scholarly journals A Whole-Brain Map and Assay Parameter Analysis of Mouse VTA Dopaminergic Activation

Author(s):  
Horea-Ioan Ioanas ◽  
Bechara John Saab ◽  
Markus Rudin

AbstractAscending dopaminergic projections from neurons located in the Ventral Tegmental Area (VTA) are key to the etiology, dysfunction, and control of motivation, learning, and addiction. Due to evolutionary conservation of this nucleus and the extensive use of mice as disease models, establishing an assay for VTA dopaminergic signalling in the mouse brain is crucial for the translational investigation of neuronal function phenotypes of diseases and interventions. In this article we use optogenetic stimulation for VTA dopaminergic neuron stimulation, in combination with functional Magnetic Resonance Imaging (fMRI), a method widely used in human deep brain imaging. We present the first whole-brain opto-fMRI map of dopaminergic activation in the mouse, and show that VTA dopaminergic system function is consistent with but diverges in a few key aspects from its structure. While the activation map predominantly includes and excludes target areas according to their relative projection densities (e.g. strong activation of the nucleus accumbens and low activation of the hippocampus), it also includes areas for which a structural connection is not well established (such as the dorsomedial striatum). We further detail assay variability with regard to multiple experimental parameters, including stimulation protocol and implant position, and provide detailed evidence-based recommendations for assay reuse.

2011 ◽  
Vol 100 (3) ◽  
pp. 95a ◽  
Author(s):  
Aswini Kanneganti ◽  
Shivaranjani Shivalingaiah ◽  
ling Gu ◽  
George Alexandrakis ◽  
Samarendra Mohanty

2021 ◽  
Vol 15 ◽  
Author(s):  
Chengyuan Wu ◽  
Caio Matias ◽  
Thomas Foltynie ◽  
Patricia Limousin ◽  
Ludvic Zrinzo ◽  
...  

Background: Neuronal loss in Parkinson’s Disease (PD) leads to widespread neural network dysfunction. While graph theory allows for analysis of whole brain networks, patterns of functional connectivity (FC) associated with motor response to deep brain stimulation of the subthalamic nucleus (STN-DBS) have yet to be explored.Objective/Hypothesis: To investigate the distributed network properties associated with STN-DBS in patients with advanced PD.Methods: Eighteen patients underwent 3-Tesla resting state functional MRI (rs-fMRI) prior to STN-DBS. Improvement in UPDRS-III scores following STN-DBS were assessed 1 year after implantation. Independent component analysis (ICA) was applied to extract spatially independent components (ICs) from the rs-fMRI. FC between ICs was calculated across the entire time series and for dynamic brain states. Graph theory analysis was performed to investigate whole brain network topography in static and dynamic states.Results: Dynamic analysis identified two unique brain states: a relative hypoconnected state and a relative hyperconnected state. Time spent in a state, dwell time, and number of transitions were not correlated with DBS response. There were no significant FC findings, but graph theory analysis demonstrated significant relationships with STN-DBS response only during the hypoconnected state – STN-DBS was negatively correlated with network assortativity.Conclusion: Given the widespread effects of dopamine depletion in PD, analysis of whole brain networks is critical to our understanding of the pathophysiology of this disease. Only by leveraging graph theoretical analysis of dynamic FC were we able to isolate a hypoconnected brain state that contained distinct network properties associated with the clinical effects of STN-DBS.


2012 ◽  
Vol 184-185 ◽  
pp. 1521-1525
Author(s):  
Yu En Wu ◽  
Yu Hui Hu ◽  
Ya Ying Jin ◽  
Jun Qiang Xi

A CAN-Bus protocol analysis and verification method with three key aspects which are static analysis, dynamic analysis and verification &control is put forward. Static analysis ascertains the communication information of each node by bus residual method; Synchronous contrast method is put in use to obtain practical and effective control protocol in the dynamic analysis; Verification &control is to verify the correctness of the analytical protocol and to achieve the control of the critical subsystems by bus gateway system. This scheme has been used to analyze a foreign parallel hybrid powertrain system, and it proves the correctness of the designed static analysis and dynamic analysis, the applicability of verification &control.


2020 ◽  
pp. 4-25
Author(s):  
Karen Polinger Foster

This chapter discusses the role of exotica in the Mesopotamian mind. By 1875, The Epic of Gilgamesh had begun to emerge from the thousands of clay tablet fragments freshly unearthed in the remains of the great royal library of Assurbanipal at Nineveh. Gilgamesh’s drive to possess the exotic is rooted in long-standing Mesopotamian tradition. From the third millennium on, when he supposedly reigned, scholar-scribes organized and classified nearly all aspects of the natural world. Thematic lists of flora and fauna, heavenly bodies, precious and semiprecious materials, and topographical features provided the educated elite with a means of conceptualizing patterns and interrelationships. For Gilgamesh, as for many Mesopotamian rulers, the acquisition and display of exotica were key aspects of kingship. Once secured within the walled, urban cores of Mesopotamian cultural identity, exotica offered tangible signs of wide-ranging military might, commercial enterprise, and political status and control.


QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
A A Ashour ◽  
A M A Nassef ◽  
E M Awad ◽  
A M Hazzou ◽  
M A Nada ◽  
...  

Abstract Background Epilepsy is a serious common neurological disorder that can affect any age. Cognitive functions are highly prevalent in patients with epilepsy and is more likely to occur in patients with idiopathic generalized epilepsy (IGE). Associations were found between cognitive functions and brain volume loss in patients with epilepsy. Objective This work was carried out to assess the volumetric changes in brain of epileptic patients to use it as a biomarker for cognitive dysfunction in adult and adolescent patients with epilepsy. Patients and Methods A case control study was conducted to include 61 patients, 20 of which diagnosed with idiopathic generalized epilepsy (IGE), 21 with temporal lobe epilepsy (TLE) and 20 with frontal lobe epilepsy (FLE) who were selected from the epilepsy outpatient clinic in Ain Shams university hospitals along with 23 age and sex matched healthy controls. Both cases and control groups were subjected to Magnetic resonance imaging MRI brain volumetry and detailed cognitive testing. An informed consent was taken from each adult patient, guardian of adolescent patient and healthy control. Results Statistically significant difference in comprehension subcategory of the Wechsler adult intelligence scale (WAIS) between patients with IGE and healthy controls denoting poorer social judgment in the IGE group. The IGE group also showed poorer performance in digit symbol subcategory of the same test denoting worse psychomotor speed and sustained attention. Also, significant difference in similarities subcategory was found between TLE group and control group denoting poorer abstract thinking among the TLE group. The IGE and TLE groups also showed lower attention and concentration than control group in the mental control subcategory of the Wechsler memory scale (WMS) yet failed to show superiority over each other. No statistically significant difference was found on comparing the whole brain volume between cases and control groups. A statistically significant direct relationship was found between the arithmetic subcategory of WAIS and the whole brain volume of the patients among the patients of the FLE group. Conclusion Patients with IGE had worse psychomotor speed, sustained attention and concentration than healthy controls in addition to poorer social judgment. Also, patients with TLE showed lower attention and concentration together with poorer abstract thinking despite normal IQ. The study also concluded that increased whole brain volume in patients with frontal lobe epilepsy is associated with better mathematical problem solving.


Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Evangelia Tsolaki ◽  
Alon Kashanian ◽  
Nader Pouratian

Abstract INTRODUCTION Traditional targeting methods rely on indirect targeting with atlas-defined coordinates that induce interpatient anatomical and functional variability. Precise targeting is crucial for successful surgical intervention associated with improved surgical outcomes. Here, we use clinically weighted probabilistic tractography to investigate the connectivity from volume of tissue activated (VTA) to whole brain in order to evaluate the relationship between structural connectivity and clinical outcome of patients that underwent thalamic deep brain stimulation (DBS). METHODS Magnetic resonance imaging and clinical outcomes from 10 essential tremor (ET) patients who were treated by VIM-DBS at the University of California Los Angeles were evaluated. LeadBDS was used for the VTA calculation and FSL was used to evaluate the whole brain probabilistic tractography of VTA. Tractography maps were binarized and weighted based on the percent of clinical improvement using the Fahn-Tolosa-Martin Tremor Rating Score. The resulting clinically weighted maps were non-linearly fused to MNI space and averaged. These population maps provide a voxel-by-voxel map of the average clinical improvement observed when the VTA demonstrates structural connectivity to the whole brain. RESULTS The VTA connectivity to the whole brain was delineated. Superior clinical improvement was associated with connectivity to voxels connecting the thalamus to the precentral gyrus and to the brainstem/cerebellum. Also, the clinical efficacy map showed that patients with higher clinical improvement (>70%) presented stronger structural connectivity to the precentral gyrus and to the caudal projection to the cerebellum. CONCLUSION Stronger connectivity to the precentral gyrus and to brainstem/cerebellum is associated with superior clinical outcome in thalamic DBS for ET. In the future, rather than focusing on connectivity to predetermined targets, these clinically weighted tractography maps can be used with a reverse algorithm to identify the optimal region of the thalamus to provide clinically superior results.


Neurology ◽  
2020 ◽  
Vol 95 (16) ◽  
pp. e2246-e2258 ◽  
Author(s):  
Scott A. Norris ◽  
Aimee E. Morris ◽  
Meghan C. Campbell ◽  
Morvarid Karimi ◽  
Babatunde Adeyemo ◽  
...  

ObjectiveTo test the hypothesis that there is shared regional or global functional connectivity dysfunction in a large cohort of patients with isolated focal dystonia affecting different body regions compared to control participants. In this case-control study, we obtained resting-state MRI scans (three or four 7.3-minute runs) with eyes closed in participants with focal dystonia (cranial [17], cervical [13], laryngeal [18], or limb [10]) and age- and sex-matched controls.MethodsRigorous preprocessing for all analyses was performed to minimize effect of head motion during scan acquisition (dystonia n = 58, control n = 47 analyzed). We assessed regional functional connectivity by computing a seed-correlation map between putamen, pallidum, and sensorimotor cortex and all brain voxels. We assessed significant group differences on a cluster-wise basis. In a separate analysis, we applied 300 seed regions across the cortex, cerebellum, basal ganglia, and thalamus to comprehensively sample the whole brain. We obtained participant whole-brain correlation matrices by computing the correlation between seed average time courses for each seed pair. Weighted object-oriented data analysis assessed group-level whole-brain differences.ResultsParticipants with focal dystonia had decreased functional connectivity at the regional level, within the striatum and between lateral primary sensorimotor cortex and ventral intraparietal area, whereas whole-brain correlation matrices did not differ between focal dystonia and control groups. Rigorous quality control measures eliminated spurious large-scale functional connectivity differences between groups.ConclusionRegional functional connectivity differences, not global network level dysfunction, contributes to common pathophysiologic mechanisms in isolated focal dystonia. Rigorous quality control eliminated spurious large-scale network differences between patients with focal dystonia and control participants.


2011 ◽  
Vol 104 ◽  
pp. 103-113 ◽  
Author(s):  
Michael Haydn ◽  
Thomas Hauer ◽  
Eberhard Abele

Uncertainty during production processes has an important influence on the product quality as well as production costs. For multilevel process chains with serially connected processes, additional uncertainty can be caused by the previous step. The manufacturing of precision holes by drilling and reaming is an important multilevel process chain. The interactions between machine, tool and pre-drilled hole cause process errors during the quality determinant final reaming process. In this paper, a systematic approach for the identification and control of uncertainty during the reaming process is presented. Thus, the influence of key aspects like skewness of pre-drilled hole or the influences of material strength gradients are analyzed. Further, simulation models for the consideration of these uncertainties are presented.


Parasitology ◽  
2015 ◽  
Vol 144 (1) ◽  
pp. 81-94 ◽  
Author(s):  
C. V. HOLLAND

SUMMARYToxocara species infect a wide range of companion, domestic and wild animals as definitive and paratenic hosts, via multiple routes of transmission, producing long-lived tissue-inhabiting larvae and resistant eggs that can survive in the external environment. Therefore Toxocara and the disease it causes in humans, toxocariasis, represents an ideal aetiological agent for the development of the one health approach. However, despite increasing awareness of the public health significance of toxocariasis, gaps in our understanding of certain key aspects of the parasite's biology and epidemiology remain. These gaps hinder our ability to integrate research effort within the veterinary, medical and environmental disciplines. This review will highlight key deficits in our understanding of nine dimensions of Toxocara epidemiology and discuss a potential scenario to develop a more integrated, one health approach to improve our understanding of the prevention and control of this complex and cryptic zoonosis.


Sign in / Sign up

Export Citation Format

Share Document