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Functional connectivity of neural oscillations (oscillation-based FC) is thought to afford dynamic information exchange across task-relevant neural ensembles. Although oscillation-based FC is classically defined relative to a prestimulus baseline, giving rise to rapid, context-dependent changes in individual connections, studies of distributed spatial patterns show that oscillation-based FC is omnipresent, occurring even in the absence of explicit cognitive demands. Thus, the issue of whether oscillation-based FC is primarily shaped by cognitive state or is intrinsic in nature remains open. Accordingly, we sought to reconcile these observations by interrogating the ECoG recordings of 18 presurgical human patients (8 females) for state dependence of oscillation-based FC in five canonical frequency bands across an array of six task states. FC analysis of phase and amplitude coupling revealed a highly similar, largely state-invariant (i.e., intrinsic) spatial component across cognitive states. This spatial organization was shared across all frequency bands. Crucially, however, each band also exhibited temporally independent FC dynamics capable of supporting frequency-specific information exchange. In conclusion, the spatial organization of oscillation-based FC is largely stable over cognitive states (i.e., primarily intrinsic in nature) and shared across frequency bands. Together, our findings converge with previous observations of spatially invariant patterns of FC derived from extremely slow and aperiodic fluctuations in fMRI signals. Our observations indicate that "background" FC should be accounted for in conceptual frameworks of oscillation-based FC targeting task-related changes. SIGNIFICANCE STATEMENT A fundamental property of neural activity is that it is periodic, enabling functional connectivity (FC) between distant regions through coupling of their oscillations. According to task-based studies, such oscillation-based FC is rapid and malleable to meet cognitive task demands. Studying distributed FC patterns instead of FC in a few individual connections, we found that oscillation-based FC is largely stable across various cognitive states and shares a common layout across oscillation frequencies. This stable spatial organization of FC in fast oscillatory brain signals parallels the known stability of fMRI-based intrinsic FC architecture. Despite the observed spatial state and frequency invariance, FC of individual connections was temporally independent between frequency bands, suggesting a putative mechanism for malleable frequency-specific FC to support cognitive tasks., (Copyright © 2021 the authors.)

The nicotinic system plays an important role in cognitive control and is implicated in several neuropsychiatric conditions. However, the contributions of genetic variability in this system to individuals' cognitive control abilities are poorly understood and the brain processes that mediate such genetic contributions remain largely unidentified. In this first large-scale neuroimaging genetics study of the human nicotinic receptor system (two cohorts, males and females, fMRI total N = 1586, behavioral total N = 3650), we investigated a common polymorphism of the high-affinity nicotinic receptor α4β2 (rs1044396 on the CHRNA4 gene) previously implicated in behavioral and nicotine-related studies (albeit with inconsistent major/minor allele impacts). Based on our prior neuroimaging findings, we expected this polymorphism to affect neural activity in the cingulo-opercular (CO) network involved in core cognitive control processes including maintenance of alertness. Consistent across the cohorts, all cortical areas of the CO network showed higher activity in heterozygotes compared with both types of homozygotes during cognitive engagement. This inverted U-shaped relation reflects an overdominant effect; that is, allelic interaction (cumulative evidence p = 1.33 * 10 -5 ). Furthermore, heterozygotes performed more accurately in behavioral tasks that primarily depend on sustained alertness. No effects were observed for haplotypes of the surrounding CHRNA4 region, supporting a true overdominant effect at rs1044396. As a possible mechanism, we observed that this polymorphism is an expression quantitative trait locus modulating CHRNA4 expression levels. This is the first report of overdominance in the nicotinic system. These findings connect CHRNA4 genotype, CO network activation, and sustained alertness, providing insights into how genetics shapes individuals' cognitive control abilities. SIGNIFICANCE STATEMENT The nicotinic acetylcholine system plays a central role in neuromodulatory regulation of cognitive control processes and is dysregulated in several neuropsychiatric disorders. Despite this functional importance, no large-scale neuroimaging genetics studies have targeted the contributions of genetic variability in this system to human brain activity. Here, we show the impact of a common polymorphism of the high-affinity nicotinic receptor α4β2 that is consistent across brain activity and behavior in two large human cohorts. We report a hitherto unknown overdominant effect (allelic interaction) at this locus, where the heterozygotes show higher activity in the cingulo-opercular network underlying alertness maintenance and higher behavioral alertness performance than both homozygous groups. This gene-brain-behavior relationship informs about the biological basis of interindividual differences in cognitive control., (Copyright © 2017 the authors 0270-6474/17/379658-10$15.00/0.)

Neural oscillations in the alpha band (8-12 Hz) are increasingly viewed as an active inhibitory mechanism that gates and controls sensory information processing as a function of cognitive relevance. Extending this view, phase synchronization of alpha oscillations across distant cortical regions could regulate integration of information. Here, we investigated whether such long-range cross-region coupling in the alpha band is intrinsically and selectively linked to activity in a distinct functionally specialized brain network. If so, this would provide new insight into the functional role of alpha band phase synchrony. We adapted the phase-locking value to assess fluctuations in synchrony that occur over time in ongoing activity. Concurrent EEG and functional magnetic resonance imaging (fMRI) were recorded during resting wakefulness in 26 human subjects. Fluctuations in global synchrony in the upper alpha band correlated positively with activity in several prefrontal and parietal regions (as measured by fMRI). fMRI intrinsic connectivity analysis confirmed that these regions correspond to the well known fronto-parietal (FP) network. Spectral correlations with this network's activity confirmed that no other frequency band showed equivalent results. This selective association supports an intrinsic relation between large-scale alpha phase synchrony and cognitive functions associated with the FP network. This network has been suggested to implement phasic aspects of top-down modulation such as initiation and change in moment-to-moment control. Mechanistically, long-range upper alpha band synchrony is well suited to support these functions. Complementing our previous findings that related alpha oscillation power to neural structures serving tonic control, the current findings link alpha phase synchrony to neural structures underpinning phasic control of alertness and task requirements.

To interact with our dynamic environment, the brain merges motion information from auditory and visual senses. However, not only "natural" auditory MOTION, but also "metaphoric" de/ascending PITCH and SPEECH (e.g., "left/right"), influence the visual motion percept. Here, we systematically investigate whether these three classes of direction signals influence visual motion perception through shared or distinct neural mechanisms. In a visual-selective attention paradigm, subjects discriminated the direction of visual motion at several levels of reliability, with an irrelevant auditory stimulus being congruent, absent, or incongruent. Although the natural, metaphoric, and linguistic auditory signals were equally long and adjusted to induce a comparable directional bias on the motion percept, they influenced visual motion processing at different levels of the cortical hierarchy. A significant audiovisual interaction was revealed for MOTION in left human motion complex (hMT+/V5+) and for SPEECH in right intraparietal sulcus. In fact, the audiovisual interaction gradually decreased in left hMT+/V5+ for MOTION > PITCH > SPEECH and in right intraparietal sulcus for SPEECH > PITCH > MOTION. In conclusion, natural motion signals are integrated in audiovisual motion areas, whereas the influence of culturally learnt signals emerges primarily in higher-level convergence regions.