As of 2005, there were over 1.5 million amputees living in the United States, more than 548,000 of them with upper extremity involvement. The total number of amputees is projected to rise to at least 2.2 million by 2020. Unfortunately, full functional use of upper extremity prosthetic devices is low. Knowledge gained regarding the cortical systems active in amputees performing motor tasks may reveal atypical motor control strategies that contribute to these issues. Substantial evidence demonstrates a strong dependence on left parietofrontal cortical areas to successfully plan and execute tool-use movements and pantomimes. It was previously unclear how this network functioned in users of prostheses. The hypothesis of this dissertation is that in order to optimally engage the typical parietofrontal network during action imitation with a prosthetic device, the action being imitated should be performed by a matching prosthesis. Also, that greater engagement of the parietofrontal network will result in increased ability to perform tool-use movements. First, this dissertation showed that when imitating motor tasks performed by intact actors, prosthesis users exhibit lower engagement of the parietofrontal action encoding system. This network is crucial for motor adaptation. Left parietofrontal engagement was only observed when prosthesis users imitated matched limb prosthesis demonstrations, which suggests that matched limb imitation may be optimal to establish motor representations. Next, intact subjects donned a fictive amputee model system (FAMS) to simulate the limb movement that transradial amputees experience. Matched limb imitation in FAMS users yielded better movement technique compared to mismatched imitation. Finally, the longitudinal effects of a matched limb training paradigm on the cortical action encoding activity and motor behavior in FAMS users were investigated. Matched limb imitation subjects showed greater engagement of the parietofrontal network and better movement technique compared to those trained with mismatched limb. This dissertation has clinical relevance as it supports the notion that matched limb imitation could play an important role in the performance of motor tasks using a prosthetic device. These findings could be used to inform the development of improved rehabilitation protocols that may lead to greater functional adaptation of prosthetic devices into the lives of amputees.

Investigating the neurophysiology behind our action encoding system offers a way of probing the underlying mechanisms regarding how we understand seen action. The ability to mentally simulate action (motor simulation) is a strong proposal to understand how we interpret others’ actions. The process of how we generate accurate motor simulations is proposed to be reliant on the context of the movement and sensory feedback from the limb. However, the neurophysiological mechanisms behind motor simulation are not yet understood. Known motor physiology for right-handed individuals show there is a left parietal-frontal network for the mental simulation of skilled movements; however, it remains unclear whether this is due to right limb dominance of the observer’s motor system because action simulation research has been focused primarily on right-handed individuals. The goal of this dissertation is to understand the underlying neurophysiology of the motor simulation process during action encoding. Generally, we propose different strategies of action simulation between right and left handed individuals. More specifically, we propose that right-handed individuals rely on their motor dominant left hemisphere for action encoding and motor simulation, while left-handed individuals will rely on their motor dominant right hemisphere. We will test this by evaluating neurobehavioral patterns of potential symmetry and asymmetry of motor simulation and action encoding based on patterns of limb dominance. We will also evaluate how impaired sensory feedback affects motor simulations, which can reveal how limb state affects the simulation process. The results of this series of studies will fill a void in our basic understanding of the motor simulation process and may generalize to populations with upper limb functional loss. Specifically, those with different hand dominance may require different rehabilitation programs in order to retrain an affected limb.

Many event-related potential (ERP) studies have tried to find out which brain processes are responsible for the subjective experience of seeing. The contribution of these studies has been crucial in order to identify the temporal and spatial dynamics of visual awareness. The negative difference wave named visual awareness negativity (VAN), observed around 200 ms after the stimulus onset, has been claimed by many as a plausible candidate for reflecting the processes correlating with conscious visual perception. Other studies argue instead that only the P3 wave, a positive wave observed around 300-400 ms, correlates with visual awareness. The aim of the present study was to shed light on the issue of the presence of VAN even when using an experimental procedure that allows to dissociate the ERP correlate of subjective awareness from those of unconscious perception, allowing a separate analysis. Data from 24 participants was collected in the present study. The experimental framework included a forced-choice localization task of a low-contrast stimulus, followed by the subjective rating of awareness. The results of the study support the idea that the VAN is the earliest electrophysiological correlate of subjective visual awareness and that the phenomenon of visual awareness emerges early in the visual area.

Despite the growing interest in the general public and popular press about the scientific research into mindfulness meditation (e.g. Pickert, 2014), several critiques of this research have been published in the past few years outlining methodological flaws in many published studies on the topic (Goyal et al., 2014; Ospina et al., 2007). One potential way to improve methodology in this field would be to find better ways of measuring skill at meditation, giving researchers an ability to compare more advanced practitioners to those who are more novice. A total of 69 participants were recruited. Pilot data were collected from 33 participants and analyzed using exploratory methods to assess whether any self-report measures of mindfulness practice might correlate with any physiological variables thought to possibly reflect a dimension of skill at meditation. Participants spent a night in the sleep lab, and prior to their sleep study spent six minutes in a baseline condition followed by six minutes in a meditation condition, and differences were recorded on a number of physiological measures. Correlational analyses revealed that, of the physiological and self-report measures, six were correlated with other measures, and principal component analysis found 2 factors, each with three components. 36 additional participants were then recruited in an attempt to determine whether these two factors would replicate, and this latter group participated only in the meditation protocol. Both factors were largely replicated independently in the second sample and remained stable collapsing the two groups together. Factor 1 combined an increase in both alpha and theta power centrally and occipitally between baseline and meditation with self-reported mindfulness practice, and Factor 2 combined the inverse of the Brief Symptom Inventory, the Mindful Attention and Awareness Scale, and the change in respiration between baseline and meditation.

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The heritability of frontal EEG asymmetry, a potential endophenotype for depression, was investigated using a large set of adolescent and young adult twins. Additionally, the relationship between polymorphisms within three serotonin genes, two receptor genes and one transporter gene, and frontal EEG asymmetry was also investigated. Using Falconer's estimate, frontal EEG asymmetry was shown to be more heritable at lateral compared to medial cites across nearly all reference montages, and greater in males compared to females. Using structural equation modeling (SEM), and investigating both additive (ACE) and non-additive (ADE) models of genetic heritability, males displayed consistently greater additive genetic contributions to heritability, with greater lateral contributions than medial ones. For female twins pairs, the additive genetic model data provided a mixed picture, with more consistent heritability estimates observed at medial sites, but with larger estimates shown at lateral channels. For non-additive genetic models, male twin pairs demonstrated exclusive non-additive contributions to heritability across channels within AVG and CZ referenced data, with metrics in the CSD and LM montages more mixed between additive and non-additive contributions. However, consistent with Falconer's estimates, lateral channels were nearly always estimated to be more heritable than medial channels regardless of gender. These models demonstrate some combination of additive and non-additive contributions to the heritability of frontal EEG asymmetry, with the CSD and AVG montages showing greater lateral compared to medial heritability and CZ and LM montages showing mixed contributions with additive heritability at lateral channels and non-additive primarily at medial channels. The complex interaction of gender and reference montage on the heritability estimates highlight the subtle yet important roles of age, gender, and recording methodology when investigating proposed endophenotypes. However, no association was found between the proposed polymorphisms in serotonin receptor 1a, 2a or serotonin transporter genes and frontal EEG asymmetry. Although the results support modest heritability of frontal EEG asymmetry, the proposed link to underlying serotonergic genetic markers remains an open question. Overall, these results indicate that frontal asymmetry may be a useful endophenotype for depressive risk with modest heritability, but is one that taps more environmental risk.

The primary goal of the proposed research is to identify how stress is internalized to affect cognitive functioning and increase the risk for Major Depressive Disorder (MDD). Dysfunctional stress reactivity has been proposed to be a risk factor for ongoing affective distress, yet mechanisms underlying this process remain unexplained. The medial prefrontal cortex (mPFC) has been implicated in the etiology of MDD, in the reactivity to stress, as well as in the adaptation of behavior to reinforcement. The combined activities of this particular neural system identify it as a focal node by which stress may be internalized to affect cognitive, emotional, and behavioral functioning. The experiments detailed here examined electroencephalographic (EEG) features that reflect cognitive control functions in the mPFC. Participants underwent EEG assessment as they completed a reinforcement (reward and punishment) learning task sensitive to mPFC-basal ganglia functioning, both with and without a laboratory stress manipulation. This experiment assessed how stress reactivity altered neural systems of reinforcement, and it contrasted these same factors with currently depressed individuals. In this series of investigations, we have identified a measure of how, and a possible mechanism by which, punishment information is internalized in stress reactivity and in the expression of MDD: error and punishment signals are increasingly coupled with the salience of "bad" outcomes. Stress-related alteration of reward and punishment learning systems - particularly in the mPFC - is a viable candidate for how dysfunctional stress reactive responses are translated into ongoing cognitive and affective distress in depression.

The brain is a complex dynamic and self-organizing system. Normal brain function emerges from synchronized neuronal firing between local neurons which are integrated into large scale networks via white matter tracts. Normal brain function and consciousness arise from the continual integration and dissolution of neuronal networks, and this fluctuation in synchronization is termed variability. Brain electrical activity is recorded as local field potentials using electroencephalography (EEG). The phase synchrony and variability of EEG waveforms can be quantified. The healthy brain exhibits a relatively low degree of phase synchrony and a high degree of variability. Clinicians are interested in using a complex system approach to brain function to provide dynamic information on neuronal physiology and pathology not available by other evaluation methods. A common challenge in paediatric critical care is evaluation of the comatose child post brain injury. Coma and medical interventions confound the clinical examination making monitoring and prognostication of outcome difficult. Brain cells and white matter tracts are disrupted post injury altering the phase synchrony between neuronal networks. It is proposed in this thesis that the estimation of the variability in EEG phase synchrony can evaluate paediatric brain function. The EEG recordings of normal children and patients in coma post brain injury are used, in a series of studies, to test the main hypothesis that slow EEG wave brain states associated with brain injury have higher magnitudes of EEG phase synchrony and lower variability values than those of EEG waves associated with consciousness. Further, the effects of age, brain development brain and the effect of a conscious slow wave EEG state (hyperventilation) on phase synchrony and variability are evaluated. Results of the studies showed that EEG phase synchrony is increased in all slow wave states and is highest in comatose children with poor neurological outcome. Younger children’s brains have higher phase synchrony than older children. The variability of the EEG phase synchrony differentiates between the awake (higher values) and unconscious states (lower values). Physiologic models underlying EEG phase synchrony are discussed. The EEG phase synchrony and variability measures provide new insight into paediatric brain function.

Cognition is dynamic and complex, requiring specific sets of brain areas to cooperate for specific tasks. Neural synchronization is a proposed mechanism for transient functional integration of specific neural populations, enabling feature flexible binding and dynamic assignment of functional connectivity in the brain according to task demands. This thesis addresses the role of neural synchronization in selective attention and perceptual consciousness. The goals of this thesis are to test the hypothesis that synchronization between brain regions is relevant to network dynamics in selective attention and for perceptual organization, and to elucidate the function of synchronization in different frequency ranges. Using a selective visuospatial cuing paradigm it is shown that deploying attention to one visual hemifield yields transient long-distance gamma-band synchronization between contralateral visual cortex and other, widespread, brain regions. This is interpreted as a mechanism for establishing anticipatory biasing of communication in the cortex. Long-distance gamma synchrony, moreover, is periodically 'refreshed' at a theta rate, possibly serving to maintain this gamma network. While local alpha-band activity was found to be greater ipsilateral to the attended visual hemifield, alpha-band synchronization between primary visual cortex and higher visual areas was greater contralateral to attended locations. This suggests that local alpha synchrony is relevant for inhibition, while long-range alpha synchronization enacts functional coupling. The onset of a new conscious percept during binocular rivalry coincides with large-scale gamma-band synchronization which recurs at a theta rate. This suggests that gamma synchronization integrates features into a unified conscious percept while the theta cycle maintains that network. Using an audiovisual speech integration paradigm it is shown that large-scale gamma synchronization is greater when incongruence is detected between auditory and visual streams. This highlights an important distinction: neural synchronization reflects neural integration, not perceptual integration. Perceptual integration typically requires neural integration (feature binding), however, in this case detection of audiovisual mismatches requires cooperation within a distributed network, whereas audiovisual speech integration is largely accomplished in superior temporal cortex. These studies indicate that long-distance gamma synchronization establishes neural integration, the theta cycle maintains gamma synchronous networks, and local and long-range alpha synchrony reflect sustained inhibition and functional coupling mechanisms, respectively.

We live in a visually rich environment yet our brains are only equipped to process a small fraction of all available information at any point in time. For successful and efficient perception, the brain relies on attention to differentiate and select specific stimuli for further analysis. Attention can be directed to features – feature based attention – which enhances the processing of other similar features independent of spatial location. I have recently shown that the benefits of feature-based attention not only apply to lower-level features, but also to processes of object perception. The aim of the thesis was to examine the behavioural and electrophysiological correlates underlying the influence of feature-based attention on object perception. Chapter 1 measured the electric field activity associated with attending to higher-level features (object contours) and comparing it with the neural activity while attending to motion stimuli. We found temporally later effects for contours relative to motion, suggesting that feature-based attention to objects might be mediated by higher-tier visual areas, such as the lateral occipital cortex. In Chapter 2, I describe a study designed to investigate the time course of neural activity while cueing attention within the feature dimension of shape that more directly targets higher-tier visual areas. Consistent with Chapter 1, I iii found temporally late modulation, but behavioural effects that were weaker than expected. To account for these findings, I proposed a “wrong-turn” model which explains the perceptual benefits and costs coupled to expecting the correct or incorrect feature by taking into consideration the hierarchical structure of the visual system. Moreover, the model also makes specific predictions about the pattern of behavioural and electrophysiological activity while attending to features of varying complexity during object perception. The aim of Chapter 3 was to test the predictions of the model; I cued attention to colour, a lower-level feature essential to perceiving the object. I found much stronger behavioural cueing effects, and a biphasic pattern (early and late) electric brain activity that confirmed the predictions of the model. Together the results indicate that feature-based attention plays an important role in object perception that is mediated by a flexible perceptual system.