Neuromagnetic signatures of the spatiotemporal transformation for manual pointing.

Movement planning involves transforming the sensory signals into a command in motor coordinates. Surprisingly, the real-time dynamics of sensorimotor transformations at the whole brain level remain unknown, in part due to the spatiotemporal limitations of fMRI and neurophysiological recordings. Here, we used magnetoencephalography (MEG) during pro-/anti-wrist pointing to determine (1) the cortical areas involved in transforming visual signals into appropriate hand motor commands, and (2) how this transformation occurs in real time, both within and across the regions involved. We computed sensory, motor, and sensorimotor indices in 16 bilateral brain regions for direction coding based on hemispherically lateralized de/synchronization in the α (7-15 Hz) and ß (15-35 Hz) bands. We found a visuomotor progression, from pure sensory codes in 'early' occipital-parietal areas, to a temporal transition from sensory to motor coding in the majority of parietal-frontal sensorimotor areas, to a pure motor code, in both the α and ß bands. Further, the timing of these transformations revealed a top-down pro/anti cue influence that propagated 'backwards' from frontal through posterior cortical areas. These data directly demonstrate a progressive, real-time transformation both within and across the entire occipital-parietal-frontal network that follows specific rules of spatial distribution and temporal order.

Evaluation of multiple-sphere head models for MEG source localization.

Magnetoencephalography (MEG) source analysis has largely relied on spherical conductor models of the head to simplify forward calculations of the brain's magnetic field. Multiple- (or overlapping, local) sphere models, where an optimal sphere is selected for each sensor, are considered an improvement over single-sphere models and are computationally simpler than realistic models. However, there is limited information available regarding the different methods used to generate these models and their relative accuracy. We describe a variety of single- and multiple-sphere fitting approaches, including a novel method that attempts to minimize the field error. An accurate boundary element method simulation was used to evaluate the relative field measurement error (12% on average) and dipole fit localization bias (3.5 mm) of each model over the entire brain. All spherical models can contribute in the order of 1 cm to the localization bias in regions of the head that depart significantly from a sphere (inferior frontal and temporal). These spherical approximation errors can give rise to larger localization differences when all modeling effects are taken into account and with more complex source configurations or other inverse techniques, as shown with a beamformer example. Results differed noticeably depending on the source location, making it difficult to recommend a fitting method that performs best in general. Given these limitations, it may be advisable to expand the use of realistic head models.

Sex differences in sensorimotor mu rhythms during selective attentional processing.

We used magnetoencephalography to investigate the effect of directed attention on sensorimotor mu (8-12 Hz) response (mu reactivity) to non-painful electrical stimulation of the median nerve in healthy adults. Mu desynchronization in the 10-12 Hz bandwidth is typically observed during higher-order cognitive functions including selective attentional processing of sensorimotor information (Pfurtscheller, Neuper, & Krauz, 2000). We found attention-related sex differences in mu reactivity, with females showing (i) prolonged mu desynchrony when attending to somatosensory stimuli, (ii) attentional modulation of the mu response based on whether attention was directed towards or away from somatosensory stimuli, which was absent in males, and (iii) a trend for greater neuronal excitability of the primary somatosensory region suggesting greater physiological responsiveness to sensory stimulation overall. Our findings suggest sex differences in attentional control strategies when processing somatosensory stimuli, whose salience may be greater for females. These sex differences in attention to somatosensory stimuli may help elucidate the well-documented sex biases in pain processing wherein females typically report greater sensitivity to experimental and clinical pain.

Neuromagnetic imaging of movement-related cortical oscillations in children and adults: age predicts post-movement beta rebound.

We measured visually-cued motor responses in two developmentally separate groups of children and compared these responses to a group of adults. We hypothesized that if post-movement beta rebound (PMBR) depends on developmentally sensitive processes, PMBR will be greatest in adults and progressively decrease in children performing a basic motor task as a function of age. Twenty children (10 young children 4-6 years; 10 adolescent children 11-13 years) and 10 adults all had MEG recorded during separate recordings of right and left index finger movements. Beta band (15-30 Hz) event-related desynchronization (ERD) of bi-lateral sensorimotor areas was observed to increase significantly from both contralateral and ipsilateral MI with age. Movement-related gamma synchrony (60-90 Hz) was also observed from contralateral MI for each age group. However, PMBR was significantly reduced in the 4-6 year group and, while more prominent, remained significantly diminished in the adolescent (11-13 year) age group as compared to adults. PMBR measures were weak or absent in the youngest children tested and appear maximally from bilateral MI in adults. Thus PMBR may reflect an age-dependent inhibitory process of the primary motor cortex which comes on-line with normal development. Previous studies have shown PMBR may be observed from MI following a variety of movement-related tasks in adult participants - however, the origin and purpose of the PMBR is unclear. The current study shows that the expected PMBR from MI observed from adults is increasingly diminished in adolescent and young children respectively. A reduction in PMBR from children may reflect reduced motor cortical inhibition. Relatively less motor inhibition may facilitate neuronal plasticity and promote motor learning in children.

Cortical dynamics of selective attention to somatosensory events.

Recent studies have shown evidence of somatosensory deficits in individuals with attentional difficulties yet relatively little is known about the role of attention in the processing of somatosensory input. Neuromagnetic imaging studies have shown that rhythmic oscillations within the human somatosensory cortex are strongly modulated by somatosensory stimulation and may reflect the normal processing of such stimuli. However, few studies have examined how attention influences these cortical oscillations. We examined attentional effects on human somatosensory oscillations during median nerve stimulation by conducting time-frequency analyses of neuromagnetic recordings in healthy adults. We found that selective attention modulated somatosensory oscillations in the alpha, beta, and gamma bands that were both phase-locked and non-phase-locked to the stimulus. In the primary somatosensory cortex (SI), directing the subject's attention toward the somatosensory stimulus resulted in increased gamma band power (30-55 Hz) that was phase-locked to stimulus onset. Directed attention also produced an initial suppression (desynchrony) followed by enhancement (synchrony) of beta band power (13-25 Hz) that was not phase-locked to the stimulus. In the secondary somatosensory cortex (SII), directing attention towards the stimulus increased phase-locked alpha (7-9 Hz) power approximately 30 ms after onset of phase-locked gamma in SI, followed by a non-phase-locked increase in alpha power. We suggest that earlier phase-locked oscillatory power may reflect the relay of input from SI to SII, whereas later non-phase-locked rhythms reflect stimulus-induced oscillations that are modulated by selective attention and may thus reflect enhanced processing of the stimulus underlying the perception of somatosensory events.

Magnetoencephalographic analysis of cortical activity in adults with and without Down syndrome.

BACKGROUND: This preliminary study served as a pilot for an ongoing analysis of spectral power in adults with Down syndrome (DS) using a 151 channel whole head magnetoencephalography (MEG). The present study is the first step for examining and comparing cortical responses during spontaneous and task related activity in DS. METHOD: Cortical responses were recorded with a 151 channel whole head MEG system in three adults with DS and three age-matched adults without DS. MEG data were obtained at rest with eyes open and during observation of point-light displays of human motion and object motion. Data from both groups were evaluated by spectral analysis. RESULTS: The preliminary results showed greater alpha (8-14 Hz) power particularly in the occipital and parietal areas during the eyes open condition in the adults with DS in relation to a normal comparison group. The visual task had little effect on alpha power in the comparison group. Engaging in the visual task reduced power in alpha across all regions in the DS group to the level observed in comparisons. In the gamma band (30-50 Hz), power values were similar across both groups for the eyes open condition. In the comparison group, large reductions in gamma were observed in the occipital and bilateral temporal areas during the visual task. This change was not observed in the DS group. CONCLUSIONS: The results from this pilot study suggest that MEG may be useful in characterizing task-specific changes in cortical activity in individuals with DS. Future studies with a larger group of individuals will further contribute to our understanding of the neurophysiology of Down syndrome.

Cerebral motor control in patients with gliomas around the central sulcus studied with spatially filtered magnetoencephalography.

OBJECTIVE: Application of spatially filtered magnetoencephalography (MEG) to investigate changes in the mechanism of cerebral motor control in patients with tumours around the central sulcus. METHODS: MEG records were made during a repetitive hand grasping task in six patients with gliomas around the central sulcus and in four control subjects. Power decreases in the alpha (8-13 Hz), beta (13-30 Hz), and low gamma bands (30-50 Hz) during the motor tasks (event related desynchronisation, ERD) were analysed statistically with synthetic aperture magnetometry. The tomography of ERD was superimposed on the individual's magnetic resonance image. RESULTS: beta ERD was consistently localised to the contralateral primary sensorimotor cortex (MI/SI) in control subjects, whereas the alpha and low gamma ERD showed considerable intersubject variability. beta ERD in patients during non-affected side hand movement was also localised to the contralateral MI/SI, but exclusively to the ipsilateral hemisphere during affected side hand movement. CONCLUSIONS: The altered pattern of ERD in the patient group during affected side hand movement suggests recruitment of diverse motor areas, especially the ipsilateral MI/SI, which may be required for the effective movement of the affected hand.

Neuromagnetic responses associated with perceptual segregation of pitch.

In recent EEG investigations [Johnson, 2003] [Hautus, 2005], we described a novel late negative ERP component associated with binaural processing of auditory pitch based solely on interaural timing differences ("dichotic pitch"), an acoustic phenomenon that is closely analogous to visual perception of stereoscopic depth based on retinal disparities. The present study extends this research with neuromagnetic recordings of auditory evoked fields (AEFs) elicited by dichotically-embedded pitches. Eight healthy adult subjects listened to control stimuli consisting of 500 ms segments of broadband acoustic noise presented identically to both ears via earphones, and dichotic pitch stimuli created by introducing a dichotic delay to a narrow frequency region of the same noise segments and resulting in a perception of a pitch lateralized to the left or right of auditory space. Auditory-evoked fields (AEFs) were recorded using a 151 channel whole-head MEG system. Comparison of control and dichotic-pitch AEFs showed reliable amplitude differences during a time window of 150-350 ms. AEFs over the left hemisphere showed larger effects for contralateral than ipsilateral pitches, while the right hemisphere showed no differences for differently lateralized sources. The results indicate a relatively late stage of neural processing of binaurally-derived cues for the perceptual segregation of concurrent sound sources and support a right-hemisphere dominance for the processing of sound-source localization.

Modulation of neuromagnetic oscillatory activity during the observation of oro-facial movements.

A number of MEG/EEG studies have shown modulation of endogenous sensorimotor (mu and beta) rhythms during the observation of hand movements. These modulations are similar to patterns that occur during execution of movement and it has been hypothesised that the neural substrates of these rhythms may play a role in action representation and understanding the actions of others. In this experiment we wished to determine whether similar responses would be obtained during the observation of oro-facial movements. Neuromagnetic recordings (151 channels, CTF Systems) were obtained from six healthy subjects while they (1) observed a video of an experimenter making oro-facial movements (2) imitated the same movements and (3) observed hand movements. Source scanning using synthetic aperture magnetometry (SAM) was used to find changes in source power between these active conditions compared to pre-stimulus control conditions where no movement occurred. SAM images were created with 5 mm resolution in the beta (15-35 Hz) and mu (8-15 Hz) bands and showed source power decreases over parietal, occipital and sensorimotor areas. Time-frequency analysis of virtual SAM sensors from sensorimotor areas showed event-related desynchronisation of mu and beta bands following the onset of movement in all three conditions. These data demonstrate comparable activations of visuomotor mechanisms during observation or imitation of mouth movements and during observation of hand movements. These results support the notion that sensorimotor mechanisms play a role in achieving a representation of the oro-facial gestures of others.

Event-related changes in neuromagnetic activity associated with syncopation and synchronization timing tasks.

For low rhythmic rates (1.0 to approximately 2.0 Hz), subjects are able to successfully coordinate finger flexion with an external metronome in either a syncopated (between the beats) or synchronized (on each beat) fashion. Beyond this rate, however, syncopation becomes unstable and subjects spontaneously switch to synchronization to maintain a 1:1 stimulus/response relationship. We used a whole-head magnetometer to investigate the spatiotemporal dynamics of neuromagnetic activity (MEG) associated with both coordinative patterns at eight different rates spanning the range 1.0-2.75 Hz. Timing changes in the event-related fields accompanied transitions from syncopation to synchronization and followed the placement of the motor response within each stimulus/response cycle. Decomposition of event-related fields into component auditory and motor brain responses revealed that the amplitude of the former decreased with increasing coordination rate whereas the motor contribution remained approximately constant across all rates. Such an interaction may contribute to changes in auditory-motor integration that cause syncopation to become unstable. Examination of event-related changes in high frequency bands revealed that MEG signal power in the beta band (15-30 Hz) was significantly lower during syncopated coordination in sensors covering the contralateral sensorimotor area suggesting a dependence of beta rhythm amplitude on task difficulty. Suppression of beta rhythms was also stronger during synchronization preceded by syncopation, e.g., after subjects had switched, when compared with a control condition in which subjects synchronized throughout the entire range of rates.

Movement-related desynchronization of the cerebral cortex studied with spatially filtered magnetoencephalography.

Event-related desynchronization (ERD) within the alpha and beta bands on unilateral index finger extension and hand grasping was investigated on six normal volunteers with magnetoencephalography (MEG). A novel spatial filtering technique for imaging cortical source power, synthetic aperture magnetometry (SAM), was employed for the tomographic demonstration of ERD. SAM source image results were transformed into statistical parametric images. On the same hand grasping task, a functional MRI (fMRI) study was conducted on two subjects and compared with the ERD result. When the MEG data were analyzed with the fast Fourier transformation, power attenuation within the alpha and beta bands was evident on the contralateral sensorimotor area just prior to movement onset. The tomographic distribution of ERD was clearly obtained with SAM statistical imaging analysis. The equivalent current dipole (ECD) for the signal-averaged motor field was localized to the hemisphere contralateral to the hand movement, roughly at the center of the region displaying beta-band ERD. The signal increase on fMRI roughly colocalized with the ERD on the contralateral sensorimotor area. In conclusion, with the novel spatial filtering technique for the brain magnetic field, SAM, cortical regions contributing to ERD on finger movement were successfully demonstrated in a tomographic manner. The relative colocalization of the contralateral SAM ERD with ECD as well as the fMRI activation suggests that SAM is a practically useful technique to extract event-related signals from brain noise.

Spatiotemporal analysis of neuromagnetic events underlying the emergence of coordinative instabilities.

A full-head 143-channel superconducting quantum interference device was used to study changes occurring in the magnetic activity of the human brain during performance of an auditory-motor coordination task in which the rate of coordination was systematically increased. Previous research using the same task paradigm demonstrated that spontaneous switches in timing behavior that arise with higher coordination rates are accompanied by qualitative changes in spatiotemporal brain activity measured by electro- and magnetoencephalography. Here we show how these patterns can be decomposed into basic physiological events, i.e., evoked brain responses to acoustic tones and self-initiated finger movements. The frequency dependence of the amplitudes of these component responses may shed new light onto why spontaneous timing transitions occur in the first place.

Challenges of recording human fetal auditory-evoked response using magnetoencephalography.

OBJECTIVE: Our goals were to successfully perform fetal auditory-evoked responses using the magnetoencephalography technique, understand its problems and limitations, and propose instrument design modifications to improve the signal quality and success rate. METHODS: Fetal auditory-evoked responses were recorded from four fetuses with gestational ages ranging from 33-40+ weeks. The signals were recorded using a gantry-based superconducting quantum interference device. Auditory stimulus was 1 kHz tone burst. The evoked signals were digitized and averaged over an 800 ms window. RESULTS: After several trials of positioning and repositioning the subjects, we were able to record auditory-evoked responses in three out of the four fetuses. Since the superconducting quantum interference device array design was not shaped to fit over the mother's abdomen, we experienced difficulty in positioning the sensors over the fetal head. CONCLUSIONS: Based on this pilot study, we propose instrument design that may improve signal quality and success rate of the fetal magnetic auditory-evoked response.

Neuromagnetic fields preceding unilateral movements in dextrals and sinistrals.

Movement-related magnetic fields were recorded with a whole-head magnetoencephalographic system in three dextrals and three sinistrals during right or left index finger extension. The motor field (MF) demonstrated an asymmetrical isofield map pattern with larger field reversal over the contralateral hemisphere for dominant hand movement and an almost symmetrical pattern for non-dominant hand movement in each subject. The equivalent current dipole moment of the MF for the contralateral hemisphere was significantly larger than the ipsilateral hemisphere for dominant hand movement, and almost equal for both hemispheres for non-dominant hand movement. These results were congruent for both dextrals and sinistrals, suggesting a more important role of the hemisphere contralateral to the dominant hand in unilateral voluntary movement, regardless of handedness.

Dynamic cortical activity in the human brain reveals motor equivalence.

That animals and humans can accomplish the same goal using different effectors and different goals using the same effectors attests to the remarkable flexibility of the central nervous system. This phenomenon has been termed 'motor equivalence', an example being the writing of a name with a pencil held between the toes or teeth. The idea of motor equivalence has reappeared because single-cell studies in monkeys have shown that parameters of voluntary movement (such as direction) may be specified in the brain, relegating muscle activation to spinal interneuronal systems. Using a novel experimental paradigms and a full-head SQUID (for superconducting quantum interference device) array to record magnetic fields corresponding to ongoing brain activity, we demonstrate: (1), a robust relationship between time-dependent activity in sensorimotor cortex and movement velocity, independent of explicit task requirements; and (2) neural activations that are specific to task demands alone. It appears, therefore, that signatures of motor equivalence in humans may be found in dynamic patterns of cortical activity.

A MEG analysis of the P300 in visual discrimination tasks.

Based on recent research that indicated that P300 scalp topography varies as a function of task and/or information to be processed, this study examined scalp-recorded magnetic fields correlated with the P300 by means of whole-head magnetoencephalography. Subjects performed two discrimination tasks, in which targets, defined on either object or spatial characteristics of the same visual stimuli, had to be discriminated. Based on the across-subject root mean square (RMS) functions a sequence of 4 components could be identified in both tasks, N1m, P3m, and two later components, which, based on their estimated neuronal sources, were classified as representing motor processes during and following the manual responses to target stimuli. Reliable between-task differences in source localization were obtained for the P3m component, but not for the other components. Inferior-medial sources were found for the P3m evoked by both spatial and object targets, with these sources being located about 3.5 cm more anterior for object targets. These results suggest that different neuronal sources, possibly located in subcortical regions in the vicinity of the thalamus, contribute to the P3m evoked by target stimuli defined by either object or spatial stimulus characteristics.

Sensory feedback contributes to early movement-evoked fields during voluntary finger movements in humans.

Neuromagnetic field changes accompanying voluntary movement in humans ('movement-evoked fields' or MEFs) were recorded over the scalp using a whole-head MEG system during the performance of self-paced finger movements in order to determine the contribution of sensory feedback to the generation of these brain responses. It was found that cooling the subject's arm resulted in delays of 8 ms or more in the latency of the early movement-evoked field component (MEFI). These delays were attributed to increases in conduction times in the afferent pathways as confirmed by electrically evoked somatosensory responses and suggest a peripheral origin of the MEFI. In a second experiment, we demonstrated the effects of sensory input to the contralateral hand during a simple button pressing task in 4 subjects. The results indicated that responses over the hemisphere ipsilateral to the side of movement which resembled previously reported ipsilateral MEFs can be elicited by the spread of mechanical stimulation to opposite side of the body when a mechanical trigger is used. These experiments provide further evidence that early movement-evoked fields produced by unilateral finger movements are observed primarily over the contralateral somatosensory cortex and represent sensory feedback to the somatosensory cortex from the periphery.

Electric and magnetic fields of the brain accompanying internal simulation of movement.

Methods of functional brain imaging have been used to identify brain structures which are active during internal simulation of movements (ISM). Between 1977 and 1993 it was consistently reported that the primary motor cortex (MI) is not active during ISM whereas other cortical areas, in particular the supplementary motor area (SMA) are active. ISM was assumed to be a situation of "internal programming'. Brain systems involved in ISM or 'programming' were hypothesized to be superior to and separable from 'executive system' including MI. We have studied electric and magnetic fields of the brain when subjects internally simulated either a single movement or a sequence of movements. Results of the studies are consistent with the assumption that MI is active with ISM. Internally subjects experienced effort which was required to inhibit overt movements during ISM. A recent EEG study showed different patterns of cortical activity with ISM and with movement inhibition suggesting that different brain structures may be active during ISM and movement inhibition [23].

Modulation of somatosensory evoked magnetic fields by sensory and motor interferences.

Modulatory influences of skilled exploratory finger movements on somatosensory evoked magnetic fields evoked by median nerve stimulation were investigated in six healthy subjects using a whole head magnetometer (MEG) system. The exploratory finger movements caused major changes in the somatosensory evoked fields. The most prominent effect was a reversal of the dipolar magnetic field around 30 ms after median nerve stimulation. Similar but less pronounced effects were exerted by repetitive finger movements and tactile stimulation of the hand. A dipole analysis and super-imposition of resulting sources on individual MRI scans showed that all somatosensory evoked fields up to 60 ms after stimulation, and the modulation of these responses were located in the primary somatosensory cortex (SI).

Motor cortex activity and predicting side of movement: neural network and dipole analysis of pre-movement magnetic fields.

Neuromagnetic fields were recorded from human subjects during the performance of left and right voluntary finger movements. Modeling of current dipole sources indicated symmetric activation of both motor cortices beginning 600 ms prior to movement onset. This activity became lateralized to the contralateral hemisphere 200-300 ms prior to movement onset, the period during which an artificial neural network showed increased ability to predict side of movement within single trials. The results describe the mechanism of lateralization of cortical brain activity preceding voluntary movement and provide further evidence of the involvement of ipsilateral motor cortex in unilateral movements.