Abstract: Two classes of functional neuroimaging methods exist: hemodynamic techniques such as PET and fMRI, and electromagnetic techniques such as EEG/ERP and MEG. In order to fusion these images with anatomical information, co-registration with volumetric MRI is needed. While such co-registration techniques are well established for hemodynamic images, additional steps are needed for electromagnetic recordings, because the activity is only recorded on the scalp surface and inverse solutions based on specific head models have to be used to estimate the 3-dimensional current distribution. To date most of the experimental and clinical studies use multi-shell concentric sphere models of the head, solve the inverse problem on this simplistic model, and then co-register the solution with the MRI using homogeneous transform operations. Contrary to this standard method, we here propose to map the MRI to the spherical system by defining transformation operations that transform the MRI to a best-fitting sphere. Once done so, the solution points are defined in the cerebral tissue of this deformed MRI and the lead field for the distributed linear inverse solutions is calculated for this solution space. The method, that we call SMAC (Spherical Model with Anatomical Constrains) is tested with simulations, as well as with the following real data: 1) estimation of the sources of visual evoked potentials to unilateral stimulation from data averaged over subjects, and 2) localization of interictal discharges of two epileptic patients, one with a temporal, the other with an occipital focus, both confirmed by seizure freedom after resection of the epileptogenic region.

Abstract: The magnetoencephalography (MEG) signal was recorded while subjects watched a video containing separate blocks of affective and cognitive advertisements and recalled slides extracted from the video a day later. An earlier behavioural study using the same video material showed that the affective advertisements were better recalled and that administration of propranolol (a beta-adrenergic blocker) abolished this effect. Magnetic field tomography (MFT) was used to extract tomographic estimates of activity millisecond by millisecond from the continuous MEG signal. Statistically significant differences between affective and cognitive blocks were identified in posterior and prefrontal areas. Cognitive blocks produced stronger activity in posterior parietal areas and superior prefrontal cortex in all three subjects. Affective blocks modulated activity in orbitofrontal and retrosplenial cortex, amygdala and brainstem. Individual contributions to the statistical maps were traced in real time from milliseconds to many seconds. Time-locked responses from the recall session were used to compare average and single trial MFT solutions and to combine activations from all subjects into a common anatomical space. The last step produced statistically significant increases in occipital and inferior ventral cortex between 100 and 200 ms compared to a prestimulus baseline.

Abstract: The aim of the present study was to investigate the relationship between different EEG measures (mean power, mean frequency, approximated entropy and coherence), and ability (creativity and intelligence). For that purpose the EEG of 115 student-teachers (Intelligence: $$\underline {\text{M}} = 115.17;\underline {{\text{SD}}} = 12.78;{\text{IQ}}_{{\text{min}}} = 82;{\text{IQ}}_{{\text{max}}} = 136;$$ Creativity - standardized scores: $$\underline {\text{M}} = 55.97;\underline {{\text{SD}}} = 10.67;{\text{C}}_{{\text{min}}} = 38;{\text{C}}_{{\text{max}}} = 84)$$ was recorded while they were resting with eyes open and closed. The study showed only weak correlations between measures based on the level of activity in different areas (mean power, mean frequency and approximated entropy) and creativity. The correlations with IQ scores were even less pronounced. On the other hand, coherence measures showed a much more intense relationship both with creativity as well as with intelligence. In the eyes-open state these differences were mainly distributed over the right hemisphere. The results are discussed in the light of different theories relating brain functioning and ability.

Abstract: Magnetoencephalogram (MEG) recordings were obtained from the brain of patients suffering from Parkinson's disease (PD) using the Superconductive Quantum Interference Device (SQUID). For each patient the magnetic activity was recorded from a total of 64 points of the skull (32 points from each temporal lobe) as defined by a recording reference system, which is based on the 10-20 Electrode Placement System. Some of the recorded points were observed to exhibit abnormal rhythmic activity, characterized by high amplitudes and low frequencies. External magnetic stimulation (EMS) with intensity 1-7.5pT, and frequency the a-rhythm of the patient (8-13 Hz) was applied in the left-right temporal, frontal-occipital and vertex (2 minutes over each of the above regions) and the brain magnetic activity was recorded again. The application of the EMS resulted in rapid attenuation of the MEG activity of PD patients. Furthermore, chaotic dynamic methods were used, in order to estimate the correlation dimension D of the reconstructed phase spaces. The estimated values of D, in conjunction with the results derived from the other data analysis methods, strongly support the existence of low dimension chaotic structures in the dynamics of cortical activity of PD patients. In addition, the increased values of D of the MEG after the application of EMS when compared with the corresponding ones obtained from the MEGs prior to the EMS, suggest that the neural dynamics are strongly influenced by the application of EMS.

Abstract: In this study, electrical conductivities of compact, spongiosum, and bulk layers of cadaver skull were determined at varying electric fields at room temperature. Current was applied and withdrawn over the top and bottom surfaces of each sample and potential drop across different layers was measured using the four-electrode method. We developed a model, which considers of variations in skull thicknesses, to determine the conductivity of the tri-layer skull and its individual anatomical structures. The results indicate that the spongiform and the two compact layers of the skull have significantly different and inhomogeneous conductivities ranging from 0.76 +/- .14 to 11.5 +/- 1.8 milliS/m.

Abstract: This paper discusses the properties and capabilities of linear inverse solutions to the neuroelectromagnetic inverse problem obtained under the assumption of smoothness (Laplacian Minimization). Simple simulated counterexamples using smooth current distributions as well as single or multiple active dipoles are presented to refute some properties attributed to a particular implementation of the Laplacian Minimization coined LORETA. The problem of the selection of the test sources to be used in the evaluation is addressed and it is demonstrated that single dipoles are far from being the worst test case for a smooth solution as generally believed. The simulations confirm that the dipole localization error cannot constitute the tool to evaluate distributed inverse solutions designed to deal with multiple sources and that the necessary condition for the correct performance of an inverse is the adequate characterization of the source space, i.e., the characterization of the properties of the actual generators.

Abstract: The differential effects of painful stimulation of skin vs. muscle on the cerebral electrophysiology have been poorly described. This study examined the somatosensory evoked potentials (SEPs) and the associated dipole models of non-painful and graded painful electrical stimulation applied to the skin and muscle in 20 healthy subjects. With the psychophysical stimulus-response functions determined, the skin stimulation showed a steeper slope than muscle stimulation. For both types of stimulation, the SEPs indicated a similar temporo-spatial activation sequence: F4/N90-P4/P95, Fc2/N135, Cz/P250, Cz/P300, and Cz/N460. The SEP amplitudes increased significantly with the stimulus intensities in these components. The peak SEP latencies of skin stimulation were in general shorter than that of muscle stimulation. The SEP amplitudes to skin stimulation were significantly larger than those caused by muscle stimulation at every stimulus intensity level, except the early mid-latency component. In this case, muscle stimulation caused higher amplitudes over the contralateral parietal-frontal sites. For both types of stimulation, the topographic maps were quite similar. Equivalent dipole modeling revealed identical site parameters (<1.0 cm) between skin and muscle stimulation. However, the electrical skin stimulation did not correlate with the pain intensity. Pain intensity, in contrast, was uniquely associated with the Cz/P250 amplitudes for the muscle stimulation. It is concluded that non-nociceptive and nociceptive electrical stimuli applied to skin and muscle are processed in the common cerebral areas, but exhibit differential SEP effects.

Abstract: The P300-amplitude evoked with an acoustic oddball-paradigm is considered the most stable late event-related potential (ERP). This amplitude-index has become a standard parameter in electrophysiology. Recently, a robust ERP-parameter (NoGo-anteriorization, NGA) has been introduced, which reflects spatial brain electrical changes in relation to execution and inhibition of a motor response elicited with a Continuous Performance Test (CPT). The current study refers to the stability of this new topographical ERP-parameter compared to the stability of the classical P300-amplitude. For that purpose, 12 healthy subjects were investigated with both paradigms during recording of a 21-channel EEG. Analysis of the resulting ERPs revealed a very high stability for both, topographical and amplitude index: In every single subject, the brain electrical fields were characterized by a more anterior location in the NoGo- compared to the Go-condition (=NGA) and by higher amplitudes after target compared to distractor condition. T-tests, analyses of the effect size and of the power revealed equivalent differences between the two contrasting conditions for the topographical compared to the amplitude index. These results indicate that the stability of the topographical ERP-parameters elicited with the CPT is sufficient for an electrophysiological standard-index. The possibility to elicit a robust and specific spatial brain activation with the CPT is an ideal completion to the classical P300 amplitude effect and, therefore, hopefully will be a useful expansion of the standard paradigms in electrophysiological laboratories.

Abstract: This paper describes a method for estimating a set of spatial components (brain maps) and temporal components (waveforms) of brain potentials. These components play the role of bases of a coordinate system, in the sense that the brain potentials of any subject can be represented as superpositions of these components. The representation is unique given the spatial and temporal components, and this decomposition is particularly appealing for comparing the brain potentials of different subjects (say alcoholics and controls). It can also be used for single trial modeling, clinical classification of patients, and data filtering. The method is based on the topographic component model (TCM, Mocks 1988) which models brain potentials in a trilinear form. We extend the TCM in two aspects. First, the diagonal amplitude matrix is replaced by a general loading matrix based on some neurophysiological considerations. Secondly, the number of spatial components and the number of temporal components can be different. The spatial components and temporal components are obtained respectively by performing singular value decomposition (SVD). This method is illustrated with visual P3 data.

Abstract: At present, our understanding of how normal aging affects in vivo brain function is rudimentary. Therefore, the aim of the present study was to investigate age effects on auditory P300 topography. A recently developed dipole source model for P300 distinguishes overlapping P300 subcomponents and enhances reliability as well as validity of the measurement. 67 healthy subjects were examined using the P300 dipole model in addition to the scalp data measurement. The results show that P300 subcomponents reflect functionally different processes concerning age changes of P300 activities. Temporo-parietal P300 is smaller in older subjects, whereas frontal P300 is not attenuated. Age affected both P300 subcomponents' latencies. Therefore, the functionally different alteration of P300 subcomponents might be the reason for P300 topography changes with the P300 maximum more frontally in older age.

Abstract: A new magnetoencephalographic (MEG) technique for imaging the cortical distribution of neuronal activity is described. An iterative algorithm is employed, which successively alters an initial estimate of cortical source structure until it corresponds to the measured magnetic field data. In this new technique, the continuum of electrical activity across the cortical surface is modeled as a dense grid of thousands of single equivalent current dipoles. MEG imaging of both compact and extended sources is facilitated by a wavelet-like transformation of the source space into a sequence of successively smaller composite source structures. Two of these composite source structures are combined during each iterative step to generate an improved estimate of the cortical source structure. Thus, inversion of the complete gain matrix corresponding to thousands of cortical sources is not performed. The technique requires only moderate PC based resources even for very large source grids. In contrast to minimum norm MEG imaging methods, this new algorithm is insensitive to random noise in the data. If available, prior knowledge of source structure from other imaging techniques, such as PET, MRI and fMRI, is easily incorporated as additional constraints on the source structure solution. Source images solutions corresponding to simulated data are presented. In addition, the technique is applied to source imaging of real MEG data incorporating cortical structure from volumetric MRI data. These results demonstrate the capability of our new technique for imaging combinations of compact and extended source structures.

Abstract: To improve our understanding of the physiology of generalized tonic-clonic (GTC) seizures, we have investigated the stationarity and redundancy of 21-electrode EEG data recorded from ten patients during GTC seizures elicited by electroconvulsive therapy (ECT). Stationarity was examined by calculating probability density functions (pdfs) and power spectra over small equal-length non-overlapping time windows and then by studying, visually and quantitatively, the evolution of these quantities over the duration of the seizures. Our analysis shows that some seizures had no demonstrable stationarity, that most seizures had time intervals of at least a few seconds that were statistically stationary by several criteria, and that, in some seizures, there were leads which were delayed in manifesting the statistical changes associated with seizure onset evident in other leads. The redundancy analysis demonstrated for the first time posterior-to-anterior time delays in the mid-ictal region of GTC seizures. The implications of these findings are discussed for the analysis of GTC seizure EEG data, for the physiology of GTC seizures, and for ECT research.

Abstract: Eighteen older adults and 18 younger adults were compared on two quantitative measures describing changes over time in the spatial distribution of running EEG. EEG was collected from 128 electrodes under resting eyes-open and eyes-closed conditions and during performance of a 13 minute sustained attention task. One EEG measure, the recrudescence rate, represented the number of changes in the location of the highest squared voltage per second. A second EEG measure consisted of the algorithmic complexity of changes in the location of the highest squared voltage over time. Regardless of the task condition, older adults had significantly higher scores than younger adults on both the recrudescence rate and the measure of algorithmic complexity. The implications of the results for neurologically-based theories of performance declines in older adults are discussed.

Abstract: Early, middle and late latency somatosensory evoked potentials (SEPs) elicited by cutaneous electrical stimulation (painful vs. non-painful) of right and left hands were recorded. The aims were to study (1) if lifelong use of dominant right hand would result in different SEP topographies compared to non-dominant left hand stimulation, (2) if painful and non-painful stimuli resulted in different SEP activation patterns for the different latency components and (3) if these results were consistent between two areas of the hand. Electrical stimuli were applied cutaneously above the thenar and hypothenar muscles of the left and right hand. A two-way repeated measures ANOVA was used to test the effects of laterality and intensity for a given peak amplitude and latency. Statistical results yielded no significant difference in peak amplitude for either thenar and hypothenar between the two hands. In contrast, a significant difference in amplitude was observed for 6 components for each stimulus location when the two intensities were compared. These components were found at early, middle and late latencies. No significant latency shift was observed between the two hands. Only the P30 component showed a significant latency shift for both locations with the painful condition having the shorter latency. Thus, life-long use of the dominant hand does not generate detectable changes in cortical evoked activity to sensory input from the skin above thenar and hypothenar muscles. Several SEP components across the time course (0-400 ms) showed increased amplitude when the stimulus was increased from non-painful to painful intensity.

Abstract: Studies based on whole-head MEG recordings are providing more and more impressive results. In such recordings, the MEG sensors are several centimeters away from the scalp and the positions of the MEG sensors with respect to the head differ from subject to subject, and from session to session for the same subject. In this paper, a method is presented and tested to estimate the scalp MEG distributions from whole-head MEG measurements. The goal is to remove the discrepancy of MEG measurements caused by the various sensor positions with respect to the head, as well as to reduce the smearing effect caused by the distance of the MEG sensors from the scalp. The MEG measurement was first projected to a hypothetical dipole layer within the head volume conductor model using the inverse solution. The scalp MEG estimation was then obtained from the resultant dipole layer by the forward solution. The results from simulation studies, phantom experiments, and the auditory evoked field analysis demonstrated that, with reasonable signal to noise ratios, this method is a feasible way to achieve our goals.

Abstract: The purpose of this paper is to propose a new algorithm for the analysis of biomagnetic field data obtained from magnetoencephalography (MEG) measurements This new method overcomes two major problems faced by the current method of data analysis The first problem is the need to determine the number of sites of brain activity before calculations can be performed The second problem is inability of the analysis to provide any information regarding the volume of the brain activity The new data analysis method, called the Moving Mesh Method (MMM), is capable of analyzing MEG data without the need to determine the number of sources beforehand In addition, the MMM determines the location of brain activity as a three dimensional volume, instead of as a point source of activity The MMM uses an iterative method of calculating the position of the sources to achieve greater accuracy, and a regularized g-inverse matrix to stabilize its solution The feasibility of the MMM was examined by two methods First, a computer simulation was used to confirm the MMM's capability to analyzing MEG data In the second experiment, the MMM was applied to analyze somatosensory evoked fields obtained using a new imaging system (Shimadzu Biomagnetic Imaging System, Model-100) From the interpretation of the results, we have concluded that the MMM is a feasible method of biomagnetic data analysis

Abstract: The effect of number of EEG electrodes on the dipole localization was studied by comparing the results obtained using the 10-20 and 10-10 electrode systems. Two anatomically detailed models with resistivity values of 177.6 omega m and 67.0 omega m for the skull were applied. Simulated potential values generated by current dipoles were applied to different combinations of the volume conductors and electrode systems. High and low resistivity models differed slightly in favour of the lower skull resistivity model when dipole localization was based on noiseless data. The localization errors were approximately three times larger using low resistivity model for generating the potentials, but applying high resistivity model for the inverse solution. The difference between the two electrode systems was minor in favour of the 10-10 electrode system when simulated, noiseless potentials were used. In the presence of noise the dipole localization algorithm operated more accurately using the denser electrode system. In conclusion, increasing the number of recording electrodes seems to improve the localization accuracy in the presence of noise. The absolute skull resistivity value also affects the accuracy, but using an incorrect value in modelling calculations seems to be the most serious source of error.

Abstract: Temporal summation is a potent central somatosensory mechanism and may be a major mechanism involved in e.g. neuropathic pain. This study assessed the long-latency somatosensory evoked potentials (SEPs) in response to trains of repeated painful electrical stimulation of human skin and muscle in order to investigate the cerebral representation of temporal summation. Forty series of stimuli were delivered at stimulus intensities corresponding to moderate pain levels in 20 young men. Each series consisted of a five-burst-pulses (1 ms) train delivered at 2 Hz, known to activate temporal summation, i.e. increased pain intensity during the series of stimuli. Grand mean averaged waveforms (31 ch. EEG) were obtained in response to the skin and muscle stimulation. In the "train" SEPs, the wave morphology was characterized by four peak components after the first stimulus (100 to 450 ms) and by three components after the fifth stimulus (2100-2145 ms). The latency was significantly prolonged for muscle stimulation only. The 3D topographic maps at the peak activation time (100, 140, 250, and 450 ms) showed clear reduction in the amplitudes and their spatial extent (P4/P100-Fc2/N100, POz/P140-Fc2/N140, Cz/P250, Cz/N460) betweenthe first and the fifth stimulus. The current source density (CSD) topology exhibited markedly differential patterns changing from the first to the fifth stimulus. For the skin stimulation, the fifth stimulus was associated with a distinct emergence of the frontal negativity source at Fc2 right frontal cortex. This was consistent across the 100,140, 250, and 450 peak components but was not even visible in the first stimulus. In the muscle, the fifth stimulus was associated with a marked reduction of the frontal positivity at contralateral F4 site in the early stages at 100 and 140 ms, and with a total disappearance of positive source at Cz. In summary, this study demonstrated a clear temporal summation of psychophysical ratings, reduction of the peak amplitudes in the last of the first stimuli, dissociation from simple amplitude increase of the cerebral responses to pain, and a concurrent transformation of the CSD patterns. This change in "rapid cortical dynamics" of short-term plasticity could be an important mechanism for wind-up and pain processing in the brain.

Abstract: Summary: A two-scale theoretical description outlines relationships between brain current sources and the resulting extracranial electric field ,r ecorded as EEG. Finding unknown sources of EEG, the so-called "inverse problem", is discussed in general terms, with emphasis on the fundamental non-uniqueness of inverse solutions. Hemodynamic signatures, measured with fMRI, are expressed as voxel integrals to facilitate comparisons with EEG. Two generally distinct cell groups (1 and 2), generating EEG and fMRI signals respectively, are embedded within the much broader class of synaptic action fields. Cell groups 1 and 2 may or may not overlap in specific experiments. Implications of this incomplete overlap for co-registration studies are considered. Each experimental measure of brain function is generally sensitive to a different kind of source activity and to different spatial and temporal scales. Failure to appreciate such distinctions can exacerbate conflicting views of brain function that emphasize either global integration or functional localization.

Abstract: Event-related potentials (ERPs) during a visual oddball paradigm with button-pressing responses were recorded in 12 right-handed subjects from 32 scalp electrodes. The single equivalent current dipole (ECD) of the target C1 (weak occipito-parietal negativity from 30-80ms) was consistently located at the primary visual cortex. From the 4-ECD localization of the target P1/N1 (temporally coincident frontal positivity and occipito-temporal negativity), it was suggested that this complex reflected activities from distributed sources along both dorsal occipito-parietal and ventral occipito-temporal areas. The stable multiple ECD solutions for the target P3b were chosen as those including the left primary motor and/or sensorimotor dipole and satisfying goodness-of-fit (GOF) of more than 98% and confidence limit (CL) of less than 1mm. The obtained frontal dipoles were discussed in terms of visual working memory and sustained attention in reference to the previous PET, fMRI and MEG studies. The distributed multiple ECDs may suggest that P3 should be interpreted as being the embodiment of the cortico-limbic-thalamic network which involves Halgren and Marinkovic's emotional and behavioral model and Mesulam's attentional circuit.

Abstract: We investigated steady-state movement-related cortical potentials elicited by fast repetitive movements (1/sec@rpar; with 50-channel EEG. The experimental design comprised a comparison @lpar;a@rpar; between unilateral movements of the digits and the toes and (b) between metronome-paced and self-paced initiation of the movements. A distinct biphasic pattern of electrical activity following movement onset was observed, namely a frontal negative peak at a latency of 90 ms (post-MP100) and a frontal positive peak at a latency of 310 ms )post-MP300(. Pacing exerted its effects mainly on the amplitude and on the latency of the post-MP300. Source analysis revealed that both peaks could be modelled by a single source. The source locations were highly reproducible across the metronome-paced and self-paced conditions, and, they followed the expected somatotopic organisation.

Abstract: Patients with medically intractable partial epilepsy and well-defined symptomatic MRI lesions were studied using phase-encoded frequency spectral analysis (PEFSA) combined with low-resolution electromagnetic tomography (LORETA) Ten patients admitted to the epilepsy monitoring unit with MRI-identified lesions and intractable partial epilepsy were studied using 31-electrode scalp EEG The scalp electrodes were located in three-dimensional space using a magnetic digitizer and coregistered with the patient's MRI PEFSA was used to obtain a phase-encoded scalp map for the ictal frequencies The ictal generators were obtained from the scalp map using LORETA In addition, the generators of interictal epileptogenic spikes were identified using time-domain LORETA The LORETA generators were rostral to the MRI lesion in 87% (7/8) of patients with temporal lobe lesions, but all were located in the mesial temporal lobe in concordance with the patients' MRI lesions In patients with frontal lobe epilepsy, the ictal generators at the time that the spectral power was maximal localized to the MRI lesions Eight of 10 patients had interictal spikes, of which 4 were bilateral independent temporal lobe spikes Only generators of the interictal spikes that were ipsilateral to seizure onset correlated with the ictal generators LORETA combined with PEFSA of the ictal discharge can localize ictal EEG discharges accurately and improve correlation with brain anatomy by allowing coregistration of the ictal generator with the MRI Analysis of interictal spikes was less useful than analysis of the ictal discharge