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Patients recovering from COVID-19 commonly exhibit cognitive and brain alterations, yet the specific neuropathological mechanisms and risk factors underlying these alterations remain elusive. Given the significant global incidence of COVID-19, identifying factors that can distinguish individuals at risk of developing brain alterations is crucial for prioritizing follow-up care. Here, we report findings from a sample of patients consisting of 73 adults with a mild to moderate SARS-CoV-2 infection without signs of respiratory failure and 27 with infections attributed to other agents and no history of COVID-19. The participants underwent cognitive screening, a decision-making task, and MRI evaluations. We assessed for the presence of anosmia and the requirement for hospitalization. Groups did not differ in age or cognitive performance. Patients who presented with anosmia exhibited more impulsive alternative changes after a shift in probabilities (r = - 0.26, p = 0.001), while patients who required hospitalization showed more perseverative choices (r = 0.25, p = 0.003). Anosmia correlated with brain measures, including decreased functional activity during the decision-making task, thinning of cortical thickness in parietal regions, and loss of white matter integrity. Hence, anosmia could be a factor to be considered when identifying at-risk populations for follow-up.
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Anosmia , Encéfalo , COVID-19 , Imagen por Resonancia Magnética , SARS-CoV-2 , Humanos , COVID-19/complicaciones , COVID-19/psicología , COVID-19/fisiopatología , COVID-19/diagnóstico por imagen , COVID-19/patología , Anosmia/etiología , Anosmia/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/fisiopatología , SARS-CoV-2/aislamiento & purificación , Anciano , Toma de Decisiones , Cognición/fisiologíaRESUMEN
Despite the well-known health benefits of physical activity, many people underexercise; what drives the prioritization of exercise over alternative options is unclear. We developed a task that enabled us to study how mice freely and rapidly alternate between wheel running and other voluntary activities, such as eating palatable food. When multiple alternatives were available, mice chose to spend a substantial amount of time wheel running without any extrinsic reward and maintained this behavior even when palatable food was added as an option. Causal manipulations and correlative analyses of appetitive and consummatory processes revealed this preference for wheel running to be instantiated by hypothalamic hypocretin/orexin neurons (HONs). The effect of HON manipulations on wheel running and eating was strongly context-dependent, being the largest in the scenario where both options were available. Overall, these data suggest that HON activity enables an eat-run arbitration that results in choosing exercise over food.
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Pupil size is a widely used metric of brain state. It is one of the few signals originating from the brain that can be readily monitored with low-cost devices in basic science, clinical, and home settings. It is, therefore, important to investigate and generate well-defined theories related to specific interpretations of this metric. What exactly does it tell us about the brain? Pupils constrict in response to light and dilate during darkness, but the brain also controls pupil size irrespective of luminosity. Pupil size fluctuations resulting from ongoing "brain states" are used as a metric of arousal, but what is pupil-linked arousal and how should it be interpreted in neural, cognitive, and computational terms? Here, we discuss some recent findings related to these issues. We identify open questions and propose how to answer them through a combination of well-defined tasks, neurocomputational models, and neurophysiological probing of the interconnected loops of causes and consequences of pupil size.
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Non-spatial attention is a fundamental cognitive mechanism that allows organisms to orient the focus of conscious awareness towards sensory information that is relevant to a behavioural goal while shifting it away from irrelevant stimuli. It has been suggested that attention is regulated by the ongoing phase of slow excitability fluctuations of neural activity in the prefrontal cortex, a hypothesis that has been challenged with no consensus. Here we developed a behavioural and non-invasive stimulation paradigm aiming at modulating slow excitability fluctuations of the inferior frontal junction. Using this approach, we show that non-spatial attention can be selectively modulated as a function of the ongoing phase of exogenously modulated excitability states of this brain structure. These results demonstrate that non-spatial attention relies on ongoing prefrontal excitability states, which are probably regulated by slow oscillatory dynamics, that orchestrate goal-oriented behaviour.
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Atención , Corteza Prefrontal , Humanos , Corteza Prefrontal/fisiología , Corteza Prefrontal/diagnóstico por imagen , Atención/fisiología , Masculino , Adulto , Adulto Joven , Femenino , Estimulación Magnética TranscranealRESUMEN
Is the role of our sensory systems to represent the physical world as accurately as possible? If so, are our preferences and emotions, often deemed irrational, decoupled from these 'ground-truth' sensory experiences? We show why the answer to both questions is 'no'. Brain function is metabolically costly, and the brain loses some fraction of the information that it encodes and transmits. Therefore, if brains maximize objective functions that increase the fitness of their species, they should adapt to the objective-maximizing rules of the environment at the earliest stages of sensory processing. Consequently, observed 'irrationalities', preferences, and emotions stem from the necessity for our early sensory systems to adapt and process information while considering the metabolic costs and internal states of the organism.
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Encéfalo , Emociones , Humanos , SensaciónRESUMEN
Humans often face the challenge of making decisions between ambiguous options. The level of ambiguity in decision-making has been linked to activity in the parietal cortex, but its exact computational role remains elusive. To test the hypothesis that the parietal cortex plays a causal role in computing ambiguous probabilities, we conducted consecutive fMRI and TMS-EEG studies. We found that participants assigned unknown probabilities to objective probabilities, elevating the uncertainty of their decisions. Parietal cortex activity correlated with the objective degree of ambiguity and with a process that underestimates the uncertainty during decision-making. Conversely, the midcingulate cortex (MCC) encodes prediction errors and increases its connectivity with the parietal cortex during outcome processing. Disruption of the parietal activity increased the uncertainty evaluation of the options, decreasing cingulate cortex oscillations during outcome evaluation and lateral frontal oscillations related to value ambiguous probability. These results provide evidence for a causal role of the parietal cortex in computing uncertainty during ambiguous decisions made by humans.
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Mapeo Encefálico , Toma de Decisiones , Humanos , Mapeo Encefálico/métodos , Asunción de Riesgos , Incertidumbre , Lóbulo Parietal , Imagen por Resonancia Magnética/métodosRESUMEN
The sense of agency is a fundamental aspect of human self-consciousness, whose neural correlates encompass widespread brain networks. Research has explored the neuromodulatory properties of the sense of agency with noninvasive brain stimulation, which induces exogenous manipulations of brain activity; however, it is unknown whether endogenous modulation of the sense of agency is also achievable. We investigated whether the sense of agency can be self-regulated with electroencephalography-based neurofeedback. We conducted 2 experiments in which healthy humans performed a motor task while their motor control was artificially disrupted, and gave agency statements on their perceived control. We first identified the electrophysiological response to agency processing, and then applied neurofeedback in a parallel, sham-controlled design, where participants learnt to self-modulate their sense of agency. We found that behavioral measures of agency and performance on the task decreased with the increasing disruption of control. This was negatively correlated with power spectral density in the theta band, and positively correlated in the alpha and beta bands, at central and parietal electrodes. After neurofeedback training of central theta rhythms, participants improved their actual control over the task, and this was associated with a significant decrease in the frequency band trained via neurofeedback. Thus, self-regulation of theta rhythms can improve sensory-guided behavior.
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Neurorretroalimentación , Humanos , Neurorretroalimentación/fisiología , Control de la Conducta , Electroencefalografía/métodos , Ritmo Teta/fisiología , EncéfaloRESUMEN
Humans are generally risk averse, preferring smaller certain over larger uncertain outcomes. Economic theories usually explain this by assuming concave utility functions. Here, we provide evidence that risk aversion can also arise from relative underestimation of larger monetary payoffs, a perceptual bias rooted in the noisy logarithmic coding of numerical magnitudes. We confirmed this with psychophysics and functional magnetic resonance imaging, by measuring behavioural and neural acuity of magnitude representations during a magnitude perception task and relating these measures to risk attitudes during separate risky financial decisions. Computational modelling indicated that participants use similar mental magnitude representations in both tasks, with correlated precision across perceptual and risky choices. Participants with more precise magnitude representations in parietal cortex showed less variable behaviour and less risk aversion. Our results highlight that at least some individual characteristics of economic behaviour can reflect capacity limitations in perceptual processing rather than processes that assign subjective values to monetary outcomes.
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Conducta de Elección , Imagen por Resonancia Magnética , Humanos , Lóbulo Parietal , ActitudRESUMEN
Owing to its unique connectivity profile with cortical brain regions, and its suggested role in the subcortical propagation of seizures, the anterior nucleus of the thalamus (ANT) has been proposed as a key deep brain stimulation (DBS) target in drug-resistant epilepsy. However, the spatio-temporal interaction dynamics of this brain structure, and the functional mechanisms underlying ANT DBS in epilepsy remain unknown. Here, we study how the ANT interacts with the neocortex in vivo in humans and provide a detailed neurofunctional characterization of mechanisms underlying the effectiveness of ANT DBS, aiming at defining intraoperative neural biomarkers of responsiveness to therapy, assessed at 6 months post-implantation as the reduction in seizure frequency. A cohort of 15 patients with drug-resistant epilepsy (n = 6 males, age = 41.6 ± 13.79 years) underwent bilateral ANT DBS implantation. Using intraoperative cortical and ANT simultaneous electrophysiological recordings, we found that the ANT is characterized by high amplitude θ (4-8 Hz) oscillations, mostly in its superior part. The strongest functional connectivity between the ANT and the scalp EEG was also found in the θ band in ipsilateral centro-frontal regions. Upon intraoperative stimulation in the ANT, we found a decrease in higher EEG frequencies (20-70 Hz) and a generalized increase in scalp-to-scalp connectivity. Crucially, we observed that responders to ANT DBS treatment were characterized by higher EEG θ oscillations, higher θ power in the ANT, and stronger ANT-to-scalp θ connectivity, highlighting the crucial role of θ oscillations in the dynamical network characterization of these structures. Our study provides a comprehensive characterization of the interaction dynamic between the ANT and the cortex, delivering crucial information to optimize and predict clinical DBS response in patients with drug-resistant epilepsy.
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Núcleos Talámicos Anteriores , Estimulación Encefálica Profunda , Epilepsia Refractaria , Epilepsia , Masculino , Humanos , Adulto , Persona de Mediana Edad , Epilepsia/terapia , Epilepsia Refractaria/terapia , Convulsiones/terapia , Tálamo/fisiologíaRESUMEN
Transcranial random noise stimulation (tRNS) has been shown to significantly improve visual perception. Previous studies demonstrated that tRNS delivered over cortical areas acutely enhances visual contrast detection of weak stimuli. However, it is currently unknown whether tRNS-induced signal enhancement could be achieved within different neural substrates along the retino-cortical pathway. In three experimental sessions, we tested whether tRNS applied to the primary visual cortex (V1) and/or to the retina improves visual contrast detection. We first measured visual contrast detection threshold (VCT; N = 24, 16 females) during tRNS delivery separately over V1 and over the retina, determined the optimal tRNS intensities for each individual (ind-tRNS), and retested the effects of ind-tRNS within the sessions. We further investigated whether we could reproduce the ind-tRNS-induced modulation on a different session (N = 19, 14 females). Finally, we tested whether the simultaneous application of ind-tRNS to the retina and V1 causes additive effects. Moreover, we present detailed simulations of the induced electric field across the visual system. We found that at the group level tRNS decreases VCT compared with baseline when delivered to the V1. Beneficial effects of ind-tRNS could be replicated when retested within the same experimental session but not when retested in a separate session. Applying tRNS to the retina did not cause a systematic reduction of VCT, regardless of whether the individually optimized intensity was considered or not. We also did not observe consistent additive effects of V1 and retina stimulation. Our findings demonstrate significant tRNS-induced modulation of visual contrast processing in V1 but not in the retina.
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Sensibilidad de Contraste , Estimulación Transcraneal de Corriente Directa , Femenino , Humanos , Percepción Visual/fisiologíaRESUMEN
Sensory information encoded by humans and other organisms is generally presumed to be as accurate as their biological limitations allow. However, perhaps counterintuitively, accurate sensory representations may not necessarily maximize the organism's chances of survival. To test this hypothesis, we developed a unified normative framework for fitness-maximizing encoding by combining theoretical insights from neuroscience, computer science, and economics. Behavioural experiments in humans revealed that sensory encoding strategies are flexibly adapted to promote fitness maximization, a result confirmed by deep neural networks with information capacity constraints trained to solve the same task as humans. Moreover, human functional MRI data revealed that novel behavioural goals that rely on object perception induce efficient stimulus representations in early sensory structures. These results suggest that fitness-maximizing rules imposed by the environment are applied at early stages of sensory processing in humans and machines.
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Redes Neurales de la Computación , Sensación , Humanos , PercepciónRESUMEN
Behavior exhibited by humans and other organisms is generally inconsistent and biased and, thus, is often labeled irrational. However, the origins of this seemingly suboptimal behavior remain elusive. We developed a behavioral task and normative framework to reveal how organisms should allocate their limited processing resources such that sensory precision and its related metabolic investment are balanced to guarantee maximal utility. We found that mice act as rational inattentive agents by adaptively allocating their sensory resources in a way that maximizes reward consumption in previously unexperienced stimulus-reward association environments. Unexpectedly, perception of commonly occurring stimuli was relatively imprecise; however, this apparent statistical fallacy implies "awareness" and efficient adaptation to their neurocognitive limitations. Arousal systems carry reward distribution information of sensory signals, and distributional reinforcement learning mechanisms regulate sensory precision via top-down normalization. These findings reveal how organisms efficiently perceive and adapt to previously unexperienced environmental contexts within the constraints imposed by neurobiology.
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Confidence, the subjective estimate of decision quality, is a cognitive process necessary for learning from mistakes and guiding future actions. The origins of confidence judgments resulting from economic decisions remain unclear. We devise a task and computational framework that allowed us to formally tease apart the impact of various sources of confidence in value-based decisions, such as uncertainty emerging from encoding and decoding operations, as well as the interplay between gaze-shift dynamics and attentional effort. In line with canonical decision theories, trial-to-trial fluctuations in the precision of value encoding impact economic choice consistency. However, this uncertainty has no influence on confidence reports. Instead, confidence is associated with endogenous attentional effort towards choice alternatives and down-stream noise in the comparison process. These findings provide an explanation for confidence (miss)attributions in value-guided behaviour, suggesting mechanistic influences of endogenous attentional states for guiding decisions and metacognitive awareness of choice certainty.
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Recent studies have suggested close functional links between overt visual attention and decision making. This suggests that the corresponding mechanisms may interface in brain regions known to be crucial for guiding visual attention - such as the frontal eye field (FEF). Here, we combined brain stimulation, eye tracking, and computational approaches to explore this possibility. We show that inhibitory transcranial magnetic stimulation (TMS) over the right FEF has a causal impact on decision making, reducing the effect of gaze dwell time on choice while also increasing reaction times. We computationally characterize this putative mechanism by using the attentional drift diffusion model (aDDM), which reveals that FEF inhibition reduces the relative discounting of the non-fixated option in the comparison process. Our findings establish an important causal role of the right FEF in choice, elucidate the underlying mechanism, and provide support for one of the key causal hypotheses associated with the aDDM.
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Toma de Decisiones/fisiología , Lóbulo Frontal/fisiología , Estimulación Magnética Transcraneal , Adulto , Atención/fisiología , Tecnología de Seguimiento Ocular , Femenino , Humanos , Masculino , Tiempo de Reacción/fisiologíaRESUMEN
Moral preferences pervade many aspects of our lives, dictating how we ought to behave, whom we can marry, and even what we eat. Despite their relevance, one fundamental question remains unanswered: Where do individual moral preferences come from? It is often thought that all types of preferences reflect properties of domain-general neural decision mechanisms that employ a common "neural currency" to value choice options in many different contexts. This view, however, appears at odds with the observation that many humans consider it intuitively wrong to employ the same scale to compare moral value (e.g., of a human life) with material value (e.g., of money). In this paper, we directly test if moral subjective values are represented by similar neural processes as financial subjective values. In a study combining fMRI with a novel behavioral paradigm, we identify neural representations of the subjective values of human lives or financial payoffs by means of structurally identical computational models. Correlating isomorphic model variables from both domains with brain activity reveals specific patterns of neural activity that selectively represent values in the moral (rTPJ) or financial (vmPFC) domain. Intriguingly, our findings show that human lives and money are valued in (at least partially) distinct neural currencies, supporting theoretical proposals that human moral behavior is guided by processes that are distinct from those underlying behavior driven by personal material benefit.
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Diverse transcranial electrical stimulation (tES) techniques have recently been developed to elucidate the role of neural oscillations, but critically, it remains questionable whether neural entrainment genuinely occurs and is causally related to the resulting behavior. Here, we provide a perspective on an emerging integrative research program across systems, species, theoretical and experimental frameworks to elucidate the potential of tES to induce neural entrainment. We argue that such an integrative agenda is a requirement to establish tES as a tool to test the causal role of neural oscillations and highlight critical issues that should be considered when adopting a translational approach.
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Fenómenos Fisiológicos del Sistema Nervioso , Sistema Nervioso/química , Estimulación Transcraneal de Corriente Directa , Animales , Relojes Biológicos , Humanos , Estimulación Transcraneal de Corriente Directa/instrumentación , Estimulación Transcraneal de Corriente Directa/métodosRESUMEN
Transcranial alternating current stimulation (tACS) was introduced about a decade ago as a non-invasive brain stimulation method to modulate neural oscillations in a relatively safe manner in humans. However, the possibility to induce genuine neural entrainment with low current intensities has been questioned. In a recent study, Johnson and colleagues provide direct evidence for the efficacy of low-intensity tACS to induce neural entrainment in awake monkeys. These findings have important translational implications for human non-invasive neuromodulation research.
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Estimulación Transcraneal de Corriente Directa , Animales , Encéfalo , Primates , VigiliaRESUMEN
Human decisions are based on finite information, which makes them inherently imprecise. But what determines the degree of such imprecision? Here, we develop an efficient coding framework for higher-level cognitive processes in which information is represented by a finite number of discrete samples. We characterize the sampling process that maximizes perceptual accuracy or fitness under the often-adopted assumption that full adaptation to an environmental distribution is possible, and show how the optimal process differs when detailed information about the current contextual distribution is costly. We tested this theory on a numerosity discrimination task, and found that humans efficiently adapt to contextual distributions, but in the way predicted by the model in which people must economize on environmental information. Thus, understanding decision behavior requires that we account for biological restrictions on information coding, challenging the often-adopted assumption of precise prior knowledge in higher-level decision systems.
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Toma de Decisiones/fisiología , Modelos Psicológicos , Adulto , Algoritmos , Conducta de Elección , Femenino , Humanos , Masculino , Análisis y Desempeño de Tareas , Adulto JovenRESUMEN
Theories and computational models of decision-making usually focus on how strongly different attributes are weighted in choice, for example, as a function of their importance or salience to the decision-maker. However, when different attributes affect the decision process is a question that has received far less attention. Here, we investigated whether the timing of attribute consideration has a unique influence on decision-making by using a time-varying drift diffusion model and data from four separate experiments. Experimental manipulations of attention and neural activity demonstrated that we can dissociate the processes that determine the relative weighting strength and timing of attribute consideration. Thus, the processes determining either the weighting strengths or the timing of attributes in decision-making can independently adapt to changes in the environment or goals. Quantifying these separate influences of timing and weighting on choice improves our understanding and predictions of individual differences in decision behaviour.
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Atención/fisiología , Toma de Decisiones/fisiología , Recompensa , Adulto , Femenino , Humanos , Masculino , Modelos Psicológicos , Tiempo de Reacción/fisiología , Factores de Tiempo , Adulto JovenRESUMEN
Several theories propose that perceptual decision making depends on the gradual accumulation of information that provides evidence in favour of one of the choice-options. The outcome of this temporally extended integration process is thought to be categorized into the 'winning' and 'losing' choice-options for action. Neural correlates of corresponding decision formation processes have been observed in various frontal and parietal brain areas, among them the frontal eye-fields (FEF). However, the specific functional role of the FEFs is debated. Recent studies in humans and rodents provide conflicting accounts, proposing that the FEF either accumulate the choice-relevant information or categorize the outcome of such evidence integration into discrete actions. Here, we used transcranial magnetic stimulation (TMS) on humans to interfere with either left or right FEF activity during different timepoints of perceptual decision-formation. Stimulation of either FEF affected performance only when delivered during information integration but not during subsequent categorical choice. However, the patterns of behavioural changes suggest that the left-FEF contributes to general evidence integration, whereas right-FEF may direct spatial attention to the contralateral hemifield. Taken together, our results indicate an FEF involvement in evidence accumulation but not categorization, and suggest hemispheric lateralization for this function in the human brain.