Neurosciences Commons^™

Astrocyte Activation And The Calcineurin/Nfat Pathway In Cerebrovascular Disease, Susan D. Kraner, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Calcineurin (CN) is a Ca²⁺/calmodulin-dependent protein phosphatase with high abundance in nervous tissue. Though enriched in neurons, CN can become strongly induced in subsets of activated astrocytes under different pathological conditions where it interacts extensively with the nuclear factor of activated T cells (NFATs). Recent work has shown that regions of small vessel damage are associated with the upregulation of a proteolized, highly active form of CN in nearby astrocytes, suggesting a link between the CN/NFAT pathway and chronic cerebrovascular disease. In this Mini Review article, we discuss CN/NFAT signaling properties in the context of vascular disease and …

In Vivo Brainstem Imaging In Alzheimer’S Disease: Potential For Biomarker Development, David J. Braun, Linda J. Van Eldik

Neuroscience Faculty Publications

The dearth of effective treatments for Alzheimer’s disease (AD) is one of the largest public health issues worldwide, costing hundreds of billions of dollars per year. From a therapeutic standpoint, research efforts to date have met with strikingly little clinical success. One major issue is that trials begin after substantial pathological change has occurred, and it is increasingly clear that the most effective treatment regimens will need to be administered earlier in the disease process. In order to identify individuals within the long preclinical phase of AD who are likely to progress to dementia, improvements are required in biomarker development. …

Chronically Implanted Intracranial Electrodes: Tissue Reaction And Electrical Changes., Andrew Campbell, Chengyuan Wu

Department of Neurosurgery Faculty Papers

The brain-electrode interface is arguably one of the most important areas of study in neuroscience today. A stronger foundation in this topic will allow us to probe the architecture of the brain in unprecedented functional detail and augment our ability to intervene in disease states. Over many years, significant progress has been made in this field, but some obstacles have remained elusive-notably preventing glial encapsulation and electrode degradation. In this review, we discuss the tissue response to electrode implantation on acute and chronic timescales, the electrical changes that occur in electrode systems over time, and strategies that are being investigated …

Cardiac Autonomic Neuropathy In Diabetes: A Predictor Of Cardiometabolic Events, Aaron I. Vinik, Carolina Casellini, Henri K. Parson, Sheri R. Colberg, Marie-Laure Nevoret

Human Movement Studies & Special Education Faculty Publications

Autonomic nervous system (ANS) imbalance manifesting as cardiac autonomic neuropathy in the diabetic population is an important predictor of cardiovascular events. Symptoms and signs of ANS dysfunction, such as resting heart rate elevations, diminished blood pressure responses to standing, and altered time and frequency domain measures of heart rate variability in response to deep breathing, standing, and the Valsalva maneuver, should be elicited from all patients with diabetes and prediabetes. With the recognition of the presence of ANS imbalance or for its prevention, a rigorous regime should be implemented with lifestyle modification, physical activity, and cautious use of medications that …

Fasudil In Combination With Bone Marrow Stromal Cells (Bmscs) Attenuates Alzheimer's Disease-Related Changes Through The Regulation Of The Peripheral Immune System., Jiezhong Yu, Yuqing Yan, Qingfang Gu, Gajendra Kumar, Hongqiang Yu, Yijin Zhao, Chunyun Liu, Ye Gao, Zhi Chai, Jasleen Chumber, Bao-Guo Xiao, Guang-Xian Zhang, Han-Ting Zhang, Yuqiang Jiang, Cun-Gen Ma

Department of Neurology Faculty Papers

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease. Its mechanism is still not clear. Majority of research focused on the central nervous system (CNS) changes, while few studies emphasize on peripheral immune system modulation. Our study aimed to investigate the regulation of the peripheral immune system and its relationship to the severity of the disease after treatment in an AD model of APPswe/PSEN1dE9 transgenic (APP/PS1 Tg) mice. APP/PS1 Tg mice (8 months old) were treated with the ROCK-II inhibitor 1-(5-isoquinolinesulfonyl)-homo-piperazine (Fasudil) (intraperitoneal (i.p.) injections, 25 mg/kg/day), bone marrow stromal cells (BMSCs; caudal vein injections, 1 × 10

Ca2+, Astrocyte Activation And Calcineurin/Nfat Signaling In Age-Related Neurodegenerative Diseases, Pradoldej Sompol, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Mounting evidence supports a fundamental role for Ca²⁺ dysregulation in astrocyte activation. Though the activated astrocyte phenotype is complex, cell-type targeting approaches have revealed a number of detrimental roles of activated astrocytes involving neuroinflammation, release of synaptotoxic factors and loss of glutamate regulation. Work from our lab and others has suggested that the Ca²⁺/calmodulin dependent protein phosphatase, calcineurin (CN), provides a critical link between Ca²⁺ dysregulation and the activated astrocyte phenotype. A proteolyzed, hyperactivated form of CN appears at high levels in activated astrocytes in both human tissue and rodent tissue around regions of amyloid and …

Mooney Face Stimuli For Visual Perception Research, Caspar M. Schwiedrzik, Lucia Melloni, Aaron Schurger

Psychology Faculty Articles and Research

In 1957, Craig Mooney published a set of human face stimuli to study perceptual closure: the formation of a coherent percept on the basis of minimal visual information. Images of this type, now known as "Mooney faces", are widely used in cognitive psychology and neuroscience because they offer a means of inducing variable perception with constant visuospatial characteristics (they are often not perceived as faces if viewed upside down). Mooney's original set of 40 stimuli has been employed in several studies. However, it is often necessary to use a much larger stimulus set. We created a new set of over …

Reversible Manifestations Of Extraparenchymal Neurocysticercosis, Edison M. Campos, Flavius D. Raslau, Robert Salinas, Daniela Di Capua, John T. Slevin, Mauricio F. Villamar

Neurology Faculty Publications

Movement disorders are uncommon manifestations of neurocysticercosis. When present, most are secondary to parenchymal lesions in the basal ganglia. Rarely, movement disorders can occur in racemose/extraparenchymal neurocysticercosis, an aggressive variant frequently associated with cerebrospinal fluid outflow obstruction and hydrocephalus. Appropriate treatment can reverse neurological manifestations.

Neural Responses To Naturalistic Clips Of Behaving Animals Under Two Different Task Contexts, Samuel A. Nastase, Yaroslav O. Halchenko, Andrew C. Connolly, M. Ida Gobbini, James V. Haxby

Dartmouth Scholarship

The human brain rapidly deploys semantic information during perception to facilitate our interaction with the world. These semantic representations are encoded in the activity of distributed populations of neurons (Haxby et al., 2001; McClelland and Rogers, 2003; Kriegeskorte et al., 2008b) and command widespread cortical real estate (Binder et al., 2009; Huth et al., 2012). The neural representation of a stimulus can be described as a location (i.e., response vector) in a high-dimensional neural representational space (Kriegeskorte and Kievit, 2013; Haxby et al., 2014). This resonates with behavioral and theoretical work describing mental representations of objects and actions as being …

Regional Microglia Are Transcriptionally Distinct But Similarly Exacerbate Neurodegeneration In A Culture Model Of Parkinson's Disease., Eric Wildon Kostuk, Jingli Cai, Lorraine Iacovitti

Department of Neuroscience Faculty Papers

BACKGROUND: Parkinson's disease (PD) is characterized by selective degeneration of dopaminergic (DA) neurons of the substantia nigra pars compacta (SN) while neighboring ventral tegmental area (VTA) DA neurons are relatively spared. Mechanisms underlying the selective protection of the VTA and susceptibility of the SN are still mostly unknown. Here, we demonstrate the importance of balance between astrocytes and microglia in the susceptibility of SN DA neurons to the PD mimetic toxin 1-methyl-4-phenylpyridinium (MPP

METHODS: Previously established methods were used to isolate astrocytes and microglia from the cortex (CTX), SN, and VTA, as well as embryonic midbrain DA neurons from the …

Cdk5 Inhibition Resolves Pka/Camp-Independent Activation Of Creb1 Signaling In Glioma Stem Cells, Subhas Mukherjee, Carol Tucker-Burden, Emily Kaissi, Austin Newsam, Hithardhi Duggireddy, Monica Chau, Changming Zhang, Bhakti Diwedi, Manali Rupji, Sandra Seby, Jeanne Kowalski, Jun Kong, Renee Read, Daniel J. Brat

Neurology Faculty Publications

Cancer stem cells promote neoplastic growth, in part by deregulating asymmetric cell division and enhancing self-renewal. To uncover mechanisms and potential therapeutic targets in glioma stem cell (GSC) self-renewal, we performed a genetic suppressor screen for kinases to reverse the tumor phenotype of our Drosophila brain tumor model and identified dCdk5 as a critical regulator. CDK5, the human ortholog of dCdk5 (79% identity), is aberrantly activated in GBMs and tightly aligned with both chromosome 7 gains and stem cell markers affecting tumor-propagation. Our investigation revealed that pharmaceutical inhibition of CDK5 prevents GSC self-renewal in vitro and in xenografted tumors, at …

Treating Adhd With Suggestion: Neurofeedback And Placebo Therapeutics, Robert T. Thibault, Samuel Vassière, Jay A. Olson, Amir Raz

Psychology Faculty Articles and Research

Objective: We propose that clinicians can use suggestion to help treat conditions such as ADHD. Methods: We use EEG neurofeedback as a case study, alongside evidence from a recent pilot experiment utilizing a sham MRI scanner to highlight the therapeutic potential of suggestion-based treatments. Results: The medical literature demonstrates that many practitioners already prescribe treatments that hardly outperform placebo comparators. Moreover, the sham MRI experiment showed that, even with full disclosure of the procedure, suggestion alone can reduce the symptomatology of ADHD. Conclusion: Non-deceptive suggestion-based treatments, especially those drawing on accessories from neuroscience, may offer a safe complement and potential …

Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin

Senior Honors Theses

The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research is …

Bilateral Facial Spasm Following Guillain-Barré Syndrome, Zain Guduru, John Morgan, Kapil Sethi

Neurology Faculty Publications

Background: We report a patient who developed lower facial muscle spasm at rest and bilateral facial synkinesis several months after treatment of Guillain–Barré syndrome (GBS); this finding, to our knowledge, is hitherto unreported.

Phenomenology Shown: Bilateral synkinesis, facial muscles spasm at rest, bilateral postparalytic facial syndrome.

Educational Value: Aberrant regeneration of nerve fibers post GBS, resulting in facial muscles spasm at rest, bilateral synkinesis.

Network Specialization During Adolescence: Hippocampal Effective Connectivity In Boys And Girls, Jeffrey D. Riley, E. Elinor Chen, Jessica Winsell, Elyssia Poggi Davis, Laura M. Glynn, Tallie Z. Baram, Curt A. Sandman, Steven L. Small, Ana Solodkin

Psychology Faculty Articles and Research

Adolescence is a complex period of concurrent mental and physical development that facilitates adult functioning at multiple levels. Despite the growing number of neuroimaging studies of cognitive development in adolescence focusing on regional activation patterns, there remains a paucity of information about the functional interactions across these participating regions that are critical for cognitive functioning, including memory. The current study used structural equation modeling (SEM) to determine how interactions among brain regions critical for memory change over the course of adolescence. We obtained functional MRI in 77 individuals aged 8–16 years old, divided into younger (ages 8–10) and older (ages …

Multiple Sclerosis Identification Based On Fractional Fourier Entropy And A Modified Jaya Algorithm, Shui-Hua Wang, Hong Cheng, Preetha Phillips, Yu-Dong Zhang

Publications and Research

Aim: Currently, identifying multiple sclerosis (MS) by human experts may come across the problem of “normal-appearing white matter”, which causes a low sensitivity. Methods: In this study, we presented a computer vision based approached to identify MS in an automatic way. This proposed method first extracted the fractional Fourier entropy map from a specified brain image. Afterwards, it sent the features to a multilayer perceptron trained by a proposed improved parameter-free Jaya algorithm. We used cost-sensitivity learning to handle the imbalanced data problem. Results: The 10 × 10-fold cross validation showed our method yielded a sensitivity of 97.40 ± 0.60%, …

Effects On Recovery And Neuroplasticity In Brain Injury Patients, Rebekkah Mclellan

Student Scholar Showcase

Abstract

According to the Centers for Disease Control, approximately 1.7 million people sustain a Traumatic Brain Injury each year, making the topic of brain plasticity and patient recovery an important area of study. An added element is understanding whether biological, social, and environmental factors can impact the recovery and plasticity of the patient’s brain.The purpose of this literature review was to evaluate if the environment surrounding an individual who has sustained a brain injury affects their recovery and neuroplasticity. The databases used for the scope of this review included LC OneSearch, Medline, EBSCOhost, and Google Scholar. Keywords included brain injury, …

The Role Of Reactive Astrocitose In The Chronological Evolution Of Traumatic Brain Injury, Roxana M. Duncea-Borca, Vladimir Belis, Mihnea Costescu, Relu G. Calota, Reka Kutasi, Cosmin A. Moldovan

Journal of Mind and Medical Sciences

Introduction and objectives. This study aims to investigate whether the cerebral modifications of posttraumatic reactive astrocitose can be considered an objective criterion for determining the age of traumatic cranio-cerebral lesions.

Materials and methods. The present study consists of a series of 23 medico-legal cases that underwent autopsy inTeleormanCounty(Romania) Department of Forensic Medicine during 2007–2016, with full immune-histochemical microscopic examination using GFAP staining. The study consists of two groups, a series of 13 cases with cranio-cerebral trauma with different posttraumatic survival periods and 9 cases as a control group.

Results and discussions. We discovered GFAP+ reactive astrocytes even when death occurred …

Vascular Neurocognitive Disorders And The Vascular Risk Factors, Carmen V. Albu, Vlad Padureanu, Mihail V. Boldeanu, Ana M. Bumbea, Anca S. Enescu, Dana M. Albulescu, Cristian A. Silosi, Aurelia Enescu

Journal of Mind and Medical Sciences

Dementias are clinical neurodegenerative diseases characterized by permanent and progressive transformation of cognitive functions such as memory, learning capacity, attention, thinking, language, passing judgments, calculation or orientation. Dementias represent a relatively frequent pathology, encountered at about 10% of the population of 65-year olds and 20% of the population of 80-year olds.

This review presents the main etiological forms of dementia, which include Alzheimer form of dementia, vascular dementia, dementia associated with alpha-synucleionopathies, and mixed forms. Regarding vascular dementia, the risk factors are similar to those for an ischemic or hemorrhagic cerebrovascular accident: arterial hypertension, diabetes mellitus, dyslipidemia, smoking, obesity, age, …

Mitochondrial Transplantation Strategies As Potential Therapeutics For Central Nervous System Trauma, Jenna L. Gollihue, Samir P. Patel, Alexander G. Rabchevsky

Spinal Cord and Brain Injury Research Center Faculty Publications

Mitochondria are essential cellular organelles critical for generating adenosine triphosphate for cellular homeostasis, as well as various mechanisms that can lead to both necrosis and apoptosis. The field of “mitochondrial medicine” is emerging in which injury/disease states are targeted therapeutically at the level of the mitochondrion, including specific antioxidants, bioenergetic substrate additions, and membrane uncoupling agents. Consequently, novel mitochondrial transplantation strategies represent a potentially multifactorial therapy leading to increased adenosine triphosphate production, decreased oxidative stress, mitochondrial DNA replacement, improved bioenergetics and tissue sparing. Herein, we describe briefly the history of mitochondrial transplantation and the various techniques used for both in …

Variant Intestinal-Cell Kinase In Juvenile Myoclonic Epilepsy, J. N. Bailey, L. De Nijs, D. Bai, T. Suzuki, H. Miyamoto, M. Tanaka, C. Patterson, Y.-C. Lin, M. T. Medina, M. E. Alonso, J. M. Serratosa, R. M. Durón, Viet-Hong Nguyen, J. E. Wight, I. E. Martínez‑Juárez, A. Ochoa, A. Jara-Prado, L. Guilhoto, Y. Molina, E. M. Yacubian, M. López‑Ruiz, Y. Inoue, S. Kaneko, S. Hirose, M. Osawa, H. Oguni, S. Fujimoto, T. M. Grisar, J. M. Stern, K. Yamakawa, B. Lakaye, A. V. Delgado-Escueta

Pharmacy Faculty Articles and Research

BACKGROUND

In juvenile myoclonic epilepsy, data are limited on the genetic basis of networks promoting convulsions with diffuse polyspikes on electroencephalography (EEG) and the subtle microscopic brain dysplasia called microdysgenesis.

METHODS

Using Sanger sequencing, we sequenced the exomes of six members of a large family affected with juvenile myoclonic epilepsy and confirmed cosegregation in all 37 family members. We screened an additional 310 patients with this disorder for variants on DNA melting-curve analysis and targeted real-time DNA sequencing of the gene encoding intestinal-cell kinase (ICK). We calculated Bayesian logarithm of the odds (LOD) scores for cosegregating variants, odds …

Amperometric Self-Referencing Ceramic Based Microelectrode Arrays For D-Serine Detection, Diana Campos-Beltrán, Åsa Konradsson-Geuken, Jorge E. Quintero, Lisa Marshall

Neuroscience Faculty Publications

D-serine is the major D-amino acid in the mammalian central nervous system. As the dominant co-agonist of the endogenous synaptic NMDA receptor, D-serine plays a role in synaptic plasticity, learning, and memory. Alterations in D-serine are linked to neuropsychiatric disorders including schizophrenia. Thus, it is of increasing interest to monitor the concentration of D-serine in vivo as a relevant player in dynamic neuron-glia network activity. Here we present a procedure for amperometric detection of D-serine with self-referencing ceramic-based microelectrode arrays (MEAs) coated with D-amino acid oxidase from the yeast Rhodotorula gracilis (RgDAAO). We demonstrate in vitro D-serine recordings with a …

Cortical Thinning And Neuropsychiatric Outcomes In Children Exposed To Prenatal Adversity: A Role For Placental Crh?, Curt A. Sandman, Megan M. Curran, Elyssia Poggi Davis, Laura M. Glynn, Kevin Head, Tallie Z. Baram

Psychology Faculty Articles and Research

Exposure to early life adversity may disrupt the development and maturation of neurons and brain circuits, which, in turn, underlie neurodevelopment and mental illnesses. During fetal life, maternal adversity is conveyed to the developing brain via several molecular signals, including the stress hormone corticotropin releasing hormone (CRH). Employing a large well characterized prospective cohort, we find that fetal exposure to placental-origin CRH levels predicts structural and functional brain outcomes in children. Specifically, elevated placental CRH levels portend thinning of selective cortical regions of exposed individuals, with commensurate cognitive and emotional deficits. Notably, the relations of placental-origin CRH to cortical thinning …

The Role Of The Leukemia Inhibitory Factor Receptor In Neuroprotective Signaling, Stephanie M. Davis, Keith R. Pennypacker

Center for Advanced Translational Stroke Science Faculty Publications

Several neurotropic cytokines relay their signaling through the leukemia inhibitory factor receptor. This 190kDa subunit couples with the 130kDa gp130 subunit to transduce intracellular signaling in neurons and oligodendrocytes that leads to expression of genes associated with neurosurvival. Moreover, activation of this receptor alters the phenotype of immune cells to an anti-inflammatory one. Although cytokines that activate the leukemia inhibitory factor receptor have been studied in the context of neurodegenerative disease, therapeutic targeting of the specific receptor subunit has been understudied in by comparison. This review examines the role of this receptor in the CNS and immune system, and its …

Binge Alcohol Exposure Causes Neurobehavioral Deficits And Gsk3Β Activation In The Hippocampus Of Adolescent Rats, Zhe Ji, Lin Yuan, Xiong Lu, Hanqing Ding, Jia Luo, Zun-Ji Ke

Pharmacology and Nutritional Sciences Faculty Publications

Heavy alcohol exposure causes profound damage to the adolescent brain, particularly the hippocampus, which underlie some behavioral deficits. However, the underlying molecular mechanisms remain inconclusive. The current study sought to determine whether binge alcohol exposure affects the hippocampus-related behaviors and key signaling proteins that may mediate alcohol neurotoxicity in adolescent rats. Alcohol exposure reduced the number of both NeuN-positive and doublecortin-positive cells in the hippocampus. Alcohol also induced neurodegeneration which was confirmed by ultrastructural analysis by electronic microscopy and was accompanied with the activation of microglia. Binge alcohol exposure impaired spatial learning and memory which was evaluated by the Morris …

Putative Adult Neurogenesis In Old World Parrots: The Congo African Grey Parrot (Psittacus Erithacus) And Timneh Grey Parrot (Psittacus Timneh), Pedzisai Mazengenya, Adhil Bhagwandin, Paul R. Manger, Amadi O. Ihunwo

Brain and Mind Institute

In the current study, we examined for the first time, the potential for adult neurogenesis throughout the brain of the Congo African grey parrot (Psittacus erithacus) and Timneh grey parrot (Psittacus timneh) using immunohistochemistry for the endogenous markers proliferating cell nuclear antigen (PCNA), which labels proliferating cells, and doublecortin (DCX), which stains immature and migrating neurons. A similar distribution of PCNA and DCX immunoreactivity was found throughout the brain of the Congo African grey and Timneh grey parrots, but minor differences were also observed. In both species of parrots, PCNA and DCX immunoreactivity was observed in …

Representing Diversity In The Dish: Using Patient-Derived In Vitro Models To Recreate The Heterogeneity Of Neurological Disease, Layla T. Ghaffari, Alexander Starr, Andrew T. Nelson, Rita Sattler

Department of Neuroscience Faculty Papers

Neurological diseases, including dementias such as Alzheimer's disease (AD) and fronto-temporal dementia (FTD) and degenerative motor neuron diseases such as amyotrophic lateral sclerosis (ALS), are responsible for an increasing fraction of worldwide fatalities. Researching these heterogeneous diseases requires models that endogenously express the full array of genetic and epigenetic factors which may influence disease development in both familial and sporadic patients. Here, we discuss the two primary methods of developing patient-derived neurons and glia to model neurodegenerative disease: reprogramming somatic cells into induced pluripotent stem cells (iPSCs), which are differentiated into neurons or glial cells, or directly converting (DC) somatic …

Specific Relationship Between The Shape Of The Readiness Potential, Subjective Decision Time, And Waiting Time Predicted By An Accumulator Model With Temporally Autocorrelated Input Noise, Aaron Schurger

Psychology Faculty Articles and Research

Self-initiated movements are reliably preceded by a gradual buildup of neuronal activity known as the readiness potential (RP). Recent evidence suggests that the RP may reflect subthreshold stochastic fluctuations in neural activity that can be modeled as a process of accumulation to bound. One element of accumulator models that has been largely overlooked in the literature is the stochastic term, which is traditionally modeled as Gaussian white noise. While there may be practical reasons for this choice, we have long known that noise in neural systems is not white – it is long-term correlated with spectral density of the form …

A Novel Method For Training Mice In Visuo-Tactile 3-D Object Discrimination And Recognition, Xian Hu, Ogaga Urhie, Kevin Chang, Rachel Hostetler, Ariel Agmon

Faculty & Staff Scholarship

Perceiving, recognizing and remembering 3-dimensional (3-D) objects encountered in the environment has a very high survival value; unsurprisingly, this ability is shared among many animal species, including humans. The psychological, psychophysical and neural basis for object perception, discrimination, recognition and memory has been extensively studied in humans, monkeys, pigeons and rodents, but is still far from understood. Nearly all 3-D object recognition studies in the rodent used the “novel object recognition” paradigm, which relies on innate rather than learned behavior; however, this procedure has several important limitations. Recently, investigators have begun to recognize the power of behavioral tasks learned through …

A Gut Feeling: A Hypothesis Of The Role Of The Microbiome In Attention-Deficit/Hyperactivity Disorders., Xue Ming, Neil Chen, Carly Ray, Gretchen Brewer, Jeffrey Kornitzer, Robert A Steer

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Attention-deficit/hyperactivity disorder (ADHD) is a neurologic disorder characterized by hyperactivity/impulsivity and/or inattentiveness, with genetic and environmental factors contributing to the disorder. With the growing recognition of the microbiome's role in many neurological disorders, the authors propose that it may also be implicated in ADHD. Here, we describe several evolving areas of research to support this hypothesis. First, a unique composition of gut bacteria has been identified and linked to behaviors in ADHD. Second, our research found an increased incidence of 2 gastrointestinal symptoms (constipation and flatulence) in children with ADHD, as compared to controls. Finally, emerging data may be interpreted …