Cardiac vagal activity changes moderated the association of cognitive and cerebral hemodynamic variations in the prefrontal cortex.

Phasic cardiac vagal activity (CVA), reflecting ongoing, moment-to-moment psychophysiological adaptations to environmental changes, can serve as a predictor of individual difference in executive function, particularly executive performance. However, the relationship between phasic CVA and executive function demands requires further validation because of previous inconsistent findings. Moreover, it remains unclear what types of phasic changes of CVA may be adaptive in response to heightened executive demands. This study used the standard N-back task to induce different levels of working memory (WM) load and combined functional Near-Infrared Spectroscopy (fNIRS) with a multipurpose polygraph to investigate the variations of CVA and its interactions with cognitive and prefrontal responses as executive demands increased in fifty-two healthy young subjects. Our results showed phasic decreases in CVA as WM load increased (t (51) = -3.758, p < 0.001, Cohen's d = 0.526). Furthermore, phasic changes of CVA elicited by increased executive demands moderated the association of cognitive and cerebral hemodynamic variations in the prefrontal cortex (B = 0.038, SE = 0.014, p < 0.05). Specifically, as executive demands increased, individuals with larger phasic CVA withdrawal showed a positive relationship between cognitive and hemodynamic variations in the prefrontal cortex (ß = 0.281, p = 0.031). No such significant relationship was observed in individuals with smaller phasic CVA withdrawal. The current findings demonstrate a decrease in CVA with increasing executive demands and provide empirical support for the notion that a larger phasic CVA withdrawal can be considered adaptive in situations requiring high executive function demands.

Unraveling how the adolescent brain deals with criticism using dynamic causal modeling.

Sensitivity to criticism, which can be defined as a negative evaluation that a person receives from someone else, is considered a risk factor for the development of psychiatric disorders in adolescents. They may be more vulnerable to social evaluation than adults and exhibit more inadequate emotion regulation strategies such as rumination. The neural network involved in dealing with criticism in adolescents may serve as a biomarker for vulnerability to depression. However, the directions of the functional interactions between the brain regions within this neural network in adolescents are still unclear. In this study, 64 healthy adolescents (aged 14 to 17 years) were asked to listen to a series of self-referential auditory segments, which included negative (critical), positive (praising), and neutral conditions, during fMRI scanning. Dynamic Causal Modeling (DCM) with Parametric Empirical Bayesian (PEB) analysis was performed to map the interactions within the neural network that was engaged during the processing of these segments. Three regions were identified to form the interaction network: the left pregenual anterior cingulate cortex (pgACC), the left dorsolateral prefrontal cortex (DLPFC), and the right precuneus (preCUN). We quantified the modulatory effects of exposure to criticism and praise on the effective connectivity between these brain regions. Being criticized was found to significantly inhibit the effective connectivity from the preCUN to the DLPFC. Adolescents who scored high on the Perceived Criticism Measure (PCM) showed less inhibition of the preCUN-to-DLPFC connectivity when being criticized, which may indicate that they required more engagement of the Central Executive Network (which includes the DLPFC) to sufficiently disengage from negative self-referential processing. Furthermore, the inhibitory connectivity from the DLPFC to the pgACC was strengthened by exposure to praise as well as criticism, suggesting a recruitment of cognitive control over emotional responses when dealing with positive and negative evaluative feedback. Our novel findings contribute to a more profound understanding of how criticism affects the adolescent brain and can help to identify potential biomarkers for vulnerability to develop mood disorders before or during adulthood.

Does transcranial direct current stimulation of the primary motor cortex improve implicit motor sequence learning in Parkinson's disease?

Implicit motor sequence learning (IMSL) is a cognitive function that is known to be associated with impaired motor function in Parkinson's disease (PD). We previously reported positive effects of transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) on IMSL in 11 individuals with PD with mild cognitive impairments (MCI), with the largest effects occurring during reacquisition. In the present study, we included 35 individuals with PD, with (n = 15) and without MCI (n = 20), and 35 age- and sex-matched controls without PD, with (n = 13) and without MCI (n = 22). We used mixed-effects models to analyze anodal M1 tDCS effects on acquisition (during tDCS), short-term (five minutes post-tDCS) and long-term reacquisition (one-week post-tDCS) of general and sequence-specific learning skills, as measured by the serial reaction time task. At long-term reacquisition, anodal tDCS resulted in smaller general learning effects compared to sham, only in the PD group, p = .018, possibly due to floor effects. Anodal tDCS facilitated the acquisition of sequence-specific learning (M = 54.26 ms) compared to sham (M = 38.98 ms), p = .003, regardless of group (PD/controls). Further analyses revealed that this positive effect was the largest in the PD-MCI group (anodal: M = 69.07 ms; sham: M = 24.33 ms), p < .001. Although the observed effect did not exceed the stimulation period, this single-session tDCS study confirms the potential of tDCS to enhance IMSL, with the largest effects observed in patients with lower cognitive status. These findings add to the body of evidence that anodal tDCS can beneficially modulate the abnormal basal ganglia network activity that occurs in PD.

Treatment Response Following Adaptive PASAT Training for Depression Vulnerability: a Systematic Review and Meta-Analysis.

In recent years, cognitive control training (CCT) has gained momentum as an intervention to remediate cognitive impairments and decrease depressive symptoms. One promising operationalization to train cognitive control is the adaptive Paced Auditory Serial Addition Task (aPASAT). In this systematic review and meta-analysis of aPASAT training, the efficacy of the intervention and potential moderators were examined. The PsycINFO, MEDLINE, Embase, Web of Science and Cochrane Library electronic databases were searched for studies examining aPASAT training for depressive symptomatology or rumination. Nineteen studies (n = 1255) were included, comprising of depressed patients, remitted depressed patients, at-risk, and healthy participants. We found small significant effects directly after training for both depressive symptomatology and rumination, with similar effect sizes at follow-up. Subgroup analyses suggest a significantly higher mean effect of aPASAT training in non-healthy populations for rumination immediately following training, but not for depressive symptomatology. The amount of training sessions did not moderate effects of CCT. aPASAT has a small but significant effect on depressive symptoms, with direct effects immediately after training, as well as sustained long-term effects. It is currently unclear how many sessions are required for sustained effects due to heterogeneity in training dosage and absence of sufficient trials. Our results suggest that aPASAT training may be most effective for at-risk, remitted- and clinically depressed populations. The effect sizes resulting from this meta-analysis could be used to adequately power future research, which could investigate a dose-response relationship and examine potential treatment gains when combining CCT with other antidepressant interventions.

Lateralized subgenual ACC metabolic connectivity patterns in refractory melancholic depression: does it matter?

Although treatment resistance to antidepressant pharmacotherapy is quite common, the phenomenon of refractory major depressive disorder (rMDD) is not well understood. Nevertheless, the metabolic activity of the subgenual anterior cingulate cortex (sgACC) has been put forward as a possible metabolic biomarker of clinical prediction and response, albeit sgACC lateralization differences in functional connectivity have not yet been extensively examined. Also not in the refractory depressed state. To examine sgACC lateralization differences in metabolic connectivity, we recruited 43 right-handed antidepressant-free unipolar melancholic rMDD patients and 32 right-handed healthy controls to participate in this 18FDG PET study and developed a searchlight-based interregional covariance connectivity approach. Compared to non-depressed individuals, sgACC covariance analysis showed stronger metabolic connections with frontolimbic brain regions known to be affected in the depressed state. Furthermore, whereas the left sgACC showed stronger metabolic connections with ventromedial prefrontal cortical regions, implicated in anhedonia, suicidal ideation, and self-referential processes, the right sgACC showed significantly stronger metabolic connections with posterior hippocampal and cerebellar regions, respectively specialized in memory and social processing. Overall, our results substantiate earlier research that the sgACC is a metabolic key player when clinically depressed and that distinct lateralized sgACC metabolic connectivity patterns are present.

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.

Increased ventral anterior insular connectivity to sports betting availability indexes problem gambling.

With the advent of digital technologies, online sports betting is spurring a fast-growing expansion. In this study, we examined how sports betting availability modulates the brain connectivity of frequent sports bettors with [problem bettors (PB)] or without [non-problem bettors (NPB)] problematic sports betting. We conducted functional connectivity analyses centred on the ventral anterior insular cortex (vAI), a brain region playing a key role in the dynamic interplay between reward-based processes. We re-analysed a dataset on sports betting availability undertaken in PB (n = 30) and NPB (n = 35). Across all participants, we observed that sports betting availability elicited positive vAI coupling with extended clusters of brain activation (encompassing the putamen, cerebellum, occipital, temporal, precentral and central operculum regions) and negative vAI coupling with the orbitofrontal cortex. Between-group analyses showed increased positive vAI coupling in the PB group, as compared with the NPB group, in the left lateral occipital cortex, extending to the left inferior frontal gyrus, the anterior cingulate gyrus and the right frontal pole. Taken together, these results are in line with the central assumptions of triadic models of addictions, which posit that the insular cortex plays a pivotal role in promoting the drive and motivation to get a reward by 'hijacking' goal-oriented processes toward addiction-related cues. Taken together, these findings showed that vAI functional connectivity is sensitive not only to gambling availability but also to the status of problematic sport betting.

Differential effects of conventional and high-definition transcranial direct-current stimulation of the motor cortex on implicit motor sequence learning.

Conventional transcranial direct-current stimulation (tDCS) delivered to the primary motor cortex (M1) has been shown to enhance implicit motor sequence learning (IMSL). Conventional tDCS targets M1 but also the motor association cortices (MAC), making the precise contribution of these areas to IMSL presently unclear. We aimed to address this issue by comparing conventional tDCS of M1 and MAC to 4 * 1 high-definition (HD) tDCS, which more focally targets M1. In this mixed-factorial, sham-controlled, crossover study in 89 healthy young adults, we used mixed-effects models to analyse sequence-specific and general learning effects in the acquisition and short- and long-term consolidation phases of IMSL, as measured by the serial reaction time task. Conventional tDCS did not influence general learning, improved sequence-specific learning during acquisition (anodal: M = 42.64 ms, sham: M = 32.87 ms, p = .041), and seemingly deteriorated it at long-term consolidation (anodal: M = 75.37 ms, sham: M = 86.63 ms, p = .019). HD tDCS did not influence general learning, slowed performance specifically in sequential blocks across all learning phases (all p's < .050), and consequently deteriorated sequence-specific learning during acquisition (anodal: M = 24.13 ms, sham: M = 35.67 ms, p = .014) and long-term consolidation (anodal: M = 60.03 ms, sham: M = 75.01 ms, p = .002). Our findings indicate that the observed superior conventional tDCS effects on IMSL are possibly attributable to a generalized stimulation of M1 and/or adjacent MAC, rather than M1 alone. Alternatively, the differential effects can be attributed to cathodal inhibition of other cortical areas involved in IMSL by the 4 * 1 HD tDCS return electrodes, and/or more variable electric field strengths induced by HD tDCS, compared with conventional tDCS.

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.

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.

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.

The Ghent Psychotherapy Study: A Pragmatic, Stratified, Randomized Parallel Trial into the Differential Efficacy of Psychodynamic and Cognitive-Behavioral Interventions in Dependent and Self-Critical Depressive Patients.

INTRODUCTION: Different types of psychotherapy are effective for treating major depressive disorder across groups yet show large within-group differences. Patient personality style is considered a potentially useful variable for treatment matching. OBJECTIVE: This study is the first experimental test of the interaction between therapeutic approach and patients' dependent versus self-critical personality styles. METHODS: A pragmatic stratified parallel trial was carried out with 100 adult patients diagnosed with DSM-IV-TR major depressive disorder. They were randomly assigned to short-term (16-20 sessions) cognitive behavioral therapy (CBT) or short-term psychodynamic psychotherapy (STPP). Patients were assessed at baseline, during therapy, post-therapy, and at 3- and 6-month follow-up. Primary outcome is depression severity measured by the Hamilton Rating Scale for Depression posttreatment. Primary analysis was by intention to treat. This trial is registered with the ISRCTN registry (www.isrctn.com), number ISRCTN17130982. RESULTS: The intention-to-treat sample consisted of 100 participants; 40 with self-critical and 60 with dependent personality styles were randomized to either CBT (n = 50) or STPP (n = 50). We observed no interaction effect (-0.34 [-6.14, 5.46]) between therapy and personality style and found no evidence for a difference in effectiveness between the treatments in general in terms of symptom reduction and maintained benefits at 6-month follow-up. CONCLUSION: We found no evidence that dependent versus self-critical personality styles moderate the relation between treatment and outcome in depression. Research using individual patient data could gain further insight into why specific therapeutic approaches work better for specific patients.

Precision targeting in prediction for rTMS clinical outcome in depression: what about sgACC lateralization, metabolic connectivity, and the potential role of the cerebellum?

Predicting clinical response to repetitive transcranial magnetic stimulation (rTMS) in medication-resistant depression (MRD) has gained great importance in recent years. Mainly, the right subgenual anterior cingulate cortex (sgACC) functional connectivity has been put forward as biomarker in relation to rTMS clinical outcome. Even though the left and right sgACC may have different neurobiological functions, little is known about the possible lateralized predictive role of the sgACC in rTMS clinical outcome. In 43 right-handed antidepressant-free MRD patients, we applied a searchlight-based interregional covariance connectivity approach using the baseline 18FDG-PET scan-collected from two previous high-frequency (HF)-rTMS treatment studies delivering stimulation to the left dorsolateral prefrontal cortex (DLPFC)-and investigated whether unilateral or bilateral sgACC glucose metabolism at baseline would result in different predictive metabolic connectivity patterns. Regardless of sgACC lateralization, the weaker the sgACC seed-based baseline metabolic functional connections with the (left anterior) cerebellar areas, the significantly better the clinical outcome. However, the seed diameter seems to be crucial. Similar significant findings on sgACC metabolic connectivity with the left anterior cerebellum, also unrelated to sgACC lateralization, in relation to clinical outcome were observed when using the HCPex atlas. Although we could not substantiate that specifically right sgACC metabolic connectivity would predict HF-rTMS clinical outcome, our findings suggest considering the entire sgACC in functional connectivity predictions. Given that the interregional covariance connectivity results were significant only when using the Beck Depression Inventory (BDI-II) and not with the Hamilton Depression Rating Scale (HDRS), our sgACC metabolic connectivity observations also suggest the possible involvement of the (left) anterior cerebellum involved in higher-order cognitive processing as part of this predictive value.

The moderating effect of resting heart rate variability on the relationship between internet addiction tendency and brain morphology.

Previous neuroimaging studies have investigated brain morphology associated with internet addiction tendency (IAT) in healthy subjects. However, whether resting vagally-mediated heart rate variability (HRV) exerting influences on the association of IAT and brain morphology remains unclear. This study used voxel-based morphometry (VBM) and multiple regression analyses to assess the interaction effect of IAT and resting vagally-mediated HRV on regional grey matter volumes in 82 healthy subjects. To further illustrate the observed interaction effect, the moderated hierarchical regression analysis was performed. The results showed that resting vagally-mediated HRV moderated the relationship between IAT scores and grey matter volume (GMV) in the precuneus and cerebellum. Specifically, individuals with higher resting vagally-mediated HRV showed a significant positive relationship between IAT scores and GMV in the precuneus, whereas individuals with lower resting vagally-mediated HRV showed a significant negative relationship between IAT scores and GMV in the precuneus. In addition, IAT scores were negatively correlated with GMV in the cerebellum among individuals with lower resting vagally-mediated HRV, but not among individuals with higher resting vagally-mediated HRV. These findings have demonstrated a moderating role of resting vagally-mediated HRV on the association of IAT and brain morphology.

Parental criticism affects adolescents' mood and ruminative state: Self-perception appears to influence their mood response.

Feeling and/or being criticized is a known risk factor for various psychiatric disorders in adolescents. However, the link between the experience of social stressors and the development of psychopathological symptoms is not yet fully understood. Identifying which adolescent subgroups are more vulnerable to parental criticism could be of great clinical relevance. In this study, 90 nondepressed 14- to 17-year-old adolescents were exposed to a sequence of auditory segments with a positive, neutral, and finally negative valence, mirroring parental criticism. Their mood and ruminative states were assessed before and after exposure to criticism. We observed an overall increase in mood disturbance and ruminative thoughts. Self-perception appeared to influence these mood changes, whereas no significant influence by perceived criticism, self-worth, or the general tendency to ruminate was found. Emotional awareness seemed to account for some of the variance in positive mood state changes. These findings point to the importance of adolescent self-perception (and emotional awareness) in dealing with parental criticism.

The effects of left dorsolateral prefrontal transcranial direct current stimulation on episodic future thinking following acute psychosocial stress.

INTRODUCTION: Research on stress-related disorders and brain imaging suggests that (acute) stress might impact the capacity to mentally simulate specific episodic future events (EFT) through the effects of cortisol on brain regions supporting this cognitive function, such as the prefrontal cortices. This study aims to examine the mechanisms underlying this link, using transcranial Direct Current Stimulation (tDCS) over the left dorsolateral prefrontal cortex. METHODS: 60 healthy participants were subjected to the Montreal Imaging Stress Task (MIST), followed by either active or sham tDCS. After stimulation, the EFT task was administered. Salivary cortisol was measured throughout the protocol. RESULTS: Higher cortisol AUCi values were linked to less specific episodic future thoughts. Moreover, active tDCS enhanced EFT specificity irrespective of cortisol, especially in high trait ruminators. We did not observe an effect from active tDCS on cortisol AUCi, and equally there was no interaction effect between cortisol AUCi and stimulation condition predictive for EFT specificity. CONCLUSION: Although we did not find evidence for the effects of tDCS on the HPA-system, our data reveal a crucial link between two critical predictors of mental health for the first time, and provide a solution to help rehabilitate EFT deficits.Trial registration: Netherlands National Trial Register identifier: ntr004..

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 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.

Brainstem glucose metabolism predicts reward dependence scores in treatment-resistant major depression.

BACKGROUND: It has been suggested that individual differences in temperament could be involved in the (non-)response to antidepressant (AD) treatment. However, how neurobiological processes such as brain glucose metabolism may relate to personality features in the treatment-resistant depressed (TRD) state remains largely unclear. METHODS: To examine how brainstem metabolism in the TRD state may predict Cloninger's temperament dimensions Harm Avoidance (HA), Novelty Seeking (NS), and Reward Dependence (RD), we collected 18fluorodeoxyglucose positron emission tomography (18FDG PET) scans in 40 AD-free TRD patients. All participants were assessed with the Temperament and Character Inventory (TCI). We applied a multiple kernel learning (MKL) regression to predict the HA, NS, and RD from brainstem metabolic activity, the origin of respectively serotonergic, dopaminergic, and noradrenergic neurotransmitter (NT) systems. RESULTS: The MKL model was able to significantly predict RD but not HA and NS from the brainstem metabolic activity. The MKL pattern regression model identified increased metabolic activity in the pontine nuclei and locus coeruleus, the medial reticular formation, the dorsal/median raphe, and the ventral tegmental area that contributed to the predictions of RD. CONCLUSIONS: The MKL algorithm identified a likely metabolic marker in the brainstem for RD in major depression. Although 18FDG PET does not investigate specific NT systems, the predictive value of brainstem glucose metabolism on RD scores however indicates that this temperament dimension in the TRD state could be mediated by different monoaminergic systems, all involved in higher order reward-related behavior.