Emergence of Cortical Activity Patterns as Infants Develop Functional Motor Skills.

Despite the careful examination of the developmental changes in overt behavior and the underlying muscle activity and joint movement patterns, there is very little empirical evidence on how the brain and its link to behavior evolves during the first year of life. The dynamic systems approach and theory of neuronal group selection provides a framework that hypothesizes the development of the CNS early in life. However, the direct examination of the changes in brain activation that underlie the development of functional motor control in infants have yet to be determined or tested. The goal of my dissertation was to use functional near-infrared spectroscopy (fNIRS) to document the changes in brain activation patterns as infants acquired functional motor skills. My studies show that fNIRS is a viable and useful tool to examine brain activity in the context of infant movements. My findings demonstrate that as the behavioral and motor outcomes improve, the underlying neural activation patterns emerge. When functional motor skills are unstable and not fully functional, larger areas of the broad brain regions are recruited. As the skills become more reliable and functional, the brain activation patterns become refined and show an increase in strength of activity. The results from the studies in my dissertation take an important first step of describing the typical neural patterns that emerge with functional motor skills early in life. This work will help future studies build the body of empirical evidence that will improve our knowledge regarding the developing link between brain development and behavior. Finally, these studies provide foundational knowledge to better understand the atypical development of the CNS in those with disabilities.PhDKinesiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/133452/1/ryonish_1.pd

Mapping cortical responses to somatosensory stimuli in human infants with simultaneous near-infrared spectroscopy and event-related potential recording

Near-infrared spectroscopy (NIRS) and electroencephalography (EEG) have recently provided fundamental new information about how the newborn brain processes innocuous and noxious somatosensory information. However, results derived independently from these two techniques are not entirely consistent, raising questions about the relationship between hemodynamic and electrophysiological responses in the study of touch and pain processing in the newborn. To address this, we have recorded NIRS and EEG responses simultaneously for the first time in the human infant following noxious (time-locked clinically required heel lances) and innocuous tactile cutaneous stimulation in 30 newborn infants. The results show that both techniques can be used to record quantifiable and distinct innocuous and noxious evoked activity at a group level in the newborn cortex. Noxious stimulation elicits a peak hemodynamic response that is 10-fold larger than that elicited by an innocuous stimulus (HbO2: 2.0 vs 0.3 µm) and a distinct nociceptive-specific N3P3 waveform in electrophysiological recordings. However, a novel single-trial analysis revealed that hemodynamic and electrophysiological responses do not always co-occur at an individual level, although when they do (64% of noxious test occasions), they are significantly correlated in magnitude. These data show that, while hemodynamic and electrophysiological touch and pain brain activity in newborn infants are comparable in group analyses, important individual differences remain. These data indicate that integrated and multimodal brain monitoring is required to understand central touch and pain processing in the newborn

Study of the Term Neonatal Brain Injury with combined Diffuse Optical Tomography and Electroencephalography

This thesis describes the application of combined diffuse optical tomography (DOT) and electroencephalography (EEG) in the investigation of neonatal term brain injury. With hypoxic ischaemic encephalopathy (HIE) and perinatal stroke being the most frequent contributors to brain injury in the term neonatal population, the first part of the thesis focuses on the description and ongoing requirement for their further investigation. In continuation to that, the characteristics and unique properties of both DOT and EEG are described and explored. The combination of these two modalities was utilised in elucidating the relationship between neuronal activity and cerebral haemodynamics both in physiological processes as well as in disease, by the infant’s cot side. This work differs to previous studies using near-infrared technologies and EEG, as a denser whole head array was used, offering the potential of 3-dimensional image reconstruction of the cortical haemodynamic events in relation to electro-cortical activity. These methods were applied in the study of critically ill infants presenting with seizures in the first few days of life. The relevant results are presented in three separate chapters of the thesis. Distinct neurophysiological phenomena such as seizures and burst suppression were detected and studied in association to underlying HIE. On the grounds of a pre-existing pilot study of our research group, distinct prolonged de-oxygenated cortical areas were identified following electrical seizure activity. Further exploration of infants with seizures provided limited supporting evidence. The investigation of burst suppression in HIE led to the first ever identification of repeated, waveform, cortical haemodynamic events in response to bursts of electrical activity with some spatial correlation to regions of brain injury. Further analysis of the low frequencies within the diffuse optical signal in cases of perinatal stroke, showed a consistent interhemispheric difference between the healthy and stroke-affected brain regions. The limitations, prospects and conclusions are presented in the final chapter. The use of simultaneous DOT and EEG offers a unique neuro-monitoring and neuro-investigating tool in the neonatal intensive care environment, which is safe, portable, and cost-effective, Ongoing research is required for the exploration and development of the methodology and its potential diagnostic properties

Stride-time variability is related to sensorimotor cortical activation during forward and backward walking

Previous research has used functional near-infrared spectroscopy (fNIRS) to show that motor areas of the cortex are activated more while walking backward compared to walking forward. It is also known that head movement creates motion artifacts in fNIRS data. The aim of this study was to investigate cortical activation during forward and backward walking, while also measuring head movement. We hypothesized that greater activation in motor areas while walking backward would be concurrent with increased head movement. Participants performed forward and backward walking on a treadmill. Participants wore motion capture markers on their head to quantify head movement and pressure sensors on their feet to calculate stride-time. fNIRS was placed over motor areas of the cortex to measure cortical activation. Measurements were compared for forward and backward walking conditions. No significant differences in body movement or head movement were observed between forward and backward walking conditions, suggesting that conditional differences in movement did not influence fNIRS results. Stride-time was significantly shorter during backward walking than during forward walking, but not more variable. There were no differences in activation for motor areas of the cortex when outliers were removed. However, there was a positive correlation between stride-time variability and activation in the primary motor cortex. This positive correlation between motor cortex activation and stride-time variability suggests that forward walking variability may be represented in the primary motor cortex

Near-Infrared Spectroscopy for Brain Computer Interfacing

A brain-computer interface (BCI) gives those suffering from neuromuscular impairments a means to interact and communicate with their surrounding environment. A BCI translates physiological signals, typically electrical, detected from the brain to control an output device. A significant problem with current BCIs is the lengthy training periods involved for proficient usage, which can often lead to frustration and anxiety on the part of the user and may even lead to abandonment of the device. A more suitable and usable interface is needed to measure cognitive function more directly. In order to do this, new measurement modalities, signal acquisition and processing, and translation algorithms need to be addressed. This work implements a novel approach to BCI design, using noninvasive near-infrared spectroscopic (NIRS) techniques to develop a userfriendly optical BCI. NIRS is a practical non-invasive optical technique that can detect characteristic haemodynamic responses relating to neural activity. This thesis describes the use of NIRS to develop an accessible BCI system requiring very little user training. In harnessing the optical signal for BCI control an assessment of NIRS signal characteristics is carried out and detectable physiological effects are identified for BCI development. The investigations into various mental tasks for controlling the BCI show that motor imagery functions can be detected using NIRS. The optical BCI (OBCI) system operates in realtime characterising the occurrence of motor imagery functions, allowing users to control a switch - a “Mindswitch”. This work demonstrates the great potential of optical imaging methods for BCI development and brings to light an innovative approach to this field of research

Assessment of White Matter Hyperintensity, Cerebral Blood Flow, and Cerebral Oxygenation in Older Subjects Stratified by Cerebrovascular Risk

Objective: Cerebrovascular disease (CVD) is the fifth most common cause of mortality in the United States. Diagnosis of CVD at an early stage is critical for optimal intervention designed to prevent ongoing and future brain injury. CVD is commonly associated with abnormalities of the cerebral microvasculature leading to tissue dysfunction, neuronal injury and death, and resultant clinical symptoms, which in turn, further impacts cerebral autoregulation (CA). This series of studies aims to test the hypothesis that white matter hyperintensities (WMH) and cerebral hemodynamics (quantified by magnetic resonance imaging (MRI) and an by innovative hybrid near-infrared diffuse optical instrument) can be used as biomarkers to distinguish cognitively healthy older subjects with high or low risk for developing CVD. Methods: Using functional MRI, WMH and cerebral blood flow (CBF) were quantified in 26 cognitively healthy older subjects (age: 77.8 ± 6.8 years). In a follow-up study, significant variability in WMH quantification methodology was addressed, with sources of variability identified in selecting image center of gravity, software compatibility, thresholding techniques, and manual editing procedures. Accordingly, post-acquisition processing methods were optimized to develop a standardized protocol with less than 0.5% inter-rater variance. Using a novel laboratory-made hybrid near-infrared spectroscopy/diffuse correlation spectroscopy (NIRS/DCS) and a finger plethysmograph, low-frequency oscillations (LFOs) of CBF, cerebral oxygenation, and main arterial pressure (MAP) were simultaneously measured before, during, and after 70° head-up-tilting (HUT). Gains (associated with CAs) to magnify LFOs were determined by transfer function analyses with MAP as the input and cerebral hemodynamic parameters as the outputs. In a follow-up study, a fast software correlator for DCS and a parallel detection technique for NIRS/DCS were adapted to improve the sampling rate of hybrid optical measurements. In addition, a new DCS probe was developed to measure CBF at the occipital lobe, which represents a novel application of the NIRS/DCS technique. Results: MRI measurements demonstrate that deep WMH (dWMH) and periventricular WMH (pWMH) volumetric measures are associated with reduced regional cortical CBF in patients at high-risk of CVD. Moreover, CBF in white matter (WM) was reduced in regions demonstrating both pWMH and dWMHs. NIRS/DCS optical measurements demonstrate that at resting baseline, LFO gains in the high-risk group were relatively lower compared to the low-risk group. The lower baseline gains in the high-risk group may be attributed to compensatory mechanisms that allow the maintenance of a stronger steady-state CA. However, HUT resulted in smaller gain reductions in the high-risk group compared to the low-risk group, suggesting weaker dynamic CA in association with increased CVD risks. A noteworthy finding in these experiments was that CVD risk more strongly influenced CBF than cerebral oxygenation. Conclusions: Regional WMH volumes, cortical and WM CBF values, and LFO gains of cerebral hemodynamics demonstrate specific associations with CA and may serve as important potential biomarkers for early diagnosis of CVD. The high spatial resolution, large penetration depth, and variety of imaging-sequences afforded by MRI make it an appealing imaging modality for evaluation of CVD, although MRI is costly, time-limited, and requires transfer of subjects from bed to imaging facility. In contrast, low-cost, portable, mobile diffuse optical technologies provide a complementary alternative for early screening of CVD, that can further allow continuous monitoring of disease attenuation or progression at the subject’s bedside. Thus, development of both methodologies is essential for progress in our future understanding of CVD as a major contributor to the morbidity and mortality associated with CVD today

Slow Potentials of the Sensorimotor Cortex during Rhythmic Movements of the Ankle

The objective of this dissertation was to more fully understand the role of the human brain in the production of lower extremity rhythmic movements. Throughout the last century, evidence from animal models has demonstrated that spinal reflexes and networks alone are sufficient to propagate ambulation. However, observations after neural trauma, such as a spinal cord injury, demonstrate that humans require supraspinal drive to facilitate locomotion. To investigate the unique nature of lower extremity rhythmic movements, electroencephalography was used to record neural signals from the sensorimotor cortex during three cyclic ankle movement experiments. First, we characterized the differences in slow movement-related cortical potentials during rhythmic and discrete movements. During the experiment, motion analysis and electromyography were used characterize lower leg kinematics and muscle activation patterns. Second, a custom robotic device was built to assist in passive and active ankle movements. These movement conditions were used to examine the sensory and motor cortical contributions to rhythmic ankle movement. Lastly, we explored the differences in sensory and motor contributions to bilateral, rhythmic ankle movements. Experimental results from all three studies suggest that the brain is continuously involved in rhythmic movements of the lower extremities. We observed temporal characteristics of the cortical slow potentials that were time-locked to the movement. The amplitude of these potentials, localized over the sensorimotor cortex, revealed a reduction in neural activity during rhythmic movements when compared to discrete movements. Moreover, unilateral ankle movements produced unique sensory potentials that tracked the position of the movement and motor potentials that were only present during active dorsiflexion. In addition, the spatiotemporal patterns of slow potentials during bilateral ankle movements suggest similar cortical mechanisms for both unilateral and bilateral movement. Lastly, beta frequency modulations were correlated to the movement-related slow potentials within medial sensorimotor cortex, which may indicate they are of similar cortical origin. From these results, we concluded that the brain is continuously involved in the production of lower extremity rhythmic movements, and that the sensory and motor cortices provide unique contributions to both unilateral and bilateral movemen