Neural models of inter-cortical networks in the primate visual system for navigation, attention, path perception, and static and kinetic figure-ground perception

Vision provides the primary means by which many animals distinguish foreground objects from their background and coordinate locomotion through complex environments. The present thesis focuses on mechanisms within the visual system that afford figure-ground segregation and self-motion perception. These processes are modeled as emergent outcomes of dynamical interactions among neural populations in several brain areas. This dissertation specifies and simulates how border-ownership signals emerge in cortex, and how the medial superior temporal area (MSTd) represents path of travel and heading, in the presence of independently moving objects (IMOs). Neurons in visual cortex that signal border-ownership, the perception that a border belongs to a figure and not its background, have been identified but the underlying mechanisms have been unclear. A model is presented that demonstrates that inter-areal interactions across model visual areas V1-V2-V4 afford border-ownership signals similar to those reported in electrophysiology for visual displays containing figures defined by luminance contrast. Competition between model neurons with different receptive field sizes is crucial for reconciling the occlusion of one object by another. The model is extended to determine border-ownership when object borders are kinetically-defined, and to detect the location and size of shapes, despite the curvature of their boundary contours. Navigation in the real world requires humans to travel along curved paths. Many perceptual models have been proposed that focus on heading, which specifies the direction of travel along straight paths, but not on path curvature. In primates, MSTd has been implicated in heading perception. A model of V1, medial temporal area (MT), and MSTd is developed herein that demonstrates how MSTd neurons can simultaneously encode path curvature and heading. Human judgments of heading are accurate in rigid environments, but are biased in the presence of IMOs. The model presented here explains the bias through recurrent connectivity in MSTd and avoids the use of differential motion detectors which, although used in existing models to discount the motion of an IMO relative to its background, is not biologically plausible. Reported modulation of the MSTd population due to attention is explained through competitive dynamics between subpopulations responding to bottom-up and top- down signals

Perceptual organization and its influence upon attention

Humans are able to control so much of their environment not through brute strength or enhanced sensory receptors, but through our ability to understand the world around us. In order to make sense of the world around us we need to organize the information that our sensory systems receive. One of the most fundamental steps in this organizational process lies in the construction of objects. By breaking down our sensory input into objects the mind provides a basis upon which it can begin to scaffold our understanding of the world. This thesis therefore explores the basic stages at which the visual system organizes our sensory input into distinct objects. It explores these stages by exploiting the fact that the brain’s limited processing resources can be selectively allocated on the basis of ‘object-hood’. This allocation of processing resources, or attention, on the basis of these early stages of segmentation is commonly referred to as ‘object based attention’. ‘Object based attention’ and perceptual organisation are explored in three sections in this thesis: Understanding the Phenomenon of Object Based Attention. The first three chapters of this thesis seeks to further our understanding of the phenomenon of ‘object based attention’, for example, chapter 3 explores whether the visual system can simultaneously parse several objects as potential units of attention, or whether it can only segment one or two objects at a time. Object Based Attention, a Tool to Explore the Nature of Perceptual Organisation The second section of this thesis attempts to use the phenomenon of ‘object based attention’ as a tool to explore the nature of perceptual representations, for example chapter 5 tests whether different modalities (in particular vision and touch) are able to directly share information about objects in order to build up an integrated model of the external world. Object Based Attention, Perceptual Organisation and Shape Processing Area LO. In the final section of this thesis the nature of perceptual organization is explored in a patient with a very specific form of brain damage that enables us to ask what areas of the brain are critically required for different aspects of perceptual organization

Visual Cortex

The neurosciences have experienced tremendous and wonderful progress in many areas, and the spectrum encompassing the neurosciences is expansive. Suffice it to mention a few classical fields: electrophysiology, genetics, physics, computer sciences, and more recently, social and marketing neurosciences. Of course, this large growth resulted in the production of many books. Perhaps the visual system and the visual cortex were in the vanguard because most animals do not produce their own light and offer thus the invaluable advantage of allowing investigators to conduct experiments in full control of the stimulus. In addition, the fascinating evolution of scientific techniques, the immense productivity of recent research, and the ensuing literature make it virtually impossible to publish in a single volume all worthwhile work accomplished throughout the scientific world. The days when a single individual, as Diderot, could undertake the production of an encyclopedia are gone forever. Indeed most approaches to studying the nervous system are valid and neuroscientists produce an almost astronomical number of interesting data accompanied by extremely worthy hypotheses which in turn generate new ventures in search of brain functions. Yet, it is fully justified to make an encore and to publish a book dedicated to visual cortex and beyond. Many reasons validate a book assembling chapters written by active researchers. Each has the opportunity to bind together data and explore original ideas whose fate will not fall into the hands of uncompromising reviewers of traditional journals. This book focuses on the cerebral cortex with a large emphasis on vision. Yet it offers the reader diverse approaches employed to investigate the brain, for instance, computer simulation, cellular responses, or rivalry between various targets and goal directed actions. This volume thus covers a large spectrum of research even though it is impossible to include all topics in the extremely diverse field of neurosciences

A Neural Model of How the Brain Computes Heading from Optic Flow in Realistic Scenes

Animals avoid obstacles and approach goals in novel cluttered environments using visual information, notably optic flow, to compute heading, or direction of travel, with respect to objects in the environment. We present a neural model of how heading is computed that describes interactions among neurons in several visual areas of the primate magnocellular pathway, from retina through V1, MT+, and MSTd. The model produces outputs which are qualitatively and quantitatively similar to human heading estimation data in response to complex natural scenes. The model estimates heading to within 1.5° in random dot or photo-realistically rendered scenes and within 3° in video streams from driving in real-world environments. Simulated rotations of less than 1 degree per second do not affect model performance, but faster simulated rotation rates deteriorate performance, as in humans. The model is part of a larger navigational system that identifies and tracks objects while navigating in cluttered environments.National Science Foundation (SBE-0354378, BCS-0235398); Office of Naval Research (N00014-01-1-0624); National-Geospatial Intelligence Agency (NMA201-01-1-2016

The hippocampus and entorhinal cortex map events across space and time

The medial temporal lobe supports the encoding of new facts and experiences, and organizes them so that we can infer relationships and make unique associations during new encounters. Evidence from studies on humans and animals suggest that the hippocampus is specifically required for our ability to form these internal representations of the world. The mechanism by which the hippocampus performs this function remains unclear, but electrophysiological recordings in the hippocampus support a general model. One component of this model suggests that the cortex represents places, times, and events separately, and then the hippocampus generates conjunctive representations that connect the three. According to this hypothesis, the hippocampus binds places and events to an existing relational structure. This dissertation explores how item and place associations develop within cortex, and then examines the relational structure that organizes these events within the hippocampus. The first study suggests that contrary to previous models, events and places are bound together outside of the hippocampus in the entorhinal cortex and perirhinal cortex. The second study shows that this relational scaffold may be embodied by a continually changing code that permits both the association and separation of information across the continuum of time. The final study suggests that the hippocampus and entorhinal cortex contain qualitatively different time codes that may act in a complementary fashion to bind events and places and relate them across time. Overall, these studies support a theory wherein time is encoded in a range of brain regions that also contain conjunctive item and position information. In these regions, conjunctive representations of items, places, and times are organized not only by their perceptual similarity but also their temporal proximity

Bimanual prehension to a solitary target

Grasping and functionally interacting with a relatively large or awkwardly shaped object requires the independent and cooperative coordination of both limbs. Acknowledging the vital role of visual information in successfully executing any prehensile movements, the present study aimed to clarify how well existing bimanual coordination models (Kelso et al, 1979; Marteniuk & Mackenzie, 1980) can account for bimanual prehension movements targeting a single end-point under varying visual conditions. We therefore, employed two experiments in which vision of the target object and limbs was available or unavailable during a bimanual movement in order to determine the affects of visual or memory-guided control (e.g. feedback vs. feed forward) on limb coordination.Ten right-handed participants (mean age = 24.5) performed a specific bimanual prehension movement targeting a solitary, static object under both visual closed loop (CL) and open loop 2s delay (OL2) conditions. Target location was varied while target amplitude remained constant. Kinematic data (bimanual coupling variables) indicated that regardless of target location, participants employed one of two highly successful movement execution strategies depending on visual feedback availability. During visual (CL) conditions participants employed a ‘dominant-hand initiation’ strategy characterized by a significantly faster right-hand (RH) reaction time and simultaneous hand contact with the target. In contrast, when no visual feedback was available (OL2), participants utilized a ‘search and follow’ strategy characterized by limb coupling at movement onset and a reliance on the dominant RH to contact the target ~62 ms before the left.In conclusion, the common goal parameters of targeting a single object with both hands are maintained and successfully achieved regardless of visual condition. Furthermore, independent programming of each limb is undeniably evident within the behaviours observed providing support for the neural cross-talk theory of bimanual coordination (Marteniuk & Mackenzie, 1980). Whether movement execution is visually (CL) or memory-guided (OL2) there is a clear preference of RH utilization possibly due to its dynamic and/or hemispheric advantages in controlling complex motor behaviours (Gonzalez et al., 2006). Therefore, we propose that bimanual grasping to a solitary target is possibly governed globally by a higher-level structure and successful execution is achieved via independent spinal pathway modulation of limbs

Epigenetic and transcriptional regulation of cortico-ponto-cerebellar circuit formation

The precerebellar system constitutes an array of nuclei located in the mammalian hindbrain and conveys movement and balance information from the cortex, spinal cord and periphery to the cerebellum (Sotelo, 2004). Within this system, the pontine nuclei (PN), including pontine gray and reticulotegmental nuclei, mostly relay cortical information (Schwarz and Thier, 1999). During the processing through the cortex, PN and cerebellum, continuous maps of sensorimotor information are transformed into a complex fractured map (Leergaard et al., 2006). To date, however, there is a paucity of knowledge on the molecular and cellular mechanisms organizing this complex circuitry. Previous work suggests an intrinsic topographic organization, according to rostro-caudal progenitor origin, that is maintained during migration and nucleation of the PN (Di Meglio et al., 2013). As a result, one of the hallmarks of the PN topography is a well-defined population of Hox paralogous group 5 (PG5) expressing neurons in the posterior part of the PN. However, the molecular mechanisms governing the spatial expression pattern of Hox PG5 genes in the PN and their functional impact on circuit formation remain largely unknown. The first part of this thesis focuses on the molecular mechanisms of Hox PG5 induction in the precerebellar system. We find that the precise spatio-temporal expression pattern of Hox PG5 genes rely on the integration of environmental signaling and the resulting modifications of the epigenetic landscape. Unlike transcripts of more anterior Hox genes, expression of Hox PG5 genes is entirely excluded from progenitors in the rhombic lip (RL) and only induced in a subset of postmitotic neurons. Mapping and manipulation of signaling pathways show that the restriction of Hox PG5 induction to the ventrally located (i.e. posterior RL-derived) postmitotic pontine neuron subsets is due to an interplay between retinoic acid (RA) and Wnt environmental signaling. Assessment of histone profiles at Hox loci indicate that the induction of Hox PG5 genes through RA is tightly linked to a depletion of the histone mark H3K27me3. However, conditional inactivation of Ezh2, a member of the polycomb repressive complex 2 responsible for setting the H3K27me3 mark (Margueron and Reinberg, 2011), does not result in a de-repression of Hox PG5 genes in the progenitor domain. In contrast, removal of H3K27me3 in Ezh2 depleted PN neurons leads to an ectopic induction of Hox PG5 in rostral PN neuron subsets of the migratory stream showing an enhanced response to RA (Di Meglio et al., 2013). Moreover, high levels of RA-induced Hox PG5 expression in postmitotic PN neurons require Jmjd3, one of the enzymes known to catalyze the removal of methyl groups at H3K27 (Agger et al., 2007; De Santa et al., 2007). We show that Jmjd3 is physically present at RA responsive elements in proximity to the Hoxa5 promoter supporting the direct involvement of Jmjd3 in Hox PG5 induction. Thus, a central function of H3K27me3 regulation during late stages of precerebellar development is the establishment of a threshold for RA mediated activation of Hox PG5 genes to allow for diversification of PN neurons. Finally, we show how the integration of environmental signaling on the epigenetic level results in distinct changes of the three dimensional (3D) organization of chromatin at Hox PG5 loci in vivo. Together, the late specification of PN neurons employs a sophisticated sequence of interactions between signaling pathways such as RA and Wnt, and histone modifying enzymes like Ezh2 and Jmjd3. The second part of the thesis addresses the functional significance of Hox PG5 genes in sub-circuit formation of PN neurons. Using multiple conditional overexpression strategies, we show that the expression of Hoxa5 is sufficient to shape the input-output relationship of PN neurons. Hoxa5 expressing neurons migrate into a posterior position in the PN and induce a distinct transcriptional program specific for topographic circuit formation. Together, this indicates a crucial role of Hoxa5 in the specification of the positional identity of PN subsets. We further describe a genetically identified Hox PG5 negative PN subset that primarily projects to the paraflocculus, a lobule in the cerebellum heavily concerned with visually related tasks. Conditional overexpression of Hoxa5 in this PN subset leads to the ectopic targeting of several other lobes in the cerebellum concerned with processing of somatosensory information. This matches with the input connectivity of the PN that has been shown to be antero-posteriorly patterned, such that visual/medioposterior projections target the anterior, Hox PG5 negative, and somatosensory projections target the posterior, Hox PG5 positive part of the PN (Di Meglio et al., 2013; Leergaard and Bjaalie, 2007). Consequently, Hoxa5 overexpressing PN neurons are largely devoid of input from the visual cortex and primarily engage in a somatosensory hindlimb specific circuitry. One single Hox gene is thus sufficient to position neurons in the posterior aspects of the PN, change their transcriptional program and rearrange both, output connectivity to the cerebellum and input connectivity from the cortex. These findings extend the function of Hox genes to orchestrating topographic circuit formation in the PN. Further, the presented results point towards an involvement of Hox genes in the longstanding problem of fracturing of the somatosensory map that is realized between the cortex and the cerebellum

Altered visual perception near the hands: a critical review of attentional and neurophysiological models

Visual perception changes as a function of hand proximity. While various theoretical accounts have been offered for this alteration (attentional prioritisation, bimodal cell involvement, detailed evaluation, and magnocellular neuron input enhancement), the current literature lacks consensus on these mechanisms. The purpose of this review, therefore, is to critically review the existing body of literature in light of these distinct theoretical accounts. We find that a growing number of results support the magnocellular (M-cell) enhancement account, and are difficult to reconcile with general attention-based explanations. Despite this key theoretical development in the field, there has been some ambiguity with interpretations offered in recent papers, for example, equating the existing attentional and M-cell based explanations, when in fact they make contrasting predictions. We therefore highlight the differential predictions arising from the distinct theoretical accounts. Importantly, however, we also offer novel perspectives that synthesises the role of attention and neurophysiological mechanisms in understanding altered visual perception near the hands. We envisage that this theoretical development will ensure that the field can progress from documenting behavioural differences, to a consensus on the underlying visual and neurophysiological mechanisms.This research was supported by an Australian Research Council (ARC) Discovery Early Career Research Award (DE140101734) awarded to S.C.G., ARC Discovery Project (DP110104553) awarded to M.E, a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grants awarded S.F. and J.P

Neural Encoding of Local vs. Global Space: From Structure to Function

The retrosplenial cortex may be important for navigating visually similar compartmentalised spaces by conjunctively encoding both local and global environments. Previously, a novel directional signal that encodes local spaces was found in the dysgranular retrosplenial cortex (dRSC) while global head direction encoding was found in both dRSC and granular retrosplenial cortex (gRSC; Jacob et al., 2017). This thesis addresses two questions arising from this finding: (i) how does the local directional signal arise? and (ii) do the downstream place cells (cells that display spatially constrained firing) display local or global encoding? The first question was explored by retrogradely labelling the neuronal inputs into the two retrosplenial regions under the hypothesis that the differences in directional encoding are due to differences in their inputs. Particularly, gRSC was found to receive more inputs from anterodorsal thalamus, which was previously shown to display global encoding (Jacob et al., 2017). In addition, gRSC, but not dRSC, received inputs from dorsal subiculum which is the main output structure of hippocampus. It is however unclear if place cell in hippocampus displayed local or global place encoding. The second question thus arises: Do place cells display local or global place encoding? As hippocampus is strongly coupled with gRSC, place cells were predicted to show a global representation similar to that in gRSC. Extracellular recording of place cells in an environment with two differentially scented, visually rotated compartments showed that no place cells that are sensitive to the local visual scene were found. Thus, place cells displayed global encoding. Together, these findings indicate that global encoding in gRSC may be a consequence of its stronger coupling with vestibular-directional nuclei and the hippocampal system, both of which displayed global encoding. In contrast, the local encoding observed in dRSC may reflect its structural disconnect from the global spatial network