Topographically selective motor inhibition under threat of pain.

ABSTRACT: Pain-related motor adaptations may be enacted predictively at the mere threat of pain, before pain occurrence. Yet, in humans, the neurophysiological mechanisms underlying motor adaptations in anticipation of pain remain poorly understood. We tracked the evolution of changes in corticospinal excitability (CSE) as healthy adults learned to anticipate the occurrence of lateralized, muscle-specific pain to the upper limb. Using a Pavlovian threat conditioning task, different visual stimuli predicted pain to the right or left forearm (experiment 1) or hand (experiment 2). During stimuli presentation before pain occurrence, single-pulse transcranial magnetic stimulation was applied over the left primary motor cortex to probe CSE and elicit motor evoked potentials from target right forearm and hand muscles. The correlation between participants' trait anxiety and CSE was also assessed. Results showed that threat of pain triggered corticospinal inhibition specifically in the limb where pain was expected. In addition, corticospinal inhibition was modulated relative to the threatened muscle, with threat of pain to the forearm inhibiting the forearm and hand muscles, whereas threat of pain to the hand inhibited the hand muscle only. Finally, stronger corticospinal inhibition correlated with greater trait anxiety. These results advance the mechanistic understanding of pain processes showing that pain-related motor adaptations are enacted at the mere threat of pain, as sets of anticipatory, topographically organized motor changes that are associated with the expected pain and are shaped by individual anxiety levels. Including such anticipatory motor changes into models of pain may lead to new treatments for pain-related disorders.

PsycAssist: A Web-Based Artificial Intelligence System Designed for Adaptive Neuropsychological Assessment and Training.

Assessing executive functions in individuals with disorders or clinical conditions can be challenging, as they may lack the abilities needed for conventional test formats. The use of more personalized test versions, such as adaptive assessments, might be helpful in evaluating individuals with specific needs. This paper introduces PsycAssist, a web-based artificial intelligence system designed for neuropsychological adaptive assessment and training. PsycAssist is a highly flexible and scalable system based on procedural knowledge space theory and may be used potentially with many types of tests. We present the architecture and adaptive assessment engine of PsycAssist and the two currently available tests: Adap-ToL, an adaptive version of the Tower of London-like test to assess planning skills, and MatriKS, a Raven-like test to evaluate fluid intelligence. Finally, we describe the results of an investigation of the usability of Adap-ToL and MatriKS: the evaluators perceived these tools as appropriate and well-suited for their intended purposes, and the test-takers perceived the assessment as a positive experience. To sum up, PsycAssist represents an innovative and promising tool to tailor evaluation and training to the specific characteristics of the individual, useful for clinical practice.

Changes in brain rhythms and connectivity tracking fear acquisition and reversal.

Fear conditioning is used to investigate the neural bases of threat and anxiety, and to understand their flexible modifications when the environment changes. This study aims to examine the temporal evolution of brain rhythms using electroencephalographic signals recorded in healthy volunteers during a protocol of Pavlovian fear conditioning and reversal. Power changes and Granger connectivity in theta, alpha, and gamma bands are investigated from neuroelectrical activity reconstructed on the cortex. Results show a significant increase in theta power in the left (contralateral to electrical shock) portion of the midcingulate cortex during fear acquisition, and a significant decrease in alpha power in a broad network over the left posterior-frontal and parietal cortex. These changes occur since the initial trials for theta power, but require more trials (3/4) to develop for alpha, and are also present during reversal, despite being less pronounced. In both bands, relevant changes in connectivity are mainly evident in the last block of reversal, just when power differences attenuate. No significant changes in the gamma band were detected. We conclude that the increased theta rhythm in the cingulate cortex subserves fear acquisition and is transmitted to other cortical regions via increased functional connectivity allowing a fast theta synchronization, whereas the decrease in alpha power can represent a partial activation of motor and somatosensory areas contralateral to the shock side in the presence of a dangerous stimulus. In addition, connectivity changes at the end of reversal may reflect long-term alterations in synapses necessary to reverse the previously acquired contingencies.

Temporal dynamics of the Rubber Hand Illusion.

It is widely accepted that the representation of the body is not fixed and immutable, but rather flexible and constantly updated based on a continuous stream of multisensory information. This mechanism can be very useful to adapt to several situations, but it would not be adaptive if the body representation was too malleable or if it wasn't capable of restoring its integrity after a transient modification. Here we used the Rubber Hand Illusion (RHI) to investigate how quickly the body representation can be modified. Previous studies have investigated the timing of the onset and offset of the illusion, however, they did not assess a fine temporal resolution. Here, we used a potentiometer to record a moment-by-moment rating of the feeling of owning the RH for two minutes during the visuo-tactile stimulation and two minutes following the stimulation. Our results suggest that the feeling of Ownership is already established during the first 19 s of stimulation then it continues to grow, but at a much slower pace. The feeling of Ownership disappears within 66 s from the end of the stimulation. This work sheds new light on the temporal dynamics of the RHI and the malleability of the body self-consciousness.

Preliminary evidence on machine learning approaches for clusterizing students' cognitive profile.

Assessing the cognitive abilities of students in academic contexts can provide valuable insights for teachers to identify their cognitive profile and create personalized teaching strategies. While numerous studies have demonstrated promising outcomes in clustering students based on their cognitive profiles, effective comparisons between various clustering methods are lacking in the current literature. In this study, we aim to compare the effectiveness of two clustering techniques to group students based on their cognitive abilities including general intelligence, attention, visual perception, working memory, and phonological awareness. 292 students, aged 11-15 years, participated in the study. A two-level approach based on the joint use of Kohonen's Self-Organizing Map (SOMs) and k-means clustering algorithm was compared with an approach based on the k-means clustering algorithm only. The resulting profiles were then predicted via AdaBoost and ANN supervised algorithms. The results showed that the two-level approach provides the best solution for this problem while the ANN algorithm was the winner in the classification problem. These results laying the foundations for developing a useful instrument for predicting the students' cognitive profile.

Theta and alpha power track the acquisition and reversal of threat predictions and correlate with skin conductance response.

The ability to flexibly adjust one's threat predictions to meet the current environmental contingencies is crucial to survival. Nevertheless, its neural oscillatory correlates remain elusive in humans. Here, we tested whether changes in theta and alpha brain oscillations mark the updating of threat predictions and correlate with response of the peripheral nervous system. To this end, electroencephalogram and electrodermal activity were recorded in a group of healthy adults, who completed a Pavlovian threat conditioning task that included an acquisition and a reversal phase. Both theta and alpha power discriminated between threat and safety, with each frequency band showing unique patterns of modulations during acquisition and reversal. While changes in midcingulate theta power may learn the timing of an upcoming danger, alpha power may reflect the preparation of the somato-motor system. Additionally, ventromedial prefrontal cortex theta may play a role in the inhibition of previously acquired threat responses, when they are no longer appropriate. Finally, theta and alpha power correlated with skin conductance response, establishing a direct relationship between activation of the central and peripheral nervous systems. Taken together these results highlight the existence of multiple oscillatory systems that flexibly regulate their activity for the successful expression of threat responses in an ever-changing environment.

Pavlovian threat learning shapes the kinematics of action.

Prompt response to environmental threats is critical to survival. Previous research has revealed mechanisms underlying threat-conditioned physiological responses, but little is known about how threats shape action. Here we tested if threat learning shapes the kinematics of reaching in human adults. In two different experiments conducted on independent samples of participants, after Pavlovian threat learning, in which a stimulus anticipated the delivery of an aversive shock, whereas another did not, the peak velocity and acceleration of reaching increased for the shocked-paired stimulus, relative to the unpaired one. These kinematic changes appeared as a direct consequence of learning, emerging even in absence of an actual threat to body integrity, as no shock occurred during reaching. Additionally, they correlated with the strength of sympathetic response during threat learning, establishing a direct relationship between previous learning and subsequent changes in action. The increase in velocity and acceleration of action following threat learning may be adaptive to facilitate the implementation of defensive responses. Enhanced action invigoration may be maladaptive, however, when defensive responses are inappropriately enacted in safe contexts, as exemplified in a number of anxiety-related disorders.

General Pavlovian-to-instrumental transfer in humans: Evidence from Bayesian inference.

When repeatedly paired with rewarding outcomes (i.e., Pavlovian conditioning), environmental cues may acquire predictive and motivational significance and later enhance instrumental responding for the same (i.e., outcome-specific transfer) or motivationally similar (i.e., general transfer) outcomes. Although outcome-specific and general Pavlovian-to-Instrumental Transfer (PIT) are characterized by different neural substrates and behavioral mechanisms, general transfer has never been studied in isolation from outcome-specific transfer in humans. The first aim of the present study was to test whether the general transfer effect could emerge in isolation and independently of outcome-specific transfer. Our results showed that general transfer can be elicited without the concurrent presence of outcome-specific transfer, supporting the idea that outcome-specific and general transfer can be studied independently of each other. The second aim of the present study was to clarify whether the affordance-like properties of the outcomes can affect the general transfer. In fact, a critical difference in current studies on general transfer concerns the use of cues associated with outcomes for which an action was previously learned (or not) during the instrumental training. This apparently minor difference affects the affordance-like properties of the outcome and may also be transferred to the cue, in turn impacting general transfer. Results revealed a general transfer of the same magnitude regardless of whether cues were associated with reward earned or not during instrumental conditioning. These findings increase the current knowledge on the incentive motivational mechanism behind general transfer, indicating that it is independent of the motor features of the outcome.

Interaction effect: Are you doing the right thing?

How to correctly interpret interaction effects has been largely discussed in scientific literature. Nevertheless, misinterpretations are still frequently observed, and neuroscience is not exempt from this trend. We reviewed 645 papers published from 2019 to 2020 and found that, in the 93.2% of studies reporting a statistically significant interaction effect (N = 221), post-hoc pairwise comparisons were the designated method adopted to interpret its results. Given the widespread use of this approach, we aim to: (1) highlight its limitations and how it can lead to misinterpretations of the interaction effect; (2) discuss more effective and powerful ways to correctly interpret interaction effects, including both explorative and model selection procedures. The paper provides practical examples and freely accessible online materials to reproduce all analyses.

Unifying Evidence on Delay Discounting: Open Task, Analysis Tutorial, and Normative Data from an Italian Sample.

Despite the widespread use of the delay discounting task in clinical and non-clinical contexts, several task versions are available in the literature, making it hard to compare results across studies. Moreover, normative data are not available to evaluate individual performances. The present study aims to propose a unified version of the delay discounting task based on monetary rewards and it provides normative values built on an Italian sample of 357 healthy participants. The most used parameters in the literature to assess the delay discount rate were compared to find the most valid index to discriminate between normative data and a clinical population who typically present impulsivity issues, i.e., patients with a lesion to the medial orbitofrontal cortex (mOFC). In line with our hypothesis, mOFC patients showed higher delay discounting scores than the normative sample and the normative group. Based on this evidence, we propose that the task and indexes here provided can be used to identify extremely high (above the 90th percentile for hyperbolic k or below the 10th percentile for AUC) or low (below the 10th percentile for hyperbolic k or above the 90th percentile for AUC) delay discounting performances. The complete dataset, the R code used to perform all analyses, a free and modifiable version of the delay discounting task, as well as the R code that can be used to extract all indexes from such tasks and compare subjective performances with the normative data here presented are available as online materials.

Visuo-motor integration, vision perception and attention in mTBI patients. Preliminary findings.

Patients with mild traumatic brain injuries (mTBI) often report difficulties in motor coordination and visuo-spatial attention. However, the consequences of mTBI on fine motor and visuo-motor coordination are still not well understood. We aimed to evaluate whether mTBI had a concomitant effect on fine motor ability and visuo-motor integration and whether this is related to visual perception and visuo-spatial attention impairments, including patients at different symptoms stage. Eleven mTBI patients (mean age 22.8 years) and ten healthy controls participated in the study. Visuo-motor integration of fine motor abilities and form recognition were measured with the Beery-Buktenica Developmental Test of Visual-Motor Integration test, motion perception was evaluated with motion coherence test, critical flicker fusion was measured with Pocket CFF tester. Visuo-spatial was assessed with the Ruff 2 & 7 Selection Attention Test. mTBI patients showed reduced visuo-motor integration, form recognition, and motor deficits as well as visuo-spatial attention impairment, while motion perception and critical flicker fusion were not impaired. These preliminary findings suggest that the temporary brain insults deriving from mTBI compromise fine motor skills, visuomotor integration, form recognition, and visuo-spatial attention. The impairment in visuo-motor coordination was associated with speed in visuo-attention and correlated with symptoms severity while motor ability was correlated with time since concussion. Given the strong correlation between visuomotor coordination and symptom severity, further investigation with a larger sample seems warranted. Since there appeared to be differences in motor skills with respect to symptom stage, further research is needed to investigate symptom profiles associated with visuomotor coordination and fine motor deficits in mTBI patients.

Modulation of cue-guided choices by transcranial direct current stimulation.

Environmental cues may anticipate the availability of rewards, thus acting as a guide towards a specific choice (i.e., cue-guided choices). Despite the lateral prefrontal cortex having a critical role in using past learning and flexibly selecting relevant information to guide behavior, the literature on the neural basis of human cue-guided choice mainly focused on the subcortical brain structures implicated, while the specific role of cortical areas remained unclear. The present study aimed to provide causal evidence for the involvement of the lateral prefrontal cortex in two forms of human cue-guided choice, namely outcome-specific and general. To do this, 2 mA cathodal, anodal or sham transcranial direct current stimulation was applied over the lateral prefrontal cortex (with the posterior parietal cortex serving as control region) in three separate groups performing a Pavlovian-to-Instrumental Transfer task. Results showed, for the first time, a dissociation in the cortical structures involved in human cue-guided choice. Cathodal stimulation of the lateral prefrontal cortex reduced the outcome-specific transfer. In striking contrast, there was no influence on the general transfer. These results argue in favor of the presence of at least two possible neural pathways underlying cue-guided choices.

Preliminary Validation of the CI-FRA Checklist: A Simple Screening Tool for Measuring the Early Signs of Reading and Spelling Disorders in Italian Primary Students.

Although several screening tests for recognizing early signs of reading and spelling difficulties have been developed, brief and methodologically grounded tools for teachers are very limited. The present study aimed to lay the foundation for a new screening tool for teachers: the Checklist for early Indicators of risk Factors in Reading Ability (CI-FRA). The proposed checklist consists of 20 items, based on a 7-point Likert scale, and it investigates five domains: reading, writing, attention, and motor skills. Six hundred sixty-seven children were evaluated by 40 teachers during the first year of primary school and, longitudinally, in the second year. Exploratory factor analysis and confirmatory factor analysis (CFA) were applied to verify structural validity. Concurrent validity was assessed by Spearman correlation to analyze the link between CI-FRA and reading and spelling standardized tests and cognitive tests. Reliability was assessed by Cronbach α and interclass correlation coefficient. The CFA reported a three-factor structure as the optimal solution, including language (reading and writing), visuospatial attention, and fine motor skills subscales. Good reliability, good internal consistency, and acceptable test-retest indices were found. Concurrent validity was confirmed by significant correlations between CI-FRA total score and standardized reading and spelling test, as well as by correlations between CI-FRA subscales and neuropsychological standardized test scores. Preliminary evaluation of sensitivity by receiver operating characteristic curves showed that the CI-FRA score has particularly high sensitivity and specificity for word reading speed deficit. In conclusion, the results confirm that CI-FRA is a theoretically grounded and statistically valid tool that could help the teachers to screen for early signs of reading and spelling difficulties.

Revaluing the Role of vmPFC in the Acquisition of Pavlovian Threat Conditioning in Humans.

The role of the ventromedial prefrontal cortex (vmPFC) in human pavlovian threat conditioning has been relegated largely to the extinction or reversal of previously acquired stimulus-outcome associations. However, recent neuroimaging evidence questions this view by also showing activity in the vmPFC during threat acquisition. Here we investigate the casual role of vmPFC in the acquisition of pavlovian threat conditioning by assessing skin conductance response (SCR) and declarative memory of stimulus-outcome contingencies during a differential pavlovian threat-conditioning paradigm in eight patients with a bilateral vmPFC lesion, 10 with a lesion outside PFC and 10 healthy participants (each group included both females and males). Results showed that patients with vmPFC lesion failed to produce a conditioned SCR during threat acquisition, despite no evidence of compromised SCR to unconditioned stimulus or compromised declarative memory for stimulus-outcome contingencies. These results suggest that the vmPFC plays a causal role in the acquisition of new learning and not just in the extinction or reversal of previously acquired learning, as previously thought. Given the role of the vmPFC in schema-related processing and latent structure learning, the vmPFC may be required to construct a detailed representation of the task, which is needed to produce a sustained conditioned physiological response in anticipation of the unconditioned stimulus during threat acquisition.SIGNIFICANCE STATEMENT Pavlovian threat conditioning is an adaptive mechanism through which organisms learn to avoid potential threats, thus increasing their chances of survival. Understanding what brain regions contribute to such a process is crucial to understand the mechanisms underlying adaptive as well as maladaptive learning, and has the potential to inform the treatment of anxiety disorders. Importantly, the role of the ventromedial prefrontal cortex (vmPFC) in the acquisition of pavlovian threat conditioning has been relegated largely to the inhibition of previously acquired learning. Here, we show that the vmPFC actually plays a causal role in the acquisition of pavlovian threat conditioning.

State-Dependent TMS over Prefrontal Cortex Disrupts Fear-Memory Reconsolidation and Prevents the Return of Fear.

Erasing maladaptive memories has been a challenge for years. A way to change fear memories is to target the process of reconsolidation, during which a retrieved memory transiently returns to a labile state, amenable to modification [1, 2]. Disruption of human fear-memory reconsolidation has been classically attempted with pharmacological [3] or behavioral (e.g., extinction) [4] treatments that, however, do not clarify the underlying brain mechanism. To address this issue, in 84 healthy humans submitted to six experiments, here, we combined a differential fear conditioning paradigm with repetitive transcranial magnetic stimulation (rTMS) administered in a state-dependent manner. In a critical condition, we stimulated the dorsolateral prefrontal cortex (dlPFC) 10 min after a reminder cue that reactivated a fear memory acquired 1 day before. At testing, 24 h after rTMS, participants exhibited decreased physiological expression of fear, as shown by their skin conductance response. Similar reductions were observed when targeting the left and the right dlPFC. In contrast, no decrease was observed in participants tested immediately after dlPFC-rTMS or in participants receiving either control rTMS (i.e., active control site and sham stimulations) or dlPFC-rTMS without preceding fear-memory reactivation, thus showing both the site and time specificity and state dependency of our rTMS intervention. Expression of fear was indeed reduced only when dlPFC-rTMS was administered within the reconsolidation time window. Moreover, dlPFC-rTMS prevented subsequent return of fear after extinction training. These findings highlight the causal role of dlPFC in fear-memory reconsolidation and suggest that rTMS can be used in humans to prevent the return of fear.

Subliminal determinants of cue-guided choice.

By anticipating potential rewards, external cues can guide behavior to achieve a goal. Whether the conscious elaboration of these cues is necessary to elicit cue-guided choices is still unknown. The goal of the present study is to test whether the subliminal presentation of a visual cue previously paired with a reward is sufficient to bias responses that can lead to the same or a similar reward. To this aim, three experiments compared the subliminal and supraliminal presentation of reward-associated cues during a Pavlovian-to-Instrumental Transfer task. In line with previous evidence, results showed that the supraliminal presentation of reward-associated Pavlovian cues biased participant's choice towards motivationally similar rewards (general transfer) as well as towards rewards sharing the precise sensory-specific properties of the cue (outcome-specific transfer). In striking contrast, subliminal cues biased choice only towards motivationally similar rewards (general transfer). Taken together, these findings suggest that cue-guided choices are modulated by the level of perceptual threshold (i.e., subliminal vs supraliminal) of reward-associated cues. Although conscious elaboration of the cue is necessary to guide choice towards a specific reward, subliminal processing is still sufficient to push towards choices sharing the motivational properties of the cue. Implications for everyday life, clinical conditions, and theoretical accounts of cue-guided choices are discussed.

Using Two-Step Cluster Analysis and Latent Class Cluster Analysis to Classify the Cognitive Heterogeneity of Cross-Diagnostic Psychiatric Inpatients.

The heterogeneity of cognitive profiles among psychiatric patients has been reported to carry significant clinical information. However, how to best characterize such cognitive heterogeneity is still a matter of debate. Despite being well suited for clinical data, cluster analysis techniques, like the Two-Step and the Latent Class, received little to no attention in the literature. The present study aimed to test the validity of the cluster solutions obtained with Two-Step and Latent Class cluster analysis on the cognitive profile of a cross-diagnostic sample of 387 psychiatric inpatients. Two-Step and Latent Class cluster analysis produced similar and reliable solutions. The overall results reported that it is possible to group all psychiatric inpatients into Low and High Cognitive Profiles, with a higher degree of cognitive heterogeneity in schizophrenia and bipolar disorder patients than in depressive disorders and personality disorder patients.

Individual differences in working memory capacity and cue-guided behavior in humans.

Information gathered via Pavlovian and Instrumental learning can be integrated to guide behavior, in a phenomenon experimentally known as Pavlovian-to-Instrumental Transfer (PIT). In particular, in appetitive PIT, a reward-associated cue is able to enhance the instrumental response previously associated with the same (outcome-specific PIT), or a similar (general PIT), reward. The PIT effect is increasingly investigated for its numerous implications in clinical contexts as well as daily life situations. Nevertheless, the precise mechanism behind it is not yet clear. The relation between the PIT effect and high-level cognitive abilities - like working memory - is still unknown, but potentially relevant to unveil its functioning. The present study aims to examine the precise relationship between individual differences in working memory and the two forms of PIT effect, namely outcome-specific and general. For this purpose, 100 participants underwent a classical PIT paradigm. Results showed a relationship between individual working memory and outcome-specific PIT, but not general PIT. Importantly, the role of working memory was not related to the acquisition of the learning contingencies, but rather linked to an imbalance between congruent and incongruent choices. The results are discussed in terms of the adaptive and maladaptive implications for human behavior.

Context-dependent extinction of threat memories: influences of healthy aging.

Although a substantial progress has been made in recent years on understanding the processes mediating extinction of learned threat, little is known about the context-dependent extinction of threat memories in elderly individuals. We used a 2-day differential threat conditioning and extinction procedure to determine whether young and older adults differed in the contextual recall of conditioned responses after extinction. On Day 1, conditioned stimuli were paired with an aversive electric shock in a 'danger' context and then extinguished in a different 'safe' context. On Day 2, the extinguished stimulus was presented to assess extinction recall (safe context), and threat renewal (danger context). Physiological and verbal report measures of threat conditioning were collected throughout the experiment. Skin conductance response (SCR data revealed no significant differences between age groups during acquisition and extinction of threat conditioning on Day 1. On Day 2, however, older adults showed impaired recall of extinction memory, with increased SCR to the extinguished stimulus in the 'safe' context, and reduced ability to process context properly. In addition, there were no age group differences in fear ratings and contingency awareness, thus revealing that aging selectively impairs extinction memories as indexed by autonomic responses. These results reveal that aging affects the capacity to use context to modulate learned responses to threat, possibly due to changes in brain structures that enable context-dependent behaviour and are preferentially vulnerable during aging.