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Background: Freezing of gait (FOG) is a debilitating symptom of Parkinson's disease (PD) characterized by paroxysmal episodes in which patients are unable to step forward. A research priority is identifying cortical changes before freezing in PD-FOG., Methods: We tested 19 patients with PD who had been assessed for FOG (n=14 with FOG and 5 without FOG). While seated, patients stepped bilaterally on pedals to progress forward through a virtual hallway while 64-channel EEG was recorded. We assessed cortical activities before and during lower limb motor blocks (LLMB), defined as a break in rhythmic pedaling, and stops, defined as movement cessation following an auditory stop cue. This task was selected because LLMB correlates with FOG severity in PD and allows recording of high-quality EEG. Patients were tested after overnight withdrawal from dopaminergic medications ("off" state) and in the "on" medications state. EEG source activities were evaluated using individual MRI and standardized low resolution brain electromagnetic tomography (sLORETA). Functional connectivity was evaluated by phase lag index between seeds and pre-defined cortical regions of interest., Results: EEG source activities for LLMB vs. cued stops localized to right posterior parietal area (Brodmann area 39), lateral premotor area (Brodmann area 6), and inferior frontal gyrus (Brodmann area 47). In these areas, PD-FOG (n=14) increased alpha rhythms (8-12 Hz) before LLMB vs. typical stepping, whereas PD without FOG (n=5) decreased alpha power. Alpha rhythms were linearly correlated with LLMB severity, and the relationship became an inverted U-shape when assessing alpha rhythms as a function of percent time in LLMB in the "off" medication state. Right inferior frontal gyrus and supplementary motor area connectivity was observed before LLMB in the beta band (13-30 Hz). This same pattern of connectivity was seen before stops. Dopaminergic medication improved FOG and led to less alpha synchronization and increased functional connections between frontal and parietal areas., Conclusions: Right inferior parietofrontal structures are implicated in PD-FOG. The predominant changes were in the alpha rhythm, which increased before LLMB and with LLMB severity. Similar connectivity was observed for LLMB and stops between the right inferior frontal gyrus and supplementary motor area, suggesting that FOG may be a form of "unintended stopping." These findings may inform approaches to neurorehabilitation of PD-FOG., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Recent evidence shows that hippocampal theta oscillations, usually linked to memory and navigation, are also observed during online language processing, suggesting a shared neurophysiological mechanism between language and memory. However, it remains to be established what specific roles hippocampal theta oscillations may play in language, and whether and how theta mediates the communication between the hippocampus and the perisylvian cortical areas, generally thought to support language processing. With whole-head magnetoencephalographic (MEG) recordings, the present study investigated these questions with two experiments. Using a violation paradigm, extensively used for studying neural underpinnings of different aspects of linguistic processing, we found increased theta power (4-8 ​Hz) in the hippocampal formation, when participants read a semantically incorrect vs. correct sentence ending. Such a pattern of results was replicated using different sentence stimuli in another cohort of participants. Importantly, no significant hippocampal theta power increase was found when participants read a semantically correct but syntactically incorrect sentence ending vs. a correct sentence ending. These findings may suggest that hippocampal theta oscillations are specifically linked to lexical-semantic related processing, and not general information processing in sentence reading. Furthermore, we found significantly transient theta phase coupling between the hippocampus and the left superior temporal gyrus, a hub area of the cortical network for language comprehension. This transient theta phase coupling may provide an important channel that links the memory and language systems for the generation of sentence meaning. Overall, these findings help specify the role of hippocampal theta in language, and provide a novel neurophysiological mechanism at the network level that may support the interface between memory and language., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

In rodents, hippocampal cell assemblies formed during learning of a navigation task are observed to re-emerge during resting (offline) periods, accompanied by high-frequency oscillations (HFOs). This phenomenon is believed to reflect mechanisms for strengthening newly-formed memory traces. Using magnetoencephalography recordings and a beamforming source location algorithm (synthetic aperture magnetometry), we investigated high-gamma (80-140 Hz) oscillations in the hippocampal region in 18 human participants during inter-trial rest periods in a virtual navigation task. We found right hippocampal gamma oscillations mirrored the pattern of theta power in the same region during navigation, varying as a function of environmental novelty. Gamma power during inter-trial rest periods was positively correlated with theta power during navigation in the first task set when the environment was new and predicted greater performance improvement in the subsequent task set two where the environment became familiar. These findings provide evidence for human hippocampal reactivation accompanied by high-gamma activities immediately after learning and establish a link between hippocampal high-gamma activities and subsequent memory performance., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Cognitive control may involve adjusting behaviour by inhibiting or altering habitual actions, requiring rapid communication between sensory, cognitive, and motor systems of the brain. Cognitive control may be achieved using top-down processing from frontal areas to inhibit prepared responses, likely mediated through frontal theta (4-8 Hz) oscillations. However there is conflicting evidence for mechanisms of response inhibition, where global and selective inhibition are either considered separate processes, or frontal areas maintain and execute goal-directed actions, including inhibition. In the current study we measured neuromagnetic oscillatory brain activity in twelve adults responding to rapidly presented visual cues. We used two tasks in the same subjects that required inhibition of a habitual "go" response. Presentation of infrequent "target" cues required subjects to completely inhibit responding (go/no-go task) or to perform an alternate response (go/switch task). Source analysis of oscillatory brain activity was compared for correct no-go and switch trials as well as error trials ("go" responses to targets). Frontal theta activity was similar in cortical location, amplitude and time course for correct no-go and switch responses reflecting an equivalent role in both global and selective response inhibition. Error-related frontal theta activity was also observed but was different in source location (errors vs correct, both tasks: p<0.005) and power (go/switch>go/no-go error, correct switch power, p=0.01). We additionally observed sensorimotor high gamma (60-90 Hz) activity accompanying motor responses, which was markedly stronger for correct switch and error responses compared with go responses, and was delayed for errors (p<0.01). These results suggest that gamma signals in the motor cortex may function to integrate inhibitory signals with sensorimotor processing, and may represent a mechanism for the overriding of habitual behaviours, as errors were predicted by a delay in gamma onset. This study supports a role for frontal areas in maintaining and executing goal-directed actions, and demonstrates that frontal theta activity and sensorimotor gamma oscillations have distinct yet complementary functional roles in monitoring and modifying habitual motor plans., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The human sensorimotor cortex demonstrates a variety of oscillatory activity that is strongly modulated by movement and somatosensory input. Studies using scalp EEG and intracranial electrical recordings have provided much of our current knowledge regarding the frequency and temporal specificity of these sensorimotor rhythms and their relationship to various movement parameters, however with limitations in identifying the underlying neural sources, and the variety of motor behaviors that can be studied, respectively. Magnetoencephalography (MEG) recordings, combined with spatial filtering source reconstruction methods, provide an ideal non-invasive method for the localization of sensorimotor rhythms and for describing their precise time course during a variety of motor tasks. This review describes the application of MEG to the study of oscillatory activity in the human sensorimotor cortex, including advances in localization techniques and recent contributions of MEG to our understanding of the functional role of these oscillations in both adult and developmental populations., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Auditory responses to speech sounds that are self-initiated are suppressed compared to responses to the same speech sounds during passive listening. This phenomenon is referred to as speech-induced suppression, a potentially important feedback-mediated speech-motor control process. In an earlier study, we found that both adults who do and do not stutter demonstrated a reduced amplitude of the auditory M50 and M100 responses to speech during active production relative to passive listening. It is unknown if auditory responses to self-initiated speech-motor acts are suppressed in children or if the phenomenon differs between children who do and do not stutter. As stuttering is a developmental speech disorder, examining speech-induced suppression in children may identify possible neural differences underlying stuttering close to its time of onset. We used magnetoencephalography to determine the presence of speech-induced suppression in children and to characterize the properties of speech-induced suppression in children who stutter. We examined the auditory M50 as this was the earliest robust response reproducible across our child participants and the most likely to reflect a motor-to-auditory relation. Both children who do and do not stutter demonstrated speech-induced suppression of the auditory M50. However, children who stutter had a delayed auditory M50 peak latency to vowel sounds compared to children who do not stutter indicating a possible deficiency in their ability to efficiently integrate auditory speech information for the purpose of establishing neural representations of speech sounds., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Previous functional neuroimaging studies have shown that maintenance of centrally presented objects in visual short-term memory (VSTM) leads to bilateral increases of BOLD activations in IPS/IOS cortex, while prior electrophysiological work suggests that maintaining stimuli encoded from a single hemifield leads to a sustained posterior contralateral negativity (SPCN) in electrophysiology and magnetoencephalography. These two findings have never been investigated using the same physiological measures. We recorded the BOLD response using fMRI, magnetoencephalography (MEG), and electrophysiology (EEG), while subjects encoded visual stimuli from a single hemifield of a balanced display. The EEG showed an SPCN. However, no SPCN-like activation was observed in the BOLD signals. The BOLD response in parietal cortex remained bilateral, even after unilateral encoding of the stimuli, but MEG showed both bilateral and contralateral activations, each likely reflecting a sub portion of the neuronal populations participating in the maintenance of information in VSTM. Contrary to the assumption that BOLD, EEG, and MEG responses - that were each linked to the maintenance of information in VSTM - are markers of the same neuronal processes, our findings suggest that each technique reveals a somewhat distinct but overlapping neural signature of the mechanisms supporting visual short-term memory., (Copyright © 2010 Elsevier Inc. All rights reserved.)

We used magnetoencephalography to investigate auditory evoked responses to speech vocalizations and non-speech tones in adults who do and do not stutter. Neuromagnetic field patterns were recorded as participants listened to a 1 kHz tone, playback of their own productions of the vowel /i/ and vowel-initial words, and actively generated the vowel /i/ and vowel-initial words. Activation of the auditory cortex at approximately 50 and 100 ms was observed during all tasks. A reduction in the peak amplitudes of the M50 and M100 components was observed during the active generation versus passive listening tasks dependent on the stimuli. Adults who stutter did not differ in the amount of speech-induced auditory suppression relative to fluent speakers. Adults who stutter had shorter M100 latencies for the actively generated speaking tasks in the right hemisphere relative to the left hemisphere but the fluent speakers showed similar latencies across hemispheres. During passive listening tasks, adults who stutter had longer M50 and M100 latencies than fluent speakers. The results suggest that there are timing, rather than amplitude, differences in auditory processing during speech in adults who stutter and are discussed in relation to hypotheses of auditory-motor integration breakdown in stuttering., (Copyright 2010 Elsevier Inc. All rights reserved.)

Using the notion of complexity and synchrony, this study presents a data-driven pipeline of nonlinear analysis of neuromagnetic sources reconstructed from human magnetoencephalographic (MEG) data collected in reaction to vibrostimulation of the right index finger. The dynamics of MEG source activity was reconstructed with synthetic aperture magnetometry (SAM) beam-forming technique. Considering brain as a complex system, we applied complexity-based tools to identify brain areas with dynamic patterns that remain regular across repeated stimulus presentations, and to characterize their synchronized behavior. Volumetric maps of brain activation were calculated using sample entropy as a measure of signal complexity. The complexity analysis identified activity in the primary somatosensory (SI) area contralateral to stimuli and bilaterally in the posterior parietal cortex (PPC) as regions with decreased complexity, consistently expressed in a group of subjects. Seeding an activated source with low complexity in the SI area, cross-sample entropy was used to generate synchrony maps. Cross-sample entropy analysis confirmed the synchronized dynamics of neuromagnetic activity between areas SI and PPC, robustly expressed across subjects. Our results extend the understanding of synchronization between co-activated brain regions, focusing on temporal coordination between events in terms of synchronized multidimensional signal patterns., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Human adaptive behaviour to potential threats involves specialized brain responses allowing rapid and reflexive processing of the sensory input and a more directed processing for later evaluation of the nature of the threat. The amygdalae are known to play a key role in emotion processing. It is suggested that the amygdalae process threat-related information through a fast subcortical route and slower cortical feedback. Evidence from human data supporting this hypothesis is lacking. The present study investigated event-related neural responses during processing of facial emotions in the unattended hemifield using magnetoencephalography (MEG) and found activations of the amygdala and anterior cingulate cortex to fear as early as 100 ms. The right amygdala exhibited temporally dissociated activations to input from different visual fields, suggesting early subcortical versus later cortical processing of fear. We also observed asymmetrical fusiform activity related to lateralized feed-forward processing of the faces in the visual-ventral stream. Results demonstrate fast, automatic, and parallel processing of unattended emotional faces, providing important insights into the specific and dissociated neural pathways in emotion and face perception., (Copyright 2010 Elsevier Inc. All rights reserved.)

Adaptive spatial filters (beamformers) have gained popularity as an effective method for the localization of brain activity from magnetoencephalography (MEG) data. Among the attractive features of some beamforming methods are high spatial resolution and no localization bias even in the presence of random noise. A drawback common to all beamforming methods, however, is significant degradation in performance in the presence of sources with high temporal correlations. Using numerical simulations and examples of auditory and visual evoked field responses, we demonstrate that, at typical signal-to-noise levels, the complete attenuation of fully correlated brain activity is less likely to occur, although significant localization and amplitude biases may occur. We compared various methods for correcting these biases and found the coherent source suppression model (CSSM) (Dalal et al., 2006) to be the most effective, with small biases for widely separated sources (e.g., bilateral auditory areas), however, amplitude biases increased systematically as distance between the sources was decreased. We assessed the performance and systematic biases that may result from the use of this model, and confirmed our findings with real examples of correlated brain activity in bilateral occipital and inferior temporal areas evoked by visually presented faces in a group of 21 adults. We demonstrated the ability to localize source activity in both regions, including correlated sources that are in close proximity ( approximately 3 cm) in bilateral primary visual cortex when using a priori information regarding source location. We conclude that CSSM, when carefully applied, can significantly improve localization accuracy, although amplitude biases may remain., (Copyright (c) 2009 Elsevier Inc. All rights reserved.)

There has been increasing interest in the functional role of high-frequency (>30 Hz) cortical oscillations accompanying various sensorimotor and cognitive tasks in humans. Similar "high gamma" activity has been observed in the motor cortex, although the role of this activity in motor control is unknown. Using whole-head MEG recordings combined with advanced source localization methods, we identified high-frequency (65 to 80 Hz) gamma oscillations in the primary motor cortex during self-paced movements of the upper and lower limbs. Brief bursts of gamma activity were localized to the contralateral precentral gyrus (MI) during self-paced index finger abductions, elbow flexions and foot dorsiflexions. In comparison to lower frequency (10-30 Hz) sensorimotor rhythms that are bilaterally suppressed prior to and during movement (Jurkiewicz et al., 2006), high gamma activity increased only during movement, reaching maximal increase 100 to 250 ms following EMG onset, and was lateralized to contralateral MI, similar to findings from intracranial EEG studies. Peak frequency of gamma activity was significantly lower during foot dorsiflexion (67.4+/-5.2 Hz) than during finger abduction (75.3+/-4.4 Hz) and elbow flexion (73.9+/-3.7 Hz) although markedly similar for left and right movements of the same body part within subjects, suggesting activation of a common underlying network for gamma oscillations in the left and right motor cortex. These findings demonstrate that voluntary movements elicit high-frequency gamma oscillations in the primary motor cortex that are effector specific, and possibly reflect the activation of cortico-subcortical networks involved in the feedback control of discrete movements.

Voluntary movements are accompanied by amplitude changes in cortical rhythms presumably as a result of functional activation of sensorimotor areas. Recently, the location of the neural generators involved in increasing power within the beta (15-30 Hz) frequency band following movement (post-movement beta rebound, PMBR) has come into question [Parkes, L.M, Bastiaansen, M.C.M, Norris, D.G., 2006. Combining EEG and fMRI to investigate the post-movement beta rebound. NeuroImage 29, 685-696.]. We used the synthetic aperture magnetometry (SAM) spatial filtering method to identify the time course and location of oscillatory changes within the beta and mu (8-14 Hz) frequency bands during the performance of voluntary movements. Neuromagnetic activity was recorded from 10 adult subjects during abduction of the right index finger. Changes in beta and mu source power were calculated for periods during and following movement, relative to pre-movement baseline activity. Decreases in beta band activity (event-related desynchronization, ERD) were observed during movement, with a strong increase (PMBR) beginning 230+/-170 ms following movement, lasting for 680+/-170 ms. Mu band ERD was observed both during and following movement, with little to no post-movement rebound. Beta and mu ERD were localized bilaterally to the hand region of postcentral gyrus whereas PMBR was localized bilaterally to the hand region of precentral gyrus (motor cortex). Both PMBR and beta ERD were strongest contralateral to the side of movement. These results provide further evidence that movement influences independent cortical rhythms in sensorimotor areas, and confirm previous reports of precentral generators of PMBR in the region of motor cortex, with postcentral generators of beta and mu ERD during movement.

We applied the synthetic aperture magnetometry (SAM) spatial filtering method to localize sensorimotor mu (8-14 Hz) and beta (15-35 Hz) rhythms following tactile (brush) stimulation. Neuromagnetic activity was recorded from 10 adult subjects. Transient brush stimuli were applied separately to the right index finger, medial right toe and lower right lip. Differential images of mu and beta band source power were created for periods during (event-related desynchronization; ERD) or following (event-related synchronization; ERS) tactile stimulation, relative to prestimulus baseline activity. Mu ERD to finger brushing was localized to the contralateral somatosensory cortex and was organized somatotopically. Mu ERS, however, was not consistently observed for each subject. Beta ERD was consistently localized to sensory cortical areas and organized somatotopically in the post-central gyrus (SI), and beta ERS was observed to be organized motorotopically in the precentral gyrus (MI). Longer duration (2-3 s) stimulation of the index finger also produced beta ERS in the primary motor cortex, and its time course demonstrated that these oscillatory changes are an off-response to the termination of the presented sensory stimulus. Interestingly, lip and toe stimulation also produced post-stimulus increases in beta rhythms in the bilateral motor hand areas for all subjects, suggesting that common neural systems in the primary motor cortex are activated during tactile stimulation of different body regions.