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The basal ganglia-thalamocortical (BGTC) loop may underlie speech deficits in developmental stuttering. In this study, we investigated the relationship between abnormal cortical neural oscillations and structural integrity alterations in adults who stutter (AWS) using a novel magnetoencephalography (MEG) guided tractography approach. Beta oscillations were analyzed using sensorimotor speech MEG, and white matter pathways were examined using tract-based spatial statistics (TBSS) and probabilistic tractography in 11 AWS and 11 fluent speakers. TBSS analysis revealed overlap between cortical regions of increased beta suppression localized to the mouth motor area and a reduced fractional anisotropy (FA) in the AWS group. MEG-guided tractography showed reduced FA within the BGTC loop from left putamen to subject-specific MEG peak. This is the first study to provide evidence that structural abnormalities may be associated with functional deficits in stuttering and reflect a network deficit within the BGTC loop that includes areas of the left ventral premotor cortex and putamen., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Recent literature on speech production in adults who stutter (AWS) has begun to investigate the neural mechanisms characterizing speech-motor preparation prior to speech onset. Compelling evidence has suggested that stuttering is associated with atypical processing within cortical and sub-cortical motor networks, particularly in the beta frequency range, that is effective before speech production even begins. Due to low stuttering frequency in experimental settings, however, the literature has so far predominantly reported on fluent speech production in AWS. Consequently, we have limited understanding of the way in which fluent speech processing in AWS is disturbed leading to a dysfluency. This preliminary study aims to characterize neural motor preparation prior to stuttered utterances in AWS., Methods: Eight AWS participated in the study. A total of 336 stuttered utterances were compared to the participants' own fluent utterance productions. Beta oscillatory activity was analyzed with magnetoencephalography (MEG) and localized using minimum-variance beamforming., Results: Preparation for speech production induced beta suppression in the bilateral premotor and motor cortex prior to speech onset. Although the data revealed some interesting trends, no significant differences between fluent and stuttered utterances were present. This may be due to a relatively low and variable number of stuttered trials analyzed in individual subjects., Conclusion: While the lack of significant differences may have resulted from the relatively low numbers of stuttered utterances across subjects, the observed trends demonstrated that the proposed methodology and experimental paradigm is a promising approach for future studies aiming to characterize differences between stuttered and fluent speech., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To assess the reliability of MEG source imaging (MSI) of anterior temporal spikes through detailed analysis of the localization and orientation of source solutions obtained for a large number of spikes that were separately confirmed by intracranial EEG to be focally generated within a single, well-characterized spike focus., Methods: MSI was performed on 64 identical right anterior temporal spikes from an anterolateral temporal neocortical spike focus. The effects of different volume conductors (sphere and realistic head model), removal of noise with low frequency filters (LFFs) and averaging multiple spikes were assessed in terms of the reliability of the source solutions., Results: MSI of single spikes resulted in scattered dipole source solutions that showed reasonable reliability for localization at the lobar level, but only for solutions with a goodness-of-fit exceeding 80% using a LFF of 3 Hz. Reliability at a finer level of intralobar localization was limited. Spike averaging significantly improved the reliability of source solutions and averaging 8 or more spikes reduced dependency on goodness-of-fit and data filtering., Conclusions: MSI performed on topographically identical individual spikes from an intracranially defined classical anterior temporal lobe spike focus was limited by low reliability (i.e., scattered source solutions) in terms of fine, sublobar localization within the ipsilateral temporal lobe. Spike averaging significantly improved reliability., Significance: MSI performed on individual anterior temporal spikes is limited by low reliability. Reduction of background noise through spike averaging significantly improves the reliability of MSI solutions., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: To assess the reliability and validity of EEG source localization of anterior temporal lobe spikes through direct comparison with simultaneously recorded intracranial spike fields., Methods: We recently showed that classical anterior temporal spikes recorded in mesial temporal lobe epilepsy (MTLE) are non-propagated potentials generated in the anterolateral temporal neocortex (Wennberg et al., 2011). In this study EEG source imaging (ESI) was performed on 64 identical right anterior temporal spikes (and 48 homologous left anterior temporal spikes) in a patient with MTLE investigated with simultaneous depth and subdural intracranial EEG and 27 channel scalp EEG. The effects of different realistic forward models, low frequency filters (LFFs) and spike averaging were assessed in terms of the reliability and physiologic validity of the source solutions., Results: Dipole mapping and distributed source modeling solutions for the grand average of all spikes were accurately localized to the superficial anterolateral temporal neocortex within 1cm of the intracranially defined spike generator, irrespective of forward model or LFF. ESI of single spikes, however, showed poor reliability (i.e., dissimilar localization results for intracranially identical spikes). Even with an optimal combination of individualized volume conductor and 3Hz LFF more than one third of single spike source solutions were physiologically invalid. Spike averaging, especially of 8 or more spikes, significantly increased the proportion of valid source solutions., Conclusions: ESI of individual anterior temporal spikes was limited by low reliability and a high likelihood of physiologically invalid source solutions. Spike averaging of 8 or more identical spikes prior to ESI, however, reliably produced accurate source solutions localized to the anterolateral temporal neocortex., Significance: ESI performed on averages of identical spikes can provide highly accurate noninvasive source localization of the anterolateral temporal neocortical region responsible for generating classical anterior temporal lobe spikes. The reliability and validity of ESI performed on individual spikes, however, is relatively limited., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: To evaluate the utility of an event-related beamforming (ERB) algorithm in source localization of interictal discharges., Methods: We analyzed interictal magnetoencephalography data in 35 children with intractable neocortical epilepsy. We used a spatiotemporal beamforming method to estimate the spatial distribution of source power in individual interictal spikes. We compared ERB results to source localization using the equivalent current dipole model and to the seizure onset zones on intracranial EEG., Results: Focal beamformer localization was observed in 66% of patients and multifocal in the remaining 34%. ERB localized within 2 cm of the equivalent current dipole cluster centroid in 77% of the patients. ERB localization was concordant with the seizure onset zone on intracranial EEG at the gyral level in 69% of patients. Focal ERB localization area was included in the resection margin in 22/23 patients. However, focal ERB localization was not statistically associated with better surgical outcome., Conclusions: ERB can be used for source localization of interictal spikes and can be predictive of the ictal onset zone in a subset of patients with neocortical epilepsy., Significance: These results support the utility of beamformer source localization as a fast semi-automated method for source localization of interictal spikes and planning the surgical strategy., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: To assess whether existing noninvasive source localization techniques can provide valid solutions for large extended cortical sources we tested the capability of various methods of EEG source imaging (ESI) and magnetic source imaging (MSI) to localize the large superficial cortical generator of the human K-complex., Methods: We recently determined the intracranial distribution of the K-complex in a study of 6 patients with epilepsy (Clin. Neurophysiol. 121 (2010) 1176). Here we use the simultaneously acquired scalp EEG data to evaluate the validity and reliability of different ESI techniques. MEG recordings were acquired in 3 of the 6 patients, and K-complexes were recorded with high density EEG and MEG in an additional subject without epilepsy. ESI forward models included finite element method and boundary element method (BEM) volume conductors; for MSI, single sphere and BEM models were assessed. Inverse models included equivalent current dipole mapping and distributed current source modeling algorithms., Results: ESI and MSI provided physiologically invalid source solutions in all subjects, incorrectly localizing K-complex generators to deep midline structures. ESI provided consistent localization results across subjects for individual and averaged K-complexes, indicating solutions were not influenced by random noise or choice of model parameters. MEG K-complexes were lower in amplitude relative to baseline than EEG K-complexes, with less consistent localization results even after signal averaging, likely due to MEG-specific signal cancellation and sensitivity to source orientation. Distributed source modeling did not resolve the known problem of excessively deep fitting of single dipole locations for extended cortical sources., Conclusions: Various noninvasive ESI and MSI techniques tested did not provide localization results for individual or averaged K-complexes that were physiologically meaningful or concordant with source locations indicated by intracranial recordings. Distributed source algorithms, though theoretically more appropriate for localizing extended cortical sources, showed the same propensity as dipole mapping to provide deep midline solutions for an extended superficial cortical source. Further studies are needed to determine appropriate modeling approaches for these large electrographic events., Significance: Existing noninvasive source localization techniques may not provide valid solutions for large extended cortical sources such as the human K-complex., (Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: There is persistent debate as to whether or not EEG and MEG recordings in patients with mesial temporal lobe epilepsy (MTLE) can detect mesial temporal interictal epileptiform discharges (spikes), and this issue is particularly relevant for source localization studies. With the aim of providing direct evidence pertinent to this debate we present detailed examples of the intracranial sources of spikes recorded with EEG and MEG in MTLE., Methods: Spikes recorded in five different patients with MTLE during intracranial EEG (n=2), intraoperative electrocorticography (ECOG; n=1), combined scalp-intracranial EEG (n=2) and combined EEG-MEG (n=1) were analyzed and the intracranial sources of the spike foci were matched with their corresponding extracranial EEG and/or MEG fields. EEG and MEG dipole source localization was performed on six independent spike foci identified in one representative patient with bilateral MTLE., Results: Spikes with an electrical field maximal at F7/8, F9/10≥T3/4 were generated in the anterolateral temporal neocortex. The absence of coincident spiking at mesial locations indicated that these were not propagated from or to the hippocampus. Spikes with an electrical field maximal at T3/4≥T9/10 were generated in the lateral temporal neocortex and likewise did not involve the hippocampus. Individual spikes generated in the mesiobasal temporal neocortex, including the fusiform gyrus, were difficult to detect with EEG (low amplitude diphasic waves most apparent after spike averaging at T3/4, T9/10≥T5/6, P9/10) and only slightly more identifiable with MEG. Spikes generated within and confined to the mesial temporal structures, as confirmed by intracranial recordings, could not be detected with EEG or MEG. Notably, such spikes could not be detected even at intracranial recording sites on the lateral surface of the temporal lobe., Conclusions: We present detailed evidence in a small case series showing that typical anterior temporal spikes recorded with EEG and MEG in MTLE arose from the anterolateral temporal neocortex and were neither propagated from nor to the hippocampus. Mid temporal EEG spikes were localized to the lateral temporal neocortex. Intracranially detected mesial temporal spikes were not detected with EEG or MEG., Significance: The spikes recorded with EEG and MEG in MTLE are localized to neocortical foci, and not to the mesial temporal structures. Current noninvasive EEG and MEG source localization studies cannot accurately identify true mesial temporal spikes., (Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Cortical oscillations in the sensorimotor region in the 8-12-Hz range ("mu rhythms") are associated with basic somatosensory and motor processes as well as top-down processes such as learning, attention, expectancy, and inhibition. Recent studies suggest that reactivity of these rhythms to sensory input reflects a link between perception and action and that abnormalities in this reactivity might reflect impairment in perception-to-action mechanisms. Individuals with attention-deficit/hyperactivity disorder (ADHD) are impaired in tasks requiring sensorimotor function, attention, expectancy, and inhibition, yet their sensorimotor mu responses are unknown. Thus, we investigated mu reactivity in a group of adults with ADHD., Methods: Sixteen adults with ADHD and 16 matched control subjects received median nerve stimulation in predictable patterns (trains of four stimuli followed by 4-sec gap) or unpredictable patterns (randomly presented trains of two, four, or six stimuli followed by 4-sec gap). With magnetoencephalography, we examined the effects of stimulus patterning (predictable, unpredictable) on mu reactivity to somatosensory stimuli., Results: Compared with control subjects, the ADHD group showed lower mu reactivity overall and no modulation by unpredictable somatosensory input. By contrast, the control group showed robust mu reactivity to stimuli presented in unpredictable but not predictable patterns. These changes were stronger in the contralateral hemisphere compared with the ADHD group., Conclusions: Cortical mu rhythms are modulated by stimulus predictability and might be involved in attentional alerting (awareness of when an unexpected stimulus occurs). Diminished mu modulation in adult ADHD suggests a possible underlying deficit in the perception-to-action system.

Objective: We studied the task-induced spatiotemporal evolution and characteristics of cortical neural oscillations in children during an auditory word recognition task., Methods: We presented abstract nouns binaurally and recorded the MEG response in eight healthy right-handed children (6-12 years). We calculated the event-related changes in cortical oscillations using a beamformer spatial filter analysis technique (SAM), then transformed each subject's statistical maps into standard space and used these to make group statistical inferences., Results: Across subjects, the cortical response to words could be divided into at least two phases: an initial event-related synchronization in both the right temporal (100-300 ms, 15-25 Hz; 200-400 ms, 5-15 Hz) and left frontal regions (200-400 ms; 15-25 Hz); followed by a strong left-lateralized event-related desynchronization in the left temporal region (500-700 ms; 5-15 Hz)., Conclusions: We found bilateral event-related synchronization followed by later left lateralized event-related desynchronization in language-related cortical areas. These data demonstrate the spatiotemporal time course of neural activation during an auditory word recognition task in a group of children. As well, this demonstrates the utility of SAM analyses to detect subtle sequential task-related neural activations.

Objective: We describe the application of a new spatial filtering technique--event-related beamforming (ERB)--for presurgical functional mapping of primary sensory areas using MEG. This method provides an alternative to equivalent current dipole (ECD) modeling that potentially eliminates problems of intracranial magnetic artifacts due to movement of ferromagnetic materials (e.g., orthodontic braces) or eye movements., Methods: We compared localization results for ERB and ECD localization of primary somatosensory (M20) and auditory (M100) evoked responses in 12 healthy control subjects and four subjects with metallic dental implants. Data were recorded with a 151-channel CTF MEG system using standard presurgical mapping protocols., Results: We found a high level of agreement between the two methods in control subjects (overall localization difference was 5.9+/-2.2 mm for M20 and 10.4+/-5.6 mm for M100). Subjects with dental implants showed severely distorted evoked responses that could not be analyzed using ECD, whereas the ERB method localized sources to expected anatomical locations., Conclusions: MEG functional mapping may be carried out without removal of orthodontic or other metallic implants using event-related beamformer analysis., Significance: Spatial filtering methods can overcome some of the limitations associated with MEG expanding its applicability, particularly in pediatric clinical environments.

Techniques for localizing auditory (AEF) sources are a topic of on-going discussion and this is particularly pertinent in pediatric research. Smaller head sizes are: (1) subject to bilateral temporal lobe source interference from both temporal lobes; and (2) further from MEG sensors resulting in poorer signal-to-noise ratios. An additional consideration in children is that the components of the AEF have distinct contributions along the development spectrum resulting in an ever-changing morphology for the pediatric AEF. These factors present a complicated picture for dipole fitting and raise the question of the most effective fitting strategy. We examined the AEF localizations in five children from 151, 70 and 47 MEG channels of data. We found evidence that bilateral source interaction could result in localization errors along the medial-lateral axis of up to 1 cm. We suggest that any modeling strategy needs to sufficiently account for this interaction and more precise models allowing for multiple sources need to be developed.