Sensitivity of amplitude and phase based MEG measures of interhemispheric connectivity during unilateral finger movements.

Interactions between different brain regions can be revealed by dependencies between their neuronal oscillations. We examined the sensitivity of different oscillatory connectivity measures in revealing interhemispheric interactions between primary motor cortices (M1s) during unilateral finger movements. Based on frequency, amplitude, and phase of the oscillations, a number of metrics have been developed to measure connectivity between brain regions, and each metric has its own strengths, weaknesses, and pitfalls. Taking advantage of the well-known movement-related modulations of oscillatory amplitude in M1s, this study compared and contrasted a number of leading connectivity metrics during distinct phases of oscillatory power changes. Between M1s during unilateral movements, we found that phase-based metrics were effective at revealing connectivity during the beta (15-35 Hz) rebound period linked to movement termination, but not during the early period of beta desynchronization occurring during the movement itself. Amplitude correlation metrics revealed robust connectivity during both periods. Techniques for estimating the direction of connectivity had limited success. Granger Causality was not well suited to studying these connections because it was strongly confounded by differences in signal-to-noise ratio linked to modulation of beta amplitude occurring during the task. Phase slope index was suggestive but not conclusive of a unidirectional influence between motor cortices during the beta rebound. Our findings suggest that a combination of amplitude and phase-based metrics is likely required to fully characterize connectivity during task protocols that involve modulation of oscillatory power, and that amplitude-based metrics appear to be more sensitive despite the lack of directional information.

Spontaneous oscillatory markers of cognitive status in two forms of dementia.

Abnormal oscillatory brain activity in dementia may indicate incipient neuronal/synaptic dysfunction, rather than frank structural atrophy. Leveraging a potential link between the degree of abnormal oscillatory activity and cognitive symptom severity, one could localize brain regions in a diseased but pre-atrophic state, which may be more amenable to interventions. In the current study, we evaluated the relationships among cognitive deficits, regional volumetric changes, and resting-state magnetoencephalography abnormalities in patients with mild cognitive impairment (MCI; N = 10; age: 75.9 ± 7.3) or primary progressive aphasia (PPA; N = 12; 69.7 ± 8.0), and compared them to normal aging [young (N = 18; 24.6 ± 3.5), older controls (N = 24; 67.2 ± 9.7]. Whole-brain source-level resting-state estimates of relative oscillatory power in the delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz), and beta (15-30 Hz) bands were combined with gray matter volumes and cognitive scores to examine between-group differences and brain-behavior correlations. Language and executive function (EF) abilities were impaired in patients with PPA, while episodic memory was impaired in MCI. Widespread oscillatory speeding and volumetric shrinkage was associated with normal aging, whereas the trajectory in PPA indicated widespread oscillatory slowing with additional volumetric reductions. Increases in delta and decreases in alpha power uniquely predicted group membership to PPA. Beyond volumetric reductions, more delta predicted poorer memory. In patients with MCI, no consistent group difference among oscillatory measures was found. The contributions of delta/alpha power on memory abilities were larger than volumetric differences. Spontaneous oscillatory abnormalities in association with cognitive symptom severity can serve as a marker of neuronal dysfunction in dementia, providing targets for promising treatments.

Electrophysiological signatures of phonological and semantic maintenance in sentence repetition.

Verbal short-term memory comprises resources for phonological rehearsal, which have been characterized anatomically, and for maintenance of semantic information, which are less understood. Sentence repetition tasks tap both processes interactively. To distinguish brain activity involved in phonological vs. semantic maintenance, we recorded magnetoencephalography during a sentence repetition task, incorporating three manipulations emphasizing one mechanism over the other. Participants heard sentences or word lists and attempted to repeat them verbatim after a 5-second delay. After MEG, participants completed a cued recall task testing how much they remembered of each sentence. Greater semantic engagement relative to phonological rehearsal was hypothesized for 1) sentences vs. word lists, 2) concrete vs. abstract sentences, and 3) well recalled vs. poorly recalled sentences. During auditory perception and the memory delay period, we found highly left-lateralized activation in the form of 8-30 Hz event-related desynchronization. Compared to abstract sentences, concrete sentences recruited posterior temporal cortex bilaterally, demonstrating a neural signature for the engagement of visual imagery in sentence maintenance. Maintenance of arbitrary word lists recruited right hemisphere dorsal regions, reflecting increased demands on phonological rehearsal. Sentences that were ultimately poorly recalled in the post-test also elicited extra right hemisphere activation when they were held in short-term memory, suggesting increased demands on phonological resources. Frontal midline theta oscillations also reflected phonological rather than semantic demand, being increased for word lists and poorly recalled sentences. These findings highlight distinct neural resources for phonological and semantic maintenance, with phonological maintenance associated with stronger oscillatory modulations.

Functional reorganization of language networks for semantics and syntax in chronic stroke: Evidence from MEG.

Using magnetoencephalography, we investigated the potential of perilesional and contralesional activity to support language recovery in patients with poststroke aphasia. In healthy young controls, left-lateralized ventral frontotemporal regions responded to semantic anomalies during sentence comprehension and bilateral dorsal frontoparietal regions responded to syntactic anomalies. Older adults showed more extensive bilateral responses to the syntactic anomalies and less lateralized responses to the semantic anomalies, with decreased activation in the left occipital and parietal regions for both semantic and syntactic anomalies. In aphasic participants, we observed compensatory recruitment in the right hemisphere (RH), which varied depending on the type of linguistic information that was processed. For semantic anomalies, aphasic patients activated some preserved left hemisphere regions adjacent to the lesion, as well as homologous parietal and temporal RH areas. Patients also recruited right inferior and dorsolateral frontal cortex that was not activated in the healthy participants. Responses for syntactic anomalies did not reach significance in patients. Correlation analyses indicated that recruitment of homologous temporoparietal RH areas is associated with better semantic performance, whereas higher accuracy on the syntactic task was related to bilateral superior temporoparietal and right frontal activity. The results suggest that better recovery of semantic processing is associated with a shift to ventral brain regions in the RH. In contrast, preservation of syntactic processing is mediated by dorsal areas, bilaterally, although recovery of syntactic processing tends to be poorer than semantic. Hum Brain Mapp 37:2869-2893, 2016. © 2016 Wiley Periodicals, Inc.

Semantic and phonological contributions to short-term repetition and long-term cued sentence recall.

The function of verbal short-term memory is supported not only by the phonological loop, but also by semantic resources that may operate on both short and long time scales. Elucidation of the neural underpinnings of these mechanisms requires effective behavioral manipulations that can selectively engage them. We developed a novel cued sentence recall paradigm to assess the effects of two factors on sentence recall accuracy at short-term and long-term stages. Participants initially repeated auditory sentences immediately following a 14-s retention period. After this task was complete, long-term memory for each sentence was probed by a two-word recall cue. The sentences were either concrete (high imageability) or abstract (low imageability), and the initial 14-s retention period was filled with either an undemanding finger-tapping task or a more engaging articulatory suppression task (Exp. 1, counting backward by threes; Exp. 2, repeating a four-syllable nonword). Recall was always better for the concrete sentences. Articulatory suppression reduced accuracy in short-term recall, especially for abstract sentences, but the sentences initially recalled following articulatory suppression were retained better at the subsequent cued-recall test, suggesting that the engagement of semantic mechanisms for short-term retention promoted encoding of the sentence meaning into long-term memory. These results provide a basis for using sentence imageability and subsequent memory performance as probes of semantic engagement in short-term memory for sentences.

Contrasting MEG effects of anodal and cathodal high-definition TDCS on sensorimotor activity during voluntary finger movements.

Introduction: Protocols for noninvasive brain stimulation (NIBS) are generally categorized as "excitatory" or "inhibitory" based on their ability to produce short-term modulation of motor-evoked potentials (MEPs) in peripheral muscles, when applied to motor cortex. Anodal and cathodal stimulation are widely considered excitatory and inhibitory, respectively, on this basis. However, it is poorly understood whether such polarity-dependent changes apply for neural signals generated during task performance, at rest, or in response to sensory stimulation. Methods: To characterize such changes, we measured spontaneous and movement-related neural activity with magnetoencephalography (MEG) before and after high-definition transcranial direct-current stimulation (HD-TDCS) of the left motor cortex (M1), while participants performed simple finger movements with the left and right hands. Results: Anodal HD-TDCS (excitatory) decreased the movement-related cortical fields (MRCF) localized to left M1 during contralateral right finger movements while cathodal HD-TDCS (inhibitory), increased them. In contrast, oscillatory signatures of voluntary motor output were not differentially affected by the two stimulation protocols, and tended to decrease in magnitude over the course of the experiment regardless. Spontaneous resting state oscillations were not affected either. Discussion: MRCFs are thought to reflect reafferent proprioceptive input to motor cortex following movements. Thus, these results suggest that processing of incoming sensory information may be affected by TDCS in a polarity-dependent manner that is opposite that seen for MEPs-increases in cortical excitability as defined by MEPs may correspond to reduced responses to afferent input, and vice-versa.

Electrophysiological connectivity markers of preserved language functions in post-stroke aphasia.

Post-stroke aphasia is a consequence of localized stroke-related damage as well as global disturbances in a highly interactive and bilaterally-distributed language network. Aphasia is increasingly accepted as a network disorder and it should be treated as such when examining the reorganization and recovery mechanisms after stroke. In the current study, we sought to investigate reorganized patterns of electrophysiological connectivity, derived from resting-state magnetoencephalography (rsMEG), in post-stroke chronic (>6 months after onset) aphasia. We implemented amplitude envelope correlations (AEC), a metric of connectivity commonly used to describe slower aspects of interregional communication in resting-state electrophysiological data. The main focus was on identifying the oscillatory frequency bands and frequency-specific spatial topology of connections associated with preserved language abilities after stroke. RsMEG was recorded for 5 min in 21 chronic stroke survivors with aphasia and in 20 matched healthy controls. Source-level MEG activity was reconstructed and summarized within 72 atlas-defined brain regions (or nodes). A 72 × 72 leakage-corrected connectivity (of AEC) matrix was obtained for frequencies from theta to low-gamma (4-50 Hz). Connectivity was compared between groups, and, the correlations between connectivity and subscale scores from the Western Aphasia Battery (WAB) were evaluated in the stroke group, using partial least squares analyses. Posthoc multiple regression analyses were also conducted on a graph theory measure of node strengths, derived from significant connectivity results, to control for node-wise properties (local spectral power and lesion sizes) and demographic and stroke-related variables. Connectivity among the left hemisphere regions, i.e. those ipsilateral to the stroke lesion, was greatly reduced in stroke survivors with aphasia compared to matched healthy controls in the alpha (8-13 Hz; p = 0.011) and beta (15-30 Hz; p = 0.001) bands. The spatial topology of hypoconnectivity in the alpha vs. beta bands was distinct, revealing a greater involvement of ventral frontal, temporal and parietal areas in alpha, and dorsal frontal and parietal areas in beta. The node strengths from alpha and beta group differences remained significant after controlling for nodal spectral power. AEC correlations with WAB subscales of object naming and fluency were significant. Greater alpha connectivity was associated with better naming performance (p = 0.045), and greater connectivity in both the alpha (p = 0.033) and beta (p = 0.007) bands was associated with better speech fluency performance. The spatial topology was distinct between these frequency bands. The node strengths remained significant after controlling for age, time post stroke onset, nodal spectral power and nodal lesion sizes. Our findings provide important insights into the electrophysiological connectivity profiles (frequency and spatial topology) potentially underpinning preserved language abilities in stroke survivors with aphasia.

Slowing is slowing: Delayed neural responses to words are linked to abnormally slow resting state activity in primary progressive aphasia.

Neurodegenerative disorders are often characterized by neuronal "slowing," which may be assessed in different ways. In the present study, we examined the latency of neural responses to linguistic stimuli in participants diagnosed with primary progressive aphasia (PPA), as well as changes in the power spectra of resting state activity, both measured with MEG. Compared to both age-matched and younger controls, patients with PPA showed a delayed latency of 8-30 Hz event-related desynchronization (ERD) in response to semantic anomalies. In addition, resting-state MEG revealed increased power in the lower frequency delta and theta bands, but decreased activity in the higher alpha and beta bands. The task-induced and spontaneous measures of neural dynamics were related, such that increased peak latencies in response to words were correlated with a shift of spontaneous oscillatory dynamics towards lower frequencies. In contrast, older controls showed similar task related ERD latencies as younger controls, but also "speeding" of spontaneous activity, i.e. a shift towards faster frequencies. In PPA patients both increased peak latencies on task and increased slow oscillations at rest were associated with less accurate performance on the language task and poorer performance on offline cognitive measures, beyond variance accounted for by structural atrophy. A mediation analysis indicated that increased theta power accounted for the relationship between delayed electrophysiological responses and reduced accuracy in PPA patients. These results indicate that the neuropathological changes in PPA result in slowing of both task-related and spontaneous neuronal activity, linked to functional decline, whereas the speeding of spontaneous activity in healthy aging seems to have a protective or compensatory effect.

Identifying Dysfunctional Cortex: Dissociable Effects of Stroke and Aging on Resting State Dynamics in MEG and fMRI.

Spontaneous signals in neuroimaging data may provide information on cortical health in disease and aging, but the relative sensitivity of different approaches is unknown. In the present study, we compared different but complementary indicators of neural dynamics in resting-state MEG and BOLD fMRI, and their relationship with blood flow. Participants included patients with post-stroke aphasia, age-matched controls, and young adults. The complexity of brain activity at rest was quantified in MEG using spectral analysis and multiscale entropy (MSE) measures, whereas BOLD variability was quantified as the standard deviation (SDBOLD), mean squared successive difference (MSSD), and sample entropy of the BOLD time series. We sought to assess the utility of signal variability and complexity measures as markers of age-related changes in healthy adults and perilesional dysfunction in chronic stroke. The results indicate that reduced BOLD variability is a robust finding in aging, whereas MEG measures are more sensitive to the cortical abnormalities associated with stroke. Furthermore, reduced complexity of MEG signals in perilesional tissue were correlated with hypoperfusion as assessed with arterial spin labeling (ASL), while no such relationship was apparent with BOLD variability. These findings suggest that MEG signal complexity offers a sensitive index of neural dysfunction in perilesional tissue in chronic stroke, and that these effects are clearly distinguishable from those associated with healthy aging.