Utilizing MRI Texture Analysis and APOE Genotype to Predict the Aging Brain as a Potential Method for Early Assessment of Alzheimer's Disease

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Description
Background: Noninvasive MRI methods that can accurately detect subtle brain changes are highly desirable when studying disease-modifying interventions. Texture analysis is a novel imaging technique which utilizes the extraction of a large number of image features with high specificity and

Background: Noninvasive MRI methods that can accurately detect subtle brain changes are highly desirable when studying disease-modifying interventions. Texture analysis is a novel imaging technique which utilizes the extraction of a large number of image features with high specificity and predictive power. In this investigation, we use texture analysis to assess and classify age-related changes in the right and left hippocampal regions, the areas known to show some of the earliest change in Alzheimer's disease (AD). Apolipoprotein E (APOE)'s e4 allele confers an increased risk for AD, so studying differences in APOE e4 carriers may help to ascertain subtle brain changes before there has been an obvious change in behavior. We examined texture analysis measures that predict age-related changes, which reflect atrophy in a group of cognitively normal individuals. We hypothesized that the APOE e4 carriers would exhibit significant age-related differences in texture features compared to non-carriers, so that the predictive texture features hold promise for early assessment of AD. Methods: 120 normal adults between the ages of 32 and 90 were recruited for this neuroimaging study from a larger parent study at Mayo Clinic Arizona studying longitudinal cognitive functioning (Caselli et al., 2009). As part of the parent study, the participants were genotyped for APOE genetic polymorphisms and received comprehensive cognitive testing every two years, on average. Neuroimaging was done at Barrow Neurological Institute and a 3D T1-weighted magnetic resonance image was obtained during scanning that allowed for subsequent texture analysis processing. Voxel-based features of the appearance, structure, and arrangement of these regions of interest were extracted utilizing the Mayo Clinic Python Texture Analysis Pipeline (pyTAP). Algorithms applied in feature extraction included Grey-Level Co-Occurrence Matrix (GLCM), Gabor Filter Banks (GFB), Local Binary Patterns (LBP), Discrete Orthogonal Stockwell Transform (DOST), and Laplacian-of-Gaussian Histograms (LoGH). Principal component (PC) analysis was used to reduce the dimensionality of the algorithmically selected features to 13 PCs. A stepwise forward regression model was used to determine the effect of APOE status (APOE e4 carriers vs. noncarriers), and the texture feature principal components on age (as a continuous variable). After identification of 5 significant predictors of age in the model, the individual feature coefficients of those principal components were examined to determine which features contributed most significantly to the prediction of an aging brain. Results: 70 texture features were extracted for the two regions of interest in each participant's scan. The texture features were coded as 70 initial components andwere rotated to generate 13 principal components (PC) that contributed 75% of the variance in the dataset by scree plot analysis. The forward stepwise regression model used in this exploratory study significantly predicted age, accounting for approximately 40% of the variance in the data. The regression model revealed 5 significant regressors (2 right PC's, APOE status, and 2 left PC by APOE interactions). Finally, the specific texture features that contributed to each significant PCs were identified. Conclusion: Analysis of image texture features resulted in a statistical model that was able to detect subtle changes in brain integrity associated with age in a group of participants who are cognitively normal, but have an increased risk of developing AD based on the presence of the APOE e4 phenotype. This is an important finding, given that detecting subtle changes in regions vulnerable to the effects of AD in patients could allow certain texture features to serve as noninvasive, sensitive biomarkers predictive of AD. Even with only a small number of patients, the ability for us to determine sensitive imaging biomarkers could facilitate great improvement in speed of detection and effectiveness of AD interventions..
Date Created
2016-05
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A Micro Analysis of Response Trends in Dogs Working to Distinguish Odors of a Common Explosive Chemical

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Description
In response to the growing prevalence of improvised explosive devices, a study was conducted that called into question the current methodology used to train explosive detection dogs. The study analyzed the effects of training these dogs using concept formation training

In response to the growing prevalence of improvised explosive devices, a study was conducted that called into question the current methodology used to train explosive detection dogs. The study analyzed the effects of training these dogs using concept formation training versus standard pure training. It was hypothesized that dogs who received concept formation training would have a higher accuracy at generalizing to mixtures. The logic behind this hypothesis was that if a dog was trained elementally with pure samples, they would not be able to accurately recognize a diluted or modified version of the target Ammonium Nitrate scent. Group Elemental dogs had slightly higher accuracies during the concept testing portion of the study compared to the Group Concept dogs. Additionally, during the generalization phase of the experiment, the Group Elemental dogs performed equally well to the Group Concept dogs. Overall, concept formation training and elemental training were suggested to be equally effective according to the results of the dogs in this study. For the future, this experiment should be repeated with a larger sample size as it has great potential for giving insight on improving the training of explosive detection dogs.
Date Created
2016-12
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Motor system integrity in older adults with autism spectrum disorder

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Description
Background: Gait disturbance, clumsiness, and other mild movement problems are often observed in children with autism spectrum disorder (ASD) (Maurer and Damasio 1982). As the brain ages, these symptoms may persist or worsen in late adulthood in those diagnosed with

Background: Gait disturbance, clumsiness, and other mild movement problems are often observed in children with autism spectrum disorder (ASD) (Maurer and Damasio 1982). As the brain ages, these symptoms may persist or worsen in late adulthood in those diagnosed with ASD. This study focused on older adults with ASD to study motor behavior and underlying brain integrity. Using a finger tapping task, motor performance was measured in a cross-sectional study comparing older adults with ASD and age-matched typically developing (TD) controls. We hypothesized that older adults with ASD would show poorer motor performance (slower finger tapping speed). We also hypothesized that underlying brain differences, measured using MRI, in regions associated with motor function including the primary motor cortex, basal ganglia, and cerebellum, as well as the white matter connecting tracts would exist between groups and be associated with the proposed disparity in motor performance.

Method: A finger oscillation (Finger Tapping) test was administered to both ASD (n=21) and TD (n=20) participants aged 40-70 year old participants as a test of fine motor speed. Magnetic resonance (MR) images were collected using a Philips 3 Tesla scanner. 3D T1-weighted and diffusion tensor images (DTI) were obtained to measure gray and white matter volume and white matter integrity, respectively. FreeSurfer, an automated volumetric measurement software, was used to determine group volumetric differences. Mean, radial, and axial diffusivity, fractional anisotropy, and local diffusion homogeneity were measured from DTI images using PANDA software in order to evaluate white matter integrity.

Results: All participants were right-handed and there were no significant differences in demographic variables (ASD/TD, means) including age (51.9/49.1 years), IQ (107/112) and years education (15/16). Total brain volume was not significantly different between groups. No statistically significant group differences were observed in finger tapping speed. ASD participants compared to TDs showed a trend of slower finger tapping (taps/10 seconds) speed on the dominant hand (47.00 (±11.2) vs. (50.5 (±6.6)) and nondominant hand (44.6 (±7.6) vs. (47.2 (±6.6)). However, a large degree of variability was observed in the ASD group, and the Levene’s test for homogeneity of variance approached significance (p=0.053) on the dominant, but not the nondominant, hand. No significant group differences in gray matter regional volume were found for brain regions associated with performing motor tasks. In contrast, group differences were found on several measures of white matter including the corticospinal tract, anterior internal capsule and middle cerebellar peduncle. Brain-behavior correlations showed that dominant finger tapping speed correlated with left hemisphere white matter integrity of the corticospinal tract and right hemisphere cerebellar white matter in the ASD group.

Conclusions: No significant differences were observed between groups in finger tapping speed but the high degree of variability seen in the ASD group. Differences in motor performance appear to be associated with observed brain differences, particularly in the integrity of white matter tracts contributing to motor functioning.
Date Created
2017-05
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Effects of Loudness Change on Tempo Perception and Action in Percussion

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Description
Tempo control is a crucial part of musicianship that can provide an obstacle for novice musicians. The current study examines why novice percussionists increase their playing tempo when they increase their loudness (in music, loudness is referred to as dynamics).

Tempo control is a crucial part of musicianship that can provide an obstacle for novice musicians. The current study examines why novice percussionists increase their playing tempo when they increase their loudness (in music, loudness is referred to as dynamics). This study tested five hypotheses: 1) As actual tempo changes, listeners perceive that the tempo is changing; 2) There is a perceptual bias to perceive increases in acoustic intensity as also increasing in tempo; 3) All individuals, regardless of percussion experience, display the bias described in hypothesis 2; 4) Unskilled or non-percussionists increase or decrease produced tempo as they respectively increase or decrease loudness; and 5) Skilled percussionist produce less change in tempo due to changes in loudness than non-percussionists. In Experiment 1, percussionists and non-percussionists listened to metronome samples that gradually change in intensity and/or tempo. Participants identified the direction and size of their perceived tempo change using a computer mouse. In Experiment 2, both groups of participants produced various tempo and dynamic changes on a drum pad. Our findings support that both percussionists and non-percussionists, to some extent, display a perceptual bias to perceive tempo changes as a function of intensity changes. We also found that non-percussionists altered their tempo as a function of changing dynamic levels, whereas percussionists did not. Overall, our findings support that listeners tend to experience some integrality between perceptual dimensions of perceived tempo and loudness. Dimensional integration also persists when playing percussion instruments though experience with percussion instruments reduces this effect.
Date Created
2014-05
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Human Auditory Biases Match Natural Regularities Found With Animal Calls

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Description
Human perceptual dimensions of sound are not necessarily simple representations of the actual physical dimensions that make up sensory input. In particular, research on the perception of interactions between acoustic frequency and intensity has shown that people exhibit a bias

Human perceptual dimensions of sound are not necessarily simple representations of the actual physical dimensions that make up sensory input. In particular, research on the perception of interactions between acoustic frequency and intensity has shown that people exhibit a bias to expect the perception of pitch and loudness to change together. Researchers have proposed that this perceptual bias occurs because sound sources tend to follow a natural regularity of a correlation between changes in intensity and frequency of sound. They postulate that the auditory system has adapted to expect this naturally occurring relationship to facilitate auditory scene analysis, the tracking and parsing sources of sound as listeners analyze their auditory environments. However, this correlation has only been tested with human speech and musical sounds. The current study explores if animal sounds also exhibit the same natural correlation between intensity and frequency and tests if people exhibit a perceptual bias to assume this correlation when listening to animal calls. Our principal hypotheses are that animal sounds will tend to exhibit a positive correlation between intensity and frequency and that, when hearing such sounds change in intensity, listeners will perceive them to also change in frequency and vice versa. Our tests with 21 animal calls and 8 control stimuli along with our experiment with participants responding to these stimuli supported these hypotheses. This research provides a further example of coupling of perceptual biases with natural regularities in the auditory domain, and provides a framework for understanding perceptual biases as functional adaptations that help perceivers more accurately anticipate and utilize reliable natural patterns to enhance scene analyses in real world environments.
Date Created
2014-05
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Does Adapting the Body Schema to a Partner Facilitate Motor Learning?

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Description
Often learning new skills, such as how to throw a basketball or how to play the piano, are better accomplished practicing with another than from self-practice. Why? We propose that during joint action, partners learn to adjust their behavior to

Often learning new skills, such as how to throw a basketball or how to play the piano, are better accomplished practicing with another than from self-practice. Why? We propose that during joint action, partners learn to adjust their behavior to each other. For example, when dancing with a partner, we must adjust the timing, the force, and the spatial locations of movements to those of the partner. We call these adjustments a joint body schema (JBS). That is, the locations of our own effectors and our own movements are adapted by interaction with the partner. Furthermore, we propose that after a JBS is established, learning new motor skills can be enhanced by the learner's attunement to the specifics of the partner's actions. We test this proposal by having partners engage in a motor task requiring cooperation (to develop the JBS). Then we determined whether a) the JBS enhances the coordination on an unrelated task, and b) whether the JBS enhances the learning of a new motor skill. In fact, participants who established a JBS showed stronger coordination with a partner and better motor learning from the partner than did control participants. Several applications of this finding are discussed.
Date Created
2015-05
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Pigeon Iridescence: Physical and Functional Properties

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Description
Rock Doves (Columba livia), also known as pigeons, are a common sight to city dwellers around the world. Often overlooked as urban pests, these birds have intriguing iridescent coloration on their necks that has been the subject of few studies.

Rock Doves (Columba livia), also known as pigeons, are a common sight to city dwellers around the world. Often overlooked as urban pests, these birds have intriguing iridescent coloration on their necks that has been the subject of few studies. Previous studies have documented the multimodal reflectance spectra of the iridescence and the keratin cortex microstructures responsible for those properties, but do not address questions about the biological context of this coloration. In this study, I explore the factors that affect how this directional signal might appear to intended receivers (assumed to be females). Pigeon neck feathers were obtained from captive-raised birds and measured for reflectance values at numerous angles in the hemisphere above the feather to obtain a directional reflectance distribution. Each feather was mounted individually, and measurements were taken at a consistent location on the feather using a spectrophotometer; the collector was positioned directly above the feather, while we moved the light source in both azimuth and elevation on a Carden arm to simulate changes in pigeon movements during courtship. Depending on the elevation and azimuth of the light source, pigeon neck feathers shift in appearance from green to purple, with an accompanying shift in the location and intensity of reflectance peaks. Additionally, this unique coloration is due to multiple reflectance peaks in the avian vision field between 300 and 700nm. These data coupled with qualitative behavioral observations of Rock Dove courtship inform our understanding of how the color signal is displayed and how it appears to a potential mate; as a female observes the movements in a male courtship display, properties of the iridescence utilize multiple viewing angles to create a dynamic color array.
Date Created
2015-05
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Baseball's Sight-Audition Farness Effect (Safe) when umpiring baserunners: competing visual and auditory cues

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Description
In baseball, the difference between a win and loss can come down to a single call, such as when an umpire judges force outs at first base by typically comparing competing auditory and visual inputs of the ball-mitt sound and

In baseball, the difference between a win and loss can come down to a single call, such as when an umpire judges force outs at first base by typically comparing competing auditory and visual inputs of the ball-mitt sound and the foot-on-base sight. Yet, because the speed of sound in air only travels about 1100 feet per second, fans observing from several hundred feet away will receive auditory cues that are delayed a significant portion of a second, and thus conceivably could systematically differ in judgments compared to the nearby umpire. The current research examines two questions. 1. How reliably and with what biases do observers judge the order of visual versus auditory events? 2. Do observers making such order judgments from far away systematically compensate for delays due to the slow speed of sound? It is hypothesized that if any temporal bias occurs it is in the direction consistent with observers not accounting for the sound delay, such that increasing viewing distance will increase the bias to assume the sound occurred later. It was found that nearby observers are relatively accurate at judging if a sound occurred before or after a simple visual event (a flash), but exhibit a systematic bias to favor visual stimuli occurring first (by about 30 msec). In contrast, distant observers did not compensate for the delay of the speed of sound such that they systematically favored the visual cue occurring earlier as a function of viewing distance. When observers judged simple visual stimuli in motion relative to the same sound burst, the distance effect occurred as a function of the visual clarity of the ball arriving. In the baseball setting, using a large screen projection of baserunner, a diminished distance effect occurred due to the additional visual cues. In summary, observers generally do not account for the delay of sound due to distance.
Date Created
2017
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Joint action enhances motor learning

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Description
ABSTRACT



Learning a novel motor pattern through imitation of the skilled performance of an expert has been shown to result in better learning outcomes relative to observational or physical practice. The aim of the present project was to

ABSTRACT



Learning a novel motor pattern through imitation of the skilled performance of an expert has been shown to result in better learning outcomes relative to observational or physical practice. The aim of the present project was to examine if the advantages of imitational practice could be further augmented through a supplementary technique derived from my previous research. This research has provided converging behavioral evidence that dyads engaged in joint action in a familiar task requiring spatial and temporal synchrony end up developing an extended overlap in their body representations, termed a joint body schema (JBS). The present research examined if inducing a JBS between a trainer and a novice trainee, prior to having the dyad engage in imitation practice on a novel motor pattern would enhance both of the training process and its outcomes.

Participants either worked with their trainer on a familiar joint task to develop the JBS (Joint condition) or performed a solo equivalent of the task while being watched by their trainer (Solo condition). Participants In both groups then engaged in blocks of alternating imitation practice and free production of a novel manual motor pattern, while their motor output was recorded. Analyses indicated that the Joint participants outperformed the Solo participants in the ability to synchronize the spatial and temporal components of their imitation movements with the trainer’s pattern-modeling movements. The same group showed superior performance when attempting to freely produce the pattern. These results carry significant theoretical and translational potentials for the fields of motor learning and rehabilitation.
Date Created
2015
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Navigating to New Frontiers in Behavioral Neuroscience: Traditional Neuropsychological Tests Predict Human Performance on a Rodent-Inspired Radial-Arm Maze

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Description

We constructed an 11-arm, walk-through, human radial-arm maze (HRAM) as a translational instrument to compare existing methodology in the areas of rodent and human learning and memory research. The HRAM, utilized here, serves as an intermediary test between the classic

We constructed an 11-arm, walk-through, human radial-arm maze (HRAM) as a translational instrument to compare existing methodology in the areas of rodent and human learning and memory research. The HRAM, utilized here, serves as an intermediary test between the classic rat radial-arm maze (RAM) and standard human neuropsychological and cognitive tests. We show that the HRAM is a useful instrument to examine working memory ability, explore the relationships between rodent and human memory and cognition models, and evaluate factors that contribute to human navigational ability. One-hundred-and-fifty-seven participants were tested on the HRAM, and scores were compared to performance on a standard cognitive battery focused on episodic memory, working memory capacity, and visuospatial ability. We found that errors on the HRAM increased as working memory demand became elevated, similar to the pattern typically seen in rodents, and that for this task, performance appears similar to Miller's classic description of a processing-inclusive human working memory capacity of 7 ± 2 items. Regression analysis revealed that measures of working memory capacity and visuospatial ability accounted for a large proportion of variance in HRAM scores, while measures of episodic memory and general intelligence did not serve as significant predictors of HRAM performance. We present the HRAM as a novel instrument for measuring navigational behavior in humans, as is traditionally done in basic science studies evaluating rodent learning and memory, thus providing a useful tool to help connect and translate between human and rodent models of cognitive functioning.

Date Created
2014-09-09
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