Role of optically pumped magnetometers in presurgical epilepsy evaluation: Commentary of the American Clinical Magnetoencephalography Society.

One of the major challenges of modern epileptology is the underutilization of epilepsy surgery for treatment of patients with focal, medication resistant epilepsy (MRE). Aggravating this distressing failure to deliver optimum care to these patients is the underuse of proven localizing tools, such as magnetoencephalography (MEG), a clinically validated, non-invasive, neurophysiological method used to directly measure and localize brain activity. A sizable mass of published evidence indicates that MEG can improve identification of surgical candidates and guide pre-surgical planning, increasing the yield of SEEG and improving operative outcomes. However, despite at least 10 common, evidence supported, clinical scenarios in MRE patients where MEG can offer non-redundant information and improve the pre-surgical evaluation, it is regularly used by only a minority of USA epilepsy centers. The current state of the art in MEG sensors employs SQUIDs, which require cooling with liquid helium to achieve superconductivity. This sensor technology has undergone significant generational improvement since whole head MEG scanners were introduced around in 1990s, but still has limitations. Further advances in sensor technology which may make ME G more easily accessible and affordable have been eagerly awaited, and development of new techniques should be encouraged. Of late, optically pumped magnetometers (OPMs) have received considerable attention, even prompting some potential acquisitions of new MEG systems to be put on hold, based on a hope that OPMs will usher in a new generation of MEG equipment and procedures. The development of any new clinical test used to guide intracranial EEG monitoring and/or surgical planning must address several specific issues. The goal of this commentary is to recognize the current state of OPM technology and to suggest a framework for it to advance in the clinical realm where it can eventually be deemed clinically valuable to physicians and patients. The American Clinical MEG Society (ACMEGS) strongly supports more advanced and less expensive technology and looks forward to continuing work with researchers to develop new sensors and clinical devices which will improve the experience and outcome for patients, and perhaps extend the role of MEG. However, currently, there are no OPM devices ready for practical clinical use. Based on the engineering obstacles and the clinical tradeoffs to be resolved, the assessment of experts suggests that there will most likely be another decade relying solely on "frozen SQUIDs" in the clinical MEG field.

Music, Math, and Working Memory: Magnetoencephalography Mapping of Brain Activation in Musicians.

Musical transposing is highly demanding of working memory, as it involves mentally converting notes from one musical key (i.e., pitch scale) to another key for singing or instrumental performance. Because musical transposing involves mental adjustment of notes up or down by a specific amount, it may share cognitive elements with arithmetical operations of addition and subtraction. We compared brain activity during high and low working memory load conditions of musical transposing versus math calculations in classically trained musicians. Magnetoencephalography (MEG) was sensitive to differences of task and working memory load. Frontal-occipital connections were highly active during transposing, but not during math calculations. Right motor and premotor regions were highly active in the more difficult condition of the transposing task. Multiple frontal lobe regions were highly active across tasks, including the left medial frontal area during both transposing and calculation tasks but the right medial frontal area only during calculations. In the more difficult calculation condition, right temporal regions were highly active. In coherence analyses and neural synchrony analyses, several similarities were seen across calculation tasks; however, latency analyses were sensitive to differences in task complexity across the calculation tasks due to the high temporal resolution of MEG. MEG can be used to examine musical cognition and the neural consequences of music training. Further systematic study of brain activity during high versus low memory load conditions of music and other cognitive tasks is needed to illuminate the neural bases of enhanced working memory ability in musicians as compared to non-musicians.

Magnetoencephalography-identified preictal spiking correlates to preictal spiking on stereotactic EEG.

Magnetoencephalography (MEG) is a noninvasive diagnostic modality that directly measures neuronal signaling by recording the magnetic field created from dendritic, intracellular, electrical currents of the neuron at the surface of the head. In clinical practice, MEG is used in the epilepsy presurgical evaluation and most commonly is an "interictal" study that can provide source localization of spike-wave discharges. However, seizures may be recorded during MEG ("ictal MEG") and mapping of these discharges may provide more accurate localization of the seizure onset zone. In addition, spike-negative EEG with unique MEG spike-waves may be present in up to 1/3 of MEG studies and unique MEG seizures (EEG-negative seizures) have been reported. This case report describes a patient with unique MEG seizures that exhibited MEG pre-ictal spiking in a tight cluster consistent with the independent interictal epileptiform activity. Stereotactic EEG demonstrated pre-ictal spiking concordant with the MEG pre-ictal spiking.

Language Mapping With Magnetoencephalography: An Update on the Current State of Clinical Research and Practice With Considerations for Clinical Practice Guidelines.

Numerous studies have shown that language processing is not limited to a few brain areas. Visual or auditory stimuli activate corresponding cortical areas, then memory identifies the word or image, Wernicke's and Broca's areas support the processing for either reading/listening or speaking and many areas of the brain are recruited. Determining how a normal person processes language helps clinicians and scientist to understand how brain pathologies such as tumor or stroke can affect changes in language processing. Patients with epilepsy may develop atypical language organization. Over time, the chronic nature of epileptic activity, or changes from a tumor or stroke, can result in a shift of language processing area from the left to the right hemisphere, or re-routing of language pathways from traditional to non-traditional areas within the dominant left hemisphere. It is important to determine where these language areas are prior to brain surgery. MEG evoked responses reflecting cerebral activation of receptive and expressive language processing can be localized using several different techniques: Single equivalent current dipole, current distribution techniques or beamformer techniques. Over the past 20 years there have been at least 25 validated MEG studies that indicate MEG can be used to determine the dominant hemisphere for language processing. The use of MEG neuroimaging techniques is needed to reliably predict altered language networks in patients and to provide identification of language eloquent cortices for localization and lateralization necessary for clinical care.

Visual Mapping With Magnetoencephalography: An Update on the Current State of Clinical Research and Practice With Considerations for Clinical Practice Guidelines.

Using visual evoked fields (VEFs) to differentiate healthy, normal brain function from dysfunctional cortex has been demonstrated to be both valid and reliable. Currently, VEFs are widely implemented to guide intracranial surgeries for epilepsy and brain tumors. There are several areas of possible future clinical use of VEFs, including early identification of disorders, such as multiple sclerosis, Parkinson's disease, stroke, and human immunodeficiency virus-associated neurocognitive disorders. These studies have suggested that VEFs could be used to study disease pathophysiology or as a biomarker for early identification of a disorder. The current clinical practice guidelines of the American Clinical Magnetoencephalography Society for VEFs are sufficient. At this time, VEFs should be used clinically to identify visual cortex and potentially tailor surgical resections.

Predictive Processing during a Naturalistic Statistical Learning Task in ASD.

Children's sensitivity to regularities within the linguistic stream, such as the likelihood that syllables co-occur, is foundational to speech segmentation and language acquisition. Yet, little is known about the neurocognitive mechanisms underlying speech segmentation in typical development and in neurodevelopmental disorders that impact language acquisition such as autism spectrum disorder (ASD). Here, we investigate the neural signals of statistical learning in 15 human participants (children ages 8-12) with a clinical diagnosis of ASD and 14 age-matched and gender-matched typically developing peers. We tracked the evoked neural responses to syllable sequences in a naturalistic statistical learning corpus using magnetoencephalography (MEG) in the left primary auditory cortex, posterior superior temporal gyrus (pSTG), and inferior frontal gyrus (IFG), across three repetitions of the passage. In typically developing children, we observed a neural index of learning in all three regions of interest (ROIs), measured by the change in evoked response amplitude as a function of syllable surprisal across passage repetitions. As surprisal increased, the amplitude of the neural response increased; this sensitivity emerged after repeated exposure to the corpus. Children with ASD did not show this pattern of learning in all three regions. We discuss two possible hypotheses related to children's sensitivity to bottom-up sensory deficits and difficulty with top-down incremental processing.

Magnetoencephalography Signal Processing, Forward Modeling, Magnetoencephalography Inverse Source Imaging, and Coherence Analysis.

Magnetoencephalography (MEG) is a noninvasive functional imaging technique for the brain. MEG directly measures the magnetic signal due to neuronal activation in gray matter with high spatial localization accuracy. The first part of this article covers the overall concepts of MEG and the forward and inverse modeling techniques. It is followed by examples of analyzing evoked and resting-state MEG signals using a high-resolution MEG source imaging technique. Next, different techniques for connectivity and network analysis are reviewed with examples showing connectivity estimates from resting-state and epileptic activity.

Presurgical Functional Mapping with Magnetoencephalography.

Noninvasive functional brain imaging with magnetoencephalography (MEG) is regularly used to map the eloquent cortex associated with somatosensory, motor, auditory, visual, and language processing before a surgical resection to determine if the functional areas have been reorganized. Most tasks can also be performed in the pediatric population. To acquire an optimal MEG study for any of these modalities, the patient needs to be well rested and attending to the stimulation.

A Combination of Particle Swarm Optimization and Minkowski Weighted K-Means Clustering: Application in Lateralization of Temporal Lobe Epilepsy.

K-Means is one of the most popular clustering algorithms that partitions observations into nonoverlapping subgroups based on a predefined similarity metric. Its drawbacks include a sensitivity to noisy features and a dependency of its resulting clusters upon the initial selection of cluster centroids resulting in the algorithm converging to local optima. Minkowski weighted K-Means (MWK-Means) addresses the issue of sensitivity to noisy features, but is sensitive to the initialization of clusters, and so the algorithm may similarly converge to local optima. Particle Swarm Optimization (PSO) uses a globalized search method to solve this issue. We present a hybrid Particle Swarm Optimization (PSO) + MWK-Means clustering algorithm to address all the above problems in a single framework, while maintaining benefits of PSO and MWK Means methods. This study investigated the utility of this approach in lateralizing the epileptogenic hemisphere for temporal lobe epilepsy (TLE) cases using magnetoencephalography (MEG) coherence source imaging (CSI) and diffusion tensor imaging (DTI). Using MEG-CSI, we analyzed preoperative resting state MEG data from 17 adults TLE patients with Engel class I outcomes to determine coherence at 54 anatomical sites and compared the results with 17 age- and gender-matched controls. Fiber-tracking was performed through the same anatomical sites using DTI data. Indices of both MEG coherence and DTI nodal degree were calculated. A PSO + MWK-Means clustering algorithm was applied to identify the side of temporal lobe epileptogenicity and distinguish between normal and TLE cases. The PSO module was aimed at identifying initial cluster centroids and assigning initial feature weights to cluster centroids and, hence, transferring to the MWK-Means module for the final optimal clustering solution. We demonstrated improvements with the use of the PSO + MWK-Means clustering algorithm compared to that of K-Means and MWK-Means independently. PSO + MWK-Means was able to successfully distinguish between normal and TLE in 97.2% and 82.3% of cases for DTI and MEG data, respectively. It also lateralized left and right TLE in 82.3% and 93.6% of cases for DTI and MEG data, respectively. The proposed optimization and clustering methodology for MEG and DTI features, as they relate to focal epileptogenicity, would enhance the identification of the TLE laterality in cases of unilateral epileptogenicity.

Deficit Versus Nondeficit Schizophrenia: An MEG-EEG Investigation of Resting State and Source Coherence-Preliminary Data.

This study investigated the magneto- and electroencephalography (MEG and EEG, respectively) resting state to identify the deviations closely associated with the deficit syndrome (DS) in schizophrenia patients. Ten subjects in each group (control, DS, and nondeficit schizophrenia [NDS]) were included. Subjects underwent MEG-EEG recordings during a resting state condition. MEG coherence source imaging (CSI) in source space and spectral analysis in sensor space were performed. Significant differences were found between the 2 patient groups: (1) MEG and EEG spectral analysis showed significantly higher power at low frequencies (delta band) at sensor space in DS compared with NDS patients; (2) source analysis revealed larger power in the DS compared with NDS group at low frequencies in the frontal region; (3) NDS patients showed significantly higher MEG signal relative power in beta bands in sensor space compared with DS patients; (4) both DS and NDS patients showed higher EEG absolute power at higher beta band compared to controls; and (5) patients with DS were found to have a significantly higher MEG CSI than controls in the beta frequency band. These data support the observation of increased power in the low-frequency EEG/MEG rhythms associated with the DS. Increased power in the beta rhythms was more associated with the NDS.

Sensorimotor Integration and GABA-ergic Activity in Embouchure Dystonia: An Assessment with Magnetoencephalography.

Background: Embouchure dystonia (ED) is a task-specific dystonia affecting musicians thought to be related to alteration in sensorimotor processing and loss of cortical inhibition. Case Report: Magnetoencephalography-coherence source imaging (MEG-CSI) was used to map connectivity between brain regions by imaging neuronal oscillations that are coherent across the brain in patient with ED at rest and while using the index finger to evoke dystonia normally triggered by playing the flute. Discussion: During rest, there was increased coherence in the bilateral frontal and parietal regions that became more focal during dystonia. Diffuse hyperexcitability and increased coherence persisted in bilateral parietal regions as well as the bilateral frontal regions.

Evoked Potentials Investigations of Deficit Versus Nondeficit Schizophrenia: EEG-MEG Preliminary Data.

Heterogeneity of schizophrenia is a major obstacle toward understanding the disorder. One likely subtype is the deficit syndrome (DS) where patients suffer from predominantly negative symptoms. This study investigated the evoked responses and the evoked magnetic fields to identify the neurophysiological deviations associated with the DS. Ten subjects were recruited for each group (Control, DS, and Nondeficit schizophrenia [NDS]). Subjects underwent magnetoencephalography (MEG) and electroencephalography (EEG) testing while listening to an oddball paradigm to generate the P300 as well as a paired click paradigm to generate the mid-latency auditory-evoked responses (MLAER) in a sensory gating paradigm. MEG-coherence source imaging (CSI) during P300 task revealed a significantly higher average coherence value in DS than NDS subjects in the gamma band (30-80 Hz), when listening to standard stimuli but only NDS subjects had a higher average coherence level in the gamma band than controls when listening to the novel sounds. P50, N100, and P3a ERP amplitudes (EEG analysis) were significantly decreased in NDS compared with DS subjects. The data suggest that the deviations in the 2 patient groups are qualitatively different. Deviances in NDS patients suggest difficulty in both early (as in the gating paradigm), as well as later top-down processes (P300 paradigm). The main deviation in the DS group was an exaggerated responsiveness to ongoing irrelevant stimuli detected by EEG whereas NDS subjects had an exaggerated response to novelty.

Preliminary Evidence for Limbic-Frontal Hyperexcitability in Psychogenic Nonepileptic Seizure Patients.

OBJECTIVES: The goal of the current pilot project was to probe the resting-state magnetoencephalography (MEG) in individuals with psychogenic nonepileptic seizures (PNES) and ascertain if there is evidence for frontal temporal cortical hyperexcitability, as evidenced by increased focal coherence in these regions. METHODS: Six patients with PNES and without any evidence of epilepsy were included. Nine healthy control (HC) subjects (age matched as a group) were also included. Subjects underwent 10 minutes of eyes open and 10 minutes of eyes closed MEG recording without any specific cognitive tasks (ie, resting state). RESULTS: Analysis shows posterior-occipital alpha power to be decreased but fronto-temporal delta/theta power increased in people with PNES compared with HC subjects. Analyses of mean interregional functional connectivity of 54 brain regions, patients with PNES tended to have reduced mean coherence in extra-fronto-temporal regions (ex-FTRs) while increased mean coherence in fronto-temporal regions (FTRs) compared with HC. Furthermore, all 6 patients with PNES had their highest coherence structure within the FTRs. This is in contrast to the HC subjects where only 3 of the 9 subjects had their highest coherence value structure in the FTRs (χ2 = 6.67, P = .010). CONCLUSIONS: The above findings are consistent with a disbalance between frontotemporal and posterior brain regions in this population with possible increased excitability in the FTRs. The data support the need for further investigations of the pathophysiology of PNES. The identification of a biomarker for PNES would not only provide for more informed therapeutic approaches, but it could also eliminate the stigma associated with the diagnosis of PNES.

Sensory Trick in a Patient with Cervical Dystonia: Insights from Magnetoencephalography.

BACKGROUND: The proposed mechanisms for the sensory trick include peripheral sensory feedback to aid in correcting abnormal posture or movement. CASE REPORT: A 53-year-old woman with cervical dystonia underwent magnetoencephalography pre- and post-botulinum toxin injection and sensory trick, which was described as yawning. Study revealed connectivity between the left frontal and inferior frontal gyrus before yawning, which changed to the visual cortex and right middle frontal gyrus with yawning. Beta frequencies reduced and gamma frequencies increased after yawning. DISCUSSION: The increase in gamma frequency bands may indicate increased GABAergic activity. Increase in connectivity in the right cerebellar region underscores the importance of cerebellum in pathogenesis of dystonia.

Patterns of altered neural synchrony in the default mode network in autism spectrum disorder revealed with magnetoencephalography (MEG): Relationship to clinical symptomatology.

Disrupted neural synchrony may be a primary electrophysiological abnormality in autism spectrum disorders (ASD), altering communication between discrete brain regions and contributing to abnormalities in patterns of connectivity within identified neural networks. Studies exploring brain dynamics to comprehensively characterize and link connectivity to large-scale cortical networks and clinical symptoms are lagging considerably. Patterns of neural coherence within the Default Mode Network (DMN) and Salience Network (SN) during resting state were investigated in 12 children with ASD (MAge = 9.2) and 13 age and gender-matched neurotypicals (NT) (MAge = 9.3) with magnetoencephalography. Coherence between 231 brain region pairs within four frequency bands (theta (4-7 Hz), alpha, (8-12 Hz), beta (13-30 Hz), and gamma (30-80 Hz)) was calculated. Relationships between neural coherence and social functioning were examined. ASD was characterized by lower synchronization across all frequencies, reaching clinical significance in the gamma band. Lower gamma synchrony between fronto-temporo-parietal regions was observed, partially consistent with diminished default mode network (DMN) connectivity. Lower gamma coherence in ASD was evident in cross-hemispheric connections between: angular with inferior/middle frontal; middle temporal with middle/inferior frontal; and within right-hemispheric connections between angular, middle temporal, and inferior/middle frontal cortices. Lower gamma coherence between left angular and left superior frontal, right inferior/middle frontal, and right precuneus and between right angular and inferior/middle frontal cortices was related to lower social/social-communication functioning. Results suggest a pattern of lower gamma band coherence in a subset of regions within the DMN in ASD (angular and middle temporal cortical areas) related to lower social/social-communicative functioning. Autism Res 2018, 11: 434-449. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Communication between different areas of the brain was observed in children with ASD and neurotypical children while awake, but not working on a task. Magnetoencephalography was used to measure tiny magnetic fields naturally generated via brain activity. The brains of children with ASD showed less communication between areas that are important for social information processing compared to the brains of neurotypical children. The amount of communication between these areas was associated with social and social communication difficulties.

The Effect of Botulinum Toxin on Network Connectivity in Cervical Dystonia: Lessons from Magnetoencephalography.

Background: Pharmacological management of cervical dystonia (CD) is considered to be symptomatic in effect, rather than targeting the underlying pathophysiology of the disease. Magnetoencephalography (MEG), a direct measure of neuronal activity, while accepted as a modality for pre-surgical mapping in epilepsy, has never been used to explore the effect of pharmacotherapy in movement disorders. Methods: Resting state MEG data were collected from patients with CD, pre- and post-botulinum toxin injections. All of these patients exhibited good clinical benefit with botulinum toxin. Resting state MEG data from four age- and gender-matched healthy controls with no neurological disorders were also collected. Results: Our exploratory study reveals a difference in coherence between controls and patients in the following regions: fronto-striatal, occipito-striatal, parieto-striatal, and striato-temporal networks. In these regions there is an increase after botulinum toxin. Specifically, increased coherence in the left putamen and right superior parietal gyrus was noticeable. Both intrahemispheric and interhemispheric networks were affected. Discussion: This is the first attempt to directly assess changes in functional connectivity with pharmacotherapy using MEG. Botulinum toxin might affect sensorimotor integration, leading to clinical benefit. The presence of increased interhemispheric coherence and intrahemispheric coherence points to the importance of global and local networks in the pathophysiology of dystonia.

Multimodal Imaging in a Patient with Hemidystonia Responsive to GPi Deep Brain Stimulation.

BACKGROUND: Dystonia is a syndrome with varied phenomenology but our understanding of its mechanisms is deficient. With neuroimaging techniques, such as fiber tractography (FT) and magnetoencephalography (MEG), pathway connectivity can be studied to that end. We present a hemidystonia patient treated with deep brain stimulation (DBS). METHODS: After 10 years of left axial hemidystonia, a 45-year-old male underwent unilateral right globus pallidus internus (GPi) DBS. Whole brain MEG before and after anticholinergic medication was performed prior to surgery. 26-direction diffusion tensor imaging (DTI) was obtained in a 3 T MRI machine along with FT. The patient was assessed before and one year after surgery by using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). RESULTS: In the eyes-closed MEG study there was an increase in brain coherence in the gamma band after medication in the middle and inferior frontal region. FT demonstrated over 50% more intense ipsilateral connectivity in the right hemisphere compared to the left. After DBS, BFMDRS motor and disability scores both dropped by 71%. CONCLUSION: Multimodal neuroimaging techniques can offer insights into the pathophysiology of dystonia and can direct choices for developing therapeutics. Unilateral pallidal DBS can provide significant symptom control in axial hemidystonia poorly responsive to medication.

Comparing EEG Nonlinearity in Deficit and Nondeficit Schizophrenia Patients: Preliminary Data.

Electroencephalogram (EEG) contains valuable information obtained noninvasively that can be used for assessment of brain's processing capacity of patients with psychiatric disorders. The purpose of the present work was to evaluate possible differences in EEG complexity between deficit (DS) and nondeficit (NDS) subtypes of schizophrenia as a reflection of the cognitive processing capacities in these groups. A particular nonlinear metric known as Lempel-Ziv complexity (LZC) was used as a computational tool in order to determine the randomness in EEG alpha band time series from 3 groups (deficit schizophrenia [n = 9], nondeficit schizophrenia [n = 10], and healthy controls [n = 10]) according to time series randomness. There was a significant difference in frontal EEG complexity between the DS and NDS subgroups ( p = .013), with DS group showing less complexity. A significant positive correlation was found between LZC values and Positive and Negative Syndrome Scale (PANSS) general psychopathology scores (ie, larger frontal EEG complexity correlated with more severe psychopathology), explained partially by the emotional component subscore of the PANSS. These findings suggest that cognitive processing occurring in the frontal networks in DS is less complex compared to NDS patients as reflected by EEG complexity measures. The data also suggest that there may be a relationship between the degree of emotionality and the complexity of the frontal EEG signal.

A magnetoencephalography investigation of coherence source imaging in panic disorder.

Limbic and frontal structures are largely implicated in panic disorder (PD). Decreased coherence imaging values, as determined by magnetoencephalography (MEG), are suggestive of decreased or inefficient communication among these structures. We have previously demonstrated that coherence source imaging (CSI) values could be similar or higher in some PD patients. The purpose of the current investigation was to replicate these finding in a larger sample. Nine strictly diagnosed PD patients and nine age-matched and sex-matched healthy controls were examined. The CSI-MEG values of 26 frontotemporal regions (FTRs) and 28 extra-frontotemporal regions (ex-FTR; Brodmann areas) were determined for each participant. MEG scans were acquired using a 151-channel whole-head biomagnetometer system. Despite the relatively small sample size, CSI values were significantly lower in a number of FTRs in PD patients. In none of the ex-FTRs (i.e. posterior regions) were there differences between panic and control groups. The above data add to the complexity of understanding the nature of the pathophysiology of PD. Our finding of decreased focal coherence imaging values may reflect decreased excitability in these areas. The preliminary finding could be interpreted as an inhibitory process guarding against the spread of activity in closer hyperexcitable areas as seen in epilepsy. The current data provide evidence for dysfunctional communication within the frontotemporal structures. The findings have implications for the understanding of the neural circuitry underlying PD.