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1.
Annu Rev Immunol ; 33: 539-61, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25861978

RESUMEN

T cells carry out the formidable task of identifying small numbers of foreign antigenic peptides rapidly and specifically against a very noisy environmental background of endogenous self-peptides. Early steps in T cell activation have thus fascinated biologists and are among the best-studied models of cell stimulation. This remarkable process, critical in adaptive immune responses, approaches and even seems to exceed the limitations set by the physical laws ruling molecular behavior. Despite the enormous amount of information concerning the nature of molecules involved in the T cell antigen receptor (TCR) signal transduction network, and the description of the nanoscale organization and real-time analysis of T cell responses, the general principles of information gathering and processing remain incompletely understood. Here we review currently accepted key data on TCR function, discuss the limitations of current research strategies, and suggest a novel model of TCR triggering and a few promising ways of going further into the integration of available data.


Asunto(s)
Activación de Linfocitos , Linfocitos T/inmunología , Linfocitos T/metabolismo , Animales , Humanos , Modelos Inmunológicos , Receptores de Antígenos de Linfocitos T/metabolismo , Transducción de Señal
2.
Annu Rev Neurosci ; 45: 403-423, 2022 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-35803585

RESUMEN

The extent to which we are affected by perceptual input of which we are unaware is widely debated. By measuring neural responses to sensory stimulation, neuroscientific data could complement behavioral results with valuable evidence. Here we review neuroscientific findings of processing of high-level information, as well as interactions with attention and memory. Although the results are mixed, we find initial support for processing object categories and words, possibly to the semantic level, as well as emotional expressions. Robust neural evidence for face individuation and integration of sentences or scenes is lacking. Attention affects the processing of stimuli that are not consciously perceived, and such stimuli may exogenously but not endogenously capture attention when relevant, and be maintained in memory over time. Sources of inconsistency in the literature include variability in control for awareness as well as individual differences, calling for future studies that adopt stricter measures of awareness and probe multiple processes within subjects.


Asunto(s)
Atención , Atención/fisiología , Humanos , Tiempo de Reacción/fisiología
3.
Proc Natl Acad Sci U S A ; 121(32): e2404909121, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39093946

RESUMEN

Human standing balance relies on the continuous monitoring and integration of sensory signals to infer our body's motion and orientation within the environment. However, when sensory information is no longer contextually relevant to balancing the body (e.g., when sensory and motor signals are incongruent), sensory-evoked balance responses are rapidly suppressed, much earlier than any conscious perception of changes in balance control. Here, we used a robotic balance simulator to assess whether associatively learned postural responses are similarly modulated by sensorimotor incongruence and contextual relevance to postural control. Twenty-nine participants in three groups were classically conditioned to generate postural responses to whole-body perturbations when presented with an initially neutral sound cue. During catch and extinction trials, participants received only the auditory stimulus but in different sensorimotor states corresponding to their group: 1) during normal active balance, 2) while immobilized, and 3) throughout periods where the computer subtly removed active control over balance. In the balancing and immobilized states, conditioned responses were either evoked or suppressed, respectively, according to the (in)ability to control movement. Following the immobilized state, conditioned responses were renewed when balance was restored, indicating that conditioning was retained but only expressed when contextually relevant. In contrast, conditioned responses persisted in the computer-controlled state even though there was no causal relationship between motor and sensory signals. These findings suggest that mechanisms responsible for sensory-evoked and conditioned postural responses do not share a single, central contextual inference and assessment of their relevance to postural control, and may instead operate in parallel.


Asunto(s)
Equilibrio Postural , Humanos , Equilibrio Postural/fisiología , Masculino , Femenino , Adulto , Adulto Joven , Postura/fisiología , Aprendizaje/fisiología
4.
Brief Bioinform ; 25(5)2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39051117

RESUMEN

Protein-protein interactions (PPIs) are important for many biological processes, but predicting them from sequence data remains challenging. Existing deep learning models often cannot generalize to proteins not present in the training set and do not provide uncertainty estimates for their predictions. To address these limitations, we present TUnA, a Transformer-based uncertainty-aware model for PPI prediction. TUnA uses ESM-2 embeddings with Transformer encoders and incorporates a Spectral-normalized Neural Gaussian Process. TUnA achieves state-of-the-art performance and, importantly, evaluates uncertainty for unseen sequences. We demonstrate that TUnA's uncertainty estimates can effectively identify the most reliable predictions, significantly reducing false positives. This capability is crucial in bridging the gap between computational predictions and experimental validation.


Asunto(s)
Biología Computacional , Incertidumbre , Biología Computacional/métodos , Mapeo de Interacción de Proteínas/métodos , Proteínas/metabolismo , Proteínas/química , Algoritmos , Aprendizaje Profundo
5.
Proc Natl Acad Sci U S A ; 120(7): e2208420120, 2023 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-36745814

RESUMEN

Some animals have the remarkable capacity for mirror self-recognition (MSR), yet any implications for self-awareness remain uncertain and controversial. This is largely because explicit tests of the two potential mechanisms underlying MSR are still lacking: mental image of the self and kinesthetic visual matching. Here, we test the hypothesis that MSR ability in cleaner fish, Labroides dimidiatus, is associated with a mental image of the self, in particular the self-face, like in humans. Mirror-naive fish initially attacked photograph models of both themselves and unfamiliar strangers. In contrast, after all fish had passed the mirror mark test, fish did not attack their own (motionless) images, but still frequently attacked those of unfamiliar individuals. When fish were exposed to composite photographs, the self-face/unfamiliar body were not attacked, but photographs of unfamiliar face/self-body were attacked, demonstrating that cleaner fish with MSR capacity recognize their own facial characteristics in photographs. Additionally, when presented with self-photographs with a mark placed on the throat, unmarked mirror-experienced cleaner fish demonstrated throat-scraping behaviors. When combined, our results provide clear evidence that cleaner fish recognize themselves in photographs and that the likely mechanism for MSR is associated with a mental image of the self-face, not a kinesthetic visual-matching model. Humans are also capable of having a mental image of the self-face, which is considered an example of private self-awareness. We demonstrate that combining mirror test experiments with photographs has enormous potential to further our understanding of the evolution of cognitive processes and private self-awareness across nonhuman animals.


Asunto(s)
Conducta Animal , Reconocimiento Facial , Humanos , Animales , Reconocimiento en Psicología , Peces , Autoimagen
6.
J Neurosci ; 44(8)2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38191569

RESUMEN

Identifying neural correlates of conscious perception is a fundamental endeavor of cognitive neuroscience. Most studies so far have focused on visual awareness along with trial-by-trial reports of task-relevant stimuli, which can confound neural measures of perceptual awareness with postperceptual processing. Here, we used a three-phase sine-wave speech paradigm that dissociated between conscious speech perception and task relevance while recording EEG in humans of both sexes. Compared with tokens perceived as noise, physically identical sine-wave speech tokens that were perceived as speech elicited a left-lateralized, near-vertex negativity, which we interpret as a phonological version of a perceptual awareness negativity. This response appeared between 200 and 300 ms after token onset and was not present for frequency-flipped control tokens that were never perceived as speech. In contrast, the P3b elicited by task-irrelevant tokens did not significantly differ when the tokens were perceived as speech versus noise and was only enhanced for tokens that were both perceived as speech and relevant to the task. Our results extend the findings from previous studies on visual awareness and speech perception and suggest that correlates of conscious perception, across types of conscious content, are most likely to be found in midlatency negative-going brain responses in content-specific sensory areas.


Asunto(s)
Concienciación , Percepción del Habla , Masculino , Femenino , Humanos , Concienciación/fisiología , Percepción Visual/fisiología , Electroencefalografía/métodos , Habla , Estado de Conciencia/fisiología
7.
J Neurosci ; 44(20)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38531633

RESUMEN

A central question in consciousness theories is whether one is dealing with a dichotomous ("all-or-none") or a gradual phenomenon. In this 7T fMRI study, we investigated whether dichotomy or gradualness in fact depends on the brain region associated with perceptual awareness reports. Both male and female human subjects performed an emotion discrimination task (fear vs neutral bodies) presented under continuous flash suppression with trial-based perceptual awareness measures. Behaviorally, recognition sensitivity increased linearly with increased stimuli awareness and was at chance level during perceptual unawareness. Physiologically, threat stimuli triggered a slower heart rate than neutral ones during "almost clear" stimulus experience, indicating freezing behavior. Brain results showed that activity in the occipitotemporal, parietal, and frontal regions as well as in the amygdala increased with increased stimulus awareness while early visual areas showed the opposite pattern. The relationship between temporal area activity and perceptual awareness best fitted a gradual model while the activity in frontoparietal areas fitted a dichotomous model. Furthermore, our findings illustrate that specific experimental decisions, such as stimulus type or the approach used to evaluate awareness, play pivotal roles in consciousness studies and warrant careful consideration.


Asunto(s)
Concienciación , Lóbulo Frontal , Imagen por Resonancia Magnética , Lóbulo Parietal , Lóbulo Temporal , Humanos , Masculino , Femenino , Imagen por Resonancia Magnética/métodos , Concienciación/fisiología , Lóbulo Parietal/fisiología , Lóbulo Parietal/diagnóstico por imagen , Adulto , Lóbulo Frontal/fisiología , Lóbulo Frontal/diagnóstico por imagen , Adulto Joven , Lóbulo Temporal/fisiología , Lóbulo Temporal/diagnóstico por imagen , Mapeo Encefálico/métodos , Estimulación Luminosa/métodos , Emociones/fisiología
8.
Proc Natl Acad Sci U S A ; 119(16): e2119868119, 2022 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-35412910

RESUMEN

The sensation of internal bodily signals, such as when your stomach is contracting or your heart is beating, plays a critical role in broad biological and psychological functions ranging from homeostasis to emotional experience and self-awareness. The evolutionary origins of this capacity and, thus, the extent to which it is present in nonhuman animals remain unclear. Here, we show that rhesus monkeys (Macaca mulatta) spend significantly more time viewing stimuli presented asynchronously, as compared to synchronously, with their heartbeats. This is consistent with evidence previously shown in human infants using a nearly identical experimental paradigm, suggesting that rhesus monkeys have a human-like capacity to integrate interoceptive signals from the heart with exteroceptive audiovisual information. As no prior work has demonstrated behavioral evidence of innate cardiac interoceptive ability in nonhuman animals, these results have important implications for our understanding of the evolution of this ability and for establishing rhesus monkeys as an animal model for human interoceptive function and dysfunction. We anticipate that this work may also provide an important model for future psychiatric research, as disordered interoceptive processing is implicated in a wide variety of psychiatric conditions.


Asunto(s)
Frecuencia Cardíaca , Interocepción , Animales , Concienciación , Corazón , Macaca mulatta , Modelos Animales
9.
Proc Natl Acad Sci U S A ; 119(18): e2116933119, 2022 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-35486693

RESUMEN

This article argues that consciousness has a logically sound, explanatory framework, different from typical accounts that suffer from hidden mysticism. The article has three main parts. The first describes background principles concerning information processing in the brain, from which one can deduce a general, rational framework for explaining consciousness. The second part describes a specific theory that embodies those background principles, the Attention Schema Theory. In the past several years, a growing body of experimental evidence-behavioral evidence, brain imaging evidence, and computational modeling-has addressed aspects of the theory. The final part discusses the evolution of consciousness. By emphasizing the specific role of consciousness in cognition and behavior, the present approach leads to a proposed account of how consciousness may have evolved over millions of years, from fish to humans. The goal of this article is to present a comprehensive, overarching framework in which we can understand scientifically what consciousness is and what key adaptive roles it plays in brain function.


Asunto(s)
Cognición , Estado de Conciencia , Animales , Atención , Encéfalo , Simulación por Computador
10.
Proc Natl Acad Sci U S A ; 119(44): e2211147119, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36302042

RESUMEN

Understanding the neural mechanisms of conscious and unconscious experience is a major goal of fundamental and translational neuroscience. Here, we target the early visual cortex with a protocol of noninvasive, high-resolution alternating current stimulation while participants performed a delayed target-probe discrimination task and reveal dissociable mechanisms of mnemonic processing for conscious and unconscious perceptual contents. Entraining ß-rhythms in bilateral visual areas preferentially enhanced short-term memory for seen information, whereas α-entrainment in the same region preferentially enhanced short-term memory for unseen information. The short-term memory improvements were frequency-specific and long-lasting. The results add a mechanistic foundation to existing theories of consciousness, call for revisions to these theories, and contribute to the development of nonpharmacological therapeutics for improving visual cortical processing.


Asunto(s)
Estado de Conciencia , Percepción Visual , Humanos , Estado de Conciencia/fisiología , Percepción Visual/fisiología , Inconsciencia , Memoria a Corto Plazo
11.
J Neurosci ; 43(37): 6447-6459, 2023 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-37591739

RESUMEN

Alpha rhythmic activity is often suggested to exert an inhibitory influence on information processing. However, relatively little is known about how reported alpha-related effects are influenced by a potential confounding element of the neural signal, power-law scaling. In the current study, we systematically examine the effect of accounting for 1/f activity on the relation between prestimulus alpha power and human behavior during both auditory and visual detection (N = 27; 19 female, 6 male, 2 nonbinary). The results suggest that, at least in the scalp-recorded EEG signal, the difference in alpha power often reported before visual hits versus misses is probably best thought of as a combination of narrowband alpha and broadband shifts. That is, changes in broadband parameters (exponent and offset of 1/f-like activity) also appear to be strong predictors of the subsequent awareness of visual stimuli. Neither changes in posterior alpha power nor changes in 1/f-like activity reliably predicted detection of auditory stimuli. These results appear consistent with suggestions that broadband changes in the scalp-recorded EEG signal may account for a portion of prior results linking alpha band dynamics to visuospatial attention and behavior, and suggest that systematic re-examination of existing data may be warranted.Significance Statement Fluctuations in alpha band (∼8-12 Hz) activity systematically follow the allocation of attention across space and sensory modality. Increases in alpha amplitude, which often precede failures to report awareness of threshold visual stimuli, are suggested to exert an inhibitory influence on information processing. However, fluctuations in alpha activity are often confounded with changes in the broadband 1/f-like pattern of the neural signal. When both factors are considered, we find that changes in broadband activity are as effective as narrowband alpha activity as predictors of subsequent visual detection. These results are consistent with emerging understanding of the potential functional importance of broadband changes in the neural signal and may have significant consequences for our understanding of alpha rhythmic activity.


Asunto(s)
Ritmo alfa , Cognición , Humanos , Femenino , Masculino , Electroencefalografía
12.
J Neurosci ; 43(35): 6176-6184, 2023 08 30.
Artículo en Inglés | MEDLINE | ID: mdl-37536981

RESUMEN

Humans can successfully correct deviations of movements without conscious detection of such deviations, suggesting limited awareness of movement details. We ask whether such limited awareness impairs confidence (metacognition). We recorded functional magnetic resonance imaging data while 31 human female and male participants detected cursor deviations during a visuomotor reaching task and rated their confidence retrospectively. We show that participants monitor a summary statistic of the unfolding visual feedback (the peak cursor error) to detect visuomotor deviations and adjust their confidence ratings, even when they report being unaware of a deviation. Crucially, confidence ratings were as metacognitively efficient for aware and unaware deviations. At the neural level, activity in the ventral striatum tracks high confidence, whereas a broad network encodes cursor error but not confidence. These findings challenge the notion of limited conscious action monitoring and uncover how humans monitor their movements as they unfold, even when unaware of ongoing deviations.SIGNIFICANCE STATEMENT We are unaware of the small corrections we apply to our movements as long as our goals are achieved. Here, although we replicate the finding that participants deny perceiving small deviations they correct, we show that their confidence reliably reflects the presence or absence of a deviation. This observation shows they can metacognitively monitor the presence of a deviation, even when they deny perceiving it. We also describe the hemodynamic correlates of confidence ratings. Our study questions the extent to which humans are unaware of the details of their movements; describes a plausible mechanism for metacognition in a visuomotor task, along with its neural correlates; and has important implications for the construction of the sense of self.


Asunto(s)
Metacognición , Humanos , Masculino , Femenino , Desempeño Psicomotor , Estudios Retrospectivos , Movimiento , Imagen por Resonancia Magnética
13.
J Neurosci ; 43(46): 7842-7852, 2023 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-37722848

RESUMEN

Our muscles are the primary means through which we affect the external world, and the sense of agency (SoA) over the action through those muscles is fundamental to our self-awareness. However, SoA research to date has focused almost exclusively on agency over action outcomes rather than over the musculature itself, as it was believed that SoA over the musculature could not be manipulated directly. Drawing on methods from human-computer interaction and adaptive experimentation, we use human-in-the-loop Bayesian optimization to tune the timing of electrical muscle stimulation so as to robustly elicit a SoA over electrically actuated muscle movements in male and female human subjects. We use time-resolved decoding of subjects' EEG to estimate the time course of neural activity which predicts reported agency on a trial-by-trial basis. Like paradigms which assess SoA over action consequences, we found that the late (post-conscious) neural activity predicts SoA. Unlike typical paradigms, however, we also find patterns of early (sensorimotor) activity with distinct temporal dynamics predicts agency over muscle movements, suggesting that the "neural correlates of agency" may depend on the level of abstraction (i.e., direct sensorimotor feedback versus downstream consequences) most relevant to a given agency judgment. Moreover, fractal analysis of the EEG suggests that SoA-contingent dynamics of neural activity may modulate the sensitivity of the motor system to external input.SIGNIFICANCE STATEMENT The sense of agency, the feeling of "I did that," when directing one's own musculature is a core feature of human experience. We show that we can robustly manipulate the sense of agency over electrically actuated muscle movements, and we investigate the time course of neural activity that predicts the sense of agency over these actuated movements. We find evidence of two distinct neural processes: a transient sequence of patterns that begins in the early sensorineural response to muscle stimulation and a later, sustained signature of agency. These results shed light on the neural mechanisms by which we experience our movements as volitional.


Asunto(s)
Movimiento , Percepción , Humanos , Masculino , Femenino , Teorema de Bayes , Movimiento/fisiología , Encéfalo , Músculos
14.
J Neurosci ; 43(40): 6760-6778, 2023 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-37607820

RESUMEN

Unconscious acquisition of sequence structure from experienced events can lead to explicit awareness of the pattern through extended practice. Although the implicit-to-explicit transition has been extensively studied in humans using the serial reaction time (SRT) task, the subtle neural activity supporting this transition remains unclear. Here, we investigated whether frequency-specific neural signal transfer contributes to this transition. A total of 208 participants (107 females) learned a sequence pattern through a multisession SRT task, allowing us to observe the transitions. Session-by-session measures of participants' awareness for sequence knowledge were conducted during the SRT task to identify the session when the transition occurred. By analyzing time course RT data using switchpoint modeling, we identified an increase in learning benefit specifically at the transition session. Electroencephalogram (EEG)/magnetoencephalogram (MEG) recordings revealed increased theta power in parietal (precuneus) regions one session before the transition (pretransition) and a prefrontal (superior frontal gyrus; SFG) one at the transition session. Phase transfer entropy (PTE) analysis confirmed that directional theta transfer from precuneus → SFG occurred at the pretransition session and its strength positively predicted learning improvement at the subsequent transition session. Furthermore, repetitive transcranial magnetic stimulation (TMS) modulated precuneus theta power and altered transfer strength from precuneus to SFG, resulting in changes in both transition rate and learning benefit at that specific point of transition. Our brain-stimulation evidence supports a role for parietal → prefrontal theta signal transfer in igniting conscious awareness of implicitly acquired knowledge.SIGNIFICANCE STATEMENT There exists a pervasive phenomenon wherein individuals unconsciously acquire sequence patterns from their environment, gradually becoming aware of the underlying regularities through repeated practice. While previous studies have established the robustness of this implicit-to-explicit transition in humans, the refined neural mechanisms facilitating conscious access to implicit knowledge remain poorly understood. Here, we demonstrate that prefrontal activity, known to be crucial for conscious awareness, is triggered by neural signal transfer originating from the posterior brain region, specifically the precuneus. By employing brain stimulation techniques, we establish a causal link between neural signal transfer and the occurrence of awareness. Our findings unveil a mechanism by which implicit knowledge becomes consciously accessible in human cognition.


Asunto(s)
Concienciación , Aprendizaje , Femenino , Humanos , Concienciación/fisiología , Aprendizaje/fisiología , Corteza Prefrontal/fisiología , Tiempo de Reacción/fisiología , Electroencefalografía
15.
Diabetologia ; 67(2): 392-402, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38010533

RESUMEN

AIMS/HYPOTHESIS: Impaired awareness of hypoglycaemia (IAH) in type 1 diabetes may develop through a process referred to as habituation. Consistent with this, a single bout of high intensity interval exercise as a novel stress stimulus improves counterregulatory responses (CRR) to next-day hypoglycaemia, referred to as dishabituation. This longitudinal pilot study investigated whether 4 weeks of high intensity interval training (HIIT) has sustained effects on counterregulatory and symptom responses to hypoglycaemia in adults with type 1 diabetes and IAH. METHODS: HIT4HYPOS was a single-centre, randomised, parallel-group study. Participants were identified using the Scottish Diabetes Research Network (SDRN) and from diabetes outpatient clinics in NHS Tayside, UK. The study took place at the Clinical Research Centre, Ninewells Hospital and Medical School, Dundee, UK. Participants were aged 18-55 years with type 1 diabetes of at least 5 years' duration and HbA1c levels <75 mmol/mol (<9%). They had IAH confirmed by a Gold score ≥4, modified Clarke score ≥4 or Dose Adjustment For Normal Eating [DAFNE] hypoglycaemia awareness rating of 2 or 3, and/or evidence of recurrent hypoglycaemia on flash glucose monitoring. Participants were randomly allocated using a web-based system to either 4 weeks of real-time continuous glucose monitoring (RT-CGM) or RT-CGM+HIIT. Participants and investigators were not masked to group assignment. The HIIT programme was performed for 20 min on a stationary exercise bike three times a week. Hyperinsulinaemic-hypoglycaemic (2.5 mmol/l) clamp studies with assessment of symptoms, hormones and cognitive function were performed at baseline and after 4 weeks of the study intervention. The predefined primary outcome was the difference in hypoglycaemia-induced adrenaline (epinephrine) responses from baseline following RT-CGM or RT-CGM+HIIT. RESULTS: Eighteen participants (nine men and nine women) with type 1 diabetes (median [IQR] duration 27 [18.75-32] years) and IAH were included, with nine participants randomised to each group. Data from all study participants were included in the analysis. During the 4 week intervention there were no significant mean (SEM) differences between RT-CGM and RT-CGM+HIIT in exposure to level 1 (28 [7] vs 22 [4] episodes, p=0.45) or level 2 (9 [3] vs 4 [1] episodes, p=0.29) hypoglycaemia. The CGM-derived mean glucose level, SD of glucose and glucose management indicator (GMI) did not differ between groups. During the hyperinsulinaemic-hypoglycaemic clamp studies, mean (SEM) change from baseline was greater for the noradrenergic responses (RT-CGM vs RT-CGM+HIIT: -988 [447] vs 514 [732] pmol/l, p=0.02) but not the adrenergic responses (-298 [687] vs 1130 [747] pmol/l, p=0.11) in those participants who had undergone RT-CGM+HIIT. There was a benefit of RT-CGM+HIIT for mean (SEM) change from baseline in the glucagon CRR to hypoglycaemia (RT-CGM vs RT-CGM+HIIT: 1 [4] vs 16 [6] ng/l, p=0.01). Consistent with the hormone response, the mean (SEM) symptomatic response to hypoglycaemia (adjusted for baseline) was greater following RT-CGM+HIIT (RT-CGM vs RT-CGM+HIIT: -4 [2] vs 0 [2], p<0.05). CONCLUSIONS/INTERPRETATION: In this pilot clinical trial in people with type 1 diabetes and IAH, we found continuing benefits of HIIT for overall hormonal and symptomatic CRR to subsequent hypoglycaemia. Our findings also suggest that HIIT may improve the glucagon response to insulin-induced hypoglycaemia. TRIAL REGISTRATION: ISRCTN15373978. FUNDING: Sir George Alberti Fellowship from Diabetes UK (CMF) and the Juvenile Diabetes Research Foundation.


Asunto(s)
Diabetes Mellitus Tipo 1 , Entrenamiento de Intervalos de Alta Intensidad , Hipoglucemia , Adulto , Masculino , Humanos , Femenino , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Automonitorización de la Glucosa Sanguínea , Glucagón , Proyectos Piloto , Glucemia/análisis , Hipoglucemia/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Epinefrina
16.
Stroke ; 55(5): 1200-1209, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38545798

RESUMEN

BACKGROUND: Predicting stroke recurrence for individual patients is difficult, but individualized prediction may improve stroke survivors' engagement in self-care. We developed PRERISK: a statistical and machine learning classifier to predict individual risk of stroke recurrence. METHODS: We analyzed clinical and socioeconomic data from a prospectively collected public health care-based data set of 41 975 patients admitted with stroke diagnosis in 88 public health centers over 6 years (2014-2020) in Catalonia-Spain. A new stroke diagnosis at least 24 hours after the index event was considered as a recurrent stroke, which was considered as our outcome of interest. We trained several supervised machine learning models to provide individualized risk over time and compared them with a Cox regression model. Models were trained to predict early, late, and long-term recurrence risk, within 90, 91 to 365, and >365 days, respectively. C statistics and area under the receiver operating characteristic curve were used to assess the accuracy of the models. RESULTS: Overall, 16.21% (5932 of 36 114) of patients had stroke recurrence during a median follow-up of 2.69 years. The most powerful predictors of stroke recurrence were time from previous stroke, Barthel Index, atrial fibrillation, dyslipidemia, age, diabetes, and sex, which were used to create a simplified model with similar performance, together with modifiable vascular risk factors (glycemia, body mass index, high blood pressure, cholesterol, tobacco dependence, and alcohol abuse). The areas under the receiver operating characteristic curve were 0.76 (95% CI, 0.74-0.77), 0.60 (95% CI, 0.58-0.61), and 0.71 (95% CI, 0.69-0.72) for early, late, and long-term recurrence risk, respectively. The areas under the receiver operating characteristic curve of the Cox risk class probability were 0.73 (95% CI, 0.72-0.75), 0.59 (95% CI, 0.57-0.61), and 0.67 (95% CI, 0.66-0.70); machine learning approaches (random forest and AdaBoost) showed statistically significant improvement (P<0.05) over the Cox model for the 3 recurrence time periods. Stroke recurrence curves can be simulated for each patient under different degrees of control of modifiable factors. CONCLUSIONS: PRERISK is a novel approach that provides a personalized and fairly accurate risk prediction of stroke recurrence over time. The model has the potential to incorporate dynamic control of risk factors.

17.
Neuroimage ; 298: 120805, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39173692

RESUMEN

The study of the neural substrates that serve conscious vision is one of the unsolved questions of cognitive neuroscience. So far, consciousness literature has endeavoured to disentangle which brain areas and in what order are involved in giving rise to visual awareness, but the problem of consciousness still remains unsolved. Availing of two different but complementary sources of data (i.e., Fast Optical Imaging and EEG), we sought to unravel the neural dynamics responsible for the emergence of a conscious visual experience. Our results revealed that conscious vision is characterized by a significant increase of activation in extra-striate visual areas, specifically in the Lateral Occipital Complex (LOC), and that, more interestingly, such activity occurred in the temporal window of the ERP component commonly thought to represent the electrophysiological signature of visual awareness, i.e., the Visual Awareness Negativity (VAN). Furthermore, Granger causality analysis, performed to further investigate the flow of activity occurring in the investigated areas, unveiled that neural processes relating to conscious perception mainly originated in LOC and subsequently spread towards visual and motor areas. In general, the results of the present study seem to advocate for an early contribution of LOC in conscious vision, thus suggesting that it could represent a reliable neural correlate of visual awareness. Conversely, striate visual areas, showing awareness-related activity only in later stages of stimulus processing, could be part of the cascade of neural events following awareness emergence.


Asunto(s)
Estado de Conciencia , Electroencefalografía , Lóbulo Occipital , Percepción Visual , Humanos , Estado de Conciencia/fisiología , Percepción Visual/fisiología , Masculino , Femenino , Adulto , Adulto Joven , Lóbulo Occipital/fisiología , Lóbulo Occipital/diagnóstico por imagen , Corteza Visual Primaria/fisiología , Corteza Visual Primaria/diagnóstico por imagen , Mapeo Encefálico , Potenciales Evocados Visuales/fisiología , Corteza Visual/fisiología , Corteza Visual/diagnóstico por imagen , Concienciación/fisiología
18.
Neuroimage ; 297: 120692, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38897398

RESUMEN

Errors typically trigger post-error adjustments aimed at improving subsequent reactions within a single task, but little work has focused on whether these adjustments are task-general or task-specific across different tasks. We collected behavioral and electrophysiological (EEG) data when participants performed a psychological refractory period paradigm. This paradigm required them to complete Task 1 and Task 2 separated by a variable stimulus onset asynchrony (SOA). Behaviorally, post-error slowing and post-error accuracy exhibited task-general features at short SOAs but some task-specific features at long SOAs. EEG results manifest that task-general adjustments had a short-lived effect, whereas task-specific adjustments were long-lasting. Moreover, error awareness specifically conduced to the improvement of subsequent sensory processing and behavior performance in Task 1 (the task where errors occurred). These findings demonstrate that post-error adjustments rely on both transient, task-general interference and longer-lasting, task-specific control mechanisms simultaneously, with error awareness playing a crucial role in determining these mechanisms. We further discuss the contribution of central resources to the task specificity of post-error adjustments.


Asunto(s)
Electroencefalografía , Desempeño Psicomotor , Humanos , Masculino , Femenino , Adulto Joven , Desempeño Psicomotor/fisiología , Adulto , Encéfalo/fisiología , Tiempo de Reacción/fisiología , Periodo Refractario Psicológico/fisiología
19.
Neuroimage ; 297: 120699, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38944172

RESUMEN

After more than 30 years of extensive investigation, impressive progress has been made in identifying the neural correlates of consciousness (NCC). However, the functional role of spatiotemporally distinct consciousness-related neural activity in conscious perception is debated. An influential framework proposed that consciousness-related neural activities could be dissociated into two distinct processes: phenomenal and access consciousness. However, though hotly debated, its authenticity has not been examined in a single paradigm with more informative intracranial recordings. In the present study, we employed a visual awareness task and recorded the local field potential (LFP) of patients with electrodes implanted in cortical and subcortical regions. Overall, we found that the latency of visual awareness-related activity exhibited a bimodal distribution, and the recording sites with short and long latencies were largely separated in location, except in the lateral prefrontal cortex (lPFC). The mixture of short and long latencies in the lPFC indicates that it plays a critical role in linking phenomenal and access consciousness. However, the division between the two is not as simple as the central sulcus, as proposed previously. Moreover, in 4 patients with electrodes implanted in the bilateral prefrontal cortex, early awareness-related activity was confined to the contralateral side, while late awareness-related activity appeared on both sides. Finally, Granger causality analysis showed that awareness-related information flowed from the early sites to the late sites. These results provide the first LFP evidence of neural correlates of phenomenal and access consciousness, which sheds light on the spatiotemporal dynamics of NCC in the human brain.


Asunto(s)
Concienciación , Estado de Conciencia , Humanos , Estado de Conciencia/fisiología , Masculino , Femenino , Adulto , Concienciación/fisiología , Percepción Visual/fisiología , Electrocorticografía , Encéfalo/fisiología , Adulto Joven , Electrodos Implantados , Corteza Prefrontal/fisiología
20.
Neuroimage ; 299: 120799, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39182710

RESUMEN

A long-standing question concerns whether sensory input can reach semantic stages of processing in the absence of attention and awareness. Here, we examine whether the N400, an event related potential associated with semantic processing, can occur under conditions of inattentional blindness. By employing a novel three-phase inattentional blindness paradigm designed to maximise the opportunity for detecting an N400, we found no evidence for it when participants were inattentionally blind to the eliciting stimuli (related and unrelated word pairs). In contrast, participants noticed the same task-irrelevant word pairs when minimal attention was allocated to them, and a small N400 became evident. When the same stimuli were fully attended and relevant to the task, a robust N400 was observed. In addition to univariate ERP measures, multivariate decoding analyses were unable to classify related from unrelated word pairs when observers were inattentionally blind to the words, with decoding reaching above-chance levels only when the words were (at least minimally) attended. By comparison, decoding reached above-chance levels when contrasting word pairs with non-word stimuli, even when participants were inattentionally blind to these stimuli. Our results also replicated several previous studies by finding a "visual awareness negativity" (VAN) that distinguished task-irrelevant stimuli that participants noticed compared with those that were not perceived, and a P3b (or "late positivity") that was evident only when the stimuli were task relevant. Together, our findings suggest that semantic processing might require at least a minimal amount of attention.


Asunto(s)
Atención , Electroencefalografía , Potenciales Evocados , Semántica , Humanos , Masculino , Femenino , Atención/fisiología , Adulto Joven , Electroencefalografía/métodos , Adulto , Potenciales Evocados/fisiología , Encéfalo/fisiología
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