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Transcranial magnetic stimulation (TMS) is a unique method for non-invasive brain imaging. The fundamental difference between TMS and other available non-invasive brain imaging techniques is that when a physiological response is evoked by stimulation of a cortical area, that specific cortical area is causally related to the response. With other imaging methods, it is only possible to detect and map a brain area that participates in a given task or reaction. TMS has been shown to be clinically accurate and effective in mapping cortical motor areas and applicable to the functional assessment of motor tracts following stroke, for example. Many hundreds of studies have been published indicating that repetitive TMS (rTMS) may also have multiple therapeutic applications. Techniques and protocols for individually targeting and dosing rTMS urgently need to be developed in order to ascertain the accuracy, repeatability and reproducibility required of TMS in clinical applications. We review the basic concepts behind navigated TMS and evaluate the currently accepted physical and physiological factors contributing to the accuracy and reproducibility of navigated TMS. The advantages of navigated TMS over functional MRI in motor cortex mapping are briefly discussed. Illustrative cases utilizing navigated TMS are shown in presurgical mapping of the motor cortex, in therapy for depression, and in the follow-up of recovery from stroke.

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BACKGROUND: Changes in T2 relaxation time (T2-TR) and apparent diffusion coefficients (ADC) have been suggested to appear in the intervertebral disc before morphological changes. Such sensitive imaging methods could be beneficial in the targeting and follow-up of intradiscal gene therapy. PURPOSE: To investigate the sensitivity of quantitative magnetic resonance (MR) imaging methods (T2-TR and ADC) in early disc degeneration, using an experimental porcine intervertebral disc injury model, and to investigate their sensitivity in depicting biochemically controlled degenerative changes in the disc. MATERIAL AND METHODS: Six juvenile pigs underwent experimental annular stab incisions, one superficial and one reaching the nucleus pulposus. The animals underwent repeated 1.5T MR imaging and were sacrificed 4 or 8 weeks after operation. Presence of degenerative changes was controlled with biochemical analysis. RESULTS: Discs with full-thickness annular incisions lost 30% of their sagittal mid-slice nucleus pulposus area in 2 weeks (P<0.05). T2-TRs of the respective discs were on average 73% of the control discs (P<0.05). Discs with full-thickness annular lesions showed increased ADC values 4 weeks and reduced ADC values 8 weeks after the operation, compared to control discs (P<0.05). Biochemical analysis showed changes consistent with early degeneration. CONCLUSION: Early traumatic or degenerative changes are detectable with both T2-TR and ADC. The ADC in the early phase after experimental trauma seems to initially increase before decreasing.

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Diffusion magnetic resonance imaging (MRI) is a method for quantifying the microscopic random motion of water molecules in tissues. Diffusion imaging provides indirect structural information of a kind not available on basic MRI sequences of many pathological conditions. Lately, especially brain tumors have been under active investigation, with numerous papers already published, and their number continues to increase. This review summarizes the heterogeneous and complex research data on diffusion imaging of brain tumors.

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Transcranial magnetic stimulation (TMS) can be used to excite the human cortex noninvasively. TMS also activates scalp muscles and sensory receptors; additionally, the loud sound from the stimulating coil activates auditory pathways. These side effects complicate the interpretation of the results of TMS studies. For control experiments, we have designed a coil that can produce both real and sham stimulation without moving the coil. The sham TMS is similar to the real TMS, except for the different relative direction of the currents in the two loops of the figure-of-eight coil. While the real TMS elicited activation of hand muscles, sham TMS had no such effect; however, the auditory-evoked potentials were similar.

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There is described a 60-channel EEG acquisition system designed for the recording of scalp-potential distributions starting just 2.5 ms after individual transcranial magnetic stimulation (TMS) pulses. The amplifier comprises gain-control and sample-and-hold circuits to prevent large artefacts from magnetically induced voltages in the leads. The maximum amplitude of the stimulus artefact during the 2.5 ms gating period is 1.7 microV, and 5 ms after the TMS pulse it is only 0.9 microV. It is also shown that mechanical forces to the electrodes under the stimulator coil are a potential source of artefacts, even though, with chlorided silver wire and Ag/AgCl-pellet electrodes, the artefact is smaller than 1 microV. The TMS-compatible multichannel EEG system makes it possible to locate TMS-evoked electric activity in the brain.

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OBJECTIVE: We have used EEG to measure effects of air- and bone-conducted sound from the coil in transcranial magnetic stimulation (TMS). METHODS: Auditory-evoked potentials to TMS were recorded in three different experimental conditions: (1) the coil 2 cm above the head, (2) the coil 2 cm above the head but rigidly connected by a plastic piece to the scalp, (3) the coil pressed against the scalp over the motor cortex. RESULTS: The acoustical click from the TMS coil evoked large auditory potentials, whose amplitude depended critically on the mechanical contact of the coil with the head. CONCLUSION: Both air- and bone-conducted sounds have to be taken into account in the design and interpretation of TMS experiments.

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Transcranial magnetic stimulation (TMS) is accompanied with loud clicks that evoke auditory responses in the brain, confounding several types of TMS studies. We investigated the effects of these clicks with high-resolution EEG by applying TMS pulses at 3 magnitudes, with the coil placed either at 10 or 50 mm over the subjects' vertex and recording event-related potentials (ERPs). The clicks were found to elicit a positively displaced response at 150-250 ms post-TMS. Furthermore, clicks were found to interact with simultaneously presented auditory sinewave stimuli, resulting in an amplitude decrease in the auditory N1 response.

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Human excitable cells can be stimulated noninvasively with externally applied time-varying electromagnetic fields. The stimulation can be achieved either by directly driving current into the tissue (electrical stimulation) or by means of electro-magnetic induction (magnetic stimulation). While the electrical stimulation of the peripheral neuromuscular system has many beneficial applications, peripheral magnetic stimulation has so far only a few. This paper analyzes theoretically the use of multiple magnetic stimulation coils to better control the excitation and also to eventually mimic electrical stimulation. Multiple coils allow electronic spatial adjustment of the shape and location of the stimulus without moving the coils. The new properties may enable unforeseen uses for peripheral magnetic stimulation, e.g., in rehabilitation of patients with neuromuscular impairment.

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Recent progress in the theory and technology of transcranial magnetic stimulation (TMS) is leading to novel approaches in brain mapping. TMS becomes a powerful functional brain mapping tool when other imaging methods are used to record TMS-evoked activity or when peripheral effects are observed as a function of stimulus location. TMS-evoked activity currently can be recorded by EEG, PET, and fMRI. In addition to providing indices of cortical excitability, these methods allow one to study brain connectivity directly, without the need for behavioral activations. When the coordinate systems in the different imaging modalities are combined, anatomical structures seen in MRI and activation sites determined by PET, fMRI, or MEG/EEG can be used for the selection of target areas in the brain. PET and fMRI can be used to map the spatial distribution of TMS-evoked activity. On the other hand, the combination of TMS and high-resolution EEG may often be the method of choice for basic neuroscience and for clinical diagnosis, for example, in the assessment of brain connectivity in patients suffering from neurodegenerative diseases or head injuries.

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Neurones can be excited by an externally applied time-varying electromagnetic field. Focused magnetic brain stimulation is attained using multiple small coils instead of one large coil, the resultant induced electric field being a superposition of the fields from each coil. In multichannel magnetic brain stimulation, partial cancellation of fields from individual coils provides a significant improvement in the focusing of the stimulating field, and independent coil channels allow targeting of the stimuli on a given spot without moving the coils. The problem of shaping the stimulating field in multichannel stimulation is analysed, and a method is derived that yields the driving currents required to induce a field with a user-defined shape. The formulation makes use of lead fields and minimum-norm estimation from magneto-encephalography. Using these methods, some properties of multichannel coil arrays are examined. Computer-assisted multichannel stimulation of the cortex will enable several new studies, including quick determination of the cortical regions, the stimulation of which disrupts cortical processing required by a task.

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This paper implements a filtering technique to enhance the signal-to-noise ratio (SNR) and, in turn, the detection of transient-evoked otoacoustic emissions (TEOAE's), generated by healthy human cochlea. One can increase the SNR by compiling an image of recorded TEOAE from more than one stimulus intensity, averaged over a few sweeps, which can be further processed by means of two-dimensional spatial mean filters. Averaging some 60 sweeps recorded to stimuli at several intensity levels requires one-forth of the collection time needed for a classical set of responses (average of 260 sweeps), and obtains approximately the same final SNR. The relation between the performances of the proposed technique and the SNR of the rapidly acquired responses before filtering is also investigated.

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Further development of magnetic brain stimulation requires smaller coils, smaller power consumption, and less coil heating. This study addresses the optimization of the complete stimulator and in particular the coil. We describe the coil structure in terms of simple mathematical functions and examine the influence of changes in the structure on several figures of merit. A few optimal coil geometries suitable for repetitive brain stimulation are depicted. It is demonstrated that today's coils are far from optimal and that, for instance, the power consumption can be reduced remarkably from the level of today's equipment. Improvements may act as a springboard toward new applications.

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The technique of magnetic stimulation (MS) has the potential to contribute to the study of the peripheral nervous system, but the uncertainty of the site of activation and problems in achieving supramaximal responses have prevented its extensive use. This paper discusses mathematical modeling of MS of the peripheral nerves. The work reveals recent theoretical advances, which may give new insight to the exact site of activation and help to understand the phenomena involved. The mechanisms of stimulation are examined: a solid comprehension of the stimulation event may boost new applications of the technique.

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In the clinical use of evoked otoacoustic emissions the identification of the cochlear response and the reduction of the duration of the recording session are of great concern, especially if the recorded responses are to be used in hearing screening tasks. The aim of this paper is two-fold: to examine the potential and limits of optimal band-pass filtering to reduce the noise and increase identification of the cochlear response, and to introduce a technique of two-dimensional processing for reducing the acquisition time of TEOAEs. Band-pass filtering must guard against the loss of significant frequency components of the response; that is, the signals have to be filtered only when the filter bandwidth meets given conditions. As to test duration, preliminary results clearly indicate that two-dimensional filtering can substantially reduce the acquisition time, with only negligible losses in the basic response features, when a set of responses recorded at different stimulus levels is filtered.

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Motor and visual cortices of normal volunteers were activated by transcranial magnetic stimulation. The electrical brain activity resulting from the brief electromagnetic pulse was recorded with high-resolution electroencephalography (HR-EEG) and located using inversion algorithms. The stimulation of the left sensorimotor hand area elicited an immediate response at the stimulated site. The activation had spread to adjacent ipsilateral motor areas within 5-10 ms and to homologous regions in the opposite hemisphere within 20 ms. Similar activation patterns were generated by magnetic stimulation of the visual cortex. This new non-invasive method provides direct information about cortical reactivity and area-to-area neuronal connections.

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Knowledge of the electric field that is induced in the brain or the limbs is of importance in magnetic stimulation of the nervous system. Here, an analytical model based on the reciprocity theorem is used to compare the induced electric field in unbounded, semi-infinite, spherical, and cylinder-like volume conductors. Typical stimulation coil arrangements are considered, including the double coil and various orientations of the single coil. The results can be used to determine when the influence of the boundaries is negligible enough to allow the use of more simplified geometries.

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A method for the analysis of variability of EEG signals is described. We examined simulated signals and real EEGs obtained from a normal subject and two epileptic patients. The first step of the method is based on autoregressive (AR) modelling of short EEG epochs. Prediction coefficients of the AR model were computed as a function of time from partially-overlapping moving windows of 2 s duration. The temporal behaviour of these coefficients was analysed to detect variability: quasi-stationary activity causes only smooth changes in the coefficients while variations in the amplitude and/or the frequency content of the signal are shown to produce sharp changes in the coefficients. A segmentation algorithm was developed to detect and quantify with a numerical value (Difference Measure, DM) the AR coefficients variations.

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