The impact of large structural brain changes in chronic stroke patients on the electric field caused by transcranial brain stimulation

Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (TDCS) are two types of non-invasive transcranial brain stimulation (TBS). They are useful tools for stroke research and may be potential adjunct therapies for functional recovery. However, stroke often causes large cerebral lesions, which are commonly accompanied by a secondary enlargement of the ventricles and atrophy. These structural alterations substantially change the conductivity distribution inside the head, which may have potentially important consequences for both brain stimulation methods. We therefore aimed to characterize the impact of these changes on the spatial distribution of the electric field generated by both TBS methods. In addition to confirming the safety of TBS in the presence of large stroke-related structural changes, our aim was to clarify whether targeted stimulation is still possible. Realistic head models containing large cortical and subcortical stroke lesions in the right parietal cortex were created using MR images of two patients. For TMS, the electric field of a double coil was simulated using the finite-element method. Systematic variations of the coil position relative to the lesion were tested. For TDCS, the finite-element method was used to simulate a standard approach with two electrode pads, and the position of one electrode was systematically varied. For both TMS and TDCS, the lesion caused electric field “hot spots” in the cortex. However, these maxima were not substantially stronger than those seen in a healthy control. The electric field pattern induced by TMS was not substantially changed by the lesions. However, the average field strength generated by TDCS was substantially decreased. This effect occurred for both head models and even when both electrodes were distant to the lesion, caused by increased current shunting through the lesion and enlarged ventricles. Judging from the similar peak field strengths compared to the healthy control, both TBS methods are safe in patients with large brain lesions (in practice, however, additional factors such as potentially lowered thresholds for seizure-induction have to be considered). Focused stimulation by TMS seems to be possible, but standard tDCS protocols appear to be less efficient than they are in healthy subjects, strongly suggesting that tDCS studies in this population might benefit from individualized treatment planning based on realistic field calculations. Keywords: Transcranial magnetic stimulation, Transcranial direct current stimulation, Chronic stroke, Brain lesions, Field simulations, Finite element metho

Numerical human head modelling and investigation for precise tDCS applications

As a non-invasive and sub-convulsive functional stimulation technique, transcranial direct current stimulation (tDCS) generates a relatively weak current intensity and applies the moderate current to the brain to modulate the level of cortical excitability. This neuromodulatory technique has been extensively used as a potential clinical treatment for various neuropsychiatric conditions, ranging from depression, addition to schizophrenia and Parkinson’s disease. Recently, tDCS has also been researched as a promising alternative treatment to alleviate neuropathic pain of cancer patients. The focus of this project is to numerically investigate the precise applications of tDCS based on a series of high resolution realistic human head model using finite element methods. Specifically, the influence of brain shift caused by gravity was firstly pre-validated using real shaped human head model. After that, this study focuses on the investigation of tDCS applications on the brain cancer patients in order to treat their neuropsychiatric conditions and neuropathic pain caused by the brain tumors. Thirdly, the role of blood vessels in shaping the induced current distributions within the cortex during tDCS was thoroughly investigated and addressed. The outcomes of this project highlight the importance of head orientation during the clinical application of tDCS. The results also clear the safety concern in applying tDCS to the patients with brain cancer. In addition, this project provides positive supports on the introduction of brain blood vessels during the precise human head modelling for tDCS though considerable workload will be involved

Transcranial Direct Current Stimulation (tDCS) to Improve Lower Limb Motor Recovery Following Stroke: A Review and Study Proposal

Strokes are the result of restricted blood flow to particular areas of the brain classified by their cause. The neural damage they cause are of growing concern as the number of young adults experiencing strokes has increased by 11% in the last decade. Following stroke, there is an imbalance of inhibitory and excitatory neuronal activity, and disruption of neural networks. These changes lead to neuronal death and loss of synaptic connections that, depending on which part of the brain is affected, result in behavioral deficits such as weakness, limb hemiparesis, and loss of coordination, as well as speech and cognitive impairments. However, this loss of function can be partly recovered due to neuroplastic processes. Non-invasive brain stimulation (NIBS) is an approach that involves implanting electrodes into targeted areas of the brain which are connected to an implantable pulse generator on the skin that delivers chronic electric pulse. There are different forms of stimulation, but one with some established success in improving upper and lower limb mobility, as well as some cognitive symptoms, is transcranial direct current stimulation (tDCS). For the treatment of stroke, tDCS aims to increase excitability of the lesioned areas to improve contralesional mobility. While past research has focused on stimulating well established motor regions, such as the cerebellum, motor cortex, and basal ganglia, sensory systems also play a key role in sending information through the ascending dorsal column medial lemniscal pathway, posterior and anterior spinocerebellar tracts, and spinoreticular tracts. Here is a review of the current research on the integration of sensory and motor information in order to carry out desired movement, a discussion about how these networks are being targeted by tDCS after stroke to help patients regain lower limb movement, and finally, a proposed study in which improvements in balance, gait, and postural stability after anodal tDCS continue up to a year post-treatment in chronic ischemic stroke patients

Individually optimized multi-channel tDCS for targeting somatosensory cortex

Objective - Transcranial direct current stimulation (tDCS) is a non-invasive neuro-modulation technique that delivers current through the scalp by a pair of patch electrodes (2-Patch). This study proposes a new multi-channel tDCS (mc-tDCS) optimization method, the distributed constrained maximum intensity (D-CMI) approach. For targeting the P20/N20 somatosensory source at Brodmann area 3b, an integrated combined magnetoencephalography (MEG) and electroencephalography (EEG) source analysis is used with individualized skull conductivity calibrated realistic head modeling. - Methods - Simulated electric fields (EF) for our new D-CMI method and the already known maximum intensity (MI), alternating direction method of multipliers (ADMM) and 2-Patch methods were produced and compared for the individualized P20/N20 somatosensory target for 10 subjects. - Results - D-CMI and MI showed highest intensities parallel to the P20/N20 target compared to ADMM and 2-Patch, with ADMM achieving highest focality. D-CMI showed a slight reduction in intensity compared to MI while reducing side effects and skin level sensations by current distribution over multiple stimulation electrodes. - Conclusion - Individualized D-CMI montages are preferred for our follow up somatosensory experiment to provide a good balance between high current intensities at the target and reduced side effects and skin sensations. - Significance - An integrated combined MEG and EEG source analysis with D-CMI montages for mc-tDCS stimulation potentially can improve control, reproducibility and reduce sensitivity differences between sham and real stimulations

Optimisation of a Wearable Neuromodulator for Migraine Using Computational Methods

Migraine is the third most common neurological disorder and the sixth cause of disability. It may be characterized by a headache, nausea, vomiting, photo- phobia and phonophobia. Available pharmaceutical treatments of migraine are not completely effective and have troublesome side-effects. Thus, there is a need for alternative treatments such as neuromodulation. Neuromodulation may be delivered invasively; however, this exposes the patients to the associated risks. Transcutaneous electrical nerve stimulation is a non-invasive technique that is widely used to relieve pain. A significant number of migraine sufferers complaint the symptoms of pain originating in the frontal region of the head. Thus, mi- graine may be associated with the supraorbital nerve and supratrochlear nerve which passes below the frontal bone exits from the orbital rim and penetrates the corrugator and frontalis muscles. Transcutaneous frontal nerve stimulation has been applied on a large group of patients who have episodic migraine us- ing a device called Cefaly. This study produced mixed results (50% response rate). A post–marketing survey led to 53% satisfaction while the most limiting factor is reported to be paraesthesia and painful sensation. The possible causes of these inconclusive results may be associated with neuroanatomical variations, patient compliance and neurophysiological effects. The most plausible cause may be related to the neuroanatomical variations across different subjects. The neu- roanatomical variations may lead to excessively high current levels being required. Since this solution is patient–operated, these relatively high required levels are not applied. In addition, as the electrodes are positioned near pain–sensitive structures, pain may be induced even at low current levels, further limiting the efficacy of the solution. There has been no robust investigation identifying the underlying causes of ineffi- cacy. This is partly due to the physical limitations of studying the neuroanatomy of each subject and different settings of electrode arrangements. Computational models may enable researchers to estimate current stimulation thresholds in neu- romodulation therapy and investigate the effects of various parameters. Such computational models are composed of a volume conductor model and an ad- vanced Hodgkin–Huxley–type model of neural tissue referred to as a hybrid model. Once the human head anatomy, the human nervous system and available solu- tions for migraine are detailed, the computational model of the human head is generated. A highly detailed human head model based on magnetic resonance imaging (MRI) studies, microscopic structure of the skin(including sweat ducts, keratinocytes and lipid) and those of a simplified head model (which built from geometric shapes) are compared based on neural excitation to assess the usabil- ity of geometrically realistic(simplified) human head models in the subsequent studies to save computations cost. The induced electric field due to an electrode setting is simulated in the volume conductor model and the resulting electric potential values along the nerve are passed on to the neural model to simulate nerve’s response. It is shown that a simplified model may be used with a marginal error (≈2%) in the subsequent work when assessing the effect of neuroanatomical variations on the efficacy of the target solution and possible ensuing optimiza- tions. The first step is to identify if neuroanatomical variations had any effect on the required stimulus current levels using state of the art computational bio–models. Ten realistic human head models are developed by varying thirteen neuroanatom- ical features including human head size, thicknesses of the tissue layers and vari- ations in the courses of the nerve by considering their respective statistical distributions as reported in the literature. A novel algorithm is developed to account for the variations of the nerve in different individuals and mimic statistically relevant large population. In each case, the required stimulus current levels are simulated. The findings show that the combined neuroanatomical variations have a significant effect on the neural response for the electrode setting used in Cefaly device. Therefore, a potential improvement is to align the axis of electrodes with the target nerve, so that the electrical potential along the trajectory of the nerve changes polarity. This may lead to lower required stimulus current levels. Align- ing electrodes with the nerve, the required current may be reduced by at least 60%. This new orientation reduces current density near pain– sensitive struc- tures by diverting the current away from them, which may lead to a higher level of patient compliance, further improving the efficacy of the solution. Using an electrodes array arrangement, the required current levels is further reduced due to incorporating multiple electrodes array elements to maximise the variations of the electrical field in the simulation of the fibres in one phase. The findings of this thesis indicate that the highly detailed human head model can be simplified while minimally affecting the outcome. Additionally, it is shown that neuroanatomical variations have a significant impact on the stimulus current thresholds but it is not possible to conclude if these thresholds solely depend on a specific neuroanatomical variation. The relatively high required levels of the stimulus currents are beyond the current capabilities of existing device and pos- sible pain thresholds. Furthermore, the proposed new electrode arrangement has multiple benefits including the reduction of the stimulus current levels and diver- sion of current spread from possible pain–sensitive structures. This improvement, based on modelling, can potentially improve the clinical outcome of the neuro- modulator substantially if confirmed in the subsequent clinical studies

Brain and Human Body Modeling 2020

​This open access book describes modern applications of computational human modeling in an effort to advance neurology, cancer treatment, and radio-frequency studies including regulatory, safety, and wireless communication fields. Readers working on any application that may expose human subjects to electromagnetic radiation will benefit from this book’s coverage of the latest models and techniques available to assess a given technology’s safety and efficacy in a timely and efficient manner. Describes computational human body phantom construction and application; Explains new practices in computational human body modeling for electromagnetic safety and exposure evaluations; Includes a survey of modern applications for which computational human phantoms are critical

The effect of anodal transcranial direct current stimulation on spatial motor skill learning in healthy and spinal cord injured humans

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Anodal transcranial direct current stimulation (tDCS) is an intervention which is thought to enhance motor learning in healthy and stroke-injured states, when applied adjunctively during skill learning. We set out to investigate whether anodal tDCS might enhance functional rehabilitation from incomplete tetraplegic SCI. To address current limitations in the measurement of task-dependent skill, a novel integrated skill training and measurement task, the Motor Skill Rehabilitation Task (MSRT) was designed and developed. Measures of performance from this task delivered the functional measure of spatial motor skill learning, Task Productivity Rate (TPR). TPR was analysed and validated as a univariate dependent outcome, which is of potential importance to the future development of clinical measures measuring goal-directed motor skills. The MSRT was included alongside conventional behavioural measures in a repeated-measures RCT pilot study, the first to investigate the effect of anodal tDCS on rehabilitation of motor skill from chronic spinal cord injury. Adjunctive application of anodal tDCS had a statistically significant benefit upon retention of skill in the incomplete spinal cord injured population, but only when the independent factor of sensory acuity was included in the analysis. Differences between the development of task-dependent skill and generic dexterity over time suggested that spatial skill development was subject to an interaction of short-term and lasting effects. A larger study in healthy persons further investigated these phenomena, also applying Transcranial Magnetic Stimulation (TMS)–evoked measurements to investigate intervention-dependent effects upon the excitability of projections between the primary motor cortex and muscles involved in the prehension task. The findings revealed that active tDCS did not enhance skill learning at 7 days beyond the training period, but did significantly alter the development of motor skill following a period of learning and subsequent skill consolidation which was associated with underlying perturbation of motor control strategy. Significant and divergent patterns of cortical plasticity were evoked in projections to muscles necessary for reaching and grasping. The main findings of this thesis do not support anodal tDCS as an effective adjunctive means of enhancing spatial motor skill in rehabilitation from incomplete tetraplegic SCI. If applied in patient populations, the clinical benefits of anodal tDCS may be contingent both on the nature of the sensorimotor deficit affecting upper limb function and the spatial demands of the behavioural task. The findings of this project serve to inform further research in relation to the effect of anodal tDCS on the brain and behavioural outcomes, the potential for efficacy in target patient groups and the sensitivity of outcome measures to spatial and temporal dimensions of practical motor skills.This study was partly supported by The Brunel University Isambard Research Scholarship, and The Orthotist Education and Training Trust

Validation of Transcranial Electrical Stimulation (TES) Finite Element Modeling Against MREIT Current Density Imaging in Human Subjects

abstract: Transcranial electrical stimulation (tES) is a non-invasive brain stimulation therapy that has shown potential in improving motor, physiological and cognitive functions in healthy and diseased population. Typical tES procedures involve application of weak current (< 2 mA) to the brain via a pair of large electrodes placed on the scalp. While the therapeutic benefits of tES are promising, the efficacy of tES treatments is limited by the knowledge of how current travels in the brain. It has been assumed that the current density and electric fields are the largest, and thus have the most effect, in brain structures nearby the electrodes. Recent studies using finite element modeling (FEM) have suggested that current patterns in the brain are diffuse and not concentrated in any particular brain structure. Although current flow modeling is useful means of informing tES target optimization, few studies have validated tES FEM models against experimental measurements. MREIT-CDI can be used to recover magnetic flux density caused by current flow in a conducting object. This dissertation reports the first comparisons between experimental data from in-vivo human MREIT-CDI during tES and results from tES FEM using head models derived from the same subjects. First, tES FEM pipelines were verified by confirming FEM predictions agreed with analytic results at the mesh sizes used and that a sufficiently large head extent was modeled to approximate results on human subjects. Second, models were used to predict magnetic flux density, and predicted and MREIT-CDI results were compared to validate and refine modeling outcomes. Finally, models were used to investigate inter-subject variability and biological side effects reported by tES subjects. The study demonstrated good agreements in patterns between magnetic flux distributions from experimental and simulation data. However, the discrepancy in scales between simulation and experimental data suggested that tissue conductivities typically used in tES FEM might be incorrect, and thus performing in-vivo conductivity measurements in humans is desirable. Overall, in-vivo MREIT-CDI in human heads has been established as a validation tool for tES predictions and to study the underlying mechanisms of tES therapies.Dissertation/ThesisDoctoral Dissertation Biomedical Engineering 201

Brain and Human Body Modeling

This open access book describes modern applications of computational human modeling with specific emphasis in the areas of neurology and neuroelectromagnetics, depression and cancer treatments, radio-frequency studies and wireless communications. Special consideration is also given to the use of human modeling to the computational assessment of relevant regulatory and safety requirements. Readers working on applications that may expose human subjects to electromagnetic radiation will benefit from this book’s coverage of the latest developments in computational modelling and human phantom development to assess a given technology’s safety and efficacy in a timely manner. Describes construction and application of computational human models including anatomically detailed and subject specific models; Explains new practices in computational human modeling for neuroelectromagnetics, electromagnetic safety, and exposure evaluations; Includes a survey of modern applications for which computational human models are critical; Describes cellular-level interactions between the human body and electromagnetic fields

Brain and Human Body Modeling

This open access book describes modern applications of computational human modeling with specific emphasis in the areas of neurology and neuroelectromagnetics, depression and cancer treatments, radio-frequency studies and wireless communications. Special consideration is also given to the use of human modeling to the computational assessment of relevant regulatory and safety requirements. Readers working on applications that may expose human subjects to electromagnetic radiation will benefit from this book’s coverage of the latest developments in computational modelling and human phantom development to assess a given technology’s safety and efficacy in a timely manner. Describes construction and application of computational human models including anatomically detailed and subject specific models; Explains new practices in computational human modeling for neuroelectromagnetics, electromagnetic safety, and exposure evaluations; Includes a survey of modern applications for which computational human models are critical; Describes cellular-level interactions between the human body and electromagnetic fields