Predicting MEG resting-state functional connectivity from microstructural information.

Understanding how human brain microstructure influences functional connectivity is an important endeavor. In this work, magnetic resonance imaging data from 90 healthy participants were used to calculate structural connectivity matrices using the streamline count, fractional anisotropy, radial diffusivity, and a myelin measure (derived from multicomponent relaxometry) to assign connection strength. Unweighted binarized structural connectivity matrices were also constructed. Magnetoencephalography resting-state data from those participants were used to calculate functional connectivity matrices, via correlations of the Hilbert envelopes of beamformer time series in the delta, theta, alpha, and beta frequency bands. Nonnegative matrix factorization was performed to identify the components of the functional connectivity. Shortest path length and search-information analyses of the structural connectomes were used to predict functional connectivity patterns for each participant. The microstructure-informed algorithms predicted the components of the functional connectivity more accurately than they predicted the total functional connectivity. This provides a methodology to understand functional mechanisms better. The shortest path length algorithm exhibited the highest prediction accuracy. Of the weights of the structural connectivity matrices, the streamline count and the myelin measure gave the most accurate predictions, while the fractional anisotropy performed poorly. Overall, different structural metrics paint very different pictures of the structural connectome and its relationship to functional connectivity.

Electrophysiological network alterations in adults with copy number variants associated with high neurodevelopmental risk.

Rare copy number variants associated with increased risk for neurodevelopmental and psychiatric disorders (referred to as ND-CNVs) are characterized by heterogeneous phenotypes thought to share a considerable degree of overlap. Altered neural integration has often been linked to psychopathology and is a candidate marker for potential convergent mechanisms through which ND-CNVs modify risk; however, the rarity of ND-CNVs means that few studies have assessed their neural correlates. Here, we used magnetoencephalography (MEG) to investigate resting-state oscillatory connectivity in a cohort of 42 adults with ND-CNVs, including deletions or duplications at 22q11.2, 15q11.2, 15q13.3, 16p11.2, 17q12, 1q21.1, 3q29, and 2p16.3, and 42 controls. We observed decreased connectivity between occipital, temporal, and parietal areas in participants with ND-CNVs. This pattern was common across genotypes and not exclusively characteristic of 22q11.2 deletions, which were present in a third of our cohort. Furthermore, a data-driven graph theory framework enabled us to successfully distinguish participants with ND-CNVs from unaffected controls using differences in node centrality and network segregation. Together, our results point to alterations in electrophysiological connectivity as a putative common mechanism through which genetic factors confer increased risk for neurodevelopmental and psychiatric disorders.

Oscillatory hyperactivity and hyperconnectivity in young APOE-ɛ4 carriers and hypoconnectivity in Alzheimer's disease.

We studied resting-state oscillatory connectivity using magnetoencephalography in healthy young humans (N = 183) genotyped for APOE-ɛ4, the greatest genetic risk for Alzheimer's disease (AD). Connectivity across frequencies, but most prevalent in alpha/beta, was increased in APOE-ɛ4 in a set of mostly right-hemisphere connections, including lateral parietal and precuneus regions of the Default Mode Network. Similar regions also demonstrated hyperactivity, but only in gamma (40-160 Hz). In a separate study of AD patients, hypoconnectivity was seen in an extended bilateral network that partially overlapped with the hyperconnected regions seen in young APOE-ɛ4 carriers. Using machine-learning, AD patients could be distinguished from elderly controls with reasonable sensitivity and specificity, while young APOE-e4 carriers could also be distinguished from their controls with above chance performance. These results support theories of initial hyperconnectivity driving eventual profound disconnection in AD and suggest that this is present decades before the onset of AD symptomology.

Neurovascular Coupling During Visual Stimulation in Multiple Sclerosis: A MEG-fMRI Study.

The process of neurovascular coupling ensures that increases in neuronal activity are fed by increases in cerebral blood flow. Evidence suggests that neurovascular coupling may be impaired in Multiple Sclerosis (MS) due to a combination of brain hypoperfusion, altered cerebrovascular reactivity and oxygen metabolism, and altered levels of vasoactive compounds. Here, we tested the hypothesis that neurovascular coupling is impaired in MS. We characterized neurovascular coupling as the relationship between changes in neuronal oscillatory power within the gamma frequency band (30-80 Hz), as measured by magnetoencephalography (MEG), and associated hemodynamic changes (blood oxygenation level dependent, BOLD, and cerebral blood flow, CBF) as measured by functional MRI. We characterized these responses in the visual cortex in 13 MS patients and in 10 matched healthy controls using a reversing checkerboard stimulus at five visual contrasts. There were no significant group differences in visual acuity, P100 latencies, occipital gray matter (GM) volumes and baseline CBF. However, in the MS patients we found a significant reduction in peak gamma power, BOLD and CBF responses. There were no significant differences in neurovascular coupling between groups, in the visual cortex. Our results suggest that neuronal and vascular responses are altered in MS. Gamma power reduction could be an indicator of GM dysfunction, possibly mediated by GABAergic changes. Altered hemodynamic responses confirm previous reports of a vascular dysfunction in MS. Despite altered neuronal and vascular responses, neurovascular coupling appears to be preserved in MS, at least within the range of damage and disability studied here.

Attenuated Post-Movement Beta Rebound Associated With Schizotypal Features in Healthy People.

INTRODUCTION: Schizophrenia and schizotypal personality disorder (SPD) lie on a single spectrum of mental illness and converging evidence suggests similarities in the etiology of the 2 conditions. However, schizotypy is a heterogeneous facet of personality in the healthy population and so may be seen as a bridge between health and mental illness. Neural evidence for such a continuity would have implications for the characterization and treatment of schizophrenia. Based on our previous work identifying a relationship between symptomology in schizophrenia and abnormal movement-induced electrophysiological response (the post-movement beta rebound [PMBR]), we predicted that if subclinical schizotypy arises from similar neural mechanisms to schizophrenia, schizotypy in healthy individuals would be associated with reduced PMBR. METHODS: One-hundred sixteen participants completed a visuomotor task while their neural activity was recorded by magnetoencephalography. Partial correlations were computed between a measure of PMBR extracted from left primary motor cortex and scores on the Schizotypal Personality Questionnaire (SPQ), a self-report measure of schizotypal personality. Correlations between PMBR and SPQ factor scores measuring cognitive-perceptual, interpersonal and disorganization dimensions of schizotypy were also computed. Effects of site, age, and sex were controlled for. RESULTS: We found a significant negative correlation between total SPQ score and PMBR. This was most strongly mediated by variance shared between interpersonal and disorganization factor scores. CONCLUSION: These findings indicate a continuum of neural deficit between schizotypy and schizophrenia, with diminution of PMBR, previously reported in schizophrenia, also measurable in individuals with schizotypal features, particularly disorganization and impaired interpersonal relations.

Spatial attention modulates visual gamma oscillations across the human ventral stream.

Oscillatory synchronization in the gamma frequency range has been proposed as a neuronal mechanism to prioritize processing of relevant stimuli over competing ones. Recent studies in animals found that selective spatial attention enhanced gamma-band synchronization in high-order visual areas (V4) and increased the gamma peak frequency in V1. The existence of such mechanisms in the human visual system is yet to be fully demonstrated. In this study, we used MEG, in combination with an optimised stimulus design, to record visual gamma oscillations from human early visual cortex, while participants performed a visuospatial attention cueing task. First, we reconstructed virtual sensors in V1/V2, where gamma oscillations were strongly induced by visual stimulation alone. Second, following the results of a statistical comparison between conditions of attention, we reconstructed cortical activity also in inferior occipital-temporal regions (V4). The results indicated that gamma amplitude was modulated by spatial attention across the cortical hierarchy, both in the early visual cortex and in higher-order regions of the ventral visual pathway. In contrast, we found no evidence for an increase in the gamma peak frequency in V1/V2 with attention. The gamma response tended to peak earlier in V1/V2 than in V4 by approximately 70 ms, consistent with a feed-forward role of gamma-band activity in propagating sensory representations across the visual cortical hierarchy. Together, these findings suggest that differences in experimental design or methodology can account for the inconsistencies in previous animal and human studies. Furthermore, our results are in line with the hypothesis of enhanced gamma-band synchronization as an attentional mechanism in the human visual cortex.

Significant reductions in human visual gamma frequency by the gaba reuptake inhibitor tiagabine revealed by robust peak frequency estimation.

The frequency of visual gamma oscillations is determined by both the neuronal excitation-inhibition balance and the time constants of GABAergic processes. The gamma peak frequency has been linked to sensory processing, cognitive function, cortical structure, and may have a genetic contribution. To disentangle the intricate relationship among these factors, accurate and reliable estimates of peak frequency are required. Here, a bootstrapping approach that provides estimates of peak frequency reliability, thereby increasing the robustness of the inferences made on this parameter was developed. The method using both simulated data and real data from two previous pharmacological MEG studies of visual gamma with alcohol and tiagabine was validated. In particular, the study by Muthukumaraswamy et al. [] (Neuropsychopharmacology 38(6):1105-1112), in which GABAergic enhancement by tiagabine had previously demonstrated a null effect on visual gamma oscillations, contrasting with strong evidence from both animal models and very recent human studies was re-evaluated. After improved peak frequency estimation and additional exclusion of unreliably measured data, it was found that the GABA reuptake inhibitor tiagabine did produce, as predicted, a marked decrease in visual gamma oscillation frequency. This result demonstrates the potential impact of objective approaches to data quality control, and provides additional translational evidence for the mechanisms of GABAergic transmission generating gamma oscillations in humans. Hum Brain Mapp 37:3882-3896, 2016. © 2016 Wiley Periodicals, Inc.

Alpha suppression and connectivity modulations in left temporal and parietal cortices index partial awareness of words.

The partial awareness hypothesis is a theoretical proposal that recently provided a reconciling solution to graded and dichotomous accounts of consciousness. It suggests that we can become conscious of distinct properties of an object independently, ranging from low-level features to complex forms of representation. We investigated this hypothesis using classic visual word masking adapted to a near-threshold paradigm. The masking intensity was adjusted to the individual perception threshold, at which individual alphabetical letters, but not words, could be perceived in approximately half of the trials. We confined perception to a pre-lexical stage of word processing that corresponded to a clear condition of partial awareness. At this level of representation, the stimulus properties began to emerge within consciousness, yet they did not escalate to full stimulus awareness. In other words, participants were able to perceive individual letters, while remaining unaware of the whole letter strings presented. Cortical activity measured with MEG was compared between physically identical trials that differed in perception (perceived, not perceived). We found that compared to no awareness, partial awareness of words was characterized by suppression of oscillatory alpha power in left temporal and parietal cortices. The analysis of functional connectivity with seeds based on the power effect in these two regions revealed sparse connections for the parietal seed, and strong connections between the temporal seed and other regions of the language network. We suggest that the engagement of language regions indexed by alpha power suppression is responsible for establishing and maintaining conscious representations of individual pre-lexical units.

The efficacy of EEG neurofeedback aimed at enhancing sensory-motor rhythm theta ratio in healthy subjects.

Scientific evidence supporting the reliability of neurofeedback (NF) in modifying the electroencephalographic (EEG) pattern is still limited. Several studies in NF research and clinical setting have been focused to increase sensory-motor rhythm (SMR) and simultaneously decrease theta activity with the aim of increasing attention performance and reducing hyperactive and impulsive behaviors. The goal of the present study was to assess the efficacy of NF training to enhance the SMR/theta ratio across sixteen sessions of training in eight healthy volunteers. Results suggested an increase of SMR/theta across weeks of training. Theta activity was strongly and steadily inhibited since the first session of training with slight decreases in the following weeks; instead, SMR was strongly inhibited at the beginning and progressively increased across sessions. These results suggest that individuals are able to inhibit theta activity easily while they fail to increase SMR in the first sessions. On the other hand, a separate analysis performed on the baseline preceding NF revealed a decreasing trend of SMR/theta ratio across the 8 weeks of training. Results point to the importance of providing EEG data in addition to behavioral modification, during NF training, to avoid possible misinterpretation of results.