RESUMEN
Spontaneous and conversational laughter are important socio-emotional communicative signals. Neuroimaging findings suggest that non-autistic people engage in mentalizing to understand the meaning behind conversational laughter. Autistic people may thus face specific challenges in processing conversational laughter, due to their mentalizing difficulties. Using fMRI, we explored neural differences during implicit processing of these two types of laughter. Autistic and non-autistic adults passively listened to funny words, followed by spontaneous laughter, conversational laughter, or noise-vocoded vocalizations. Behaviourally, words plus spontaneous laughter were rated as funnier than words plus conversational laughter, and the groups did not differ. However, neuroimaging results showed that non-autistic adults exhibited greater medial prefrontal cortex activation while listening to words plus conversational laughter, than words plus genuine laughter, while autistic adults showed no difference in medial prefrontal cortex activity between these two laughter types. Our findings suggest a crucial role for the medial prefrontal cortex in understanding socio-emotionally ambiguous laughter via mentalizing. Our study also highlights the possibility that autistic people may face challenges in understanding the essence of the laughter we frequently encounter in everyday life, especially in processing conversational laughter that carries complex meaning and social ambiguity, potentially leading to social vulnerability. Therefore, we advocate for clearer communication with autistic people.
Asunto(s)
Trastorno Autístico , Mapeo Encefálico , Encéfalo , Risa , Imagen por Resonancia Magnética , Humanos , Risa/fisiología , Risa/psicología , Masculino , Femenino , Adulto , Trastorno Autístico/fisiopatología , Trastorno Autístico/diagnóstico por imagen , Trastorno Autístico/psicología , Adulto Joven , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Encéfalo/fisiología , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiopatología , Corteza Prefrontal/fisiología , Estimulación AcústicaRESUMEN
Although emotional mimicry is ubiquitous in social interactions, its mechanisms and roles remain disputed. A prevalent view is that imitating others' expressions facilitates emotional understanding, but the evidence is mixed and almost entirely based on facial emotions. In a preregistered study, we asked whether inhibiting orofacial mimicry affects authenticity perception in vocal emotions. Participants listened to authentic and posed laughs and cries, while holding a pen between the teeth and lips to inhibit orofacial responses (n = 75), or while responding freely without a pen (n = 75). They made authenticity judgments and rated how much they felt the conveyed emotions (emotional contagion). Mimicry inhibition decreased the accuracy of authenticity perception in laughter and crying, and in posed and authentic vocalizations. It did not affect contagion ratings, however, nor performance in a cognitive control task, ruling out the effort of holding the pen as an explanation for the decrements in authenticity perception. Laughter was more contagious than crying, and authentic vocalizations were more contagious than posed ones, regardless of whether mimicry was inhibited or not. These findings confirm the role of mimicry in emotional understanding and extend it to auditory emotions. They also imply that perceived emotional contagion can be unrelated to mimicry. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Asunto(s)
Llanto , Emociones , Expresión Facial , Risa , Percepción Social , Humanos , Femenino , Masculino , Adulto , Adulto Joven , Risa/fisiología , Llanto/fisiología , Emociones/fisiología , Conducta Imitativa/fisiología , Percepción Auditiva/fisiologíaRESUMEN
This mini-review discusses the existing evidence on various forms of humour and humour-like behaviour in non-human animals, combining ontogenetic and phylogenetic perspectives. The first section describes humour-like behaviours, from the simplest to the most complex form (from laughing, tickling, joking, and chasing to ToM humour). In the second section, we propose the SPeCies (Social, Physiological, and Cognitive) Perspective, which frames the various types of humour based on Social motivation, Physiological state, and Cognitive skills. Finally, in the third section, we discuss future directions for further development.
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Risa , Filogenia , Risa/fisiología , Risa/psicologíaRESUMEN
Laughter is one of the most common non-verbal features; however, contrary to the previous assumptions, it may also act as signals of bonding, affection, emotional regulation agreement or empathy (Scott et al. Trends Cogn Sci 18:618-620, 2014). Although previous research agrees that laughter does not form a uniform group in many respects, different types of laughter have been defined differently by individual research. Due to the various definitions of laughter, as well as their different methodologies, the results of the previous examinations were often contradictory. The analysed laughs were often recorded in controlled, artificial situations; however, less is known about laughs from social conversations. Thus, the aim of the present study is to examine the acoustic realisation, as well as the automatic classification of laughter that appear in human interactions according to whether listeners consider them to be voluntary or involuntary. The study consists of three parts using a multi-method approach. Firstly, in the perception task, participants had to decide whether the given laughter seemed to be rather involuntary or voluntary. In the second part of the experiment, those sound samples of laughter were analysed that were considered to be voluntary or involuntary by at least 66.6% of listeners. In the third part, all the sound samples were grouped into the two categories by an automatic classifier. The results showed that listeners were able to distinguish laughter extracted from spontaneous conversation into two different types, as well as the distinction was possible on the basis of the automatic classification. In addition, there were significant differences in acoustic parameters between the two groups of laughter. The results of the research showed that, although the distinction between voluntary and involuntary laughter categories appears based on the analysis of everyday, spontaneous conversations in terms of the perception and acoustic features, there is often an overlap in the acoustic features of voluntary and involuntary laughter. The results will enrich our previous knowledge of laughter and help to describe and explore the diversity of non-verbal vocalisations.
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Risa , Humanos , Risa/fisiología , Risa/psicología , Comunicación , Empatía , Acústica , SonidoRESUMEN
The ability to distinguish spontaneous from volitional emotional expressions is an important social skill. How do blind individuals perceive emotional authenticity? Unlike sighted individuals, they cannot rely on facial and body language cues, relying instead on vocal cues alone. Here, we combined behavioral and ERP measures to investigate authenticity perception in laughter and crying in individuals with early- or late-blindness onset. Early-blind, late-blind, and sighted control participants (n = 17 per group, N = 51) completed authenticity and emotion discrimination tasks while EEG data were recorded. The stimuli consisted of laughs and cries that were either spontaneous or volitional. The ERP analysis focused on the N1, P2, and late positive potential (LPP). Behaviorally, early-blind participants showed intact authenticity perception, but late-blind participants performed worse than controls. There were no group differences in the emotion discrimination task. In brain responses, all groups were sensitive to laughter authenticity at the P2 stage, and to crying authenticity at the early LPP stage. Nevertheless, only early-blind participants were sensitive to crying authenticity at the N1 and middle LPP stages, and to laughter authenticity at the early LPP stage. Furthermore, early-blind and sighted participants were more sensitive than late-blind ones to crying authenticity at the P2 and late LPP stages. Altogether, these findings suggest that early blindness relates to facilitated brain processing of authenticity in voices, both at early sensory and late cognitive-evaluative stages. Late-onset blindness, in contrast, relates to decreased sensitivity to authenticity at behavioral and brain levels.
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Risa , Voz , Humanos , Emociones/fisiología , Ceguera , Risa/fisiología , Percepción Social , Electroencefalografía , Potenciales Evocados/fisiologíaRESUMEN
Deception and humor are ubiquitous in interpersonal interactions and intricately interrelated. In this article, we review and integrate prior research on humor and deception and propose a theoretical model - the Interpersonal Humor Deception Model (IHDM) - to understand the interpersonal effects of humor on deception. We argue that humor can both promote and curtail the use of deception, as well as influence the detection of deception and responses to detected deception (retraction, retaliation, and the restoration of trust). The specific effects of humor depend on whether it is successful or unsuccessful. In all, our article provides a theoretical framework to guide research on humor and deception and offers important insights into the costs and benefits of humor in negotiations, organizations, and everyday life.
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Risa , Humanos , Risa/fisiología , Relaciones Interpersonales , Confianza , Modelos Teóricos , DecepciónRESUMEN
Depressive symptoms are common in the postpartum period and can affect mother-infant interaction. To better understand the role of depressive symptoms in the mother-infant interchange, this study examined whether maternal depressive symptoms are associated with self-reported, physiological, and facial expressive responses to infant crying and laughing sounds. A nonclinical sample was used, consisting of 101 mothers (Age M = 30.88 years, 33% scored 7 or higher on the Edinburgh Postnatal Depression Scale) with a young child. Mothers were exposed to standard infant crying and laughing sounds. Affect, perception of crying and laughing, intended caregiving responses, skin conductance level reactivity, and facial expressive responses to infant crying and laughing were measured. Higher levels of depressive symptoms were associated with more self-reported negative affect in general and a more negative perception of infant crying. Depressive symptoms were not associated with intended caregiving responses and physiological responses to infant crying. Infant laughing increased self-reported positive affect and happy facial expressions in mothers with all levels of depressive symptoms. Higher levels of depressive symptoms were associated with higher sad facial expressivity in general. Depressive symptoms were not related to positive perception of infant laughing, intended caregiving responses, and physiological responses to infant laughing. The findings suggest that mothers who score high on depressive symptoms send subtle facial cues showing sadness, which may overshadow happy facial expressions during infant laughing and may affect mother-infant interaction. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Llanto , Risa , Femenino , Niño , Lactante , Humanos , Adulto , Llanto/fisiología , Llanto/psicología , Depresión , Madres/psicología , Risa/fisiología , Relaciones Madre-Hijo/psicologíaRESUMEN
As cold actions (i.e. actions devoid of an emotional content), also emotions are expressed with different vitality forms. For example, when an individual experiences a positive emotion, such as laughing as expression of happiness, this emotion can be conveyed to others by different intensities of face expressions and body postures. In the present study, we investigated whether the observation of emotions, expressed with different vitality forms, activates the same neural structures as those involved in cold action vitality forms processing. To this purpose, we carried out a functional magnetic resonance imaging study in which participants were tested in 2 conditions: emotional and non-emotional laughing both conveying different vitality forms. There are 3 main results. First, the observation of emotional and non-emotional laughing conveying different vitality forms activates the insula. Second, the observation of emotional laughing activates a series of subcortical structures known to be related to emotions. Furthermore, a region of interest analysis carried out in these structures reveals a significant modulation of the blood-oxygen-leveldependent (BOLD) signal during the processing of different vitality forms exclusively in the right amygdala, right anterior thalamus/hypothalamus, and periaqueductal gray. Third, in a subsequent electromyography study, we found a correlation between the zygomatic muscles activity and BOLD signal in the right amygdala only.
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Emociones , Risa , Humanos , Emociones/fisiología , Risa/fisiología , Amígdala del Cerebelo/fisiología , Imagen por Resonancia Magnética/métodos , Mapeo Encefálico/métodosRESUMEN
A substantial body of acoustic and behavioural evidence points to the existence of two broad categories of laughter in humans: spontaneous laughter that is emotionally genuine and somewhat involuntary, and volitional laughter that is produced on demand. In this study, we tested the hypothesis that these are also physiologically distinct vocalizations, by measuring and comparing them using real-time magnetic resonance imaging (rtMRI) of the vocal tract. Following Ruch and Ekman (Ruch and Ekman 2001 In Emotions, qualia, and consciousness (ed. A Kaszniak), pp. 426-443), we further predicted that spontaneous laughter should be relatively less speech-like (i.e. less articulate) than volitional laughter. We collected rtMRI data from five adult human participants during spontaneous laughter, volitional laughter and spoken vowels. We report distinguishable vocal tract shapes during the vocalic portions of these three vocalization types, where volitional laughs were intermediate between spontaneous laughs and vowels. Inspection of local features within the vocal tract across the different vocalization types offers some additional support for Ruch and Ekman's predictions. We discuss our findings in light of a dual pathway hypothesis for the neural control of human volitional and spontaneous vocal behaviours, identifying tongue shape and velum lowering as potential biomarkers of spontaneous laughter to be investigated in future research. This article is part of the theme issue 'Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience'.
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Risa , Voz , Adulto , Emociones , Humanos , Risa/fisiología , Risa/psicología , Imagen por Resonancia Magnética , VoliciónRESUMEN
Laughter is an ambiguous phenomenon in response to both positive and negative events and a social signal that coordinates social interactions. We assessed (i) who laughs and why, and (ii) if the type of laughter and whether the observer approves of it impact on facial mimicry as a proxy for shared laughter. For this, 329 participants watched funny, schadenfreude and disgusting scenes and then saw individuals who purportedly reacted to each scene while participants' facial expressions were recorded and analysed. Participants laughed more in response to funny than in response to schadenfreude scenes and least in response to disgust scenes, and laughter within each scene could be explained both by situational perceptions of the scenes as well as by individual differences. Furthermore, others' laughter in response to funny scenes was perceived as more appropriate, elicited more closeness and more laughter mimicry than others' laughter in response to schadenfreude and especially in response to disgust scenes. Appropriateness and closeness as well as individual differences could explain laughter mimicry within each scene. This is in line with the notion that laughter is not per se an affiliative signal and that different types of laughter have distinct social implications. This article is part of the theme issue 'Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience'.
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Asco , Risa , Expresión Facial , Humanos , Risa/fisiología , Risa/psicología , Interacción SocialRESUMEN
In anthropoid primates, social grooming is the principal mechanism (mediated by the central nervous system endorphin system) that underpins social bonding. However, the time available for social grooming is limited, and this imposes an upper limit on the size of group that can be bonded in this way. I suggest that, when hominins needed to increase the size of their groups beyond the limit that could be bonded by grooming, they co-opted laughter (a modified version of the play vocalization found widely among the catarrhine primates) as a form of chorusing to fill the gap. I show, first, that human laughter both upregulates the brain's endorphin system and increases the sense of bonding between those who laugh together. I then use a reverse engineering approach to model group sizes and grooming time requirements for fossil hominin species to search for pinch points where a phase shift in bonding mechanisms might have occurred. The results suggest that the most likely time for the origin of human-like laughter is the appearance of the genus Homo ca 2.5 Ma. This article is part of the theme issue 'Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience'.
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Endorfinas , Hominidae , Risa , Animales , Aseo Animal/fisiología , Humanos , Risa/fisiología , PrimatesRESUMEN
This opinion piece aims to tackle the biological, psychological, neural and cultural underpinnings of laughter from a naturalistic and evolutionary perspective. A naturalistic account of laughter requires the revaluation of two dogmas of a longstanding philosophical tradition, that is, the quintessential link between laughter and humour, and the uniquely human nature of this behaviour. In the spirit of Provine's and Panksepp's seminal studies, who firstly argued against the anti-naturalistic dogmas, here we review compelling evidence that (i) laughter is first and foremost a social behaviour aimed at regulating social relationships, easing social tensions and establishing social bonds, and that (ii) homologue and homoplasic behaviours of laughter exist in primates and rodents, who also share with humans the same underpinning neural circuitry. We make a case for the hypothesis that the contagiousness of laughter and its pervasive social infectiousness in everyday social interactions is mediated by a specific mirror mechanism. Finally, we argue that a naturalistic account of laughter should not be intended as an outright rejection of classic theories; rather, in the last part of the piece we argue that our perspective is potentially able to integrate previous viewpoints-including classic philosophical theories-ultimately providing a unified evolutionary explanation of laughter. This article is part of the theme issue 'Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience'.
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Risa , Neurociencias , Animales , Evolución Biológica , Humanos , Relaciones Interpersonales , Risa/fisiología , Risa/psicología , Conducta SocialRESUMEN
According to an evolutionist approach, laughter is a multifaceted behaviour affecting social, emotional, motor and speech functions. Albeit previous studies have suggested that high-frequency electrical stimulation (HF-ES) of the pregenual anterior cingulate cortex (pACC) may induce bursts of laughter-suggesting a crucial contribution of this region to the cortical control of this behaviour-the complex nature of laughter implies that outward connections from the pACC may reach and affect a complex network of frontal and limbic regions. Here, we studied the effective connectivity of the pACC by analysing the cortico-cortical evoked potentials elicited by single-pulse electrical stimulation of pACC sites whose HF-ES elicited laughter in 12 patients. Once these regions were identified, we studied their clinical response to HF-ES, to reveal the specific functional target of pACC representation of laughter. Results reveal that the neural representation of laughter in the pACC interacts with several frontal and limbic regions, including cingulate, orbitofrontal, medial prefrontal and anterior insular regions-involved in interoception, emotion, social reward and motor behaviour. These results offer neuroscientific support to the evolutionist approach to laughter, providing a possible mechanistic explanation of the interplay between this behaviour and emotion regulation, speech production and social interactions. This article is part of the theme issue 'Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience'.
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Giro del Cíngulo , Risa , Estimulación Eléctrica/métodos , Emociones/fisiología , Potenciales Evocados , Giro del Cíngulo/fisiología , Humanos , Risa/fisiología , Risa/psicologíaRESUMEN
Who has not experienced that sensation of losing the power of speech owing to an involuntary bout of laughter? An investigation of this phenomenon affords an insight into the neuronal processes that underlie laughter. In our functional magnetic resonance imaging study, participants were made to laugh by tickling in a first condition; in a second one they were requested to produce vocal utterances under the provocation of laughter by tickling. This investigation reveals increased neuronal activity in the sensorimotor cortex, the anterior cingulate gyrus, the insula, the nucleus accumbens, the hypothalamus and the periaqueductal grey for both conditions, thereby replicating the results of previous studies on ticklish laughter. However, further analysis indicates the activity in the emotion-associated regions to be lower when tickling is accompanied by voluntary vocalization. Here, a typical pattern of activation is identified, including the primary sensory cortex, a ventral area of the anterior insula and the ventral tegmental field, to which belongs to the nucleus ambiguus, namely, the common effector organ for voluntary and involuntary vocalizations. During the conflictual voluntary-vocalization versus laughter experience, the laughter-triggering network appears to rely heavily on a sensory and a deep interoceptive analysis, as well as on motor effectors in the brainstem. This article is part of the theme issue 'Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience'.
Asunto(s)
Risa , Emociones/fisiología , Giro del Cíngulo/fisiología , Humanos , Risa/fisiología , Imagen por Resonancia Magnética , HablaRESUMEN
Laughter is a contagious prosocial signal that conveys bonding motivation; adult crying conversely communicates desire for social proximity by signalling distress. Endogenous mu-opioid receptors (MORs) modulate sociability in humans and non-human primates. In this combined PET-fMRI study (n = 17), we tested whether central MOR tone is associated with regional brain responses to social signals of laughter and crying. MOR availability was measured with positron emission tomography (PET) using the high-affinity agonist radioligand [11C]carfentanil. Haemodynamic responses to social laughter and crying vocalizations were measured using functional magnetic resonance imaging (fMRI). Social laughter evoked activation in the auditory cortex, insula, cingulate cortex, amygdala, primary and secondary somatosensory cortex, and primary and secondary motor cortex; crying sounds led to more restricted activation in the auditory cortex and nearby areas. MOR availability was negatively correlated with the haemodynamic responses to social laughter in the primary and secondary somatosensory cortex, primary and secondary motor cortex, posterior insula, posterior cingulate cortex, precuneus, cuneus, temporal gyri and lingual gyrus. For crying-evoked activations, MOR availability was negatively correlated with medial and lateral prefrontal haemodynamic responses. Altogether our findings highlight the role of the MOR system in modulating acute brain responses to both positive and negative social signals. This article is part of the theme issue 'Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience'.
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Mapeo Encefálico , Risa , Adulto , Encéfalo/fisiología , Humanos , Risa/fisiología , Imagen por Resonancia Magnética/métodos , Tomografía de Emisión de PositronesRESUMEN
BACKGROUND: Whereas previous studies revealed positive effects of emotional expressions such as swearing and laughing on acute pain, systematic research on the effects of crying on pain is missing. The rationale for the current study is that either a mere emotional distraction or changes in oxytocin and opioid levels represent a mechanism through which crying modulates pain, with the timing of mood changes as crucial information for distinguishing between potential mechanisms. METHODS: In two studies, we exposed participants (Study 1: n = 57; Study 2: n = 70) to a sad movie and measured their mood, and exposed them to pain induction procedures (electric shock and cold-pressor test, respectively) before and after the film. Dependent variables were pain threshold, tolerance, and intensity. In addition to baseline and one immediate post-crying mood and pain response measurement in both studies, in Study 2, we repeated these procedures 20 and 50 min later to discern between the potential role of neurobiological substances and distraction. RESULTS: Crying was elicited in 28 participants in Study 1 (49.1%) and 49 (70%) in Study 2. We found no systematic differences in pain and mood changes between criers and non-criers and no systematic dose-response relationship between crying and pain responses and mood. The only significant effects ran contrary to our hypotheses, showing detrimental effects of the occurrence (Study 1) and frequency of crying (both studies) on pain threshold. CONCLUSIONS: Results do not support the idea that crying has pain-alleviating effects, either via distraction or direct biological mechanisms. SIGNIFICANCE: Despite previous findings on pain alleviating effects of emotional expression and the widespread idea about the generally beneficial consequences of emotional crying, research on the possible pain alleviating effects of crying is largely missing. Two quasi-experimental studies demonstrated that crying induced in laboratory conditions does not alleviate acute pain responses, suggesting that role of crying in pain interventions is doubtful. Less directly, results cast light on the role of emotional distraction from acute pain and possible crying-related neurochemical changes.
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Dolor Agudo , Risa , Llanto/fisiología , Emociones/fisiología , Humanos , Risa/fisiología , Percepción del DolorRESUMEN
It has been shown that the acoustical signal of posed laughter can convey affective information to the listener. However, because posed and spontaneous laughter differ in a number of significant aspects, it is unclear whether affective communication generalises to spontaneous laughter. To answer this question, we created a stimulus set of 381 spontaneous laughter audio recordings, produced by 51 different speakers, resembling different types of laughter. In Experiment 1, 159 participants were presented with these audio recordings without any further information about the situational context of the speakers and asked to classify the laughter sounds. Results showed that joyful, tickling, and schadenfreude laughter could be classified significantly above chance level. In Experiment 2, 209 participants were presented with a subset of 121 laughter recordings correctly classified in Experiment 1 and asked to rate the laughter according to four emotional dimensions, i.e., arousal, dominance, sender's valence, and receiver-directed valence. Results showed that laughter types differed significantly in their ratings on all dimensions. Joyful laughter and tickling laughter both showed a positive sender's valence and receiver-directed valence, whereby tickling laughter had a particularly high arousal. Schadenfreude had a negative receiver-directed valence and a high dominance, thus providing empirical evidence for the existence of a dark side in spontaneous laughter. The present results suggest that with the evolution of human social communication laughter diversified from the former play signal of non-human primates to a much more fine-grained signal that can serve a multitude of social functions in order to regulate group structure and hierarchy.
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Risa , Voz , Animales , Nivel de Alerta , Emociones/fisiología , Humanos , Risa/fisiología , Risa/psicología , SensaciónRESUMEN
Previous research has documented perceptual and brain differences between spontaneous and volitional emotional vocalizations. However, the time course of emotional authenticity processing remains unclear. We used event-related potentials (ERPs) to address this question, and we focused on the processing of laughter and crying. We additionally tested whether the neural encoding of authenticity is influenced by attention, by manipulating task focus (authenticity versus emotional category) and visual condition (with versus without visual deprivation). ERPs were recorded from 43 participants while they listened to vocalizations and evaluated their authenticity (volitional versus spontaneous) or emotional meaning (sad versus amused). Twenty-two of the participants were blindfolded and tested in a dark room, and 21 were tested in standard visual conditions. As compared to volitional vocalizations, spontaneous ones were associated with reduced N1 amplitude in the case of laughter, and increased P2 in the case of crying. At later cognitive processing stages, more positive amplitudes were observed for spontaneous (versus volitional) laughs and cries (1000-1400 msec), with earlier effects for laughs (700-1000 msec). Visual condition affected brain responses to emotional authenticity at early (P2 range) and late processing stages (middle and late LPP ranges). Task focus did not influence neural responses to authenticity. Our findings suggest that authenticity information is encoded early and automatically during vocal emotional processing. They also point to a potentially faster encoding of authenticity in laughter compared to crying.
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Risa , Voz , Percepción Auditiva/fisiología , Emociones/fisiología , Potenciales Evocados , Humanos , Risa/fisiologíaRESUMEN
Angelman syndrome (AS) is a rare genetic neurodevelopmental disorder characterized by intellectual disabilities, motor and balance deficits, impaired communication, and a happy, excitable demeanor with frequent laughter. We sought to elucidate a preclinical outcome measure in male and female rats that addressed communication abnormalities of AS and other neurodevelopmental disorders in which communication is atypical and/or lack of speech is a core feature. We discovered, and herein report for the first time, excessive laughter-like 50 kHz ultrasonic emissions in the Ube3amat-/pat+ rat model of AS, which suggests an excitable, playful demeanor and elevated positive affect, similar to the demeanor of individuals with AS. Also in line with the AS phenotype, Ube3amat-/pat+ rats demonstrated aberrant social interactions with a novel partner, distinctive gait abnormalities, impaired cognition, an underlying LTP deficit, and profound reductions in brain volume. These unique, robust phenotypes provide advantages compared with currently available mouse models and will be highly valuable as outcome measures in the evaluation of therapies for AS.SIGNIFICANCE STATEMENT Angelman syndrome (AS) is a severe neurogenetic disorder for which there is no cure, despite decades of research using mouse models. This study used a recently developed rat model of AS to delineate disease-relevant outcome measures to facilitate therapeutic development. We found the rat to be a strong model of AS, offering several advantages over mouse models by exhibiting numerous AS-relevant phenotypes, including overabundant laughter-like vocalizations, reduced hippocampal LTP, and volumetric anomalies across the brain. These findings are unconfounded by detrimental motor abilities and background strain, issues plaguing mouse models. This rat model represents an important advancement in the field of AS, and the outcome metrics reported herein will be central to the therapeutic pipeline.
Asunto(s)
Síndrome de Angelman/genética , Modelos Animales de Enfermedad , Risa/fisiología , Microcefalia/genética , Ubiquitina-Proteína Ligasas/genética , Vocalización Animal/fisiología , Síndrome de Angelman/metabolismo , Síndrome de Angelman/psicología , Animales , Encéfalo/metabolismo , Femenino , Eliminación de Gen , Risa/psicología , Masculino , Microcefalia/metabolismo , Microcefalia/psicología , Técnicas de Cultivo de Órganos , Biosíntesis de Proteínas/fisiología , Ratas , Ratas Sprague-Dawley , Ratas Transgénicas , Reflejo de Sobresalto/fisiología , Conducta Social , Ubiquitina-Proteína Ligasas/deficienciaRESUMEN
The study of pathological laughter and crying (PLC) allows insights into the neural basis of laughter and crying, two hallmarks of human nature. PLC is defined by brief, intense and frequent episodes of uncontrollable laughter or crying provoked by trivial stimuli. It occurs secondary to CNS disorders such as stroke, tumours or neurodegenerative diseases. Based on case studies reporting various lesions locations, PLC has been conceptualized as dysfunction in a cortico-limbic-subcortico-thalamo-ponto-cerebellar network. To test whether the heterogeneous lesion locations are indeed linked in a common network, we applied 'lesion network-symptom-mapping' to 70 focal lesions identified in a systematic literature search for case reports of PLC. In lesion network-symptom-mapping normative connectome data (resting state functional MRI, n = 100) is used to identify the brain regions that are likely affected by diaschisis based on the lesion locations. With lesion network-symptom-mapping we were able to identify a common network specific for PLC when compared with a control cohort (n = 270). This bilateral network is characterized by positive connectivity to the cingulate and temporomesial cortices, striatum, hypothalamus, mesencephalon and pons, and negative connectivity to the primary motor and sensory cortices. In the most influential pathophysiological model of PLC, a centre for the control and coordination of facial expressions, respiration and vocalization in the periaqueductal grey is assumed, which is controlled via two pathways: an emotional system that exerts excitatory control of the periaqueductal grey descending from the temporal and frontal lobes, basal ganglia and hypothalamus; and a volitional system descending from the lateral premotor cortices that can suppress laughter or crying. To test whether the positive and negative PLC subnetworks identified in our analyses can indeed be related to an emotional system and a volitional system, we identified lesions causing emotional (n = 15) or volitional facial paresis (n = 46) in a second literature search. Patients with emotional facial paresis show preserved volitional movements but cannot trigger emotional movements in the affected hemiface, while the reverse is true for volitional facial paresis. Importantly, these lesions map differentially onto the PLC subnetworks: the 'positive PLC subnetwork' is part of the emotional system and the 'negative PLC subnetwork' overlaps with the volitional system for the control of facial movements. Based on this network analysis we propose a two-hit model of PLC: a combination of direct lesion and indirect diaschisis effects cause PLC through the loss of inhibitory cortical control of a dysfunctional emotional system.