Neuromagnetic source analysis using magnetic resonance images for the construction of source and volume conductor model

Summary Sources of the somatosensory evoked fields (SEF) for one subject were estimated using constraints from the magnetic resonance images (MRI) of the same subject. A realistic volume conductor model was shaped corresponding to the inside of the skull. Sources were restricted to a dipole patch riding on the surface of the cortex, reconstructed from the individual MRI. Such a patch can be considered as a uniformly activated cortical area giving rise to distributed currents which flow perpendicular to the cortical surface. Source locations obtained for the SEF in response to separate stimulations of lower lip, first and fifth digit, and collarbone followed the course of the contralateral central sulcus. The order of the estimated source locations was in agreement with the somatosensory homunculus of Penfield and Rasmussen. Similar results were obtained with the simple model of a current dipole in a homogeneous sphere. In contrast, combining a current dipole model with a realistic volume conductor model was rather problematic as it overestimates the radial dipole component by an order of magnitude.This work was supported by a grant from the Deutsche Forschungsgemeinschaft (Klinische Forschergruppe Biomagnetismus und Biosignalanalyse).     

Cross-modal generality of the gating deficit

Auditory P50/M50 paired-click studies have established an association between schizophrenia and impaired sensory gating in the auditory modality. However, the presumed cross-modal generality of the gating deficit has received little study. The present study examined gating in area 3b of primary somatosensory cortex to evaluate patients' somatosensory gating at this first stage of cortical processing. One hundred twenty-two channels of magnetoencephalography (MEG) data were collected from 27 subjects with chronic schizophrenia and 21 controls during a somatosensory paired-pulse paradigm with a 75- or 500-ms interstimulus interval. M20 somatosensory responses were localized using magnetic source imaging, and a gating ratio was calculated. In a subset of these subjects, MEG was also done for the standard auditory paradigm to assess M50 gating. Patients showed abnormal auditory M50 gating but normal somatosensory M20 gating. Results argue against a cross-modal gating deficit in primary somatosensory cortex.     

Localization of human somatosensory cortex using spatially filtered magnetoencephalography

A spatial filter algorithm based on minimum-variance beamforming (synthetic aperture magnetometry (SAM)) was applied to single trial neuromagnetic recordings in order to localize primary somatosensory cortex. Magnetoencephalography (MEG) responses to electrical stimulation of the right and left median nerve were recorded using a whole-head MEG system and localized using both SAM spatial filtering and dipole analysis. Spatial filtering was applied to single trial neuromagnetic recordings to produce 3-dimensional difference images of source power between active (0–50 ms) and control states (−50–0 ms) in the range of 15–300 Hz. Average difference between N20m dipole location and location of maximal increase in power in the SAM images was 3.7 mm (1.5 mm SD) and localized to primary somatosensory cortex. Time-frequency analysis of spatially filtered output for the peak SAM locations showed a brief (10 ms) increase in the 60–100 Hz band coincident with the N20m response and a longer duration (approx. 80 ms) increase in power in the 10–40 Hz band following N20m onset. These results indicate that beamformer based spatial filter methods such as SAM can be used to localize temporally discrete cortical activity produced by median nerve stimulation.     

Cytoprotection does not preserve brain functionality in rats during the acute post-stroke phase despite evidence of non-infarction provided by MRI

In animal models of stroke the promise of a therapy is commonly judged from infarct size measurements, assuming that a reduction in infarct size results in reduction of the functional deficits. We have evaluated the validity of the concept that structural integrity translates into functional integrity during the acute post-stroke period (24 h). Unilateral permanent middle cerebral artery occlusion (pMCAO) in Fischer F344 rats leads to infarcts comprising the ipsilateral striatum and cortical structures, including the somatosensory cortex. Infarct volumes were assessed using magnetic resonance imaging (MRI) methods (T(2), diffusion, perfusion MRI). The functional integrity of the somatosensory cortex was assessed by functional MRI (fMRI) measuring changes in local cerebral blood volume, and by assessing the forelimb grip strength and the beam-walking performance of the animals. Treatment with the calcium antagonist isradipine (2.5 mg/kg injected s.c. immediately after pMCAO) reduced the total infarct size by more than 40% compared to vehicle-injected controls. In particular, the ipsilateral somatosensory cortex appeared normal in diffusion- and T(2)-weighted MRI images. In sham-operated rats simultaneous electrical stimulation of both forepaws led to similar activation of both somatosensory cortices, while in pMCAO animals given vehicle only the contralateral cortex showed an fMRI response. Similarly, in pMCAO rats treated with isradipine, functional activation following bilateral electrical stimulation was only detected in the contralateral somatosensory cortex despite the normal appearance of the ipsilateral cortex in MRI images. Furthermore, fMRI responses to pharmacological stimulation with bicuculline were virtually absent in the ipsilateral somatosensory cortices both in vehicle- and isradipine-treated rats. Finally there was no significant difference between vehicle- and isradipine-treated animals upon the performance of beam-walking test or in forelimb grip strength. It is concluded that during the acute (24 h) post-occlusion period, structural integrity in the somatosensory cortex revealed by MRI does not translate into preservation of function.     

Anatomically constrained minimum variance beamforming applied to EEG

Neural activity as measured non-invasively using electroencephalography (EEG) or magnetoencephalography (MEG) originates in the cortical gray matter. In the cortex, pyramidal cells are organized in columns and activated coherently, leading to current flow perpendicular to the cortical surface. In recent years, beamforming algorithms have been developed, which use this property as an anatomical constraint for the locations and directions of potential sources in MEG data analysis. Here, we extend this work to EEG recordings, which require a more sophisticated forward model due to the blurring of the electric current at tissue boundaries where the conductivity changes. Using CT scans, we create a realistic three-layer head model consisting of tessellated surfaces that represent the cerebrospinal fluid-skull, skull-scalp, and scalp-air boundaries. The cortical gray matter surface, the anatomical constraint for the source dipoles, is extracted from MRI scans. EEG beamforming is implemented on simulated sets of EEG data for three different head models: single spherical, multi-shell spherical, and multi-shell realistic. Using the same conditions for simulated EEG and MEG data, it is shown (and quantified by receiver operating characteristic analysis) that EEG beamforming detects radially oriented sources, to which MEG lacks sensitivity. By merging several techniques, such as linearly constrained minimum variance beamforming, realistic geometry forward solutions, and cortical constraints, we demonstrate it is possible to localize and estimate the dynamics of dipolar and spatially extended (distributed) sources of neural activity.     

A method for a mechanical characterisation of human gluteal tissue.

The most common complication associated with immobilization is pressure sores caused by sustained localized tissue strain and stress. Computational simulations have provided insight into tissue stress-strain distribution, subject to loading conditions. In the simulation process, adequate soft tissue material parameters are indispensable. An in vivo procedure to characterise material parameters of human gluteal skin/fat and muscle tissue has been developed. It employs a magnetic resonance imaging (MRI) device together with an MRI compatible loading device. Using the derived data as constraints in an iterative optimization process the inverse finite element (FE) method was applied. FE-models were built and the material constants describing skin/fat and muscle tissue were parameterized and optimized. Separate parameter sets for human gluteal skin/fat and muscle were established. The long-term shear modulus for human gluteal skin/fat was G_{infinity, S/F}= 1182 Pa and for muscle G_{infinity, M} = 1025 Pa. The Ogden form for slightly compressible materials was chosen to define passive human gluteal soft tissue material behaviour. To verify the approach, the human skin/fat-muscle tissue compound was simulated using the derived material parameter sets and the simulation result was compared to empirical values. A correlation factor of R;{2} = 0.997 was achieved.     

Localization of the human female breast in primary somatosensory cortex

Rationale: Despite an extensive body of research on the topography of the primary somatosensory cortex (S1) little is known about the representation of the trunk. Aim: The aim of this study was to determine the representation of the breast in S1 in human females. Results: The representation of the human breast in primary somatosensory cortex was determined in ten healthy female subjects. Non-painful electrical stimulation of the mammilla (Th4 dermatome), groin (L1 dermatome) and the first digit of both sides of the body activated cutaneous receptors and thus elicited somatosensory evoked potentials. The representation of these body parts in primary somatosensory cortex (S1) was determined using neuroelectric source imaging. Equivalent current dipole localizations were overlaid with individual structural magnetic resonance images to account for individual cortical differences. The breast representation was localized between the representation of the groin and the first digit. In the medial–lateral direction the representation of the breast was approximately 15 mm lateral of the longitudinal fissure in the contralateral hemisphere. Source localizations were stable across subjects. However, one subject showed ipsilateral representation of the breast, which might be related to bilateral receptive fields of the ventral body midline representation. This study confirms the Penfield and Rasmussen (1950) invasive data by use of noninvasive source imaging.     

Optimized individual mismatch negativity source localization using a realistic head model and the Talairach coordinate system

The purpose of this study is to evaluate the difference between anatomical locations of mismatch negativity (MMN) generators using a realistic head model and the Talairach coordinate system. This was performed by dipole source analysis by using a high density 128 channel electroencephalography (EEG) acquisition system and the subjects' individual 3D magnetic resonance images (MRI) for the realistic head model, in 24 healthy subjects. For dipole source localization, both the Talairach coordinate system and the individual MRI realistic head models were used and location results were compared. The MMN generators were clearly localized in the superior temporal gyri, especially in Heschl's gyrus, according to each individual's structural MRI. Only 37.5% of subjects showed the same anatomical locations of the MMN generator in both hemispheres in the realistic head model and in Talairach coordinate system, but fifteen subjects (62.5%) didn't. This result indicates that individually registered functional locations are desirable for the precise localization of activated areas in functional imaging studies and that a brain coordinate system is needed which adequately accounts for ethnic differences.     

Somatosensory stimulus entrains spindle oscillations in the thalamic VPL nucleus in barbiturate anesthetized rats

This study reports the effect of external stimuli on spindle oscillations in the somatosensory thalamus of barbiturate anesthetized rats. Multi-unit responses to somatosensory stimuli were measured from the contralateral thalamic ventral posterior lateral (VPL) nucleus at different stimulus strengths and periods. Spindle oscillations could be entrained by the somatosensory stimuli at periods between 2 and 5 s. A resonance phenomenon described as a quiescent pre-stimulus period followed by entrained post-stimulus oscillations, was observed for somatosensory stimuli above the threshold for eliciting cortical evoked potentials and a stimulus period between 2 and 5 s. This study demonstrates an ascending pathway for localized modulation of spindle oscillations.     

Neuromagnetic investigation of somatotopy of human hand somatosensory cortex

Summary In order to investigate functional topography of human hand somatosensory cortex we recorded somatosensory evoked fields (SEFs) on MEG during the first 40 ms after stimulation of median nerve, ulnar nerve, and the 5 digits. We applied dipole modeling to determine the three-dimensional cortial representations of different peripheral receptive fields. Median nerve and ulnar nerve SEFs exhibited the previously described N20 and P30 components with a magnetic field pattern emerging from the head superior and re-entering the head inferior for the N20 component; the magnetic field pattern of the P30 component was of reversed orientation. Reversals of field direction were oriented along the anterior-posterior axis. SEFs during digit stimulation showed analogous N22 and P32 components and similar magnetic field patterns. Reversals of field direction showed a shift from lateral inferior to medial superior for thumb to little finger. Dipole modeling yielded good fits at these peak latencies accounting for an average of 83% of the data variance. The cortical digit representations were arranged in an orderly somatotopic way from lateral inferior to medial superior in the sequence thumb, index finger, middle finger, ring finger, and little finger. Median nerve cortical representation was lateral inferior to that of ulnar nerve. Isofield maps and dipole locations for these components are consistent with neuronal activity in the posterior bank of central fissure corresponding to area 3b. We conclude that SEFs recorded on MEG in conjunction with source localization techniques are useful to investigate functional topography of human hand somatosensory cortex non-invasively.     

The somatosensory evoked magnetic fields

Averaged magnetoencephalography (MEG) following somatosensory stimulation, somatosensory evoked magnetic field(s) (SEF), in humans are reviewed. The equivalent current dipole(s) (ECD) of the primary and the following middle-latency components of SEF following electrical stimulation within 80-100 ms are estimated in area 3b of the primary somatosensory cortex (SI), the posterior bank of the central sulcus, in the hemisphere contralateral to the stimulated site.Their sites are generally compatible with the homunculus which was reported by Penfield using direct cortical stimulation during surgery. SEF to passive finger movement is generated in area 3a or 2 of SI, unlike with electrical stimulation. Long-latency components with peaks of approximately 80-120 ms are recorded in the bilateral hemispheres and their ECD are estimated in the secondary somatosensory cortex (SII) in the bilateral hemispheres.We also summarized (1) the gating effects on SEF by interference tactile stimulation or movement applied to the stimulus site, (2) clinical applications of SEF in the fields of neurosurgery and neurology and (3) cortical plasticity (reorganization) of the SI. SEF specific to painful stimulation is also recorded following painful stimulation by CO(2) laser beam. Pain-specific components are recorded over 150 ms after the stimulus and their ECD are estimated in the bilateral SII and the limbic system. We introduced a newly-developed multi (12)-channel gradiometer system with the smallest and highest quality superconducting quantum interference device (micro-SQUID) available to non-invasively detect the magnetic fields of a human peripheral nerve. Clear nerve action fields (NAFs) were consistently recorded from all subjects.     

Temporal analysis of the flow from V1 to the extrastriate cortex in humans

We previously examined the cortical processing in response to somatosensory, auditory and noxious stimuli, using magnetoencephalography in humans. Here, we performed a similar analysis of the processing in the human visual cortex for comparative purposes. After flash stimuli applied to the right eye, activations were found in eight cortical areas: the left medial occipital area around the calcarine fissure (primary visual cortex, V1), the left dorsomedial area around the parietooccipital sulcus (DM), the ventral (MOv) and dorsal (MOd) parts of the middle occipital area of bilateral hemispheres, the left temporo-occipito-parietal cortex corresponding to human MT/V5 (hMT), and the ventral surface of the medial occipital area (VO) of the bilateral hemispheres. The mean onset latencies of each cortical activity were (in ms): 27.5 (V1), 31.8 (DM), 32.8 (left MOv), 32.2 (right MOv), 33.4 (left MOd), 32.3 (right MOv), 37.8 (hMT), 46.9 (left VO), and 46.4 (right VO). Therefore the cortico-cortical connection time of visual processing at the early stage was 4-6 ms, which is very similar to the time delay between sequential activations in somatosensory and auditory processing. In addition, the activities in V1, MOd, DM, and hMT showed a similar biphasic waveform with a reversal of polarity after 10 ms, which is a common activation profile of the cortical activity for somatosensory, auditory, and pain-evoked responses. These results suggest similar mechanisms of the serial cortico-cortical processing of sensory information among all sensory areas of the cortex.     

Muscarinic receptor blockade has differential effects on the excitability of intracortical circuits in the human motor cortex

The aim of the present study was to investigate whether muscarinic receptor blockade with scopolamine modifies the excitability of specific cortical networks of the human motor cortex as tested with transcranial magnetic stimulation. The effects of scopolamine on the excitability of human motor cortex were investigated in four healthy subjects using transcranial magnetic stimulation before and after an intravenous dose of scopolamine (0.006 mg/kg). We measured the threshold for motor responses, amplitude of motor responses, the duration of the cortical silent period, intracortical inhibition and facilitation, and short-latency inhibition produced by somatosensory input from the hand. In addition, we evaluated the amplitude of motor responses evoked by electrical anodal stimulation, since these responses originate from direct activation of corticospinal axons in the white matter and are not sensitive to changes in cortical excitability. Scopolamine decreased the threshold to magnetic stimuli and increased the amplitude of motor responses evoked by magnetic stimulation. In contrast, motor responses evoked by electrical stimulation were unaffected by administration of scopolamine. Scopolamine also led to a highly significant reduction in the amount of short-latency inhibition produced by somatosensory input from the hand. In contrast, short-latency intracortical inhibition and facilitation were not modified by scopolamine. The differential effect of scopolamine on motor responses evoked by magnetic and electrical stimulation of the motor cortex and the selective effect on somatosensory inhibition demonstrate that muscarinic blockade modifies the excitability of specific cortical networks in the human motor cortex.     

Integrated approach for studying adaptation mechanisms in the human somatosensory cortical network

Magnetoencephalography and independent component analysis (ICA) was utilized to study and characterize neural adaptation in the somatosensory cortical network. Repetitive punctate tactile stimuli were applied unilaterally to the dominant hand and face using a custom-built pneumatic stimulator called the TAC-Cell. ICA-based source estimation from the evoked neuromagnetic responses indicated cortical activity in the contralateral primary somatosensory cortex (SI) for face stimulation, while hand stimulation resulted in robust contralateral SI and posterior parietal cortex (PPC) activation. Activity was also observed in the secondary somatosensory cortical area (SII) with reduced amplitude and higher variability across subjects. There was a significant difference in adaptation rate between SI and higher-order somatosensory cortices for hand stimulation. Adaptation was significantly dependent on stimulus frequency and pulse index within the stimulus train for both hand and face stimulation. The peak latency of the activity was significantly dependent on stimulation site (hand vs. face) and cortical area (SI vs. PPC). The difference in the peak latency of activity in SI and PPC is presumed to reflect a hierarchical serial-processing mechanism in the somatosensory cortex.     

Using multimodal MRI to investigate alterations in brain structure and function in the BBZDR/Wor rat model of type 2 diabetes

BackgroundThis is an exploratory study using multimodal magnetic resonance imaging (MRI) to interrogate the brain of rats with type 2 diabetes (T2DM) as compared to controls. It was hypothesized there would be changes in brain structure and function that reflected the human disorder, thus providing a model system by which to follow disease progression with noninvasive MRI.MethodsThe transgenic BBZDR/Wor rat, an animal model of T2MD, and age‐matched controls were studied for changes in brain structure using voxel‐based morphometry, alteration in white and gray matter microarchitecture using diffusion weighted imaging with indices of anisotropy, and functional coupling using resting‐state BOLD functional connectivity. Images from each modality were registered to, and analyzed, using a 3D MRI rat atlas providing site‐specific data on over 168 different brain areas.ResultsThere was an overall reduction in brain volume focused primarily on the somatosensory cortex, cerebellum, and white matter tracts. The putative changes in white and gray matter microarchitecture were pervasive affecting much of the brain and not localized to any region. There was a general increase in connectivity in T2DM rats as compared to controls. The cerebellum presented with strong functional coupling to pons and brainstem in T2DM rats but negative connectivity to hippocampus.ConclusionThe neuroradiological measures collected in BBBKZ/Wor rats using multimodal imaging methods did not reflect those reported for T2DB patients in the clinic. The data would suggest the BBBKZ/Wor rat is not an appropriate imaging model for T2DM.     

Synchronized spikes of thalamocortical axonal terminals and cortical neurons are detectable outside the pig brain with MEG.

We show that it is feasible to monitor the synchronized population spikes of the thalamocortical axonal terminals and cortical neurons outside the brain using high-resolution magnetoencephalography (MEG). Electrical stimulation of the snout elicited somatic-evoked magnetic fields (SEFs) above the primary somatosensory cortex (SI) of the piglet. The SEFs contained high-frequency oscillations (HFOs) around 600 Hz similar in many respects to the noninvasively measured HFOs from humans with MEG and electroencephalography (EEG). These HFOs were highly correlated with those in simultaneously measured intracortical somatic-evoked potentials (SEPs) in the snout projection area in SI. Both HFOs in SEFs and SEPs consisted of an initial component insensitive to cortically injected kynurenic acid (Kyna, 20 mM), a nonspecific antagonist of glutamatergic receptors, and a subsequent Kyna-sensitive component. The former was localized in cortical layer IV, indicating that it was due to spikes produced by the specific thalamocortical axonal terminals, whereas the latter was initially localized in layer IV and subsequently in the superficial and deeper layers. These results suggest that it may be possible to study properties of the thalamocortical and cortical spike activities in humans with MEG.     

Timing-dependent plasticity in human primary somatosensory cortex

Animal experiments suggest that cortical sensory representations may be remodelled as a consequence of changing synaptic efficacy by timing-dependent associative neuronal activity. Here we describe a timing-based associative form of plasticity in human somatosensory cortex. Paired associative stimulation (PAS) was performed by combining repetitive median nerve stimulation with transcranial magnetic stimulation (TMS) over the contralateral postcentral region. PAS increased exclusively the amplitude of the P25 component of the median nerve-evoked somatosensory-evoked potential (MN-SSEP), which is probably generated in the superficial cortical layers of area 3b. SSEP components reflecting neuronal activity in deeper cortical layers (N20 component) or subcortical regions (P14 component) remained constant. PAS-induced enhancement of P25 amplitude displayed topographical specificity both for the recording (MN-SSEP versus tibial nerve-SSEP) and the stimulation (magnetic stimulation targeting somatosensory versus motor cortex) arrangements. Modulation of P25 amplitude was confined to a narrow range of interstimulus intervals (ISIs) between the MN pulse and the TMS pulse, and the sign of the modulation changed with ISIs differing by only 15 ms. The function describing the ISI dependence of PAS effects on somatosensory cortex resembled one previously observed in motor cortex, shifted by ∼7 ms. The findings suggest a simple model of modulation of excitability in human primary somatosensory cortex, possibly by mechanisms related to the spike-timing-dependent plasticity of neuronal synapses located in upper cortical layers.     

An fMRI Compatible Wrist Robotic Interface to Study Brain Development in Neonates

A comprehensive understanding of the mechanisms that underlie brain development in premature infants and newborns is crucial for the identification of interventional therapies and rehabilitative strategies. fMRI has the potential to identify such mechanisms, but standard techniques used in adults cannot be implemented in infant studies in a straightforward manner. We have developed an MR safe wrist stimulating robot to systematically investigate the functional brain activity related to both spontaneous and induced wrist movements in premature babies using fMRI. We present the technical aspects of this development and the results of validation experiments. Using the device, the cortical activity associated with both active and passive finger movements were reliably identified in a healthy adult subject. In two preterm infants, passive wrist movements induced a well localized positive BOLD response in the contralateral somatosensory cortex. Furthermore, in a single preterm infant, spontaneous wrist movements were found to be associated with an adjacent cluster of activity, at the level of the infant’s primary motor cortex. The described device will allow detailed and objective fMRI studies of somatosensory and motor system development during early human life and following neonatal brain injury.     

Persistent pain inhibits contralateral somatosensory cortical activity in humans

To assess cortical activity during pain perception, regional cerebral blood flow (rCBF) studies were done in humans using single photon emission computed tomography (SPECT) with the radiotracer Tc99m-HMPAO and magnetic resonance imaging localization. Normalized SPECT data were analyzed by region of interest and change distribution. Contralateral somatosensory rCBF was decreased when the digits of the hand were immersed in a hot water bath for 3 min which was rated as moderately painful (persistent pain). No decrease was observed when the hand was immersed in tepid water (control). In contrast, cortical rCBF was increased during vibratory and sensorimotor tasks, in the contralateral somatosensory and sensorimotor areas, respectively. These results indicate that pain perception in man is associated with somatosensory cortical inhibition.     

An embedded four‐channel receive‐only RF coil array for fMRI experiments of the somatosensory pathway in conscious awake marmosets

fMRI has established itself as the main research tool in neuroscience and brain cognitive research. The common marmoset (Callithrix jacchus) is a non‐human primate model of increasing interest in biomedical research. However, commercial MRI coils for marmosets are not generally available. The present work describes the design and construction of a four‐channel receive‐only surface RF coil array with excellent signal‐to‐noise ratio (SNR) specifically optimized for fMRI experiments in awake marmosets in response to somatosensory stimulation. The array was designed as part of a helmet‐based head restraint system used to prevent motion during the scans. High SNR was obtained by building the coil array using a thin and flexible substrate glued to the inner surface of the restraint helmet, so as to minimize the distance between the array elements and the somatosensory cortex. Decoupling between coil elements was achieved by partial geometrical overlapping and by connecting them to home‐built low‐input‐impedance preamplifiers. In vivo images show excellent coverage of the brain cortical surface with high sensitivity near the somatosensory cortex. Embedding the coil elements within the restraint helmet allowed fMRI data in response to somatosensory stimulation to be collected with high sensitivity and reproducibility in conscious, awake marmosets. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.