Observation of respiration-entrained brain oscillations with scalp EEG.

In animal models, oscillations of local field potentials are entrained by nasal respiration at the frequency of breathing cycle in olfactory brain regions, such as the olfactory bulb and piriform cortex, as well as in the other brain regions. Studies in humans also confirmed these respiration-entrained oscillations in several brain regions using intracranial electroencephalogram (EEG). Here we extend these findings by analyzing coherence between cortical activity and respiration using high-density scalp EEG in twenty-seven healthy human subjects. Results indicated the occurrence of significant coherence between scalp EEG and respiration signals, although the number and locations of electrodes showing significant coherence were different among subjects. These findings suggest that scalp EEG can detect respiration-entrained oscillations. It remained to be determined whether these oscillations are volume conducted from the olfactory brain regions or reflect the local cortical activity.

Detailed magnetoelectric analysis of a nerve impulse propagation along the brachial plexus.

OBJECTIVE: To visualize impulse conduction along the brachial plexus through simultaneous electromagnetic measurements. METHODS: Neuromagnetic fields following median nerve stimulation were recorded above the clavicle with a superconducting quantum interference device biomagnetometer system in 7 healthy volunteers. Compound nerve action potentials (CNAPs) were obtained from 12 locations. Pseudocolor maps of equivalent currents reconstructed from magnetic fields and isopotential contour maps were superimposed onto X-ray images. Surface potentials and current waveforms at virtual electrodes along the brachial plexus were compared. RESULTS: In magnetic field analysis, the leading axonal current followed by a trailing backward current traveled rostrally along the brachial plexus. The spatial extent of the longitudinal intra-axonal currents corresponded to the extent of the positive-negative-positive potential field reflecting transmembrane volume currents. The peaks and troughs of the intra-axonal biphasic current waveforms coincided with the zero-crossings of triphasic CNAP waveforms. The amplitudes of CNAPs and current moments were linearly correlated. CONCLUSIONS: Reconstructed neural activity in magnetic field analysis visualizes not only intra-axonal currents, but also transmembrane volume currents, which are in good agreement with the surface potential field. SIGNIFICANCE: Magnetoneurography is a novel non-invasive functional imaging modality for the brachial plexus whose performance can surpass that of electric potential measurement.

Noninvasive measurement of sensory action currents in the cervical cord by magnetospinography.

OBJECTIVE: To obtain magnetic recordings of electrical activities in the cervical cord and visualize sensory action currents of the dorsal column, intervertebral foramen, and dorsal horn. METHODS: Neuromagnetic fields were measured at the neck surface upon median nerve stimulation at the wrist using a magnetospinography system with high-sensitivity superconducting quantum interference device sensors. Somatosensory evoked potentials (SEPs) were also recorded. Evoked electrical currents were reconstructed by recursive null-steering beamformer and superimposed on cervical X-ray images. RESULTS: Estimated electrical currents perpendicular to the cervical cord ascended sequentially. Their peak latency at C5 and N11 peak latency of SEP were well-correlated in all 16 participants (r = 0.94, p < 0.0001). Trailing axonal currents in the intervertebral foramens were estimated in 10 participants. Estimated dorsal-ventral electrical currents were obtained within the spinal canal at C5. Current density peak latency significantly correlated with cervical N13-P13 peak latency of SEPs in 13 participants (r = 0.97, p < 0.0001). CONCLUSIONS: Magnetospinography shows excellent spatial and temporal resolution after median nerve stimulation and can identify the spinal root entry level, calculate the dorsal column conduction velocity, and analyze segmental dorsal horn activity. SIGNIFICANCE: This approach is useful for functional electrophysiological diagnosis of somatosensory pathways.

Visualization of electrophysiological activity at the carpal tunnel area using magnetoneurography.

OBJECTIVE: To establish a noninvasive method to measure the neuromagnetic fields of the median nerve at the carpal tunnel after electrical digital nerve stimulation and evaluate peripheral nerve function. METHODS: Using a vector-type biomagnetometer system with a superconducting quantum interference device, neuromagnetic fields at the carpal tunnel were recorded after electrical stimulation of the index or middle digital nerve in five healthy volunteers. A novel technique for removing stimulus-induced artifacts was applied, and current distributions were calculated using a spatial filter algorithm and superimposed on X-ray. RESULTS: A neuromagnetic field propagating from the palm to the carpal tunnel was observed in all participants. Current distributions estimated from the magnetic fields had five components: leading and trailing components parallel to the conduction pathway, outward current preceding the leading component, inward currents between the leading and trailing components, and outward current following the trailing component. The conduction velocity and peak latency of the inward current agreed well with those of sensory nerve action potentials. CONCLUSION: Removing stimulus-induced artifacts enabled magnetoneurography to noninvasively visualize with high spatial resolution the electrophysiological neural activity from the palm to the carpal tunnel. SIGNIFICANCE: This is the first report of using magnetoneurography to visualize electrophysiological nerve activity at the palm and carpal tunnel.

Novel functional imaging technique for the brachial plexus based on magnetoneurography.

OBJECTIVE: To visualize neural activity in the brachial plexus using magnetoneurography (MNG). METHODS: Using a 124- or 132-channel biomagnetometer system with a superconducting quantum interference device, neuromagnetic fields above the clavicle and neck region were recorded in response to electrical stimulation of the median and ulnar nerves in five asymptomatic volunteers (four men and one woman; age, 27-45 years old). Equivalent currents were computationally reconstructed from neuromagnetic fields and visualized as pseudocolor maps. Reconstructed currents at the depolarization site and compound nerve action potentials (CNAPs) at Erb's point were compared. RESULTS: Neuromagnetic fields were recorded in all subjects. The reconstructed equivalent currents propagated into the vertebral foramina, and the main inflow levels differed between the median nerve (C5/C6-C7/T1 vertebral foramen) and the ulnar nerve (C7/T1-T1/T2). The inward current peaks at the depolarization site and CNAPs showed high linear correlation. CONCLUSIONS: MNG visualizes neural activity in the brachial plexus and can differentiate the conduction pathways after median and ulnar nerve stimulations. In addition, it can visualize not only the leading and trailing components of intra-axonal currents, but also inward currents at the depolarization site. SIGNIFICANCE: MNG is a novel and promising functional imaging modality for the brachial plexus.

The effects of voluntary control of respiration on the excitability of the primary motor hand area, evaluated by end-tidal CO2 monitoring.

OBJECTIVE: To investigate the effects of voluntary deep breathing on the excitability of the hand area in the primary motor cortex (M1). METHODS: We applied near-threshold transcranial magnetic stimulation (TMS) over M1 during the early phase of inspiration or expiration in both normal automatic and voluntary deep, but not "forced", breathing in eight healthy participants at rest. We monitored exhaled CO2 levels continuously, and recorded motor-evoked potentials (MEPs) simultaneously from the abductor pollicis brevis, first dorsal interosseous, abductor digiti minimi, flexor digitorum superficialis, and extensor incidis muscles. RESULTS: We observed that, during voluntary deep breathing, MEP amplitude increased by up to 50% for all recorded muscles and the latency of MEPs decreased by approximately 1ms, compared with normal automatic breathing. We found no difference in the amplitude or latency of MEPs between inspiratory and expiratory phases in either normal automatic or voluntary deep breathing. CONCLUSIONS: Voluntary deep breathing at rest facilitates MEPs following TMS over the hand area of M1, and MEP enhancement occurs throughout the full respiratory cycle. SIGNIFICANCE: The M1 hand region is continuously driven by top-down neural signals over the entire respiratory cycle of voluntary deep breathing.

The respiratory cycle modulates brain potentials, sympathetic activity, and subjective pain sensation induced by noxious stimulation.

To test the hypothesis that a respiratory cycle influences pain processing, we conducted an experimental pain study in 10 healthy volunteers. Intraepidermal electrical stimulation (IES) with a concentric bipolar needle electrode was applied to the hand dorsum at pain perceptual threshold or four times the perceptual threshold to produce first pain during expiration or inspiration either of which was determined by the abrupt change in an exhaled CO2 level. IES-evoked potentials (IESEPs), sympathetic skin response (SSR), digital plethysmogram (DPG), and subjective pain intensity rating scale were simultaneously recorded. With either stimulus intensity, IES during expiration produced weaker pain feeling compared to IES during inspiration. The mean amplitude of N200/P400 in IESEPs and that of SSR were smaller when IES was applied during expiration. The magnitude of DPG wave gradually decreased after IES, but a decrease in the magnitude of DPG wave was less evident when IES was delivered during expiration. Regardless of stimulus timing or stimulus intensity, pain perception was always concomitant with appearance of IESEPs and SSR, and changes in DPG. Our findings suggest that pain processing fluctuates during normal breathing and that pain is gated within the central nervous system during expiration.

Publication criteria for evoked magnetic fields of the human brain: a proposal.

Magnetoencephalography (MEG) is a record of the magnetic fields produced by the electrical activities of the brain using MEG systems. There are three types of sensors for MEG systems: magnetometer and two types of gradiometer. Among them, two types of gradiometer, axial and planar, have been used worldwide. Unfortunately, the waveforms recorded by the two types of gradiometer are often different from each other. This poses a serious problem in comparing and evaluating the data from the two gradiometers. We consider that the MEG study should be published in a way that allows other workers using different types of gradiometer to evaluate and replicate the results of MEG studies. There have been, however, no publication criteria for reports of studies on stimulus-evoked or event-related magnetic fields in human subjects. In this article, we propose publication criteria for evoked or event-related magnetic fields of the human brain: original waveforms of selected channels covering a region of interest, a root mean-squared (RMS) waveform and a contour map at an appropriate time.

Exploring the physiology and function of high-frequency oscillations (HFOs) from the somatosensory cortex.

A brief review of previous studies is presented on high frequency oscillations (HFOs)>300 Hz overlying the cortical response in the somatosensory evoked potential (SEP) or magnetic field (SEF) in humans as well as other mammals. The characteristics of somatosensory HFOs are described about reproducibility and origin (area 3b and 1) of the HFOs, changes during a wake-sleep cycle, effects of stimulus rate or tactile interference, and pharmacological effects. Also, several hypotheses on the neural mechanisms of the HFOs are reconsidered; the early HFO burst is probably generated from action potentials of thalamocortical fibers at the time when they arrive at the area 3b (and 1), since this component is resistant to higher stimulus rate >10 Hz, general anesthesia, or application of glutamatergic receptor antagonist: by contrast, the late HFO burst is sensitive to higher stimulus rate and eliminated after application of glutamatergic receptor antagonist, reflecting activities of a postsynaptic neural network in areas 3b and 1 of the somatosensory cortex. In view of physiological features of the somatosensory HFOs and their pathological or pharmacological changes, possible mechanisms of the late HFO burst genesis are discussed: a fast-spiking interneuron hypothesis, a fast pyramidal cell IPSP hypothesis and a chattering cell hypothesis.

High-frequency transcutaneous electrical nerve stimulation (TENS) differentially modulates sensorimotor cortices: an MEG study.

OBJECTIVE: Transcutaneous electrical nerve stimulation (TENS) affects excitability of the central motor system as well as the somatosensory system. To determine whether TENS has influence on excitability in the sensorimotor cortices of TENS-treated finger muscle, we investigated magnetoencephalogram associated with voluntary, self-paced finger movement before and after TENS. METHODS: High-frequency TENS was applied on the extensor digitorum muscle for 15 min. Subjects underwent alternate middle finger and thumb extension movements before and after the TENS. We recorded movement-related cortical magnetic field (MRCF) associated with TENS-treated middle finger movement and that from untreated thumb movement. RESULTS: The current source for motor field (MF) was located in the pre-central motor cortex and anteriorly-oriented, and that for motor evoked field one (MEF1) was found in the post-central somatosensory cortex and posteriorly-oriented. The amplitude of MF for TENS-treated middle finger movement decreased but unchanged for untreated thumb movement after TENS. The amplitude of MEF1 decreased for either finger movement after TENS. CONCLUSION: High-frequency TENS to the forearm muscle modulates excitability of the limited area of motor cortex but wider area of primary somatosensory cortex. SIGNIFICANCE: High-frequency TENS to the forearm muscle modulates excitability of the primary somatosensory cortex and motor cortex in a different manner.

Impulse propagation along thalamocortical fibers can be detected magnetically outside the human brain.

Orchestrating cortical network activity with synchronous oscillations of neurons across distant regions of the brain underlies information processing in humans (Knight, 2007) and monkeys (Saalmann et al., 2007; Womelsdorf et al., 2007). Frequencies of oscillatory activities depend, to a considerable extent, on the length and conduction velocity of the tracts connecting the neural areas that participate in oscillations (Buzsáki, 2006). However, the impulse propagation along the fiber tracts in the white matter has never been visualized in humans. Here, we show, by recording magnetoencephalogram (MEG) following median nerve stimulation, that a magnetic field component, we labeled "M15," changes dynamically within 1.6-1.8 ms before the onset of magnetic M20 response generated from the primary somatosensory cortex. This new M15 component corresponds to the intracellular depolarizing action current in the thalamocortical fibers propagating with the mean conduction velocity of 29 m/s. The findings challenge the traditional view that MEG is blind to the activity of deep subcortical structures. We argue that the MEG technique holds the promise of providing novel information in impulse transmissions along not only the thalamocortical pathway but also other fiber tracts connecting distant brain areas in humans.

Dynamic movement of N100m current sources in auditory evoked fields: comparison of ipsilateral versus contralateral responses in human auditory cortex.

We recorded auditory evoked magnetic fields (AEFs) to monaural 400Hz tone bursts and investigated spatio-temporal features of the N100m current sources in the both hemispheres during the time before the N100m reaches at the peak strength and 5ms after the peak. A hemispheric asymmetry was evaluated as the asymmetry index based on the ratio of N100m peak dipole strength between right and left hemispheres for either ear stimulation. The results of asymmetry indices showed right-hemispheric dominance for left ear stimulation but no hemispheric dominance for right ear stimulation. The current sources for N100m in both hemispheres in response to monaural 400Hz stimulation moved toward anterolateral direction along the long axis of the Heschl gyri during the time before it reaches the peak strength; the ipsilateral N100m sources were located slightly posterior to the contralateral N100m ones. The onset and peak latencies of the right hemispheric N100m in response to right ear stimulation are shorter than those of the left hemispheric N100m to left ear stimulation. The traveling distance of the right hemispheric N100m sources following right ear stimulation was longer than that for the left hemispheric ones following left ear stimulation. These results suggest the right-dominant hemispheric asymmetry in pure tone processing.

Human tonotopic maps and their rapid task-related changes studied by magnetic source imaging.

A brief review of previous studies is presented on tonotopic organization of primary auditory cortex (AI) in humans. Based on the place theory for pitch perception, in which place information from the cochlea is used to derive pitch, a well-organized layout of tonotopic map is likely in human AI. The conventional view of tonotopy in human AI is a layout inwhich the medial-to-lateral portion of Heschl's gyrus represents high-to-low frequency tones. However, we have shown that the equivalent current dipole (ECD) in auditory evoked magnetic fields in the rising phase of N100m response dynamically moves along the long axis of Heschl's gyrus. Based on analyses of the current sources for high-pitched and low-pitched tones in the right and left hemispheres, we propose an alternative tonotopic map in human AI. In the right AI, isofrequency bands for each tone frequency are parallell to the first transverse sulcus; on the other hand, the layout for tonotopy in the left AI seems poorly organized. The validity of single dipole modelling in the calculation of a moving source and the discrepancy as to tonotopic maps in the results between auditory evoked fields or intracerebral recordings and neuroimaging studies also are discussed. The difference in the layout of isofrequency bands between the right and left auditory cortices may reflect distinct functional roles in auditory information processing such as pitch versus phonetic analysis.

Neural mechanisms of the ultrafast activities.

A brief review of previous studies is presented on ultra-fast activities > 300 Hz (high frequency oscillations, HFOs) overlying the cortical response in the somatosensory evoked potential (SEP) or magnetic field (SEF). The characteristics of somatosensory HFOs are described in terms of reproducibility and origin (area 3b and 1) of the HFOs, changes during a wake-sleep cycle, effects of higher stimulus rate or tactile interference, etc. Also, several hypotheses on the neural mechanisms of the HFOs are introduced; the early HFO burst is probably generated from action potentials of thalamocortical fibers at the time when they arrive at the area 3b (and 1), since this component is resistant to higher stimulus rate > 10Hz or general anesthesia: by contrast, the late HFO burst is sensitive to higher stimulus rate, reflecting activities of a postsynaptic neural network in the somatosensory cortices, area 3b and 1. As to possible mechanisms of the late HFO burst genesis, an interneuron hypothesis, a fast inhibitory postsynaptic potential (IPSP) hypothesis of the pyramidal cell and a chattering cell hypothesis will be discussed on the basis of physiological and pathological features of the somatosensory HFOs.

Rapid change of tonotopic maps in the human auditory cortex during pitch discrimination.

OBJECTIVE: To study early cognitive processes and hemispheric differences in the primary auditory cortex during selective attention. METHODS: We measured auditory evoked magnetic fields (AEFs) to 400 and 4000 Hz tone pips that were randomly presented at the right or left ear. Subjects paid attention to target stimuli during pitch (high or low) or laterality (left or right) discrimination tasks. In the control session, 400 or 4000 Hz tone alone was presented at the left or right ear. We calculated the location and strength of N100m dipole for 400 and 4000 Hz tones, based on the AEFs obtained from the hemisphere contralateral to the stimulated ear. RESULTS: N100m amplitude increased in both hemispheres in pitch or laterality discriminating conditions. N100m latency also shortened during selective attention. The N100m dipole distance between 400 and 4000 Hz tones was enlarged, especially in the right auditory cortex during pitch discrimination task, but was unchanged during the laterality discrimination task. CONCLUSIONS: We conclude that these dynamic changes in the N100m dipole reflect short-term plastic changes in the primary auditory cortex, supporting early selection models. SIGNIFICANCE: This work is the first to disclose short-term plastic changes during pitch discrimination in the human auditory cortex based on the analysis of magnetoencephalography.

Dynamic movement of N100m dipoles in evoked magnetic field reflects sequential activation of isofrequency bands in human auditory cortex.

OBJECTIVE: To investigate spatiotemporal features of the isofrequency bands for 400 and 4000 Hz tones in human auditory cortex and on the hemispheric differences in the arrangement of isofrequency bands. METHODS: We recorded auditory evoked magnetic fields (AEFs) to 400 or 4000 Hz tone pips presented at right or left ear from 31 normal subjects. The dipole location for the N100m sources was successively calculated from the AEFs obtained from the hemisphere contralateral to the stimulated ear. RESULTS: In the right hemisphere, the current sources for 400 and 4000 Hz moved toward the anterolateral direction before the N100m peak, showing parallel arrangement of the isofrequency bands (4000 Hz in medial location). In the left hemisphere, the movement direction of 400 Hz dipoles was anterolateral, while that of 4000 Hz dipoles was lateral. CONCLUSIONS: This difference in the organization of isofrequency bands between right and left auditory cortices reflects distinct functional roles in auditory information processing such as pitch vs. language discrimination. SIGNIFICANCE: This work is the first to disclose isofrequency bands in human auditory cortex based on the analysis of magnetoencephalography.

Dynamic anterolateral movement of N100m dipoles in evoked magnetic field reflects activation of isofrequency bands through horizontal fibers in human auditory cortex.

To analyze the temporal changes in localization of an equivalent current dipole (ECD) for the auditory N100m, we recorded auditory evoked magnetic fields (AEFs) to 400 Hz tone pips presented at the right or left ear. Using a single ECD model, the dipole location for the N100m sources was successively calculated from the AEFs obtained from the hemisphere contralateral to the stimulated ear. We found that the location of the N100m current sources moved dynamically in medio-lateral and postero-anterior directions before the N100m peak. This direction was parallel to the surface of the supratemporal cortex. We propose that the dynamic movement of the N100m dipole reflects spread of intracortical activation through horizontal fibers of pyramidal neurons in the auditory cortex, forming the isofrequency bands in humans.