Long-Term Consequences of Early Eye Enucleation on Audiovisual Processing

A growing body of research shows that complete deprivation of the visual system from the loss of both eyes early in life results in changes in the remaining senses. Is the adaptive plasticity observed in the remaining intact senses also found in response to partial sensory deprivation specifically, the loss of one eye early in life? My dissertation examines evidence of adaptive plasticity following the loss of one eye (unilateral enucleation) early in life. Unilateral eye enucleation is a unique model for examining the consequences of the loss of binocularity since the brain is completely deprived of all visual input from that eye. My dissertation expands our understanding of the long-term effects of losing one eye early in life on the development of audiovisual processing both behaviourally and in terms of the underlying neural representation. The over-arching goal is to better understand neural plasticity as a result of sensory deprivation. To achieve this I conducted seven experiments, divided into 5 experimental chapters, that focus on the behavioural and structural correlates of audiovisual perception in a unique group of adults who lost one eye in the first few years of life. Behavioural data (Chapters II-V) in conjunction with neuroimaging data (Chapter VI) relate structure and function of the auditory, visual and audiovisual systems in this rare patient group allowing a more refined understanding of cross sensory effects of early sensory deprivation. This information contributes to us better understanding how audiovisual information is experienced by people with one eye. This group can be used as a model to learn how to accommodate and maintain the health of less extreme forms of visual deprivation and to promote overall long-term visual health

MyoPS A Benchmark of Myocardial Pathology Segmentation Combining Three-Sequence Cardiac Magnetic Resonance Images

Assessment of myocardial viability is essential in diagnosis and treatment management of patients suffering from myocardial infarction, and classification of pathology on myocardium is the key to this assessment. This work defines a new task of medical image analysis, i.e., to perform myocardial pathology segmentation (MyoPS) combining three-sequence cardiac magnetic resonance (CMR) images, which was first proposed in the MyoPS challenge, in conjunction with MICCAI 2020. The challenge provided 45 paired and pre-aligned CMR images, allowing algorithms to combine the complementary information from the three CMR sequences for pathology segmentation. In this article, we provide details of the challenge, survey the works from fifteen participants and interpret their methods according to five aspects, i.e., preprocessing, data augmentation, learning strategy, model architecture and post-processing. In addition, we analyze the results with respect to different factors, in order to examine the key obstacles and explore potential of solutions, as well as to provide a benchmark for future research. We conclude that while promising results have been reported, the research is still in the early stage, and more in-depth exploration is needed before a successful application to the clinics. Note that MyoPS data and evaluation tool continue to be publicly available upon registration via its homepage (www.sdspeople.fudan.edu.cn/zhuangxiahai/0/myops20/)

Toward a comprehensive account of orientation selectivity in the retina.

Retinal Ganglion Cells (RGCs) form functionally distinct signaling channels that selectively encode features of the visual input including direction of motion, contrast polarity, size, and color. A highly conserved visual channel amongst vertebrates conveys orientation selectivity, i.e., the selective firing of neuronal cells in response to elongated stimuli along a preferred orientation. Orientation selectivity is an apparent critical computation and several studies have reported aspects of it, including cell type identity in anatomical reconstructions, and functional characterization of at least four different identified RGC types. But how cell types in the different studies relate is not well resolved; the mechanisms that generate the orientation selective responses in mice remain incompletely understood; and the retinofugal projections of OS RGC types are unknown. The goal of this study was to comprehensively characterize Orientation Selective (OS) RGC types in the mouse retina, and to elucidate the mechanisms that contribute to their tuning properties. We used population calcium imaging and hierarchical clustering to identify orientation selective RCGs in retinal explants. We then targeted these cells for detailed morphological and electrophysiological study. Our survey of RGC populations and subsequent morphological analysis distinguished 10 morphological types with apparent OS tuning. Electrophysiological analysis of 5 types identified specific tuning mechanisms, including a type with tuned excitation and inhibition, and a type with just tuned inhibition. Retrograde tracing from dLGN indicates that OS cells project to the shell region of the dorsal Lateral Geniculate Nucleus (dLGN), indicating that at least some OS RGC types contribute to dLGN OS tuning. This work provides new insight into the morphology and function of RGC types that exhibit OS properties. Additional studies will be necessary to further solidify the full complement of OS types in the retina and resolve their detailed circuit-level mechanisms, synaptic partners, molecular profiles, and retinofugal projections

Modulation of Hippocampal-Prefrontal Circuitry During Spatial Working Memory

Spatial working memory (SWM) is an essential feature of goal-directed action. Locating a resource, a threat, or even oneself within a dynamic or unfamiliar environment requires a cached representation of relevant spatial features that must be continuously updated, preserved, and applied as needed to the execution of appropriate behaviors (Baddeley and Hitch 1974). SWM is disrupted in schizophrenia, as well as in multiple animal models of the disease. Patients with schizophrenia show impairment on tasks with both verbal and spatial working memory demands (Park and Holzman 1992, Conklin, Curtis et al. 2000) and exhibit abnormalities in neurophysiological signals that are associated with normal cognitive performance. More specifically, convergent data from diverse studies suggests that disruption of long-range functional connectivity may underlie diverse cognitive and physiological symptoms of the schizophrenia. It is therefore imperative that pathways of long-range functional connectivity that support the cognitive processes impaired in schizophrenia be identified and characterized, so that effective interventions can be targeted to the appropriate neural structures and pathways. Despite long-standing interest in the neurobiological underpinnings of working memory, its multiple cognitive components, distributed anatomical constituents, and distinct temporal phases have rendered its investigation elusive (Logie 1995, Miyake and Shah 1999, Andrade 2001, de Zubicaray, McMahon et al. 2001, Baddeley 2003, Klauer and Zhao 2004). Despite these challenges, an extensive body of work supports the idea that the prefrontal cortex (PFC) plays a central role in the successful execution of tasks requiring spatial working memory (Curtis and D'Esposito 2004). Moreover, the joint contribution of medial prefrontal cortex (mPFC) and hippocampus (HPC) supports successful spatial working memory in rodents (Lee and Kesner 2003, Jones and Wilson 2005, Wang and Cai 2006, Hyman, Zilli et al. 2010, Sigurdsson, Stark et al. 2010). It remains unclear, however, which phase(s) of SWM (encoding, maintenance, and/or retrieval) require the joint participation of HPC and mPFC, what behaviorally relevant information is conveyed between the two structures, and by what anatomical pathway(s) they interact. Although HPC and mPFC share multiple second-degree anatomical connections, including via striatum, amygdala, entorhinal cortex, and midline thalamic nuclei, direct connectivity between the two structures is confined to a unidirectional projection from the Ca1/subiculum of the ventral hippocampus (vHPC) to prelimbic (PL) and infralimbic (IL) regions of the mPFC (Jay and Witter 1991, Hoover and Vertes 2007, Oh 2014). Cells of both vHPC and mPFC exhibit location-specific firing that could function to encode spatial cues critical to SWM (Jung, Wiener et al. 1994, Poucet, Thinus-Blanc et al. 1994, Jung, Qin et al. 1998, Hok, Save et al. 2005, Kjelstrup, Solstad et al. 2008, Burton, Hok et al. 2009, Royer, Sirota et al. 2010, Keinath, Wang et al. 2014). Moreover, damage to the vHPC disrupts representations of salient locations in mPFC (Burton, Hok et al. 2009), suggesting that the vHPCmPFC projection may transmit SWM critical location information. We therefore tested the role of vHPC-mPFC afferents in spatial working memory using an a projection silencing approach that afforded anatomical and temporal precision and found that the vHPC-mPFC direct input is necessary for encoding, not maintenance or retrieval, of SWM-dependent cues. Combining this approach with in vivo extracellular recordings of mPFC single units, we found that location-selective firing in the mPFC during SWM is dependent on vHPC direct input exclusively during the encoding phase of each trial. Finally, we found evidence that the transmission of task-critical information in the vHPC-mPFC pathway is mediated by the synchronizing of mPFC cells to gamma oscillations in the vHPC. Together, these findings suggest a role for the vHPC-mPFC pathway in the encoding of cues critical to SWM and may indicate a potential locus of pathophysiological disruption underlying the cognitive impairments associated with schiziphrenia