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.

How well do you know your mutation? Complex effects of genetic background on expressivity, complementation, and ordering of allelic effects.

For a given gene, different mutations influence organismal phenotypes to varying degrees. However, the expressivity of these variants not only depends on the DNA lesion associated with the mutation, but also on factors including the genetic background and rearing environment. The degree to which these factors influence related alleles, genes, or pathways similarly, and whether similar developmental mechanisms underlie variation in the expressivity of a single allele across conditions and among alleles is poorly understood. Besides their fundamental biological significance, these questions have important implications for the interpretation of functional genetic analyses, for example, if these factors alter the ordering of allelic series or patterns of complementation. We examined the impact of genetic background and rearing environment for a series of mutations spanning the range of phenotypic effects for both the scalloped and vestigial genes, which influence wing development in Drosophila melanogaster. Genetic background and rearing environment influenced the phenotypic outcome of mutations, including intra-genic interactions, particularly for mutations of moderate expressivity. We examined whether cellular correlates (such as cell proliferation during development) of these phenotypic effects matched the observed phenotypic outcome. While cell proliferation decreased with mutations of increasingly severe effects, surprisingly it did not co-vary strongly with the degree of background dependence. We discuss these findings and propose a phenomenological model to aid in understanding the biology of genes, and how this influences our interpretation of allelic effects in genetic analysis.

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.

High definition transcranial direct current stimulation modulates abnormal neurophysiological activity in post-stroke aphasia.

Recent findings indicate that measures derived from resting-state magnetoencephalography (rsMEG) are sensitive to cortical dysfunction in post-stroke aphasia. Spectral power and multiscale entropy (MSE) measures show that left-hemispheric areas surrounding the stroke lesion (perilesional) exhibit pathological oscillatory slowing and alterations in signal complexity. In the current study, we tested whether individually-targeted high-definition transcranial direct current stimulation (HD-tDCS) can reduce MEG abnormalities and transiently improve language performance. In eleven chronic aphasia survivors, we devised a method to localize perilesional areas exhibiting peak MSE abnormalities, and subsequently targeted these areas with excitatory/anodal-tDCS, or targeted the contralateral homolog areas with inhibitory/cathodal-tDCS, based on prominent theories of stroke recovery. Pathological MEG slowing in these patients was correlated with aphasia severity. Sentence/phrase repetition accuracy was assessed before and after tDCS. A delayed word reading task was administered inside MEG to assess tDCS-induced neurophysiological changes in relative power and MSE computed on the pre-stimulus and delay task time windows. Results indicated increases in repetition accuracy, decreases in contralateral theta (4-7 Hz) and coarse-scale MSE (slow activity), and increases in perilesional low-gamma (25-50 Hz) and fine-scale MSE (fast activity) after anodal-tDCS, indicating reversal of pathological abnormalities. RsMEG may be a sensitive measure for guiding therapeutic tDCS.