Publications by authors named "Jaakko O Nieminen"

37 Publications

Multi-locus transcranial magnetic stimulation system for electronically targeted brain stimulation.

Brain Stimul 2021 Nov 21. Epub 2021 Nov 21.

Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland; BioMag Laboratory, HUS Medical Imaging Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Transcranial magnetic stimulation (TMS) allows non-invasive stimulation of the cortex. In multi-locus TMS (mTMS), the stimulating electric field (E-field) is controlled electronically without coil movement by adjusting currents in the coils of a transducer.

Objective: To develop an mTMS system that allows adjusting the location and orientation of the E-field maximum within a cortical region.

Methods: We designed and manufactured a planar 5-coil mTMS transducer to allow controlling the maximum of the induced E-field within a cortical region approximately 30 mm in diameter. We developed electronics with a design consisting of independently controlled H-bridge circuits to drive up to six TMS coils. To control the hardware, we programmed software that runs on a field-programmable gate array and a computer. To induce the desired E-field in the cortex, we developed an optimization method to calculate the currents needed in the coils. We characterized the mTMS system and conducted a proof-of-concept motor-mapping experiment on a healthy volunteer. In the motor mapping, we kept the transducer placement fixed while electronically shifting the E-field maximum on the precentral gyrus and measuring electromyography from the contralateral hand.

Results: The transducer consists of an oval coil, two figure-of-eight coils, and two four-leaf-clover coils stacked on top of each other. The technical characterization indicated that the mTMS system performs as designed. The measured motor evoked potential amplitudes varied consistently as a function of the location of the E-field maximum.

Conclusion: The developed mTMS system enables electronically targeted brain stimulation within a cortical region.
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http://dx.doi.org/10.1016/j.brs.2021.11.014DOI Listing
November 2021

Trade-off between stimulation focality and the number of coils in multi-locus transcranial magnetic stimulation.

J Neural Eng 2021 Nov 12;18(6). Epub 2021 Nov 12.

Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland.

. Coils designed for transcranial magnetic stimulation (TMS) must incorporate trade-offs between the required electrical power or energy, focality and depth penetration of the induced electric field (E-field), coil size, and mechanical properties of the coil, as all of them cannot be optimally met at the same time. In multi-locus TMS (mTMS), a transducer consisting of several coils allows electronically targeted stimulation of the cortex without physically moving a coil. In this study, we aimed to investigate the relationship between the number of coils in an mTMS transducer, the focality of the induced E-field, and the extent of the cortical region within which the location and orientation of the maximum of the induced E-field can be controlled.We applied convex optimization to design planar and spherically curved mTMS transducers of different E-field focalities and analyzed their properties. We characterized the trade-off between the focality of the induced E-field and the extent of the cortical region that can be stimulated with an mTMS transducer with a given number of coils.At the expense of the E-field focality, one can, with the same number of coils, design an mTMS transducer that can control the location and orientation of the peak of the induced E-field within a wider cortical region.. With E-fields of moderate focality, the problem of electronically targeted TMS becomes considerably easier compared with highly focal E-fields; this may speed up the development of mTMS and the emergence of new clinical and research applications.
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http://dx.doi.org/10.1088/1741-2552/ac3207DOI Listing
November 2021

Effect of stimulus orientation and intensity on short-interval intracortical inhibition (SICI) and facilitation (SICF): A multi-channel transcranial magnetic stimulation study.

PLoS One 2021 22;16(9):e0257554. Epub 2021 Sep 22.

Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland.

Besides stimulus intensities and interstimulus intervals (ISI), the electric field (E-field) orientation is known to affect both short-interval intracortical inhibition (SICI) and facilitation (SICF) in paired-pulse transcranial magnetic stimulation (TMS). However, it has yet to be established how distinct orientations of the conditioning (CS) and test stimuli (TS) affect the SICI and SICF generation. With the use of a multi-channel TMS transducer that provides electronic control of the stimulus orientation and intensity, we aimed to investigate how changes in the CS and TS orientation affect the strength of SICI and SICF. We hypothesized that the CS orientation would play a major role for SICF than for SICI, whereas the CS intensity would be more critical for SICI than for SICF. In eight healthy subjects, we tested two ISIs (1.5 and 2.7 ms), two CS and TS orientations (anteromedial (AM) and posteromedial (PM)), and four CS intensities (50, 70, 90, and 110% of the resting motor threshold (RMT)). The TS intensity was fixed at 110% RMT. The intensities were adjusted to the corresponding RMT in the AM and PM orientations. SICI and SICF were observed in all tested CS and TS orientations. SICI depended on the CS intensity in a U-shaped manner in any combination of the CS and TS orientations. With 70% and 90% RMT CS intensities, stronger PM-oriented CS induced stronger inhibition than weaker AM-oriented CS. Similar SICF was observed for any CS orientation. Neither SICI nor SICF depended on the TS orientation. We demonstrated that SICI and SICF could be elicited by the CS perpendicular to the TS, which indicates that these stimuli affected either overlapping or strongly connected neuronal populations. We concluded that SICI is primarily sensitive to the CS intensity and that CS intensity adjustment resulted in similar SICF for different CS orientations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257554PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457500PMC
November 2021

Individual head models for estimating the TMS-induced electric field in rat brain.

Sci Rep 2020 10 15;10(1):17397. Epub 2020 Oct 15.

Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland.

In transcranial magnetic stimulation (TMS), the initial cortical activation due to stimulation is determined by the state of the brain and the magnitude, waveform, and direction of the induced electric field (E-field) in the cortex. The E-field distribution depends on the conductivity geometry of the head. The effects of deviations from a spherically symmetric conductivity profile have been studied in detail in humans. In small mammals, such as rats, these effects are more pronounced due to their less spherical head, proportionally much thicker neck region, and overall much smaller size compared to the TMS coils. In this study, we describe a simple method for building individual realistically shaped head models for rats from high-resolution X-ray tomography images. We computed the TMS-induced E-field with the boundary element method and assessed the effect of head-model simplifications on the estimated E-field. The deviations from spherical symmetry have large, non-trivial effects on the E-field distribution: for some coil orientations, the strongest stimulation is in the brainstem even when the coil is over the motor cortex. With modelling prior to an experiment, such problematic coil orientations can be avoided for more accurate targeting.
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http://dx.doi.org/10.1038/s41598-020-74431-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567095PMC
October 2020

Automated search of stimulation targets with closed-loop transcranial magnetic stimulation.

Neuroimage 2020 10 25;220:117082. Epub 2020 Jun 25.

Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland; BioMag Laboratory, HUS Medical Imaging Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Transcranial magnetic stimulation (TMS) protocols often include a manual search of an optimal location and orientation of the coil or peak stimulating electric field to elicit motor responses in a target muscle. This target search is laborious, and the result is user-dependent. Here, we present a closed-loop search method that utilizes automatic electronic adjustment of the stimulation based on the previous responses. The electronic adjustment is achieved by multi-locus TMS, and the adaptive guiding of the stimulation is based on the principles of Bayesian optimization to minimize the number of stimuli (and time) needed in the search. We compared our target-search method with other methods, such as systematic sampling in a predefined cortical grid. Validation experiments on five healthy volunteers and further offline simulations showed that our adaptively guided search method needs only a relatively small number of stimuli to provide outcomes with good accuracy and precision. The automated method enables fast and user-independent optimization of stimulation parameters in research and clinical applications of TMS.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117082DOI Listing
October 2020

Interhemispheric symmetry of µ-rhythm phase-dependency of corticospinal excitability.

Sci Rep 2020 05 12;10(1):7853. Epub 2020 May 12.

Department of Neurology & Stroke, University of Tübingen, Tübingen, Germany.

Oscillatory activity in the µ-frequency band (8-13 Hz) determines excitability in sensorimotor cortex. In humans, the primary motor cortex (M1) in the two hemispheres shows significant anatomical, connectional, and electrophysiological differences associated with motor dominance. It is currently unclear whether the µ-oscillation phase effects on corticospinal excitability demonstrated previously for the motor-dominant M1 are also different between motor-dominant and motor-non-dominant M1 or, alternatively, are similar to reflect a ubiquitous physiological trait of the motor system at rest. Here, we applied single-pulse transcranial magnetic stimulation to the hand representations of the motor-dominant and the motor-non-dominant M1 of 51 healthy right-handed volunteers when electroencephalography indicated a certain µ-oscillation phase (positive peak, negative peak, or random). We determined resting motor threshold (RMT) as a marker of corticospinal excitability in the three µ-phase conditions. RMT differed significantly depending on the pre-stimulus phase of the µ-oscillation in both M1, with highest RMT in the positive-peak condition, and lowest RMT in the negative-peak condition. µ-phase-dependency of RMT correlated directly between the two M1, and interhemispheric differences in µ-phase-dependency were absent. In conclusion, µ-phase-dependency of corticospinal excitability appears to be a ubiquitous physiological trait of the motor system at rest, without hemispheric dominance.
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http://dx.doi.org/10.1038/s41598-020-64390-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217936PMC
May 2020

The shaky ground truth of real-time phase estimation.

Neuroimage 2020 07 18;214:116761. Epub 2020 Mar 18.

Department of Neurology & Stroke, And Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. Electronic address:

Instantaneous phase of brain oscillations in electroencephalography (EEG) is a measure of brain state that is relevant to neuronal processing and modulates evoked responses. However, determining phase at the time of a stimulus with standard signal processing methods is not possible due to the stimulus artifact masking the future part of the signal. Here, we quantify the degree to which signal-to-noise ratio and instantaneous amplitude of the signal affect the variance of phase estimation error and the precision with which "ground truth" phase is even defined, using both the variance of equivalent estimators and realistic simulated EEG data with known synthetic phase. Necessary experimental conditions are specified in which pre-stimulus phase estimation is meaningfully possible based on instantaneous amplitude and signal-to-noise ratio of the oscillation of interest. An open source toolbox is made available for causal (using pre-stimulus signal only) phase estimation along with a EEG dataset consisting of recordings from 140 participants and a best practices workflow for algorithm optimization and benchmarking. As an illustration, post-hoc sorting of open-loop transcranial magnetic stimulation (TMS) trials according to pre-stimulus sensorimotor μ-rhythm phase is performed to demonstrate modulation of corticospinal excitability, as indexed by the amplitude of motor evoked potentials.
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http://dx.doi.org/10.1016/j.neuroimage.2020.116761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284312PMC
July 2020

Graph Theoretical Analysis of Cortical Networks based on Conscious Experience.

Annu Int Conf IEEE Eng Med Biol Soc 2019 Jul;2019:3373-3376

The aim of the study was to investigate differences in cortical networks based on the state of consciousness. Five subjects performed a serial-awakening paradigm with electroencephalography (EEG) recordings. We considered four states of consciousness: (1) non-rapid eye movement (NREM) sleep with no conscious experience, (2) NREM sleep with conscious experience, (3) rapid eye movement (REM) sleep with conscious experience, and (4) wakefulness. We applied graph theoretical analysis to explore the cortical connectivity and network properties in five frequency bands. Connectivity between EEG channels was evaluated with the weighted phase lag index (wPLI). The characteristic path length, transitivity, and clustering coefficient were computed to evaluate functional integration and segregation of the associated brain network. There were no significant differences in wPLI among the four states of consciousness. In the beta band, functional integration in wakefulness was higher than in NREM sleep. Regarding functional segregation, in the theta band, transitivity and clustering coefficient in NREM sleep with no conscious experience were stronger than in wakefulness or REM sleep, but clustering in the beta band showed an opposite effect. The observed differences may be related to cortical bistability and add to previously observed neural correlates of consciousness.
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http://dx.doi.org/10.1109/EMBC.2019.8857648DOI Listing
July 2019

Short-interval intracortical inhibition in human primary motor cortex: A multi-locus transcranial magnetic stimulation study.

Neuroimage 2019 12 13;203:116194. Epub 2019 Sep 13.

Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland; BioMag Laboratory, HUS Medical Imaging Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Short-interval intracortical inhibition (SICI) has been studied with paired-pulse transcranial magnetic stimulation (TMS) by administering two pulses at a millisecond-scale interstimulus interval (ISI) to a single cortical target. It has, however, been difficult to study the interaction of nearby cortical targets with paired-pulse TMS. To overcome this limitation, we have developed a multi-locus TMS (mTMS) device, which allows controlling the stimulus location electronically. Here, we applied mTMS to study SICI in primary motor cortex with paired pulses targeted to adjacent locations, aiming to quantify the extent of the cortical region producing SICI in the location of a test stimulus. We varied the location and timing of the conditioning stimulus with respect to a test stimulus targeted to the cortical hotspot of the abductor pollicis brevis (APB) in order to study their effects on motor evoked potentials. We further applied a two-coil protocol with the conditioning stimulus given by an oval coil only to the surroundings of the APB hotspot, to which a subsequent test stimulus was administered with a figure-of-eight coil. The strongest SICI occurred at ISIs below 1 ms and at ISIs around 2.5 ms. These ISIs increased when the conditioning stimulus receded from the APB hotspot. Our two-coil paired-pulse TMS study suggests that SICI at ISIs of 0.5 and 2.5 ms originate from different mechanisms or neuronal elements.
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http://dx.doi.org/10.1016/j.neuroimage.2019.116194DOI Listing
December 2019

Brain State-dependent Brain Stimulation with Real-time Electroencephalography-Triggered Transcranial Magnetic Stimulation.

J Vis Exp 2019 08 20(150). Epub 2019 Aug 20.

Department of Neurology & Stroke, University of Tübingen; Hertie Institute for Clinical Brain Research, University of Tübingen.

The effect of a stimulus to the brain depends not only on the parameters of the stimulus but also on the dynamics of brain activity at the time of the stimulation. The combination of electroencephalography (EEG) and transcranial magnetic stimulation (TMS) in a real-time brain state-dependent stimulation system allows the study of relations of dynamics of brain activity, cortical excitability, and plasticity induction. Here, we demonstrate a newly developed method to synchronize the timing of brain stimulation with the phase of ongoing EEG oscillations using a real-time data analysis system. This real-time EEG-triggered TMS of the human motor cortex, when TMS is synchronized with the surface EEG negative peak of the sensorimotor µ-alpha (8-14 Hz) rhythm, has shown differential corticospinal excitability and plasticity effects. The utilization of this method suggests that real-time information about the instantaneous brain state can be used for efficacious plasticity induction. Additionally, this approach enables personalized EEG-synchronized brain stimulation which may lead to the development of more effective therapeutic brain stimulation protocols.
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http://dx.doi.org/10.3791/59711DOI Listing
August 2019

The effect of experimental pain on short-interval intracortical inhibition with multi-locus transcranial magnetic stimulation.

Exp Brain Res 2019 Jun 27;237(6):1503-1510. Epub 2019 Mar 27.

Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, AALTO, P.O. Box 12200, 00076, Espoo, Finland.

Chronic neuropathic pain is known to alter the primary motor cortex (M1) function. Less is known about the normal, physiological effects of experimental neurogenic pain on M1. The objective of this study is to determine how short-interval intracortical inhibition (SICI) is altered in the M1 representation area of a muscle exposed to experimental pain compared to SICI of another muscle not exposed to pain. The cortical representation areas of the right abductor pollicis brevis (APB) and biceps brachii (BB) muscles of 11 subjects were stimulated with a multi-locus transcranial magnetic stimulation device while the resulting motor-evoked potentials (MEPs) were recorded with electromyography. Single- and paired-pulse TMS was administered in seven conditions, including one with the right hand placed in cold water. The stimulation intensity for the conditioning pulses in the paired-pulse examination was 80% of the resting motor threshold (RMT) of the stimulated site and 120% of RMT for both the test and single pulses. The paired-pulse MEP amplitudes were normalized with the mean amplitude of the single-pulse MEPs of the same condition and muscle. SICI was compared between conditions. After the cold pain, the normalized paired-pulse MEP amplitudes decreased in APB, but not in BB, indicating that SICI was potentially increased only in the cortical area of the muscle subjected to pain. These data suggest that SICI is increased in the M1 representation area of a hand muscle shortly after exposure to pain has ended, which implies that short-lasting pain can alter the inhibitory balance in M1.
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http://dx.doi.org/10.1007/s00221-019-05502-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525662PMC
June 2019

Connectivity differences between consciousness and unconsciousness in non-rapid eye movement sleep: a TMS-EEG study.

Sci Rep 2019 03 26;9(1):5175. Epub 2019 Mar 26.

Department of Brain and Cognitive Engineering, Korea University, Seoul, Korea.

The neuronal connectivity patterns that differentiate consciousness from unconsciousness remain unclear. Previous studies have demonstrated that effective connectivity, as assessed by transcranial magnetic stimulation combined with electroencephalography (TMS-EEG), breaks down during the loss of consciousness. This study investigated changes in EEG connectivity associated with consciousness during non-rapid eye movement (NREM) sleep following parietal TMS. Compared with unconsciousness, conscious experiences during NREM sleep were associated with reduced phase-locking at low frequencies (<4 Hz). Transitivity and clustering coefficient in the delta and theta bands were also significantly lower during consciousness compared to unconsciousness, with differences in the clustering coefficient observed in scalp electrodes over parietal-occipital regions. There were no significant differences in Granger-causality patterns in frontal-to-parietal or parietal-to-frontal connectivity between reported unconsciousness and reported consciousness. Together these results suggest that alterations in spectral and spatial characteristics of network properties in posterior brain areas, in particular decreased local (segregated) connectivity at low frequencies, is a potential indicator of consciousness during sleep.
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http://dx.doi.org/10.1038/s41598-019-41274-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435892PMC
March 2019

Evoked Alpha Power is Reduced in Disconnected Consciousness During Sleep and Anesthesia.

Sci Rep 2018 11 9;8(1):16664. Epub 2018 Nov 9.

Department of Anesthesiology, University of Wisconsin, Madison, 53792, USA.

Sleep and anesthesia entail alterations in conscious experience. Conscious experience may be absent (unconsciousness) or take the form of dreaming, a state in which sensory stimuli are not incorporated into conscious experience (disconnected consciousness). Recent work has identified features of cortical activity that distinguish conscious from unconscious states; however, less is known about how cortical activity differs between disconnected states and normal wakefulness. We employed transcranial magnetic stimulation-electroencephalography (TMS-EEG) over parietal regions across states of anesthesia and sleep to assess whether evoked oscillatory activity differed in disconnected states. We hypothesized that alpha activity, which may regulate perception of sensory stimuli, is altered in the disconnected states of rapid eye movement (REM) sleep and ketamine anesthesia. Compared to wakefulness, evoked alpha power (8-12 Hz) was decreased during disconnected consciousness. In contrast, in unconscious states of propofol anesthesia and non-REM (NREM) sleep, evoked low-gamma power (30-40 Hz) was decreased compared to wakefulness or states of disconnected consciousness. These findings were confirmed in subjects in which dream reports were obtained following serial awakenings from NREM sleep. By examining signatures of evoked cortical activity across conscious states, we identified novel evidence that suppression of evoked alpha activity may represent a promising marker of sensory disconnection.
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http://dx.doi.org/10.1038/s41598-018-34957-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226534PMC
November 2018

Multi-locus transcranial magnetic stimulation-theory and implementation.

Brain Stimul 2018 Jul - Aug;11(4):849-855. Epub 2018 Mar 23.

Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland; BioMag Laboratory, HUS Medical Imaging Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method: a magnetic field pulse from a TMS coil can excite neurons in a desired location of the cortex. Conventional TMS coils cause focal stimulation underneath the coil centre; to change the location of the stimulated spot, the coil must be moved over the new target. This physical movement is inherently slow, which limits, for example, feedback-controlled stimulation.

Objective: To overcome the limitations of physical TMS-coil movement by introducing electronic targeting.

Methods: We propose electronic stimulation targeting using a set of large overlapping coils and introduce a matrix-factorisation-based method to design such sets of coils. We built one such device and demonstrated the electronic stimulation targeting in vivo.

Results: The demonstrated two-coil transducer allows translating the stimulated spot along a 30-mm-long line segment in the cortex; with five coils, a target can be selected from within a region of the cortex and stimulated in any direction. Thus, far fewer coils are required by our approach than by previously suggested ones, none of which have resulted in practical devices.

Conclusion: Already with two coils, we can adjust the location of the induced electric field maximum along one dimension, which is sufficient to study, for example, the primary motor cortex.
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http://dx.doi.org/10.1016/j.brs.2018.03.014DOI Listing
February 2019

Noninvasive extraction of microsecond-scale dynamics from human motor cortex.

Hum Brain Mapp 2018 06 2;39(6):2405-2411. Epub 2018 Mar 2.

Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland.

State-of-the-art noninvasive electromagnetic recording techniques allow observing neuronal dynamics down to the millisecond scale. Direct measurement of faster events has been limited to in vitro or invasive recordings. To overcome this limitation, we introduce a new paradigm for transcranial magnetic stimulation. We adjusted the stimulation waveform on the microsecond scale, by varying the duration between the positive and negative phase of the induced electric field, and studied corresponding changes in the elicited motor responses. The magnitude of the electric field needed for given motor-evoked potential amplitude decreased exponentially as a function of this duration with a time constant of 17 µs. Our indirect noninvasive measurement paradigm allows studying neuronal kinetics on the microsecond scale in vivo.
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http://dx.doi.org/10.1002/hbm.24010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6866442PMC
June 2018

Erratum to: Minimum-Norm Estimation of Motor Representations in Navigated TMS Mappings.

Brain Topogr 2017 11;30(6):723

Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, P. O. Box 12200, 00076, Aalto, Espoo, Finland.

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http://dx.doi.org/10.1007/s10548-017-0587-6DOI Listing
November 2017

Minimum-Norm Estimation of Motor Representations in Navigated TMS Mappings.

Brain Topogr 2017 Nov 18;30(6):711-722. Epub 2017 Jul 18.

Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, P. O. Box 12200, FI-00076, Aalto, Espoo, Finland.

Navigated transcranial magnetic stimulation (nTMS) can be applied to locate and outline cortical motor representations. This may be important, e.g., when planning neurosurgery or focused nTMS therapy, or when assessing plastic changes during neurorehabilitation. Conventionally, a cortical location is considered to belong to the motor cortex if the maximum electric field (E-field) targeted there evokes a motor-evoked potential in a muscle. However, the cortex is affected by a broad E-field distribution, which tends to broaden estimates of representation areas by stimulating also the neighboring areas in addition to the maximum E-field location. Our aim was to improve the estimation of nTMS-based motor maps by taking into account the E-field distribution of the stimulation pulse. The effect of the E-field distribution was considered by calculating the minimum-norm estimate (MNE) of the motor representation area. We tested the method on simulated data and then applied it to recordings from six healthy volunteers and one stroke patient. We compared the motor representation areas obtained with the MNE method and a previously introduced interpolation method. The MNE hotspots and centers of gravity were close to those obtained with the interpolation method. The areas of the maps, however, depend on the thresholds used for outlining the areas. The MNE method may improve the definition of cortical motor areas, but its accuracy should be validated by comparing the results with maps obtained with direct cortical stimulation of the cortex where the E-field distribution can be better focused.
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http://dx.doi.org/10.1007/s10548-017-0577-8DOI Listing
November 2017

Coil optimisation for transcranial magnetic stimulation in realistic head geometry.

Brain Stimul 2017 Jul - Aug;10(4):795-805. Epub 2017 Apr 15.

Department of Neuroscience and Biomedical Engineering, Aalto University, P.O. Box 12200, FI-00076 AALTO, Espoo, Finland; BioMag Laboratory, HUS Medical Imaging Center, University of Helsinki and Helsinki University Hospital, P.O. Box 340, FI-00029 HUS, Helsinki, Finland.

Background: Transcranial magnetic stimulation (TMS) allows focal, non-invasive stimulation of the cortex. A TMS pulse is inherently weakly coupled to the cortex; thus, magnetic stimulation requires both high current and high voltage to reach sufficient intensity. These requirements limit, for example, the maximum repetition rate and the maximum number of consecutive pulses with the same coil due to the rise of its temperature.

Objective: To develop methods to optimise, design, and manufacture energy-efficient TMS coils in realistic head geometry with an arbitrary overall coil shape.

Methods: We derive a semi-analytical integration scheme for computing the magnetic field energy of an arbitrary surface current distribution, compute the electric field induced by this distribution with a boundary element method, and optimise a TMS coil for focal stimulation. Additionally, we introduce a method for manufacturing such a coil by using Litz wire and a coil former machined from polyvinyl chloride.

Results: We designed, manufactured, and validated an optimised TMS coil and applied it to brain stimulation. Our simulations indicate that this coil requires less than half the power of a commercial figure-of-eight coil, with a 41% reduction due to the optimised winding geometry and a partial contribution due to our thinner coil former and reduced conductor height. With the optimised coil, the resting motor threshold of abductor pollicis brevis was reached with the capacitor voltage below 600 V and peak current below 3000 A.

Conclusion: The described method allows designing practical TMS coils that have considerably higher efficiency than conventional figure-of-eight coils.
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http://dx.doi.org/10.1016/j.brs.2017.04.001DOI Listing
February 2018

Consciousness and cortical responsiveness: a within-state study during non-rapid eye movement sleep.

Sci Rep 2016 08 5;6:30932. Epub 2016 Aug 5.

Department of Psychiatry, University of Wisconsin, Madison, WI, USA.

When subjects become unconscious, there is a characteristic change in the way the cerebral cortex responds to perturbations, as can be assessed using transcranial magnetic stimulation and electroencephalography (TMS-EEG). For instance, compared to wakefulness, during non-rapid eye movement (NREM) sleep TMS elicits a larger positive-negative wave, fewer phase-locked oscillations, and an overall simpler response. However, many physiological variables also change when subjects go from wake to sleep, anesthesia, or coma. To avoid these confounding factors, we focused on NREM sleep only and measured TMS-evoked EEG responses before awakening the subjects and asking them if they had been conscious (dreaming) or not. As shown here, when subjects reported no conscious experience upon awakening, TMS evoked a larger negative deflection and a shorter phase-locked response compared to when they reported a dream. Moreover, the amplitude of the negative deflection-a hallmark of neuronal bistability according to intracranial studies-was inversely correlated with the length of the dream report (i.e., total word count). These findings suggest that variations in the level of consciousness within the same physiological state are associated with changes in the underlying bistability in cortical circuits.
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http://dx.doi.org/10.1038/srep30932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4974655PMC
August 2016

Recovering TMS-evoked EEG responses masked by muscle artifacts.

Neuroimage 2016 Oct 9;139:157-166. Epub 2016 Jun 9.

Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, P.O. Box 12200, FI-00076 AALTO, Finland; BioMag Laboratory, HUS Medical Imaging Center, University of Helsinki and Helsinki University Hospital, P.O. Box 340, FI-00029 HUS, Finland.

Combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) often suffers from large muscle artifacts. Muscle artifacts can be removed using signal-space projection (SSP), but this can make the visual interpretation of the remaining EEG data difficult. We suggest to use an additional step after SSP that we call source-informed reconstruction (SIR). SSP-SIR improves substantially the signal quality of artifactual TMS-EEG data, causing minimal distortion in the neuronal signal components. In the SSP-SIR approach, we first project out the muscle artifact using SSP. Utilizing an anatomical model and the remaining signal, we estimate an equivalent source distribution in the brain. Finally, we map the obtained source estimate onto the original signal space, again using anatomical information. This approach restores the neuronal signals in the sensor space and interpolates EEG traces onto the completely rejected channels. The introduced algorithm efficiently suppresses TMS-related muscle artifacts in EEG while retaining well the neuronal EEG topographies and signals. With the presented method, we can remove muscle artifacts from TMS-EEG data and recover the underlying brain responses without compromising the readability of the signals of interest.
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http://dx.doi.org/10.1016/j.neuroimage.2016.05.028DOI Listing
October 2016

Experimental Characterization of the Electric Field Distribution Induced by TMS Devices.

Brain Stimul 2015 May-Jun;8(3):582-9. Epub 2015 Jan 12.

Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland; BioMag Laboratory, HUS Medical Imaging Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Aalto TMS Laboratory, Aalto Neuroimaging, Aalto University, Espoo, Finland.

Background: In transcranial magnetic stimulation (TMS) a strong, brief current pulse driven through a coil is used for non-invasively stimulating the cortex. Properties of the electric field (E-field) induced by the pulse together with physiological parameters determine the outcome of the stimulation. In research and clinical use, TMS is delivered using a wide range of different coils and stimulator units, all having their own characteristics; however, the parameters of the induced E-field are often inadequately known by the user.

Objective: To better understand how the use of a specific TMS device may affect the resulting cortical stimulation, our objective was to develop an instrument for automated measurement of the E-fields induced by TMS coils in spherically symmetric conductors approximating the head.

Methods: We built a saline-free, robotized measurement tool based on the triangle construction. The 5-mm-wide measurement probe allows complete sampling of the induced E-field at the studied depth. We used the instrument to characterize TMS coils and stimulators made by two companies.

Results: The measurements revealed that all tested stimulators performed as expected, but we also found significant differences between the different stimulators. Measurements of different coil specimens of the same stimulator models agreed with each other.

Conclusion: The presented TMS calibrator allows a straightforward characterization of the E-fields induced by TMS coils. By performing measurements using this kind of a tool helps in ensuring that an investigator knows the properties of the E-field.
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http://dx.doi.org/10.1016/j.brs.2015.01.004DOI Listing
January 2016

Minimum-energy coils for transcranial magnetic stimulation: application to focal stimulation.

Brain Stimul 2015 Jan-Feb;8(1):124-34. Epub 2014 Oct 13.

Department of Biomedical Engineering and Computational Science (BECS), Aalto University, P.O. Box 12200, FI-00076 AALTO, Espoo, Finland.

Background: In transcranial magnetic stimulation (TMS), the stimulation-coil current is typically increased from 0 to over 5000 A in less than 100 μs. At the peak current, the energy stored in the magnetic field is over 300 J. Thus, the average power during a pulse exceeds 3 MW; the stimulator needs to be built from high-power electronics. The power requirements often limit the duration and frequency of repetitive TMS, for example, via coil heating.

Objective: We introduce a method for finding the minimum-energy solution for a TMS coil with given focality constraints.

Methods: This optimization is performed by using a spherically symmetric head model and by expressing the coil as a continuous surface current density, which is eventually discretized to form the coil windings. For the optimization, we defined TMS focality separately for the directions parallel and perpendicular to the field direction at the maximum of induced electric field.

Results: The computational model used for optimization was verified by manufacturing a prototype coil and measuring the electric field it induces in a spherically symmetric conductor. The optimized coil design requires significantly less power than existing TMS coil designs (a 73% reduction compared to an existing TMS coil with similar focality).

Conclusion: The described method allows for more efficient, more focal TMS coils, which may reduce coil heating and the coil click.
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http://dx.doi.org/10.1016/j.brs.2014.10.002DOI Listing
May 2015

Current-density imaging using ultra-low-field MRI with zero-field encoding.

Magn Reson Imaging 2014 Jul 28;32(6):766-70. Epub 2014 Jan 28.

Department of Biomedical Engineering and Computational Science, Aalto University School of Science, P.O. Box 12200, FI-00076 AALTO, Finland.

Electric current density can be measured noninvasively with magnetic resonance imaging (MRI). Determining all three components of the current density, however, requires physical rotation of the sample or current injection from several directions when done with conventional methods. However, the emerging technology of ultra-low-field (ULF) MRI, in which the signal encoding and acquisition is conducted at a microtesla-range magnetic field, offers new possibilities. The low applied magnetic fields can even be switched off completely within the pulse sequence, increasing the flexibility of the available sequences. In this article, we present a ULF-MRI sequence designed for obtaining all three components of a current-density pattern without the need of sample rotations. The sequence consists of three steps: prepolarization of the sample, signal encoding in the current-density-associated magnetic field without applying any MRI fields, and spatial encoding in a microtesla-range field using any standard ULF-MRI sequence. The performance of the method is evaluated by numerical simulations. The method may find applications, e.g., in noninvasive conductivity imaging of tissue.
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http://dx.doi.org/10.1016/j.mri.2014.01.012DOI Listing
July 2014

An advanced phantom study assessing the feasibility of neuronal current imaging by ultra-low-field NMR.

J Magn Reson 2013 Dec 30;237:182-190. Epub 2013 Oct 30.

Physikalisch-Technische Bundesanstalt (PTB), Abbestrasse 2-12, 10587 Berlin, Germany.

In ultra-low-field (ULF) NMR/MRI, a common scheme is to magnetize the sample by a polarizing field of up to hundreds of mT, after which the NMR signal, precessing in a field on the order of several μT, is detected with superconducting quantum interference devices (SQUIDs). In our ULF-NMR system, we polarize with up to 50mT and deploy a single-stage DC-SQUID current sensor with an integrated input coil which is connected to a wire-wound Nb gradiometer. We developed this system (white noise 0.50fT/√Hz) for assessing the feasibility of imaging neuronal currents by detecting their effect on the ULF-NMR signal. Magnetoencephalography investigations of evoked brain activity showed neuronal dipole moments below 50nAm. With our instrumentation, we have studied two different approaches for neuronal current imaging. In the so-called DC effect, long-lived neuronal activity shifts the Larmor frequency of the surrounding protons. An alternative strategy is to exploit fast neuronal activity as a tipping pulse. This so-called AC effect requires the proton Larmor frequency to match the frequency of the neuronal activity, which ranges from near-DC to ∼kHz. We emulated neuronal activity by means of a single dipolar source in a physical phantom, consisting of a hollow sphere filled with an aqueous solution of CuSO4 and NaCl. In these phantom studies, with physiologically relevant dipole depths, we determined resolution limits for our set-up for the AC and the DC effect of ∼10μAm and ∼50nAm, respectively. Hence, the DC effect appears to be detectable in vivo by current ULF-NMR technology.
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http://dx.doi.org/10.1016/j.jmr.2013.10.011DOI Listing
December 2013

Current-density imaging using ultra-low-field MRI with adiabatic pulses.

Magn Reson Imaging 2014 Jan 15;32(1):54-9. Epub 2013 Oct 15.

Department of Biomedical Engineering and Computational Science, Aalto University School of Science, P.O. Box 12200, FI-00076 AALTO, Finland. Electronic address:

Magnetic resonance imaging (MRI) allows measurement of electric current density in an object. The measurement is based on observing how the magnetic field of the current density affects the associated spins. However, as high-field MRI is sensitive to static magnetic field variations of only the field component along the main field direction, object rotations are typically needed to image three-dimensional current densities. Ultra-low-field (ULF) MRI, on the other hand, with B0 on the order of 10-100 μT, allows novel MRI sequences. We present a rotation-free method for imaging static magnetic fields and current densities using ULF MRI. The method utilizes prepolarization pulses with adiabatic switch-off ramps. The technique is designed to reveal complete field and current-density information without the need to rotate the object. The method may find applications, e.g., in conductivity imaging. We present simulation results showing the feasibility of the sequence.
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http://dx.doi.org/10.1016/j.mri.2013.07.012DOI Listing
January 2014

Temperature dependence of relaxation times and temperature mapping in ultra-low-field MRI.

J Magn Reson 2013 Oct 27;235:50-7. Epub 2013 Jul 27.

Department of Biomedical Engineering and Computational Science, Aalto University School of Science, P.O. Box 12200, FI-00076 AALTO, Finland; AMI Centre, Aalto University School of Science, P.O. Box 13000, FI-00076 AALTO, Finland. Electronic address:

Ultra-low-field MRI is an emerging technology that allows MRI and NMR measurements in microtesla-range fields. In this work, the possibilities of relaxation-based temperature measurements with ultra-low-field MRI were investigated by measuring T1 and T2 relaxation times of agarose gel at 50 μT-52 mT and at temperatures 5-45°C. Measurements with a 3T scanner were made for comparison. The Bloembergen-Purcell-Pound relaxation theory was combined with a two-state model to explain the field-strength and temperature dependence of the data. The results show that the temperature dependencies of agarose gel T1 and T2 in the microtesla range differ drastically from those at 3T; the effect of temperature on T1 is reversed at approximately 5 mT. The obtained results were used to reconstruct temperature maps from ultra-low-field scans. These time-dependent temperature maps measured from an agarose gel phantom at 50 μT reproduced the temperature gradient with good contrast.
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http://dx.doi.org/10.1016/j.jmr.2013.07.009DOI Listing
October 2013

Efficient concomitant and remanence field artifact reduction in ultra-low-field MRI using a frequency-space formulation.

Magn Reson Med 2014 Mar;71(3):955-65

Department of Mathematics, National Taiwan University, Taipei, Taiwan; Department of Biomedical Engineering and Computational Science, Aalto University School of Science, Espoo, Finland.

Purpose: For ultra-low-field MRI, the spatial-encoding magnetic fields generated by gradient coils can have strong concomitant fields leading to prominent image distortion. Additionally, using superconducting magnet to pre-polarize magnetization can improve the signal-to-noise ratio of ultra-low-field MRI. Yet the spatially inhomogeneous remanence field due to the permanently trapped flux inside a superconducting pre-polarizing coil modulates magnetization and causes further image distortion.

Method: We propose a two-stage frequency-space (f-x) formulation to accurately describe the dynamics of spatially-encoded magnetization under the influence of concomitant and remanence fields, which allows for correcting image distortion due to concomitant and remanence fields.

Results: Our method is computationally efficient as it uses a combination of the fast Fourier transform algorithm and a linear equation solver. With sufficiently dense discretization in solving the linear equation, the performance of this f-x method was found to be stable among different choices of the regularization parameter and the regularization matrix.

Conclusion: We present this method together with numerical simulations and experimental data to demonstrate how concomitant and remanence field artifacts in ultra-low-field MRI can be corrected efficiently.
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http://dx.doi.org/10.1002/mrm.24745DOI Listing
March 2014

TMS-evoked changes in brain-state dynamics quantified by using EEG data.

Front Hum Neurosci 2013 25;7:155. Epub 2013 Apr 25.

Department of Biomedical Engineering and Computational Science, Aalto University School of Science Espoo, Finland ; BioMag Laboratory, HUSLAB, Helsinki University Central Hospital Helsinki, Finland.

To improve our understanding of the combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) method in general, it is important to study how the dynamics of the TMS-modulated brain activity differs from the dynamics of spontaneous activity. In this paper, we introduce two quantitative measures based on EEG data, called mean state shift (MSS) and state variance (SV), for evaluating the TMS-evoked changes in the brain-state dynamics. MSS quantifies the immediate TMS-elicited change in the brain state, whereas SV shows whether the rate at which the brain state changes is modulated by TMS. We report a statistically significant increase for a period of 100-200 ms after the TMS pulse in both MSS and SV at the group level. This indicates that the TMS-modulated brain state differs from the spontaneous one. Moreover, the TMS-modulated activity is more vigorous than the natural activity.
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http://dx.doi.org/10.3389/fnhum.2013.00155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635036PMC
May 2013

Suppressing multi-channel ultra-low-field MRI measurement noise using data consistency and image sparsity.

PLoS One 2013 23;8(4):e61652. Epub 2013 Apr 23.

Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.

Ultra-low-field (ULF) MRI (B 0 = 10-100 µT) typically suffers from a low signal-to-noise ratio (SNR). While SNR can be improved by pre-polarization and signal detection using highly sensitive superconducting quantum interference device (SQUID) sensors, we propose to use the inter-dependency of the k-space data from highly parallel detection with up to tens of sensors readily available in the ULF MRI in order to suppress the noise. Furthermore, the prior information that an image can be sparsely represented can be integrated with this data consistency constraint to further improve the SNR. Simulations and experimental data using 47 SQUID sensors demonstrate the effectiveness of this data consistency constraint and sparsity prior in ULF-MRI reconstruction.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0061652PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633989PMC
November 2013

Gradient-excitation encoding combined with frequency and phase encodings for three-dimensional ultra-low-field MRI.

Annu Int Conf IEEE Eng Med Biol Soc 2012 ;2012:1093-7

Department of Biomedical Engineering and Computational Science, Aalto University School of Science, Aalto, Finland.

Ultra-low-field magnetic resonance imaging (ULF MRI) in microtesla fields is a new technology with features unseen in tesla-range MRI. Instead of induction coils as sensors, superconducting quantum interference device (SQUID) sensors are used, providing a frequency-independent signal-to-noise ratio (SNR). Owing to its tolerance for large relative imaging-field inhomogeneities, electromagnet shimming is not necessary. ULF MRI can also be combined with magnetoencephalography (MEG) to image the brain with close to millimetre-millisecond resolution. In this paper, the hybrid MEG-MRI device developed at Aalto University will be presented, as well as a 3D imaging scheme combining gradient-excitation encoding with frequency and phase and encodings. It is noteworthy that, regarding the presented gradient-excitation encoding in ULF MRI, the kilohertz-range Larmor frequencies allow MR signals to propagate unattenuated through tissue, which is not the case in tesla-range MRI with Larmor frequencies even above 100 MHz. Thus, the presented encoding method is especially compatible with ULF MRI, where the use of three different encoding mechanisms for three-dimensional imaging is possible. The feasibility of image reconstruction with the gradient-excitation-encoding method is demonstrated by simulations.
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http://dx.doi.org/10.1109/EMBC.2012.6346125DOI Listing
August 2013
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