Jeffrey David Lewine

N400-like Magnetoencephalography Responses Modulated by Semantic Context, Word Frequency, and Lexical Class in Sentences

Words have been found to elicit a negative potential at the scalp peaking at approximately 400 ms that is strongly modulated by semantic context. The current study used whole-head magnetoencephalography (MEG) as male subjects read sentences ending with semantically congruous or incongruous words. Compared with congruous words, sentence-terminal incongruous words consistently evoked a large magnetic field over the left hemisphere, peaking at approximately 450 ms. Source modeling at this latency with conventional equivalent current dipoles (ECDs) placed the N400 m generator in or near the left superior temporal sulcus. A distributed solution constrained to the cortical surface suggested a sequence of differential activation, beginning in Wernickes area at approximately 250 ms, spreading to anterior temporal sites at approximately 270 ms, to Brocas area by approximately 300 ms, to dorsolateral prefrontal cortices by approximately 320 ms, and to anterior orbital and frontopolar cortices by approximately 370 ms. Differential activity was exclusively left-sided until >370 ms, and then involved right anterior temporal and orbital cortices. At the peak of the N400 m, activation in the left hemisphere was estimated to be widespread in the anterior temporal, perisylvian, orbital, frontopolar, and dorsolateral prefrontal cortices. In the right hemisphere, the orbital, as well as, weakly, the right anterior temporal cortices were activated. Similar but weaker field patterns were evoked by intermediate words in the sentences, especially to low-frequency words occurring in early sentence positions where there is little preceding context. The locations of the N400 m sources identified with the distributed solution correspond well with those previously demonstrated with direct intracranial recordings, and suggested by functional magnetic resonance imaging (fMRI). These results help identify a distributed cortical network that supports online semantic processing.

Magnetic source imaging: a review of the Magnes system of biomagnetic technologies incorporated.

Magnetic source imaging (MSI) is a new, noninvasive technique for defining the relationship between brain function and structure on a patient-to-patient basis. It achieves this by combining detailed neurophysiological data derived from magnetoencephalography with high-quality neuroanatomical data derived via magnetic resonance imaging. By the use of mathematical models, the spatial locations of those neurons that generate neuromagnetic signals of interest are estimated and subsequently marked on spatially aligned magnetic resonance images. There are three prominent types of clinical MSI examinations. These are: 1) functional mapping examinations in which sensory and motor functions are localized; 2) examinations of interictal epileptiform activity; and 3) examinations of abnormal low-frequency magnetic activity, which has been found to be present in a wide range of pathophysiological conditions. Functional mapping provides useful information regarding the relationship between the cortical representation of eloquent function and the location of pathological lesions that may be surgically resectable. This application is of particular utility in cases of intracortical masses that distort and obscure the local neuroanatomy. By defining the primary sites of interictal epileptiform activity, MSI examinations are useful in the surgical planning for the implantation of depth electrodes and the planning of partial lobectomies. Abnormal low-frequency magnetic activity appears to be a neurophysiological correlate of ischemic penumbra associated with stroke, neoplasms, and vascular malformations. Abnormal low-frequency magnetic activity has also been found to be present in several other conditions, including head trauma and psychiatric dysfunction, although the exact pathophysiological mechanisms are presently unclear.(ABSTRACT TRUNCATED AT 250 WORDS)

Utilization of multichannel magnetoencephalography in the guidance of ablative seizure surgery

Abstract Magnetoencephalography (MEG) was used to evaluate 50 seizure surgery candidates. Interictal spikes were recorded in 42 cases. Of 20 cases with other data suggesting a convexity (lateral neocortical) focus, MEG spikes were recorded from 19. In 17, MEG and electrographic data were localized to the same region. Invasive studies were or could have been avoided in 11 cases based on MEG and other noninvasive data. MEG spike data were present in 14 of 18 cases with anteromesial temporal foci, being localized to the same lobe as electrographic data in 11. MEG was not of value in surgical planning of cases with orbitofrontal foci, or depth nonlocalized seizures. Twenty-seven patients with MEG epileptiform data have had postoperative follow-up. Fourteen of 19 with electrographic and MEG data localized to the same region are seizure-free. Four of eight with spatial discordance of MEG and electrographic data are seizure-free. Preliminary conclusions are as follows: When MEG and electrographic data are localized to the same region, seizure-free surgical outcome is more likely. In convexity cases with MEG and noninvasive electrographic data localized to the same region, preoperative invasive studies may be unnecessary.

Fluctuating asymmetry and the human brain

Adaptive development requires the organism to resist genetic and environmental stresses that disrupt the genetic plan for growth, a buffering capacity termed developmental stability. Developmental instability is revealed by fluctuating asymmetry (FA), which has been demonstrated in many species to reflect phenotypic and genetic quality. We report (1) that a measure of developmental instability based on body FA predicts deviation from typical brain asymmetry, (2) that a combined measure of atypical brain asymmetry and body FA correlated negatively with the area of the corpus callosum, especially the portion connecting the left and right planum temporale, and (3) that this combined measure also predicted atypical asymmetry of the size of the somatosensory representation of the two hands, as determined from magnetic source imaging.

A review of traditional and novel treatments for seizures in autism spectrum disorder: findings from a systematic review and expert panel

Despite the fact that seizures are commonly associated with autism spectrum disorder (ASD), the effectiveness of treatments for seizures has not been well studied in individuals with ASD. This manuscript reviews both traditional and novel treatments for seizures associated with ASD. Studies were selected by systematically searching major electronic databases and by a panel of experts that treat ASD individuals. Only a few anti-epileptic drugs (AEDs) have undergone carefully controlled trials in ASD, but these trials examined outcomes other than seizures. Several lines of evidence point to valproate, lamotrigine, and levetiracetam as the most effective and tolerable AEDs for individuals with ASD. Limited evidence supports the use of traditional non-AED treatments, such as the ketogenic and modified Atkins diet, multiple subpial transections, immunomodulation, and neurofeedback treatments. Although specific treatments may be more appropriate for specific genetic and metabolic syndromes associated with ASD and seizures, there are few studies which have documented the effectiveness of treatments for seizures for specific syndromes. Limited evidence supports l-carnitine, multivitamins, and N-acetyl-l-cysteine in mitochondrial disease and dysfunction, folinic acid in cerebral folate abnormalities and early treatment with vigabatrin in tuberous sclerosis complex. Finally, there is limited evidence for a number of novel treatments, particularly magnesium with pyridoxine, omega-3 fatty acids, the gluten-free casein-free diet, and low-frequency repetitive transcranial magnetic simulation. Zinc and l-carnosine are potential novel treatments supported by basic research but not clinical studies. This review demonstrates the wide variety of treatments used to treat seizures in individuals with ASD as well as the striking lack of clinical trials performed to support the use of these treatments. Additional studies concerning these treatments for controlling seizures in individuals with ASD are warranted.

Comparison of primary motor cortex localization using functional magnetic resonance imaging and magnetoencephalography

The primary goal of the study was to compare estimates of motor cortex localization from functional magnetic resonance imaging (FMRI) and magnetoencephalography (MEG). Thirteen normal volunteers were studied using both methods. FMRI was performed on a clinical 1.5 T system using gradient‐echo acquisitions and basic t‐test processing. MEG primary motor field was characterized by a single dipole model. Comparisons between the location of the best‐fitting MEG dipole and the FMRI activation results were made using both fixed regions‐of‐interest weighted averaging and clustering analysis to reduce the observed FMRI activations to a single representative location.

American Clinical Magnetoencephalography Society Clinical Practice Guideline 2: Presurgical Functional Brain Mapping Using Magnetic Evoked Fields

The following are “minimum standards” for the routine clinical recording of magnetic evoked fields (MEFs) in all age-groups. Practicing at minimum standards should not be the goal of a magnetoencephalography (MEG) center but rather a starting level for continued improvement. Minimum standards meet only the most basic responsibilities to the patient and the referring physician. These minimum standards have been put forth to improve standardization of procedures, to facilitate interchange of recordings and reports among laboratories in the United States, and to confirm the expectations of referring physicians. Recommendations regarding Laboratory (Center) Environment and Preparation for MEG Recordings are detailed in the American Clinical Magnetoencephalography Society Clinical Practice Guideline (CPG) 1 : Recording and Analysis of Spontaneous Cerebral Activity, except for its EEG aspect that is not considered necessary (although may be helpful in trained hands) for MEFs (presurgical functional brain mapping).

Reduced auditory M100 asymmetry in schizophrenia and dyslexia : Applying a developmental instability approach to assess atypical brain asymmetry

Although atypical structural and functional superior temporal gyrus (STG) asymmetries are frequently observed in patients with schizophrenia and individuals with dyslexia, their significance is unclear. One possibility is that atypical asymmetries reflect a general risk factor that can be seen across multiple neurodevelopmental conditions--a risk factor whose origins are best understood in the context of Developmental Instability (DI) theory. DI measures (minor physical anomalies (MPAs) and fluctuating asymmetries (FAs)) reflect perturbation of the genetic plan. The present study sought to assess whether the presence of peripheral indices of DI predicts anomalous functional auditory cortex asymmetry in schizophrenia patients and dyslexia subjects. The location of the auditory M100 response was used as a measure of functional STG asymmetry, as it has been reported that in controls (but not in subjects with schizophrenia or dyslexia) the M100 source location in the right hemisphere is shifted anterior to that seen for the left hemisphere. Whole-brain auditory evoked magnetic field data were successfully recorded from 14 male schizophrenia patients, 21 male subjects with dyslexia, and 16 normal male control subjects. MPA and FA measures were also obtained. Replicating previous studies, both schizophrenia and dyslexia groups showed less M100 asymmetry than did controls. Schizophrenia and dyslexia subjects also had higher MPA scores than normal controls. Although neither total MPA nor FA measures predicted M100 asymmetry, analyses on individual MPA items revealed a relationship between high palate and M100 asymmetry. Findings suggest that M100 positional asymmetry is not a diagnostically specific feature in several neurodevelopmental conditions. Continued research examining DI and brain asymmetry relationships is warranted.

The role of magnetoencephalography in “nonlesional” epilepsy

The surgical management of neocortical epilepsy is challenging because many patients are without obvious structural lesions, or lesions are small and easily overlooked during routine clinical interpretation of magnetic resonance imaging (MRI) data. Even when functional imaging data suggest focal epileptiform pathology, in the absence of a concordant structural lesion, invasive monitoring is often required to confirm that an appropriate surgical target has been identified. This study sought to determine the extent to which knowledge of magnetoencephalography (MEG) data can augment the MRI‐based detection of structural brain lesions. MRI and whole‐head MEG data were obtained from 40 patients with neocortical epilepsy. As a result of MEG data, 29 cases were sent for MRI reevaluation. In seven of these cases, MEG‐guided review led to specification of now clear, but previously unidentified, lesions. There were two additional cases for which follow‐up high‐resolution imaging did not confirm structural abnormalities. In patients with neocortical epilepsy, MEG is a useful adjunct to MRI for the identification of structural lesions.

Areas of interictal spiking are associated with Metabolic dysfunction in MRI-negative temporal lobe epilepsy

Summary:  Purpose: The objective of our study was to determine noninvasively whether metabolic dysfunction is present in focal areas of interictal electrophysiologic abnormality and whether metabolic dysfunction correlates with frequency of spiking.