Developing High-Density Diffuse Optical Tomography for Neuroimaging

Clinicians who care for brain-injured patients and premature infants desire a bedside monitor of brain function. A decade ago, there was hope that optical imaging would be able to fill this role, as it combined fMRI\u27s ability to construct cortical maps with EEG\u27s portable, cap-based systems. However, early optical systems had poor imaging performance, and the momentum for the technique slowed. In our lab, we develop diffuse optical tomography: DOT), which is a more advanced method of performing optical imaging. My research has been to pioneer the in vivo use of DOT for advanced neuroimaging by: 1) quantifying the advantages of DOT through both in silico simulation and in vivo performance metrics,: 2) restoring confidence in the technique with the first retinotopic mapping of the visual cortex: a benchmark for fMRI and PET), and: 3) creating concepts and methods for the clinical translation of DOT. Hospitalized patients are unable to perform complicated neurological tasks, which has motivated us to develop the first DOT methods for resting-state brain mapping with functional connectivity. Finally, in collaboration with neonatologists, I have extended these methods with proof-of-principle imaging of brain-injured premature infants. This work establishes DOT\u27s improvements in imaging performance and readies it for multiple clinical and research roles

Properties of Visual Field Maps in Health and Disease

The visual world that surrounds us is represented in and processed by multiple topographically organised maps in the human brain. The organising principle underlying these retinotopic maps is also apparent across other sensory modalities and appears highly conserved across species. Moreover, the template for these visual maps is laid down during development, without the need for visual experience. This thesis binds and summarises seven publications describing work to characterise the functional properties of visual maps in the human brain. Initially, we describe TMS and fMRI measurements designed to probe the functional specificity of two spatially distinct but spatially adjacent maps, LO-1 and LO-2. Concurrently I developed software (visualisation tools) for precise dissection of these areas and to more broadly facilitate the visualisation of neuroimaging data. Our experiment revealed a double dissociation in the functional specificity of these areas, with preferential processing of orientation and shape information by LO-1 and LO-2, respectively. We then used fMRI to examine the effect of spatial attention on the responses measured from visual field maps. We showed that attention modulated visual responses by both enhancing attended locations and suppressing unattended locations; these effects were evident in the maps of early visual cortex and subcortical structures including the lateral geniculate and pulvinar nuclei. Finally, we examined the properties of visual field maps in patients with retinal lesions. Although maps can be abnormally organised with certain congenital visual deficits, we asked whether normally developed maps were able to reorganise when input to them is lost later in life, specifically due to central retinal lesions. Our measurements showed no evidence of reorganisation in the maps of patients with macular degeneration: the extent of activity measured in these maps was both highly predictable based on individual retinal lesions and could be reliably simulated in normally sighted individuals

Neural Correlates of Conscious Perception. The Role of Primary Visual Cortex in Visual Awareness.

This study investigates which neural populations represent low-level dimensions of conscious perception. First, a general framework is presented that will allow the separation of different aspects of visual awareness. A set of six criteria is developed that allows one to assess whether a neural population could in principle represent a dimension of conscious perception. These criteria are then applied to previous studies on the neurophysiology and neuropsychology of conscious perception. In the following empirical section a study on the relationship between perceived contrast and activity in primary visual cortex is performed using a combination of EEG, MEG and psychophysics. Lateral masking was used to dissociate the physical and the perceived contrast of a target grating. Transient potentials and magnetic fields evoked by the flashed target gratings were recorded and compared to psychophysical judgements of perceived contrast. At all investigated contrast levels, the amplitudes of electrophysiological transients correlated better with perceived than with physical target contrast. This held especially for the late transient. Source localisation indicated that the transients in question are likely to originate in primary visual cortex. The study presented here is the first ever to study perceptual constancy by recording psychophysics and physiological responses synchronously. The results identify the activity of primary visual cortex as the most likely neural basis of perceived contrast

Spatial Updating in Human Cortex

Single neurons in several cortical areas in monkeys update visual information in conjunction with eye movements. This remapping of stimulus representations is thought to contribute to spatial constancy. The central hypothesis here is that spatial updating also occurs in humans and that it can be visualized with functional MRI.In Chapter 2, we describe experiments in which we tested the role of human parietal cortex in spatial updating. We scanned subjects during a task that involved remapping of visual signals across hemifields. This task is directly analogous to the single-step saccade task used to test spatial updating in monkeys. We observed an initial response in the hemisphere contralateral to the visual stimulus, followed by a remapped response in the hemisphere ipsilateral to the stimulus. Our results demonstrate that updating of visual information occurs in human parietal cortex and can be visualized with fMRI.The experiments in Chapter 2 show that updated visual responses have a characteristic latency and response shape. Chapter 3 describes a statistical model for estimating these parameters. The method is based on a nonlinear, fully Bayesian, hierarchical model that decomposes the fMRI time series data into baseline, smooth drift, activation signal, and noise. This chapter shows that this model performs well relative to commonly-used general linear models. In Chapter 4, we use the statistical method described in Chapter 3 to test for the presence of spatial updating activity in human extrastriate visual cortex. We identified the borders of several retinotopically defined visual areas in the occipital lobe. We then tested for spatial updating using the single step saccade task. We found a roughly monotonic relationship between the strength of updating activity and position in the visual area hierarchy. We observed the strongest responses in area V4, and the weakest response in V1. We conclude that updating is not restricted to brain regions involved primarily in attention and the generation of eye movements, but rather, is present in occipital lobe visual areas as well

Cerebral hemodynamics and oxidative metabolism dynamics observed by calibration of functional MRI

Thesis (Ph. D.)--Massachusetts Institute of Technology, Whitaker College of Health Sciences and Technology, 1998.Includes bibliographical references.by Timothy Lloyd Davis.Ph.D

Top-down signals in visual selective attention.

This thesis describes experimental work on the brain mechanisms underlying human visual selective attention, with a focus on top-down activity changes in visual cortex. Using a combination of methods, the experiments addressed related questions concerning the functional significance and putative origins of such activity modulations due to selective attention. More specifically, the experiment described in Chapter 2 shows with TMS-elicited phosphenes that anticipatory selective attention can change excitability of visual cortex in a spatially-specific manner, even when thalamic gating of afferent input is ruled out. The behavioural and fMRI experiments described in Chapter 3 indicate that top-down influences of selective attention are not limited to enhancements of visual target processing, but may also involve anticipatory processes that minimize the impact of visual distractor stimuli. Chapters 4-6 then address questions about potential origins of such top-down activity modulations in visual cortex, using concurrent TMS-fMRI and psychophysics. These experiments show that TMS applied to the right human frontal eye field can causally influence visual cortex activity in a spatially-specific manner (Chapter 4), which has direct functional consequences for visual perception (Chapter 5), and is reliably different from that caused by TMS to the right intra-parietal sulcus (Chapter 6). The data presented in this thesis indicate that visual selective attention may involve top-down signals that bias visual processing towards behaviourally relevant stimuli, at the expense of distracting information present in the scene. Moreover, the experiments provide causal evidence in the human brain that distinct top-down signals can originate in anatomical feedback loops from frontal or parietal areas, and that such regions may have different functional influences on visual processing. These findings provide neural confirmation for some theoretical proposals in the literature on visual selective attention, and they introduce and corroborate new methods that might be of considerable utility for addressing such mechanisms directly

The multifocal visual evoked cortical potential in visual field mapping: a methodological study.

The application of multifocal techniques to the visual evoked cortical potential permits objective electrophysiological mapping of the visual field. The multifocal visual evoked cortical potential (mfVECP) presents several technical challenges. Signals are small, are influenced by a number of sources of noise and waveforms vary both across the visual field and between subjects due to the complex geometry of the visual cortex. Together these factors hamper the ability to distinguish between a mfVECP response from the healthy visual pathway, and a response that is reduced or absent and is therefore representative of pathology. This thesis presents a series of methodological investigations with the aim of maximising the information available in the recorded electrophysiological response, thereby improving the performance of the mfVECP. A novel method of calculating the signal to noise ratio (SNR) of mfVECP waveform responses is introduced. A noise estimate unrelated to the response of the visual cortex to the visual stimulus is created. This is achieved by cross-correlating m-sequences which are created when the orthogonal set of m-sequences are created but are not used to control a stimulus region, with the physiological record. This metric is compared to the approach of defining noise within a delayed time window and shows good correlation. ROC analysis indicates a small improvement in the ability to distinguish between physiological waveform responses and noise. Defining the signal window as 45-250ms is recommended. Signal quality is improved by post-acquisition bandwidth filtering. A wide range of bandwidths are compared and the greatest gains are seen with a bandpass of 3 to 20Hz applied after cross-correlation. Responses evoked when stimulation is delivered using a cathode ray tube (CRT) and a liquid crystal display (LCD) projector system are compared. The mode of stimulus delivery affects the waveshape of responses. A significantly higher SNR is seen in waveforms is shown in waveforms evoked by an m=16 bit m-sequence delivered by a CRT monitor. Differences for shorter m-sequences were not statistically significant. The area of the visual field which can usefully be tested is investigated by increasing the field of view of stimulation from 20° to 40° of radius in 10° increments. A field of view of 30° of radius is shown to provide stimulation of as much of the visual field as possible without losing signal quality. Stimulation rates of 12.5 to 75Hz are compared. Slowing the stimulation rate produced increases waveform amplitudes, latencies and SNR values. The best performance was achieved with 25Hz stimulation. It is shown that a six-minute recording stimulated at 25Hz is superior to an eight-minute, 75Hz acquisition. An electrophysiology system capable of providing multifocal stimulation, synchronising with the acquisition of data from a large number of electrodes and performing cross-correlation has been created. This is a powerful system which permits the interrogation of the dipoles evoked within the complex geometry of the visual cortex from a very large number of orientations, which will improve detection ability. The system has been used to compare the performance of 16 monopolar recording channels in detecting responses to stimulation throughout the visual field. A selection of four electrodes which maximise the available information throughout the visual field has been made. It is shown that a several combinations of four electrodes provide good responses throughout the visual field, but that it is important to have them distributed on either hemisphere and above and below Oz. A series of investigations have indicated methods of maximising the available information in mfVECP recordings and progress the technique towards becoming a robust clinical tool. A powerful multichannel multifocal electrophysiology system has been created, with the ability to simultaneously acquire data from a very large number of bipolar recording channels and thereby detect many small dipole responses to stimulation of many small areas of the visual field. This will be an invaluable tool in future investigations. Performance has been shown to improve when the presence or absence of a waveform is determined by a novel SNR metric, when data is filtered post-acquisition through a 3-20Hz bandpass after cross-correlation and when a CRT is used to deliver the stimulus. The field of view of stimulation can usefully be extended to a radius of 30° when a 60-region dartboard pattern is employed. Performance can be enhanced at the same time as acquisition time is reduced by 25%, by the use of a 25Hz rate of stimulation instead of the frequently employed rate of 75Hz

The role of human motion processing complex, MT+, during sustained perception and attention

Thesis advisor: Scott D. SlotnickThe overarching aim of this dissertation is to examine the role of human motion processing complex, MT+ during sustained perception and attention. MT+ is comprised of sub-region MT, which processes motion in the contralateral visual field (i.e., left hemisphere MT processes motion in the right visual field and vice versa), and sub-region MST, which processes motion in both the contralateral and ipsilateral visual fields. Whereas previous transcranial magnetic stimulation (TMS) research has provided compelling evidence that region MT+ is necessary for low-level motion processing, Chapter 1 describes an experiment testing whether the sub-region MT is necessary for contralateral low-level motion processing. Chapter 2 describes an experiment that dissociates low-level sensory attentional modulation in MT+ from high-level attentional control processing in the parietal cortex (i.e., during sustained attention). Chapter 3 describes an experiment investigating the role of MT+ during aesthetic processing when viewing visual art. Importantly, this experiment tests whether the aesthetic is tied to not only low-level motion processing in MT+ but also high-level processing in frontal regions. Taken together, the results across the three experiments provide novel evidence for the role of MT+ during low-level motion processing during sustained perception and attention. Moreover, these low-level motion processing effects together with the observed high-level processes in frontal-parietal regions provide neural mechanisms for the cognitive processes of sustained perception and attention.Thesis (PhD) — Boston College, 2012.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Psychology