Image-guided Placement of Magnetic Neuroparticles as a Potential High-Resolution Brain-Machine Interface

We are developing methods of noninvasively delivering magnetic neuroparticles™ via intranasal administration followed by image-guided magnetic propulsion to selected locations in the brain. Once placed, the particles can activate neurons via vibrational motion or magnetoelectric stimulation. Similar particles might be used to read out neuronal electrical pulses via spintronic or liquid-crystal magnetic interactions, for fast bidirectional brain-machine interface. We have shown that particles containing liquid crystals can be read out with magnetic resonance imaging (MRI) using embedded magnetic nanoparticles and that the signal is visible even for voltages comparable to physiological characteristics. Such particles can be moved within the brain (e.g., across midline) without causing changes to neurological firing

Design, Construction and Validation of a New Generation of Bioreactors for Tissue Engineering Applications.

132 p.The thesis reports on the design, fabrication and validation of a new generation of bioreactors for cell culture stimulation, in order to improve cell proliferation in advanced tissue engineering strategies. Bioreactors are developed to take advantage of responsive materials allowing to mimic cell microenvironments, resembling some of the most common physical stimuli within the human body. Some stimuli can be produced by polymer-based scaffolds such as magnetoelectric, which can work as mechanical and electrical actuators.Two types of bioreactors were developed: one for bone tissue engineering through magnetoelectric stimulation (through mechanical vibration and piezoelectricity) and another for muscle tissue engineering through mechanical stretching and controlled current impulses.This project encompasses several fields of engineering such as device engineering, design, mechanics and electronics, having also into account proper material selection and the final biomedical application

Моделирование магнитотаргетинга лекарственных средств, основанное на вычислении проницаемости электромагнитного поля в ткани организма человека

Analysis of studies in the field of targeted delivery of drugs, genes and stem cells showed a low level of accuracy of both applied and practical research in this area. Sufficiently encouraging results were obtained with extracorporeal electromagnetic action on a pharmacological complex with a ferromagnetic nanoparticle. With this approach, it is rather difficult to implement the algorithm for introducing the drug into the topographic region (target organ), since in practice, approaches to the clinical application of drug transport technology, taking into account the physicochemical properties of human body tissues, have not been studied in detail. The available models represent various physical and mathematical approaches that do not take into account the bioelectrical and electrostatic properties of the tissues of the organisms of experimental animals and humans. The creation of algorithms and software simulation of this technology will allow calculating variable frequency variables for magnetotargeting in a human digital phantom, which will reduce time spent at the stage of pilot and clinical trials and in the future will form the applied part of the innovative technology. The article presents the methodology and results of multiphysics and mathematical modeling in the Sim4Life for Science, V7.0 package on the example of calculating the control parameters of the electromagnetic field of the region in the area of normal administration of drugs – the vessels of the forearm.Анализ исследований в области таргетной доставки препаратов, генов и стволовых клеток показал низкий уровень точности прикладных и практических исследований в данной области. В настоящее время применяется экстракорпоральное электромагнитное воздействие на фармакологический комплекс с наночастицей ферромагнетика. Однако при таком подходе достаточно сложно реализовать алгоритм введения препарата в топографическую область (орган-мишень), поскольку на практике клиническое применение технологии транспорта лекарственных средств с учетом физико-химических свойств тканей организма человека детально не изучено. Существующие модели представляют различные физико-математические подходы, которые не учитывают биоэлектрические и электростатические свойства тканей изучаемых организмов животных и человека. Разработка алгоритмов и программного моделирования данной технологии позволит рассчитать переменные частоты для магнитотаргетинга в цифровом фантоме человека. Это уменьшит временные затраты на стадии пилотных и клинических испытаний. В статье приведены методология и результаты мультифизического и математического моделирования в пакете Sim4Life for Science, V7.0 на примере вычислений управляющих параметров электромагнитного поля региона в области обычного введения препаратов – в сосуды предплечья

Simulation of Magnetotargeting of Medicines Based on the Calculation of Permeability of Human Tissues by the Electromagnetic Field

Анализ исследований в области таргетной доставки препаратов, генов и стволовых клеток показал низкий уровень точности прикладных и практических исследований в данной области. В настоящее время применяется экстракорпоральное электромагнитное воздействие на фармакологический комплекс с наночастицей ферромагнетика. Однако при таком подходе достаточно сложно реализовать алгоритм введения препарата в топографическую область (орган-мишень), поскольку на практике клиническое применение технологии транспорта лекарственных средств с учетом физико-химических свойств тканей организма человека детально не изучено. Существующие модели представляют различные физико-математические подходы, которые не учитывают биоэлектрические и электростатические свойства тканей изучаемых организмов животных и человека. Разработка алгоритмов и программного моделирования данной технологии позволит рассчитать переменные частоты для магнитотаргетинга в цифровом фантоме человека. Это уменьшит временные затраты на стадии пилотных и клинических испытаний. В статье приведены методология и результаты мультифизического и математического моделирования в пакете Sim4Life for Science, V7.0 на примере вычислений управляющих параметров электромагнитного поля региона в области обычного введения препаратов – в сосуды предплечья

The value of electrical stimulation as an exercise training modality

Voluntary exercise is the traditional way of improving performance of the human body in both the healthy and unhealthy states. Physiological responses to voluntary exercise are well documented. It benefits the functions of bone, joints, connective tissue, and muscle. In recent years, research has shown that neuromuscular electrical stimulation (NMES) simulates voluntary exercise in many ways. Generically, NMES can perform three major functions: suppression of pain, improve healing of soft tissues, and produce muscle contractions. Low frequency NMES may gate or disrupt the sensory input to the central nervous system which results in masking or control of pain. At the same time NMES may contribute to the activation of endorphins, serotonin, vasoactive intestinal polypeptides, and ACTH which control pain and may even cause improved athletic performances. Soft tissue conditions such as wounds and inflammations have responded very favorably to NMES. NMES of various amplitudes can induce muscle contractions ranging from weak to intense levels. NMES seems to have made its greatest gains in rehabilitation where directed muscle contractions may improve joint ranges of motion correct joint contractures that result from shortening muscles; control abnormal movements through facilitating recruitment or excitation into the alpha motoneuron in orthopedically, neurologically, or healthy subjects with intense sensory, kinesthetic, and proprioceptive information; provide a conservative approach to management of spasticity in neurological patients; by stimulation of the antagonist muscle to a spastic muscle stimulation of the agonist muscle, and sensory habituation; serve as an orthotic substitute to conventional bracing used with stroke patients in lieu of dorsiflexor muscles in preventing step page gait and for shoulder muscles to maintain glenohumeral alignment to prevent subluxation; and of course NMES is used in maintaining or improving the performance or torque producing capability of muscle. NMES in exercise training is our major concern

Модель воздействия электромагнитного поля на биологические ткани .

The design of modern devices for extracorporeal magnetotherapy should be preceded by physical and mathematical modeling of all stages of the technology of the effect of magnetic fields on various types of body tissues, taking into account their dielectric properties. This is necessary to create an electromagnetic field with the necessary biotropic parameters. In this work, a mathematical model of the effect of electromagnetic field on biological tissues, such as muscles, skin and adipose tissue, is constructed. The mathematical model takes into account various parameters of biological tissue, such as electrical conductivity and relative dielectric constant. Based on the model, the parameters of the response in biological tissues (the amplitude of the response in the tissue and the maximum value of the current in the tissue) were calculated in the innovative Sim4Life 5.2 platform. To test the mathematical model, a laboratory model was used to measure the electrical characteristics of biological tissue. During the research, experiments were carried out with three biological samples: adipose tissue, muscle tissue and skin. The dependences of the response amplitude in biological samples on the output signal power are plotted. The results obtained characterize the use of the proposed operation algorithm in a complex based on the Sim4Life 5.2 platform and simulation of electromagnetic field with a biological object that is optimal for the creation and examination of technologies and devices for magnetotherapy and inductors of extracorporeal effects of magnetic field. This work will make it possible to familiarize a wider range of different experts with the capabilities of the platform not only for modeling new medical devices, but also for the examination of available and those already applied in healthcare.Проектированию современных приборов экстракорпоральной магнитотерапии должно предшествовать физико-математическое моделирование всех этапов технологии воздействия магнитных полей на различные типы тканей организма с учетом их диэлектрических свойств. Это нужно для создания электромагнитного поля с необходимыми биотропными параметрами. В данной работе построена математическая модель воздействия электромагнитного поля на биологические ткани, такие как мышцы, кожа и жировая ткань. Математическая модель учитывает различные параметры биологической ткани, такие как удельная электропроводность и относительная диэлектрическая проницаемость. На основе модели рассчитаны параметры отклика в биологических тканях (амплитуда отклика в ткани и максимальное значение тока в ткани) в инновационной платформе Sim4Life 5.2. Для проверки математической модели использовался лабораторный макет для измерений электрических характеристик биологической ткани. В ходе проведения исследований были проведены эксперименты с тремя биологическими образцами: жировая ткань, мышечная ткань и кожа. Построены зависимости амплитуды отклика в биологических образцах от мощности выходного сигнала. Полученные результаты показывают использование предложенного алгоритма работы в комплексе на базе платформы Sim4Life 5.2 и симуляции электромагнитного поля с биологическим объектом, оптимальным для создания и экспертизы технологий и приборов магнитотерапии и индукторов экстракорпорального воздействия магнитного поля. Данная работа позволит ознакомить более широкий круг разного профиля специалистов с возможностями платформы Sim4Life 5.2 не только для моделирования новых приборов медицинского назначения, но и для экспертизы имеющихся и применяющихся в здравоохранении

Magnetic bioreactor for magneto-, mechano- and electroactive tissue engineering strategies

Biomimetic bioreactor systems are increasingly being developed for tissue engineering applications, due to their ability to recreate the native cell/tissue microenvironment. Regarding bone-related diseases and considering the piezoelectric nature of bone, piezoelectric scaffolds electromechanically stimulated by a bioreactor, providing the stimuli to the cells, allows a biomimetic approach and thus, mimicking the required microenvironment for effective growth and differentiation of bone cells. In this work, a bioreactor has been designed and built allowing to magnetically stimulate magnetoelectric scaffolds and therefore provide mechanical and electrical stimuli to the cells through magnetomechanical or magnetoelectrical effects, depending on the piezoelectric nature of the scaffold. While mechanical bioreactors need direct application of the stimuli on the scaffolds, the herein proposed magnetic bioreactors allow for a remote stimulation without direct contact with the material. Thus, the stimuli application (23 mT at a frequency of 0.3 Hz) to cells seeded on the magnetoelectric, leads to an increase in cell viability of almost 30% with respect to cell culture under static conditions. This could be valuable to mimic what occurs in the human body and for application in immobilized patients. Thus, special emphasis has been placed on the control, design and modeling parameters governing the bioreactor as well as its functional mechanism.FCT—Fundação para a Ciência e Tecnologia: UID/FIS/04650/2020; PTDC/BTM-MAT/28237/2017; PTDC/EMD-EMD/28159/2017 and SFRH/BPD/121464/2016. Spanish Ministry of Economy and Competitiveness (MINECO): MAT2016–76039-C4–3-R (AEI/FEDER, UE). Basque Government Industry and Education Department: ELKARTEK, PIB and PIBA (PIBA−2018–06) programs, respectively.info:eu-repo/semantics/publishedVersio

Does a single session of theta-burst transcranial magnetic stimulation of inferior temporal cortex affect tinnitus perception?

<p>Abstract</p> <p>Background</p> <p>Cortical excitability changes as well as imbalances in excitatory and inhibitory circuits play a distinct pathophysiological role in chronic tinnitus. Repetitive transcranial magnetic stimulation (rTMS) over the temporoparietal cortex was recently introduced to modulate tinnitus perception. In the current study, the effect of theta-burst stimulation (TBS), a novel rTMS paradigm was investigated in chronic tinnitus. Twenty patients with chronic tinnitus completed the study. Tinnitus severity and loudness were monitored using a tinnitus questionnaire (TQ) and a visual analogue scale (VAS) before each session. Patients received 600 pulses of continuous TBS (cTBS), intermittent TBS (iTBS) and intermediate TBS (imTBS) over left inferior temporal cortex with an intensity of 80% of the individual active or resting motor threshold. Changes in subjective tinnitus perception were measured with a numerical rating scale (NRS).</p> <p>Results</p> <p>TBS applied to inferior temporal cortex appeared to be safe. Although half of the patients reported a slight attenuation of tinnitus perception, group analysis resulted in no significant difference when comparing the three specific types of TBS. Converting the NRS into the VAS allowed us to compare the time-course of aftereffects. Only cTBS resulted in a significant short-lasting improvement of the symptoms. In addition there was no significant difference when comparing the responder and non-responder groups regarding their anamnestic and audiological data. The TQ score correlated significantly with the VAS, lower loudness indicating less tinnitus distress.</p> <p>Conclusion</p> <p>TBS does not offer a promising outcome for patients with tinnitus in the presented study.</p

A clinical study of motor evoked potentials using a triple stimulation technique

Amplitudes of motor evoked potentials (MEPs) are usually much smaller than those of motor responses to maximal peripheral nerve stimulation, and show marked variation between normal subjects and from one stimulus to another. Consequently, amplitude measurements have low sensitivity to detect central motor conduction failures due to the broad range of normal values. Since these characteristics are mostly due to varying desynchronization of the descending action potentials, causing different degrees of phase cancellation, we applied the recently developed triple stimulation technique (TST) to study corticospinal conduction to 489 abductor digiti minimi muscles of 271 unselected patients referred for possible corticospinal dysfunction. The TST allows resynchronization of the MEP, and thereby a quantification of the proportion of motor units activated by the transcranial stimulus. TST results were compared with those of conventional MEPs. In 212 of 489 sides, abnormal TST responses suggested conduction failure of various degrees. By contrast, conventional MEPs detected conduction failures in only 77 of 489 sides. The TST was therefore 2.75 times more sensitive than conventional MEPs in disclosing corticospinal conduction failures. When the results of the TST and conventional MEPs were combined, 225 sides were abnormal: 145 sides showed central conduction failure, 13 sides central conduction slowing and 67 sides both conduction failure and slowing. It is concluded that the TST is a valuable addition to the study of MEPs, since it improves detection and gives quantitative information on central conduction failure, an abnormality which appears to be much more frequent than conduction slowing. This new technique will be useful in following the natural course and the benefit of treatments in disorders affecting central motor conductio

Influence of Gut Microbiota on Behavior and Its Disturbances

Hippocrates statement that “All disease begins in the gut” continues to be up to date more than 2000 years later. Growing number of scientific reports focus on the important role of intestinal microorganisms for modulation of many systems and human behavior. As a key component of the gut brain, gut microbiota influences the development and maturation of the hypothalamic-pituitary-adrenal axis, affects the development and function of the immune system, regulates the blood-brain barrier, modulates the synthesis and recognition of neurotransmitters, regulates neurogenesis, formation of myelination and supports the development and function of the brain. Disruption of gut-brain axis function is associated with alterations in the stress response and might contribute to neuropsychiatric diseases as depression, autistic spectrum disorders, rapid eye movement sleep behavior disorder, Parkinson disease, Alzheimer disease and other mental conditions. Studies in animal models are crucial for guiding research on brain-gut-microbiome axis in humans, as the impact of microbiota on specific brain regions and aspects of animal behavior will help in the selection of tasks for cognitive assessment. Exploring the interaction of gut microbes and human brain will not only allow us to better understand the pathogenesis of neuropsychiatric disorders, but will also provide us new opportunities for the design of novel immuno- or microbe-based therapies