Spontaneous Fluctuations in Oscillatory Brain State Cause Differences in Transcranial Magnetic Stimulation Effects Within and Between Individuals

Transcranial magnetic stimulation (TMS) can cause measurable effects on neural activity and behavioral performance in healthy volunteers. In addition, TMS is increasingly used in clinical practice for treating various neuropsychiatric disorders. Unfortunately, TMS-induced effects show large intra- and inter-subject variability, hindering its reliability, and efficacy. One possible source of this variability may be the spontaneous fluctuations of neuronal oscillations. We present recent studies using multimodal TMS including TMS-EMG (electromyography), TMS-tACS (transcranial alternating current stimulation), and concurrent TMS-EEG-fMRI (electroencephalography, functional magnetic resonance imaging), to evaluate how individual oscillatory brain state affects TMS signal propagation within targeted networks. We demonstrate how the spontaneous oscillatory state at the time of TMS influences both immediate and longer-lasting TMS effects. These findings indicate that at least part of the variability in TMS efficacy may be attributable to the current practice of ignoring (spontaneous) oscillatory fluctuations during TMS. Ignoring this state-dependent spread of activity may cause great individual variability which so far is poorly understood and has proven impossible to control. We therefore also compare two technical solutions to directly account for oscillatory state during TMS, namely, to use (a) tACS to externally control these oscillatory states and then apply TMS at the optimal (controlled) brain state, or (b) oscillatory state-triggered TMS (closed-loop TMS). The described multimodal TMS approaches are paramount for establishing more robust TMS effects, and to allow enhanced control over the individual outcome of TMS interventions aimed at modulating information flow in the brain to achieve desirable changes in cognition, mood, and behavior.

Absolute contrast estimation for soft X-ray photon fluctuation spectroscopy using a variational droplet model

X-ray photon fluctuation spectroscopy using a two-pulse mode at the Linac Coherent Light Source has great potential for the study of quantum fluctuations in materials as it allows for exploration of low-energy physics. However, the complexity of the data analysis and interpretation still prevent recovering real-time results during an experiment, and can even complicate post-analysis processes. This is particularly true for high-spatial resolution applications using CCDs with small pixels, which can decrease the photon mapping accuracy resulting from the large electron cloud generation at the detector. Droplet algorithms endeavor to restore accurate photon maps, but the results can be altered by their hyper-parameters. We present numerical modeling tools through extensive simulations that mimic previous x-ray photon fluctuation spectroscopy experiments. By modification of a fast droplet algorithm, our results demonstrate how to optimize the precise parameters that lift the intrinsic counting degeneracy impeding accuracy in extracting the speckle contrast. These results allow for an absolute determination of the summed contrast from multi-pulse x-ray speckle diffraction, the modus operandi by which the correlation time for spontaneous fluctuations can be measured.

On the equilibrium and stability of a fluidized bed as a thermodynamic system

The transfer of the dispersed layer into a fluidized state makes it possible to intensify the drying process. The small size of the particles leads to an increase in the surface of their contact with the coolant at a relatively low hydrodynamic resistance. Other positive qualities of fluidization are listed, which is very important when carrying out exothermic processes. We studied the behavior of the fluidized bed during the drying process. The curve of fluidization of beet chips is shown. The suspended state of the material began when the forces of the hydrodynamic layer were equal to the weight of all its particles per unit area of the cross-section of the working chamber. The region of existence of the fluidized bed is marked. In this area, the flow was relatively equilibrium (fluidized). On the surface of the layer, small waves were observed with different frequencies and amplitudes of oscillations, as well as with spontaneous fluctuations. This mode of operation was achieved as a result of the study of the structures of the support - gas distribution grid and the drying chamber. The flow velocity profile in the working chamber is investigated. An efficient equalization of velocities with the help of flat stamped grids has been established. The results were confirmed by the spectra of the flow in the drying chamber. Oscillations on the free surface of a fluidized bed are considered. The Euler equation was written, which made it possible, as a result of various transformations, to obtain a formula for calculating the oscillation frequency of the fluidized bed. The studies carried out made it possible to establish the regimes of pseudo-fluidization, to a certain extent minimizing the heterogeneity of the layer, which is of significant practical importance. However, the operating parameters need to be adjusted depending on the type of material to be dried and other indicators. The research results do not obscure the general provisions of nonequilibrium thermodynamics. The fluidized bed cannot be in an equilibrium state, since the transfer of substances is obvious: energy, mass and momentum. It is correct to regard the fluidized bed as unstable. Small and spontaneous fluctuations always exist in the layer. The absence of conditions for their decay becomes a condition for the instability of the process.

Coupling between Trigeminal-Induced Asymmetries in Locus Coeruleus Activity and Cognitive Performance

In humans, the asymmetry in the masseter electromyographic (EMG) activity during clenching is positively correlated with the degree of pupil size asymmetry (anisocoria) at rest. Anisocoria reveals an asymmetry in LC activity, which may lead to an imbalance in cortical excitability, detrimental to performance. Hereby, we investigated, in individual subjects, the possibility that occlusal correction, which decreases EMG asymmetry, improves performance by balancing LC activity. Cognitive performance, task-related mydriasis, and pupil size at rest were modified by changing the occlusal condition. Occlusal-related changes in performance and mydriasis were negatively correlated with anisocoria changes in only 12/20 subjects. Within this population, spontaneous fluctuations in mydriasis and anisocoria also appeared negatively coupled. Occlusal-related changes in performance and mydriasis were negatively correlated with those in average pupil size (a proxy of average LC activity) in 19/20 subjects. The strongest association was observed for the pupil changes occurring on the side with higher EMG activity during clenching. These findings indicate that the effects of occlusal conditions on cognitive performance were coupled to changes in the asymmetry of LC activity in about half of the subjects, while they were related to changes in the average tonic LC activity in virtually all of them.

Potential and Realized Impact of Astroglia Ca2 + Dynamics on Circuit Function and Behavior

Astroglia display a wide range of spontaneous and behavioral state-dependent Ca2+ dynamics. During heightened vigilance, noradrenergic signaling leads to quasi-synchronous Ca2+ elevations encompassing soma and processes across the brain-wide astroglia network. Distinct from this vigilance-associated global Ca2+ rise are apparently spontaneous fluctuations within spatially restricted microdomains. Over the years, several strategies have been pursued to shed light on the physiological impact of these signals including deletion of endogenous ion channels or receptors and reduction of intracellular Ca2+ through buffering, extrusion or inhibition of release. Some experiments that revealed the most compelling behavioral alterations employed chemogenetic and optogenetic manipulations to modify astroglia Ca2+ signaling. However, there is considerable contrast between these findings and the comparatively modest effects of inhibiting endogenous sources of Ca2+. In this review, we describe the underlying mechanisms of various forms of astroglia Ca2+ signaling as well as the functional consequences of their inhibition. We then discuss how the effects of exogenous astroglia Ca2+ modification combined with our knowledge of physiological mechanisms of astroglia Ca2+ activation could guide further refinement of behavioral paradigms that will help elucidate the natural Ca2+-dependent function of astroglia.

Subcortical Structures and Creative Divergent Thinking: A Resting-State functional MRI Analysis

This study aimed to testify whether spontaneous fluctuations in the subcortex contribute to creative divergent thinking. Individuals at high- and low levels of creativity were recruited and the resting-state fMRI data was collected. Seed-wise and dynamic functional connectivity (FC) were used to identify differences between the two groups. The topological properties of the subcortical network were measured, and their relationship with performance of creative divergent thinking was calculated using brain-behaviour correlation analyses. The results revealed higher FC between the putamen, pallidum, and thalamus in high creativity group (HCG) compared to low creativity group (LCG) within the subcortex. Whole-brain FC results showed stronger connection across subcortical (i.e., the thalamus and pallidum) and cerebral regions (i.e., the insula, middle frontal gyrus, and middle temporal gyrus) in HCG compared to LCG. In addition, the subcortical FC demonstrated a positive correlation with performance of creative thinking across the pallidum, putamen, and thalamus. Our findings may provide novel insights into the relationship between creative divergent thinking and the activities of the subcortex. It is likely that not only fronto-striatal dopaminergic pathways, but also “motor” pathways, are involved in creative thinking processing.

Spontaneous neural oscillations influence behavior and sensory representations by suppressing neuronal excitability

The ability to process and respond to external input is critical for adaptive behavior. Why, then, do neural and behavioral responses vary across repeated presentations of the same sensory input? Spontaneous fluctuations of neuronal excitability are currently hypothesized to underlie the trial-by-trial variability in sensory processing. To test this, we capitalized on invasive electrophysiology in neurosurgical patients performing an auditory discrimination task with visual cues: specifically, we examined the interaction between prestimulus alpha oscillations, excitability, task performance, and decoded neural stimulus representations. We found that strong prestimulus oscillations in the alpha+ band (i.e., alpha and neighboring frequencies), rather than the aperiodic signal, correlated with a low excitability state, indexed by reduced broadband high-frequency activity. This state was related to slower reaction times and reduced neural stimulus encoding strength. We propose that the alpha+ rhythm modulates excitability, thereby resulting in variability in behavior and sensory representations despite identical input.