Computational models of the thalamocortical circuit: sleep oscillations and receptive fields.

The thalamus is a subcortical structure, which consists of a collection of functionally and morphologically defined nuclei. A subset of these, the sensory nuclei, receive information from the periphery and relay it to the related primary cortical area. Hence the thalamus was traditionaUy assumed to passively relay afferent information. However, the fact that thalamic relay cells receive a large proportion of their sjoiaptic inputs from the cortical cells to which they project, has led to the consensus that there is a more significant thalamic contribution to sensory processing. This thesis investigates the role of the thalamocortical feedback loop using population-level computational models. In particular two states of thalamocortical activity are investigated: early sleep, and active visual processing. During early sleep, the network displays 7-14Hz spindle oscillations. These osciUations have been previously modelled using conductance-based paradigms, but here the activity is investigated through the nonhnear dynamics of the circuitry. It is shown that the circuit has an intrinsic resonant frequency in the spindles range. During visual processing, the role of the lateral geniculate nucleus (the primary visual thalamic nucleus) was previously overlooked, as thalamic receptive fields are spatially identical to those in the retina. Temporally however, thalamic and retinal responses differ in magnitude, and the second model in this thesis shows how cortical feedback can have a role in augmenting thalamic temporal responses. This model was reduced in order to find the minimal thalamic circuitry that can produce such responses, and this final model can also exhibit steady state oscillatory behaviour. The transition from transient visual activity to sustained oscillatory activity in this model, required a switch in the relative cortical feedback weights to the thalamocortical and the reticular populations. Together, these results indicate that the contribution of the thalamus to neural activity can no longer be ignored

Mapping the current flow in sacral nerve stimulation using computational modelling

© The Institution of Engineering and Technology 2019Sacral nerve stimulation (SNS) is an established treatment for faecal incontinence involving the implantation of a quadripolar electrode into a sacral foramen, through which an electrical stimulus is applied. Little is known about the induced spread of electric current around the SNS electrode and its effect on adjacent tissues, which limits optimisation of this treatment. The authors constructed a 3-dimensional imaging based finite element model in order to calculate and visualise the stimulation induced current and coupled this to biophysical models of nerve fibres. They investigated the impact of tissue inhomogeneity, electrode model choice and contact configuration and found a number of effects. (i) The presence of anatomical detail changes the estimate of stimulation effects in size and shape. (ii) The difference between the two models of electrodes is minimal for electrode contacts of the same length. (iii) Surprisingly, in this arrangement of electrode and neural fibre, monopolar and bipolar stimulation induce a similar effect. (iv) Interestingly when the active contact is larger, the volume of tissue activated reduces. This work establishes a protocol to better understand both therapeutic and adverse stimulation effects and in the future will enable patient-specific adjustments of stimulation parameters.Peer reviewe

A population model of deep brain stimulation in movement disorders from circuits to cells

Copyright © 2020 Yousif, Bain, Nandi and Borisyuk.For more than 30 years, deep brain stimulation (DBS) has been used to target the symptoms of a number of neurological disorders and in particular movement disorders such as Parkinson's disease (PD) and essential tremor (ET). It is known that the loss of dopaminergic neurons in the substantia nigra leads to PD, while the exact impact of this on the brain dynamics is not fully understood, the presence of beta-band oscillatory activity is thought to be pathological. The cause of ET, however, remains uncertain, however pathological oscillations in the thalamocortical-cerebellar network have been linked to tremor. Both of these movement disorders are treated with DBS, which entails the surgical implantation of electrodes into a patient's brain. While DBS leads to an improvement in symptoms for many patients, the mechanisms underlying this improvement is not clearly understood, and computational modeling has been used extensively to improve this. Many of the models used to study DBS and its effect on the human brain have mainly utilized single neuron and single axon biophysical models. We have previously shown in separate models however, that the use of population models can shed much light on the mechanisms of the underlying pathological neural activity in PD and ET in turn, and on the mechanisms underlying DBS. Together, this work suggested that the dynamics of the cerebellar-basal ganglia thalamocortical network support oscillations at frequency range relevant to movement disorders. Here, we propose a new combined model of this network and present new results that demonstrate that both Parkinsonian oscillations in the beta band and oscillations in the tremor frequency range arise from the dynamics of such a network. We find regions in the parameter space demonstrating the different dynamics and go on to examine the transition from one oscillatory regime to another as well as the impact of DBS on these different types of pathological activity. This work will allow us to better understand the changes in brain activity induced by DBS, and allow us to optimize this clinical therapy, particularly in terms of target selection and parameter setting.Peer reviewe

Modelling a permanent magnet synchronous motor in FEniCSx for parallel high-performance simulations

© 2022 The Authors. Published by Elsevier B.V. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/There are concerns that the extreme requirements of heavy-duty vehicles and aviation will see them left behind in the electrification of the transport sector, becoming the most significant emitters of greenhouse gases. Engineers extensively use the finite element method to analyse and improve the performance of electric machines, but new highly scalable methods with a linear (or near) time complexity are required to make extreme-scale models viable. This paper introduces a three-dimensional permanent magnet synchronous motor model using FEniCSx, a finite element platform tailored for efficient computing and data handling at scale. The model demonstrates comparable magnetic flux density distributions to a verification model built in Ansys Maxwell with a maximum deviation of 7% in the motor’s static regions. Solving the largest mesh, comprising over eight million cells, displayed a speedup of 198 at 512 processes. A preconditioned Krylov subspace method was used to solve the system, requiring 92% less memory than a direct solution. It is expected that advances built on this approach will allow system-level multiphysics simulations to become feasible within electric machine development. This capability could provide the near real-world accuracy needed to bring electric propulsion systems to large vehicles.Peer reviewe

Movement speed is biased by prior experience

© 2013 The American Physiological Society. This is an Open Access article licensed under the Creative Commons Attribution license CC BY 3.0 https://creativecommons.org/licenses/by/3.0/deed.en_US which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.How does the motor system choose the speed for any given movement? Many current models assume a process that finds the optimal balance between the costs of moving fast and the rewards of achieving the goal. Here, we show that such models also need to take into account a prior representation of preferred movement speed, which can be changed by prolonged practice. In a time-constrained reaching task, human participants made 25-cm reaching movements within 300, 500, 700, or 900 ms. They were then trained for 3 days to execute the movement at either the slowest (900-ms) or fastest (300-ms) speed. When retested on the 4th day, movements executed under all four time constraints were biased toward the speed of the trained movement. In addition, trial-to-trial variation in speed of the trained movement was significantly reduced. These findings are indicative of a use-dependent mechanism that biases the selection of speed. Reduced speed variability was also associated with reduced errors in movement amplitude for the fast training group, which generalized nearly fully to a new movement direction. In contrast, changes in perpendicular error were specific to the trained direction. In sum, our results suggest the existence of a relatively stable but modifiable prior of preferred movement speed that influences the choice of movement speed under a range of task constraints.Peer reviewedFinal Published versio

English Intensifiers as Devices of Emotional Enhancement

Intensifiers are adverbials or adverbial phrases that are used to enhance the meanings of certain constructions. The study aims to investigate English intensifiers and their functions as devices of emotional enhancement .Moreover; they identify students with this grammatical item. The significance of the research is that intensifiers function as linguistic devices to maximize the meaning or, in a certain sense, intensify the emotional tone of words and expressions. Some commonly used intensifiers include very, too, at all, absolutely, extremely, really, wh-words or expressions, etc. e.g. what on earth are you doing? In terms of their semantic classes, intensifiers can be divided into Amplifiers, Emphasizers and Downtoners. The problem of this research is that the students find it difficult to comprehend the functions of English intensifiers. In terms of the method used in this research, the researcher tries to give a detailed analysis of the most common English intensifiers. An exercise relevant to the topic is adopted to enhance the research. The analysis of the results reveals that the third-year Iraqi college students succeed in operating intensifiers in a way that shows their ability to handle this grammatical item.

The evolution of ventral intermediate nucleus targeting in MRI-guided focused ultrasound thalamotomy for essential tremor: an international multi-center evaluation

© 2024 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Background: The ventral intermediate nucleus (VIM) is the premiere target in magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for tremor; however, there is no consensus on the optimal coordinates for ablation. This study aims to ascertain the various international VIM targeting approaches (VIM-TA) and any evolution in practice. Methods: International MRgFUS centers were invited to share VIM-TAs in 2019 and 2021. Analyses of any modification in practice and of anatomical markers and/or tractography in use were carried out. Each VIM-TA was mapped in relation to the mid-commissural point onto a 3D thalamic nucleus model created from the Schaltenbrand–Wahren atlas. Results: Of the 39 centers invited, 30 participated across the study period, providing VIM-TAs from 26 centers in 2019 and 23 in 2021. The results are reported as percentages of the number of participating centers in that year. In 2019 and 2021, respectively, 96.2% (n = 25) and 95.7% (n = 22) of centers based their targeting on anatomical landmarks rather than tractography. Increased adoption of tractography in clinical practice and/or for research was noted, changing from 34.6% to 78.3%. There was a statistically significant change in VIM-TAs in the superior-inferior plane across the study period; the percentage of VIM-TAs positioned 2 mm above the intercommissural line (ICL) increased from 16.0% in 2019 to 40.9% in 2021 (WRST, p < 0.05). This position is mapped at the center of VIM on the 3D thalamic model created based on the Schaltenbrand–Wahren atlas. In contrast, the VIM-TA medial-lateral and anterior-posterior positions remained stable. In 2022, 63.3% of participating centers provided the rationale for their VIM-TAs and key demographics. The centers were more likely to target 2 mm above the ICL if they had increased experience (more than 100 treatments) and/or if they were North American. Conclusion: Across the study period, FUS centers have evolved their VIM targeting superiorly to target the center of the VIM (2 mm above the ICL) and increased the adoption of tractography to aid VIM localization. This phenomenon is observed across autonomous international centers, suggesting that it is a more optimal site for FUS thalamotomy in tremors.Peer reviewe

Dopamine Activation Preserves Visual Motion Perception Despite Noise Interference of Human V5/MT

Copyright © 2016 Yousif et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License Creative Commons Attribution 4.0 International, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.When processing sensory signals, the brain must account for noise, both noise in the stimulus and that arising from within its own neuronal circuitry. Dopamine receptor activation is known to enhance both visual cortical signal-to-noise-ratio (SNR) and visual perceptual performance; however, it is unknown whether these two dopamine-mediated phenomena are linked. To assess this, we used single-pulse transcranial magnetic stimulation (TMS) applied to visual cortical area V5/MT to reduce the SNR focally and thus disrupt visual motion discrimination performance to visual targets located in the same retinotopic space. The hypothesis that dopamine receptor activation enhances perceptual performance by improving cortical SNR predicts that dopamine activation should antagonize TMS disruption of visual perception. We assessed this hypothesis via a double-blinded, placebo-controlled study with the dopamine receptor agonists cabergoline (a D2 agonist) and pergolide (a D1/D2 agonist) administered in separate sessions (separated by 2 weeks) in 12 healthy volunteers in a William's balance-order design. TMS degraded visual motion perception when the evoked phosphene and the visual stimulus overlapped in time and space in the placebo and cabergoline conditions, but not in the pergolide condition. This suggests that dopamine D1 or combined D1 and D2 receptor activation enhances cortical SNR to boost perceptual performance. That local visual cortical excitability was unchanged across drug conditions suggests the involvement of long-range intracortical interactions in this D1 effect. Because increased internal noise (and thus lower SNR) can impair visual perceptual learning, improving visual cortical SNR via D1/D2 agonist therapy may be useful in boosting rehabilitation programs involving visual perceptual training.Peer reviewe

Evaluation of Imprint Cytology of Endoscopic Gastric Mucosa Biopsy in the Diagnosis of Helicobacter pylori Infection

Background:Helicobacter pylori colonization of the gastric mucosa is associated with the pathogenesis of gastritis, peptic ulcer disease, and gastric malignancy. There are several methods to detect the presence of Helicobacter pylori.These tests include noninvasive method (serology, urea breath test, or stool antigen test) and invasive methods, such as, culture, histological examination, and rapid urease test. Method:This descriptive prospective cross sectional study was conducted in Gezira state in Wad Madeni from March - August 2016;it aimed to determine the sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of imprint cytology in the detection of H. pylori compared with stool Ag test. H.pylori stool Ag test was done for 50 clinically suspected patients for H.pylori infection and one gastric biopsy from each patient was collected during endoscopy. Air-dried imprint smears of gastric biopsies were stained by the Diff-Quik method and examined for H.pylori. The presence of inflammation and intestinal metaplasia were documented. Results: The H. pylori prevalence was 38% by stool Ag test and 42% by imprint cytology. The sensitivity and specificity of imprint cytology in the detection of H. pylori were 89.5% and 87.1% respectively. The PPV and NPV were 80.1% and 93.1%, respectively. The accuracy of the test was 88.0%. Conclusion:This study concludes that gastric imprint smears stained with Diff-Quik method is a rapid, cheap, and reliable method for the detection of H.pylori infection.It recommends the use of Imprint cytology for detection of Helicobacter pylori inpatients undergoing upper gastrointestinal endoscopy

Illusions of Self‐Motion during Magnetic Resonance ‐Guided Focused Ultrasound Thalamotomy for Tremor

© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Objective: Brain networks mediating vestibular perception of self‐motion overlap with those mediating balance. A systematic mapping of vestibular perceptual pathways in the thalamus may reveal new brain modulation targets for improving balance in neurological conditions. Methods: Here, we systematically report how magnetic resonance‐guided focused ultrasound surgery of the nucleus ventralis intermedius of the thalamus commonly evokes transient patient‐reported illusions of self‐motion. In 46 consecutive patients, we linked the descriptions of self‐motion to sonication power and 3‐dimensional (3D) coordinates of sonication targets. Target coordinates were normalized using a standard atlas, and a 3D model of the nucleus ventralis intermedius and adjacent structures was created to link sonication target to the illusion. Results: A total of 63% of patients reported illusions of self‐motion, which were more likely with increased sonication power and with targets located more inferiorly along the rostrocaudal axis. Higher power and more inferiorly targeted sonications increased the likelihood of experiencing illusions of self‐motion by 4 and 2 times, respectively (odds ratios = 4.03 for power, 2.098 for location). Interpretation: The phenomenon of magnetic vestibular stimulation is the most plausible explanation for these illusions of self‐motion. Temporary unilateral modulation of vestibular pathways (via magnetic resonance‐guided focused ultrasound) unveils the central adaptation to the magnetic field‐induced peripheral vestibular bias, leading to an explicable illusion of motion. Consequently, systematic mapping of vestibular perceptual pathways via magnetic resonance‐guided focused ultrasound may reveal new intracerebral targets for improving balance in neurological conditions. ANN NEUROL 2024Peer reviewe