THE RELATIONSHIP BETWEEN P300 EVOKED POTENTIALS AND PREFRONTAL CORTEX OXYGEN USE: A COMBINED EEG AND NIRS STUDY

The P300 subcomponent, P3b, is an event related potential detected at the scalp surface when a working memory comparison results in differences between the contents of working memory and incoming stimulus information. Previous research has indicated that as infrequent targets become more difficult to detect (morphologically similar to a frequent non-target stimulus) the P300 becomes attenuated. fMRI research has also indicated increased prefrontal cortex (PFC) activity during P300 generation. To examine the relationship between P3b amplitude and PFC activity participants performed an easy and difficult target detection task in both EEG and NIRS called the oddball. The EEG and behavioral results confirmed prior reports that difficult to detect targets result in attenuated P3b amplitude, as well as increased misses and reaction time, in comparison to easy to detect targets. NIRS results indicated that detection of targets generally lead to greater increases in oxygenated hemoglobin and decreases in deoxygenated hemoglobin in lateral compared to medial optodes. Additionally, oxygenated hemoglobin increased in the right medial PFC in easy compared to difficult conditions. Taken together, the results of this study and theories behind P3b attenuation suggest that the right medial PFC is involved in attention to salient stimulus features (bottom-up attention) and the lateral PFC is involved in sustained attention to the task (top-down attention). Thus, P3b attenuation is reflective of delimiting attention to salient features and allowing task driven attention to initiate the working memory comparison

How does the brain extract acoustic patterns? A behavioural and neural study

In complex auditory scenes the brain exploits statistical regularities to group sound elements into streams. Previous studies using tones that transition from being randomly drawn to regularly repeating, have highlighted a network of brain regions involved during this process of regularity detection, including auditory cortex (AC) and hippocampus (HPC; Barascud et al., 2016). In this thesis, I seek to understand how the neurons within AC and HPC detect and maintain a representation of deterministic acoustic regularity. I trained ferrets (n = 6) on a GO/NO-GO task to detect the transition from a random sequence of tones to a repeating pattern of tones, with increasing pattern lengths (3, 5 and 7). All animals performed significantly above chance, with longer reaction times and declining performance as the pattern length increased. During performance of the behavioural task, or passive listening, I recorded from primary and secondary fields of AC with multi-electrode arrays (behaving: n = 3), or AC and HPC using Neuropixels probes (behaving: n = 1; passive: n = 1). In the local field potential, I identified no differences in the evoked response between presentations of random or regular sequences. Instead, I observed significant increases in oscillatory power at the rate of the repeating pattern, and decreases at the tone presentation rate, during regularity. Neurons in AC, across the population, showed higher firing with more repetitions of the pattern and for shorter pattern lengths. Single-units within AC showed higher precision in their firing when responding to their best frequency during regularity. Neurons in AC and HPC both entrained to the pattern rate during presentation of the regular sequence when compared to the random sequence. Lastly, development of an optogenetic approach to inactivate AC in the ferret paves the way for future work to probe the causal involvement of these brain regions

From locomotion to dance and back : exploring rhythmic sensorimotor synchronization

Le rythme est un aspect important du mouvement et de la perception de l’environnement. Lorsque l’on danse, la pulsation musicale induit une activité neurale oscillatoire qui permet au système nerveux d’anticiper les évènements musicaux à venir. Le système moteur peut alors s’y synchroniser. Cette thèse développe de nouvelles techniques d’investigation des rythmes neuraux non strictement périodiques, tels que ceux qui régulent le tempo naturellement variable de la marche ou la perception rythmes musicaux. Elle étudie des réponses neurales reflétant la discordance entre ce que le système nerveux anticipe et ce qu’il perçoit, et qui sont nécessaire pour adapter la synchronisation de mouvements à un environnement variable. Elle montre aussi comment l’activité neurale évoquée par un rythme musical complexe est renforcée par les mouvements qui y sont synchronisés. Enfin, elle s’intéresse à ces rythmes neuraux chez des patients ayant des troubles de la marche ou de la conscience.Rhythms are central in human behaviours spanning from locomotion to music performance. In dance, self-sustaining and dynamically adapting neural oscillations entrain to the regular auditory inputs that is the musical beat. This entrainment leads to anticipation of forthcoming sensory events, which in turn allows synchronization of movements to the perceived environment. This dissertation develops novel technical approaches to investigate neural rhythms that are not strictly periodic, such as naturally tempo-varying locomotion movements and rhythms of music. It studies neural responses reflecting the discordance between what the nervous system anticipates and the actual timing of events, and that are critical for synchronizing movements to a changing environment. It also shows how the neural activity elicited by a musical rhythm is shaped by how we move. Finally, it investigates such neural rhythms in patient with gait or consciousness disorders

Direction-Dependent Responses To Traumatic Brain Injury In Pediatric Pigs

Traumatic brain injury (TBI) in children is a costly and alarmingly prevalent public health concern. Children (4-11 years of age) in the US have the highest rate of TBI-related emergency department visits. The plane of head rotation significantly affects neurocognitive deficits and pathophysiological responses such as axonal injury, but is largely ignored in TBI literature. In Chapter 1, an outline of existing research is provided, including the lack of attention to diagnosis, treatment, and prevention in children, who exhibit distinct biomechanical and neuropathological responses to TBI. Additionally, we hypothesize that the plane of head rotation in TBI induces a) region-specific changes in axonal injury, which lead to acute and chronic changes in electrophysiological responses; b) changes to event-related potentials and resting state electroencephalography (EEG) and c) tract-oriented strain and strain rate alterations in the white matter. All work in this dissertation is based on a well-established piglet model of TBI. In Chapter 2, we assess a novel rotational head kinematic metric, rotational work (RotWork), which incorporates head rotation rate, direction, and brain shape, as a predictor of acute axonal injury. This metric provides an improvement over existing metrics and could be useful in the development of effective child safety equipment used in recreation or transportation. In Chapter 3, we generate functional networks from auditory event-related potentials and use the patterns of change to distinguish injured brains from non-injured; the resulting algorithm showed an 82% predictive accuracy. In Chapter 4, we find elevations in network nodal strength, modularity and clustering coefficient after TBI across all frequency bands relative to baseline, whereas both metrics were reduced in shams. We report the first study using resting state EEG to create functional networks in relation to pediatric TBI, noting that this work may assist in the development of TBI biomarkers. In Chapter 5, we use a high-resolution finite element model to examine the effects of head rotation plane on the distribution of regional strains and strain rates. Sagittal rapid head rotations induced significantly larger volume fraction of damaged brainstem than axial and coronal rotations. We also found that local tissue deformation and histopathology were head direction- and region- dependent but poorly correlated at a local scale. Finally, in Chapter 6, we conclude that the work presented in this dissertation is novel and contributes valuable knowledge to the study of pediatric TBI, and that consideration of the plane of head rotation is critical to the understanding and accurate prediction of pediatric functional and region-dependent responses to TBI

Identifying Electrophysiological Components of Covert Awareness in Patients with Disorders of Consciousness

Naturalistic stimuli evoke synchronous patterns of neural activity between individuals in sensory and higher cognitive, “executive” networks of the brain. fMRI paradigms developed to measure this inter-subject synchronization have been extended to test for executive processing in behaviourally non-responsive patients as a neural marker of awareness. This thesis adapted one such paradigm for use in EEG, a low-cost, portable neuroimaging technique that can be administered at a patient’s bedside. Healthy participants listened to a suspenseful auditory narrative during EEG recording. Significant inter-subject synchronization was found throughout the audio but was significantly reduced during a scrambled control condition. This paradigm was then used to evaluate executive processing in a cohort of patients. One locked-in patient and one patient in a vegetative state were significantly synchronized to healthy controls during the audio. EEG is a suitable tool to detect executive processing, a proxy measure of awareness, in patients who are behaviourally non-responsive

Posttraumatic Stress Disorder or Combat Experience? A Functional Near-infrared Spectroscopy Study of Trauma-related Auditory and Olfactory Cues

While the clinical communities are aware of the prevalence of posttraumatic stress disorder (PTSD) among OEF/OIF/OND veterans, further efforts are necessary to bolster comprehensive strategies for assessment and treatment. The purpose of this study was to investigate whether a combat-related PTSD symptom provocation paradigm would elicit unique neurological responses via functional near-infrared spectroscopy across three groups – combat veterans with PTSD, combat veterans without PTSD, and nonmilitary participants without PTSD. Results indicated that combat veterans with PTSD demonstrated significant activation during exposure to a trauma-related sound compared to nonmilitary personnel at channels 14 (d = 1.03) and 15 (d = 1.30) and combat veterans without PTSD at channel 14 (d = 0.87). Specifically, this increased neural activation was approximately located in the right superior/medial prefrontal cortex (BA 9/10), associated with evaluating cue-familiarity and emotional detachment. Results were less clear with respect to a combat-related odor. These results suggest a specific neurophysiological response to trauma-related cues and if replicated, may offer a biomarker for combat-related PTSD. Such a response could provide incremental validity over diagnostic assessments alone and assist in planning and monitoring of treatment outcome

Early brain activity : Translations between bedside and laboratory

Neural activity is both a driver of brain development and a readout of developmental processes. Changes in neuronal activity are therefore both the cause and consequence of neurodevelopmental compromises. Here, we review the assessment of neuronal activities in both preclinical models and clinical situations. We focus on issues that require urgent translational research, the challenges and bottlenecks preventing translation of biomedical research into new clinical diagnostics or treatments, and possibilities to overcome these barriers. The key questions are (i) what can be measured in clinical settings versus animal experiments, (ii) how do measurements relate to particular stages of development, and (iii) how can we balance practical and ethical realities with methodological compromises in measurements and treatments.Peer reviewe

Functional integration in the cortical neuronal network of conscious and anesthetized animals

General anesthesia consists of amnesia, analgesia, areflexia and unconsciousness. How anesthetics suppress consciousness has been a mystery for more than one and a half centuries. The overall goal of my research has been to determine the neural correlates of anesthetic-induced loss of consciousness. I hypothesized that anesthetics induce unconsciousness by interfering with the functional connectivity of neuronal networks of the brain and consequently, reducing the brain\u27s capacity for information processing. To test this hypothesis, I performed experiments in which neuronal spiking activity was measured with chronically implanted microelectrode arrays in the visual cortex of freely-moving rats during wakefulness and at graded levels of anesthesia produced by the inhalational anesthetic agent desflurane. I then applied linear and non-parametric information-theoretic analyses to quantify the concentration-dependent effect of general anesthetics on spontaneous and visually evoked spike firing activity in rat primary visual cortex. Results suggest that desflurane anesthesia disrupts cortical neuronal integration as measured by monosynaptic connectivity, spike burst coherence and information capacity. This research furthers our understanding of the mechanisms involved with the anesthetic-induced LOC which may facilitate in the development of better anesthetic monitoring devices and the creation of effective anesthetic agents that will be free of unwanted side effects

An Exploration of the Feasibility of Functional Near-Infrared Spectroscopy as a Neurofeedback Cueing System for the Mitigation of the Vigilance Decrement

Vigilance is the capacity for observers to maintain attention over extended periods of time, and has most often been operationalized as the ability to detect rare and critical signals (Davies & Parasuraman, 1982; Parasuraman, 1979; Warm, 1984). Humans, however, have natural physical and cognitive limitations that preclude successful long-term vigilance performance and consequently, without some means of assistance, failures in operator vigilance are likely to occur. Such a decline in monitoring performance over time has been a robust finding in vigilance experiments for decades and has been called the vigilance decrement function (Davies & Parasuraman, 1982; Mackworth, 1948). One of the most effective countermeasures employed to maintain effective performance has been cueing: providing the operator with a reliable prompt concerning signal onset probability. Most protocols have based such cues on task-related or environmental factors. The present dissertation examines the efficacy of cueing when nominally based on operator state (i.e., blood oxygenation of cortical tissue) in a novel vigilance task incorporating dynamic displays over three studies. Results pertaining to performance outcomes, physiological measures (cortical blood oxygenation and heart rate variability), and perceived workload and stress are interpreted via Signal Detection Theory and the Resource Theory of vigilance