An atlas of genetic effects on cellular composition of the tumor microenvironment.

Deciphering the composition of the tumor microenvironment (TME) is critical for understanding tumorigenesis and to design immunotherapies. In the present study, we mapped genetic effects on cell-type proportions using single-cell and bulk RNA sequencing data, identifying 3,494 immunity quantitative trait loci (immunQTLs) across 23 cancer types from The Cancer Genome Atlas. Functional annotation revealed regulatory potential and we further assigned 1,668 genes that regulate TME composition. We constructed a combined immunQTL map by integrating data from European and Chinese colorectal cancer (CRC) samples. A polygenic risk score that incorporates these immunQTLs and hits on a genome-wide association study outperformed in CRC risk stratification within 447,495 multiethnic individuals. Using large-scale population cohorts, we identified that the immunQTL rs1360948 is associated with CRC risk and prognosis. Mechanistically, the rs1360948-G-allele increases CCL2 expression, recruiting regulatory T cells that can exert immunosuppressive effects on CRC progression. Blocking the CCL2-CCR2 axis enhanced anti-programmed cell death protein 1 ligand therapy. Finally, we have established a database (CancerlmmunityQTL2) to serve the research community and advance our understanding of immunogenomic interactions in cancer pathogenesis.

Genetic architectures of the human hippocampus and those involved in neuropsychiatric traits.

BACKGROUND: The hippocampus, with its complex subfields, is linked to numerous neuropsychiatric traits. While most research has focused on its global structure or a few specific subfields, a comprehensive analysis of hippocampal substructures and their genetic correlations across a wide range of neuropsychiatric traits remains underexplored. Given the hippocampus's high heritability, considering hippocampal and subfield volumes (HASV) as endophenotypes for neuropsychiatric conditions is essential. METHODS: We analyzed MRI-derived volumetric data of hippocampal and subfield structures from 41,525 UK Biobank participants. Genome-wide association studies (GWAS) on 24 HASV traits were conducted, followed by genetic correlation, overlap, and Mendelian randomization (MR) analyses with 10 common neuropsychiatric traits. Polygenic risk scores (PRS) based on HASV traits were also evaluated for predicting these traits. RESULTS: Our analysis identified 352 independent genetic variants surpassing a significance threshold of 2.1 × 10-9 within the 24 HASV traits, located across 93 chromosomal regions. Notably, the regions 12q14.3, 17q21.31, 12q24.22, 6q21, 9q33.1, 6q25.1, and 2q24.2 were found to influence multiple HASVs. Gene set analysis revealed enrichment of neural differentiation and signaling pathways, as well as protein binding and degradation. Of 240 HASV-neuropsychiatric trait pairs, 75 demonstrated significant genetic correlations (P < 0.05/240), revealing 433 pleiotropic loci. Particularly, genes like ACBD4, ARHGAP27, KANSL1, MAPT, ARL17A, and ARL17B were involved in over 50 HASV-neuropsychiatric pairs. Leveraging Mendelian randomization analysis, we further confirmed that atrophy in the left hippocampus, right hippocampus, right hippocampal body, and right CA1-3 region were associated with an increased risk of developing Parkinson's disease (PD). Furthermore, PRS for all four HASVs were significantly linked to a higher risk of Parkinson's disease (PD), with the highest hazard ratio (HR) of 1.30 (95% CI 1.18-1.43, P = 6.15 × 10⁻8) for right hippocampal volume. CONCLUSIONS: These findings highlight the extensive distribution of pleiotropic genetic determinants between HASVs and neuropsychiatric traits. Moreover, they suggest a significant potential for effectively managing and intervening in these diseases during their early stages.

Dynamic causal modeling of cerebello-cerebral connectivity when sequencing trait-implying actions.

Prior studies suggest that the cerebellum contributes to the prediction of action sequences as well as the detection of social violations. In this dynamic causal modeling study, we explored the effective connectivity of the cerebellum with the cerebrum in processing social action sequences. A first model aimed to explore functional cerebello-cerebral connectivity when learning trait/stereotype-implying action sequences. We found many significant bidirectional connectivities between mentalizing areas of the cerebellum and the cerebrum including the temporo-parietal junction (TPJ) and medial prefrontal cortex (mPFC). Within the cerebrum, we found significant connectivity between the right TPJ and the mPFC, and between the TPJ bilaterally. A second model aimed to investigate cerebello-cerebral connectivity when conflicting information arises. We found many significant closed loops between the cerebellum and cerebral mentalizing (e.g. dorsal mPFC) and executive control areas (e.g. medial and lateral prefrontal cortices). Additional closed loops were found within the cerebral mentalizing and executive networks. The current results confirm prior research on effective connectivity linking the cerebellum with mentalizing areas in the cerebrum for predicting social sequences, and extend it to cerebral executive areas for social violations. Overall, this study emphasizes the critical role of cerebello-cerebral connectivity in understanding social sequences.

Two is company: The posterior cerebellum and sequencing for pairs versus individuals during social preference prediction.

Previous studies have identified that the posterior cerebellum, which plays a role in processing temporal sequences in social events, is consistently and robustly activated when we predict future action sequences based on personality traits (Haihambo Haihambo et al. Social Cognitive and Affective Neuroscience 17(2), 241-251, 2022) and intentions (Haihambo et al. Cognitive, Affective, and Behavioral Neuroscience 23(2), 323-339, 2023). In the current study, we investigated whether these cerebellar areas are selectively activated when we predict the sequences of (inter)actions based on protagonists' preferences. For the first time, we also compared predictions based on person-to-person interactions or single person activities. Participants were instructed to predict actions of one single or two interactive protagonists by selecting them and putting them in the correct chronological order after being informed about one of the protagonists' preferences. These conditions were contrasted against nonsocial (involving objects) and nonsequencing (prediction without generating a sequence) control conditions. Results showed that the posterior cerebellar Crus 1, Crus 2, and lobule IX, alongside the temporoparietal junction and dorsal medial prefrontal cortex were more robustly activated when predicting sequences of behavior of two interactive protagonists, compared to one single protagonist and nonsocial objects. Sequence predictions based on one single protagonist recruited lobule IX activation in the cerebellum and more ventral areas of the medial prefrontal cortex compared to a nonsocial object. These cerebellar activations were not found when making predictions without sequences. Together, these findings suggest that cerebellar mentalizing areas are involved in social mentalizing processes which require temporal sequencing, especially when they involve social interactions, rather than behaviors of single persons.

To Do or Not to Do: The cerebellum and neocortex contribute to predicting sequences of social intentions.

Humans read the minds of others to predict their actions and efficiently navigate social environments, a capacity called mentalizing. Accumulating evidence suggests that the cerebellum, especially Crus 1 and 2, and lobule IX are involved in identifying the sequence of others' actions. In the current study, we investigated the neural correlates that underly predicting others' intentions and how this plays out in the sequence of their actions. We developed a novel intention prediction task, which required participants to put protagonists' behaviors in the correct chronological order based on the protagonists' honest or deceitful intentions (i.e., inducing true or false beliefs in others). We found robust activation of cerebellar lobule IX and key mentalizing areas in the neocortex when participants ordered protagonists' intentional behaviors compared with not ordering behaviors or to ordering object scenarios. Unlike a previous task that involved prediction based on personality traits that recruited cerebellar Crus 1 and 2, and lobule IX (Haihambo et al., 2021), the present task recruited only the cerebellar lobule IX. These results suggest that cerebellar lobule IX may be generally involved in social action sequence prediction, and that different areas of the cerebellum are specialized for distinct mentalizing functions.

The posterior cerebellum and social action sequences in a cooperative context.

Recent research has suggested that the posterior cerebellum encodes predictions and sequences of social actions, and also supports detecting inconsistent trait-implying actions of individuals as discussed by Pu et al. (2020, 2021). However, little is known about the role of the posterior cerebellum in detecting sequencing and inconsistencies by a group of individuals during social interaction. Therefore, the present study investigates these cerebellar functions during inconsistent trait-implying actions in a cooperative context. We presented scenarios in which two fictitious protagonists work together to accomplish a common (positive or negative) goal, followed by six sentences describing actions that implied a personality trait of the protagonists. Participants had to memorize the sequence of these actions. Crucially, the implied trait of the actions of the first protagonist contributed to achieving the goal, whereas the implied trait of the second protagonist was either consistent or inconsistent with that goal. As comparison, we added control conditions where participants had to memorize sequences of nonsocial events (implying the same characteristic of two objects), or simply read the social actions without memorizing their order. We found that the posterior cerebellum was activated while memorizing the sequence of social actions compared to simply reading these actions. More importantly, the cerebellar Crus was more strongly activated when detecting inconsistent (as opposed to consistent) actions, especially when inconsistent negative actions impeded a positive goal, relative to consistent negative actions that supported a negative goal. In conclusion, these findings confirm the crucial role of the posterior cerebellum in memorizing social action sequences and extend the cerebellar function in identifying inconsistencies in an individual's actions in a social collaborative context.

A Functional Atlas of the Cerebellum Based on NeuroSynth Task Coordinates.

Although the human cerebellum has a surface that is about 80% of that of the cerebral cortex and has about four times as many neurons, its functional organization is still very much uncharted. Despite recent attempts to provide resting-state and task-based parcellations of the cerebellum, these two approaches lead to large discrepancies. This article describes a comprehensive task-based functional parcellation of the human cerebellum based on a large-scale functional database, NeuroSynth, involving an unprecedented diversity of tasks, which were reliably associated with ontological key terms referring to psychological functions. Involving over 44,500 participants from this database, we present a parcellation that exhibits replicability with earlier resting-state parcellations across cerebellar and neocortical structures. The functional parcellation of the cerebellum confirms the major networks revealed in prior work, including sensorimotor, directed (dorsal) attention, divided (ventral) attention, executive control, mentalizing (default mode) networks, tiny patches of a limbic network, and also a unilateral language network (but not the visual network), and the association of these networks with underlying ontological key terms confirms their major functionality. The networks are revealed at locations that are roughly similar to prior resting-state cerebellar parcellations, although they are less symmetric and more fragmented across the two hemispheres. This functional parcellation of the human cerebellum and associated key terms can provide a useful guide in designing studies to test specific functional hypotheses and provide a reference for interpreting the results.

Effects of HMW-GSs at Glu-B1 locus on starch-protein interaction and starch digestibility during thermomechanical processing of wheat dough.

BACKGROUND: The composition of glutenin protein significantly affects protein-starch interactions and starch digestion characteristics in wheat dough matrices. To elucidate the effects of high molecular weight glutenin subunits at the Glu-B1 locus on dough processing quality, the detailed structural changes of protein, starch, and their complexes were compared in Mixolab dough samples of two near isogenic lines 7 + 8 and 7 + 9. RESULTS: The results showed that the degree of protein aggregation increased continuously during dough processing, as did the destruction and rearrangement of the gluten network. Compared to 7 + 8, the stronger and more stable protein network formed in 7 + 9 dough induced intensive interactions between protein and starch, primarily through hydrogen bonds and isomeric glycosidic bonds. In 7 + 9 dough, the more compact and extensive protein-starch network significantly inhibited starch gelatinization during dough pasting, while during the dough cooling stage [from C4 (82.8 °C) to C5 (52.8 °C)], more protein-starch complexes composed of monomeric proteins and short-chain starch were generated, which remarkably inhibited starch retrogradation. All protein-starch interactions in the 7 + 9 dough improved the starch digestion resistance, as reflected by the high content of resistant starch. CONCLUSION: The more extensive and intensive protein-starch interactions in the 7 + 9 dough inhibited the gelatinization and enzymatic hydrolysis of starch, thereby producing more slowly digestible starch and resistant starch. These findings demonstrate the feasibility of optimizing the texture and digestibility of wheat-based food products by regulating the behavior and interactions of proteins and starch during dough processing. © 2022 Society of Chemical Industry.

The posterior cerebellum and temporoparietal junction support explicit learning of social belief sequences.

This study tests the hypothesis that the posterior cerebellum is involved in social cognition by identifying and automatizing sequences of social actions. We applied a belief serial reaction time task (Belief SRT task), which requires mentalizing about two protagonists' beliefs about how many flowers they receive. The protagonists' beliefs could either be true or false depending on their orientation (true belief: oriented towards and directly observing the flowers; or false belief: oriented away and knowing only prior information about flowers). A Control SRT task was created by replacing protagonists and their beliefs with shapes and colors. Participants were explicitly told that there was a standard sequence related to the two protagonists' belief orientations (Belief SRT task) or the shapes' colors (Control SRT task). Both tasks included a Training phase where the standard sequence was repeated and a Test phase where this standard sequence was interrupted by random sequences. As hypothesized, compared with the Control SRT task, the Belief SRT task recruited the posterior cerebellar Crus II and the temporoparietal junction (TPJ) more. Faster response times were correlated with less Crus II activation and with more TPJ activation, suggesting that the Crus II supported automatizing the belief sequence while the TPJ supported inferring the protagonists' beliefs. Also as hypothesized, compared with an implicit version of the Belief SRT task (i.e., participants did not know about the existence of sequences; Ma, Pu, et al., 2021b), the cerebellar Crus I &II was engaged less during initial training and automatic application of the sequence, and the cortical TPJ was activated more in processing random sequences.

This is not who you are: The posterior cerebellum and stereotype-inconsistent action sequences.

Recent research has indicated that the posterior cerebellum plays a crucial role in social cognition by encoding sequences of social actions. This study investigates its role in learning sequences of stereotype-implying actions by group members. We presented a set of five sentences that each described a group member who performed either stereotype-consistent or inconsistent actions. Participants were instructed to memorize the temporal order of the sentences and infer a common stereotype of the group. As a comparison, we included control conditions where participants had to memorize sequences of nonsocial consistent events or simply read stereotype-consistent sentences without memorizing their order. The results showed that the posterior cerebellum was strongly activated when participants were memorizing the order of the social actions, as opposed to simply reading these social actions. More importantly, when the social actions were inconsistent as opposed to consistent with the stereotype of the group, the posterior cerebellum was activated more strongly. This activation occurred together with cortical recruitment of the mentalizing network involving the dorsomedial prefrontal cortex (dmPFC) during social actions, and additionally the conflict monitoring network involving the lateral prefrontal cortex (PFC) and posterior medial frontal cortex (pmFC) during stereotype-inconsistent actions. These findings suggest that the cerebellum supports not only learning of low-level action sequences, but also of their high-level social implications.

The Involvement of the Posterior Cerebellum in Reconstructing and Predicting Social Action Sequences.

Recent advances in social neuroscience have highlighted the critical role of the cerebellum and especially the posterior cerebellar Crus in social mentalizing (i.e., theory of mind). Research in the past 5 years has provided growing evidence supporting the view that the posterior cerebellum builds internal action models of our social interactions to predict how other people's actions will be executed, and what our most likely responses to these actions will be. This paper presents an overview of a series of fMRI experiments on novel tasks involving a combination of (a) the learning or generation of chronological sequences of social actions either in an explicit or implicit manner, which (b) require social mentalizing on another person's mental state such as goals, beliefs, and implied traits. Together, the results strongly confirm the central role of the posterior cerebellar Crus in identifying and automatizing action sequencing during social mentalizing, and in predicting future action sequences based on social mentalizing inferences about others. This research program has important implications: It provides for the first time (a) fruitful starting points for diagnosing and investigating social sequencing dysfunctions in a variety of mental disorders which have also been related to cerebellar dysfunctions, (b) provides the necessary tools for testing whether non-invasive neurostimulation targeting the posterior cerebellum has a causal effect on social functioning, and (c) whether these stimulation techniques and training programs guided by novel cerebellar social sequencing insights, can be exploited to increase posterior cerebellar plasticity in order to alleviate social impairments in mental disorders.

The posterior cerebellum supports implicit learning of social belief sequences.

Recent studies have documented the involvement of the posterior cerebellar Crus (I & II) in social mentalizing, when sequences play a critical role. We investigated for the first time implicit learning of belief sequences. We created a novel task in which true and false beliefs of other persons were alternated in an adapted serial reaction time (SRT) paradigm (Belief SRT task). Participants observed two protagonists whose beliefs concerning reality were manipulated, depending on their orientation toward the scene (true belief: directly observing the situation) or away from it (false belief: knowing only the prior situation). Unbeknownst to the participants, a fixed sequence related to the two protagonists' belief orientations was repeated throughout the task (Training phase); and to test the acquisition of this fixed sequence, it was occasionally interrupted by random sequences (Test phase). As a nonsocial control, the two protagonists and their orientations were replaced by two different shapes of different colors respectively (Control SRT task). As predicted, the posterior cerebellar Crus I & II were activated during the Belief SRT task and not in the Control SRT task. The Belief SRT task revealed that Crus I was activated during the initial learning of the fixed sequence (Training phase) and when this learned sequence was interrupted by random sequences (Test phase). Moreover, Crus II was activated during occasional reappearance of the learned sequence in the context of sequence violations (Test phase). Our results demonstrate the contribution of the posterior cerebellar Crus during implicit learning and predicting new belief sequences.

Ten days of complete fasting affected subjective sensations but not cognitive abilities in healthy adults.

PURPOSE: People may be unable to obtain anything edible for days under some circumstances, but they must maintain their calmness and cognition to navigate solutions. Our aim was to study changes in subjective sensations and cognition in healthy adults during a 10-day complete fasting experiment. METHODS: Thirteen healthy male volunteers voluntarily participated in the 22-day experiment comprising 4 phases: 3 days of baseline consumption, 10 days of complete fasting (only water ad libitum), 4 days of calorie restriction, and a 5-day recovery period. The volunteers' subjective sensations, cognitive performance, and serum energy substances were measured at 6 time points. RESULTS: Across the 6 time points, the trajectories of subjective sensations in response to fasting were "U"- or " ∩ "-shaped curves instead of progressive discomfort or mood enhancement. A significant fasting time effect was found on depression-dejection (baseline: 16.85 ± 2.88; highest score on the third day of completing fasting: 17.69 ± 3.97, P = 0.04) and self-rated anxiety (baseline: 26.23 ± 4.75; highest score on the sixth day of completing fasting: 30.85 ± 5.58, P = 0.01), and the change curves were consistent with the inflection point of the energy substrates shifting from serum glucose to ketone. In addition, basic cognitive functions appeared to be unaffected during the 10-day fast. CONCLUSIONS: Our study showed strong influences on the sensations from the third to sixth days of the prolonged fasting period but no significant effects on basic cognitive abilities associated with the energy substance switch. These findings could contribute to the development and understanding of survival strategies in food-shortage emergencies or of intermittent fasting programmes.

The posterior cerebellum supports the explicit sequence learning linked to trait attribution.

Recent research has indicated that the cerebellum is responsible for social judgments, such as making trait attributions. The present study investigated the function of the posterior cerebellum in supporting sequence learning linked to trait inferences about persons. We conducted a memory paradigm that required participants to learn a given temporal order of six behavioral sentences that all implied the same personality trait of the protagonist. We then asked participants to infer the trait of the person and to recall the correct order of the sentences and to rate their confidence in their trait judgments and retrieval accuracy. Two control conditions were created: a nonsocial comparison control, involving six nonsocial sentences implying a feature of an object, and a nonsocial nonsequential reading baseline condition. While learning the specific sequence of the sentences, the posterior cerebellum (Crus 2) was more activated for social trait-related sequencing than nonsocial object-related sequencing. Also, given a longer duration to learn the sequences, the precuneus and posterior cingulate cortex were more activated when participants attempted to retrieve the sequences linked to social traits. In addition, confidence in retrieving the correct order of the social sequences modulated the posterior cerebellum (Crus 1) given a longer duration to learn. Our findings highlight the important function of the posterior cerebellum in supporting an active process of sequencing trait-implying actions.

Consensus Paper: Cerebellum and Social Cognition.

The traditional view on the cerebellum is that it controls motor behavior. Although recent work has revealed that the cerebellum supports also nonmotor functions such as cognition and affect, only during the last 5 years it has become evident that the cerebellum also plays an important social role. This role is evident in social cognition based on interpreting goal-directed actions through the movements of individuals (social "mirroring") which is very close to its original role in motor learning, as well as in social understanding of other individuals' mental state, such as their intentions, beliefs, past behaviors, future aspirations, and personality traits (social "mentalizing"). Most of this mentalizing role is supported by the posterior cerebellum (e.g., Crus I and II). The most dominant hypothesis is that the cerebellum assists in learning and understanding social action sequences, and so facilitates social cognition by supporting optimal predictions about imminent or future social interaction and cooperation. This consensus paper brings together experts from different fields to discuss recent efforts in understanding the role of the cerebellum in social cognition, and the understanding of social behaviors and mental states by others, its effect on clinical impairments such as cerebellar ataxia and autism spectrum disorder, and how the cerebellum can become a potential target for noninvasive brain stimulation as a therapeutic intervention. We report on the most recent empirical findings and techniques for understanding and manipulating cerebellar circuits in humans. Cerebellar circuitry appears now as a key structure to elucidate social interactions.

The impact of social isolation on smartphone addiction among college students: the multiple mediating effects of loneliness and COVID-19 anxiety.

Background: The widespread use of smartphones has significantly increased smartphone addiction among college students, especially during the COVID-19 pandemic. Since the COVID-19 outbreak, university campuses in mainland China have strictly followed the Chinese government's strict quarantine policy, including closed campus management, prohibitions against gatherings, and social distancing, increasing student loneliness and anxiety and thus increasing the risk of smartphone addiction. Extant Studies have revealed that social isolation is a prominent predictor of smartphone addiction but have failed to systematically explore the complex relationship between social isolation and smartphone addiction in the context of COVID-19; therefore, the underlying mechanisms of these factors in the post-pandemic era are unclear. Objective: This study is the first attempt to consider loneliness, COVID-19 anxiety and social isolation as a whole and to clarify the underlying mechanisms of social isolation and smartphone addiction by constructing a multiple mediating model. Method: This study included students enrolled at eight higher education institutions in Conghua District (Guangzhou city). Quota proportional sampling was adopted, 900 self-report questionnaires were distributed through the WeChat groups of these universities from December 10 to December 15, 2022, and 868 valid questionnaires (620 females, 248 males) were ultimately obtained. Results: The direct effect of social isolation on smartphone addiction was significant, and loneliness and COVID-19 anxiety mediated the association between social isolation and smartphone addiction in both parallel and sequential ways. Moreover, a reverse mediation model with COVID-19 anxiety as the first mediator and loneliness as the second mediator was found. Conclusion: College students who experience social isolation are at greater risk for smartphone addiction, and the core factor leading to their smartphone addiction is the subjective psychological state triggered by campus isolation and social distancing, such as loneliness and anxiety. These risky behaviors of people should receive extra attention, and psychological factors such as loneliness and COVID-19 anxiety should be considered in future therapies aimed at reducing addiction.

The lgi-miR-2d is Potentially Involved in Shell Melanin Synthesis by Targeting mitf in Manila Clam Ruditapes philippinarum.

Shell color as an important economic trait is also the crucial target trait for breeding and production. MicroRNA (miRNA) is an endogenous small non-coding RNA that can post-transcriptionally regulate the expression of target genes, it plays important roles in many life activities and physiological processes, such as shell color, stress response, and disease traits. In this study, we investigated the function of lgi-miR-2d in shell melanin formation and the expression patterns of lgi-miR-2d and target gene Rpmitf in Manila clam Ruditapes philippinarum. We further explored and verified the relationship between Rpmitf and lgi-miR-2d and identified the expression level of shell color-related gene changes by RNAi and injecting the antagomir of lgi-miR-2d, respectively. Our results indicated that lgi-miR-2d antagomir affected the expression of its target gene Rpmitf. In addition, the dual-luciferase reporter assay was conducted to confirm the direct interaction between lgi-miR-2d and Rpmitf. The results showed that the expression levels of melanin-related genes such as Rpmitf and tyr were significantly decreased in the positive treatment group compared with the blank control group after the Rpmitf dsRNA injection, indicating Rpmitf plays a crucial role in the melanin synthesis pathway. Taken together, we speculated that lgi-miR-2d might be negatively modulating Rpmitf, which might regulate other shell color-related genes, thereby affecting melanin synthesis in R. philippinarum.

Exciting the social butterfly: Anodal cerebellar transcranial direct current stimulation modulates neural activation during predictive social mentalizing.

Transcranial Direct Current Stimulation (tDCS) has emerged as a promising tool for enhancing social cognition. The posterior cerebellum, which is part of the mentalizing network, has been implicated in social processes. In our combined tDCS-fMRI study, we investigated the effects of offline anodal cerebellar tDCS on activation in the cerebellum during social action prediction. Forty-one participants were randomly assigned to receive either anodal (2 mA) or sham (0 mA) stimulation over the midline of the posterior cerebellum for 20 min. Twenty minutes post stimulation, participants underwent a functional MRI scan to complete a social action prediction task, during which they had to correctly order randomly presented sentences that described either actions of social agents (based on their personality traits) or events of objects (based on their characteristics). As hypothesized, our results revealed that participants who received anodal cerebellar tDCS exhibited increased activation in the posterior cerebellar Crus 2 and lobule IX, and in key cerebral mentalizing areas, including the medial prefrontal cortex, temporo-parietal junction, and precuneus. Contrary to our hypotheses, participants who received anodal stimulation demonstrated faster responses to non-social objects compared to social agents, while sham participants showed no significant differences. We did not find a significant relationship between electric field magnitude, neural activation and behavioral outcomes. These findings suggest that tDCS targeting the posterior cerebellum selectively enhances activation in social mentalizing areas, while only facilitating behavioral performance of non-social material, perhaps because of a ceiling effect due to familiarity with social processing.

Large flour aggregates containing ordered B + V starch crystals significantly improved the digestion resistance of starch in pretreated multigrain flour.

The starch digestibility of flour is influenced by both physicochemical treatment and flour particle size, but the interactive effect of these two factors is still unclear. In this study, the effect of pullulanase debranching, combined with heat-moisture treatment (P-HMT), on starch digestibility of multi-grain flours (including oat, buckwheat and wheat) differing in particle size was investigated. The results showed that the larger-size flour always resulted in a higher resistant starch (RS) content either in natural or treated multi-grain flour (NMF or PHF). P-HMT doubled the RS content in NMFs and the large-size PHF yielded the highest RS content (78.43 %). In NMFs, the cell wall integrity and flour particle size were positively related to starch anti-digestibility. P-HMT caused the destruction of cell walls and starch granules, as well as the formation of rigid flour aggregates with B + V starch crystallite. The largest flour aggregates with the most ordered B + V starch were found in large-size PHF, which contributed to its highest RS yield, while the medium- and small-size PHFs with smaller aggregates were sensitive to P-HMT, resulting in the lower ordered starch but stronger interactions between starch and free lipid or monomeric proteins, eventually leading to their lower RS but higher SDS yield.

One step too far: social cerebellum in norm-violating navigation.

Social norms are pivotal in guiding social interactions. The current study investigated the potential contribution of the posterior cerebellum, a critical region involved in perceiving and comprehending the sequential dynamics of social actions, in detecting actions that either conform to or deviate from social norms. Participants engaged in a goal-directed task in which they observed others navigating towards a goal. The trajectories demonstrated either norm-violating (trespassing forbidden zones) or norm-following behaviors (avoiding forbidden zones). Results revealed that observing social norm-violating behaviors engaged the bilateral posterior cerebellar Crus 2 and the right temporoparietal junction (TPJ) from the mentalizing network, and the parahippocampal gyrus (PHG) to a greater extent than observing norm-following behaviors. These mentalizing regions were also activated when comparing social sequences against non-social and non-sequential control conditions. Reproducing norm-violating social trajectories observed earlier, activated the left cerebellar Crus 2 and the right PHG compared to reproducing norm-following trajectories. These findings illuminate the neural mechanisms in the cerebellum associated with detecting norm transgressions during social navigation, emphasizing the role of the posterior cerebellum in detecting and signaling deviations from anticipated sequences.