Neural Correlates of Auditory Perceptual Awareness and Release from Informational Masking Recorded Directly from Human Cortex: A Case Study.

In complex acoustic environments, even salient supra-threshold sounds sometimes go unperceived, a phenomenon known as informational masking. The neural basis of informational masking (and its release) has not been well-characterized, particularly outside auditory cortex. We combined electrocorticography in a neurosurgical patient undergoing invasive epilepsy monitoring with trial-by-trial perceptual reports of isochronous target-tone streams embedded in random multi-tone maskers. Awareness of such masker-embedded target streams was associated with a focal negativity between 100 and 200 ms and high-gamma activity (HGA) between 50 and 250 ms (both in auditory cortex on the posterolateral superior temporal gyrus) as well as a broad P3b-like potential (between ~300 and 600 ms) with generators in ventrolateral frontal and lateral temporal cortex. Unperceived target tones elicited drastically reduced versions of such responses, if at all. While it remains unclear whether these responses reflect conscious perception, itself, as opposed to pre- or post-perceptual processing, the results suggest that conscious perception of target sounds in complex listening environments may engage diverse neural mechanisms in distributed brain areas

Does Success on the Grid-Iron and Court Increase Applications to Football Bowl Subdivision (FBS) Schools?

Division I athletics require a substantial financial commitment from a university. Previous research suggests that athletic success may provide benefits to a university. These benefits might include advertising, which may lead to increased applications. I used 2000-2010 application data from the Integrated Postsecondary Education Data System (IPEDS) to investigate if athletic success for Football Bowl Subdivision (FBS) football and basketball programs affects the number of applications these universities receive. Key independent variables used are past values of Sagarin ratings, Associated Press Top 20 College Football Poll ratings, and NCAA Basketball Tournament performance. I find that some measures of athletic success do not increase applications for a university at all, whereas other measures of athletic success increase applications only marginally

Effects of cardiac gating on fMRI of the human auditory system

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2008.Includes bibliographical references (leaves 20-22).Guimaraes et al. (1998) showed that sound-evoked fMRI activation in the auditory midbrain was significantly improved by a method which reduces image signal variability associated with cardiac-related brainstem motion. The method, cardiac gating, synchronizes image acquisition to a constant phase of the cardiac cycle. Since that study, several improvements to auditory fMRI have been made, and it is unclear whether cardiac gating still yields worthwhile benefits. The present study re-evaluated the effects of cardiac gating for detecting fMRI activation with current auditory fMRI standards. In 11 experiments, we directly compared fMRI activation for images acquired with a fixed repetition time (ungated) vs. those acquired by triggering image acquisition (gated) to the oxygen saturation at the fingertip (SpO2), an indirect measure of cardiac activity. Three of these experiments compared the effects of gating with the Sp02 signal vs. gating with the R-wave of the electrocardiogram (ECG). fMRI activation was routinely detected at all levels of the auditory pathway from the cochlear nucleus to the auditory cortex. Compared to ungated acquisitions, cardiac gating with the SpO2 reduced image signal variability in all centers of the auditory system and increased the magnitude of activation in the inferior colliculus (p < 0.01) and medial geniculate body (p < 0.1).(cont.) Simultaneous measurements of the SpO2 and ECG indicated that the peak of the SpO2 signal followed the ECG R-wave by approximately 400 ms, placing early images in a motion-stable phase of the cardiac cycle during Sp02-gated experiments. This may account for the fact that image signal variability with Sp02-gated acquisitions was always lower than with ECG-gated acquisitions. That sound-evoked activation could be regularly detected without cardiac gating indicates that gating may not be worth the minimal experimental complexity it entails. However, in experiments attempting to measure responses to sounds that evoke small changes in fMRI signal, especially in the auditory midbrain or thalamus, or when one interested in individual variability rather than group averages, gating may prove extremely beneficial.by Andrew R. Dykstra.S.M

Advanced Techniques in Mass Spectrometry for Qualitative and Quantitative Protein Characterization

Though mass spectrometry has earned a central role in the field of proteomics due to its versatility in a wide range of experiments, challenges and complications are still encountered when using mass spectrometry to characterize protein structures, post-translational modifications (PTMs), and abundances. In this dissertation, analytical methods utilizing mass spectrometry have been developed to address challenges associated with both qualitative and quantitative protein characterization. The effectiveness of using multiple pepsin-like proteases, both separately and in mixtures, combined with online proteolysis using a special triaxial probe has been demonstrated on an amyloid beta peptide related to the onset of Alzheimer’s disease. These findings have broad implications in protein structural characterization studies using hydrogen-deuterium exchange mass spectrometry. A wider range of proteases (Lys-C, Glu-C, and trypsin) and multiple fragmentation methods (collisionally activated dissociation, electron transfer dissociation, and decision tree) have been utilized in the discovery-based PTM characterization of extracellular cellulosome proteins of the bioenergy-relevent organism Clostridium thermocellum, resulting in the identification of 85 previously unknown modification sites in 28 cellulosome proteins. These modifications may contribute to the structure and/or function of the cellulosome protein complex. By using peptide internal standards and a triple quadrupole mass spectrometer operating in selected reaction monitoring mode, a method has been developed for the absolute quantitation of the Clostridium thermocellum cellulosome protein machine in samples ranging in complexity from purified cellulosome samples to whole cell lysates as an alternative to a previously-developed enzyme-linked immunosorbent assay method of cellulosome quantitation. The precision of the cellulosome mass concentration in technical replicates is better than 5% relative standard deviation for all samples, indicating high precision of cellulosome mass concentration for this method. Though methods and results presented in this dissertation have implications in the study of Alzheimer’s disease and bioenergy research, more broadly this dissertation focuses on development of methods to contend with some of the more complex challenges associated with protein characterization currently presented to the field of proteomics

Structural Evidence for the Tetrameric Assembly of Chemokine CCL11 and the Glycosaminoglycan Arixtra™.

Understanding chemokine interactions with glycosaminoglycans (GAG) is critical as these interactions have been linked to a number of inflammatory medical conditions, such as arthritis and asthma. To better characterize in vivo protein function, comprehensive knowledge of multimeric species, formed by chemokines under native conditions, is necessary. Herein is the first report of a tetrameric assembly of the human chemokine CCL11, which was shown bound to the GAG Arixtra™. Isothermal titration calorimetry data indicated that CCL11 interacts with Arixtra, and ion mobility mass spectrometry (IM-MS) was used to identify ions corresponding to the CCL11 tetrameric species bound to Arixtra. Collisional cross sections (CCS) of the CCL11 tetramer-Arixtra noncovalent complex were compared to theoretical CCS values calculated using a preliminary structure of the complex deduced using X-ray crystallography. Experimental CCS values were in agreement with theoretical values, strengthening the IM-MS evidence for the formation of the noncovalent complex. Tandem mass spectrometry data of the complex indicated that the tetramer-GAG complex dissociates into a monomer and a trimer-GAG species, suggesting that two CC-like dimers are bridged by Arixtra. As development of chemokine inhibitors is of utmost importance to treatment of medical inflammatory conditions, these results provide vital insights into chemokine-GAG interactions

Subsystems of Transitive Subshifts with Linear Complexity

We bound the number of distinct minimal subsystems of a given transitive subshift of linear complexity, continuing work of Ormes and Pavlov [On the complexity function for sequences which are not uniformly recurrent. Dynamical Systems and Random Processes (Contemporary Mathematics, 736). American Mathematical Society, Providence, RI, 2019, pp. 125--137]. We also bound the number of generic measures such a subshift can support based on its complexity function. Our measure-theoretic bounds generalize those of Boshernitzan [A unique ergodicity of minimal symbolic flows with linear block growth. J. Anal. Math.44(1) (1984), 77–96] and are closely related to those of Cyr and Kra [Counting generic measures for a subshift of linear growth. J. Eur. Math. Soc.21(2) (2019), 355–380]

Neural correlates of auditory perceptual organization measured with direct cortical recordings in humans

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, September 2011."August, 2011." Vita. Cataloged from PDF version of thesis.Includes bibliographical references.One of the primary functions of the human auditory system is to separate the complex mixture of sound arriving at the ears into neural representations of individual sound sources. This function is thought to be crucial for survival and communication in noisy settings, and allows listeners to selectively and dynamically attend to a sound source of interest while suppressing irrelevant information. How the brain works to perceptually organize the acoustic environment remains unclear despite the multitude of recent studies utilizing microelectrode recordings in experimental animals or non-invasive human neuroimaging. In particular, the role that brain areas outside the auditory cortex might play is, comparatively, vastly understudied. The experiments described in this thesis combined classic behavioral paradigms with electrical recordings made directly from the cortical surface of neurosurgical patients undergoing clinically-indicated invasive monitoring for localization of epileptogenic foci. By sampling from widespread brain areas with high temporal resolution while participants simultaneously engaged in streaming and jittered multi-tone masking paradigms, the present experiments sought to overcome limitations inherent in previous work, namely sampling extent, resolution in time and space, and direct knowledge of the perceptual experience of the listener. In experiment 1, participants listened to sequences of tones alternating in frequency (i.e., ABA-) and indicated whether they perceived the tones as grouped ("1 stream") or segregated ("2 streams"). As has been reported in neurologically-normal listeners since the 1950s, patients heard the sequences as grouped when the frequency separation between the A and B tones was small and segregated when it was large. Evoked potentials from widespread brain areas showed amplitude correlations with frequency separation but surprisingly did not differ based solely on perceptual organization in the absence of changes in the stimuli. In experiment 2, participants listened to sequences of jittered multi-tone masking stimuli on which a regularly-repeating target stream of tones was sometimes superimposed and indicated when they heard the target stream. Target detectability, as indexed behaviorally, increased throughout the course of each sequence. Evoked potentials and high-gamma activity differed strongly based on the listener's subjective perception of the target tones. These results extend and constrain theories of how the brain subserves auditory perceptual organization and suggests several new avenues of research for understanding the neural mechanisms underlying this critical function.by Andrew R. Dykstra.Ph.D