Functional cerebral asymmetries of emotional processes in the healthy and bipolar brain

The perception and processing of emotions are of primary importance for social interaction, which confers faculties such as inferring what another person’s feels. Brain organisation of emotion perception has shown to primarily involve right hemisphere functioning. However, the brain may be functionally organised according to fundamental aspects of emotion such as valence, rather than involving processing of emotions in general. It should be noted, however, that emotion perception is not merely a perceptual process consisting in the input of emotional information, but also involves one’s emotional response. Therefore, the functional brain organisation of emotional processing may also be influenced by emotional experience. An experimental model for testing functional cerebral asymmetries (FCAs) of valenced emotional experience is uniquely found in bipolar disorder (BD) involving impaired ability to regulate emotions and eventually leading to depressive or manic episodes. Previous models have only explained hemispheric asymmetries for manic and depressive mood episodes, but not for BD euthymia. The present thesis sought to investigate FCAs in emotional processing in two major ways. First, FCAs underlying facial emotion perception under normal functioning was examined in healthy controls. Secondly, functional brain organisation in emotional processing was further investigated by assessing FCAs in the bipolarity continuum, used as an experimental model for studying the processing of emotions. In contrast with previous asymmetry models, results suggested a right hemisphere involvement in emotional experience regardless of valence. Atypical FCAs were found in euthymic BD patients reflecting inherent aspects of BD functional brain organisation that are free of symptomatic influence. Also, BD patients exhibited atypical connectivity in a default amygdala network particularly affecting the right hemisphere, suggesting intrinsic mechanisms associated with internal emotional states. Last, BD patients were associated with a reduced right hemisphere specialisation in visuospatial attention, therefore suggesting that right hemisphere dysfunction can also affect non-emotional processes. Taken together, the findings emphasize a BD continuum model relying on euthymia as a bridging state between usual mood and acute mood phases

Upper Limb Asymmetries of Movement Sense and Sense of Effort: The Contribution of Gender and Handedness.

Asymmetry in upper limb performances may have multiple origins. The aim of this research is to determine the contribution of sensory and motor processes to asymmetries in movement sense and sense of effort when considering gender and handedness. The distinction between gender and handedness effects, while often ignored, may shed new light on human performances. The first study investigated asymmetry in movement sense using contralateral reproductions of vibration induced illusions of movements in right (RH) and left (LH) handed young adults of both genders. Females were found more sensitive to vibratory stimulations and less asymmetric than males in movement reproduction. The asymmetry observed in males was related to handedness. Both asymmetry and sensitivity were primarily sensory in origin. The second study investigated asymmetries in the sense of effort and targeted the motor component. Both RH and LH adults were divided into three groups based on hand strength differences. A 20% MVC reference grip force was matched with the same or opposite hand (of the reference). The matching error increased with hand strength differences for RH only, suggesting that the sense of effort is a consequence of both muscle strength differences and an intrinsic asymmetry of the motor component that may vary with handedness. The last study investigated the relative contributions of efferent copy and sensory feedback to the sense of effort. Vibration was used to distort the sensory information from muscles providing the reference in the grip matching task. Visual feedback of the reference hand was also manipulated. The hand/hemisphere systems were found to differ significantly in their dependence on proprioceptive information during force reproduction, with the left hand being more feedback dependent. These findings lead us to suggest that hand preference and gender contribute to differences in movement representation, force production and sense of effort that may result from the combination of cortical structural differences and information processing specific to each hemisphere, gender and handedness group.PhDIndustrial & Operations EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/99857/1/sscotlan_1.pd

Micro-, Meso- and Macro-Connectomics of the Brain

Neurosciences, Neurolog

Form in Darkness: Linking Visual Cortex Structure With Spontaneous Neural Function

Spontaneous neural activity within visual cortex is synchronized at varying spatial scales, from the cytoarchitecural level of individual neurons to the coarse scale of whole regions. The neural basis of this synchronicity remains ambiguous. In this thesis, we focus on the role visual experience plays in organizing the spontaneous activity within the visual system. We start in Chapter 2 by creating a means by which to analyze homologous patches of cortex between sighted and blind individuals, as lack of vision precludes the use of traditional stimulus-driven mapping techniques. We find that anatomy alone could indeed predict the retinotopic organization of an individual\u27s striate cortex with an accuracy equivalent to the length of a typical mapping experiment. Chapter 3 applies this approach to analyze the organization of spontaneous signals within the striate cortex of blind and sighted subjects. We find that lack of visual experience produces a subtle change in the pattern of corticocortico correlations only between the hemispheres, and that these correlations are best modeled as function of cortical distance, not retinotopy. Chapter 4 expands our analysis to include areas V2 and V3. Here, we find that persistent visual experience supports network-level neural synchrony between spatially distributed cortical visual areas at both a coarse (regional) and fine (topographic) scale. Together, these results allow us model the organization of spontaneous activity in visual cortex as a combination of network signals linked to visual function and intrinsic signals coupled to structural connections. In the final chapter, we examine possible top-down mediators that may further modulate this network-level correlation. Minimal change in synchronicity is observed in a subject with a corpus callosotomy, suggesting the preeminence of bottom-up inputs. Taken together, this work advances our understanding of the origins of coherent spontaneous neural activity within visual cortex

Cognitive and Neurophysiological Models of Brain Asymmetry

Asymmetry is an inherent characteristic of brain organization in both humans and other vertebrate species, and is evident at the behavioral, neurophysiological, and structural levels. Brain asymmetry underlies the organization of several cognitive systems, such as emotion, communication, and spatial processing. Despite this ubiquity of asymmetries in the vertebrate brain, we are only beginning to understand the complex neuronal mechanisms underlying the interaction between hemispheric asymmetries and cognitive systems. Unfortunately, despite the vast number of empirical studies on brain asymmetries, theoretical models that aim to provide mechanistic explanations of hemispheric asymmetries are sparse in the field. Therefore, this Special Issue aims to highlight empirically based mechanistic models of brain asymmetry. Overall, six theoretical and four empirical articles were published in the Special Issue, covering a wide range of topics, from human handedness to auditory laterality in bats. Two key challenges for theoretical models of brain asymmetry are the integration of increasingly complex molecular data into testable models, and the creation of theoretical models that are robust and testable across different species

Examining Inter- And Intra-Individual Differences In The Neurobiological Mechanisms Associated With Inhibitory Control

Adolescence is an ideal time to measure the development of the neural mechanisms associated with inhibitory control because this age period is marked by impulsive and risk taking behaviors. Maturational brain changes in the prefrontal cortex that are associated with the emergence of inhibitory control are thought to occur during this age. With knowledge of how this system develops, it may be possible to identify the development of disorders that arise from poor inhibitory control such as attention deficit hyperactivity disorder (ADHD) and substance use. The goal of the current dissertation is to examine the neurobiological correlates associated with individual differences in inhibitory ability, and examine the age-related changes in neurobiological mechanisms of inhibitory control. This report will be the first of its size (n = 538) to examine within-subject changes longitudinally over five years of adolescent development (age 14 to 19). Furthermore, we supplement the longitudinal data with findings from a split-brain patient on the lateralization of inhibitory control, and we explore a subtle nuance that may have large implications on how to best measure inhibition-related brain activity. In the second chapter of the dissertation, we examine the lateralization of inhibitory control by measuring hemispheric differences in the ability to inhibit a motor response in a split-brain patient. Here, we found patient J.W.’s right hemisphere performed better than his left hemisphere on three different inhibitory control tasks. Interestingly, although inferior to the performance of the right hemisphere, the left hemisphere still performed relatively well on the three tasks, suggesting the left hemisphere can perform response inhibition independently. The third chapter examines both the functional correlates of Stop Signal Task performance, and the age-related differences in the functional mechanisms of response inhibition. At age 14 and age 19, similar patterns of activation were associated with performance, however relatively little overall activity exhibited performance-related effects. Superior performance was associated with greater right inferior frontal gyrus (rIFG) activation, as well as greater activation in a set of regions potentially involved with a stimulus-detection and attention-orienting system. However, at age 14 performance was also negatively associated with default mode network activity, and at age 19 performance was also positively associated with left amygdala activity. In the absence of within-subject differences in performance between ages 14 to 19, there were significant decreases in functional activation associated with successful inhibition. The potential mechanisms by which activity decreases over time while performance remains stable are discussed. The fourth chapter of the dissertation examines the effect of objective task difficulty on the magnitude of activation associated with successful inhibition. The Stop Signal Task employs an adaptive algorithm that alters task difficulty to meet participants’ abilities. Typically, when capturing functional activation associated with response inhibition, activation is extracted from all successful trials. Here, we find that individual differences in activation are expanded when using the activation from the extreme, rather than average, aspects of task performance variables. Individual differences in performance may best be captured by examining the maximum difficultly at which a participant is able to inhibit a response, rather than the average of all successful inhibitions. These results also lend support to the minimal activity associated with performance in Chapter 3, and we discuss how improving the measure of stop-related activity may help explain both inter- and intra-individual differences in inhibitory control

The shape of the language-ready brain

Our core hypothesis is that the emergence of our species-specific language-ready brain ought to be understood in light of the developmental changes expressed at the levels of brain morphology and neural connectivity that occurred in our species after the split from Neanderthals-Denisovans and that gave us a more globular braincase configuration. In addition to changes at the cortical level, we hypothesize that the anatomical shift that led to globularity also entailed significant changes at the subcortical level. We claim that the functional consequences of such changes must also be taken into account to gain a fuller understanding of our linguistic capacity. Here we focus on the thalamus, which we argue is central to language and human cognition, as it modulates fronto-parietal activity. With this new neurobiological perspective in place, we examine its possible molecular basis. We construct a candidate gene set whose members are involved in the development and connectivity of the thalamus, in the evolution of the human head, and are known to give rise to language-associated cognitive disorders. We submit that the new gene candidate set opens up new windows into our understanding of the genetic basis of our linguistic capacity. Thus, our hypothesis aims at generating new testing grounds concerning core aspects of language ontogeny and phylogeny