Daniel S. Barth

The magnetic and electric fields agree with intracranial localizations of somatosensory cortex

We measured the magnetoencephalogram (MEG), electroencephalogram (EEG), and electrocorticogram (ECoG) after stimulation of contralateral median nerve in four patients with partial epilepsy evaluated for surgery. Quantitative localization estimates from equivalent source modeling were compared with locations of central fissure in hand sensorimotor area determined by cortical stimulations, intraoperative photographs, and examination after excision in frontal lobe. We also measured MEG and EEG in nine control subjects. MEG and EEG localizations were within 2.5 cm of the estimated location of central fissure in all 13 subjects. In the three patients who had complete mapping of all three fields, the average distance of localizations from central fissure was approximately 4 mm in both MEG and EEG, 3 mm in ECoG, and 3 mm in combined MEG and EEG. MEG was simpler than EEG, which was simpler than ECoG. MEG resolved ambiguities in both EEG and ECoG. The combination of the three fields added information about the spatiotemporal activity of somatosensory cortex. Localization of central fissure was essential to surgical treatment.

Comparisons of MEG, EEG, and ECoG source localization in neocortical partial epilepsy in humans

In order to delineate the characteristics of epileptic spikes, 1946 different spikes were studied in 6 patients with complex partial epilepsy. Non-invasive MEG and EEG source analysis of interictal spikes were contrasted to ECoG localization, surgical outcome and presence of lesions on MRI. Results indicated that: (1) using the most frequent occurring spike topography patterns from a large sample of spikes improved goodness-of-fit values for both MEG and EEG localization, (2) when spike patterns could be appropriately matched on several successive MEG measurements to provide an adequate matrix (3 of 6 subjects), there was excellent agreement between MEG dipole sources and ECoG sources as well as surgical outcome and presence of MRI lesions, (3) EEG source analyses also gave good results but not as consistently as MEG.

Neuromagnetic investigation of somatotopy of human hand somatosensory cortex

SummaryIn 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 spatiotemporal organization of auditory, visual, and auditory-visual evoked potentials in rat cortex

Four placements of an 8 x 8 channel microelectrode array were used to map auditory, visual, and combined auditory-visual evoked potentials (AEP, VEP, AVEP) from a total of 256 electrode sites over a 7 x 7 mm2 area including most of somatosensory, auditory, and visual cortex in the right hemisphere of the rat. The unimodal AEP and VEP consisted of an archetypal response sequence representing a systematic spatial and temporal activation of primary and secondary sensory cortex. Spatiotemporal analysis of these waveforms indicated that they could be decomposed into a small number of spatial and temporal components; components that are related to patterns of specific and non-specific thalamocortical projections connecting the auditory and visual nuclei of the thalamus with primary and secondary auditory and visual cortex. These data suggest that the AEP and VEP complex are the cortical reflection of asynchronous activation of parallel thalamocortical projection systems. The areal distribution of the AEP and VEP also overlapped, primarily in secondary auditory and visual cortex, indicating that these regions contain populations of cells responding to either modality. Polymodal auditory-visual stimulation resulted in unique activation of two isolated populations of neurons positioned in secondary auditory and secondary visual cortex which were revealed by difference waveforms, computed by subtracting the sum of the AEP and VEP from the AVEP complex. Retrograde labeling of the polymodal zones indicated that they receive parallel thalamocortical projections primarily from non-specific auditory and visual thalamic nuclei including the medial and dorsal divisions of the medial geniculate nucleus (MGm and MGd), the suprageniculate nucleus (SGN), and the lateral posterior nucleus (LP). The polymodal zone in visual cortex also receives specific projections from the dorsal division of the lateral geniculate nucleus (LGd). These data conform to a general model of thalamocortical organization in which specific thalamic nuclei with a high degree of modality specificity make restricted projections to primary sensory cortex and parts of secondary sensory cortex, and association thalamic nuclei with a high degree of sensory convergence make more divergent cortical projections. Primary and secondary sensory cortex, as well as distinct zones of polysensory cortex appear to be activated in tandem via parallel thalamocortical projections. Thus, the cerebral cortex must have simultaneous access to both unimodal and polymodal sensory information.

The magnetic field of epileptic spikes agrees with intracranial localizations in complex partial epilepsy

The magnetoencephalogram (MEG) and electroencephalogram (EEG) were measured during interictal epileptic spikes in nine patients with complex partial seizures. The MEG localization estimates were compared with localizations by intraoperative cortical electrodes, subdural electrodes, stereotaxic depth electrodes, anatomic imaging, postoperative pathologic analysis, and postoperative follow-up. In all patients, MEG localization estimates were in the same lobe as the epileptic focus determined by invasive methods and EEG. In two patients, it was possible to quantify precisely the accuracy of MEG localization by mapping a spike focus that was visually indistinguishable on MEG and cortical recordings. In both patients, MEG localization was approximately 12 mm from the center of the cortical spike focus on intracranial recordings. In eight patients, MEG showed tangential dipolar field patterns on the spontaneous record, but EEG did not. In one patient, a cortical epileptic discharge was detected only on MEG for some discharges and only on EEG for other discharges. The MEG did not detect deep spikes with present levels of environmental noise.

Magnetic localization of a dipolar current source implanted in a sphere and a human cranium

Magnetic fields produced by a dipolar source implanted in a spherical conductor and a human cranial specimen were measured in the magnetoencephalogram (MEG). The location of the source was accurately computed in the spherical conductor from the identified magnetic field extrema using equations for a current dipole in a sphere. This same method was insufficient for localizing the source in a human cranium, where magnetic field maps appeared as distortions from the classical dipolar pattern. A more complete computer modeling procedure was used, adjusting for the non-spherical dimensions of the recording matrix on the cranium. By fitting the gradient of computer simulated fields to those measured outside the cranium, the accuracy of source localization was substantially improved. The greatest distortion of the extracranial magnetic field was an inequality in the measured amplitude of the two extrema, produced by an increased distance and angle of the MEG probe when recording over the lower face and ear. However, gross heterogeneities in the resistance of the skull due to a craniectomy and an implanted insulating balloon had a negligible effect on the extracranial magnetic field pattern.

The cortical innate immune response increases local neuronal excitability leading to seizures

Brain glial cells, five times more prevalent than neurons, have recently received attention for their potential involvement in epileptic seizures. Microglia and astrocytes, associated with inflammatory innate immune responses, are responsible for surveillance of brain damage that frequently results in seizures. Thus, an intriguing suggestion has been put forward that seizures may be facilitated and perhaps triggered by brain immune responses. Indeed, recent evidence strongly implicates innate immune responses in lowering seizure threshold in experimental models of epilepsy, yet, there is no proof that they can play an independent role in initiating seizures in vivo. Here, we show that cortical innate immune responses alone produce profound increases of brain excitability resulting in focal seizures. We found that cortical application of lipopolysaccharide, binding to toll-like receptor 4 (TLR4), triples evoked field potential amplitudes and produces focal epileptiform discharges. These effects are prevented by pre-application of interleukin-1 receptor antagonist. Our results demonstrate how the innate immune response may participate in acute seizures, increasing neuronal excitability through interleukin-1 release in response to TLR4 detection of the danger signals associated with infections of the central nervous system and with brain injury. These results suggest an important role of innate immunity in epileptogenesis and focus on glial inhibition, through pharmacological blockade of TLR4 and the pro-inflammatory mediators released by activated glia, in the study and treatment of seizure disorders in humans.

A multisensory zone in rat parietotemporal cortex: intra- and extracellular physiology and thalamocortical connections.

Multisensory integration is essential for the expression of complex behaviors in humans and animals. However, few studies have investigated the neural sites where multisensory integration may occur. Therefore, we used electrophysiology and retrograde labeling to study a region of the rat parietotemporal cortex that responds uniquely to auditory and somatosensory multisensory stimulation. This multisensory responsiveness suggests a functional organization resembling multisensory association cortex in cats and primates. Extracellular multielectrode surface mapping defined a region between auditory and somatosensory cortex where responses to combined auditory/somatosensory stimulation were larger in amplitude and earlier in latency than responses to either stimulus alone. Moreover, multisensory responses were nonlinear and differed from the summed unimodal responses. Intracellular recording found almost exclusively multisensory cells that responded to both unisensory and multisensory stimulation with excitatory postsynaptic potentials (EPSPs) and/or action potentials, conclusively defining a multisensory zone (MZ). In addition, intracellular responses were similar to extracellular recordings, with larger and earlier EPSPs evoked by multisensory stimulation, and interactions suggesting nonlinear postsynaptic summation to combined stimuli. Thalamic input to MZ from unimodal auditory and somatosensory thalamic relay nuclei and from multisensory thalamic regions support the idea that parallel thalamocortical projections may drive multisensory functions as strongly as corticocortical projections. Whereas the MZ integrates uni‐ and multisensory thalamocortical afferent streams, it may ultimately influence brainstem multisensory structures such as the superior colliculus. J. Comp. Neurol. 460:223–237, 2003.

Auditory, Somatosensory, and Multisensory Insular Cortex in the Rat

Compared with other areas of the forebrain, the function of insular cortex is poorly understood. This study examined the unisensory and multisensory function of the rat insula using high-resolution, whole-hemisphere, epipial evoked potential mapping. We found the posterior insula to contain distinct auditory and somatotopically organized somatosensory fields with an interposed and overlapping region capable of integrating these sensory modalities. Unisensory and multisensory responses were uninfluenced by complete lesioning of primary and secondary auditory and somatosensory cortices, suggesting a high degree of parallel afferent input from the thalamus. In light of the established connections of the posterior insula with the amygdala, we propose that integration of auditory and somatosensory modalities reported here may play a role in auditory fear conditioning.

Spatiotemporal modeling of cerebral evoked magnetic fields to median nerve stimulation

We measured somatosensory evoked magnetic fields during median nerve stimulation in 6 normal subjects. We applied multiple dipole models to study the spatiotemporal structure of early somatosensory evoked magnetic fields (SEFs), as well as the number, 3-dimensional location and time activity of their underlying neuronal sources. Two dipole sources were necessary to model the first 40 msec of SEFs explaining 85% of the data variance. Source 1 was located deeper than source 2, showed primarily a tangential orientation, and accounted for a larger part of the variance; source 2 showed no consistent orientation across subjects. Both sources showed biphasic time activities corresponding to the previously described N20-P30 and P25-N35 components. Spatiotemporal modeling could identify sources which could not be modeled consistently above noise by single moving dipoles (P25 component), revealed small latency differences of the two sources in some subjects suggesting parallel activation of these sources, and allowed separation of sources overlapping considerably both in space and time. We conclude that spatiotemporal modeling of SEFs may be useful to study functional anatomy of human sensorimotor cortex non-invasively.