a special role in modulating conscious states; injury to the region can result in coma and its activation using deep brain stimulation (DBS) drives behavioral improvements in minimally conscious patients. The intralaminar nuclei, in particular, may serve as a critical hub, containing neuromodulatory projections from brainstem arousal systems and sending fibers diffusely across cortex. We employed a non-human primate model of general anesthesia to study how these brain networks mediate changes across conscious states. We simultaneously recorded spikes and local field potentials (LFPs) from chronically implanted multielectrode arrays in prefrontal, posterior parietal, and auditory cortex and from laminar probes within the central thalamus during the intravenous administration of the GABAergic anesthetic propofol. Sensory stimuli were delivered throughout each session, with loss-of-consciousness (LOC) determined as the time of discontinued electromyographic eye-blink responses to an air puff. At the deepest stages of anesthesia, we observed dynamics similar to previously reported intracranial human and macaque studies: cortical neurons decreased their firing rates, while large-amplitude cortical slow oscillations (< 1 Hz) and isolelectric periods (i.e. burst-suppression) emerged in LFPs as higher-frequency power decreased. We sought to establish a causal role for the thalamus in maintaining this unconscious state by activating the intralaminar nuclei with high-frequency electrical stimulation. Bipolar DBS (biphasic 180 Hz pulse trains) elicited an immediate state of apparent wakefulness characterized by eye opening, puff responses, and restored limb movement, despite continued propofol infusion. Thalamic stimulation produced an awake-like cortical state, eliminating slow oscillatory activity across brain regions and inducing a shift to higher frequency rhythms with increased neuronal firing rates. Behavioral and physiologic changes regularly outlasted DBS offset, with LOC reoccurring up to minutes later. Together, these results shed light on the anatomical pathways and network states required to support cortical processing, cognition, and consciousness.