The effect of transcranial direct current stimulation on the interplay between executive control, behavioral variability and mind wandering: A registered report

Mind wandering (MW) is a mental phenomenon humans experience daily. Yet, we lack a complete understanding of the neural basis of this pervasive mental state. Over the past decade there has been an increase in publications using transcranial direct current stimulation (tDCS) to modulate the propensity to mind wander, but findings are diverse, and a satisfactory conclusion is missing. Recently, Boayue et al. (2020) reported successful reduction of mind wandering using high-definition tDCS (HD-tDCS) over the dorsolateral prefrontal cortex, providing preliminary evidence for the efficacy of HD-tDCS in interfering with mind wandering. The current study is a high-powered, pre-registered direct replication attempt of the effect found by Boayue et al. (2020). In addition, we investigated whether the effects of HD-tDCS on mind wandering would be prolonged and assessed the underlying processes of mind wandering using electroencephalography (EEG) and pupillometry during a finger-tapping random sequence generation task that requires the use of executive resources. We failed to find any evidence of the original effect of reduced MW during and after stimulation. When combining our data with the data from Boayue et al. (2020), the original effect of reduced MW caused by HD-tDCS disappeared. In addition, we observed increased occipital alpha power as task duration increased and increased midfrontal theta power preceding response patterns signaling high executive function use. Finally, tonic and phasic pupil size decreased as task duration increased yet, phasic responses were increased, while tonic responses were reduced preceding reports of MW. Additionally phasic pupil size also showed a tendency to be increased during periods of high executive function use. Importantly, none of the EEG or pupil measures were modulated by HD-tDCS. We conclude that HD-tDCS over the dorsolateral prefrontal cortex does not affect MW propensity and its neural signatures. Furthermore, we recommend that previously reported effects of tDCS on mind wandering and other cognitive functions should only be accepted after a successful pre-registered replication

Subjective Evaluation of the In-Line Phase-Sensitive Imaging Systems in Breast Cancer Screening and Diagnosis

Breast x-ray imaging remains the gold standard screening tool despite the various imaging modalities. The phase-sensitive breast imaging is an evolving technology that may provide higher diagnostic accuracy and potentially reduce the patient radiation dose. Many studies evaluate the performance of the In-line phase-sensitive breast imaging to improve this imaging modality further. Whereas radiologists are the end-users of this imaging technology, the primary goal of this dissertation project is to investigate the performance of human observers in varying conditions for further improvement of the in-line phase-sensitive x-ray imaging system. A CDMAM phantom and an ACR mammography phantom are used in the observer performance study to compare the high-energy in-line phase-sensitive system with a mid-energy system as an alternative approach to balancing the attenuation-based image contrast with the accuracy of single-projection PAD-base phase-retrieval. Additionally, a series of ROC studies are designed by a contrast-detail phantom to evaluate the diagnostic accuracy of digital breast tomosynthesis (DBT) and the phase-sensitive prototype imaging system (PBT). The area under the ROC curves (AUC) and partial area under the ROC curves (pAUC) are estimated as a figure of merits in the two systems, delivering the equivalent radiation doses. A two-alternative-forced choice (2AFC) study is also designed to determine the preferred image in identifying the suspicious lesions within a heterogeneous pattern acquired by the DBT and PBT systems under an equivalent radiation dose. The observer performance studies show that the mid-energy system has a potential advantage in providing a relatively higher image quality while the radiation dose is reduced in the mid-energy system compared with a high-energy system. The ROC study shows that the diagnostic accuracy of observers is more significant in the prototype PBT system than in a commercial DBT system, delivering the same radiation dose. The 2AFC study also revealed that observers prefer the PBT system in detecting and distinguishing the conspicuity of tumors in the images with structural noise, and the results were statistically significant. The dissertation also introduces a mathematical approach for estimating the half-value-layer (HVL) from measured or simulated x-ray spectra. The HVL measurement is expected to be less accurate or experimentally challenging in some clinical equipment or when a quick beam quality evaluation is needed. Additionally, the impact of varying thicknesses of external filtration is subjectively and objectively investigated to evaluate the feasibility of reducing the image acquisition time in a mid-energy system without compromising the observer's performance and detectability. The preliminary results from phase-contrast images suggest that an in-line phase-sensitive system operated at 59 kV shows a comparable image quality with the x-ray beams filtered by 1.3 mm and 2.5 mm-thick aluminum filters. This finding could help shorten the exposure time by 34% in the mid-energy system, where image blurring is a concern due to patient movement in a longer image acquisition time. In summary, and as expected, the subjective analyses of the in-line phase-sensitive imaging system align with the previous findings. However, the PBT imaging system may benefit from further improvement in image processing algorithms and optimizing the system with the most appropriate x-ray beam quality, considering the acquisition time, breast glandular composition, breast thickness, and different x-ray energies. Keywords: Phase-sensitive X-ray Imaging, Breast Imaging, Image Quality, Human Observer Performance Stud

Nonparametric and semiparametric methods in medical diagnostics

In medical diagnostics, biomarkers are used as the basis for detecting or predicting disease. There has been an increased interest in using the Receiver Operating Characteristic (ROC) curve to assess the accuracy of biomarkers. In many situations, a single biomarker is not sufficient for the desired level of accuracy; furthermore, newly discovered biomarkers can provide additional information for a specific disease. Even though numerous methods have been developed to evaluate a single biomarker, few statistical methods exist to accommodate multiple biomarkers simultaneously. The first paper proposes a semiparametric transformation model for multiple biomarkers in ROC analysis to optimize classification accuracy. This model assumes that some unknown and marker-specific transformations of biomarkers follow a multivariate normal distribution; it incorporates random effects to account for within-subject correlation among biomarkers. Nonparametric maximum likelihood estimation is used for inference, and the parameter estimators are shown to be asymptotically normal and semiparametrically efficient. The proposed method is applied to analyze brain tumor imaging data and prostate cancer data. In the second paper, we focus on assessing the accuracy of biomarkers by adjusting for covariates that can influence the performance of biomarkers. Therefore, we develop an accelerated ROC model in which the effect of covariates relates to rescaling the original ROC curve. The proposed model generalizes the usual accelerated failure time model in the survival context to the ROC analysis. An innovative method is developed to construct estimating equations for parameter estimation. The bootstrapping method is used for inference, and the parameter estimators are shown to be asymptotically normal. We apply the proposed method to data from a prostate cancer study. The paired-reader, paired-patient design is commonly used in reader studies when evaluating the diagnostic performance of radiological imaging systems. In this design, multiple readers interpret all test results of patients who undergo multiple diagnostic tests under study. In the third paper, we develop a method to estimate and compare accuracies of diagnostic tests in a paired-reader, paired-patient design by introducing a latent model for test results. The asymptotic property of the proposed test statistics is derived based on the theory of U-statistics. Furthermore, a method for correcting an imperfect gold standard bias and sample size formula are presented. The proposed method is applied to comparing the diagnostic performance of digital mammography and screen-film mammography in discriminating breast tumors