Pneumatic artificial muscle-based stimulator for passive functional magnetic resonance imaging sensorimotor mapping in patients with brain tumours.

BACKGROUND: Two concerns with respect to pre-operative task-based motor functional magnetic resonance imaging (fMRI) in patients with brain tumours are inadequate performance due to patients' impaired motor function and head motion artefacts. NEW METHOD: In the present study we validate the use of a stimulator based on a pneumatic artificial muscle (PAM) for fMRI mapping of the primary sensorimotor (SM1) cortex in twenty patients with rolandic or perirolandic brain tumours. All patients underwent both active and passive motor block-design fMRI paradigms, performing comparable active and passive PAM-induced flexion-extensions of the icontralesional index finger. RESULTS: PAM-induced movements resulted in a significant BOLD signal increase in contralateral primary motor (M1) and somatosensory (S1) cortices in 18/20 and 19/20 (p<.05 FWE corrected in 16/18 and 18/19) patients, versus 18/20 and 16/20 (p<.05 FWE corrected) during active movements. The two patients in whom the PAM-based stimulator failed to induce any significant BOLD signal change in the contralateral M1 cortex differed from the two in whom active motion was conversely ineffective. At the group level, no significant difference in contrast magnitude was observed within the contralateral SM1 cortex when comparing active with passive movements. During passive movements, head motion was significantly reduced. Comparison with existing method(s) As compared to the several robotic devices for passive motion that were introduced in the past decades, our PAM-based stimulator appears smaller, handier, and easier to use. CONCLUSION: The use of PAM-based stimulators should be included in routine pre-operative fMRI protocols along with active paradigms in such patients' population.

Neocortical activity tracks the hierarchical linguistic structures of self-produced speech during reading aloud.

How the human brain uses self-generated auditory information during speech production is rather unsettled. Current theories of language production consider a feedback monitoring system that monitors the auditory consequences of speech output and an internal monitoring system, which makes predictions about the auditory consequences of speech before its production. To gain novel insights into underlying neural processes, we investigated the coupling between neuromagnetic activity and the temporal envelope of the heard speech sounds (i.e., cortical tracking of speech) in a group of adults who 1) read a text aloud, 2) listened to a recording of their own speech (i.e., playback), and 3) listened to another speech recording. Reading aloud was here used as a particular form of speech production that shares various processes with natural speech. During reading aloud, the reader's brain tracked the slow temporal fluctuations of the speech output. Specifically, auditory cortices tracked phrases (<1 â€‹Hz) but to a lesser extent than during the two speech listening conditions. Also, the tracking of words (2-4 â€‹Hz) and syllables (4-8 â€‹Hz) occurred at parietal opercula during reading aloud and at auditory cortices during listening. Directionality analyses were then used to get insights into the monitoring systems involved in the processing of self-generated auditory information. Analyses revealed that the cortical tracking of speech at <1 â€‹Hz, 2-4 â€‹Hz and 4-8 â€‹Hz is dominated by speech-to-brain directional coupling during both reading aloud and listening, i.e., the cortical tracking of speech during reading aloud mainly entails auditory feedback processing. Nevertheless, brain-to-speech directional coupling at 4-8 â€‹Hz was enhanced during reading aloud compared with listening, likely reflecting the establishment of predictions about the auditory consequences of speech before production. These data bring novel insights into how auditory verbal information is tracked by the human brain during perception and self-generation of connected speech.

Evidence for genetically determined degeneration of proprioceptive tracts in Friedreich ataxia.

OBJECTIVE: To assess with magnetoencephalography the developmental vs progressive character of the impairment of spinocortical proprioceptive pathways in Friedreich ataxia (FRDA). METHODS: Neuromagnetic signals were recorded from 16 right-handed patients with FRDA (9 female patients, mean age 27 years, mean Scale for the Assessment and Rating Of ataxia [SARA] score 22.25) and matched healthy controls while they performed right finger movements either actively or passively. The coupling between movement kinematics (i.e., acceleration) and neuromagnetic signals was assessed by the use of coherence at sensor and source levels. Such coupling, that is, the corticokinematic coherence (CKC), specifically indexes proprioceptive afferent inputs to the contralateral primary sensorimotor (cSM1) cortex. Nonparametric permutations and Spearman rank correlation test were used for statistics. RESULTS: In both groups of participants and movement conditions, significant coupling peaked at the cSM1 cortex. Coherence levels were 70% to 75% lower in patients with FRDA than in healthy controls in both movement conditions. In patients with FRDA, coherence levels correlated with genotype alteration (i.e., the size of GAA1 triplet expansion) and the age at symptom onset but not with disease duration or SARA score. CONCLUSION: This study provides electrophysiologic evidence demonstrating that proprioceptive impairment in FRDA is mostly genetically determined and scarcely progressive after symptom onset. It also positions CKC as a reliable, robust, specific marker of proprioceptive impairment in FRDA.

Cortical Tracking of Speech-in-Noise Develops from Childhood to Adulthood.

In multitalker backgrounds, the auditory cortex of adult humans tracks the attended speech stream rather than the global auditory scene. Still, it is unknown whether such preferential tracking also occurs in children whose speech-in-noise (SiN) abilities are typically lower compared with adults. We used magnetoencephalography (MEG) to investigate the frequency-specific cortical tracking of different elements of a cocktail party auditory scene in 20 children (age range, 6-9 years; 8 females) and 20 adults (age range, 21-40 years; 10 females). During MEG recordings, subjects attended to four different 5 min stories, mixed with different levels of multitalker background at four signal-to-noise ratios (SNRs; noiseless, +5, 0, and -5 dB). Coherence analysis quantified the coupling between the time courses of the MEG activity and attended speech stream, multitalker background, or global auditory scene, respectively. In adults, statistically significant coherence was observed between MEG signals originating from the auditory system and the attended stream at <1, 1-4, and 4-8 Hz in all SNR conditions. Children displayed similar coupling at <1 and 1-4 Hz, but increasing noise impaired the coupling more strongly than in adults. Also, children displayed drastically lower coherence at 4-8 Hz in all SNR conditions. These results suggest that children's difficulties to understand speech in noisy conditions are related to an immature selective cortical tracking of the attended speech streams. Our results also provide unprecedented evidence for an acquired cortical tracking of speech at syllable rate and argue for a progressive development of SiN abilities in humans.SIGNIFICANCE STATEMENT Behaviorally, children are less proficient than adults at understanding speech-in-noise. Here, neuromagnetic signals were recorded while healthy adults and typically developing 6- to 9-year-old children attended to a speech stream embedded in a multitalker background noise with varying intensity. Results demonstrate that auditory cortices of both children and adults selectively track the attended speaker's voice rather than the global acoustic input at phrasal and word rates. However, increments of noise compromised the tracking significantly more in children than in adults. Unexpectedly, children displayed limited tracking of both the attended voice and the global acoustic input at the 4-8 Hz syllable rhythm. Thus, both speech-in-noise abilities and cortical tracking of speech syllable repetition rate seem to mature later in adolescence.

Similarities and differences between on-scalp and conventional in-helmet magnetoencephalography recordings.

The development of new magnetic sensor technologies that promise sensitivities approaching that of conventional MEG technology while operating at far lower operating temperatures has catalysed the growing field of on-scalp MEG. The feasibility of on-scalp MEG has been demonstrated via benchmarking of new sensor technologies performing neuromagnetic recordings in close proximity to the head surface against state-of-the-art in-helmet MEG sensor technology. However, earlier work has provided little information about how these two approaches compare, or about the reliability of observed differences. Herein, we present such a comparison, based on recordings of the N20m component of the somatosensory evoked field as elicited by electric median nerve stimulation. As expected from the proximity differences between the on-scalp and in-helmet sensors, the magnitude of the N20m activation as recorded with the on-scalp sensor was higher than that of the in-helmet sensors. The dipole pattern of the on-scalp recordings was also more spatially confined than that of the conventional recordings. Our results furthermore revealed unexpected temporal differences in the peak of the N20m component. An analysis protocol was therefore developed for assessing the reliability of this observed difference. We used this protocol to examine our findings in terms of differences in sensor sensitivity between the two types of MEG recordings. The measurements and subsequent analysis raised attention to the fact that great care has to be taken in measuring the field close to the zero-line crossing of the dipolar field, since it is heavily dependent on the orientation of sensors. Taken together, our findings provide reliable evidence that on-scalp and in-helmet sensors measure neural sources in mostly similar ways.

Benchmarking for On-Scalp MEG Sensors.

OBJECTIVE: We present a benchmarking protocol for quantitatively comparing emerging on-scalp magnetoencephalography (MEG) sensor technologies to their counterparts in state-of-the-art MEG systems. METHODS: As a means of validation, we compare a high-critical-temperature superconducting quantum interference device (high Tc SQUID) with the low- Tc SQUIDs of an Elekta Neuromag TRIUX system in MEG recordings of auditory and somatosensory evoked fields (SEFs) on one human subject. RESULTS: We measure the expected signal gain for the auditory-evoked fields (deeper sources) and notice some unfamiliar features in the on-scalp sensor-based recordings of SEFs (shallower sources). CONCLUSION: The experimental results serve as a proof of principle for the benchmarking protocol. This approach is straightforward, general to various on-scalp MEG sensors, and convenient to use on human subjects. The unexpected features in the SEFs suggest on-scalp MEG sensors may reveal information about neuromagnetic sources that is otherwise difficult to extract from state-of-the-art MEG recordings. SIGNIFICANCE: As the first systematically established on-scalp MEG benchmarking protocol, magnetic sensor developers can employ this method to prove the utility of their technology in MEG recordings. Further exploration of the SEFs with on-scalp MEG sensors may reveal unique information about their sources.

Left Superior Temporal Gyrus Is Coupled to Attended Speech in a Cocktail-Party Auditory Scene.

Using a continuous listening task, we evaluated the coupling between the listener's cortical activity and the temporal envelopes of different sounds in a multitalker auditory scene using magnetoencephalography and corticovocal coherence analysis. Neuromagnetic signals were recorded from 20 right-handed healthy adult humans who listened to five different recorded stories (attended speech streams), one without any multitalker background (No noise) and four mixed with a "cocktail party" multitalker background noise at four signal-to-noise ratios (5, 0, -5, and -10 dB) to produce speech-in-noise mixtures, here referred to as Global scene. Coherence analysis revealed that the modulations of the attended speech stream, presented without multitalker background, were coupled at ∼0.5 Hz to the activity of both superior temporal gyri, whereas the modulations at 4-8 Hz were coupled to the activity of the right supratemporal auditory cortex. In cocktail party conditions, with the multitalker background noise, the coupling was at both frequencies stronger for the attended speech stream than for the unattended Multitalker background. The coupling strengths decreased as the Multitalker background increased. During the cocktail party conditions, the ∼0.5 Hz coupling became left-hemisphere dominant, compared with bilateral coupling without the multitalker background, whereas the 4-8 Hz coupling remained right-hemisphere lateralized in both conditions. The brain activity was not coupled to the multitalker background or to its individual talkers. The results highlight the key role of listener's left superior temporal gyri in extracting the slow ∼0.5 Hz modulations, likely reflecting the attended speech stream within a multitalker auditory scene. SIGNIFICANCE STATEMENT: When people listen to one person in a "cocktail party," their auditory cortex mainly follows the attended speech stream rather than the entire auditory scene. However, how the brain extracts the attended speech stream from the whole auditory scene and how increasing background noise corrupts this process is still debated. In this magnetoencephalography study, subjects had to attend a speech stream with or without multitalker background noise. Results argue for frequency-dependent cortical tracking mechanisms for the attended speech stream. The left superior temporal gyrus tracked the ∼0.5 Hz modulations of the attended speech stream only when the speech was embedded in multitalker background, whereas the right supratemporal auditory cortex tracked 4-8 Hz modulations during both noiseless and cocktail-party conditions.

Accelerometer-based automatic voice onset detection in speech mapping with navigated repetitive transcranial magnetic stimulation.

BACKGROUND: The use of navigated repetitive transcranial magnetic stimulation (rTMS) in mapping of speech-related brain areas has recently shown to be useful in preoperative workflow of epilepsy and tumor patients. However, substantial inter- and intraobserver variability and non-optimal replicability of the rTMS results have been reported, and a need for additional development of the methodology is recognized. In TMS motor cortex mappings the evoked responses can be quantitatively monitored by electromyographic recordings; however, no such easily available setup exists for speech mappings. NEW METHOD: We present an accelerometer-based setup for detection of vocalization-related larynx vibrations combined with an automatic routine for voice onset detection for rTMS speech mapping applying naming. COMPARISON WITH EXISTING METHOD(S): The results produced by the automatic routine were compared with the manually reviewed video-recordings. RESULTS: The new method was applied in the routine navigated rTMS speech mapping for 12 consecutive patients during preoperative workup for epilepsy or tumor surgery. The automatic routine correctly detected 96% of the voice onsets, resulting in 96% sensitivity and 71% specificity. Majority (63%) of the misdetections were related to visible throat movements, extra voices before the response, or delayed naming of the previous stimuli. The no-response errors were correctly detected in 88% of events. CONCLUSION: The proposed setup for automatic detection of voice onsets provides quantitative additional data for analysis of the rTMS-induced speech response modifications. The objectively defined speech response latencies increase the repeatability, reliability and stratification of the rTMS results.

Preserved coupling between the reader's voice and the listener's cortical activity in autism spectrum disorders.

PURPOSE: Investigating the steadiness of the phase-coupling between the time-course of the reader's voice and brain signals of subjects with autism spectrum disorder (ASD) passively listening to connected speech using magnetoencephalography (MEG). In typically developed subjects, such coupling occurs at the right posterior temporal sulcus (pSTS) for frequencies below 1 Hz, and reflects the neural processing of sentence-level rhythmic prosody at the prelexical level. METHODS: Cortical neuromagnetic signals were recorded with MEG (Elekta Oy, Finland) while seven right-handed and native French-speaking ASD subjects (six males, one female, range: 13-20 years) listened to live (Live) or recorded (Recorded) voices continuously reading a text in French for five minutes. Coherence was computed between the reader's voice time-course and ASD subjects' MEG signals. Coherent neural sources were subsequently reconstructed using a beamformer. KEY FINDINGS: Significant coupling was found at 0.5 Hz in all ASD subjects in Live and in six subjects in Recorded. Coherent sources were located close to the right pSTS in both conditions. No significant difference was found in coherence levels between Live and Recorded, and between ASD subjects and ten typically developed subjects (right-handed, native French-speaking adults, 5 males, 5 females, age range: 21-38 years) included in a previous study. SIGNIFICANCE: This study discloses a preserved coupling between the reader's voice and ASD subjects' cortical activity at the right pSTS. These findings support the existence of preserved neural processing of sentence-level rhythmic prosody in ASD. The preservation of early cortical processing of prosodic elements in verbal language might be exploited in therapeutic interventions in ASD.

Comprehensive functional mapping scheme for non-invasive primary sensorimotor cortex mapping.

We introduce a novel multimodal scheme for primary sensorimotor hand area (SM1ha) mapping integrating multiple functional indicators from functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG). Ten right-handed healthy subjects (19-33 years; 5 females, 5 males) and four patients (24-64 years; 2 females, 2 males) suffering from space-occupying brain lesion close to the central sulcus were studied. Functional indicators of the SM1ha were obtained from block-design fMRI motor protocol, and six MEG protocols: somatosensory evoked fields to electrical median-nerve stimulation, mu-rhythm suppression (~10 and ~20 Hz), corticomuscular coherence, and corticokinematic coherence with and without finger contacts. To assess the spatial spread of the functional indicators, their coordinates were subjected to principal component analysis to produce a centered ellipsoid with axis along principal components. Five to seven functional indicators were obtained for each participant. In all participants, the ellipsoid co-localized with the anatomical SM1ha. In healthy subjects, 50-100% of functional indicators were located within 10 mm from the center of the ellipsoid. In patients, 17-100% of functional indicators were located within 10 mm from the center of the ellipsoid. In conclusion, the multimodal scheme proposed led to a functional mapping of SM1ha that co-localized with anatomical SM1ha in all participants. The spread of the SM1ha functional indicators in some patients with brain lesions highlights the potential benefit of the proposed multimodal approach to assess the reliability of the non-invasive SM1ha mapping.

MEG dual scanning: a procedure to study real-time auditory interaction between two persons.

Social interactions fill our everyday life and put strong demands on our brain function. However, the possibilities for studying the brain basis of social interaction are still technically limited, and even modern brain imaging studies of social cognition typically monitor just one participant at a time. We present here a method to connect and synchronize two faraway neuromagnetometers. With this method, two participants at two separate sites can interact with each other through a stable real-time audio connection with minimal delay and jitter. The magnetoencephalographic (MEG) and audio recordings of both laboratories are accurately synchronized for joint offline analysis. The concept can be extended to connecting multiple MEG devices around the world. As a proof of concept of the MEG-to-MEG link, we report the results of time-sensitive recordings of cortical evoked responses to sounds delivered at laboratories separated by 5 km.

Supplementary motor cortex involvement in reading epilepsy revealed by magnetic source imaging.

Reading epilepsy (RE) is an idiopathic reflex epilepsy syndrome characterized by perioral myoclonic jerks (PMJs) during reading associated with left-dominant frontotemporal spike-wave discharges (SWDs). To better understand the pathophysiology of this syndrome, we studied a 45-year-old patient using magnetic source imaging (MSI). The patient underwent two whole-head magnetoencephalography (MEG) recordings (Elekta Neuromag Oy) within 2 months while reading aloud. Forty-two SWDs associated with PMJs were recorded and averaged with respect to SWDs peak power. Epileptic discharges were then reconstructed using conventional equivalent current dipoles (ECDs) modeling, distributed sources sLORETA modeling, and beamformer approach. These methods identified two brain sources located in the left supplementary motor cortex (SMC) and the left primary sensorimotor face area (PSMFA). The spatiotemporal pattern of the sources was characterized by a cross-talk between these two brain regions, with an initial source in the left SMC. This MSI investigation suggests that RE-PMJs are associated with reading-induced activation of hyperexcitable neurons in the left SMC, followed by secondary propagation to the left PSMFA producing the myoclonus.

Cortical responses to Aδ-fiber stimulation: magnetoencephalographic recordings in a subject lacking large myelinated afferents.

Controversy persists over the role of the primary somatosensory cortex (SI) in processing small-fiber peripheral afferent input. We therefore examined subject I.W, who, due to sensory neuronopathy syndrome, has no large-fiber afferents below C3 level. Cortical evoked responses were recorded with a whole-scalp neuromagnetometer to high-intensity electrical stimulation of the distal right radial, median, and tibial nerves and skin over the forearm and mechanical stimulation of (neurologically intact) lip. The responses to electrical stimulation in the Abeta-denervated limbs peaked at 110-140 ms in contralateral SI and at 140-220 ms in contralateral secondary somatosensory cortex (SII), consistent with Adelta-mediated input. I.W. was able to localize pin-prick stimuli with 4 cm accuracy. Responses to laser stimuli on the radial dorsum of the hand peaked in contralateral SII cortex at 215 ms, also compatible with Adelta-mediated input. These results support the role of the SI cortex in processing the sensory discriminative aspects of Adelta-mediated input.

Abnormal activation of face processing systems at early and intermediate latency in individuals with autism spectrum disorder: a magnetoencephalographic study.

The neurological basis of developmental psychopathology in autism is a matter of intense debate. Magnetoencephalography (MEG) was used to study the neuronal responses associated with the processing of faces in 12 able adults with autism spectrum disorders (ASD), performing image categorization and image identification tasks. The neuromagnetic data were analysed using nonparametric time-series analysis and equivalent current dipole estimation. Comparison data were obtained from 22 normally developing adults. In individuals with ASD, the neural responses to images of faces, observed in right extrastriate cortices at approximately 145 ms after stimulus onset, were significantly weaker, less lateralized and less affected by stimulus repetition than in control subjects. Early latency (30-60 ms) responses to face images, over right anterior temporal regions, differed significantly between the two subject groups in the image identification task. No such difference was observed for images of mugs or meaningless geometrical patterns. These findings suggest that, during the course of development in individuals with ASD, the cortical activity associated with the processing of human faces assumes a different-from-normal localization in extrastriate brain regions. This abnormal localization may be associated with unusual, but nevertheless face-specific, fast processing pathways.

Human cortical representation of virtual auditory space: differences between sound azimuth and elevation.

Sounds convolved with individual head-related transfer functions and presented through headphones can give very natural percepts of the three-dimensional auditory space. We recorded whole-scalp neuromagnetic responses to such stimuli to compare reactivity of the human auditory cortex to sound azimuth and elevation. The results suggest that the human auditory cortex analyses sound azimuth, based on both binaural and monaural localization cues, mainly in the hemisphere contralateral to the sound, whereas elevation in the anterior space and in the lateral auditory space in general, both strongly relying on monaural spectral cues, are analyzed in more detail in the right auditory cortex. The binaural interaural time and interaural intensity difference cues were processed in the auditory cortex around 100-150 ms and the monaural spectral cues later around 200-250 ms.

Neuromagnetic responses to frequency-tagged sounds: a new method to follow inputs from each ear to the human auditory cortex during binaural hearing.

Binaural cortical responses are mixtures of inputs from both ears. We introduce here a novel method that allows, for the first time, to selectively follow these inputs in humans up to the cortex during binaural hearing. We recorded neuromagnetic cortical responses to amplitude-modulated continuous tones, with different modulation frequencies at each ear. During binaural hearing, the left- and right-ear inputs competed strongly in both auditory cortices: the right-hemisphere responses were symmetrically suppressed, compared with monaural stimulation, for sounds of both ears, whereas the left-hemisphere responses were suppressed significantly more for ipsilateral than contralateral sounds, thereby intensifying the right-ear dominance of the left auditory cortex. This type of hemisphere- and ear-selective information on cortical binaural interaction could have important applications in human auditory neuroscience.