Neural circuit basis of placebo pain relief.

Placebo effects are notable demonstrations of mind-body interactions1,2. During pain perception, in the absence of any treatment, an expectation of pain relief can reduce the experience of pain-a phenomenon known as placebo analgesia3-6. However, despite the strength of placebo effects and their impact on everyday human experience and the failure of clinical trials for new therapeutics7, the neural circuit basis of placebo effects has remained unclear. Here we show that analgesia from the expectation of pain relief is mediated by rostral anterior cingulate cortex (rACC) neurons that project to the pontine nucleus (rACC→Pn)-a precerebellar nucleus with no established function in pain. We created a behavioural assay that generates placebo-like anticipatory pain relief in mice. In vivo calcium imaging of neural activity and electrophysiological recordings in brain slices showed that expectations of pain relief boost the activity of rACC→Pn neurons and potentiate neurotransmission in this pathway. Transcriptomic studies of Pn neurons revealed an abundance of opioid receptors, further suggesting a role in pain modulation. Inhibition of the rACC→Pn pathway disrupted placebo analgesia and decreased pain thresholds, whereas activation elicited analgesia in the absence of placebo conditioning. Finally, Purkinje cells exhibited activity patterns resembling those of rACC→Pn neurons during pain-relief expectation, providing cellular-level evidence for a role of the cerebellum in cognitive pain modulation. These findings open the possibility of targeting this prefrontal cortico-ponto-cerebellar pathway with drugs or neurostimulation to treat pain.

Electrocortical Responses in Anticipation of Avoidable and Inevitable Threats: A Multisite Study.

When faced with danger, human beings respond with a repertoire of defensive behaviors, including freezing and active avoidance. Previous research has revealed a pattern of physiological responses, characterized by heart rate bradycardia, reduced visual exploration, and heightened sympathetic arousal in reaction to avoidable threats, suggesting a state of attentive immobility in humans. However, the electrocortical underpinnings of these behaviors remain largely unexplored. To investigate the visuocortical components of attentive immobility, we recorded parieto-occipital alpha activity, along with eye movements and autonomic responses, while participants awaited either an avoidable, inevitable, or no threat. To test the robustness and generalizability of our findings, we collected data from a total of 101 participants (76 females, 25 males) at two laboratories. Across sites, we observed an enhanced suppression of parieto-occipital alpha activity during avoidable threats, in contrast to inevitable or no threat trials, particularly toward the end of the trial that prompted avoidance responses. This response pattern coincided with heart rate bradycardia, centralization of gaze, and increased sympathetic arousal. Furthermore, our findings expand on previous research by revealing that the amount of alpha suppression, along with centralization of gaze, and heart rate changes predict the speed of motor responses. Collectively, these findings indicate that when individuals encounter avoidable threats, they enter a state of attentive immobility, which enhances perceptual processing and facilitates action preparation. This state appears to reflect freezing-like behavior in humans.

Integration of Prior Expectations and Suppression of Prediction Errors During Expectancy-Induced Pain Modulation: The Influence of Anxiety and Pleasantness.

Pain perception arises from the integration of prior expectations with sensory information. Although recent work has demonstrated that treatment expectancy effects (e.g., placebo hypoalgesia) can be explained by a Bayesian integration framework incorporating the precision level of expectations and sensory inputs, the key factor modulating this integration in stimulus expectancy-induced pain modulation remains unclear. In a stimulus expectancy paradigm combining emotion regulation in healthy male and female adults, we found that participants' voluntary reduction in anticipatory anxiety and pleasantness monotonically reduced the magnitude of pain modulation by negative and positive expectations, respectively, indicating a role of emotion. For both types of expectations, Bayesian model comparisons confirmed that an integration model using the respective emotion of expectations and sensory inputs explained stimulus expectancy effects on pain better than using their respective precision. For negative expectations, the role of anxiety is further supported by our fMRI findings that (1) functional coupling within anxiety-processing brain regions (amygdala and anterior cingulate) reflected the integration of expectations with sensory inputs and (2) anxiety appeared to impair the updating of expectations via suppressed prediction error signals in the anterior cingulate, thus perpetuating negative expectancy effects. Regarding positive expectations, their integration with sensory inputs relied on the functional coupling within brain structures processing positive emotion and inhibiting threat responding (medial orbitofrontal cortex and hippocampus). In summary, different from treatment expectancy, pain modulation by stimulus expectancy emanates from emotion-modulated integration of beliefs with sensory evidence and inadequate belief updating.

Continuous decision to wait for a future reward is guided by fronto-hippocampal anticipatory dynamics.

Deciding whether to wait for a future reward is crucial for surviving in an uncertain world. While seeking rewards, agents anticipate a reward in the present environment and constantly face a trade-off between staying in their environment or leaving it. It remains unclear, however, how humans make continuous decisions in such situations. Here, we show that anticipatory activity in the anterior prefrontal cortex, ventrolateral prefrontal cortex, and hippocampus underpins continuous stay-leave decision-making. Participants awaited real liquid rewards available after tens of seconds, and their continuous decision was tracked by dynamic brain activity associated with the anticipation of a reward. Participants stopped waiting more frequently and sooner after they experienced longer delays and received smaller rewards. When the dynamic anticipatory brain activity was enhanced in the anterior prefrontal cortex, participants remained in their current environment, but when this activity diminished, they left the environment. Moreover, while experiencing a delayed reward in a novel environment, the ventrolateral prefrontal cortex and hippocampus showed anticipatory activity. Finally, the activity in the anterior prefrontal cortex and ventrolateral prefrontal cortex was enhanced in participants adopting a leave strategy, whereas those remaining stationary showed enhanced hippocampal activity. Our results suggest that fronto-hippocampal anticipatory dynamics underlie continuous decision-making while anticipating a future reward.

Fifty Percent of the Time, Tones Come Every Time: Stronger Prediction Error Effects on Neurophysiological Sensory Attenuation for Self-generated Tones.

The N1/P2 amplitude reduction for self-generated tones in comparison to external tones in EEG, which has recently also been described for action observation, is an example of the so-called sensory attenuation. Whether this effect is dependent on motor-based or general predictive mechanisms is unclear. Using a paradigm, in which actions (button presses) elicited tones in only half the trials, this study examined how the processing of the tones is modulated by the prediction error in each trial in a self-performed action compared with action observation. In addition, we considered the effect of temporal predictability by adding a third condition, in which visual cues were followed by external tones in half the trials. The attenuation result patterns differed for N1 and P2 amplitudes, but neither showed an attenuation effect beyond temporal predictability. Interestingly, we found that both N1 and P2 amplitudes reflected prediction errors derived from a reinforcement learning model, in that larger errors coincided with larger amplitudes. This effect was stronger for tones following button presses compared with cued external tones, but only for self-performed and not for observed actions. Taken together, our results suggest that attenuation effects are partially driven by general predictive mechanisms irrespective of self-performed actions. However, the stronger prediction-error effects for self-generated tones suggest that distinct motor-related factors beyond temporal predictability, potentially linked to reinforcement learning, play a role in the underlying mechanisms. Further research is needed to validate these initial findings as the calculation of the prediction errors was limited by the design of the experiment.

Performing a Motor Action Enhances Social Reward Processing and Modulates the Neural Processing of Predictive Cues.

Associative learning affects many areas of human behavior. Recently, we showed that the neural response to monetary reward is enhanced by performing an action, suggesting interactions between neural systems controlling motor behavior and reward processing. Given that many psychiatric disorders are associated with social anhedonia, a key open question is whether such effects generalize to social rewards, and in how far they affect associative learning. We developed a novel task in which participants (n = 66) received social reward feedback and social punishment either by pressing a button or waiting. Predictive cues were linked to feedback valence with 80% accuracy. Using EEG, we measured the neural response to both predictive cues and social feedback. We found enhanced reward positivity for social reward preceded by an action, and an enhanced N2 for cues predicting negative feedback. Cue-locked P3 amplitude was reduced for cues associated with negative feedback in passive trials only, showing a modulation of outcome anticipation by performing a motor action. This was supported by connectivity analyses showing stronger directed theta synchronization, in line with increased top-down modulation of attention, in active compared with passive trials. These findings suggest that actively obtaining social feedback enhances reward sensitivity and modulates outcome anticipation.

Prior Context and Individual Alpha Frequency Influence Predictive Processing during Language Comprehension.

The extent to which the brain predicts upcoming information during language processing remains controversial. To shed light on this debate, the present study reanalyzed Nieuwland and colleagues' (2018) [Nieuwland, M. S., Politzer-Ahles, S., Heyselaar, E., Segaert, K., Darley, E., Kazanina, N., et al. Large-scale replication study reveals a limit on probabilistic prediction in language comprehension. eLife, 7, e33468, 2018] replication of DeLong and colleagues (2015) [DeLong, K. A., Urbach, T. P., & Kutas, M. Probabilistic word pre-activation during language comprehension inferred from electrical brain activity. Nature Neuroscience, 8, 1117-1121, 2005]. Participants (n = 356) viewed sentences containing articles and nouns of varying predictability, while their EEG was recorded. We measured ERPs preceding the critical words (namely, the semantic prediction potential), in conjunction with postword N400 patterns and individual neural metrics. ERP activity was compared with two measures of word predictability: cloze probability and lexical surprisal. In contrast to prior literature, semantic prediction potential amplitudes did not increase as cloze probability increased, suggesting that the component may not reflect prediction during natural language processing. Initial N400 results at the article provided evidence against phonological prediction in language, in line with Nieuwland and colleagues' findings. Strikingly, however, when the surprisal of the prior words in the sentence was included in the analysis, increases in article surprisal were associated with increased N400 amplitudes, consistent with prediction accounts. This relationship between surprisal and N400 amplitude was not observed when the surprisal of the two prior words was low, suggesting that expectation violations at the article may be overlooked under highly predictable conditions. Individual alpha frequency also modulated the relationship between article surprisal and the N400, emphasizing the importance of individual neural factors for prediction. The present study extends upon existing neurocognitive models of language and prediction more generally, by illuminating the flexible and subject-specific nature of predictive processing.

Action expectancy modulates activity in the mirror neuron system and mentalizing system.

Action understanding involves two distinct processing levels that engage separate neural mechanisms: perception of concrete kinematic information and recognition of abstract action intentions. The mirror neuron system and the mentalizing system have both been linked to concrete action and abstract information processing, but their specific roles remain debatable. Here, we conducted a functional magnetic resonance imaging study with 26 participants who passively observed expected and unexpected actions. We performed whole-brain activation, region of interest, and effective connectivity analyses to investigate the neural correlates of these actions. Whole-brain activation analyses revealed that expected actions were associated with increased activation in the left medial superior frontal gyrus, while unexpected actions were linked to heightened activity in the left supramarginal gyrus, left superior parietal lobule, right inferior temporal gyrus, and left middle frontal gyrus. Region of interest analyses demonstrated that the left ventral premotor cortex exhibited greater activation during the observation of expected actions compared to unexpected actions, while the left inferior frontal gyrus, left superior parietal lobule, and left precuneus showed stronger activation during the observation of unexpected actions. Effective connectivity was observed between the left ventral premotor cortex and the left angular gyrus, left intraparietal sulcus, left dorsal premotor cortex, and left ventromedial prefrontal cortex with the middle frontal gyrus when observing unexpected, but not expected, actions. These findings suggest that expected actions are primarily processed by the mirror neuron system, whereas unexpected actions engage both the mirror neuron system and the mentalizing system, with these systems playing complementary roles in the understanding of unexpected actions.

The strength of anticipated distractors shapes EEG alpha and theta oscillations in a Working Memory task.

Working Memory (WM) requires maintenance of task-relevant information and suppression of task-irrelevant/distracting information. Alpha and theta oscillations have been extensively investigated in relation to WM. However, studies that examine both theta and alpha bands in relation to distractors, encompassing not only power modulation but also connectivity modulation, remain scarce. Here, we depicted, at the EEG-source level, the increase in power and connectivity in theta and alpha bands induced by strong relative to weak distractors during a visual Sternberg-like WM task involving the encoding of verbal items. During retention, a strong or weak distractor was presented, predictable in time and nature. Analysis focused on the encoding and retention phases before distractor presentation. Theta and alpha power were computed in cortical regions of interest, and connectivity networks estimated via spectral Granger causality and synthetized using in/out degree indices. The following modulations were observed for strong vs. weak distractors. In theta band during encoding, the power in frontal regions increased, together with frontal-to-frontal and bottom-up occipital-to-temporal-to-frontal connectivity; even during retention, bottom-up theta connectivity increased. In alpha band during retention, but not during encoding, the power in temporal-occipital regions increased, together with top-down frontal-to-occipital and temporal-to-occipital connectivity. From our results, we postulate a proactive cooperation between theta and alpha mechanisms: the first would mediate enhancement of target representation both during encoding and retention, and the second would mediate increased inhibition of sensory areas during retention only, to suppress the processing of imminent distractor without interfering with the processing of ongoing target stimulus during encoding.

A U-shaped relationship between chronic academic stress and the dynamics of reward processing.

Despite the potential link between stress-induced reward dysfunctions and the development of mental problems, limited human research has investigated the specific impacts of chronic stress on the dynamics of reward processing. Here we aimed to investigate the relationship between chronic academic stress and the dynamics of reward processing (i.e., reward anticipation and reward consumption) using event-related potential (ERP) technology. Ninety healthy undergraduates who were preparing for the National Postgraduate Entrance Examination (NPEE) participated in the study and completed a two-door reward task, their chronic stress levels were assessed via the Perceived Stress Scale (PSS). The results showed that a lower magnitude of reward elicited more negative amplitudes of cue-N2 during the anticipatory phase, and reward omission elicited more negative amplitudes of FRN compared to reward delivery especially in high reward conditions during the consummatory phase. More importantly, the PSS score exhibited a U-shaped relationship with cue-N2 amplitudes regardless of reward magnitude during the anticipatory phase; and FRN amplitudes toward reward omission in high reward condition during the consummatory phase. These findings suggest that individuals exposed to either low or high levels of chronic stress, as opposed to moderate stress levels, exhibited a heightened reward anticipation, and an augmented violation of expectations or affective response when faced with relatively more negative outcomes.

Contextual expectations shape the motor coding of movement kinematics during the prediction of observed actions: A TMS study.

Contextual information may shape motor resonance and support intention understanding during observation of incomplete, ambiguous actions. It is unclear, however, whether this effect is contingent upon kinematics ambiguity or contextual information is continuously integrated with kinematics to predict the overarching action intention. Moreover, a differentiation between the motor mapping of the intention suggested by context or kinematics has not been clearly demonstrated. In a first action execution phase, 29 participants were asked to perform reaching-to-grasp movements towards big or small food objects with the intention to eat or to move; electromyography from the First Dorsal Interosseous (FDI) and Abductor Digiti Minimi (ADM) was recorded. Depending on object size, the intentions to eat or to move were differently implemented by a whole-hand or a precision grip kinematics, thus qualifying an action-muscle dissociation. Then, in a following action prediction task, the same participants were asked to observe an actor performing the same actions and to predict his/her intention while motor resonance was assessed for the same muscles. Of note, videos were interrupted at early or late action phases, and actions were embedded in contexts pointing toward an eating or a moving intention, congruently or incongruently with kinematics. We found greater involvement of the FDI or ADM in the execution of precision or whole-hand grips, respectively. Crucially, this pattern of activation was mirrored during observation of the same actions in congruent contexts, but it was cancelled out or reversed in the incongruent ones, either when videos were interrupted at either early or long phases of action deployment. Our results extend previous evidence by showing that contextual information shapes motor resonance not only under conditions of perceptual uncertainty but also when more informative kinematics is available.

Predictive posture stabilization before contact with moving objects: equivalence of smooth pursuit tracking and peripheral vision.

Postural stabilization is essential to effectively interact with our environment. Humans preemptively adjust their posture to counteract impending disturbances, such as those encountered during interactions with moving objects, a phenomenon known as anticipatory postural adjustments (APAs). APAs are thought to be influenced by predictive models that incorporate object motion via retinal motion and extraretinal signals. Building on our previous work that examined APAs in relation to the perceived momentum of moving objects, here we explored the impact of object motion within different visual field sectors on the human capacity to anticipate motion and prepare APAs for contact between virtual moving objects and the limb. Participants interacted with objects moving toward them under different gaze conditions. In one condition, participants fixated on either a central point (central fixation) or left-right of the moving object (peripheral fixation), whereas in another, they followed the moving object with smooth pursuit eye movements (SPEMs). We found that APAs had the smallest magnitude in the central fixation condition and that no notable differences in APAs were apparent between the SPEM and peripheral fixation conditions. This suggests that the visual system can accurately perceive motion of objects in peripheral vision for posture stabilization. Using Bayesian model averaging, we also evaluated the contribution of different gaze variables, such as eye velocity and gain (ratio of eye and object velocity) and showed that both eye velocity and gain signals were significant predictors of APAs. Taken together, our study underscores the roles of oculomotor signals in the modulation of APAs.NEW & NOTEWORTHY We show that the human visuomotor system can detect motion in peripheral vision and make anticipatory adjustments to posture before contact with moving objects, just as effectively as when the eye movement system tracks those objects with smooth pursuit eye movements. These findings pave the way for research into how age-induced changes in spatial vision, eye movements, and motion perception could affect the control of limb movements and postural stability during motion-mediated interactions with objects.

Bumpy ride ahead: Anticipated effort as emotional evidence?

Conscious reportable (un)pleasantness feelings were shown to be successfully described by a process in which evidence favoring pleasant and unpleasant feelings accumulates until one response wins the race. This approach is challenged by (a) insufficient specification of "evidence," and (b) incomplete verification that participants report their truly experienced (un)pleasant feelings and not what they expect to feel. In each trial in this preregistered experiment, the (un)pleasant feeling reports regarding emotion evoking pictures was embedded in a period when participants expected a low-effort task (feature visual search) or a high-effort task (feature-conjunction search). Fitting the Linear Ballistic Accumulator model to the feeling report data shows that anticipated effort was associated with a higher rate of unpleasant evidence accumulation, but only when the emotion evoking pictures were normatively unpleasant and not when they were normatively pleasant. These results suggest that anticipated effort may be one source of "evidence," but only given a certain interpretation of the findings, and that genuinely felt emotions contribute to the emotion reports, assuming that participants intended to react to the pictures, as instructed, and not to the anticipated effort.

Concurrent expectation and experience-based metacontrol: EEG insights and the role of working memory capacity.

We investigated the simultaneous influence of expectation and experience on metacontrol, which we define as the instantiation of context-specific control states. These states could entail heightened control states in preparation for frequent task switching or lowered control states for task repetition. Specifically, we examined whether "expectations" regarding future control demands prompt proactive metacontrol, while "experiences" with items associated with specific control demands facilitate reactive metacontrol. In Experiment 1, we utilized EEG with a high temporal resolution to differentiate between brain activities associated with proactive and reactive metacontrol. We successfully observed cue-locked and image-locked ERP patterns associated with proactive and reactive metacontrol, respectively, supporting concurrent instantiation of two metacontrol modes. In Experiment 2, we focused on individual differences to investigate the modulatory role of working memory capacity (WMC) in the concurrent instantiation of two metacontrol modes. Our findings revealed that individuals with higher WMC exhibited enhanced proactive metacontrol, indicated by smaller response time variability (RTV). Additionally, individuals with higher WMC showed a lower tendency to rely on reactive metacontrol, indicated by a smaller item-specific switch probability (ISSP) effect. In conclusion, our results suggest that proactive and reactive metacontrol can coexist, but their interplay is influenced by individuals' WMC. Higher WMC promotes the use of proactive metacontrol while attenuating reliance on reactive metacontrol. This study provides insights into the interplay between proactive and reactive metacontrol and highlights the impact of WMC on their concurrent instantiation.

Conclusions Regarding the Role of Expectations in Placebo Analgesia Studies May Depend on How We Investigate It: A Meta-Analysis, Systematic Review, and Proposal for Methodological Discussions.

OBJECTIVE: Expectations are highlighted as a key component in placebo effects. However, there are different approaches to whether and how placebo studies should account for expectations, and the direct contribution has yet to be estimated in meta-analyses. Using different methodological approaches, this meta-analysis and systematic review examines the extent to which expectations contribute to pain in placebo studies. METHODS: The databases PubMed, PsycINFO, Embase, and Web of Science were searched for placebo analgesia mechanism studies with numerical measures of both expectations and pain. Thirty-one studies, comprising 34 independent study populations (1566 subjects: patients and healthy participants) were included. Two meta-analyses were conducted: meta-analysis 1, using study-level data, estimated the effect of expectation interventions without taking measures of expectations into account (expectations assumed); and meta-analysis 2, using individual-level data, estimated the direct impact of participants' expectations on pain (expectations assessed). Risk of bias was assessed using the Cochrane risk-of-bias tool. RESULTS: Meta-analysis 1 showed a moderate effect of expectation interventions over no expectation intervention on pain intensity (Hedges g = 0.45, I2 = 54.19). Based on 10 studies providing individual-level data, meta-analysis 2 showed that expectations predicted pain intensity in placebo and control groups ( b = 0.36, SE = 0.05), although inconsistently across study methodologies. CONCLUSIONS: Participants' expectations contributed moderately to pain in placebo analgesia studies. However, this may largely be influenced by how we measure expectations and how their contribution is conceptualized and analyzed-both within and across studies.

Consolidation Enhances Sequential Multistep Anticipation but Diminishes Access to Perceptual Features.

Many experiences unfold predictably over time. Memory for these temporal regularities enables anticipation of events multiple steps into the future. Because temporally predictable events repeat over days, weeks, and years, we must maintain-and potentially transform-memories of temporal structure to support adaptive behavior. We explored how individuals build durable models of temporal regularities to guide multistep anticipation. Healthy young adults (Experiment 1: N = 99, age range = 18-40 years; Experiment 2: N = 204, age range = 19-40 years) learned sequences of scene images that were predictable at the category level and contained incidental perceptual details. Individuals then anticipated upcoming scene categories multiple steps into the future, immediately and at a delay. Consolidation increased the efficiency of anticipation, particularly for events further in the future, but diminished access to perceptual features. Further, maintaining a link-based model of the sequence after consolidation improved anticipation accuracy. Consolidation may therefore promote efficient and durable models of temporal structure, thus facilitating anticipation of future events.

Reward anticipation-related neural activation following cued reinforcement in adults with psychotic psychopathology and biological relatives.

BACKGROUND: Schizophrenia is associated with hypoactivation of reward sensitive brain areas during reward anticipation. However, it is unclear whether these neural functions are similarly impaired in other disorders with psychotic symptomatology or individuals with genetic liability for psychosis. If abnormalities in reward sensitive brain areas are shared across individuals with psychotic psychopathology and people with heightened genetic liability for psychosis, there may be a common neural basis for symptoms of diminished pleasure and motivation. METHODS: We compared performance and neural activity in 123 people with a history of psychosis (PwP), 81 of their first-degree biological relatives, and 49 controls during a modified Monetary Incentive Delay task during fMRI. RESULTS: PwP exhibited hypoactivation of the striatum and anterior insula (AI) during cueing of potential future rewards with each diagnostic group showing hypoactivations during reward anticipation compared to controls. Despite normative task performance, relatives demonstrated caudate activation intermediate between controls and PwP, nucleus accumbens activation more similar to PwP than controls, but putamen activation on par with controls. Across diagnostic groups of PwP there was less functional connectivity between bilateral caudate and several regions of the salience network (medial frontal gyrus, anterior cingulate, AI) during reward anticipation. CONCLUSIONS: Findings implicate less activation and connectivity in reward processing brain regions across a spectrum of disorders involving psychotic psychopathology. Specifically, aberrations in striatal and insular activity during reward anticipation seen in schizophrenia are partially shared with other forms of psychotic psychopathology and associated with genetic liability for psychosis.

Cerebellar Direct Current Stimulation Reveals the Causal Role of the Cerebellum in Temporal Prediction.

Temporal prediction (TP) influences our perception and cognition. The cerebellum could mediate this multi-level ability in a context-dependent manner. We tested whether a modulation of the cerebellar neural activity, induced by transcranial Direct Current Stimulation (tDCS), changed the TP ability according to the temporal features of the context and the duration of target interval. Fifteen healthy participants received anodal, cathodal, and sham tDCS (15 min × 2 mA intensity) over the right cerebellar hemisphere during a TP task. We recorded reaction times (RTs) to a target during the task in two contextual conditions of temporal anticipation: rhythmic (i.e., interstimulus intervals (ISIs) were constant) and single-interval condition (i.e., the estimation of the timing of the target was based on the prior exposure of the train of stimuli). Two ISIs durations were explored: 600 ms (short trials) and 900 ms (long trials). Cathodal tDCS improved the performance during the TP task (shorter RTs) specifically in the rhythmic condition only for the short trials and in the single-interval condition only for the long trials. Our results suggest that the inhibition of cerebellar activity induced a different improvement in the TP ability according to the temporal features of the context. In the rhythmic context, the cerebellum could integrate the temporal estimation with the anticipatory motor responses critically for the short target interval. In the single-interval context, for the long trials, the cerebellum could play a main role in integrating representation of time interval in memory with the elapsed time providing an accurate temporal prediction.

Age-related changes in reticulospinal contributions to anticipatory postural adjustments between back extensors and abdominal muscles.

Anticipatory postural adjustments (APAs) give feedforward postural control of the trunk, but they are delayed with ageing, affecting balance and mobility in older individuals. The reticulospinal tract contributes to postural control of the trunk; however, the extent to which age-related changes affect the reticulospinal contributions to APAs of the trunk remains unknown in humans. Here, we tested the hypothesis that a startling acoustic sound, which activates the reticulospinal tract, improves delayed APAs in older individuals. Twenty-two old (75 ± 6 years) and 20 healthy young adults (21 ± 4 years) performed a self-initiated fast bilateral shoulder flexion or shoulder extension task in response to visual, visual and auditory (80 dB), or visual and startling (115 dB) cues. Electromyography (EMG) was recorded from bilateral anterior deltoid (AD) and erector spinae (ES) during shoulder flexion and from bilateral posterior deltoid (PD) and rectus abdominis (RA) during shoulder extension. EMG onset of all muscles shortened during the startling cue in both age groups, suggesting a non-specific modulation of the reticulospinal tract on prime movers (AD or PD) and non-prime movers (ES or RA). Interestingly, APAs of the ES were accelerated in older participants to a similar degree as in younger participants during the startling cue. Conversely, APAs of the RA were not influenced by the startling cue in older participants. Our results suggest differential effects of ageing on functional contributions of the reticulospinal tract to APAs between back extensors and abdominal muscles.

Examination-related anticipatory levels of dehydroepiandrosterone and cortisol predict positive affect, examination marks and support-seeking in college students.

Dehydroepiandrosterone (DHEA) and cortisol release appear to have contrasting effects on stress perception during stressful tasks. This study aimed to investigate anticipatory examination stress in college students by considering DHEA, cortisol, psycho-emotional aspects and examination performance. Seventy-six students (66 females, 10 males; age range 18-25 years) provided saliva samples and completed questionnaires in two sessions 48 hours apart. During the second session, the students performed the examination. The questionnaires used were the State-Trait Anxiety Inventory, the Positive and Negative Affect Scale, and the Brief-Coping Orientation to Problems Experienced Inventory. DHEA, cortisol, anxiety and negative affect showed an anticipatory rise before the examination (all ps < 0.001). This rise of DHEA and cortisol was associated with lower positive affect (p = 0.001 and p = 0.043, respectively). However, only the DHEA anticipatory levels were linked to poorer examination marks (p = 0.020). Higher levels of the DHEA/cortisol ratio in anticipation of the examination were related to lower scores on the support-seeking strategy (p = 0.022). There was no association between DHEA and cortisol levels and anxiety, negative affect, active and avoidant coping strategies, or academic record. These results suggest that how DHEA and cortisol respond in anticipation of examination stress significantly impacts students' emotional well-being during examination periods and how they cope with stress. They also suggest that levels of DHEA in anticipation of an academic stressor have detrimental effects on stress management.