Faculty Scholarship

Showing 11 - 20 of 733 Items

Neural correlates of behavior therapy for Tourette's disorder

Date: 2014-01-01

Creator: Thilo Deckersbach, Tina Chou, Jennifer C. Britton, Lindsay E. Carlson, Hannah E., Reese, Jedidiah Siev, Lawrence Scahill, John C. Piacentini, Douglas W. Woods, John T. Walkup, Alan L. Peterson, Darin D. Dougherty, Sabine Wilhelm

Access: Open access

Tourette's disorder, also called Tourette syndrome (TS), is characterized by motor and vocal tics that can cause significant impairment in daily functioning. Tics are believed to be due to failed inhibition of both associative and motor cortico-striato-thalamo-cortical pathways. Comprehensive Behavioral Intervention for Tics (CBIT), which is an extension of Habit Reversal Therapy (HRT), teaches patients to become more aware of sensations that reliably precede tics (premonitory urges) and to initiate competing movements that inhibit the occurrence of tics. In this study, we used functional magnetic resonance imaging (fMRI) to investigate the neural changes associated with CBIT treatment in subjects with TS. Eight subjects with TS were matched with eight healthy controls in gender, education, age, and handedness. Subjects completed the Visuospatial Priming (VSP) task, a measure of response inhibition, during fMRI scanning before and after CBIT treatment (or waiting period for controls). For TS subjects, we found a significant decrease in striatal (putamen) activation from pre- to post-treatment. Change in VSP task-related activation from pre- to post-treatment in Brodmann's area 47 (the inferior frontal gyrus) was negatively correlated with changes in tic severity. CBIT may promote normalization of aberrant cortico-striato-thalamo-cortical associative and motor pathways in individuals with TS.


Genome plasticity in candida albicans is driven by long repeat sequences

Date: 2019-06-01

Creator: Robert T. Todd, Tyler D. Wikoff, Anja Forche, Anna Selmecki

Access: Open access

Genome rearrangements resulting in copy number variation (CNV) and loss of heterozygosity (LOH) are frequently observed during the somatic evolution of cancer and promote rapid adaptation of fungi to novel environments. In the human fungal pathogen Candida albicans, CNV and LOH confer increased virulence and antifungal drug resistance, yet the mechanisms driving these rearrangements are not completely understood. Here, we unveil an extensive array of long repeat sequences (65–6499 bp) that are associated with CNV, LOH, and chromosomal inversions. Many of these long repeat sequences are uncharacterized and encompass one or more coding sequences that are actively transcribed. Repeats associated with genome rearrangements are predominantly inverted and separated by up to ~1.6 Mb, an extraordinary distance for homology-based DNA repair/recombination in yeast. These repeat sequences are a significant source of genome plasticity across diverse strain backgrounds including clinical, environmental, and experimentally evolved isolates, and represent previously uncharacterized variation in the reference genome.


Fgf signaling is required for zebrafish tooth development

Date: 2004-10-01

Creator: William R. Jackman, Bruce W. Draper, David W. Stock

Access: Open access

We have investigated fibroblast growth factor (FGF) signaling during the development of the zebrafish pharyngeal dentition with the goal of uncovering novel roles for FGFs in tooth development as well as phylogenetic and topographic diversity in the tooth developmental pathway. We found that the tooth-related expression of several zebrafish genes is similar to that of their mouse orthologs, including both epithelial and mesenchymal markers. Additionally, significant differences in gene expression between zebrafish and mouse teeth are indicated by the apparent lack of fgf8 and pax9 expression in zebrafish tooth germs. FGF receptor inhibition with SU5402 at 32 h blocked dental epithelial morphogenesis and tooth mineralization. While the pharyngeal epithelium remained intact as judged by normal pitx2 expression, not only was the mesenchymal expression of lhx6 and lhx7 eliminated as expected from mouse studies, but the epithelial expression of dlx2a, dlx2b, fgf3, and fgf4 was as well. This latter result provides novel evidence that the dental epithelium is a target of FGF signaling. However, the failure of SU5402 to block localized expression of pitx2 suggests that the earliest steps of tooth initiation are FGF-independent. Investigations of specific FGF ligands with morpholino antisense oligonucleotides revealed only a mild tooth shape phenotype following fgf4 knockdown, while fgf8 inhibition revealed only a subtle down-regulation of dental dlx2b expression with no apparent effect on tooth morphology. Our results suggest redundant FGF signals target the dental epithelium and together are required for dental morphogenesis. Further work will be required to elucidate the nature of these signals, particularly with respect to their origins and whether they act through the mesenchyme. © 2004 Elsevier Inc. All rights reserved.


“Unmotivated bias” and partisan hostility: Empirical evidence

Date: 2019-04-01

Creator: Daniel F. Stone

Access: Open access

Extreme partisan animosity has been on the rise in the US and is prevalent around the world. This hostility is typically attributed to social group identity, motivated reasoning, or a combination thereof. In this paper, I empirically examine a novel contributing factor: the “unmotivated” cognitive bias of overprecision (overconfidence in precision of beliefs). Overprecision could cause partisan hostility indirectly via inflated confidence in one's own ideology, partisan identity, or perceptions of social distance between the parties. Overprecision could also cause this hostility directly by causing excessively strong inferences from observed information that is either skewed against the out-party or simply misunderstood. Using a nationally representative sample, I find consistent support for direct effects of overprecision and mixed support for indirect effects. The point estimates imply a one standard deviation increase in a respondent's overprecision predicts as much as a 0.71 standard deviation decline in relative out-party favorability.


Feasibility and acceptability of an online mindfulness-based group intervention for adults with tic disorders

Date: 2021-12-01

Creator: Hannah E. Reese, W. Alan Brown, Berta J. Summers, Jin Shin, Grace, Wheeler, Sabine Wilhelm

Access: Open access

Abstract: Background: Preliminary research suggests that a mindfulness-based treatment approach may be beneficial for adults with tic disorders. In the present study, we report on the feasibility, acceptability, safety, and symptomatic effect of a novel online mindfulness-based group intervention for adults with Tourette syndrome or persistent tic disorder. Data from this study will directly inform the conduct of a funded randomized controlled trial comparing the efficacy of this intervention to another active psychological intervention. Methods: One cohort of adults with Tourette syndrome participated in an 8-week online mindfulness-based group intervention. Measures of feasibility, acceptability, and safety were administered throughout and at posttreatment. Self-reported measures of mindfulness and clinician-rated measures of tic severity and impairment were administered at baseline and posttreatment. Results: Data on refusal, dropout rate, attendance, participant satisfaction, and safety suggest that this is a feasible and acceptable intervention. However, participant adherence to home practice was lower than anticipated. Mindfulness, tic severity, and tic-related impairment only modestly improved from baseline to posttreatment. Qualitative analysis of participant feedback revealed aspects of the intervention that were most helpful and also areas for improvement. Conclusions: Data suggest that although this is a feasible and acceptable intervention, it should be modified to enhance participant adherence, more successfully engage the target mechanism, and optimize outcomes. Trial registration: Clinicaltrials.gov registration #NCT03525626. Registered on 24 April 2018


Continuity Trumps Change: The First Year of Trump's Administrative Presidency

Date: 2019-10-01

Creator: Rachel Augustine Potter, Andrew Rudalevige, Sharece Thrower, Adam L. Warber

Access: Open access

From campaign rhetoric to tweets, President Trump has positioned himself as disrupter in chief, often pointing to administrative action as the avenue by which he is leaving a lasting mark. However, research on the administrative presidency begins with the premise that all presidents face incentives to use administrative tools to gain substantive or political traction. If, as this article suggests, Trump's institutional standing differs little from his recent predecessors, then how much of the Trump presidency represents a change from past norms and practices' How much represents continuity, or the perennial dynamics of a far-from-omnipotent executive in an ongoing world of separate institutions sharing powers (Neustadt 1990, 29)' To answer this, we tracked presidential directives and regulatory policy during Trump's first year in office. We found evidence of continuity, indicating that in its use of administrative tactics to shape policy, the Trump White House largely falls in line with recent presidencies.


Rapid evolution of a coadapted gene complex: Evidence from the segregation Distorter (SD) system of meiotic drive in Drosophila melanogaster

Date: 1996-09-11

Creator: Michael F. Palopoli, Chung I. Wu

Access: Open access

Segregation Distorter (SD) is a system of meiotic drive found in natural populations of Drosophila melanogaster. Males heterozygous for an SD second chromosome and a normal homologue (SD+) produce predominantly SD- bearing sperm. The coadapted gene complex responsible for this transmission advantage spans the second chromosome centromere, consisting of three major and several minor interacting loci. To investigate the evolutionary history of this system, we surveyed levels of polymorphism and divergence at six genes that together encompass this pericentromeric region and span seven map units. Interestingly, there was no discernible divergence between SD and SD1 chromosomes for any of these molecular markers. Furthermore, SD chromosomes harbored much less polymorphism than did SD+ chromosomes. The results suggest that the SD system evolved recently, swept to appreciable frequencies worldwide, and carried with it the entire second chromosome centromeric region (roughly 10% of the genome). Despite its well-documented genetic complexity, this coadapted systems appears to have evolved on a time scale that is much shorter than can be gauge using nucleotide substitution data. Finally, the large genomic region hitchhiking with SD indicates that a multilocus, epistatically selected could affect the levels of DNA polymorphism observed in regions of reduced recombination.


BCJ relations from a new symmetry of gauge-theory amplitudes

Date: 2016-10-01

Creator: Robert W. Brown, Stephen G. Naculich

Access: Open access

We introduce a new set of symmetries obeyed by tree-level gauge-theory amplitudes involving at least one gluon. The symmetry acts as a momentum-dependent shift on the color factors of the amplitude. Using the radiation vertex expansion, we prove the invariance under this color-factor shift of the n-gluon amplitude, as well as amplitudes involving massless or massive particles in an arbitrary representation of the gauge group with spin zero, one-half, or one. The Bern-Carrasco-Johansson relations are a direct consequence of this symmetry. We also introduce the cubic vertex expansion of an amplitude, and use it to derive a generalized-gauge-invariant constraint on the kinematic numerators of the amplitude. We show that the amplitudes of the bi-adjoint scalar theory are invariant under the color-factor symmetry, and use this to derive the null eigenvectors of the propagator matrix. We generalize the color-factor shift to loop level, and prove the invariance under this shift of one-loop n-gluon amplitudes in any theory that admits a color-kinematic-dual representation of numerators. We show that the one-loop color-factor symmetry implies known relations among the integrands of one-loop color-ordered amplitudes.


Traveling waves in 2D hexagonal granular crystal lattices

Date: 2014-01-01

Creator: A. Leonard, C. Chong, P. G. Kevrekidis, C. Daraio

Access: Open access

This study describes the dynamic response of a two-dimensional hexagonal packing of uncompressed stainless steel spheres excited by localized impulsive loadings. The dynamics of the system are modeled using the Hertzian normal contact law. After the initial impact strikes the system, a characteristic wave structure emerges and continuously decays as it propagates through the lattice. Using an extension of the binary collision approximation for one-dimensional chains, we predict its decay rate, which compares well with numerical simulations and experimental data. While the hexagonal lattice does not support constant speed traveling waves, we provide scaling relations that characterize the directional power law decay of the wave velocity for various angles of impact. Lastly, we discuss the effects of weak disorder on the directional amplitude decay rates. © 2014 The Author(s).


Neurocognitive predictors of treatment response to randomized treatment in adults with tic disorders

Date: 2017-03-06

Creator: Amitai Abramovitch, Lauren S. Hallion, Hannah E. Reese, Douglas W. Woods, Alan, Peterson, John T. Walkup, John Piacentini, Lawrence Scahill, Thilo Deckersbach, Sabine Wilhelm

Access: Open access

Tourette's disorder (TS) and chronic tic disorder (CTD) are neurodevelopmental disorders characterized by involuntary vocal and motor tics. Consequently, TS/CTD have been conceptualized as disorders of cognitive and motor inhibitory control. However, most neurocognitive studies have found comparable or superior inhibitory capacity among individuals with TS/CTD relative to healthy controls. These findings have led to the hypothesis that individuals with TS/CTD develop increased inhibitory control due to the constant need to inhibit tics. However, the role of cognitive control in TS/CTD is not yet understood, particularly in adults. To examine the role of inhibitory control in TS/CTD, the present study investigated this association by assessing the relationship between inhibitory control and treatment response in a large sample of adults with TS/CTD. As part of a large randomized trial comparing behavior therapy versus supportive psychotherapy for TS/CTD, a battery of tests, including tests of inhibitory control was administered to 122 adults with TS/CTD at baseline. We assessed the association between neuropsychological test performance and change in symptom severity, as well as compared the performance of treatment responders and non-responders as defined by the Clinical Global Impression Scale. Results indicated that change in symptoms, and treatment response were not associated with neuropsychological performance on tests of inhibitory control, intellectual ability, or motor function, regardless of type of treatment. The finding that significant change in symptom severity of TS/CTD patients is not associated with impairment or change in inhibitory control regardless of treatment type suggests that inhibitory control may not be a clinically relevant facet of these disorders in adults.