Medicine and Health Sciences Commons^™

The Hidden Daubert Factor: How Judges Use Error Rates In Assessing Scientific Evidence, John B. Meixner Jr., Shari Seidman Diamond

Scholarly Works

In Daubert v. Merrell Dow Pharmaceuticals, the United States Supreme Court provided a framework under which trial judges must assess the evidentiary reliability of scientific evidence whose admissibility is challenged. One factor of the Daubert test, the “known or potential rate of error” of the expert’s method, has received considerably less scholarly attention than the other factors, and past empirical study has indicated that judges have a difficult time understanding the factor and use it less frequently in their analyses as compared to other factors. In this paper, we examine one possible interpretation of the “known or potential rate of …

Blast-Induced Tinnitus: A Combined Behavioral, Memri, And Electrophysiology Study, Jessica Pengyun Ouyang

Wayne State University Dissertations

ABSTRACT

BLAST-INDUCED TINNITUS: A COMBINED BEHAVIORAL, MEMRE, AND ELECTROPHYSIOLOGY STUDY

by

JESSICA OUYANG

May 2014 Advisor: Drs. Steve Cala & Jinsheng Zhang

Major: Physiology

Degree: Doctor of Philosophy

Tinnitus and hearing loss are the frequent auditory-related co-morbidities of blast trauma. The etiology of blast-induced tinnitus is also muddled by brain mechanisms associated with emotional and cognitive problems such as anxiety, memory loss, and depression. We set out to develop a realistic and ecologically valid model to address changes of cognitive status and psychological state that are associated with blast- induced tinnitus. In this study, 19 adult rats were randomly divided …

Accumulation Of Subcortical Iron As A Modifier Of Volumetric And Cognitive Decline In Healthy Aging: Two Longitudinal Studies, Ana Marie Daugherty

Wayne State University Dissertations

Accumulation of non-heme iron in the brain has been theorized as a cellular mechanism underlying global neural and cognitive decline in normal aging and neurodegenerative disease. Relatively few studies of brain iron in normal aging exist and extant studies are almost exclusively cross-sectional. Here, I estimated iron content via T2* and measured volumes in several brain regions in two independent samples of healthy adults. The first sample (N = 89) was measured twice with a two-year delay; and the second sample (N = 32) was assessed four times over a span of 7 years. Latent models estimated change in iron …

Linking Molecular, Electrical And Anatomical Properties Of Human Epileptic Brain, Shruti Bagla

Wayne State University Dissertations

Epilepsy is a common neurological disorder of recurrent unprovoked seizures. It affects almost 1% of the world population. Although there is a wide range of anti-epileptic drugs (AEDs) available, they only treat the seizure symptoms and do not cure the disease itself. The poor role of AEDs can be attributed to the lack of knowledge of exact mechanisms and networks that produce epileptic activities in the neocortex. At present, the best cure for epilepsy is surgical removal of electrically localized epileptic brain tissue. Surgically removed brain tissue presents an excellent opportunity to discover the molecular and cellular basis of human …

The Quetiapine Active Metabolite N-Desalkylquetiapine And The Neurotensin Nts1 Receptor Agonist Pd149163 Exhibit Antidepressant-Like Effects On Operant Responding In Male Rats, Todd M. Hillhouse, Zachary Shankland, Katelin S. Matazel, Ashley Keiser, Adam J. Prus

Journal Articles

Major depressive disorder (MDD) is the most common mood disorder in the United States and European Union; however, the limitations of clinically available antidepressant drugs have led researchers to pursue novel pharmacological treatments. Clinical studies have reported that monotherapy with the atypical antipsychotic drug quetiapine produces a rapid reduction in depressive symptoms that are apparent following one week of quetiapine treatment, and it is possible that the active metabolite N-Desalkylquetiapine, which structurally resembles an antidepressant drug, produces antidepressant effects. Neuropharmacological evaluations of the neurotensin NTS₁ receptor agonist PD149163 are suggestive of antidepressant efficacy, but the effects of a NTS …

Detecting Knowledge Of Incidentally Acquired, Real-World Memories Using A P300-Based Concealed-Information Test, John B. Meixner Jr., J. Peter Rosenfeld

Scholarly Works

Autobiographical memory for events experienced during normal daily life has been studied at the group level, but no studies have yet examined the ability to detect recognition of incidentally acquired memories among individual subjects. We present the first such study here, which employed a concealed-information test in which subjects were shown words associated with activities they had experienced the previous day. Subjects wore a video-recording device for 4 hr on Day 1 and then returned to the laboratory on Day 2, where they were shown words relating to events recorded with the camera (probe items) and words of the same …

Three‐Dimensional Brain Mri For Dbs Patients Within Ultra‐Low Radiofrequency Power Limits, Subhendra N. Sarkar, Efstathios Papavassiliou, David Hackney, David Alsop, Ananth Madhuranthakam, Ludy Shih, Reed Busse, Susan Laruche, Rafeeque Bhadelia

Publications and Research

Background: For patients with deep brain stimulators (DBS), local absorbed radiofrequency (RF) power is unknown and is much higher than what the system estimates. We developed a comprehensive, highquality brain magnetic resonance imaging (MRI) protocol for DBS patients utilizing three-dimensional (3D) magnetic resonance sequences at very low RF power. Methods: Six patients with DBS were imaged (10 sessions) using a transmit/receive head coil at 1.5 Tesla with modified 3D sequences within ultra-low specific absorption rate (SAR) limits (0.1 W/kg) using T2, fast fluid-attenuated inversion recovery (FLAIR) and T1- weighted image contrast. Tissue signal and tissue contrast from the low-SAR images …

The Contribution Of Purinergic P2x And P2y Receptors To The Excitability Of Mouse Vomeronasal Sensory Neurons, Jonathan Vick

Graduate College Dissertations and Theses

Olfaction, the sense of smell, allows animals to perceive the multitude of volatile and nonvolatile molecules present in the environment. In many mammals, such as mice and rats, there are four unique chemosensory organs including the (1) main olfactory epithelium (MOE), (2) septal organ, (3) Grüneberg ganglion, and (4) vomeronasal organ (VNO). While the VNO detects some general volatile odorants, it is further specialized for the detection of behaviorally relevant nonvolatile odorants or pheromones. In rodents, the VNO is encased within a bony capsule and located at the base of the nasal cavity. Odorants are detected by vomeronasal sensory neuron …

Factors That Contribute To Balance And Mobility Impairments In Individuals With Huntington's Disease, Travis Cruickshank, Alvaro Reyes, Luis Peñailillo, Jennifer Thompson, Mel Ziman

Research outputs 2014 to 2021

Mobility and balance problems are common and often debilitating features of Huntington's disease (HD). In this exploratory study we aimed to investigate the influence of disease severity, severity of motor deficits, lower limb muscle strength, cognition, executive function, lean muscle mass and reactivity on mobility and balance.Twenty-two individuals with HD were recruited from the North Metropolitan Area Mental Health Service, Perth, Australia. Pertinent demographic, genetic and disease progression information was recorded prior to testing. Balance was assessed using dynamic and static balance tasks. Mobility was assessed using self-paced and fast-paced mobility measures. Cognitive and executive measures were used to assess …

An Anemia Of Alzheimer's Disease, N G. Faux, A Rembach, J Wiley, K A. Ellis, D Ames, C J. Fowler, Ralph N. Martins, K K. Pertile, R L. Rumble, B Trounson, C L. Masters, A I. Bush

Research outputs 2014 to 2021

Lower hemoglobin is associated with cognitive impairment and Alzheimer's disease (AD). Since brain iron homeostasis is perturbed in AD, we investigated whether this is peripherally reflected in the hematological and related blood chemistry values from the Australian Imaging Biomarker and Lifestyle (AIBL) study (a community-based, cross-sectional cohort comprising 768 healthy controls (HC), 133 participants with mild cognitive impairment (MCI) and 211 participants with AD). We found that individuals with AD had significantly lower hemoglobin, mean cell hemoglobin concentrations, packed cell volume and higher erythrocyte sedimentation rates (adjusted for age, gender, APOE-ε4 and site). In AD, plasma iron, transferrin, transferrin saturation …

Anxiety Symptoms, Cerebral Amyloid Burden And Memory Decline In Healthy Older Adults Without Dementia: 3-Year Prospective Cohort Study, Robert H. Pietrzak, J C. Scott, Alexander Neumeister, Yen Ying Lim, David Ames, Kathyrn A. Ellis, Kara Harrington, Nicola T. Lautenschlager, Cassandra Szoeke, Ralph Martins, Colin L. Masters, Victor L. Villemagne, Christopher C. Rowe, Paul Maruff

Research outputs 2014 to 2021

Although beta-amyloid, anxiety and depression have been linked cross-sectionally to reduced memory function in healthy older adults without dementia, prospective data evaluating these associations are lacking. Using data from an observational cohort study of 178 healthy older adults without dementia followed for 3 years, we found that anxiety symptoms significantly moderated the relationship between beta-amyloid level and decline in verbal (Cohen's d = 0.65) and episodic (Cohen's d = 0.38) memory. Anxiety symptoms were additionally linked to greater decline in executive function, irrespective of beta-amyloid and other risk factors. These findings suggest that interventions to mitigate anxiety symptoms may help …

Impact Of Nutrition On Cognition And Its Association With Blood And Brain Alzheimer Disease Related Biomarkers, Samantha Gardener

Theses: Doctorates and Masters

Alzheimer’s disease (AD), the most common form of senile dementia, currently affects over 35 million people worldwide. While there is no cure or effective treatment, early intervention programs hold considerable promise. Following particular dietary patterns represents one potential intervention strategy accessible to all.

Results from previous studies investigating the association of diet, cognition and biomarkers of AD are inconsistent: Positive results have been reported (1-7), whilst others have shown no associations. Prior to this thesis, no study has assessed the relationship of four dietary patterns to cognition, blood-based and neuroimaging biomarkers of AD in a large highly-characterised ageing cohort. Participants …

Differential Effects Of Fatigue On Movement Variability, N. Cortes, J. Onate, S. Morrison

Rehabilitation Sciences Faculty Publications

When individuals perform purposeful actions to fatigue, there is typically a general decline in their movement performance. This study was designed to investigate the effects exercise-induced fatigue has on lower limb kinetics and kinematics during a side-step cutting task. In particular, it was of interest to determine what changes could be seen in mean amplitude and all metrics of signal variability with fatigue. The results of the study revealed that post-fatigue there was an overall decrease in absolute force production as reflected by a decline in mean amplitude and variability (SD) of the ground reaction forces (GRF_V and GRF …

Adolescent Crash Rates And School Start Times In Two Central Virginia Counties, 2009-2011: A Follow-Up Study To A Southeastern Virginia Study, 2007-2008, Robert Daniel Vorona, Mariana Szklo-Coxe, Rajan Lamichhane, J. Catesby Ware, Ann Mcnallen, David Leszczyszyn

Community & Environmental Health Faculty Publications

Background and Objective: Early high school start times (EHSST) may lead to sleep loss in adolescents ("teens"), thus resulting in higher crash rates. (Vorona et al., 2011). In this study, we examined two other adjacent Virginia counties for the two years subsequent to the above-mentioned study. We again hypothesized that teens from jurisdictions with EHSST (versus later) experience higher crash rates.

Methods: Virginia Department of Motor Vehicles supplied de-identified aggregate data on weekday crashes and time-of- day for 16-18 year old (teen) and adult drivers for school years 2009-2010 and 2010-2011 in Henrico and Chesterfield Counties (HC and CC, respectively). …

Law And Neuroscience: Recommendations Submitted To The President's Bioethics Commission, Owen D. Jones, Richard J. Bonnie, B. J. Casey, Andre Davis, David L. Faigman, Morris Hoffman, Read Montague, Stephen J. Morse, Marcus E. Raichle, Jennifer A. Richeson, Elizabeth Scott, Laurence Steinberg, Kim Taylor-Thompson, Anthony Wagner, Gideon Yaffe

All Faculty Scholarship

President Obama charged the Presidential Commission for the Study of Bioethical Issues to identify a set of core ethical standards in the neuroscience domain, including the appropriate use of neuroscience in the criminal-justice system. The Commission, in turn, called for comments and recommendations. The MacArthur Foundation Research Network on Law and Neuroscience submitted a consensus statement, published here, containing 16 specific recommendations. These are organized within three main themes: 1) what steps should be taken to enhance the capacity of the criminal justice system to make sound decisions regarding the admissibility and weight of neuroscientific evidence?; 2) to what extent …

Effects Of Hyperbaric Oxygen On Eye Tracking Abnormalities In Males After Mild Traumatic Brain Injury, Joanna R. Wares, David X. Cifu, Kathy W. Hoke, Paul A. Wetzel, George Gitchel, William Carne

Department of Math & Statistics Faculty Publications

The effects of hyperbaric oxygen (HBO2) on eye movement abnormalities in 60 military servicemembers with at least one mild traumatic brain injury (mTBI) from combat were examined in a single-center, randomized, double-blind, sham-controlled, prospective study at the Naval Medicine Operational Training Center. During the 10 wk of the study, each subject was delivered a series of 40, once a day, hyperbaric chamber compressions at a pressure of 2.0 atmospheres absolute (ATA). At each session, subjects breathed one of three preassigned oxygen fractions (10.5%, 75%, or 100%) for 1 h, resulting in an oxygen exposure equivalent to breathing either surface air, …

Differential Eye Movements In Mild Traumatic Brain Injury Vs. Normal Controls, Joanna R. Wares, David X. Cifu, Kathy W. Hoke, Paul A. Wetzel, George Gitchel, William Carne

Department of Math & Statistics Faculty Publications

Objective measures to diagnose and to monitor improvement of symptoms following mild traumatic brain injury (mTBI) are lacking. Computerized eye tracking has been advocated as a rapid, user friendly and field ready technique to meet this need. Eye tracking data collected via a head mounted, video-based binocular eye tracker was used to examine saccades, fixations and smooth pursuit movement in 60 military Service Members with post concussive syndrome (PCS) and 26 asymptomatic control subjects in an effort to determine if eye movement differences could be found and quantified. The diagnosis of mTBI was confirmed by the study physiatrist’s history, physical …

Short-Duration Stimulation Of The Supplementary Eye Fields Perturbs Anti-Saccade Performance While Potentiating Contralateral Head Orienting., Brendan B Chapman, Brian D Corneil

Brain and Mind Institute Researchers' Publications

Many forms of brain stimulation utilize the notion of state dependency, whereby greater influences are observed when a given area is more engaged at the time of stimulation. Here, by delivering intracortical microstimulation (ICMS) to the supplementary eye fields (SEF) of monkeys performing interleaved pro- and anti-saccades, we show a surprising diversity of state-dependent effects of ICMS-SEF. Short-duration ICMS-SEF passed around cue presentation selectively disrupted anti-saccades by increasing reaction times and error rates bilaterally, and also recruited neck muscles, favoring contralateral head turning to a greater degree on anti-saccade trials. These results are consistent with the functional relevance of the …

Bilateral Saccadic Deficits Following Large And Reversible Inactivation Of Unilateral Frontal Eye Field., Tyler R Peel, Kevin Johnston, Stephen G Lomber, Brian D Corneil

Brain and Mind Institute Researchers' Publications

Inactivation permits direct assessment of the functional contribution of a given brain area to behavior. Previous inactivation studies of the frontal eye field (FEF) have either used large permanent ablations or reversible pharmacological techniques that only inactivate a small volume of tissue. Here we evaluated the impact of large, yet reversible, FEF inactivation on visually guided, delayed, and memory-guided saccades, using cryoloops implanted in the arcuate sulcus. While FEF inactivation produced the expected triad of contralateral saccadic deficits (increased reaction time, decreased accuracy and peak velocity) and performance errors (neglect or misdirected saccades), we also found consistent increases in reaction …

An Invitation To The Study Of Brain Networks, With Some Statistical Analysis Of Thresholding Techniques, Mark Daley

Brain and Mind Institute Researchers' Publications

We provide a brief introduction to the nascent application of network theory to mesoscale networks in the human brain. Following an overview of the typical data-gathering, processing, and analysis methods employed in this field, we describe the process for inferring a graph from neural time series. A crucial step in the construction of a graph from time series is the thresholding of graph edges to ensure that the graphs represent physiological relationships rather than artifactual noise. We discuss the most popular currently employed methodologies and then introduce one of our own, based on the theory of random matrices. Finally, we …

Observing Object Lifting Errors Modulates Cortico-Spinal Excitability And Improves Object Lifting Performance., Gavin Buckingham, Jeremy D Wong, Minnie Tang, Paul L Gribble, Melvyn A Goodale

Brain and Mind Institute Researchers' Publications

Observing the actions of others has been shown to modulate cortico-spinal excitability and affect behaviour. However, the sensorimotor consequences of observing errors are not well understood. Here, participants watched actors lift identically weighted large and small cubes which typically elicit expectation-based fingertip force errors. One group of participants observed the standard overestimation and underestimation-style errors that characterise early lifts with these cubes (Error video--EV). Another group watched the same actors performing the well-adapted error-free lifts that characterise later, well-practiced lifts with these cubes (No error video--NEV). We then examined actual object lifting performance in the subjects who watched the EV …

Sign Language Ability In Young Deaf Signers Predicts Comprehension Of Written Sentences In English., Kathy N Andrew, Jennifer Hoshooley, Marc F Joanisse

Brain and Mind Institute Researchers' Publications

We investigated the robust correlation between American Sign Language (ASL) and English reading ability in 51 young deaf signers ages 7;3 to 19;0. Signers were divided into 'skilled' and 'less-skilled' signer groups based on their performance on three measures of ASL. We next assessed reading comprehension of four English sentence structures (actives, passives, pronouns, reflexive pronouns) using a sentence-to-picture-matching task. Of interest was the extent to which ASL proficiency provided a foundation for lexical and syntactic processes of English. Skilled signers outperformed less-skilled signers overall. Error analyses further indicated greater single-word recognition difficulties in less-skilled signers marked by a higher …

Sensitivity Of Human Auditory Cortex To Rapid Frequency Modulation Revealed By Multivariate Representational Similarity Analysis., Marc F Joanisse, Diedre D Desouza

Brain and Mind Institute Researchers' Publications

Functional Magnetic Resonance Imaging (fMRI) was used to investigate the extent, magnitude, and pattern of brain activity in response to rapid frequency-modulated sounds. We examined this by manipulating the direction (rise vs. fall) and the rate (fast vs. slow) of the apparent pitch of iterated rippled noise (IRN) bursts. Acoustic parameters were selected to capture features used in phoneme contrasts, however the stimuli themselves were not perceived as speech per se. Participants were scanned as they passively listened to sounds in an event-related paradigm. Univariate analyses revealed a greater level and extent of activation in bilateral auditory cortex in response …

Dopaminergic Medication Impairs Feedback-Based Stimulus-Response Learning But Not Response Selection In Parkinson's Disease., Andrew Vo, Nole M Hiebert, Ken N Seergobin, Stephanie Solcz, Allison Partridge, Penny A Macdonald

Brain and Mind Institute Researchers' Publications

Cognitive dysfunction is a feature of Parkinson's Disease (PD). Some cognitive functions are impaired by dopaminergic medications prescribed to address the movement symptoms that typify PD. Learning appears to be the cognitive function most frequently worsened by dopaminergic therapy. However, this result could reflect either impairments in learning (i.e., acquisition of associations among stimuli, responses, and outcomes) or deficits in performance based on learning (e.g., selecting responses). We sought to clarify the specific effects of dopaminergic medication on (a) stimulus-response association learning from outcome feedback and (b) response selection based on learning, in PD. We tested 28 PD patients on …

Rule-Based Category Learning In Children: The Role Of Age And Executive Functioning., Rahel Rabi, John Paul Minda

Brain and Mind Institute Researchers' Publications

Rule-based category learning was examined in 4-11 year-olds and adults. Participants were asked to learn a set of novel perceptual categories in a classification learning task. Categorization performance improved with age, with younger children showing the strongest rule-based deficit relative to older children and adults. Model-based analyses provided insight regarding the type of strategy being used to solve the categorization task, demonstrating that the use of the task appropriate strategy increased with age. When children and adults who identified the correct categorization rule were compared, the performance deficit was no longer evident. Executive functions were also measured. While both working …

Biomarkers Of Alzheimer's Disease Risk In Peripheral Tissues; Focus On Buccal Cells, Maxime François, Wayne Leifert, Ralph Martins, Philip Thomas, Michael Fenech

Research outputs 2014 to 2021

Alzheimer's disease (AD) is a progressive degenerative disorder of the brain and is the most common form of dementia. To-date no simple, inexpensive and minimally invasive procedure is available to confirm with certainty the early diagnosis of AD prior to the manifestations of symptoms characteristic of the disease. Therefore, if population screening of individuals is to be performed, more suitable, easily accessible tissues would need to be used for a diagnostic test that would identify those who exhibit cellular pathology indicative of mild cognitive impairment (MCI) and AD risk so that they can be prioritized for primary prevention. This need …

Altered Cytological Parameters In Buccal Cells From Individuals With Mild Cognitive Impairment And Alzheimer's Disease, Maxime François, Wayne Leifert, Jane Hecker, Jeffrey Faunt, Ralph Martins, Philip Thomas, Michael Fenech

Research outputs 2014 to 2021

Previous studies have shown that mild cognitive impairment (MCI) may be reflective of the early stages of more pronounced neurodegenerative disorders such as Alzheimer's disease (AD). There is a need for a minimally invasive and inexpensive diagnostic to identify those who exhibit cellular pathology indicative of MCI and AD risk so that they can be prioritized for primary preventative measures. The hypothesis was that a minimally invasive approach using cytological markers in isolated buccal mucosa cells can be used to identify individuals of both MCI and AD. An automated buccal cell assay was developed using laser scanning cytometry (LSC) to …

Empirical Models Of Scalp-Eeg Responses Using Non-Concurrent Intracranial Responses, Komalpreet Kaur, Jerry J. Shih, Dean J. Krusienski

Electrical & Computer Engineering Faculty Publications

Objective- This study presents inter-subject models of scalp-recorded electroencephalographic (sEEG) event-related potentials (ERPs) using intracranially recorded ERPs from electrocorticography and stereotactic depth electrodes in the hippocampus, generally termed as intracranial EEG (iEEG).

Approach- The participants were six patients with medically-intractable epilepsy that underwent temporary placement of intracranial electrode arrays to localize seizure foci. Participants performed one experimental session using a brain-computer interface matrix spelling paradigm controlled by sEEG prior to the iEEG electrode implantation, and one or more identical sessions controlled by iEEG after implantation. All participants were able to achieve excellent spelling accuracy using sEEG, four of the participants …

Pediatric Super-Refractory Status Epilepticus Treated With Allopregnanolone, Eileen Broomall, Joanne Natale, Michele Grimason, Joshua Goldstein, Craig Smith, Celia Chang, Stephen Kanes, Michael Rogawski, Mark Wainwright

Michael A. Rogawski

Super-refractory status epilepticus is a life-threatening condition. Resistance to benzodiazepine and barbiturate treatment for this disorder is thought to be due to internalization of synaptic GABA-A receptors, and withdrawal of benzodiazepines and barbiturates during treatment often triggers seizure recurrence. The neurosteroid allopregnanolone acts as a positive allosteric modulator of synaptic and extrasynaptic GABA-A receptors. Here we describe the use of allopregnanolone in two pediatric patients with super-refractory status epilepticus. This treatment allowed the general anesthetic infusions to be weaned with resolution of status epilepticus. This is the first report of allopregnanolone use to treat status epilepticus in children.

The Potential Of Antiseizure Drugs And Agents That Act On Novel Molecular Targets As Antiepileptogenic Treatments, Rafal M. Kaminski, Michael A. Rogawski, Henrik Klitgaard

Michael A. Rogawski

A major goal of contemporary epilepsy research is the identification of therapies to prevent the development of recurrent seizures in individuals at risk, including those with brain injuries, infections, or neoplasms; status epilepticus; cortical dysplasias; or genetic epilepsy susceptibility. In this review we consider the evidence largely from preclinical models for the antiepileptogenic activity of a diverse range of potential therapies, including some marketed antiseizure drugs, as well as agents that act by immune and inflammatory mechanisms; reduction of oxidative stress; activation of the mammalian target of rapamycin or peroxisome proliferator-activated receptors γ pathways; effects on factors related to thrombolysis, …