Pre-requisites: High school chemistry or equivalent preparation, or consent of instructor. Strengthen your knowledge of the biological principals governing the nervous system. New More information. Fall Instructor: Dr. Tania Lam Tel: Email: tania. Tania Lam Tel: More information. Republic Polytechnic. Office Phone: email: More information. I post grades in Blackboard, but I don t regularly monitor the mail feature in Blackboard. Murray Jensen, Instructor More information. Course Information.
Gross anatomical structure More information. Rm , More information. General Psychology. Course Description. Course Objectives. Office Hours: Spring Dr. Academic I Room More information. Bernstein, Elizabeth Chicago: University of Chicago Press. This course follows More information. Describe the five basic functions of living More information. The cells, organs, and organ More information. Course outline. Praphaporn Ton Stewart Email: More information.
To make this website work, we log user data and share it with processors. Pericytes are enveloping brain microvessels and capillaries and are found in close proximity to astrocytes and neurons. The ratio of pericytes to endothelial cells is assessed to be [ 11 ]. Using multiple signaling pathways, pericytes seems to play a critical role in the formation and maturation of the BBB during development and regulation of tissue-survival [ 12 ].
In addition, pericytes control over cerebral blood flow due to regulation of capillary diameter through actin fibers in the pericytic cell body [ 13 ]. Dysfunction of pericytes through aging was reported in animal models [ 14 ] and their absence results in loss of BBB integrity and reduction in regional cerebral blood flow [ 15 ]. Astrocytes interact with pericytes and microvascular endothelial cells by endfeet protrusions ensheathing the capillaries.
Interactions may also exist with smooth muscle cells at arterioles. Astrocytes play important roles in maintenance of the BBB, in homeostasis of extracellular concentration of transmitters, metabolites, ions and water, but also serve as stem cells during development and provide for templates for migratory neuronal streams.
Interaction between astrocytes and neurons determine synaptic transmission, clearance of neurotransmitters, plasticity, and blood flow reviewed by [ 16 ]. A key developmental phase of the BBB lies in the early communications of the embryonic endothelium with neural cells [ 17 ]. The BBB matures during fetal life and is well formed by birth [ 18 — 23 ]. Transport mechanisms may continue to develop in mammals born in a relatively immature state such as the rat and mouse and become fully functional only in the peri- or post-natal period [ 24 ].
An early feature of BBB development is the formation of tight junctions. In humans, a brain of a 14 week fetus express occludin and claudin-5 in the capillary endothelium with the same distribution at cell margins as seen in the adult [ 28 ].
Human post-mortem studies of perinatal deaths and stillborn fetuses from approximately 12 weeks gestation have demonstrated that a barrier to trypan blue exist from at least the beginning of the second trimester, equivalently to that of the adult human Grontoft, Culture studies suggest that astrocytes have a key role in regulating the tightness of the BBB [ 30 ].
Each of the three main CNS interface layers: the BBB, choroid plexus epithelium and the epithelium of the arachnoid mater, functions as a physical, transport, metabolic, and immunologic barrier.
The barrier functions are dynamic and respond to regulatory signals from both blood and brain. Tight junctions between adjacent cells restrict diffusion of polar solutes through the intercellular cleft paracellular pathway. The barriers are permeable to O 2 and CO 2 and other gaseous molecules such as helium, xenon, N 2 and many gaseous anesthetics.
The permeability to xenon may provide a high resolution magnetic resonance imaging tool by which small morphological alteration may be detectable within the living tissue and also permit the analysis of binding sites using molecular probing techniques. Lipid soluble substances can pass the barrier by diffusion. Principally, the BBB is also permeable to water, however solute carriers on the apical and basal membranes together with ectoenzymes and endoenzymes regulate small solute entry and efflux.
Transfer of some molecules is regulated by multidrug transporters that can limit their concentrations within the central nervous system. Multidrug transporters are ubiquitous transport proteins that exploit ATP hydrolysis to funnel molecules across lipid membranes; they facilitate transport of molecules into cells but may also prevent accumulation of molecules within the brain interstitial space. Multidrug transporters and Pgp-like proteins are expressed at the BBB and limit access of drugs to brain tissue but also other lipophilic molecules, including for example bilirubin, the degradation product of hemoglobin, which - if entering the central nervous system — is neurotoxic and can cause significant damage [ 31 ].
Recent studies suggest that upregulation of transporter molecules in pathological conditions may reduce drug levels within the brain, and explain treatment failures pharmacoresistant in neurological and psychiatric disorders [ 32 ].
Large molecules e. The barriers also regulate the recruitment and entry of leukocytes and innate immune elements and involve in both the reactive and surveillance functions of CNS immunity. Leukocyte migration involves a complex set of adhesion molecules at the surface of leukocytes and vascular endothelial cells. Transport systems across the blood-brain barrier are illustrated in Figure 1. Cells may cross the BBB through or adjacent to the tight junctions.
Solutes may passively diffuse through the cell membrane. Active efflux carriers may pump some of these passively penetrating solutes out of the endothelial cell.
Carrier-mediated influx passive or secondarily active can transport essential polar molecules, such as amino acids, glucose and nucleosides into the CNS. Receptor-mediated transcytosis RMT can transport macromolecules such as peptides and proteins across the endothelium. Adsorptive-mediated transcytosis AMT is induced non-specifically by positively charged macromolecules and can result in passage across the BBB. Customers who bought this item also bought. Stock Image. Published by McGraw-Hill Education McGraw-Hill can trace its roots back more than years, and throughout that time it has dedicated itself to creating high quality books on business, education and other academic subjects.
McGraw-Hill Education Coupons. Unlock Deals Now. After the completion of the study the results were challenged and agreed upon in an additional international scientific advisory board meeting by independent experts not otherwise involved in the study. The full data of the study are currently not publicly available due to ongoing additional analyses, however, individual summary data concerning this manuscript may be available on reasonable request from the authors.
The study was a randomized, placebo-controlled, double-blind, two-period cross-over trial with an explorative design with confirmatory principles. For every participant, the study consisted of three visits. Medical and psychological symptoms were screened on Day 0. Each participant completed psychometric tests about personality traits, life experiences and sensitivities between 3 to 7 days before randomization Day 1. At bedtime the evening before and in the morning of Day 1 after awakening, the participant collected saliva to determine the cortisol awakening response CAR.
Participants who received verum on Day 1 got placebo on Day 2 and vice versa. Apart from that, study procedures on Day 1 and Day 2 were identical. The participant took a single dose three pills of Nx4 or placebo 40 to 60 minutes prior to the second scan.
The second MRI scan was acquired with simultaneous EEG data collection and comprised three tasks: first, the Hariri task; second, the Expectancy task; and, third, the ScanSTRESS task; as well as a pre-task resting-state and a post-task resting-state scan of 12 minutes each.
Concurrent EEG was necessary to ascertain awake state during resting-state runs given the literature on sleep incidents 40 and visual inspection of EPI data was performed to exclude potential signal losses due to the EEG net see Supplementary Figure S1. To investigate the physiological stress response further, saliva samples for cortisol measurements were collected directly before and after stress induction and again 20 minutes and 40 minutes after stress induction.
The Hariri task, on which we focus in this manuscript, is an emotional face-matching task. This task induced an amygdala response and, thus, allowed us to investigate the effect of Nx4 on emotional response. In a block design, facial expressions showing negative fear and anger and positive happiness emotions as well as forms were presented.
A schematic illustration of the block design is shown in Fig. In each trial, a reference i. Two samples faces or forms, respectively were presented at the bottom of the screen. Eight consecutive trials were presented during each block, and each trial was displayed for 2. Participants were instructed to match the sample with the same emotional expression or form as shown in the reference by pressing the left or the right key on a button box. Five blocks of positive emotions, five blocks of negative emotions, and ten blocks of forms were presented during the eight-minute MRI data acquisition.
The exact KDEF stimuli will be provided by request. The Hariri task is a face-matching task with a form condition as control.
Each block begins with a cue announcing the current condition face or form for 2 seconds, followed by a fixation cross shown for 0. Eight trials of face-matching or form-matching, respectively, were presented during each block, and each test was displayed for 2.
In total, the eight-minute task consisted of five blocks with happy faces, five blocks with negative afraid and angry faces and ten blocks with forms. Pictures of head-on faces were taken from the Karolinska Directed Emotional Faces KDEF set, which has been used in several experiments before 42 , 57 , 58 , 59 , The Hariri task was followed by two other tasks inside the scanner that will be reported in separate manuscripts.
The emotional Expectancy task used visual cues and pictures inducing different emotions Half of the pictures from each category were preceded by a visual cue expectancy period and half were presented instantly after fixation period with no visual cues.
Visual cues depicted by an arrow pointing up indicated a positive picture followed 10 times by a picture and 5 times by fixation periods , an arrow pointing horizontally indicated a neutral picture and an arrow pointing down indicated a negative picture followed 10 times by a picture and 5 times by fixation periods. The purpose of the cue-picture-mismatch events was to bring new stimuli to the participants therefore increase their attention to pictures. The same number of pictures followed directly after fixation.
Each picture presentation was followed by a fixation period depicted by a small cross in the middle of the screen. For both types of task control blocks without any social evaluative feedback, time pressure, or difficult questions and stress blocks with feedback about the correctness and speed of the answers as well as more demanding questions alternated. During the whole experiment two panel members observed the performance of the participants, who were continuously exposed to a video feed of the reactions of the panel.
One run of rest took 12 minutes and subjects were asked to keep their eyes closed and not engage in any specific tasks while trying not to fall asleep Thus, the Hariri task was performed 12 minutes after the subjects entered the scanner for the second time after taking the IMP outside the scanner.
In this study, 40 healthy, mildly to moderately stressed male participants aged 31 to 59 years were enrolled. During baseline MR measurements, one subject was excluded due to an incidental finding thus 39 subjects were treated in this study.
Healthy for the purpose of screening means without any lifetime episode of any mental disorder and abuse of any substance in respect of a Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorder 4 th edition DSM-IV Axis I SCID , assessment of medication use, medical examination and history as well as blood count.
All participants needed to be nonsmokers for at least three months, MRI compatible, fluent in German, and able to understand the explanations and instructions given during the study; in addition, they had to be willing to adhere to all specified prohibitions and restrictions.
All participants were screened 7 to 21 days before randomization and filled in questionnaires at home 3 to 7 days before the randomization visit Day 1 , which was at the same time the day of first study treatment and assessments. The second treatment after cross-over was administered 7 to 35 days after the first treatment on Day 2.
Measurements were done on the same day. There was one dropout due to an incidental cerebral finding at the first MR measurement. The participant did not receive the IMP. Ingredients of Nx4 are Passiflora incarnata purple passionflower D2 0. Additional information regarding these ingredients may be seen in more detail in Supplementary Table S 1.
Excipients include lactose monohydrate and magnesium stearate. Placebo tablets were composed of lactose monohydrate and magnesium stearate. Twenty participants took three tablets of Nx4 on the first measurement day Day 1 and, after a washout period 7—35 days , received three tablets of placebo on the second measurement day Day 2.
Due to the cross-over design, the other 19 participants received placebo and Nx4 in the opposite order. The oral intake of three tablets took place 40 to 60 minutes before the second MRI scan post-treatment scan. Primary Outcome 1: Effect of drug, driven by significantly reduced amygdala activations in the contrast negative faces versus forms in verum compared to placebo conditions. Primary Outcome 2: Interaction of time and drug, driven by significantly greater reductions of amygdala FCD in verum compared to placebo conditions.
Primary Outcome 3: Interaction of time and drug, driven by significantly greater changes smaller and greater, two-sided effects because of inclusion of top-down and bottom-up processes in different regions of amygdala-seeded connectivities in verum compared to placebo conditions. Primary Outcome 4: Interaction of time and drug, driven by significantly greater reductions of local resting-state activity of amygdala amplitude of low-frequency fluctuations ALFF in verum compared to placebo conditions.
Primary Outcome 5: Influence of drug on directed connectivity in an effective connectivity model Dynamic Causal Modeling [DCM] from ventral prefrontal cortex vPFC towards amygdala, driven by positive effects of verum on directed negative effective top-down connectivity from vPFC to amygdala.
Primary Outcome 6: Effect of drug, driven by significantly reduced stress network activation in terms of smaller activations in ACC, medio-orbitofrontal cortex, hippocampus, amygdala, and hypothalamus in the contrast hard versus easy in verum compared to placebo conditions.
Multiplicity due to multiple primary hypotheses was controlled by means of the principle of a priori ordered hypotheses. If the first test shows statistical significance, the second hypothesis can be tested in a confirmatory manner with the same alpha as the first test.
The same principle applies to subsequent hypotheses, as long as all preceding hypotheses show statistical significance. A register in the human voice is a particular series of tones, produced in the same vibratory pattern of the vocal folds , and possessing the same quality. Registers originate in laryngeal functioning. They occur because the vocal folds are capable of producing several different vibratory patterns. The term register can be used to refer to any of the following: .
In linguistics , a register language is a language that combines tone and vowel phonation into a single phonological system. Within speech pathology , the term vocal register has three constituent elements: a certain vibratory pattern of the vocal folds, a certain series of pitches, and a certain type of sound. Speech pathologists identify four vocal registers based on the physiology of laryngeal function: the vocal fry register , the modal register , the falsetto register , and the whistle register.
This view is also adopted by many vocal pedagogists. Various terms related to the resonation process include amplification, enrichment, enlargement, improvement, intensification, and prolongation; although in strictly scientific usage acoustic authorities would question most of them.
The main point to be drawn from these terms by a singer or speaker is that the end result of resonation is, or should be, to make a better sound. In sequence from the lowest within the body to the highest, these areas are the chest, the tracheal tree, the larynx itself, the pharynx, the oral cavity, the nasal cavity, and the sinuses. The twelve-tone musical scale , upon which a large portion of all music western popular music in particular is based, may have its roots in the sound of the human voice during the course of evolution , according to a study published by the New Scientist.
Analysis of recorded speech samples found peaks in acoustic energy that mirrored the distances between notes in the twelve-tone scale. There are many disorders that affect the human voice; these include speech impediments , and growths and lesions on the vocal folds.
Talking improperly for long periods of time causes vocal loading , which is stress inflicted on the speech organs. Histology: Explore interactive slides to learn microscopy anatomy of cells tissues. Imaging: Correlate dissected human anatomy with quality histology and radiologic images to explore tissues. Labeled X-ray, MRI and CT images help you visualize internal structures using imaging techniques often encountered in clinical settings.
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