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Jed A. Meltzer

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8 papers

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YNICL Journal 2023 Journal Article

Spectral slowing in chronic stroke reflects abnormalities in both periodic and aperiodic neural dynamics

Phillip R. Johnston
Anthony R. McIntosh
Jed A. Meltzer

Decades of electrophysiological work have demonstrated the presence of "spectral slowing" in stroke patients - a prominent shift in the power spectrum towards lower frequencies, most evident in the vicinity of the lesion itself. Despite the reliability of this slowing as a marker of dysfunctional tissue across patient groups as well as animal models, it has yet to be explained in terms of the pathophysiological processes of stroke. To do so requires clear understanding of the neural dynamics that these differences represent, acknowledging the often overlooked fact that spectral power reflects more than just the amplitude of neural oscillations. To accomplish this, we used a combination of frequency domain and time domain measures to disambiguate and quantify periodic (oscillatory) and aperiodic (non-oscillatory) neural dynamics in resting state magnetoencephalography (MEG) recordings from chronic stroke patients. We found that abnormally elevated low frequency power in these patients was best explained by a steepening of the aperiodic component of the power spectrum, rather than an enhancement of low frequency oscillations, as is often assumed. However, genuine oscillatory activity at higher frequencies was also found to be abnormal, with patients showing alpha slowing and diminished oscillatory activity in the beta band. These aperiodic and periodic abnormalities were found to covary, and could be detected even in the un-lesioned hemisphere, however they were most prominent in perilesional tissue, where their magnitude was predictive of cognitive impairment. This work redefines spectral slowing as a pattern of changes involving both aperiodic and periodic neural dynamics and narrows the gap in understanding between non-invasive markers of dysfunctional tissue and disease processes responsible for altered neural dynamics.

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YNICL Journal 2022 Journal Article

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

Priyanka Shah-Basak
Gayatri Sivaratnam
Selina Teti
Tiffany Deschamps
Aneta Kielar
Regina Jokel
Jed A. Meltzer

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.

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YNIMG Journal 2021 Journal Article

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

Hsi T. Wei
Alex Francois-Nienaber
Tiffany Deschamps
Buddhika Bellana
Melissa Hebscher
Gayatri Sivaratnam
Maryam Zadeh
Jed A. Meltzer

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.

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YNIMG Journal 2017 Journal Article

Electrophysiological signatures of phonological and semantic maintenance in sentence repetition

Jed A. Meltzer
Aneta Kielar
Lilia Panamsky
Kira A. Links
Tiffany Deschamps
Rosie C. Leigh

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.

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YNIMG Journal 2015 Journal Article

Localization of electrophysiological responses to semantic and syntactic anomalies in language comprehension with MEG

Aneta Kielar
Lilia Panamsky
Kira A. Links
Jed A. Meltzer

Syntactically and semantically anomalous words encountered during sentence comprehension are known to elicit dissociable electrophysiological responses, which are thought to reflect distinct aspects of language processing. However, the sources of these responses have not been well characterized. We used beamforming analysis of magnetoencephalography (MEG) data to map generators of electrophysiological responses to linguistic anomalies. Anomalous words occurred in the context of a sentence acceptability judgement task conducted in both visual and auditory modalities. Time–frequency analysis revealed that both kinds of violations elicited event-related synchronization (ERS) in the delta–theta frequency range (1–5Hz), and desynchronization (ERD) in the alpha–beta range (8–30Hz). In addition, these responses were differentially modulated by violation type and presentation modality. 1–5Hz responses were consistently localized within medial prefrontal cortex and did not vary significantly across violation types, but were stronger for visual presentation. In contrast, 8–30Hz ERD occurred in different regions for different violation types. For semantic violations the distribution was predominantly in the bilateral occipital cortex and left temporal and inferior frontal regions, and these effects did not differ for visual and auditory presentation. In contrast, syntactic responses were strongly affected by presentation modality. Under visual presentation, syntactic violations elicited bilateral 8–30Hz ERD extending into dorsal parietal and frontal regions, whereas effects were much weaker and mostly statistically insignificant in the auditory modality. These results suggest that delta–theta ERS reflects generalized increases in working memory demands related to linguistic anomaly detection, while alpha–beta ERD reflects specific activation of cortical regions involved in distinct aspects of linguistic processing, such as semantic vs. phonological short-term memory. Beamforming analysis of time-domain average signals (ERFs) revealed an N400m effect for semantic anomalies in both modalities, localized to left superior temporal and posterior frontal regions, and a later P600-like effect for syntactic anomalies in both modalities, widespread over bilateral frontal, posterior temporal, and parietal regions. These results indicate that time-domain averaged responses and induced oscillatory responses have distinct properties, including localization and modality dependence, and likely reflect dissociable and complementary aspects of neural activity related to language comprehension and additional task-related processes.

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YNICL Journal 2015 Journal Article

MEG-based detection and localization of perilesional dysfunction in chronic stroke

Ron K.O. Chu
Allen R. Braun
Jed A. Meltzer

Post-stroke impairment is associated not only with structural lesions, but also with dysfunction in surviving perilesional tissue. Previous studies using equivalent current dipole source localization of MEG/EEG signals have demonstrated a preponderance of slow-wave activity localized to perilesional areas. Recent studies have also demonstrated the utility of nonlinear analyses such as multiscale entropy (MSE) for quantifying neuronal dysfunction in a wide range of pathologies. The current study utilized beamformer-based reconstruction of signals in source space to compare spectral and nonlinear measures of electrical activity in perilesional and healthy cortices. Data were collected from chronic stroke patients and healthy controls, both young and elderly. We assessed relative power in the delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz) and beta (15-30 Hz) frequency bands, and also measured the nonlinear complexity of electrical activity using MSE. Perilesional tissue exhibited a general slowing of the power spectrum (increased delta/theta, decreased beta) as well as a reduction in MSE. All measures tested were similarly sensitive to changes in the posterior perilesional regions, but anterior perilesional dysfunction was detected better by MSE and beta power. The findings also suggest that MSE is specifically sensitive to electrophysiological dysfunction in perilesional tissue, while spectral measures were additionally affected by an increase in rolandic beta power with advanced age. Furthermore, perilesional electrophysiological abnormalities in the left hemisphere were correlated with the degree of language task-induced activation in the right hemisphere. Finally, we demonstrate that single subject spectral and nonlinear analyses can identify dysfunctional perilesional regions within individual patients that may be ideal targets for interventions with noninvasive brain stimulation.

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YNIMG Journal 2009 Journal Article

Strategies for longitudinal neuroimaging studies of overt language production

Jed A. Meltzer
Whitney A. Postman-Caucheteux
Joseph J. McArdle
Allen R. Braun

Longitudinal fMRI studies of language production are of interest for evaluating recovery from post-stroke aphasia, but numerous methodological issues remain unresolved, particularly regarding strategies for evaluating single subjects at multiple timepoints. To address these issues, we studied overt picture naming in eleven healthy subjects, scanned four times each at one-month intervals. To evaluate the natural variability present across repeated sessions, repeated scans were directly contrasted in a unified statistical framework on a per-voxel basis. The effect of stimulus familiarity was evaluated using explicitly overtrained pictures, novel pictures, and untrained pictures that were repeated across sessions. For untrained pictures, we found that activation declined across multiple sessions, equally for both novel and repeated stimuli. Thus, no repetition priming for individual stimuli at one-month intervals was found, but rather a general effect of task habituation was present. Using a set of overtrained pictures identical in each session, no decline was found, but activation was minimized and produced less consistent patterns across participants, as measured by intra-class correlation coefficients. Subtraction of a baseline task, in which subjects produced a stereotyped utterance to scrambled pictures, resulted in specific activations in the left inferior frontal gyrus and other language areas for untrained items, while overlearned stimuli relative to pseudo pictures activated only the fusiform gyrus and supplementary motor area. These findings indicate that longitudinal fMRI is an effective means of detecting changes in neural activation magnitude over time, as long as the effect of task habituation is taken into account.

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YNIMG Journal 2005 Journal Article

Activation of human hippocampal formation reflects success in both encoding and cued recall of paired associates

Jed A. Meltzer
R. Todd Constable

Contemporary theories of hippocampal function suggest that both encoding and retrieval of episodic memories may be accomplished by neural circuitry embedded within the same anatomical structures, but neuroimaging support for this hypothesis has been ambiguous. Recent studies suggest that the best available indicators of hippocampal encoding and retrieval operations are selective activations due to novelty, encoding success, and recall success in a paired associate learning paradigm. In the current study, both encoding and cued recall of paired associate words were conducted during a single session of fMRI scanning. Bilateral activation in the medial temporal lobe was detected for encoding word pairs vs. a fixation baseline and for encoding novel word pairs vs. repeated word pairs. These activations were stronger in subjects who successfully memorized more word pairs. In cued recall, greater responses were seen in higher performing subjects. In lower performing subjects, responses were greater to cue words whose paired associate was correctly recalled than to cue words whose correct associate had been forgotten (or not encoded). The difference between correct and incorrect trials was more pronounced on repeated presentations of the same cue words, but not apparent on their first presentation alone. Overlap of encoding and retrieval effects was maximal in the middle of the longitudinal extent of the right hippocampus, with one additional locus of overlap outside the MTL, in left occipitotemporal cortex. The conjunction of these effects suggests that it is correct to view both encoding and recall of associative memories as functions of an integrated hippocampal system.

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