RESUMEN
As classically captured in the notion of affordance, the natural environment presents animals with multiple opportunities for action and locomotion appears as the privileged form of action to cover distance in the extrapersonal space/environment. We have recently described a facilitation effect, known as "macro-affordance", for the execution of walking-related actions in response to distant vs. near objects/locations in the extrapersonal space. However, since the manipulation of distance was coextensive to landmark-objects contained in the environment and to the environmental layout per se, the relative contribution of these two factors remains undetermined. In addition, since the effect was originally described in the context of an incidental priming paradigm, it is still unknown whether it was specifically associated with an implicit coding of environmental distance. Here, across three experiments, we examined the degree to which the "macro-affordance" effect reflects (i) the encoding of environmental vs. landmark-objects' distance, (ii) the involvement of an implicit vs. controlled system, (iii) a foot-effector specificity. The results showed that the "macro-affordance" effect is more efficiently triggered by the framing distance of the environmental layout (far/wide/panoramic vs. near/close/restricted) rather than of isolated landmark-objects in the environment and that it only emerges when the distance dimension is implicitly processed within the incidental priming paradigm. The results additionally suggested a specificity of the effect for foot- vs. hand-related actions. The present findings suggest that macro-affordances reflect an implicit coding of spatial features of the environmental layout and viewer-environment relationships that preferentially guide a walking-related exploration of the spatial environment.
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Locomoción , Caminata , Animales , Humanos , Pie , Extremidad Inferior , ManoRESUMEN
Respiration and heartbeat continuously interact within the living organism at many different levels, representing two of the main oscillatory rhythms of the body and providing major sources of interoceptive information to the brain. Despite the modulatory effect of respiration on exteroception and cognition has been recently established in humans, its role in shaping interoceptive perception has been scarcely investigated so far. In two independent studies, we investigated the effect of spontaneous breathing on cardiac interoception by assessing the Heartbeat Evoked Potential (HEP) in healthy humans. In Study 1, we compared HEP activity for heartbeats occurred during inhalation and exhalation in 40 volunteers at rest. We found higher HEP amplitude during exhalation, compared to inhalation, over fronto-centro-parietal areas. This suggests increased brain-heart interactions and improved cortical processing of the heartbeats during exhalation. Further analyses revealed that this effect was moderated by heart rate changes. In Study 2, we tested the respiratory phase-dependent modulation of HEP activity in 20 volunteers during Exteroceptive and Interoceptive conditions of the Heartbeat Detection (HBD) task. In these conditions, participants were requested to tap at each heartbeat, either listened to or felt, respectively. Results showed higher HEP activity and higher detection accuracy at exhalation than inhalation in the Interoceptive condition only. Direct comparisons of Interoceptive and Exteroceptive conditions confirmed stronger respiratory phase-dependent modulation of HEP and accuracy when attention was directed towards the interoceptive stimuli. Moreover, HEP changes during the Interoceptive condition were independent of heart physiology, but were positively correlated with higher detection accuracy at exhalation than inhalation. This suggests a link between optimization of cortical processing of cardiac signals and detection of heartbeats across the respiratory cycle. Overall, we provide data showing that respiration shapes cardiac interoception at the neurophysiological and behavioural levels. Specifically, exhalation may allow attentional shift towards the internal bodily states.
Asunto(s)
Electroencefalografía , Interocepción , Atención/fisiología , Concienciación/fisiología , Encéfalo/fisiología , Electroencefalografía/métodos , Frecuencia Cardíaca/fisiología , Humanos , Interocepción/fisiología , Frecuencia RespiratoriaRESUMEN
Brain tumor surgery requires a delicate tradeoff between complete removal of neoplastic tissue while minimizing loss of brain function. Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) have emerged as valuable tools for non-invasive assessment of human brain function and are now used to determine brain regions that should be spared to prevent functional impairment after surgery. However, image analysis requires different software packages, mainly developed for research purposes and often difficult to use in a clinical setting, preventing large-scale diffusion of presurgical mapping. We developed a specialized software able to implement an automatic analysis of multimodal MRI presurgical mapping in a single application and to transfer the results to the neuronavigator. Moreover, the imaging results are integrated in a commercially available wearable device using an optimized mixed-reality approach, automatically anchoring 3-dimensional holograms obtained from MRI with the physical head of the patient. This will allow the surgeon to virtually explore deeper tissue layers highlighting critical brain structures that need to be preserved, while retaining the natural oculo-manual coordination. The enhanced ergonomics of this procedure will significantly improve accuracy and safety of the surgery, with large expected benefits for health care systems and related industrial investors.
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Neoplasias Encefálicas , Neurocirugia , Mapeo Encefálico/métodos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Imagen de Difusión Tensora , Humanos , Imagen por Resonancia Magnética/métodosRESUMEN
The sense of agency (SoA) refers to a constitutional aspect of the self describing the extent to which individuals feel in control over their actions and consequences thereof. Although the SoA has been associated with mental health and well-being, it is still unknown how interindividual variability in the SoA is embedded in the intrinsic brain organization. We hypothesized that the prospective component of an implicit SoA is associated with brain networks related to SoA and sensorimotor predictions on multiple spatial scales. We replicated previous findings by showing a significant prospective SoA as indicated by intentional binding effects. Then, using task-free fMRI and graph analysis, we analyzed associations between intentional binding effects and the intrinsic brain organization at regional, modular, and whole-brain scales. The results showed that intermodular connections of a frontoparietal module including the premotor cortex, supramarginal gyrus, and dorsal precuneus are associated with individual differences in prospective intentional binding. Notably, prospective intentional binding effects were also related to global brain modularity within a specific structural resolution range. These findings suggest that an implicit SoA generated through sensorimotor predictions relies on the intrinsic organization of the brain connectome on both local and global scales.
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Conectoma , Desempeño Psicomotor , Encéfalo/diagnóstico por imagen , Emociones , Humanos , Estudios ProspectivosRESUMEN
Temporal encoding is a key feature in multisensory processing that leads to the integration versus segregation of perceived events over time. Whether or not two events presented at different offsets are perceived as simultaneous varies widely across the general population. Such tolerance to temporal delays is known as the temporal binding window (TBW). It has been recently suggested that individual oscillatory alpha frequency (IAF) peak may represent the electrophysiological correlate of TBW, with IAF also showing a wide variability in the general population (8-12 Hz). In our work, we directly tested this hypothesis by measuring each individual's TBW during a visuotactile simultaneity judgment task while concurrently recording their electrophysiological activity. We found that the individual's TBW significantly correlated with their left parietal IAF, such that faster IAF accounted for narrower TBW. Furthermore, we found that higher prestimulus alpha power measured over the same left parietal regions accounted for more veridical responses of non-simultaneity, which may be explained either by accuracy in perceptual simultaneity or, alternatively, in line with recent proposals by a shift in response bias from more conservative (high alpha power) to more liberal (low alpha power). We propose that the length of an alpha cycle constrains the temporal resolution within which perceptual processes take place.
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Ritmo alfa/fisiología , Lóbulo Parietal/fisiología , Percepción del Tiempo/fisiología , Percepción del Tacto/fisiología , Percepción Visual/fisiología , Adulto , Electroencefalografía , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
Humans experience a sense of self, which is proposed to emerge from the integration of intrinsic and extrinsic self-processing through the propagation of information across brain systems. Using a novel functional magnetic resonance imaging (fMRI) paradigm, we tested this hypothesis in a non-clinical sample by modulating the intrinsic and extrinsic self-relatedness of auditory action consequences in terms of identity and agency, respectively. In addition, the relevance of individual traits associated with altered self-experiences (e.g., psychosis-like experiences) was examined. The task-evoked fMRI results showed distinctive associations between the neural coding of identity and negative affect traits, and between agency and psychosis-like experiences. Most importantly, regarding the functional connectivity analysis, graph theoretical measures demonstrated that the simultaneous processing of identity and agency relies on the functional integration and segregation of default mode, sensorimotor, language, and executive brain networks. Finally, cross-network interactions mediated by executive and sensorimotor regions were negatively associated with psychosis-like experiences when the intrinsic and extrinsic self-relatedness of action consequences conflicted. These findings provide evidence that the self is a multidimensional phenomenon rooted in the functional interactions between large-scale neuronal networks. Such interactions may have particular relevance for self-experience alterations.
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Afecto/fisiología , Corteza Cerebral/fisiología , Conectoma , Ego , Red Nerviosa/fisiología , Trastornos Psicóticos/fisiopatología , Adulto , Función Ejecutiva/fisiología , Retroalimentación Sensorial/fisiología , Femenino , Humanos , Lenguaje , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/diagnóstico por imagen , Desempeño Psicomotor/fisiología , Trastornos Psicóticos/diagnóstico por imagen , Adulto JovenRESUMEN
The present study investigates the neural pathways underlying individual susceptibility to affective or cognitive information in persuasive communication, also known as the structural matching effect. Expanding on the presumed involvement of the ventromedial prefrontal cortex (vMPFC) in persuasion, we hypothesized that the vMPFC contributes to the evaluation of persuasive information depending on its match with the recipient's affective or cognitive predominance. During functional magnetic resonance imaging, 30 participants evaluated 10 consumable products presented with both affective and cognitive persuasive messages. All participants were characterized on a continuum regarding their personal orientation in terms of individual differences in need for affect (NFA) and need for cognition (NFC). The results showed that the vMPFC, posterior cingulate cortex, and cerebellum are more strongly activated when the persuasive message content, either affective or cognitive, matched the recipient's individual affective or cognitive orientation. Interestingly, this effect in the vMPFC was found specifically when participants evaluated the products presented by the persuasive messages, whereas the correlation in the posterior cingulate cortex and cerebellum activity was detected when reading the messages. These results confirm the hypothesis that the vMPFC plays a role in subjectively weighting persuasive message content depending on individual differences in affective and cognitive orientation. Such a structural matching effect might involve the vMPFC particularly during explicit expressions of subjective valuations. These novel findings also further develop the conceptualization of the role of the vMPFC in self-related processing.
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Afecto/fisiología , Cognición/fisiología , Individualidad , Juicio/fisiología , Comunicación Persuasiva , Corteza Prefrontal/fisiología , Adolescente , Adulto , Mapeo Encefálico , Cerebelo/diagnóstico por imagen , Cerebelo/fisiología , Comportamiento del Consumidor , Femenino , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/fisiología , Humanos , Imagen por Resonancia Magnética , Masculino , Corteza Prefrontal/diagnóstico por imagen , Adulto JovenRESUMEN
The spontaneous activity of the brain is characterized by an elaborate temporal structure with scale-free properties as indexed by the power law exponent (PLE). We test the hypothesis that spontaneous brain activity modulates task-evoked activity during interactions with animate versus inanimate stimuli. For this purpose, we developed a paradigm requiring participants to actively touch either animate (real hand) or inanimate (mannequin hand) stimuli. Behaviorally, participants perceived the animate target as closer in space, temporally more synchronous with their own self, and more personally relevant, compared with the inanimate. Neuronally, we observed a modulation of task-evoked activity by animate versus inanimate interactions in posterior insula, in medial prefrontal cortex, comprising anterior cingulate cortex, and in medial superior frontal gyrus. Among these regions, an increased functional connectivity was shown between posterior insula and perigenual anterior cingulate cortex (PACC) during animate compared with inanimate interactions and during resting state. Importantly, PLE during spontaneous brain activity in PACC correlated positively with PACC task-evoked activity during animate versus inanimate stimuli. In conclusion, we demonstrate that brain spontaneous activity in PACC can be related to the distinction between animate and inanimate stimuli and thus might be specifically tuned to align our brain with its animate environment.
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Encéfalo/fisiología , Percepción del Tacto/fisiología , Tacto/fisiología , Adulto , Mapeo Encefálico , Femenino , Mano , Humanos , Imagen por Resonancia Magnética , Masculino , Estimulación Física , Autoimagen , Percepción Espacial/fisiología , Percepción del Tiempo/fisiología , Adulto JovenRESUMEN
Humans acquire a sense of agency through their interactions with the world and their sensory consequences. Previous studies have highlighted stable agency-related phenomena like intentional binding, which depend on both prospective, context-dependent and retrospective, outcome-dependent processes. In the current study, we investigated the interaction between prospective and retrospective processes underlying the adaptation of an ongoing sense of agency. The results showed that prospective intentional binding developed during a temporal window of up to 20 prior events was independent of the nature of the ongoing event. By contrast, the characteristics of the ongoing event retrospectively influenced prospective intentional binding developed during a temporal window narrower than 6 prior events. These findings characterize the interaction between prospective and retrospective mechanisms as a fundamental process to continuously update the sense of agency through sensorimotor learning. High psychosis-like experience traits weakened this interaction, suggesting that reduced adaption to the context contributes to altered self-experience.
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Retroalimentación Sensorial/fisiología , Intención , Aprendizaje/fisiología , Personalidad/fisiología , Desempeño Psicomotor/fisiología , Trastornos Psicóticos/fisiopatología , Percepción del Tiempo/fisiología , Adulto , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
Neurobiological research has classically focused on perceptual decision-making, although many real-life decisions are based on information that is not currently available but stored in long-term memory. Previous studies have suggested that the lateral parietal cortex encodes decision-related signals during item recognition judgments. In the present fMRI study, we employed a parametric manipulation of evidence for source memory judgments and tested several hypotheses concerning memory decision signals in parietal cortex. As expected, the mean BOLD signal in several parietal regions was modulated by decision evidence. An analysis of the locally distributed pattern of activity, moreover, identified a parietal cluster showing significant choice-predictive activity even at the lowest level of decision evidence, with decoding accuracy that increased as a function of evidence. Decoding patterns were consistent across subjects as shown by a leave-one-subject-out classification analysis. Finally, we found that the pattern of choice-predictive activity in parietal lobe was temporally correlated with that observed in medial temporal regions traditionally associated with long-term memory functions. The present findings are consistent with a general role of lateral parietal regions located around the intraparietal sulcus in representing a decision variable for memory-based decisions.
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Aprendizaje por Asociación/fisiología , Mapeo Encefálico/métodos , Toma de Decisiones/fisiología , Memoria Episódica , Recuerdo Mental/fisiología , Lóbulo Parietal/fisiología , Reconocimiento Visual de Modelos/fisiología , Adulto , Conducta de Elección/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Lóbulo Parietal/diagnóstico por imagen , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/fisiología , Adulto JovenRESUMEN
Fluid reasoning is considered central to general intelligence. How its psychometric structure relates to brain function remains poorly understood. For instance, what is the dynamic composition of ability-specific processes underlying fluid reasoning? We investigated whether distinct fluid reasoning abilities could be differentiated by electroencephalography (EEG) microstate profiles. EEG microstates specifically capture rapidly altering activity of distributed cortical networks with a high temporal resolution as scalp potential topographies that dynamically vary over time in an organized manner. EEG was recorded simultaneously with functional magnetic resonance imaging (fMRI) in twenty healthy adult participants during cognitively distinct fluid reasoning tasks: induction, spatial relationships and visualization. Microstate parameters successfully discriminated between fluid reasoning and visuomotor control tasks as well as between the fluid reasoning tasks. Mainly, microstate B coverage was significantly higher during spatial relationships and visualization, compared to induction, while microstate C coverage was significantly decreased during spatial relationships and visualization, compared to induction. Additionally, microstate D coverage was highest during spatial relationships and microstate A coverage was most strongly reduced during the same condition. Consistently, multivariate analysis with a leave-one-out cross-validation procedure accurately classified the fluid reasoning tasks based on the coverage parameter. These EEG data and their correlation with fMRI data suggest that especially the tasks most strongly relying on visuospatial processing modulated visual and default mode network activity. We propose that EEG microstates can provide valuable information about neural activity patterns with a dynamic and complex temporal structure during fluid reasoning, suggesting cognitive ability-specific interplays between multiple brain networks.
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Corteza Cerebral/fisiología , Electroencefalografía/métodos , Neuroimagen Funcional/métodos , Red Nerviosa/fisiología , Reconocimiento Visual de Modelos/fisiología , Desempeño Psicomotor/fisiología , Pensamiento/fisiología , Adulto , Aptitud/fisiología , Corteza Cerebral/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Imagen Multimodal , Red Nerviosa/diagnóstico por imagen , Adulto JovenRESUMEN
The sense of agency concerns the experience of being the source of one's own actions and their consequences. An altered sense of agency can occur due to task automation and in psychosis. We tested in a non-clinical sample the hypothesis that reducing voluntary task control diminishes intentional binding as an implicit indicator of the sense of agency, possibly interacting with psychosis-relevant personality traits. Agent-device interactions were manipulated obtaining positive-control (voluntary interaction), no-control (automation), and negative-control (device-commanded interaction) groups. The main results showed reduced prospective intentional binding (predictive coding of action consequences) in the no-control and negative-control groups, compared to the positive-control group. Psychosis-like experiences covaried positively with intentional binding in the no-control group, but negatively in the negative-control group. Moreover, positive-social traits were associated with increased intentional binding in the positive-control group. These findings demonstrate the interplay between environmental and individual differences variables in establishing the implicit sense of agency.
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Ambiente , Intención , Personalidad/fisiología , Trastornos Psicóticos/fisiopatología , Trastorno de la Personalidad Esquizotípica/fisiopatología , Adulto , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
Fundamental problems in neuroscience today are understanding how patterns of ongoing spontaneous activity are modified by task performance and whether/how these intrinsic patterns influence task-evoked activation and behavior. We examined these questions by comparing instantaneous functional connectivity (IFC) and directed functional connectivity (DFC) changes in two networks that are strongly correlated and segregated at rest: the visual (VIS) network and the dorsal attention network (DAN). We measured how IFC and DFC during a visuospatial attention task, which requires dynamic selective rerouting of visual information across hemispheres, changed with respect to rest. During the attention task, the two networks remained relatively segregated, and their general pattern of within-network correlation was maintained. However, attention induced a decrease of correlation in the VIS network and an increase of the DANâVIS IFC and DFC, especially in a top-down direction. In contrast, within the DAN, IFC was not modified by attention, whereas DFC was enhanced. Importantly, IFC modulations were behaviorally relevant. We conclude that a stable backbone of within-network functional connectivity topography remains in place when transitioning between resting wakefulness and attention selection. However, relative decrease of correlation of ongoing "idling" activity in visual cortex and synchronization between frontoparietal and visual cortex were behaviorally relevant, indicating that modulations of resting activity patterns are important for task performance. Higher order resting connectivity in the DAN was relatively unaffected during attention, potentially indicating a role for simultaneous ongoing activity as a "prior" for attention selection.
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Atención/fisiología , Visión Ocular/fisiología , Adulto , Animales , Conducta Animal , Encéfalo/fisiología , Humanos , Imagen por Resonancia Magnética , Adulto JovenRESUMEN
We live in a dynamic environment, constantly confronted with approaching objects that we may either avoid or be forced to address. A multisensory and sensorimotor interface, the peripersonal space (PPS), mediates every physical interaction between our body and the environment. Behavioral investigations show high variability in the extension of PPS across individuals, but there is a lack of evidence on the neural underpinnings of these large individual differences. Here, we used approaching auditory stimuli and fMRI to capture the individual boundary of PPS and examine its neural underpinnings. Precisely, we tested the hypothesis that intertrial variability (ITV) in brain regions coding PPS predicts individual differences of its boundary at the behavioral level. Selectively in the premotor cortex, we found that ITV, rather than trial-averaged amplitude, of BOLD responses to far rather than near dynamic stimuli predicts the individual extension of PPS. Our results provide the first empirical support for the relevance of ITV of brain responses for individual differences in human behavior. SIGNIFICANCE STATEMENT: Peripersonal space (PPS) is a multisensory and sensorimotor interface mediating every physical interaction between the body and the environment. A major characteristic of the boundary of PPS in humans is the extremely high variability of its location across individuals. We show that interindividual differences in the extension of the PPS are predicted by variability of BOLD responses in the premotor cortex to far stimuli approaching our body. Our results provide the first empirical support to the relevance of variability of evoked responses for human behavior and its variance across individuals.
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Corteza Motora/fisiología , Espacio Personal , Estimulación Acústica , Adulto , Conducta/fisiología , Ambiente , Femenino , Humanos , Individualidad , Imagen por Resonancia Magnética , Masculino , Oxígeno/sangre , Estimulación Física , Desempeño Psicomotor/fisiología , Tiempo de Reacción/fisiología , Localización de Sonidos/fisiología , Tacto/fisiología , Adulto JovenRESUMEN
Visual selection requires mechanisms for representing object salience and for shifting the focus of processing to novel objects. It is not clear from computational or neural models whether these operations are performed within the same or different brain regions. Here, we use repetitive transcranial magnetic stimulation to briefly interfere with neural activity in individually localized regions of human posterior parietal cortex (PPC) that are putatively involved in attending to contralateral locations or shifting attention between locations. Stimulation over right ventral intraparietal sulcus impaired target discrimination at contralateral locations, whereas stimulation over right medial superior parietal lobule impaired target discrimination after a shift of attention regardless of its location. This double dissociation is consistent with neuroimaging studies and indicates that mechanisms of visual selection are partly anatomically segregated in human PPC.
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Atención/fisiología , Conducta de Elección/fisiología , Discriminación en Psicología/fisiología , Lóbulo Parietal/fisiología , Adulto , Femenino , Lateralidad Funcional , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Orientación/fisiología , Oxígeno/sangre , Lóbulo Parietal/irrigación sanguínea , Estimulación Luminosa , Estimulación Magnética Transcraneal , Adulto JovenRESUMEN
It has been suggested that our perception of the internal milieu, or the body's internal state, is shaped by our beliefs and previous knowledge about the body's expected state, rather than being solely based on actual interoceptive experiences. This study investigated whether heartbeat perception could be illusorily distorted towards prior subjective beliefs, such that threat expectations suffice to induce a misperception of heartbeat frequency. Participants were instructed to focus on their cardiac activity and report their heartbeat, either tapping along to it (Experiment 1) or silently counting (Experiment 2) while ECG was recorded. While completing this task, different cues provided valid predictive information about the intensity of an upcoming cutaneous stimulation (high- vs. low- pain). Results showed that participants expected a heart rate increase over the anticipation of high- vs. low-pain stimuli and that this belief was perceptually instantiated, as suggested by their interoceptive reports. Importantly, the perceived increase was not mirrored by the real heart rate. Perceptual modulations were absent when participants executed the same task but with an exteroceptive stimulus (Experiment 3). The findings reveal, for the first time, an interoceptive illusion of increased heartbeats elicited by threat expectancy and shed new light on interoceptive processes through the lenses of Bayesian predictive processes, providing tantalizing insights into how such illusory phenomena may intersect with the recognition and regulation of people's internal states.
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Ilusiones , Interocepción , Humanos , Ilusiones/fisiología , Teorema de Bayes , Interocepción/fisiología , Señales (Psicología) , Frecuencia Cardíaca/fisiología , Dolor , Concienciación/fisiologíaRESUMEN
Respiration and cardiac activity intricately interact through complex physiological mechanisms. The heartbeat-evoked potential (HEP) is an EEG fluctuation reflecting the cortical processing of cardiac signals. We recently found higher HEP amplitude during exhalation than inhalation during a task involving attention to cardiac sensations. This may have been due to reduced cardiac perception during inhalation and heightened perception during exhalation through attentional mechanisms. To investigate relationships between HEP, attention, and respiration, we introduced an experimental setup that included tasks related to cardiac and respiratory interoceptive and exteroceptive attention. Results revealed HEP amplitude increases during the interoceptive tasks over fronto-central electrodes. When respiratory phases were taken into account, HEP increases were primarily driven by heartbeats recorded during exhalation, specifically during the cardiac interoceptive task, while inhalation had minimal impact. These findings emphasize the role of respiration in cardiac interoceptive attention and could have implications for respiratory interventions to fine-tune cardiac interoception.
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The phasic cardiovascular activity influences the central nervous system through the systolic baroreceptor inputs, inducing widespread inhibitory effects on behavior. Through transcranial magnetic stimulation (TMS) delivered during resting-state over the left primary motor cortex and across the different cardiac phases, we measured corticospinal excitability (CSE) and distinct indices of intracortical motor inhibition: short (SICI) and long (LICI) interval, corresponding to GABAA and GABAB neurotransmission, respectively. We found a significant effect of the cardiac phase on short-intracortical inhibition, without any influence on LICI. Specifically, SICI was stronger at systole compared to diastole. These results show a tight relationship between the cardiac cycle and the inhibitory neurotransmission within M1, and in particular with GABAA-ergic-mediated motor inhibition. We hypothesize that this process requires greater motor control via the gating mechanism and that this, in turn, needs to be recalibrated through the modulation of intracortical inhibition.
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Treatment-Resistant Depression (TRD) poses a substantial health and economic challenge, persisting as a major concern despite decades of extensive research into novel treatment modalities. The considerable heterogeneity in TRD's clinical manifestations and neurobiological bases has complicated efforts toward effective interventions. Recognizing the need for precise biomarkers to guide treatment choices in TRD, herein we introduce the SelecTool Project. This initiative focuses on developing (WorkPlane 1/WP1) and conducting preliminary validation (WorkPlane 2/WP2) of a computational tool (SelecTool) that integrates clinical data, neurophysiological (EEG) and peripheral (blood sample) biomarkers through a machine-learning framework designed to optimize TRD treatment protocols. The SelecTool project aims to enhance clinical decision-making by enabling the selection of personalized interventions. It leverages multi-modal data analysis to navigate treatment choices towards two validated therapeutic options for TRD: esketamine nasal spray (ESK-NS) and accelerated repetitive Transcranial Magnetic Stimulation (arTMS). In WP1, 100 subjects with TRD will be randomized to receive either ESK-NS or arTMS, with comprehensive evaluations encompassing neurophysiological (EEG), clinical (psychometric scales), and peripheral (blood samples) assessments both at baseline (T0) and one month post-treatment initiation (T1). WP2 will utilize the data collected in WP1 to train the SelecTool algorithm, followed by its application in a second, out-of-sample cohort of 20 TRD subjects, assigning treatments based on the tool's recommendations. Ultimately, this research seeks to revolutionize the treatment of TRD by employing advanced machine learning strategies and thorough data analysis, aimed at unraveling the complex neurobiological landscape of depression. This effort is expected to provide pivotal insights that will promote the development of more effective and individually tailored treatment strategies, thus addressing a significant void in current TRD management and potentially reducing its profound societal and economic burdens.