A Study to Evaluate LY3154207 on the Brain of Healthy Participants

2020 ◽  
Author(s):  
Keyword(s):  
The Brain ◽  
Healthy Participants

scholarly journals A Robust and Reproducible Connectome Fingerprint of Ketamine is Highly Associated with the Connectomic Signature of Antidepressants

2020 ◽  
Author(s):  
Chadi G. Abdallah ◽  
Kyung-Heup Ahn ◽  
Lynnette A. Averill ◽  
Samaneh Nemati ◽  
Christopher L. Averill ◽  
...  
Keyword(s):  
Brain Connectivity ◽  
Imaging Study ◽  
Seed Selection ◽  
Major Depressive ◽  
Brain Circuitry ◽  
Brain Functional Connectivity ◽  
The Brain ◽  
Healthy Participants ◽  
Placebo Cohort ◽  
Model Approach

ABSTRACTOver the past decade, various N-Methyl-D-Aspartate modulators have failed in clinical trials, underscoring the challenges of developing novel rapid-acting antidepressants based solely on the receptor or regional targets of ketamine. Thus, identifying the effect of ketamine on the brain circuitry and networks is becoming increasingly critical. In this longitudinal functional magnetic resonance imaging study of data from 265 participants, we used a validated predictive model approach that allows the full assessment of brain functional connectivity, without the need for seed selection or connectivity summaries. First, we identified a connectome fingerprint (CFP) in healthy participants (Cohort A, n=25) during intravenous infusion of a subanesthetic dose of ketamine, compared to normal saline. We then demonstrated the robustness and reproducibility of the discovered Ketamine CFP in two separate healthy samples (Cohort B, n=22; Cohort C, n=18). Finally, we investigated the Ketamine CFP connectivity at 1-week post treatment in major depressive disorder patients randomized to 8 weeks of sertraline or placebo (Cohort D, n=200). We found a significant, robust, and reproducible Ketamine CFP, consistent with reduced connectivity within the primary cortices and within the executive network, but increased connectivity between the executive network and the rest of the brain. Compared to placebo, the Ketamine CFP connectivity changes at 1-week predicted response to sertraline at 8-weeks. In each of Cohort A-C, ketamine significantly increased connectivity in a previously identified Antidepressant CFP. Investigating the brain connectivity networks, we successfully identified a robust and reproducible ketamine biomarker that is related to the mechanisms of antidepressants.Graphical Abstract

scholarly journals The Behavioral and ERP Responses to Self- and Other- Referenced Adjectives

2020 ◽  
Vol 10 (11) ◽  
pp. 782
Author(s):  
Alexander Savostyanov ◽  
Andrey Bocharov ◽  
Tatiana Astakhova ◽  
Sergey Tamozhnikov ◽  
Alexander Saprygin ◽  
...  
Keyword(s):  
Emotional Valence ◽  
Event Related Potential ◽  
Behavioral Reactions ◽  
Temporal Area ◽  
Time Dynamics ◽  
Self And Other ◽  
Emotional Appraisal ◽  
Cortical Localization ◽  
The Brain ◽  
Healthy Participants

The aim was to investigate behavioral reactions and event-related potential (ERP) responses in healthy participants under conditions of personalized attribution of emotional appraisal vocabulary to one-self or to other people. One hundred and fifty emotionally neutral, positive and negative words describing people’s traits were used. Subjects were asked to attribute each word to four types of people: one-self, loved, unpleasant and neutral person. The reaction time during adjectives attribution to one-self and a loved person was shorter than during adjectives attribution to neutral and unpleasant people. Self-related adjectives induced higher amplitudes of the N400 ERP peak in the medial cortical areas in comparison with adjectives related to other people. The amplitude of P300 and P600 depended on the emotional valence of assessments, but not on the personalized attribution. The interaction between the attribution effect and the effect of emotional valence of assessments was observed for the N400 peak in the left temporal area. The maximal amplitude of N400 was revealed under self-attributing of emotionally positive adjectives. Our results supported the hypothesis that the emotional valence of assessments and the processing of information about one-self or others were related to the brain processes that differ from each other in a cortical localization or time dynamics.

scholarly journals First-in-human imaging and kinetic analysis of vesicular acetylcholine transporter density in the heart using [18F]FEOBV PET

2020 ◽  
Author(s):  
Zacharie Saint-Georges ◽  
Vanessa K. Zayed ◽  
Katie Dinelle ◽  
Clifford Cassidy ◽  
Jean-Paul Soucy ◽  
...  
Keyword(s):  
Similar Distribution ◽  
Cholinergic Activity ◽  
Time Activity ◽  
Female Age ◽  
Tissue Compartment ◽  
Cholinergic Dysfunction ◽  
Parasympathetic Function ◽  
Volume Estimates ◽  
The Brain ◽  
Healthy Participants

Abstract In contrast to cardiac sympathetic activity which can be assessed with established PET tracers, there are currently no suitable radioligands to measure cardiac parasympathetic (cholinergic) activity. A radioligand able to measure cardiac cholinergic activity would be an invaluable clinical and research tool since cholinergic dysfunction has been associated with a wide array of pathologies (e.g., chronic heart failure, myocardial infarction, arrythmias). [18F]Fluoroethoxybenzovesamicol (FEOBV) is a cholinergic radiotracer that has been extensively validated in the brain. Whether FEOBV PET can be used to assess cholinergic activity in the heart is not known. Hence, this study aimed to evaluate the properties of FEOBV for cardiac PET imaging and cholinergic activity mapping. PET data were collected for 40 minutes after injection of 230 ± 50 MBq of FEOBV in four healthy participants (1 female; Age: 37 ± 10; BMI: 25 ± 2). Dynamic LV time activity curves were fitted with Logan graphical, 1-tissue compartment, and 2-tissue compartment models, yielding similar distribution volume estimates for each participant. Our initial data show that FEOBV PET has favorable tracer kinetics for quantification of cholinergic activity and is a promising new method for assessing parasympathetic function in the heart.

The effects of a mid-task break on the brain connectome in healthy participants: A resting-state functional MRI study

NeuroImage ◽  
2017 ◽  
Vol 152 ◽  
pp. 19-30 ◽  
Author(s):  
Yu Sun ◽  
Julian Lim ◽  
Zhongxiang Dai ◽  
KianFoong Wong ◽  
Fumihiko Taya ◽  
...  
Keyword(s):  
Functional Mri ◽  
Resting State ◽  
Brain Connectome ◽  
Mri Study ◽  
The Brain ◽  
Healthy Participants

scholarly journals The Brain is Hypothermic in Patients with Mitochondrial Diseases

2014 ◽  
Vol 34 (5) ◽  
pp. 915-920 ◽  
Author(s):  
Mario Rango ◽  
Andrea Arighi ◽  
Cristiana Bonifati ◽  
Roberto Del Bo ◽  
Giacomo Comi ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Visual Stimulation ◽  
Brain Temperature ◽  
Mitochondrial Diseases ◽  
High Energy ◽  
Phosphate Content ◽  
High Energy Phosphate ◽  
Dna Mutations ◽  
The Brain ◽  
Healthy Participants

We sought to study brain temperature in patients with mitochondrial diseases in different functional states compared with healthy participants. Brain temperature and mitochondrial function were monitored in the visual cortex and the centrum semiovale at rest and during and after visual stimulation in seven individuals with mitochondrial diseases ( n = 5 with mitochondrial DNA mutations and n = 2 with nuclear DNA mutations) and in 14 age- and sex-matched healthy control participants using a combined approach of visual stimulation, proton magnetic resonance spectroscopy (MRS), and phosphorus MRS. Brain temperature in control participants exhibited small changes during visual stimulation and a consistent increase, together with an increase in high-energy phosphate content, after visual stimulation. Brain temperature was persistently lower in individuals with mitochondrial diseases than in healthy participants at rest, during activation, and during recovery, without significant changes from one state to another and with a decrease in the high-energy phosphate content. The lowest brain temperature was observed in the patient with the most deranged mitochondrial function. In patients with mitochondrial diseases, the brain is hypothermic because of malfunctioning oxidative phosphorylation. Neuronal activity is reduced at rest, during physiologic brain stimulation, and after stimulation.

Changes in Speed of Information Processing in the Brain Following Tendon Repair

2008 ◽  
Vol 33 (6) ◽  
pp. 760-764 ◽  
Author(s):  
M. W. STENEKES ◽  
C. K. VAN DER SLUIS ◽  
J. -P. A. NICOLAI ◽  
J. H. B. GEERTZEN ◽  
TH. MULDER
Keyword(s):  
Information Processing ◽  
Flexor Tendon ◽  
Tendon Repair ◽  
Repeated Measurements ◽  
Flexor Tendon Repair ◽  
Preparation Time ◽  
Significant Deterioration ◽  
Speed Of Information Processing ◽  
The Brain ◽  
Healthy Participants

The objective of this study was to measure the “preparation time” that is the speed of information processing in the brain, and discuss the relevance of this parameter in the restoration of hand function following flexor tendon repair. The preparation time of 48 healthy adult participants was measured twice at a 6-week interval and compared with that of 12 patients after flexor tendon repair. There was no difference between the left and right hands of the healthy participants. The correlation between repeated measurements was high, although healthy participants performed 2.6% faster 6 weeks after the first measurement. After 6 weeks of immobilisation, patients showed a significant deterioration with respect to the speed of information processing by the brain on both the injured and uninjured sides compared with healthy participants, who had improved between the first and the second measurements. The results indicate that a period of lack of normal use of the hand leads to a change in cerebral control of hand movements.

scholarly journals Association between COMT gene Val158Met heterozygote polymorphism and enhanced brain predicting processes

2020 ◽  
Author(s):  
L. Bonetti ◽  
N.A. Sedghi ◽  
S.E.P. Bruzzone ◽  
N.T. Haumann ◽  
T. Paunio ◽  
...  
Keyword(s):  
Inferior Frontal Gyrus ◽  
Survival Function ◽  
Comt Gene ◽  
Genetic Mutations ◽  
Neural Responses ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Middle Temporal ◽  
The Brain ◽  
Healthy Participants

AbstractPredicting events in the ever-changing environment is a fundamental survival function intrinsic to the physiology of sensory systems, whose efficiency varies among the population. Even though it is established that a major source of such variations is genetic heritage, there are no studies tracking down auditory predicting processes to genetic mutations. Thus, we examined the neurophysiological responses to deviant stimuli recorded with magnetoencephalography (MEG) in 108 healthy participants carrying different variants of the Val158Met single-nucleotide polymorphism (SNP) within the catechol-O-methyltransferase (COMT) gene, which is responsible for the majority of catecholamines degradation in the prefrontal cortex. Our results showed significant amplitude enhancement of neural responses localized within inferior frontal gyrus, superior and middle temporal cortices to deviant auditory stimuli in heterozygote genotype carriers (Val/Met) vs homozygote (Val/Val and Met/Met) carriers. Integrating neurophysiology and genetics, this study provided new and broader insights into the brain mechanisms underlying optimal deviant detection.

scholarly journals Same Brain, Different Look?—The Impact of Scanner, Sequence and Preprocessing on Diffusion Imaging Outcome Parameters

2021 ◽  
Vol 10 (21) ◽  
pp. 4987
Author(s):  
Ronja Thieleking ◽  
Rui Zhang ◽  
Maria Paerisch ◽  
Kerstin Wirkner ◽  
Alfred Anwander ◽  
...  
Keyword(s):  
Data Acquisition ◽  
Diffusion Imaging ◽  
Mean Diffusivity ◽  
Brain Regions ◽  
Clinical Diagnostics ◽  
Neuroimaging Data ◽  
Age Range ◽  
The Impact ◽  
The Brain ◽  
Healthy Participants

In clinical diagnostics and longitudinal studies, the reproducibility of MRI assessments is of high importance in order to detect pathological changes, but developments in MRI hard- and software often outrun extended periods of data acquisition and analysis. This could potentially introduce artefactual changes or mask pathological alterations. However, if and how changes of MRI hardware, scanning protocols or preprocessing software affect complex neuroimaging outcomes from, e.g., diffusion weighted imaging (DWI) remains largely understudied. We therefore compared DWI outcomes and artefact severity of 121 healthy participants (age range 19–54 years) who underwent two matched DWI protocols (Siemens product and Center for Magnetic Resonance Research sequence) at two sites (Siemens 3T Magnetom Verio and Skyrafit). After different preprocessing steps, fractional anisotropy (FA) and mean diffusivity (MD) maps, obtained by tensor fitting, were processed with tract-based spatial statistics (TBSS). Inter-scanner and inter-sequence variability of skeletonised FA values reached up to 5% and differed largely in magnitude and direction across the brain. Skeletonised MD values differed up to 14% between scanners. We here demonstrate that DTI outcome measures strongly depend on imaging site and software, and that these biases vary between brain regions. These regionally inhomogeneous biases may exceed and considerably confound physiological effects such as ageing, highlighting the need to harmonise data acquisition and analysis. Future studies thus need to implement novel strategies to augment neuroimaging data reliability and replicability.

scholarly journals A functional connectome phenotyping dataset including cognitive state and personality measures

2017 ◽  
Author(s):  
Natacha Mendes ◽  
Sabine Oligschläger ◽  
Mark E. Lauckner ◽  
Johannes Golchert ◽  
Julia M. Huntenburg ◽  
...  
Keyword(s):  
Cognitive Abilities ◽  
Mind Wandering ◽  
Cognitive State ◽  
Mental Experience ◽  
Cognitive Faculties ◽  
Magnetic Resonance Imaging Mri ◽  
Personality Features ◽  
The Brain ◽  
Healthy Participants ◽  
Scanning Session

AbstractThe dataset enables exploration of higher-order cognitive faculties, self-generated mental experience, and personality features in relation to the intrinsic functional architecture of the brain. We provide multimodal magnetic resonance imaging (MRI) data and a broad set of state and trait phenotypic assessments: mind-wandering, personality traits, and cognitive abilities. Specifically, 194 healthy participants (between 20 and 75 years of age) filled out 31 questionnaires, performed 7 tasks, and reported 4 probes of in-scanner mind-wandering. The scanning session included four 15.5-min resting-state functional MRI runs using a multiband EPI sequence and a high-resolution structural scan using a 3D MP2RAGE sequence. This dataset constitutes one part of the MPI-Leipzig Mind-Brain-Body database.

scholarly journals Velocity Pulsatility and Arterial Distensibility Along the Internal Carotid Artery

2020 ◽  
Vol 9 (16) ◽  
Author(s):  
Rick J. van Tuijl ◽  
Ynte M. Ruigrok ◽  
Birgitta K. Velthuis ◽  
Irene C. van der Schaaf ◽  
Gabriël J. E. Rinkel ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Internal Carotid Artery ◽  
Pulsatility Index ◽  
Internal Carotid ◽  
Arterial Distensibility ◽  
Carotid Siphon ◽  
Carotid Canal ◽  
The Brain ◽  
Healthy Participants

Background Attenuation of velocity pulsatility along the internal carotid artery (ICA) is deemed necessary to protect the microvasculature of the brain. The role of the carotid siphon within the whole ICA trajectory in pulsatility attenuation is still poorly understood. This study aims to assess arterial variances in velocity pulsatility and distensibility over the whole ICA trajectory, including effects of age and sex. Methods and Results We assessed arterial velocity pulsatility and distensibility using flow‐sensitized 2‐dimensional phase‐contrast 3.0 Tesla magnetic resonance imaging in 118 healthy participants. Velocity pulsatility index (vPI=(V max −V min )/V mean ) and arterial distensibility defined as area pulsatility index (A max −A min )/A mean ) were calculated at C1, C3, and C7 segments of the ICA. vPI increased between C1 and C3 (0.85±0.13 versus 0.93±0.13, P <0.001 for averaged right+left ICA) and decreased between C3 and C7 (0.93±0.13 versus 0.84±0.13, P <0.001) with overall no effect (C1–C7). Conversely, the area pulsatility index decreased between C1 and C3 (0.18±0.06 versus 0.14±0.04, P <0.001) and increased between C3 and C7 (0.14±0.04 versus 0.31±0.09, P <0.001). vPI in men is higher than in women and increases with age ( P <0.015). vPI over the carotid siphon declined with age but remained stable over the whole ICA trajectory. Conclusions Along the whole ICA trajectory, vPI increased from extracranial C1 up to the carotid siphon C3 with overall no effect on vPI between extracranial C1 and intracranial C7 segments. This suggests that the bony carotid canal locally limits the arterial distensibility of the ICA, increasing the vPI at C3 which is consequently decreased again over the carotid siphon. In addition, vPI in men is higher and increases with age.

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