Life Sciences Commons^™

Immediate Neurophysiological Effects Of Transcranial Electrical Stimulation, Anli Liu, Mihály Vöröslakos, Gregory Kronberg, Simon Henin, Matthew R. Krause, Yu Huang, Alexander Opitz, Ashesh Mehta, Christopher C. Pack, Bart Krekelberg, Antal Berényi, Lucas C. Parra, Lucia Melloni, Orrin Devinsky, György Buzsáki

Publications and Research

Noninvasive brain stimulation techniques are used in experimental and clinical fields for their potential effects on brain network dynamics and behavior. Transcranial electrical stimulation (TES), including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), has gained popularity because of its convenience and potential as a chronic therapy. However, a mechanistic understanding of TES has lagged behind its widespread adoption. Here, we review data and modelling on the immediate neurophysiological effects of TES in vitro as well as in vivo in both humans and other animals. While it remains unclear how typical TES protocols affect neural activity, we …

Contextual Fear Memory Modulates Psd95 Phosphorylation, Ampar Subunits, Pkmζ And Pi3k Differentially Between Adult And Juvenile Rats, Roseanna M. Zanca, Shirley Sanay, Jorge A. Avila, Edgar Rodriguez, Harry N. Shair, Peter A. Serrano

Publications and Research

It is well known that young organisms do not maintain memories as long as adults, but the mechanisms for this ontogenetic difference are undetermined. Previous work has revealed that the α-amino-3-hydroxy-5-methyl-4isoxazolepropionic acidreceptor (AMPAr)subunits aretraffickedinto the synaptic membranefollowing memory retrieval in adults. Additionally, phosphorylated PSD-95-pS295 promotes AMPAr stabilization at the synapse. We investigated these plasticity related proteins as potential mediators in the differential contextual stress memory retrieval capabilities observed between adult and juvenile rats. Rats were assigned to either pedestal stress (1h) or no stress control (home cage). Each animal was placed alone in an open field for 5minat the base …

Identification And Characterization Of Early Photoreceptor Cis-Regulatory Elements And Their Relation To Onecut1, Nathalie Jean-Charles, Diego F. Buenaventura, Mark M. Emerson

Publications and Research

Background: Cone and rod photoreceptors are two of the primary cell types affected in human retinal disease. Potential strategies to combat these diseases are the use of gene therapy to rescue compromised photoreceptors or to generate new functional photoreceptors to replace those lost in the diseased retina. Cis-regulatory elements specific to cones, rods, or both types of photoreceptors are critical components of successful implementation of these two strategies. The purpose of this study was to identify and characterize the cell type specificity and activity of cis-regulatory elements active in developing photoreceptors.

Methods: Cis-regulatory elements were introduced into the developing chicken …

Association Of The Haptoglobin Gene Polymorphism With Cognitive Function And Decline In Elderly African American Adults With Type 2 Diabetes: Findings From The Action To Control Cardiovascular Risk In Diabetes–Memory In Diabetes (Accord-Mind) Study, Michael Beeri, Hung-Mo Lin, Mary Sano, Ramit Ravona-Springer, Xiaoyu Liu, Barbara B. Bendlin, Carey E. Gleason, Elizabeth Guerrero-Berroa, Laili Soleimani, Lenore J. Launer, Scott Ehrenberg, Orit Lache, Yaakov K. Seligman, Andrew P. Levy

Publications and Research

IMPORTANCE African American individuals have higher dementia risk than individuals of white race/ethnicity. They also have higher rates of type 2 diabetes, which may contribute to this elevated risk. This study examined the association of the following 2 classes of alleles at the haptoglobin (Hp) locus that are associated with poor cognition, cardiovascular disease, and mortality: Hp 1-1 (associated with poor cognition and cerebrovascular disease) and Hp 2-1 and Hp 2-2 (associated with greater risk ofmyocardial infarction and mortality). An additional polymorphism in the promoter region of the Hp 2 allele, restricted to individuals of African descent, yields a fourth …

Manipulation Of Human Verticality Using High-Definition Transcranial Direct Current Stimulation, Taiza E. G. Santos, Diandra B. Favoretto, Iman Ghodratti Toostani, Diego C. Nascimento, Brunna P. Rimoli, Eduardo Bergonzoni, Tenysson Will Lemos, Dennis Quangvinh Truong, Alexandre C. B. Delbem, Bahador Makkiabadi, Renato Moraes, Francisco Louzada, Marom Bikson, Joao P. Leite, Dylan J. Edwards

Publications and Research

Background: Using conventional tDCS over the temporo-parietal junction (TPJ) we previously reported that it is possible to manipulate subjective visual vertical (SVV) and postural control. We also demonstrated that high-definition tDCS (HD-tDCS) can achieve substantially greater cortical stimulation focality than conventional tDCS. However, it is critical to establish dose-response effects using well-defined protocols with relevance to clinically meaningful applications.

Objective: To conduct three pilot studies investigating polarity and intensity-dependent effects of HD-tDCS over the right TPJ on behavioral and physiological outcome measures in healthy subjects. We additionally aimed to establish the feasibility, safety, and tolerability of this stimulation protocol.

Methods: …

Hyperphosphorylation Of Tau Associates With Changes In Its Function Beyond Microtubule Stability, Alejandra D. Alonso, Leah S. Cohen, Christopher Corbo, Viktoriya Morozova, Abdeslem Elldrissi, Greg R. Phillips, Frida E. Kleiman

Publications and Research

Tau is a neuronal microtubule associated protein whose main biological functions are to promote microtubule self-assembly by tubulin and to stabilize those already formed. Tau also plays an important role as an axonal microtubule protein. Tau is an amazing protein that plays a key role in cognitive processes, however, deposits of abnormal forms of tau are associated with several neurodegenerative diseases, including Alzheimer disease (AD), the most prevalent, and Chronic Traumatic Encephalopathy (CTE) and Traumatic Brain Injury (TBI), the most recently associated to abnormal tau. Tau post-translational modifications (PTMs) are responsible for its gain of toxic function. Alonso et al. …

Developmental Transitions In Amygdala Pkc Isoforms And Ampa Receptor Expression Associated With Threat Memory In Infant Rats, Maya Opendak, Roseanna M. Zanca, Eben Anane, Peter Serrano, Regina M. Sullivan

Publications and Research

Although infants learn and remember, they rapidly forget, a phenomenon known as infantile amnesia. While myriad mechanisms impact this rapid forgetting, the molecular events supporting memory maintenance have yet to be explored. To explore memory mechanisms across development, we used amygdala-dependent odor-shock conditioning and focused on mechanisms important in adult memory, the AMPA receptor subunits GluA1/2 and upstream protein kinases important for trafficking AMPAR, protein kinase M zeta (PKMζ) and iota/lambda (PKCι/λ). We use odor-shock conditioning in infant rats because it is late-developing (postnatal day, PN10) and can be modulated by corticosterone during a sensitive period in early life. Our …

The Impact Of Perineuronal Net Digestion Using Chondroitinase Abc On The Intrinsic Physiology Of Cortical Neurons, Philip Chu, Reena Abraham, Kumarie Budhu, Usma Khan, Natalie De Marco Garcia, Joshua C. Brumberg

Publications and Research

Perineuronal nets (PNNs) are a form of aggregate Extracellular Matrix (ECM) in the brain. Recent evidence suggests that the postnatal deposition of PNNs may play an active role in regulating neuroplasticity and, potentially, neurological disorders. Observations of high levels of PNNs expression around somas, proximal dendrites, and axon initial segments of a subtype of neurons have also led to proposals that PNNs may modulate the intrinsic properties of the neurons they ensheathe. While high levels of PNNs are postnatally expressed throughout the neocortex, it is still unclear how they impact the neuronal physiology of the many classes and subtypes of …

Tributyltin Inhibits Neural Induction Of Human Induced Pluripotent Stem Cells, Shigeru Yamada, Yusuke Kubo, Daiju Yamazaki, Yuko Sekino, Yoko Nomura, Sachiko Yoshida, Yusunari Kanda

Publications and Research

Tributyltin (TBT), one of the organotin compounds, is a well-known environmental pollutant. In our recent study, we reported that TBT induces mitochondrial dysfunction, in human-induced pluripotent stem cells (iPSCs) through the degradation of mitofusin1 (Mfn1), which is a mitochondrial fusion factor. However, the effect of TBT toxicity on the developmental process of iPSCs was not clear. The present study examined the effect of TBT on the differentiation of iPSCs into the ectodermal, mesodermal, and endodermal germ layers. We found that exposure to nanomolar concentration of TBT (50 nM) selectively inhibited the induction of iPSCs into the ectoderm, which is the …

An Interview With Cesare Montecucco, Mandë Holford, Andreas Rummel

Publications and Research

Cesare Montecucco is a member of the board of various leading scientific journals. His research focus is on the regeneration of the peripheral nervous system and on the mechanisms of action of toxins and related diseases, including tetanus, botulism, anthrax and Helicobacter pylori-associated diseases. In this interview, we talked to Cesare Montecucco about his career, learning and culture.

Prmt5-Mediated Regulation Of Developmental Myelination, Antonella Scaglione, Julia Patzig, Jialiang Liang, Rebecca Frawley, Jabez Bok, Angeliki Mela, Camila Yattah, Jingxian Zhang, Shun Xie Teo, Ting Zhou, Shuibing Chen, Emily Bernstein, Peter Canoll, Ernesto Guccione, Patricia Casaccia

Publications and Research

Oligodendrocytes (OLs) are the myelin-forming cells of the central nervous system. They are derived from differentiation of oligodendrocyte progenitors through a process requiring cell cycle exit and histone modifications. Here we identify the histone arginine methyl-transferase PRMT5, a molecule catalyzing symmetric methylation of histone H4R3, as critical for developmental myelination. PRMT5 pharmacological inhibition, CRISPR/cas9 targeting, or genetic ablation decrease p53-dependent survival and impair differentiation without affecting proliferation. Conditional ablation of Prmt5 in progenitors results in hypomyelination, reduced survival and differentiation. Decreased histone H4R3 symmetric methylation is followed by increased nuclear acetylation of H4K5, and is rescued by pharmacological inhibition of …

Direct Current Stimulation Of Endothelial Monolayers Induces A Transient And Reversible Increase In Transport Due To The Electroosmotic Effect, Limary M. Cancel, Katherin Arias, Marom Bikson, John M. Tarbell

Publications and Research

We investigated the effects of direct current stimulation (DCS) on fluid and solute transport across endothelial cell (EC) monolayers in vitro. Our motivation was transcranial direct current stimulation (tDCS) that has been investigated for treatment of neuropsychiatric disorders, to enhance neurorehabilitation, and to change cognition in healthy subjects. The mechanisms underlying this diversity of applications remain under investigation. To address the possible role of blood-brain barrier (BBB) changes during tDCS, we applied direct current to cultured EC monolayers in a specially designed chamber that generated spatially uniform direct current. DCS induced fluid and solute movement across EC layers that persisted …

Carbonic Anhydrase Inhibition Selectively Prevents Amyloid B Neurovascular Mitochondrial Toxicity, María E. Solesio, Pablo M. Peixoto, Ludovic Debure, Stephen M. Madamba, Mony J. De Leon, Thomas Wisniewski, Evgeny V. Pavlov, Silvia Fossati

Publications and Research

Mounting evidence suggests that mitochondrial dysfunction plays a causal role in the etiology and progression of Alzheimer’s disease (AD). We recently showed that the carbonic anhydrase inhibitor (CAI) methazolamide (MTZ) prevents amyloid b (Ab)-mediated onset of apoptosis in the mouse brain. In this study, we used MTZ and, for the first time, the analog CAI acetazolamide (ATZ) in neuronal and cerebral vascular cells challenged with Ab, to clarify their protective effects and mitochondrial molecular mechanism of action. The CAIs selectively inhibited mitochondrial dysfunction pathways induced by Ab, without affecting metabolic function. ATZ was effective at concentrations 10 times lower than …

Neural And Behavioral Correlates Of Attentional Inhibition Training And Perceptual Discrimination Training In A Visual Flanker Task, Robert D. Melara, Shalini Singh, Denise A. Hien

Publications and Research

Two groups of healthy young adults were exposed to 3 weeks of cognitive training in a modified version of the visual flanker task, one group trained to discriminate the target (discrimination training) and the other group to ignore the flankers (inhibition training). Inhibition training, but not discrimination training, led to significant reductions in both Garner interference, indicating improved selective attention, and in Stroop interference, indicating more efficient resolution of stimulus conflict. The behavioral gains from training were greatest in participants who showed the poorest selective attention at pretest. Electrophysiological recordings revealed that inhibition training increased the magnitude of Rejection Positivity …

At-Home Transcranial Direct Current Stimulation (Tdcs) With Telehealth Support For Symptom Control In Chronically-Ill Patients With Multiple Symptoms, Alexa Riggs, Vaishali Patel, Bhaskar Paneri, Russell K. Portenoy, Marom Bikson, Helena Knotkova

Publications and Research

Transcranial direct current stimulation (tDCS) delivered in multiple sessions can reduce symptom burden, but access of chronically ill patients to tDCS studies is constrained by the burden of office-based tDCS administration. Expanded access to this therapy can be accomplished through the development of interventions that allow at-home tDCS applications.

Objective: We describe the development and initial feasibility assessment of a novel intervention for the chronically ill that combines at-home tDCS with telehealth support. Methods: In the developmental phase, the tDCS procedure was adjusted for easy application by patients or their informal caregivers at home, and a tDCS protocol with specific …

Addictions, Behavioral Addictions, And Pathological Internet Use As Internet Addiction - A Literature Review, Vy K. Nguyen

Publications and Research

Excessive and pathological uses of the Internet are observed and discussed often in our modern conversations. Access to the Internet has become so convenient that these behaviors can lead to consequences in many areas of our lives from social relationships to academic and professional work performance. A common term that people use to address this pattern of behaviors is “Internet Addiction” or more specific ones, such as “Social Media Addiction” or “Online Gaming Addiction.” However, in clinical psychology, addiction has its own specific definitions. It refers to a category and set of criteria that are distinguished from other mental disorders …

The Fata Morgana Of Unconscious Perception, Marjan Persuh

Publications and Research

No abstract provided.

Working Memory And Consciousness: The Current State Of Play, Marjan Persuh, Eric Larock, Jacob Berger

Publications and Research

Working memory (WM), an important posit in cognitive science, allows one to temporarily store and manipulate information in the service of ongoing tasks. WM has been traditionally classified as an explicit memory system—that is, as operating on and maintaining only consciously perceived information. Recently, however, several studies have questioned this assumption, purporting to provide evidence for unconscious WM. In this article, we focus on visual working memory (VWM) and critically examine these studies as well as studies of unconscious perception that seem to provide indirect evidence for unconscious WM. Our analysis indicates that current evidence does not support an unconscious …

A Computational Assessment Of Target Engagement In The Treatment Of Auditory Hallucinations With Transcranial Direct Current Stimulation, Won Hee Lee, Nigel I. Kennedy, Marom Bikson, Sophia Frangou

Publications and Research

We use auditory verbal hallucinations (AVH) to illustrate the challenges in defining and assessing target engagement in the context of transcranial direct current stimulation (tDCS) for psychiatric disorders. We defined the target network as the cluster of regions of interest (ROIs) that are consistently implicated in AVH based on the conjunction of multimodal meta-analytic neuroimaging data. These were prescribed in the New York Head (a population derived model) and head models of four single individuals. We appraised two potential measures of target engagement, tDCS-induced peak electric field strength and tDCS-modulated volume defined as the percentage of the volume of the …

To Do Or Not To Do: Dopamine, Affordability And The Economics Of Opportunity, Jeff A. Beeler, Devry Mourra

Publications and Research

Five years ago, we introduced the thrift hypothesis of dopamine (DA), suggesting that the primary role of DA in adaptive behavior is regulating behavioral energy expenditure to match the prevailing economic conditions of the environment. Here we elaborate that hypothesis with several new ideas. First, we introduce the concept of affordability, suggesting that costs must necessarily be evaluated with respect to the availability of resources to the organism, which computes a value not only for the potential reward opportunity, but also the value of resources expended. Placing both costs and benefits within the context of the larger economy in which …

Liposomal Tricurin, A Synergistic Combination Of Curcumin, Epicatechin Gallate And Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, And Eliminates Glioblastoma (Gbm) And Gbm Stem Cells, Sumit Mukherjee, Juliet N. E. Baidoo, Samay Sampat, Andrew Manusco, Lovena David, Leah S. Cohen, Shuiqin Zhou, Probal Banerjee

Publications and Research

Glioblastoma (GBM) is a deadly brain tumor with a current mean survival of 12–15 months. Despite being a potent anti-cancer agent, the turmeric ingredient curcumin (C) has limited anti-tumor efficacy in vivo due to its low bioavailability. We have reported earlier a strategy involving the use two other polyphenols, epicatechin gallate (E) from green tea and resveratrol (R) from red grapes at a unique, synergistic molar ratio with C (C:E:R: 4:1:12.5, termed TriCurin) to achieve superior potency against HPV+ tumors than C alone at C:E:R (M): 32:8:100 (termed 32 M+ TriCurin). We have now prepared liposomal TriCurin (TrLp) and demonstrated …

The Variability Of Neural Responses To Naturalistic Videos Change With Age And Sex, Agustin Petroni, Samantha Cohen, Lei Ai, Nicolas Langer, Simon Henin, Tamara Vanderwal, Michael P. Milham, Lucas C. Parra

Publications and Research

Neural development is generally marked by an increase in the efficiency and diversity of neural processes. In a large sample (n=114) of human children and adults with ages ranging from 5 to 44 yr, we investigated the neural responses to naturalistic video stimuli. Videos from both real-life classroom settings and Hollywood feature films were used to probe different aspects of attention and engagement. For all stimuli, older ages were marked by more variable neural responses. Variability was assessed by the intersubject correlation of evoked electroencephalographic responses. Young males also had less-variable responses than young females. These results were replicated in …

Collective Adhesion And Displacement Of Retinal Progenitor Cells Upon Extracellular Matrix Substrates Of Transplantable Biomaterials, Ankush Thakur, Shawn Mishra, Juan Pena, Jing Zhou, Stephen Redenti, Robert Majeska, Maribel Vazquez

Publications and Research

Strategies to replace retinal photoreceptors lost to damage or disease rely upon the migration of replacement cells transplanted into sub-retinal spaces. A significant obstacle to the advancement of cell transplantation for retinal repair is the limited migration of transplanted cells into host retina. In this work, we examine the adhesion and displacement responses of retinal progenitor cells on extracellular matrix substrates found in retina as well as widely used in the design and preparation of transplantable scaffolds. The data illustrate that retinal progenitor cells exhibit unique adhesive and displacement dynamics in response to poly-l-lysine, fibronectin, laminin, hyaluronic acid, and Matrigel. …

Single Olfactory Receptors Set Odor Detection Thresholds, Adam Dewan, Annika Cichy, Jingji Zhang, Kayla Miguel, Paul Feinstein, Dmitry Rinberg, Thomas Bozza

Publications and Research

In many species, survival depends on olfaction, yet the mechanisms that underlie olfactory sensitivity are not well understood. Here we examine how a conserved subset of olfactory receptors, the trace amine-associated receptors (TAARs), determine odor detection thresholds of mice to amines. We find that deleting all TAARs, or even single TAARs, results in significant odor detection deficits. This finding is not limited to TAARs, as the deletion of a canonical odorant receptor reduced behavioral sensitivity to its preferred ligand. Remarkably, behavioral threshold is set solely by the most sensitive receptor, with no contribution from other highly sensitive receptors. In addition, …

Finding Influential Nodes For Integration In Brain Networks Using Optimal Percolation Theory, Gino Del Ferraro, Andrea Moreno, Byungjoon Min, Flaviano Morone, Úrsula Pérez-Ramírez, Laura Pérez-Cervera, Lucas C. Parra, Andrei Holodny, Santiago Canals, Hernán A. Makse

Publications and Research

Global integration of information in the brain results from complex interactions of segregated brain networks. Identifying the most influential neuronal populations that efficiently bind these networks is a fundamental problem of systems neuroscience. Here, we apply optimal percolation theory and pharmacogenetic interventions in vivo to predict and subsequently target nodes that are essential for global integration of a memory network in rodents. The theory predicts that integration in the memory network is mediated by a set of low-degree nodes located in the nucleus accumbens. This result is confirmed with pharmacogenetic inactivation of the nucleus accumbens, which eliminates the formation of …

Associations Of Lifestyle And Vascular Risk Factors With Alzheimer's Brain Biomarker Changes During Middle Age: A 3 Year Longitudinal Study In The Broader New York City Area, Michelle J. Walters, Joanna Sterling, Crystal Quinn, Christine Ganzer, Ricardo S. Osorio, Randolph D. Andrews, Dawn C. Matthews, Shankar Vallabhajosula, Mony J. De Leon, Richard S. Isaacson, Lisa Mosconi

Publications and Research

Objective To investigate the associations between lifestyle and vascular risk factors and changes in Alzheimer’s disease (AD) biomarkers (beta-amyloid load via ¹¹C-PiB PET, glucose metabolism via ¹⁸F-FDG PET and neurodegeneration via structural MRI) and global cognition in middle-aged asymptomatic participants at risk for AD.

Design Prospective, longitudinal.

Setting The study was conducted at New York University Langone/Weill Cornell Medical Centres in New York City.

Participants Seventy cognitively normal participants from multiple community sources, aged 30–60 years with lifestyle measures (diet, intellectual activity and physical activity), vascular risk measures and two imaging biomarkers visits over at least 2 years, …

Depressive Symptoms Are Associated With Cognitive Function In The Elderly With Type 2 Diabetes, Elizabeth Guerrero-Berroa, Ramit Ravona-Springer, James Schmeidler, Anthony Heymann, Laili Soleimani, Mary Sano, Derek Leroith, Rachel Preiss, Ruth Zukran, Jeremy M. Silverman, Michal Schnaider Beeri

Publications and Research

Background: Type 2 diabetes (T2D) is a metabolic condition associated with poor clinical and cognitive outcomes including vascular disease, depressive symptoms, cognitive impairment, and dementia. In the general elderly population, depression has been consistently identified as a risk factor for cognitive impairment/decline. However, the association between depression and cognitive function in T2D has been understudied.

Objective: We investigated the association between depression and cognitive function in a large sample of cognitively normal elderly with T2D.

Methods: In this cross-sectional study, we examined 738 participants, aged 65–88 years old, enrolled in the Israel Diabetes and Cognitive Decline study. For each …