Medicine and Health Sciences Commons^™

Mechanical Loading And Hyperosmolarity As A Daily Resetting Cue For Skeletal Circadian Clocks, Michal Dudek, Dharshika R J Pathiranage, Beatriz Bano-Otalora, Anna Paszek, Natalie Rogers, Cátia F Gonçalves, Craig Lawless, Dong Wang, Zhuojing Luo, Liu Yang, Farshid Guilak, Judith A Hoyland, Qing-Jun Meng

2020-Current year OA Pubs

Daily rhythms in mammalian behaviour and physiology are generated by a multi-oscillator circadian system entrained through environmental cues (e.g. light and feeding). The presence of tissue niche-dependent physiological time cues has been proposed, allowing tissues the ability of circadian phase adjustment based on local signals. However, to date, such stimuli have remained elusive. Here we show that daily patterns of mechanical loading and associated osmotic challenge within physiological ranges reset circadian clock phase and amplitude in cartilage and intervertebral disc tissues in vivo and in tissue explant cultures. Hyperosmolarity (but not hypo-osmolarity) resets clocks in young and ageing skeletal tissues …

Liposome-Based Carriers For Crispr Genome Editing, Xing Yin, Romain Harmancey, David D Mcpherson, Hyunggun Kim, Shao-Ling Huang

Journal Articles

The CRISPR-based genome editing technology, known as clustered regularly interspaced short palindromic repeats (CRISPR), has sparked renewed interest in gene therapy. This interest is accompanied by the development of single-guide RNAs (sgRNAs), which enable the introduction of desired genetic modifications at the targeted site when used alongside the CRISPR components. However, the efficient delivery of CRISPR/Cas remains a challenge. Successful gene editing relies on the development of a delivery strategy that can effectively deliver the CRISPR cargo to the target site. To overcome this obstacle, researchers have extensively explored non-viral, viral, and physical methods for targeted delivery of CRISPR/Cas9 and …

Genome-Wide Association Analysis Identifies Ancestry-Specific Genetic Variation Associated With Acute Response To Metformin And Glipizide In Sugar-Mgh, Josephine H Li, Laura N Brenner, Varinderpal Kaur, Katherine Figueroa, Philip Schroeder, Alicia Huerta-Chagoya, Miriam S Udler, Aaron Leong, Josep M Mercader, Jose C Florez

Journal Articles

AIMS/HYPOTHESIS: Characterisation of genetic variation that influences the response to glucose-lowering medications is instrumental to precision medicine for treatment of type 2 diabetes. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH) examined the acute response to metformin and glipizide in order to identify new pharmacogenetic associations for the response to common glucose-lowering medications in individuals at risk of type 2 diabetes.

METHODS: One thousand participants at risk for type 2 diabetes from diverse ancestries underwent sequential glipizide and metformin challenges. A genome-wide association study was performed using the Illumina Multi-Ethnic Genotyping …

Cueing Natural Event Boundaries Improves Memory In People With Post-Traumatic Stress Disorder, Barbara L Pitts, Michelle L Eisenberg, Heather R Bailey, Jeffrey M Zacks

2020-Current year OA Pubs

People with post-traumatic stress disorder (PTSD) often report difficulty remembering information in their everyday lives. Recent findings suggest that such difficulties may be due to PTSD-related deficits in parsing ongoing activity into discrete events, a process called event segmentation. Here, we investigated the causal relationship between event segmentation and memory by cueing event boundaries and evaluating its effect on subsequent memory in people with PTSD. People with PTSD (n = 38) and trauma-matched controls (n = 36) watched and remembered videos of everyday activities that were either unedited, contained visual and auditory cues at event boundaries, or contained visual and …

Errorless, Errorful, And Retrieval Practice For Naming Treatment In Aphasia: A Scoping Review Of Learning Mechanisms And Treatment Ingredients, Kristen Nunn, Sofia Vallila-Rohter, Erica L. Middleton

Moss-Magee Rehabilitation Papers

PURPOSE: Increasingly, mechanisms of learning are being considered during aphasia rehabilitation. Well-characterized learning mechanisms can inform "how" interventions should be administered to maximize the acquisition and retention of treatment gains. This systematic scoping review mapped hypothesized mechanisms of action (MoAs) and treatment ingredients in three learning-based approaches targeting naming in aphasia: errorless learning (ELess), errorful learning (EFul), and retrieval practice (RP). The rehabilitation treatment specification system was leveraged to describe available literature and identify knowledge gaps within a unified framework.

METHOD: PubMed and CINHAL were searched for studies that compared ELess, EFul, and/or RP for naming in aphasia. Independent reviewers …

Fakestack: Hierarchical Tri-Bert-Cnn-Lstm Stacked Model For Effective Fake News Detection., Ashfia Jannat Keya, Hasibul Hossain Shajeeb, Md Saifur Rahman, M F Mridha

Journal Articles

False news articles pose a serious challenge in today's information landscape, impacting public opinion and decision-making. Efforts to counter this issue have led to research in deep learning and machine learning methods. However, a gap exists in effectively using contextual cues and skip connections within models, limiting the development of comprehensive detection systems that harness contextual information and vital data propagation. Thus, we propose a model of deep learning, FakeStack, in order to identify bogus news accurately. The model combines the power of pre-trained Bidirectional Encoder Representation of Transformers (BERT) embeddings with a deep Convolutional Neural Network (CNN) having skip …

A Central Alarm System That Gates Multi-Sensory Innate Threat Cues To The Amygdala, Sukjae J Kang, Shijia Liu, Mao Ye, Dong-Il Kim, Gerald M Pao, Bryan A Copits, Benjamin Z Roberts, Kuo-Fen Lee, Michael R Bruchas, Sung Han

2020-Current year OA Pubs

Perception of threats is essential for survival. Previous findings suggest that parallel pathways independently relay innate threat signals from different sensory modalities to multiple brain areas, such as the midbrain and hypothalamus, for immediate avoidance. Yet little is known about whether and how multi-sensory innate threat cues are integrated and conveyed from each sensory modality to the amygdala, a critical brain area for threat perception and learning. Here, we report that neurons expressing calcitonin gene-related peptide (CGRP) in the parvocellular subparafascicular nucleus in the thalamus and external lateral parabrachial nucleus in the brainstem respond to multi-sensory threat cues from various …

Apples To Apples? Neural Correlates Of Emotion Regulation Differences Between High- And Low-Risk Adolescents, Michael T Perino, João F Guassi Moreira, Ethan M Mccormick, Eva H Telzer

2010-2019 OA Pubs

Adolescence has been noted as a period of increased risk taking. The literature on normative neurodevelopment implicates aberrant activation of affective and regulatory regions as key to inhibitory failures. However, many of these studies have not included adolescents engaging in high rates of risky behavior, making generalizations to the most at-risk populations potentially problematic. We conducted a comparative study of nondelinquent community (n = 24, mean age = 15.8 years, 12 female) and delinquent adolescents (n = 24, mean age = 16.2 years, 12 female) who completed a cognitive control task during functional magnetic resonance imaging, where behavioral inhibition was …

Reward Improves Response Inhibition By Enhancing Attentional Capture, Yanqing Wang, Todd S Braver, Shouhang Yin, Xueping Hu, Xiangpeng Wang, Antao Chen

2010-2019 OA Pubs

Reward plays a crucial role in enhancing response inhibition. While it is generally assumed that the process of response inhibition involves attentional capture and the stopping of action, it is unclear whether this reflects a direct impact of reward on response inhibition or rather an indirect mediation via attentional capture. Here, we employed a revised stop-signal task (SST) that separated these two cognitive elements, by including a continue signal that required the same motor response as in go trials, but also attention to a cue, as in stop trials. We first confirmed the engagement of the right inferior frontal gyrus …

Vocabulary Learning Benefits From Rem After Slow-Wave Sleep., Laura J Batterink, Carmen E Westerberg, Ken A Paller

Brain and Mind Institute Researchers' Publications

Memory reactivation during slow-wave sleep (SWS) influences the consolidation of recently acquired knowledge. This reactivation occurs spontaneously during sleep but can also be triggered by presenting learning-related cues, a technique known as targeted memory reactivation (TMR). Here we examined whether TMR can improve vocabulary learning. Participants learned the meanings of 60 novel words. Auditory cues for half the words were subsequently presented during SWS in an afternoon nap. Memory performance for cued versus uncued words did not differ at the group level but was systematically influenced by REM sleep duration. Participants who obtained relatively greater amounts of REM showed a …

N-Acetylcysteine Reduces Cocaine-Cue Attentional Bias And Differentially Alters Cocaine Self-Administration Based On Dosing Order, B. Levi Bolin, Joseph L. Alcorn Iii, Joshua A. Lile, Craig R. Rush, Abner O. Rayapati, Lon R. Hays, William W. Stoops

Behavioral Science Faculty Publications

Background—Disrupted glutamate homeostasis is thought to contribute to cocaine-use disorder, in particular, by enhancing the incentive salience of cocaine stimuli. n-Acetylcysteine might be useful in cocaine-use disorder by normalizing glutamate function. In prior studies, n-acetylcysteine blocked the reinstatement of cocaine seeking in laboratory animals and reduced the salience of cocaine stimuli and delayed relapse in humans.

Methods—The present study determined the ability of maintenance on n-acetylcysteine (0 or 2400 mg/day, counterbalanced) to reduce the incentive salience of cocaine stimuli, as measured by an attentional bias task, and attenuate intranasal cocaine self-administration (0, 30, and 60 mg). Fourteen individuals …

A Pilot Investigation Of Acute Inhibitory Control Training In Cocaine Users, Joseph L. Alcorn, Erika Pike, William W. Stoops, Joshua A. Lile, Craig R. Rush

Behavioral Science Faculty Publications

Background—Disrupted response inhibition and presence of drug-cue attentional bias in cocaine-using individuals have predicted poor treatment outcomes. Inhibitory control training could help improve treatment outcomes by strengthening cognitive control. This pilot study assessed the effects of acute inhibitory control training to drug- and non-drug-related cues on response inhibition performance and cocaine-cue attentional bias in cocaine-using individuals.

Methods—Participants who met criteria for a cocaine-use disorder underwent five sessions of inhibitory control training to either non-drug-related cues (i.e., rectangles) or cocaine cues (n=10/condition) in a single day. Response inhibition and attentional bias were assessed prior to and following training using …

Sleep-Based Memory Processing Facilitates Grammatical Generalization: Evidence From Targeted Memory Reactivation., Laura J Batterink, Ken A Paller

Brain and Mind Institute Researchers' Publications

Generalization-the ability to abstract regularities from specific examples and apply them to novel instances-is an essential component of language acquisition. Generalization not only depends on exposure to input during wake, but may also improve offline during sleep. Here we examined whether targeted memory reactivation during sleep can influence grammatical generalization. Participants gradually acquired the grammatical rules of an artificial language through an interactive learning procedure. Then, phrases from the language (experimental group) or stimuli from an unrelated task (control group) were covertly presented during an afternoon nap. Compared to control participants, participants re-exposed to the language during sleep showed larger …

Gene Networks Activated By Specific Patterns Of Action Potentials In Dorsal Root Ganglia Neurons, P Lee, J Cohen, Dumitru Iacobas, Sanda Iacobas, R Fields

NYMC Faculty Publications

Gene regulatory networks underlie the long-term changes in cell specification, growth of synaptic connections, and adaptation that occur throughout neonatal and postnatal life. Here we show that the transcriptional response in neurons is exquisitely sensitive to the temporal nature of action potential firing patterns. Neurons were electrically stimulated with the same number of action potentials, but with different inter-burst intervals. We found that these subtle alterations in the timing of action potential firing differentially regulates hundreds of genes, across many functional categories, through the activation or repression of distinct transcriptional networks. Our results demonstrate that the transcriptional response in neurons …

Rat Behavioral Discrimination Of Temporal Cues In Species-Specific Vocalization, Kevin Mathews Tharakan

Honors Scholar Theses

Current behavioral and neurophysiologic studies propose that many animals can detect and discriminate the invariant statistics found in natural vocalization (Geffen et. al., 2011; Rodriguez et al., 2010). However, according to current research the neuronal mechanisms underlying the sound discrimination process is still unclear. While numerous auditory statistics have been manipulated, none has varied the temporal and tonal frequency cues independently in their synthetic call sequences, thus it is still uncertain whether rats rely on temporal cues in the sound envelope for communication.

The aim of this research is to determine whether or not rats rely on temporal cues in …

Effects Of A Consistent Target Or Masker Voice On Target Speech Intelligibility In Two- And Three-Talker Mixtures., Fabienne Samson, Ingrid S Johnsrude

Brain and Mind Institute Researchers' Publications

When the spatial location or identity of a sound is held constant, it is not masked as effectively by competing sounds. This suggests that experience with a particular voice over time might facilitate perceptual organization in multitalker environments. The current study examines whether listeners benefit from experience with a voice only when it is the target, or also when it is a masker, using diotic presentation and a closed-set task (coordinate response measure). A reliable interaction was observed such that, in two-talker mixtures, consistency of masker or target voice over 3-7 trials significantly benefited target recognition performance, whereas in three-talker …

Phase Of Spontaneous Slow Oscillations During Sleep Influences Memory-Related Processing Of Auditory Cues., Laura J Batterink, Jessica D Creery, Ken A Paller

Brain and Mind Institute Researchers' Publications

UNLABELLED: Slow oscillations during slow-wave sleep (SWS) may facilitate memory consolidation by regulating interactions between hippocampal and cortical networks. Slow oscillations appear as high-amplitude, synchronized EEG activity, corresponding to upstates of neuronal depolarization and downstates of hyperpolarization. Memory reactivations occur spontaneously during SWS, and can also be induced by presenting learning-related cues associated with a prior learning episode during sleep. This technique, targeted memory reactivation (TMR), selectively enhances memory consolidation. Given that memory reactivation is thought to occur preferentially during the slow-oscillation upstate, we hypothesized that TMR stimulation effects would depend on the phase of the slow oscillation. Participants learned …

Categorizing Fetal Heart Rate Variability With And Without Visual Aids, Amanda J. Ashdown, Mark W. Scerbo, Lee A. Belfore Ii, Stephen S. Davis, Alfred Z. Abuhamad

Psychology Faculty Publications

Objective This study examined the ability of clinicians to correctly categorize images of fetal heart rate (FHR) variability with and without the use of exemplars.

Study Design A sample of 33 labor and delivery clinicians inspected static FHR images and categorized them into one of four categories defined by the National Institute of Child Health and Human Development (NICHD) based on the amount of variability within absent, minimal, moderate, or marked ranges. Participants took part in three conditions: two in which they used exemplars representing FHR variability near the center or near the boundaries of each range, and a third …

Equal-Magnitude Size-Weight Illusions Experienced Within And Between Object Categories., Gavin Buckingham, Melvyn A Goodale, Justin A White, David A Westwood

Brain and Mind Institute Researchers' Publications

In the size-weight illusion (SWI), small objects feel heavier than larger objects of the same mass. This effect is typically thought to be a consequence of the lifter's expectation that the large object will outweigh the small object, because objects of the same type typically get heavier as they get larger. Here, we show that this perceptual effect can occur across object category, where there are no strong expectations about the correspondence between size and mass. One group of participants lifted same-colored large and small cubes with the same mass as one another, while another group lifted differently-colored large and …

Search Strategies Used By Older Adults In A Virtual Reality Place Learning Task, Rebecca L. Davis, Catherine Weisbeck

Peer Reviewed Articles

Purpose of the study: Older adults often have problems finding their way in novel environments such as senior living residences and hospitals. The purpose of this study was to examine the types of self-reported search strategies and cues that older adults use to find their way in a virtual maze

Design and Methods: Healthy, independently living older adults (n = 129) aged 55–96 were tested in a virtual maze task over a period of 3 days in which they had to repeatedly find their way to a specified goal. They were interviewed about their strategies on days 1 and 3. …

Deficits In Audiovisual Speech Perception In Normal Aging Emerge At The Level Of Whole-Word Recognition., Ryan A Stevenson, Caitlin E Nelms, Sarah H Baum, Lilia Zurkovsky, Morgan D Barense, Paul A Newhouse, Mark T Wallace

Brain and Mind Institute Researchers' Publications

Over the next 2 decades, a dramatic shift in the demographics of society will take place, with a rapid growth in the population of older adults. One of the most common complaints with healthy aging is a decreased ability to successfully perceive speech, particularly in noisy environments. In such noisy environments, the presence of visual speech cues (i.e., lip movements) provide striking benefits for speech perception and comprehension, but previous research suggests that older adults gain less from such audiovisual integration than their younger peers. To determine at what processing level these behavioral differences arise in healthy-aging populations, we administered …

Effector-Independent Motor Sequence Representations Exist In Extrinsic And Intrinsic Reference Frames., Tobias Wiestler, Sheena Waters-Metenier, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

Many daily activities rely on the ability to produce meaningful sequences of movements. Motor sequences can be learned in an effector-specific fashion (such that benefits of training are restricted to the trained hand) or an effector-independent manner (meaning that learning also facilitates performance with the untrained hand). Effector-independent knowledge can be represented in extrinsic/world-centered or in intrinsic/body-centered coordinates. Here, we used functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis to determine the distribution of intrinsic and extrinsic finger sequence representations across the human neocortex. Participants practiced four sequences with one hand for 4 d, and then performed these sequences …

A Dedicated Binding Mechanism For The Visual Control Of Movement., Alexandra Reichenbach, David W Franklin, Peter Zatka-Haas, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

The human motor system is remarkably proficient in the online control of visually guided movements, adjusting to changes in the visual scene within 100 ms [1-3]. This is achieved through a set of highly automatic processes [4] translating visual information into representations suitable for motor control [5, 6]. For this to be accomplished, visual information pertaining to target and hand need to be identified and linked to the appropriate internal representations during the movement. Meanwhile, other visual information must be filtered out, which is especially demanding in visually cluttered natural environments. If selection of relevant sensory information for online control …

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 …

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 …

Two-Category Place Representations Persist Over Body Rotations, Hyoun Kyoung Pyoun, Jesse Sargent, Stephen Dopkins, John W. Philbeck

Neurological Surgery Faculty Publications

We explored a system that constructs environment-centered frames of reference and coordinates memory for the azimuth of an object in an enclosed space. For one group, we provided two environmental cues (doors): one in the front, and one in the rear. For a second group, we provided two object cues: a front and a rear cue.For a third group, we provided no external cues; we assumed that for this group, their reference frames would be determined by the orthogonal geometry of the floor-and-wall junction that divides a space in half or into multiple territories along the horizontal …

Sweetened Drink And Snacking Cues In Adolescents. A Study Using Ecological Momentary Assessment, Jerry L. Grenard, Alan W. Stacy, Saul Shiffman, Amanda N. Baraldi, David P. Mackinnon, Ginger Lockhart, Yasemin Kisbu-Sakarya, Sarah Boyle Abd, Yuliyana Beleva Abd, Carol Koprowski, Susan L. Ames, Kim D. Reynolds

CGU Faculty Publications and Research

The objective of this study was to identify physical, social, and intrapersonal cues that were associated with the consumption of sweetened beverages and sweet and salty snacks among adolescents from lower SES neighborhoods. Students were recruited from high schools with a minimum level of 25% free or reduced cost lunches. Using ecological momentary assessment, participants (N=158) were trained to answer brief questionnaires on handheld PDA devices: (a) each time they ate or drank, (b) when prompted randomly, and (c) once each evening. Data were collected over 7days for each participant. Participants reported their location (e.g., school grounds, home), mood, social …

Perceptual Fluency Can Be Used As A Cue For Categorization Decisions., Sarah J Miles, John Paul Minda

Brain and Mind Institute Researchers' Publications

Learning in the prototype distortion task is thought to involve perceptual learning in which category members experience an enhanced visual response (Ashby & Maddox. Annual Review of Psychology, 56, 149-178, 2005). This response likely leads to more-efficient processing, which in turn may result in a feeling of perceptual fluency for category members. We examined the perceptual-fluency hypothesis by manipulating fluency independently from category membership. We predicted that when perceptual fluency was induced using subliminal priming, this fluency would be misattributed to category membership and would affect categorization decisions. In a prototype distortion task, the participants were more likely to judge …

Dominance Of The Proximal Coordinate Frame In Determining The Locations Of Hippocampal Place Cell Activity During Navigation, Jennifer J Siegel, Joshua P Neunuebel, James J Knierim

Journal Articles

The place-specific activity of hippocampal cells provides downstream structures with information regarding an animal's position within an environment and, perhaps, the location of goals within that environment. In rodents, recent research has suggested that distal cues primarily set the orientation of the spatial representation, whereas the boundaries of the behavioral apparatus determine the locations of place activity. The current study was designed to address possible biases in some previous research that may have minimized the likelihood of observing place activity bound to distal cues. Hippocampal single-unit activity was recorded from six freely moving rats as they were trained to perform …