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Funding Information: The authors acknowledge the Finnish National Agency for Education and Päivikki and Sakari Sohlberg Foundation for funding for Olesia Korsun, and the Academy of Finland (grant number 321460) and Paulo Foundation for funding for Hanna Renvall. The authors acknowledge Kati Valkonen for providing the clinical patient data, and all the patients for their participation. Open access funding enabled and organized by Projekt DEAL. Publisher Copyright: © 2022 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd. Despite optimal oral drug treatment, about 90% of patients with Parkinson's disease develop motor fluctuation and dyskinesia within 5–10 years from the diagnosis. Moreover, the patients show non-motor symptoms in different sensory domains. Bilateral deep brain stimulation (DBS) applied to the subthalamic nucleus is considered the most effective treatment in advanced Parkinson's disease, and it has been suggested to affect sensorimotor modulation and relate to motor improvement in patients. However, observations on the relationship between sensorimotor activity and clinical improvement have remained sparse. Here, we studied the somatosensory evoked magnetic fields in 13 right-handed patients with advanced Parkinson's disease before and 7 months after stimulator implantation. Somatosensory processing was addressed with magnetoencephalography during alternated median nerve stimulation at both wrists. The strengths and the latencies of the ~60-ms responses at the contralateral primary somatosensory cortices were highly variable but detectable and reliably localized in all patients. The response strengths did not differ between preoperative and postoperative DBSON measurements. The change in the response strength between preoperative and postoperative condition in the dominant left hemisphere of our right-handed patients correlated with the alleviation of their motor symptoms (p =.04). However, the result did not survive correction for multiple comparisons. Magnetoencephalography appears an effective tool to explore non-motor effects in patients with Parkinson's disease, and it may help in understanding the neurophysiological basis of DBS. However, the high interindividual variability in the somatosensory responses and poor tolerability of DBSOFF condition warrants larger patient groups and measurements also in non-medicated patients.

Exaggerated subthalamic beta oscillatory activity and increased beta range cortico-subthalamic synchrony have crystallized as the electrophysiological hallmarks of Parkinson's disease. Beta oscillatory activity is not tonic but occurs in 'bursts' of transient amplitude increases. In Parkinson's disease, the characteristics of these bursts are altered especially in the basal ganglia. However, beta oscillatory dynamics at the cortical level and how they compare with healthy brain activity is less well studied. We used magnetoencephalography (MEG) to study sensorimotor cortical beta bursting and its modulation by subthalamic deep brain stimulation in Parkinson's disease patients and age-matched healthy controls. We show that the changes in beta bursting amplitude and duration typical of Parkinson's disease can also be observed in the sensorimotor cortex, and that they are modulated by chronic subthalamic deep brain stimulation, which, in turn, is reflected in improved motor function at the behavioural level. In addition to the changes in individual beta bursts, their timing relative to each other was altered in patients compared to controls: bursts were more clustered in untreated Parkinson's disease, occurring in 'bursts of bursts', and re-burst probability was higher for longer compared to shorter bursts. During active deep brain stimulation, the beta bursting in patients resembled healthy controls' data. In summary, both individual bursts' characteristics and burst patterning are affected in Parkinson's disease, and subthalamic deep brain stimulation normalizes some of these changes to resemble healthy controls' beta bursting activity, suggesting a non-invasive biomarker for patient and treatment follow-up.

Objective: We assessed in extremely preterm born (EPB) children whether secondary somatosensory cor-tex (SII) responses recorded with magnetoencephalography (MEG) at term-equivalent age (TEA) correlate with neurodevelopmental outcome at age 6 years. Secondly, we assessed whether SII responses differ between 6-year-old EPB and term-born (TB) children. Methods: 39 EPB children underwent MEG with tactile stimulation at TEA. At age 6 years, 32 EPB and 26 TB children underwent MEG including a sensorimotor task requiring attention and motor inhibition. SII responses to tactile stimulation were modeled with equivalent current dipoles. Neurological outcome, motor competence, and general cognitive ability were prospectively evaluated at age 6 years. Results: Unilaterally absent SII response at TEA was associated with abnormal motor competence in 6-year-old EPB children (p = 0.03). At age 6 years, SII responses were bilaterally detectable in most EPB (88%) and TB (92%) children (group comparison, p = 0.69). Motor inhibition was associated with decreased SII peak latencies in TB children, but EPB children lacked this effect (p = 0.02). Conclusions: Unilateral absence of an SII response at TEA predicted poorer motor outcome in EPB children. Significance: Neurophysiological methods may provide new means for outcome prognostication in EPB children. (c) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Deep brain stimulation (DBS) has proven its clinical efficacy in Parkinson's disease (PD), but its exact mechanisms and cortical effects continue to be unclear. Subthalamic (STN) DBS acutely modifies auditory evoked responses, but its long-term effect on auditory cortical processing remains ambiguous. We studied with magnetoencephalography the effect of long-term STN DBS on auditory processing in patients with advanced PD. DBS resulted in significantly increased contra-ipsilateral auditory response latency difference at ~100 ms after stimulus onset compared with preoperative state. The effect is likely due to normalization of neuronal asynchrony in the auditory pathways. The present results indicate that STN DBS in advanced PD patients has long-lasting effects on cortical areas outside those confined to motor processing. Whole-head magnetoencephalography provides a feasible tool to study motor and non-motor neural networks in PD, and to track possible changes related to cortical reorganization or plasticity induced by DBS.

Running shoe cushioning has become a standard method for managing impact loading and consequent injuries due to running. However, despite decades of shoe technology developments and the fact that shoes have become increasingly cushioned, aimed to ease the impact on runners’ legs, running injuries have not decreased. To better understand the shoe cushioning paradox, we examined impact loading and the spring-like mechanics of running in a conventional control running shoe and a highly cushioned maximalist shoe at two training speeds, 10 and 14.5 km/h. We found that highly cushioned maximalist shoes alter spring-like running mechanics and amplify rather than attenuate impact loading. This surprising outcome was more pronounced at fast running speed (14.5 km/h), where ground reaction force impact peak and loading rate were 10.7% and 12.3% greater, respectively, in the maximalist shoe compared to the conventional shoe, whereas only a slightly higher impact peak (6.4%) was found at the 10 km/h speed with the maximalist shoe. We attribute the greater impact loading with the maximalist shoes to stiffer leg during landing compared to that of running with the conventional shoes. These discoveries may explain why shoes with more cushioning do not protect against impact-related running injuries.

Advanced Parkinson's disease (PD) is characterized by an excessive oscillatory beta band activity in the sub thalamic nucleus (STN). Deep brain stimulation (DBS) of STN alleviates motor symptoms in PD and suppresses the STN beta band activity. The effect of DBS on cortical sensorimotor activity is more ambiguous; both increases and decreases of beta band activity have been reported. Non-invasive studies with simultaneous DBS are problematic due to DBS-induced artifacts. We recorded magnetoencephalography (MEG) from 16 advanced PD patients with and without STN DBS during rest and wrist extension. The strong magnetic artifacts related to stimulation were removed by temporal signal space separation. MEG oscillatory activity at 5-25 Hz was suppressed during DBS in a widespread frontoparietal region, including the sensorimotor cortex identified by the cortico-muscular coherence. The strength of suppression did not correlate with clinical improvement. Our results indicate that alpha and beta band oscillations are suppressed at the frontoparietal cortex by STN DBS in PD.

The mapping of the sensorimotor cortex gives information about the cortical motor and sensory functions. Typical mapping methods are navigated transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG). The differences between these mapping methods are, however, not fully known. TMS center of gravities (CoGs), MEG somatosensory evoked fields (SEFs), corticomuscular coherence (CMC), and corticokinematic coherence (CKC) were mapped in ten healthy adults. TMS mapping was performed for first dorsal interosseous (FDI) and extensor carpi radialis (ECR) muscles. SEFs were induced by tactile stimulation of the index finger. CMC and CKC were determined as the coherence between MEG signals and the electromyography or accelerometer signals, respectively, during voluntary muscle activity. CMC was mapped during the activation of FDI and ECR muscles separately, whereas CKC was measured during the waving of the index finger at a rate of 3–4 Hz. The maximum CMC was found at beta frequency range, whereas maximumCKC was found at the movement frequency. The mean Euclidean distances between different localizations were within 20 mm. The smallest distance was found between TMS FDI and TMS ECR CoGs and longest between CMC FDI and CMC ECR sites. TMS-inferred localizations (CoGs) were less variable across participants than MEG-inferred localizations (CMC, CKC). On average, SEF locations were 8 mm lateral to the TMS CoGs (p < 0.01). No differences between hemispheres were found. Based on the results, TMS appears to be more viable than MEG in locating motor cortical areas.

Objective Cortico-muscular coherence (CMC) is thought to reflect the interplay between cortex and muscle in motor coordination. In Parkinson's disease (PD) patients, levodopa has been shown to enhance CMC. This study examined whether subthalamic nucleus (STN) deep brain stimulation (DBS) affects the CMC in advanced PD. Methods Magnetoencephalography (MEG) and electromyography (EMG) measurements were done simultaneously both with DBS on and off to determine the CMC during wrist extension. The spatiotemporal signal space separation (tSSS) was used for artifact suppression. Results CMC peaks between 13 and 25Hz were found in 15 out of 19 patients. The effect of DBS on CMC was variable. Moreover, the correlation between CMC and motor performance was inconsistent; stronger CMC did not necessarily indicate better function albeit tremor and rigidity may diminish the CMC. Patients having CMC between 13 and 25Hz had the best motor scores at the group level. Conclusions DBS modifies the CMC in advanced PD with large interindividual variability. Significance DBS does not systematically modify CMC amplitude in advanced PD. The results suggest that some components of the CMC may be related to the therapeutic effects of DBS.

Objective Our aim was to assess the effectiveness and reliability of spatiotemporal signal space separation (tSSS) and movement correction (MC) in magnetoencephalography (MEG) recordings disturbed by head movements and magnetized material on the head. Methods We recorded MEG from 20 healthy adults in stationary (reference) head position and during controlled head movements. Nearby magnetic interference sources were simulated by attaching magnetized particles on the subject’s head. Auditory and somatosensory stimuli were presented. MC, tSSS and averaging were performed to obtain auditory (AEF) and somatosensory (SEF) evoked fields. Neuronal sources were modeled as equivalent current dipoles. MC was also validated by reconstructing signals generated by current dipoles in a phantom. Results After MC, the AEF and SEF responses recorded during intermittent head movements were similar in amplitude to the reference recordings and differed by 5–7 mm in source location. The tSSS method removed artifacts due to the attached magnetized particles but did not affect the reference data. Conclusions The methods are able to reliably recover MEG responses contaminated by movements and magnetic artifacts on the head. Significance The combination of tSSS and MC methods is especially useful in clinical measurements, where movements and magnetic disturbances are commonly present.

Motor symptoms of Parkinson's disease (PD) can be relieved by deep brain stimulation (DBS). The mechanism of action of DBS is largely unclear. Magnetoencephalography (MEG) studies on DBS patients have been unfeasible because of strong magnetic artifacts. An artifact suppression method known as spatiotemporal signal space separation (tSSS) has mainly overcome these difficulties. We wanted to clarify whether tSSS enables noninvasive measurement of the modulation of cortical activity caused by DBS. We have studied auditory and somatosensory-evoked fields (AEFs and SEFs) of advanced PD patients with bilateral subthalamic nucleus (STN) DBS using MEG. AEFs were elicited by 1-kHz tones and SEFs by electrical pulses to the median nerve with DBS on and off. Data could be successfully acquired and analyzed from 12 out of 16 measured patients. The motor symptoms were significantly relieved by DBS, which clearly enhanced the ipsilateral auditory N100m responses in the right hemisphere. Contralateral N100m responses and somatosensory P60m responses also had a tendency to increase when bilateral DBS was on. MEG with tSSS offers a novel and powerful tool to investigate DBS modulation of the evoked cortical activity in PD with high temporal and spatial resolution. The results suggest that STN-DBS modulates auditory processing in advanced PD. Hum Brain Mapp, 2011. © 2010 Wiley-Liss, Inc.

Biomagnetic instruments usually employ sensors with approximately radial normal vectors arranged on a near-spherical surface. The multipole expansion employed in the recently introduced signal space separation method (SSS) reveals limitations in this traditional sensor array design. Specifically, we show that the excessive symmetry of the sensor array impedes separation of multipole components arising from inside and outside of the array. This motivates consideration of novel instrument designs that would sample the field in a more comprehensive way. We evaluated several simulated sensor arrays that employ vector sensors in one or two layers, giving information on multiple field components and the radial dependence of the field. Our results indicate that this kind of sensor array design could significantly improve SSS performance, leading to enhanced shielding against external interference and reduced noise after signal reconstruction. The best two-layer array evaluated here attains a shielding factor of nearly 1000 or 60 dB with about 400 sensors. Due to limited spatial coverage, a traditional reference array geometry does not give the same level of improvement. In addition to improved software shielding, enhanced detection of different multipole components increases the information obtained about the magnetic field, which has fundamental importance.

The early dissociation in cortical responses to faces and objects was explored with magnetoencephalographic (MEG) recordings and source localization. To control for differences in the low‐level stimulus features, which are known to modulate early brain responses, we created a novel set of stimuli so that their combinations did not have any differences in the visual‐field location, spatial frequency, or luminance contrast. Differing responses to face and object (flower) stimuli were found at about 100 ms after stimulus onset in the occipital cortex. Our data also confirm that the brain response to a complex visual stimulus is not merely a sum of the responses to its constituent parts; the nonlinearity in the response was largest for meaningful stimuli. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.

Therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) are extensively studied in patients with Parkinson's disease (PD). rTMS to primary motor cortex (M1) induces dopamine release in the putamen: consequently M1 is an interesting target for rTMS in PD. The rTMS over M1 in PD patients reduces the reaction time, improves the Unified Parkinson's Disease Rating Scale (UPDRS) scores and alleviates bradykinesia and hypokinesia. However, the effects of rTMS on spontaneous brain activity are not known. We investigated whether subthreshold rTMS to M1 modulated spontaneous oscillations recorded with magnetoencephalography (MEG). MEG from nine medicated, non-demented PD patients displayed a significant increase in beta oscillations after rTMS in the stimulated hemisphere. Minimum current estimate calculations revealed an increase of beta oscillatory activity after the rTMS treatment over the Rolandic regions. The rTMS in PD patients alters spontaneous brain activity as seen with MEG, probably by modulating cortico-thalamo-basal ganglia networks.

Different head positions of the subjects hamper the comparison of data from different measurement sessions. Signal space separation (SSS) is a method that, besides its ability to suppress external interference signals, can be used for standardization of MEG data. In order to evaluate the performance of SSS in transforming MEG data between different head positions, three different kinds of steps were followed. The first step included phantom measurements by placing a spherical phantom in seven different positions. One position was used as reference and six other positions were used for representing different head positions. All data were transformed to correspond to the reference position. In addition to visualizing the recorded signals before and after the transformation, amplitude-weighted correlation algorithm was applied to compare the transformed and the reference data. Our results reveal excellent performance of the SSS method with phantom simulations of superficial medium-strength dipoles (100 nAm) or deeper high-strength dipoles (1000 nAm) activation. For the second step of the evaluation, data from two healthy subjects were recorded. In separate measurement runs, the subjects were asked to place their heads in four different positions as well as in one reference location within the sensory array. Auditory evoked fields were recorded. The same evaluation procedure was followed as in phantom measurements resulting in very satisfactory results. The third step included SSS transformation of data from a pharmacological study with auditory and visual stimulation on 13 subjects. Head location in the centre of the sensor array from one session was used as a reference. After the transformation, significantly stronger responses were revealed in some cases over channels around the responding cortical area. The data were generally less noisy, likely due to suppression of external fields by SSS. The SSS transformation seems to substantially promote the reproducibility and comparability of measured MEG waveforms.

Objective : Our objective was to characterize the effects of sleep stages on tactile somatosensory evoked responses in full-term newborns. Methods : Somatosensory evoked potentials (SEPs) and magnetic fields (SEFs) to tactile stimulation of the tip of the index finger and/or thenar eminence were measured from 14 healthy newborns. The stimulus was a gentle tap produced by a moving membrane driven by an air-pressure pulse. Results : SEPs and SEFs to tactile stimulation of the skin were similar in waveform and latency to SEPs known to be produced by electrical stimulation of the fingertip of neonates. The two most distinguishable positive deflections of SEPs, P1 and P2, within 300 ms of the stimulation, and their magnetic counterparts were clearly smaller in active compared to quiet sleep. Conclusions : Our study demonstrates for the first time that it is possible to record SEFs in neonates, and that clear late cortical somatosensory responses are produced by tactile stimulation. In addition, the effect of sleep stage on these responses indicates differences in the processing of the incoming information, at least in the somatosensory modality, in active and quiet sleep. Significance : Tactile stimulation may be useful as a completely non-invasive technique for studying the physiology of the somatosensory system in neonates. Methodologically, since the effect of sleep stage is profound, one must carefully monitor the sleep stages in studies of event-related responses in newborns, or else this effect may confound the phenomena being studied.

Corticokinematic coherence (CKC), i.e., coherence calculated between MEG and an accelerometer signal, recording movement kinematics, can be used for functional mapping of the sensorimotor cortex. Cortical sources of CKC, induced by both voluntary and passive movements, localize at the proximity of sensorimotor cortex. We tested the CKC during a static muscle contraction to compare it with simultaneously measured cortico-muscular coherence (CMC) estimated between MEG and surface EMG to study the role of postural tremor in CMC in ten healthy volunteers. CKC was detectable also during this static task. CKC and CMC spectra had similar power distributions, and sources of CMC and CKC colocalized at the cortex in close proximity of the central sulcus. During the static hold task, the accelerometer signal originates from the postural tremor. The similarities between CMC and CKC indicate that postural tremor is related to CMC in healthy subjects.

HyperscanningMost neuroimaging studies of human social cognition have focused on brain activity of single subjects. More recently, "two-person neuroimaging" has been introduced, with simultaneous recordings of brain signals from two subjects involved in social interaction. These simultaneous "hyperscanning" recordings have already been carried out with a spectrum of neuroimaging modalities, such as functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and functional near-infrared spectroscopy (fNIRS).Dual meg setupWe have recently developed a setup for simultaneous magnetoencephalographic (MEG) recordings of two subjects that communicate in real time over an audio link between two geographically separated MEG laboratories. Here we present an extended version of the setup, where we have added a video connection and replaced the telephone-landline-based link with an Internet connection. Our setup enabled transmission of video and audio streams between the sites with a one-way communication latency of about 130 ms. Our software that allows reproducing the setup is publicly available.ValidationWe demonstrate that the audiovisual Internet-based link can mediate real-time interaction between two subjects who try to mirror each others' hand movements that they can see via the video link. All the nine pairs were able to synchronize their behavior. In addition to the video, we captured the subjects' movements with accelerometers attached to their index fingers; we determined from these signals that the average synchronization accuracy was 215 ms. In one subject pair we demonstrate inter-subject coherence patterns of the MEG signals that peak over the sensorimotor areas contralateral to the hand used in the task.

Objective Parkinsonian patients have abnormal oscillatory activity within the basal ganglia-thalamocortical circuitry. Particularly, excessive beta band oscillations are thought to be associated with akinesia. We studied whether cortical spontaneous activity is modified by deep brain stimulation (DBS) in advanced Parkinson’s disease and if the modifications are related to the clinical symptoms. Methods We studied the effects of bilateral electrical stimulation of subthalamic nucleus (STN) on cortical spontaneous activity by magnetoencephalography (MEG) in 11 Parkinsonian patients. The artifacts produced by DBS were suppressed by tSSS algorithm. Results During DBS, UPDRS (Unified Parkinson’s Disease Rating Scale) rigidity scores correlated with 6–10 Hz and 12–20 Hz somatomotor source strengths when eyes were open. When DBS was off UPDRS action tremor scores correlated with pericentral 6–10 Hz and 21–30 Hz and occipital alpha source strengths when eyes open. Occipital alpha strength decreased during DBS when eyes closed. The peak frequency of occipital alpha rhythm correlated negatively with total UPDRS motor scores and with rigidity subscores, when eyes closed. Conclusion STN DBS modulates brain oscillations both in alpha and beta bands and these oscillations reflect the clinical condition during DBS. Significance MEG combined with an appropriate artifact rejection method enables studies of DBS effects in Parkinson’s disease and presumably also in the other emerging DBS indications.

This study was performed to assess the effectiveness of the spatiotemporal Signal Space Separation (tSSS) and head movement compensation (MC). Continuous MEG data were acquired from 20 adult and 10 child subjects in four conditions: (1) A reference with a static head position, (2) the subject changed the head position twice, (3) the subject moved the head constantly, and (4) two magnetized pieces were attached to the scalp and the subject moved the head. The recordings were repeated with two whole-head MEG systems.

We developed a prototype of a mobile, high-resolution, multichannel magnetoencephalography (MEG) system, called babySQUID, for assessing brain functions in newborns and infants. Unlike electroencephalography, MEG signals are not distorted by the scalp or the fontanels and sutures in the skull. Thus, brain activity can be measured and localized with MEG as if the sensors were above an exposed brain. The babySQUID is housed in a moveable cart small enough to be transported from one room to another. To assess brain functions, one places the baby on the bed of the cart and the head on its headrest with MEG sensors just below. The sensor array consists of 76 first-order axial gradiometers, each with a pickup coil diameter of 6mm and a baseline of 30mm, in a high-density array with a spacing of 12–14mm center-to-center. The pickup coils are 6±1mm below the outer surface of the headrest. The short gap provides unprecedented sensitivity since the scalp and skull are thin (as little as 3–4mm altogether) in babies....