Electrical eddy currents can be induced inside biological tissue by time-varying magnetic fields according to Faraday's law of induction. These eddy currents are responsible for biological effects such as visual sensations in eyes called magnetophosphenes and they accelerate the healing process of fractured bones in magnetotherapy operation. Induced eddy currents also cause neuromuscular stimulation of cardiac muscle, shown as a disturbance in the electrocardiogram and respiratory disturbance shown as a brief period of apnoea (stopped breathing) and muscle contraction in the forearm and finger. Brain cortex also can be stimulated by pulsed magnetic fields. A transient decrease in blood flow in the human skin is seen as a result of exposing the skin to pulsed magnetic fields. To study the effects of time-varying magnetic field, a method is needed to assess and measure induced current densities. Many attempts have been made to find such a method, both theoretically and practically. A theoretical model with homogenous and isotropic concentric loops of tissue was suggested but biological tissues are neither homogenous nor isotropic. A Hall effect method using a slab of semiconductor was suggested for measurement of current densities inside tissues, but this method ignored disturbances in the current pathways inside the tissue as a result of differences in impedances between the semiconductor and the tissue. A cube substitution method using platinized conductive faces implanted in the tissue does not consider problems of alignment of the probes with the direction of isopotential lines or electrode-electrolyte impedance. Also, such electrodes measure only dc current. In a method using a three dimensional electrode to provide three-dimensional information, the author did not give evidence that these electrodes have a zero field distortion, and also did not give information about measurements made using his electrodes. None of the above methods provide a solid approach to the problems of measuring induced current densities. This thesis attempts to present a method of measuring induced current density. The method is capable of measuring both the magnitude and direction of induced current densities. It uses five point electrodes, four of them applied inside the tissue while the fifth one is just in electrical contact with the tissue. The method consists of a probe configuration system, an open-loop operational amplifier and a balanced semi-floating current driver. Leakage current, which goes to the ground and causes error, can be adjusted to be very low (about 0.01% of the total output current). A pair of Helmoltz coils was employed to provide a system for producing time-varying magnetic field. The core of the coil pair was shielded and grounded by a cut metal shield, to avoid any interference from time-varying electric field. The shield was also used as a metal incubator to keep biological samples at body temperature. The heat to the shield was supplied by a unit consisting of four power transistors, and a circuit of sensing, and controlling components. The method used in this study was tested by making measurements of eddy current densities induced in physiological saline solution as a model of a biological conducting fluid. The measurements were represented by arrows, each representing a single measurement, with the length of the arrow representing the magnitude of current density and the direction representing the direction of the induced current. Because electrically induced eddy currents are dependent on electric charge density available inside tissue, and therefore dependent on tissue electrical conductivity, this thesis presents a direct and simple method for measuring complex tissue electrical conductivity. The method uses the same five-electrode system and shares the same point electrode configurations and balanced semi-floating current driver as used for eddy current measurements. The method measures both real and imaginary components of tissue complex conductivity. Both systems are gathered into one box and their functions are separated by four toggle switches. Measurements of electrical induced current densities and complex electrical conductivities for body fluids and tissues have been carried out on saline solutions with different ionic concentrations, expired human whole blood, expired human plasma, human cerebrospinal fluid (CSF) and human urine. Solid tissue such as bovine cardiac muscle and liver were also examined. Current-to-field ratios were obtained for experiments in both fluid and tissues.

Thesis (Ph.D.)--University of Canterbury, 2009. / Typescript (photocopy). "29th April 2009." Includes bibliographical references (p. 256-277). Also available via the World Wide Web.

Thesis (Ph. D.)--University of Oregon, 2002. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 195-205). Also available for download via the World Wide Web; free to University of Oregon users.

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Bridging the fields of engineering and psychiatry, this dissertation proposes a novel framework for the rational dosing of electric and magnetic seizure therapy, including electroconvulsive therapy (ECT) and magnetic seizure therapy (MST), for the treatment of psychiatric disorders such as medication resistant major depression and schizophrenia. The objective of this dissertation is to develop computational modeling tools that allow ECT and MST stimulation paradigms to be biophysically optimized ex vivo, prior to testing safety and efficacy in preclinical and clinical trials. Despite therapeutic advances, treatment resistant depression (TRD) remains a largely unmet clinical need. ECT is highly effective for TRD, but its side effects limit its real-world clinical utility. Modifications of treatment technique (e.g., electrode placement, stimulus parameters, novel paradigms such as MST) significantly improve the tolerability of convulsive therapy. However, we know relatively little about the distribution of the electric field (E-field) induced in the brain to inform spatial targeting of ECT and MST. Lacking an understanding of biophysical and physiological mechanisms, refinements in ECT/MST technique rely exclusively on time-consuming and costly clinical trials. Consequently, key questions remain unanswered about how to position the ECT electrodes or MST coil for targeted brain stimulation. Addressing this knowledge gap, this dissertation proposes a new platform that will inform an improved spatial targeting of ECT and MST through state-of-the-art computer simulations of the E-field distribution in human and nonhuman primate (NHP) brain. Part I of this dissertation aims to develop anatomically realistic finite element models of transcranial electric and magnetic stimulation in human and NHPs incorporating tissue heterogeneity and anisotropy derived from structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) data. The NHP models of ECT and MST are created alongside the human model since NHPs are used in preclinical studies on the mechanisms of seizure therapy. Part II of this dissertation aims to apply the model developed in Part I to electric and magnetic seizure therapy. We compute the strength and spatial distributions of the E-field induced in the brain by various ECT and MST paradigms. The relative E-field strength among various regions of interest (ROIs) is examined to select electrode/coil configurations that produce most focal stimulation of target ROIs that are considered to mediate the therapeutic action of ECT and MST. Since E-field alone is insufficient to account for individual differences in neurophysiological response, we calibrate the E-field maps relative to the neural activation threshold via in vivo measurements of the corticospinal tract response to single pulses (motor threshold, MT). We derive an empirical estimate of the neural activation threshold by coupling simulated E-field strength with individually measured MT. The E-field strength relative to an empirical neural activation threshold and corresponding volume of suprathreshold stimulation (focality) is examined to inform the selection of ECT and MST stimulus pulse amplitude that will result in focal ROI stimulation. We contrast the ECT/MST stimulation strength and focality with conventional fixed and individually titrated pulse amplitude necessary to induce a seizure (seizure threshold, ST) to study pulse amplitude adjustment as a novel means of controlling stimulation strength and focality. This work provides a basis for rational dosing of seizure therapies that could help improve their risk/benefit ratio and guide the development of safer alternatives for patients with severe psychiatric disorders.

This thesis tested whether the human frontal eye fields (FEFs) have visuospatial functions that are dissociable from FEF oculomotor functions. Functional magnetic resonance imaging (fMRI) was used to localize the FEFs, and transcranial magnetic stimulation (TMS) was applied in a series of experiments to transiently disrupt information processing in the FEFs. It was shown that TMS applied over the right FEFs degrades subjects' performance on a visual conjunction search task in which eye movements were not required and were not made. A TMS timing protocol subsequently showed that computations in the FEFs that occur between 40 and 80ms after the onset of a visual search array are critical for accurate performance. This suggests that, as in the monkey, the human FEFs may accumulate and use visual evidence from extrastriate cortex, which forms the basis for accurate visuospatial discrimination. A training protocol showed that the right FEFs are no longer critical for accurate visuospatial discrimination performance once a search task has been extensively practised. This study further suggested that the FEFs may have a previously unknown role in the perception of left-right rotated shapes. A study on feature and spatial priming indicated that these two phenomena have distinct causal mechanisms. The left FEFs appear to access a spatial memory signal during the process of saccade programming. When TMS is applied during this period, the spatial priming benefit is abolished. Altogether, this thesis presents evidence that visuospatial and oculomotor functions can be dissociated in the human FEFs. The data on timing and the effects of learning correspond well with results reported in monkeys. The priming experiment offers the first evidence that the left FEFs are crucial for spatial priming, while the learning study suggests the novel hypothesis that the FEFs are crucial for left-right rotated shape perception.