Individual differences in intracortical inhibition predict action control when facing emotional stimuli.

Efficient inhibitory control in the context of prepotent actions is vital. However, such action inhibition may be profoundly influenced by affective states. Interestingly, research indicates that action control can be either impaired or improved by emotional stimuli. Thus, a great deal of confusion surrounds our knowledge of the complex dynamics subtending emotions and action control. Here, we aimed to investigate whether negative stimuli, even when non-consciously presented and task-irrelevant, can affect action control relative to neutral stimuli. Additionally, we tested whether individual differences in intracortical excitability may predict action control capabilities. To address these issues, we asked participants to complete a modified version of the Stop Signal Task (SST) in which fearful or neutral stimuli were subliminally presented before the go signals as primes. Moreover, we assessed participants' resting-state corticospinal excitability, short intracortical inhibition (SICI), and intracortical facilitation (ICF). Results demonstrated better action control capabilities when fearful stimuli were subliminally presented and interindividual SICI predicted stronger action inhibition capabilities. Taken together, these results shed new light on the intricate dynamics between action, consciousness, and motor control, suggesting that intracortical measures can be used as potential biomarkers of reduced motor inhibition in research and clinical settings.

'Nip it in the bud': Low-frequency rTMS of the prefrontal cortex disrupts threat memory consolidation in humans.

It is still unclear how the human brain consolidates aversive (e.g., traumatic) memories and whether this process can be disrupted. We hypothesized that the dorsolateral prefrontal cortex (dlPFC) is crucially involved in threat memory consolidation. To test this, we used low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) within the memory stabilization time window to disrupt the expression of threat memory. We combined a differential threat-conditioning paradigm with LF-rTMS targeting the dlPFC in the critical condition, and occipital cortex stimulation, delayed dlPFC stimulation, and sham stimulation as control conditions. In the critical condition, defensive reactions to threat were reduced immediately after brain stimulation, and 1 h and 24 h later. In stark contrast, no decrease was observed in the control conditions, thus showing both the anatomical and temporal specificity of our intervention. We provide causal evidence that selectively targeting the dlPFC within the early consolidation period prevents the persistence and return of conditioned responses. Furthermore, memory disruption lasted longer than the inhibitory window created by our TMS protocol, which suggests that we influenced dlPFC neural activity and hampered the underlying, time-dependent consolidation process. These results provide important insights for future clinical applications aimed at interfering with the consolidation of aversive, threat-related memories.

The role of pre-supplementary motor cortex in action control with emotional stimuli: A repetitive transcranial magnetic stimulation study.

Swiftly halting ongoing motor actions is essential to react to unforeseen and potentially perilous circumstances. However, the neural bases subtending the complex interplay between emotions and motor control have been scarcely investigated. Here, we used an emotional stop signal task (SST) to investigate whether specific neural circuits engaged by action suppression are differently modulated by emotional signals with respect to neutral ones. Participants performed an SST before and after the administration of one session of repetitive transcranial magnetic stimulation (rTMS) over the pre-supplementary motor cortex (pre-SMA), the right inferior frontal gyrus (rIFG), and the left primary motor cortex (lM1). Results show that rTMS over the pre-SMA improved the ability to inhibit prepotent action (i.e., better action control) when emotional stimuli were presented. In contrast, action control in a neutral context was fostered by rTMS over the rIFG. No changes were observed after lM1 stimulation. Intriguingly, individuals with higher impulsivity traits exhibited enhanced motor control when facing neutral stimuli following rIFG stimulation. These results further our understanding of the interplay between emotions and motor functions, shedding light on the selective modulation of neural pathways underpinning these processes.

Driving Hebbian plasticity over ventral premotor-motor projections transiently enhances motor resonance.

BACKGROUND: Making sense of others' actions relies on the activation of an action observation network (AON), which maps visual information about observed actions onto the observer's motor system. This motor resonance process manifests in the primary motor cortex (M1) as increased corticospinal excitability finely tuned to the muscles engaged in the observed action. Motor resonance in M1 is facilitated by projections from higher-order AON regions. However, whether manipulating the strength of AON-to-M1 connectivity affects motor resonance remains unclear. METHODS: We used transcranial magnetic stimulation (TMS) in 48 healthy humans. Cortico-cortical paired associative stimulation (ccPAS) was administered over M1 and the ventral premotor cortex (PMv), a key AON node, to induce spike-timing-dependent plasticity (STDP) in the pathway connecting them. Single-pulse TMS assessed motor resonance during action observation. RESULTS: Before ccPAS, action observation increased corticospinal excitability in the muscles corresponding to the observed movements, reflecting motor resonance in M1. Notably, ccPAS aimed at strengthening projections from PMv to M1 (PMv→M1) induced short-term enhancement of motor resonance. The enhancement specifically occurred with the ccPAS configuration consistent with forward PMv→M1 projections and dissipated 20 min post-stimulation; ccPAS administered in the reverse order (M1→PMv) and sham stimulation did not affect motor resonance. CONCLUSIONS: These findings provide the first evidence that inducing STDP to strengthen PMv input to M1 neurons causally enhances muscle-specific motor resonance in M1. Our study sheds light on the plastic mechanisms that shape AON functionality and demonstrates that exogenous manipulation of AON connectivity can influence basic mirror mechanisms that underlie social perception.

rTMS over the human medial parietal cortex impairs online reaching corrections.

Indirect correlational evidence suggests that the posteromedial sector of the human parietal cortex (area hV6A) is involved in reaching corrections. We interfered with hV6A functions using repetitive transcranial magnetic stimulation (rTMS) while healthy participants performed reaching movements and in-flight adjustments of the hand trajectory in presence of unexpected target shifts. rTMS over hV6A specifically altered action reprogramming, causing deviations of the shifted trajectories, particularly along the vertical dimension (i.e., distance). This study provides evidence of the functional relevance of hV6A in action reprogramming while a sudden event requires a change in performance and shows that hV6A also plays a role in state estimation during reaching. These findings are in line with neurological data showing impairments in actions performed along the distance dimension when lesions occur in the dorsal posterior parietal cortex.

Task-related modulation of motor response to emotional bodies: A TMS motor-evoked potential study.

Exposure to emotional body postures during perceptual decision-making tasks has been linked to transient suppression of motor reactivity, supporting the monitoring of emotionally relevant information. However, it remains unclear whether this effect occurs implicitly, i.e., when emotional information is irrelevant to the task. To investigate this issue, we used single-pulse transcranial magnetic stimulation (TMS) to assess motor excitability while healthy participants were asked to categorize pictures of body expressions as emotional or neutral (emotion recognition task) or as belonging to a male or a female actor (gender recognition task) while receiving TMS over the motor cortex at 100 and 125 ms after picture onset. Results demonstrated that motor-evoked potentials (MEPs) were reduced for emotional body postures relative to neutral postures during the emotion recognition task. Conversely, MEPs increased for emotional body postures relative to neutral postures during the gender recognition task. These findings indicate that motor inhibition, contingent upon observing emotional body postures, is selectively associated with actively monitoring emotional features. In contrast, observing emotional body postures prompts motor facilitation when task-relevant features are non-emotional. These findings contribute to embodied cognition models that link emotion perception and action tendencies.

Increasing associative plasticity in temporo-occipital back-projections improves visual perception of emotions.

The posterior superior temporal sulcus (pSTS) is a critical node in a network specialized for perceiving emotional facial expressions that is reciprocally connected with early visual cortices (V1/V2). Current models of perceptual decision-making increasingly assign relevance to recursive processing for visual recognition. However, it is unknown whether inducing plasticity into reentrant connections from pSTS to V1/V2 impacts emotion perception. Using a combination of electrophysiological and neurostimulation methods, we demonstrate that strengthening the connectivity from pSTS to V1/V2 selectively increases the ability to perceive facial expressions associated with emotions. This behavior is associated with increased electrophysiological activity in both these brain regions, particularly in V1/V2, and depends on specific temporal parameters of stimulation that follow Hebbian principles. Therefore, we provide evidence that pSTS-to-V1/V2 back-projections are instrumental to perception of emotion from facial stimuli and functionally malleable via manipulation of associative plasticity.

Antivax attitude in the general population along the autism-schizophrenia continuum and the impact of socio-demographic factors.

Introduction: One of the most important inventions in human history is vaccines. However, to date a consistent amount of people exhibit a hesitant approach toward them and mixed results have emerged in the attempt to characterize which factors may play a role in predicting such negative attitude. Here, we aimed at investigating how the individual scoring along the autism-schizophrenic continuum component and socio-cultural factors contribute toward vaccination attitudes in the general population. Methods: To test whether individual position along the autism-schizophrenic continuum could predict vaccine attitude, we used principal component analysis (PCA) to extract the component showing diametric loading between the Schizotypal Personality Questionnaire (SPQ) and Autistic Quotient (AQ) subscales. Then, we performed a series of multiple linear regression analyses to understand the relation between the ASD-SSD continuum component and Vax scores. We also included socio-demographic factors (i.e., gender, education level, and age) as predictors. Results: Multiple regression analysis revealed that the closer the individual lied on the positive schizotypal pole, the higher was their negative attitude toward vaccines. A diametric, more favorable disposition was found for individuals closer to the autistic end of the continuum. Furthermore, we reported that among the socio-cultural factors, only age can be considered a significant predictor of vaccination attitudes, with younger participants showing a more positive attitudes toward vaccination, while the level of education is an important protective factor in mitigating the negative impact that the proximity to the SSD pole and age play against vaccination disposition. Discussion: These findings are relevant to improve targeted public health interventions, highlighting the crucial role of demographic, psychological, and social correlates in predicting anti-vax beliefs, which have the devasting potential to increase the spread of infectious disease.

A Short Route for Reach Planning between Human V6A and the Motor Cortex.

In the macaque monkey, area V6A, located in the medial posterior parietal cortex, contains cells that encode the spatial position of a reaching target. It has been suggested that during reach planning this information is sent to the frontal cortex along a parieto-frontal pathway that connects V6A-premotor cortex-M1. A similar parieto-frontal network may also exist in the human brain, and we aimed here to study the timing of this functional connection during planning of a reaching movement toward different spatial positions. We probed the functional connectivity between human area V6A (hV6A) and the primary motor cortex (M1) using dual-site, paired-pulse transcranial magnetic stimulation with a short (4 ms) and a longer (10 ms) interstimulus interval while healthy participants (18 men and 18 women) planned a visually-guided or a memory-guided reaching movement toward positions located at different depths and directions. We found that, when the stimulation over hV6A is sent 4 ms before the stimulation over M1, hV6A inhibits motor-evoked potentials during planning of either rightward or leftward reaching movements. No modulations were found when the stimulation over hV6A was sent 10 ms before the stimulation over M1, suggesting that only short medial parieto-frontal routes are active during reach planning. Moreover, the short route of hV6A-premotor cortex-M1 is active during reach planning irrespectively of the nature (visual or memory) of the reaching target. These results agree with previous neuroimaging studies and provide the first demonstration of the flow of inhibitory signals between hV6A and M1.SIGNIFICANCE STATEMENT All our dexterous movements depend on the correct functioning of the network of brain areas. Knowing the functional timing of these networks is useful to gain a deeper understanding of how the brain works to enable accurate arm movements. In this article, we probed the parieto-frontal network and demonstrated that it takes 4 ms for the medial posterior parietal cortex to send inhibitory signals to the frontal cortex during reach planning. This fast flow of information seems not to be dependent on the availability of visual information regarding the reaching target. This study opens the way for future studies to test how this timing could be impaired in different neurological disorders.

Complementary contribution of the medial and lateral human parietal cortex to grasping: a repetitive TMS study.

The dexterous control of our grasping actions relies on the cooperative activation of many brain areas. In the parietal lobe, 2 grasp-related areas collaborate to orchestrate an accurate grasping action: dorsolateral area AIP and dorsomedial area V6A. Single-cell recordings in monkeys and fMRI studies in humans have suggested that both these areas specify grip aperture and wrist orientation, but encode these grasping parameters differently, depending on the context. To elucidate the causal role of phAIP and hV6A, we stimulated these areas, while participants were performing grasping actions (unperturbed grasping). rTMS over phAIP impaired the wrist orientation process, whereas stimulation over hV6A impaired grip aperture encoding. In a small percentage of trials, an unexpected reprogramming of grip aperture or wrist orientation was required (perturbed grasping). In these cases, rTMS over hV6A or over phAIP impaired reprogramming of both grip aperture and wrist orientation. These results represent the first direct demonstration of a different encoding of grasping parameters by 2 grasp-related parietal areas.

Stopping in (e)motion: Reactive action inhibition when facing valence-independent emotional stimuli.

Emotions are able to impact our ability to control our behaviors. However, it is not clear whether emotions play a detrimental or an advantageous effect on action control and whether the valence of the emotional stimuli differently affects such motor abilities. One way to measure reactive inhibitory control is the stop-signal task (SST), which estimates the ability to cancel outright a response to the presentation of a stop signal by means of the stop signal reaction times (SSRT). Impaired as well as facilitated action control has been found when faced with emotional stimuli such as stop signals in SSTs and mixed results were observed for positive versus negative stimuli. Here, we aimed to investigate these unresolved issues more deeply. Action control capabilities were tested in 60 participants by means of a SST, in which the stop signals were represented by a fearful and a happy body posture together with their neutral counterpart. Results showed that both positive and negative body postures enhanced the ability to suppress an ongoing action compared to neutral body postures. These results demonstrate that emotional valence-independent emotional stimuli facilitate action control and suggest that emotional stimuli may trigger increased sensory representation and/or attentional processing that may have promote stop-signal processing and hence improved inhibitory performance.

The Influence of Vicarious Fear-Learning in "Infecting" Reactive Action Inhibition.

Since the dawn of cognitive neuroscience, emotions have been recognized to impact on several executive processes, such as action inhibition. However, the complex interplay between emotional stimuli and action control is not yet fully understood. One way to measure inhibitory control is the stop-signal task (SST), which estimates the ability to cancel outright an action to the presentation of a stop signal by means of the stop-signal reaction times (SSRTs). Impaired as well as facilitated action control has been found when faced with intrinsic emotional stimuli as stop signals in SSTs. Here, we aimed at investigating more deeply the power of negative stimuli to influence our action control, testing the hypothesis that a previously neutral stimulus [i.e., the image of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)], which has been conditioned through vicarious fear learning, has the same impact on reactive action inhibition performance as an intrinsically negative stimulus (i.e., a fearful face or body). Action control capabilities were tested in 90 participants by means of a SST, in which the stop signals were represented by different negative stimuli. Results showed that the SARS-CoV-2 image enhanced the ability to suppress an ongoing action similarly to observing fearful facial expressions or fearful body postures. Interestingly, we found that this effect was predicted by impulsivity traits: for example, the less self-control the participants had, the less they showed emotional facilitation for inhibitory performance. These results demonstrated that vicarious fear learning has a critical impact on cognitive abilities, making a neutral image as threatening as phylogenetically innate negative stimuli and able to impact on our behavioral control.

Mu rhythm and corticospinal excitability capture two different frames of motor resonance: A TMS-EEG co-registration study.

Humans are equipped with an extraordinary ability to understand and imitate actions by mapping the observed movement onto their own cortical motor system. Long-established lines of research have identified two correlates of this motor resonance following action observation: the mu rhythm event-related desynchronization (mu-ERD) recorded through electroencephalography (EEG) and the facilitation of motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) of the primary motor cortex (M1). Yet, whether mu-ERD and MEP facilitation reflect unique or distinct mechanisms is not conclusive, as prior work did not combine simultaneous TMS-EEG recording with a trial-by-trial analysis of the two markers. To address this issue, here, we used TMS-EEG co-registration while participants observed and executed finger movements. EEG was continuously recorded while single-pulse TMS was administered over the left M1 and MEPs were recorded from the right hand. We found stronger motor cortex recruitment during action execution and observation as shown by mu-ERD. MEPs instead were larger overall during action execution and showed a facilitation specific to the muscles involved in the observed movements. Interestingly, when analyzing these two parameters using a trial-by-trial statistical approach, we did not find any relationship between mu-ERD and MEPs within the action observation condition. Our findings support the notion that EEG and TMS indices of motor resonance reflect distinct neural mechanisms.

Characterizing cardiac autonomic dynamics of fear learning in humans.

Understanding transient dynamics of the autonomic nervous system during fear learning remains a critical step to translate basic research into treatment of fear-related disorders. In humans, it has been demonstrated that fear learning typically elicits transient heart rate deceleration. However, classical analyses of heart rate variability (HRV) fail to disentangle the contribution of parasympathetic and sympathetic systems, and crucially, they are not able to capture phasic changes during fear learning. Here, to gain deeper insight into the physiological underpinnings of fear learning, a novel frequency-domain analysis of heart rate was performed using a short-time Fourier transform, and instantaneous spectral estimates extracted from a point-process modeling algorithm. We tested whether spectral transient components of HRV, used as a noninvasive probe of sympathetic and parasympathetic mechanisms, can dissociate between fear conditioned and neutral stimuli. We found that learned fear elicited a transient heart rate deceleration in anticipation of noxious stimuli. Crucially, results revealed a significant increase in spectral power in the high frequency band when facing the conditioned stimulus, indicating increased parasympathetic (vagal) activity, which distinguished conditioned and neutral stimuli during fear learning. Our findings provide a proximal measure of the involvement of cardiac vagal dynamics into the psychophysiology of fear learning and extinction, thus offering new insights for the characterization of fear in mental health and illness.

The Neurobiological Correlates of Gaze Perception in Healthy Individuals and Neurologic Patients.

The ability to adaptively follow conspecific eye movements is crucial for establishing shared attention and survival. Indeed, in humans, interacting with the gaze direction of others causes the reflexive orienting of attention and the faster object detection of the signaled spatial location. The behavioral evidence of this phenomenon is called gaze-cueing. Although this effect can be conceived as automatic and reflexive, gaze-cueing is often susceptible to context. In fact, gaze-cueing was shown to interact with other factors that characterize facial stimulus, such as the kind of cue that induces attention orienting (i.e., gaze or non-symbolic cues) or the emotional expression conveyed by the gaze cues. Here, we address neuroimaging evidence, investigating the neural bases of gaze-cueing and the perception of gaze direction and how contextual factors interact with the gaze shift of attention. Evidence from neuroimaging, as well as the fields of non-invasive brain stimulation and neurologic patients, highlights the involvement of the amygdala and the superior temporal lobe (especially the superior temporal sulcus (STS)) in gaze perception. However, in this review, we also emphasized the discrepancies of the attempts to characterize the distinct functional roles of the regions in the processing of gaze. Finally, we conclude by presenting the notion of invariant representation and underline its value as a conceptual framework for the future characterization of the perceptual processing of gaze within the STS.

Editorial: "Neuromodulation of Language, Cognition and Emotion".

Neuromodulation can be defined as the alteration of brain activity by delivering physical stimuli to a specific neural region [...].

Functional Connectivity at Rest between the Human Medial Posterior Parietal Cortex and the Primary Motor Cortex Detected by Paired-Pulse Transcranial Magnetic Stimulation.

The medial posterior parietal cortex (PPC) is involved in the complex processes of visuomotor integration. Its connections to the dorsal premotor cortex, which in turn is connected to the primary motor cortex (M1), complete the fronto-parietal network that supports important cognitive functions in the planning and execution of goal-oriented movements. In this study, we wanted to investigate the time-course of the functional connectivity at rest between the medial PPC and the M1 using dual-site transcranial magnetic stimulation in healthy humans. We stimulated the left M1 using a suprathreshold test stimulus to elicit motor-evoked potentials in the hand, and a subthreshold conditioning stimulus was applied over the left medial PPC at different inter-stimulus intervals (ISIs). The conditioning stimulus affected the M1 excitability depending on the ISI, with inhibition at longer ISIs (12 and 15 ms). We suggest that these modulations may reflect the activation of different parieto-frontal pathways, with long latency inhibitions likely recruiting polisynaptic pathways, presumably through anterolateral PPC.

Early Right Motor Cortex Response to Happy and Fearful Facial Expressions: A TMS Motor-Evoked Potential Study.

The ability to rapidly process others' emotional signals is crucial for adaptive social interactions. However, to date it is still unclear how observing emotional facial expressions affects the reactivity of the human motor cortex. To provide insights on this issue, we employed single-pulse transcranial magnetic stimulation (TMS) to investigate corticospinal motor excitability. Healthy participants observed happy, fearful and neutral pictures of facial expressions while receiving TMS over the left or right motor cortex at 150 and 300 ms after picture onset. In the early phase (150 ms), we observed an enhancement of corticospinal excitability for the observation of happy and fearful emotional faces compared to neutral expressions specifically in the right hemisphere. Interindividual differences in the disposition to experience aversive feelings (personal distress) in interpersonal emotional contexts predicted the early increase in corticospinal excitability for emotional faces. No differences in corticospinal excitability were observed at the later time (300 ms) or in the left M1. These findings support the notion that emotion perception primes the body for action and highlights the role of the right hemisphere in implementing a rapid and transient facilitatory response to emotional arousing stimuli, such as emotional facial expressions.

Frozen in (e)motion: How reactive motor inhibition is influenced by the emotional content of stimuli in healthy and psychiatric populations.

Efficient inhibitory control is vital. However, environmental cues can influence motor control especially in an emotional context. One common task to measure inhibitory control is the stop-signal task (SST), which asks participants to respond to go stimuli knowing that on some trials a stop signal will be presented, requiring them to inhibit their response. This paradigm estimates the ability to inhibit already-initiated responses by calculating participants' stop-signal reaction times (SSRT), an index of inhibitory control. Here, we aim to review the existing, often contradictory, evidence on the influence of emotional stimuli on the inhibitory process. We aim to discuss which factors may reveal an interference as well as an advantage of emotional stimuli on action inhibition performance. Finally, we review the existing evidence that has investigated the effect of such stimuli on action inhibition in the psychiatric population. Important factors are the relevance, the intensity and the valence of the emotional stimulus, as well as the affected component of the motor control. From all this evidence, it is clear that understand precisely how emotion is integrated into core executive functions, such as inhibitory control, is essential not only for cognitive neuroscience, but also for refining neurocognitive models of psychopathology.