Brain dynamics and spatiotemporal trajectories during threat processing.

In the past decades, functional MRI research has investigated mental states and their brain bases in largely static fashion based on evoked responses during blocked and event-related designs. Despite some progress in naturalistic designs, our understanding of threat processing remains largely limited to those obtained with standard paradigms. In the present paper, we applied Switching Linear Dynamical Systems to uncover the dynamics of threat processing during a continuous threat-of-shock paradigm. Importantly, unlike studies in systems neuroscience that frequently assume that systems are decoupled from external inputs, we characterized both endogenous and exogenous contributions to dynamics. First, we demonstrated that the SLDS model learned the regularities of the experimental paradigm, such that states and state transitions estimated from fMRI time series data from 85 ROIs reflected both the proximity of the circles and their direction (approach vs. retreat). After establishing that the model captured key properties of threat-related processing, we characterized the dynamics of the states and their transitions. The results revealed that threat processing can profitably be viewed in terms of dynamic multivariate patterns whose trajectories are a combination of intrinsic and extrinsic factors that jointly determine how the brain temporally evolves during dynamic threat. We propose that viewing threat processing through the lens of dynamical systems offers important avenues to uncover properties of the dynamics of threat that are not unveiled with standard experimental designs and analyses.

Noncortical cognition: integration of information for close-proximity behavioral problem-solving.

Animals face behavioral problems that can be conceptualized in terms of a gradient of spatial and temporal proximity. I propose that solving close-proximity behavioral problems involves integrating disparate types of information in complex and flexible ways. In this framework, the midbrain periaqueductal gray (PAG) is understood as a key region involved in close-proximity motivated cognition. Anatomically, the PAG has access to signals across the neuroaxis via extensive connectivity with cortex, subcortex, and brainstem. However, the flow of signals is not unidirectional, as the PAG projects to the cortex directly, and further ascending signal flow is attained via the midline thalamus. Overall, the anatomical organization of the PAG allows is to be a critical hub engaged in cognition "here and now".

The Spiraling Cognitive-Emotional Brain: Combinatorial, Reciprocal, and Reentrant Macro-organization.

This article proposes a framework for understanding the macro-scale organization of anatomical pathways in the mammalian brain. The architecture supports flexible behavioral decisions across a spectrum of spatio-temporal scales. The proposal emphasizes the combinatorial, reciprocal, and reentrant connectivity-called CRR neuroarchitecture-between cortical, BG, thalamic, amygdala, hypothalamic, and brainstem circuits. Thalamic nuclei, especially midline/intralaminar nuclei, are proposed to act as hubs routing the flow of signals between noncortical areas and pFC. The hypothalamus also participates in multiregion circuits via its connections with cortex and thalamus. At slower timescales, long-range behaviors integrate signals across levels of the neuroaxis. At fast timescales, parallel engagement of pathways allows urgent behaviors while retaining flexibility. Overall, the proposed architecture enables context-dependent, adaptive behaviors spanning proximate to distant spatio-temporal scales. The framework promotes an integrative perspective and a distributed, heterarchical view of brain function.

Characterization and bioactivities of coffee husks extract encapsulated with polyvinylpyrrolidone.

Coffee processing generates large amounts of residues of which a portion still has bioactive properties due to their richness in phenolic compounds. This study aimed to obtain a coffee husks extract (CHE) and to encapsulate it (ECHE) with polyvinylpyrrolidone using a one-step procedure of solid dispersion. The extraction and encapsulation yields were 9.1% and 92%, respectively. Thermal analyses revealed that the encapsulation increased the thermal stability of CHE and dynamic light scattering analyses showed a bimodal distribution of size with 81% of the ECHE particles measuring approximately 711 nm. Trigonelline and caffeine were the main alkaloids and quercetin the main phenolic compound in CHE, and the encapsulation tripled quercetin extraction. The total phenolics content and the antioxidant activity of ECHE, assayed with three different procedures, were higher than those of CHE. The antioxidant activity and the bioaccessibility of the phenolic compounds of ECHE were also higher than those of CHE following simulated gastrointestinal digestion (SGID). Both CHE and ECHE were not toxic against Alliumcepa cells and showed similar capacities for inhibiting the pancreatic α-amylase in vitro. After SGID, however, ECHE became a 1.9-times stronger inhibitor of the α-amylase activity in vitro (IC50 = 8.5 mg/mL) when compared to CHE. Kinetic analysis revealed a non-competitive mechanism of inhibition and in silico docking simulation suggests that quercetin could be contributing significantly to the inhibitory action of both ECHE and CHE. In addition, ECHE (400 mg/kg) was able to delay by 50% the increases of blood glucose in vivo after oral administration of starch to rats. This finding shows that ECHE may be a candidate ingredient in dietary supplements used as an adjuvant for the treatment of diabetes.

Multimodal measures of spontaneous brain activity reveal both common and divergent patterns of cortical functional organization.

Large-scale functional networks have been characterized in both rodent and human brains, typically by analyzing fMRI-BOLD signals. However, the relationship between fMRI-BOLD and underlying neural activity is complex and incompletely understood, which poses challenges to interpreting network organization obtained using this technique. Additionally, most work has assumed a disjoint functional network organization (i.e., brain regions belong to one and only one network). Here, we employ wide-field Ca2+ imaging simultaneously with fMRI-BOLD in mice expressing GCaMP6f in excitatory neurons. We determine cortical networks discovered by each modality using a mixed-membership algorithm to test the hypothesis that functional networks exhibit overlapping organization. We find that there is considerable network overlap (both modalities) in addition to disjoint organization. Our results show that multiple BOLD networks are detected via Ca2+ signals, and networks determined by low-frequency Ca2+ signals are only modestly more similar to BOLD networks. In addition, the principal gradient of functional connectivity is nearly identical for BOLD and Ca2+ signals. Despite similarities, important differences are also detected across modalities, such as in measures of functional connectivity strength and diversity. In conclusion, Ca2+ imaging uncovers overlapping functional cortical organization in the mouse that reflects several, but not all, properties observed with fMRI-BOLD signals.

Controversies and progress on standardization of large-scale brain network nomenclature.

Progress in scientific disciplines is accompanied by standardization of terminology. Network neuroscience, at the level of macroscale organization of the brain, is beginning to confront the challenges associated with developing a taxonomy of its fundamental explanatory constructs. The Workgroup for HArmonized Taxonomy of NETworks (WHATNET) was formed in 2020 as an Organization for Human Brain Mapping (OHBM)-endorsed best practices committee to provide recommendations on points of consensus, identify open questions, and highlight areas of ongoing debate in the service of moving the field toward standardized reporting of network neuroscience results. The committee conducted a survey to catalog current practices in large-scale brain network nomenclature. A few well-known network names (e.g., default mode network) dominated responses to the survey, and a number of illuminating points of disagreement emerged. We summarize survey results and provide initial considerations and recommendations from the workgroup. This perspective piece includes a selective review of challenges to this enterprise, including (1) network scale, resolution, and hierarchies; (2) interindividual variability of networks; (3) dynamics and nonstationarity of networks; (4) consideration of network affiliations of subcortical structures; and (5) consideration of multimodal information. We close with minimal reporting guidelines for the cognitive and network neuroscience communities to adopt.

The Effect of Month of Harvesting and Temperature-Humidity Index on the Number and Quality of Oocytes and In Vitro Embryo Production in Holstein Cows and Heifers.

The aim of this study was to evaluate the effect of the month of oocyte harvesting and the temperature-humidity index on oocyte number and quality harvested from Holstein cows and heifers, oocyte developmental competence, and total embryos produced in an area of intense ambient temperature for most of the year. A total of 5064 multiparous lactating cows and 2988 nulliparous heifers were used as oocyte donors and distributed across the months of the year. Overall, total oocytes per collection did not differ (p > 0.05) between cows (16.6 ± 2.7) and heifers (15.1 ± 1.8), but oocyte developmental competence was lower (p < 0.05) in cows (21.3 ± 5.4) than heifers (25.5 ± 4.0). For cows, the total number of oocytes harvested was two-fold higher (p < 0.05) in November than in May. For heifers, the total number of oocytes harvested was highest in April (17.19 ± 0.53) and lowest in May (10.94 ± 0.32; p < 0.05). For cows, total embryos were highest in November (2.58 ± 0.42) and lowest in August (1.28 ± 0.10; p < 0.05). Thus, taken together, these results indicate that severe heat stress impaired the number and quality of oocytes harvested from donor Holstein multiparous cows and heifers, oocyte developmental competence, and total embryos produced in this area of intense ambient temperature for most of the year.

Multimodal measures of spontaneous brain activity reveal both common and divergent patterns of cortical functional organization.

Large-scale functional networks have been characterized in both rodent and human brains, typically by analyzing fMRI-BOLD signals. However, the relationship between fMRI-BOLD and underlying neural activity is complex and incompletely understood, which poses challenges to interpreting network organization obtained using this technique. Additionally, most work has assumed a disjoint functional network organization (i.e., brain regions belong to one and only one network). Here, we employed wide-field Ca2+ imaging simultaneously with fMRI-BOLD in mice expressing GCaMP6f in excitatory neurons. We determined cortical networks discovered by each modality using a mixed-membership algorithm to test the hypothesis that functional networks are overlapping rather than disjoint. Our results show that multiple BOLD networks are detected via Ca2+ signals; there is considerable network overlap (both modalities); networks determined by low-frequency Ca2+ signals are only modestly more similar to BOLD networks; and, despite similarities, important differences are detected across modalities (e.g., brain region "network diversity"). In conclusion, Ca2+ imaging uncovered overlapping functional cortical organization in the mouse that reflected several, but not all, properties observed with fMRI-BOLD signals.

Threat and Reward Imminence Processing in the Human Brain.

In the human brain, aversive and appetitive processing have been studied with controlled stimuli in rather static settings. In addition, the extent to which aversive-related and appetitive-related processing engage distinct or overlapping circuits remains poorly understood. Here, we sought to investigate the dynamics of aversive and appetitive processing while male and female participants engaged in comparable trials involving threat avoidance or reward seeking. A central goal was to characterize the temporal evolution of responses during periods of threat or reward imminence. For example, in the aversive domain, we predicted that the bed nucleus of the stria terminalis (BST), but not the amygdala, would exhibit anticipatory responses given the role of the former in anxious apprehension. We also predicted that the periaqueductal gray (PAG) would exhibit threat-proximity responses based on its involvement in proximal-threat processes, and that the ventral striatum would exhibit threat-imminence responses given its role in threat escape in rodents. Overall, we uncovered imminence-related temporally increasing ("ramping") responses in multiple brain regions, including the BST, PAG, and ventral striatum, subcortically, and dorsal anterior insula and anterior midcingulate, cortically. Whereas the ventral striatum generated anticipatory responses in the proximity of reward as expected, it also exhibited threat-related imminence responses. In fact, across multiple brain regions, we observed a main effect of arousal. In other words, we uncovered extensive temporally evolving, imminence-related processing in both the aversive and appetitive domain, suggesting that distributed brain circuits are dynamically engaged during the processing of biologically relevant information regardless of valence, findings further supported by network analysis.SIGNIFICANCE STATEMENT In the human brain, aversive and appetitive processing have been studied with controlled stimuli in rather static settings. Here, we sought to investigate the dynamics of aversive/appetitive processing while participants engaged in trials involving threat avoidance or reward seeking. A central goal was to characterize the temporal evolution of responses during periods of threat or reward imminence. We uncovered imminence-related temporally increasing ("ramping") responses in multiple brain regions, including the bed nucleus of the stria terminalis, periaqueductal gray, and ventral striatum, subcortically, and dorsal anterior insula and anterior midcingulate, cortically. Overall, we uncovered extensive temporally evolving, imminence-related processing in both the aversive and appetitive domain, suggesting that distributed brain circuits are dynamically engaged during the processing of biologically relevant information regardless of valence.

How many brain regions are needed to elucidate the neural bases of fear and anxiety?

We suggest that to understand complex behaviors associated with fear and anxiety, we need to understand brain processes at the collective, network level. But what should be the type and spatial scale of the targeted circuits/networks? Not only are multi-region interactions essential-including complex reciprocal interactions, loops, and other types of arrangement-but it is profitable to characterize circuits spanning the entire neuroaxis. In particular, it is productive to conceptualize the circuits contributing to fear/anxiety as embedded into large-scale connectional systems. We discuss circuits involving the basolateral amygdala that contribute to aversive conditioning and fear extinction. In addition, we highlight the importance of the extended amygdala (central nucleus of the amygdala and bed nucleus of the stria terminalis) cortical-subcortical loop, which allows large swaths of cortex and subcortex to influence fear and anxiety. In this manner, fear/anxiety can be understood not only based on traditional "descending" mechanisms involving the hypothalamus and brainstem, but in terms of a considerably broader reentrant organization.

Threat and reward imminence processing in the human brain.

In the human brain, aversive and appetitive processing have been studied with controlled stimuli in rather static settings. In addition, the extent to which aversive- and appetitive-related processing engage distinct or overlapping circuits remains poorly understood. Here, we sought to investigate the dynamics of aversive and appetitive processing while male and female participants engaged in comparable trials involving threat-avoidance or reward-seeking. A central goal was to characterize the temporal evolution of responses during periods of threat or reward imminence . For example, in the aversive domain, we predicted that the bed nucleus of the stria terminalis (BST), but not the amygdala, would exhibit anticipatory responses given the role of the former in anxious apprehension. We also predicted that the periaqueductal gray (PAG) would exhibit threat-proximity responses based on its involvement in proximal-threat processes, and that the ventral striatum would exhibit threat-imminence responses given its role in threat escape in rodents. Overall, we uncovered imminence-related temporally increasing ("ramping") responses in multiple brain regions, including the BST, PAG, and ventral striatum, subcortically, and dorsal anterior insula and anterior midcingulate, cortically. Whereas the ventral striatum generated anticipatory responses in the proximity of reward as expected, it also exhibited threat-related imminence responses. In fact, across multiple brain regions, we observed a main effect of arousal. In other words, we uncovered extensive temporally-evolving, imminence-related processing in both the aversive and appetitive domain, suggesting that distributed brain circuits are dynamically engaged during the processing of biologically relevant information irrespective of valence, findings further supported by network analysis. Significance Statement: In the human brain, aversive and appetitive processing have been studied with controlled stimuli in rather static settings. Here, we sought to investigate the dynamics of aversive/appetitive processing while participants engaged in trials involving threat-avoidance or reward-seeking. A central goal was to characterize the temporal evolution of responses during periods of threat or reward imminence . We uncovered imminence-related temporally increasing ("ramping") responses in multiple brain regions, including the bed nucleus of the stria terminalis, periaqueductal gray, and ventral striatum, subcortically, and dorsal anterior insula and anterior midcingulate, cortically. Overall, we uncovered extensive temporally-evolving, imminence-related processing in both the aversive and appetitive domain, suggesting that distributed brain circuits are dynamically engaged during the processing of biologically relevant information irrespective of valence.

The Entangled Brain.

The Entangled Brain (Pessoa, L., 2002. MIT Press) promotes the idea that we need to understand the brain as a complex, entangled system. Why does the complex systems perspective, one that entails emergent properties, matter for brain science? In fact, many neuroscientists consider these ideas a distraction. We discuss three principles of brain organization that inform the question of the interactional complexity of the brain: (1) massive combinatorial anatomical connectivity; (2) highly distributed functional coordination; and (3) networks/circuits as functional units. To motivate the challenges of mapping structure and function, we discuss neural circuits illustrating the high anatomical and functional interactional complexity typical in the brain. We discuss potential avenues for testing for network-level properties, including those relying on distributed computations across multiple regions. We discuss implications for brain science, including the need to characterize decentralized and heterarchical anatomical-functional organization. The view advocated has important implications for causation, too, because traditional accounts of causality provide poor candidates for explanation in interactionally complex systems like the brain given the distributed, mutual, and reciprocal nature of the interactions. Ultimately, to make progress understanding how the brain supports complex mental functions, we need to dissolve boundaries within the brain-those suggested to be associated with perception, cognition, action, emotion, motivation-as well as outside the brain, as we bring down the walls between biology, psychology, mathematics, computer science, philosophy, and so on.

A call for more clarity around causality in neuroscience.

In neuroscience, the term 'causality' is used to refer to different concepts, leading to confusion. Here we illustrate some of those variations, and we suggest names for them. We then introduce four ways to enhance clarity around causality in neuroscience.

Chemometric evaluation of enzymatic hydrolysis in the production of fish protein hydrolysates with acetylcholinesterase inhibitory activity.

Fish protein hydrolysates (FPH) obtained from industrial processing residues are sources of bioactive peptides. The enzymatic hydrolysis process is essential in obtaining specific bioactivities such as inhibition of the enzyme acetylcholinesterase (AChE). In this study the effect of different hydrolysis conditions on the properties of FPH to inhibit the enzyme acetylcholinesterase. A chemometric evaluation, based on a central composite rotatable design and principal component analysis, was applied to select hydrolysis conditions with best yield, degree of hydrolysis and acetylcholinesterase inhibition. Experimental design results for AChE inhibition were between 10.51 and 40.45% (20, 30 and 50 mg.mL-1 of FPH), and three hydrolysis conditions were selected based on PCA evaluation. The amino acids profile, FTIR and AChE inhibition kinetics were evaluated. Results showed a mixed type of inhibition behavior and, the docking molecular analyzes suggest that the inhibition AChE occurred due to the basic amino acids, mainly by arginine.

Effectiveness of soil conditioners to enhance salt extraction ability of Salicornia ramosissima in saline-sodic soil for different soil moisture contents.

Soil salinity is considered one of the main types of soil degradation in semiarid environments around the globe. This work aims to evaluate the effectiveness of soil conditioners to enhance the growth and salt extraction ability of Salicornia ramosíssima for different soil moisture contents. Salicornia plants were cultivated in pots in which the soils were treated with the following conditioners: control; gypsum + organic matter; elemental sulfur + organic matter; and gypsum + elemental sulfur + organic matter. Salicornia plants were subjected to two soil moisture rates - at 35 and 85% field capacity. Soil conditioners associated with higher contents of soil moisture promoted significant increases, compared to control, in fresh (6.20 - 11.13 g) and dry matter (1.20 - 2.07 g), relative biomass (100 - 179%) as well as significantly increased the concentrations of Na+ (56.09 - 65.64 mg kg-1) and Cl- (110.83 - 150.0 mg kg-1) in plant tissues. Soil conditioners significantly increased salt extraction ability under the two moisture levels, mainly by promoting higher values for both transfer factor and phytoremediation potential. The best performance of Salicornia in terms of plant yield and salt extraction, regardless of the moisture level, was the gypsum + organic matter.Novelty statementThere are no studies in the literature relating the use of conditioners as a strategy to enhance Salicornia's ability to extract salts.This work contributes to the management of salinized areas around the globe in two main aspects. The first is that many of these salt-degraded areas are desertified and through this study, it is possible to revegetate and recover them. The second one is that, since Salicornia is a plant with economic value, this can serve as an incentive for farmers to grow Salicornia in saline areas.

Distributed and Multifaceted Effects of Threat and Safety.

In the present fMRI study, we examined how anxious apprehension is processed in the human brain. A central goal of the study was to test the prediction that a subset of brain regions would exhibit sustained response profiles during threat periods, including the anterior insula, a region implicated in anxiety disorders. A second important goal was to evaluate the responses in the amygdala and the bed nucleus of the stria terminals, regions that have been suggested to be involved in more transient and sustained threat, respectively. A total of 109 participants performed an experiment in which they encountered "threat" or "safe" trials lasting approximately 16 sec. During the former, they experienced zero to three highly unpleasant electrical stimulations, whereas in the latter, they experienced zero to three benign electrical stimulations (not perceived as unpleasant). The timing of the stimulation during trials was randomized, and as some trials contained no stimulation, stimulation delivery was uncertain. We contrasted responses during threat and safe trials that did not contain electrical stimulation, but only the potential that unpleasant (threat) or benign (safe) stimulation could occur. We employed Bayesian multilevel analysis to contrast responses to threat and safe trials in 85 brain regions implicated in threat processing. Our results revealed that the effect of anxious apprehension is distributed across the brain and that the temporal evolution of the responses is quite varied, including more transient and more sustained profiles, as well as signal increases and decreases with threat.

Refocusing neuroscience: moving away from mental categories and towards complex behaviours.

Mental terms-such as perception, cognition, action, emotion, as well as attention, memory, decision-making-are epistemically sterile. We support our thesis based on extensive comparative neuroanatomy knowledge of the organization of the vertebrate brain. Evolutionary pressures have moulded the central nervous system to promote survival. Careful characterization of the vertebrate brain shows that its architecture supports an enormous amount of communication and integration of signals, especially in birds and mammals. The general architecture supports a degree of 'computational flexibility' that enables animals to cope successfully with complex and ever-changing environments. Here, we suggest that the vertebrate neuroarchitecture does not respect the boundaries of standard mental terms, and propose that neuroscience should aim to unravel the dynamic coupling between large-scale brain circuits and complex, naturalistic behaviours. This article is part of the theme issue 'Systems neuroscience through the lens of evolutionary theory'.

Learning brain dynamics for decoding and predicting individual differences.

Insights from functional Magnetic Resonance Imaging (fMRI), as well as recordings of large numbers of neurons, reveal that many cognitive, emotional, and motor functions depend on the multivariate interactions of brain signals. To decode brain dynamics, we propose an architecture based on recurrent neural networks to uncover distributed spatiotemporal signatures. We demonstrate the potential of the approach using human fMRI data during movie-watching data and a continuous experimental paradigm. The model was able to learn spatiotemporal patterns that supported 15-way movie-clip classification (∼90%) at the level of brain regions, and binary classification of experimental conditions (∼60%) at the level of voxels. The model was also able to learn individual differences in measures of fluid intelligence and verbal IQ at levels comparable to that of existing techniques. We propose a dimensionality reduction approach that uncovers low-dimensional trajectories and captures essential informational (i.e., classification related) properties of brain dynamics. Finally, saliency maps and lesion analysis were employed to characterize brain-region/voxel importance, and uncovered how dynamic but consistent changes in fMRI activation influenced decoding performance. When applied at the level of voxels, our framework implements a dynamic version of multivariate pattern analysis. Our approach provides a framework for visualizing, analyzing, and discovering dynamic spatially distributed brain representations during naturalistic conditions.

How representative are neuroimaging samples? Large-scale evidence for trait anxiety differences between fMRI and behaviour-only research participants.

Over the past three decades, functional magnetic resonance imaging (fMRI) has become crucial to study how cognitive processes are implemented in the human brain. However, the question of whether participants recruited into fMRI studies differ from participants recruited into other study contexts has received little to no attention. This is particularly pertinent when effects fail to generalize across study contexts: for example, a behavioural effect discovered in a non-imaging context not replicating in a neuroimaging environment. Here, we tested the hypothesis, motivated by preliminary findings (N = 272), that fMRI participants differ from behaviour-only participants on one fundamental individual difference variable: trait anxiety. Analysing trait anxiety scores and possible confounding variables from healthy volunteers across multiple institutions (N = 3317), we found robust support for lower trait anxiety in fMRI study participants, consistent with a sampling or self-selection bias. The bias was larger in studies that relied on phone screening (compared with full in-person psychiatric screening), recruited at least partly from convenience samples (compared with community samples), and in pharmacology studies. Our findings highlight the need for surveying trait anxiety at recruitment and for appropriate screening procedures or sampling strategies to mitigate this bias.