Editorial: “Neuromodulation of Language, Cognition and Emotion”

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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 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

Long-latency modulation of motor cortex excitability by ipsilateral posterior inferior frontal gyrus and pre-supplementary motor area

The primary motor cortex (M1) is strongly influenced by several frontal regions. Dual-site transcranial magnetic stimulation (dsTMS) has highlighted the timing of early (<40 ms) prefrontal/premotor influences over M1. Here we used dsTMS to investigate, for the first time, longer-latency causal interactions of the posterior inferior frontal gyrus (pIFG) and pre-supplementary motor area (pre-SMA) with M1 at rest. A suprathreshold test stimulus (TS) was applied over M1 producing a motor-evoked potential (MEP) in the relaxed hand. Either a subthreshold or a suprathreshold conditioning stimulus (CS) was administered over ipsilateral pIFG/pre-SMA sites before the TS at different CS-TS inter-stimulus intervals (ISIs: 40-150 ms). Independently of intensity, CS over pIFG and pre-SMA (but not over a control site) inhibited MEPs at an ISI of 40 ms. The CS over pIFG produced a second peak of inhibition at an ISI of 150 ms. Additionally, facilitatory modulations were found at an ISI of 60 ms, with supra-but not subthreshold CS intensities. These findings suggest differential modulatory roles of pIFG and pre-SMA in M1 excitability. In particular, the pIFG-but not the pre-SMA-exerts intensity-dependent modulatory influences over M1 within the explored time window of 40-150 ms, evidencing fine-tuned control of M1 output

Your emotion moves into my motor system

In the present PhD thesis, using Transcranial Magnetic Stimulation, we tested the role of the motor system on visual recognition of emotional body expression. We tested both right and left primary motor cortices (M1) from 100 to 300 ms after stimulus onset. Our findings outline a 3-stage model of the motor system’s involvement in processing others’ emotions. In the first stage (100 ms), we find that, regardless of the stimulated hemisphere, the facilitatory intracortical connections are inhibited when subjects observe fearful stimuli, suggesting the existence of fast motor reactions that we interpret as suppression of motor readiness when seeing potentially harmful stimuli. At a second stage (150 ms), the right M1 shows an inhibitory modulation that is independent of the emotional meaning of the stimuli. We interpret this response, which is also paralleled by a general drop in categorization accuracy, as the sign of an orienting reaction toward emotionally relevant stimuli. In the meantime, left M1 shows a facilitatory response to negative stimuli to prepare a motor reaction of the dominant hand. In the last stage (300 ms), we bilaterally record sign of motor simulation of the implied motion of the stimuli. Our data demonstrate that, as proposed by evolutionary theorists, fast reactions towards threat-related stimuli are detectable in the motor system. On the other hand, as proposed by embodied simulation theorists, we found motor resonance processes observing dynamic stimuli. However, our data show that motor resonance processes are not necessary to extract the emotional meaning of such stimuli

Temporal dynamics of motor cortex excitability during perception of emotional IAPS stimuli

INTRODUCTION: Perceiving and immediately reacting to potential threats is critical for survival. However, previous TMS studies have failed to disclose a selective modulation of the dominant hand motor representation when seeing unpleasant stimuli (Hajcak et al., 2007; Borgomaneri et al., 2012), at least during resting conditions (see Van loon et al., 2010; Coombes et al., 2009 for investigation during action planning or execution). These studies have reported comparable motor facilitations for both emotionally positive and negative pictures in the observers\u2019 motor system. However, in all previous studies, motor excitability was tested in a relatively late time window, i.e. at >300ms after stimulus onset. Using single-pulse TMS we tested the hypothesis that motor reactions to unpleasant visual stimuli can be detected earlier than reactions to pleasant stimuli. METHODS: MEPs to single-pulse TMS of the left motor cortex were recorded from two right hand muscles (FDI, APB) during observation and active categorization of negative, positive, and emotionally neutral scenes from the International Affective Picture System (IAPS) database (Lang et al., 1999) (32 pictures for each condition). MEPs were recorded at 150 ms and 300 ms after stimulus onset. After TMS, subjects completed the Interpersonal Reactivity Index (IRI) (Davis, 1996). RESULTS: The Muscle x Time x Stimulus ANOVA revealed a Time x Stimulus interaction (p=0.02) but no triple interaction. At 150 ms from stimulus onset, MEP amplitudes were higher for negative relative to positive and neutral images (p<0.05) which in turn did not differ from one another. IRI\u2019s Personal Distress scores were significant predictors of this early selective motor facilitation for unpleasant stimuli (\u3b2=1.04, p<0.001). At 300 ms, MEP amplitudes were comparable for negative and positive images (p=0.15) and greater than for neutral images (p<0.05). CONCLUSIONS: Seeing unpleasant visual pictures increased motor excitability earlier than seeing pleasant pictures, supporting the view that potentially negative stimuli require processing and response resources to be more intensely and urgently mobilized to minimize negative consequences associated with the unpleasant cues (Ekman, 1992; Ohman et al., 1992). Notably, people with greater dispositional personal distress showed greater early motor facilitation when facing negative images, suggesting that interpersonal anxiety-related traits may promote valence specific fast motor reactivity. In keeping with previous research (Hajcak et al., 2007; Borgomaneri et al., 2012), at a later time (300 ms), both positive and negative stimuli elicited comparable motor facilitation relative to neutral pictures. These findings highlight the different time course of corticospinal reactivity when facing with positive and negative emotional visual stimuli

Causative connectivity of sensorimotor regions during embodied empathy for pain as revealed by perturb-and-measure TMS

INTRODUCTION: TMS studies indicate that watching painful stimuli shown on the body of a human model induces a decrease of corticospinal excitability in the onlooker\u2019s muscle correspondent to the one stimulated in the model (Avenanti et al., 2005). This muscle-specific, pain observation-related inhibition (PORI) is similar to that found during actual pain perception (Farina et al., 2003), suggesting that seeing pain in others triggers pain embodied resonance in the onlooker\u2019s corticospinal system. However, information on the relation between PORI and the activity of sensorimotor cortical regions recruited during pain perception is meagre. METHODS: In two experiments we used a perturb-and-measure TMS paradigm (Avenanti et al., 2007), combining repetitive TMS (15 min 1Hz-rTMS, to suppress neural activity in selected cortical regions) and single-pulse TMS (spTMS, to assess PORI by recording MEPs during pain observation). In both experiments MEPs were recorded in 3 spTMS sessions (1 baseline, and 2 post-rTMS sessions) during the observation of videos showing needles penetrating the FDI muscle of a human model (needle-in-FDI) and control videos (needles-in-foot, needle-in-tomato). MEPs were collected from the FDI (target) and the ADM (control) muscle. In exp1 (N=11), we applied image-guided rTMS over the hand representation in dorsal premotor (PMc) and primary motor cortex (M1). In exp2 (N=11), we applied rTMS over the hand representation in the somatosensory cortex (S1) and over the visual cortex (V1). After TMS, subjects judged the pain supposedly felt by the model and filled-out the Interpersonal Reactivity Index, assessing dispositional empathy. RESULTS: In the baseline sessions (no rTMS) of exp1-2, we found a typical PORI effect: watching needle-in-FDI stimuli brought about a reduction of MEPs recorded from the very same muscle in the observer (relative to visual controls), without modulating the ADM control muscle. The effect was stronger in the subjects who showed greater dispositional empathy and provided higher observed-pain scores. Exp1: After M1 suppression, the PORI effect was disrupted: MEPs were comparable in the three visual conditions. After PMc suppression, the PORI effect was reversed: MEPs from the FDI muscle were greater during \u201cneedle-in-FDI\u201d than during \u201cneedle-in-foot\u201d and \u201cneedle-in-tomato\u201d conditions. Exp2: After V1 suppression, the PORI was not different from the baseline session. After S1 suppression PORI was enhanced with greater inhibitory response for \u201cneedle-in the-hand\u201d stimuli relative to baseline. CONCLUSIONS: PORI was disrupted and enhanced by M1 and S1 suppression, respectively, and left unaffected by V1 suppression. Importantly, suppression of PMc changed the PORI into a muscle-specific facilitatory response. Thus, while S1 normal functioning seems to keep under control a potentially excessive embodiment of others\u2019 pain, normal functioning of PMc and M1 exert a same-direction, different-strength modulatory effect that allows an optimal tuning of resonant corticospinal mapping of observed pain. Our findings highlight the causal connectivity between PMc-M1-S1 regions and the corticospinal system during embodied empathy for pain and suggest that TMS can disclose specific inter-regional neural interactions during social perception. REFERENCES: Avenanti A et al. (2005) Nature Neuroscience 8:955-960. Avenanti A et al. (2007) Current Biology 17:2129-2135. Farina S et al. (2003) Neurological Research 25:130-142

Emotional bodies triggers fast motor reactions and motor resonance: single and paired-pulse TMS studies

Perceiving and reacting to the emotional body expressions of conspecifics is critical for effective social functioning. Imaging studies suggest that perceiving emotional bodies recruits action-related fronto-parietal regions. However, it is unclear whether motor system involvement reflects “resonance” with the observed body movement or reaction (e.g. fight/flight) to emotional signs. To address this issue we used Transcranial Magnetic Stimulation (TMS) to explore changes in corticospinal (exp1) and cortical (exp2) motor excitability during observation of emotional body expressions. MEPs were recorded from the FDI muscle during active categorization of pictures of joyful and fearful expressions, neutral gestures (i.e. body configurations with implied motion similar to the emotional expressions but no emotional meaning) and static neutral postures. In experiment 1, corticospinal excitability was assessed in both hemispheres at 150 and 300 ms after picture presentation. In the earlier time window, MEPs to TMS of the right motor cortex were reduced for emotional relative to neutral gestures. Conversely, at 300 ms, greater excitability for dynamic emotional and non-emotional relative to static bodies was found in both hemispheres. The magnitude of the early (150 ms) and late (300 ms) motor modulations correlated with distinct personality dispositions, namely the tendency to feel personal-distress and to take the perspective of others, respectively. In experiment 2, using paired-pulse TMS, we further explored early changes in the excitability of the right motor cortex by assessing short intracortical inhibition (SICI) and facilitation (ICF) at 100-125 ms after picture onset. We found that emotional expressions reduced ICF relative to neutral bodies, and fearful reduced ICF more than joyful expressions. No modulation was seen for SICI or corticospinal excitability. Our findings highlight the temporal dynamics of the motor system during perception of emotional expressions. Seeing emotional - in particular fearful – bodies induced an early reduction in intracortical facilitation (100-125 ms) of the right motor cortex. Then, a reduction of corticospinal excitability for emotion bodies emerged at 150 ms in the right but not left motor cortex. These modulations were independent from “motion” features of the expressions, were greater in participants with higher interpersonal anxiety-related personality traits and likely reflected a freezing-like orienting response toward emotional body cues. An increase in corticospinal excitability occurred at 300 ms in both hemispheres independently from the emotional meaning of the gestures and was greater in participants with higher cognitive empathy. This later response likely reflected the simulation of the body movement implied in the observed gestures. These findings suggest that fast reactions to emotional cues occur well before motor features of the observed emotional gesture are simulated in the motor system