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1.
Cereb Cortex ; 33(5): 1768-1781, 2023 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-35510942

RESUMEN

Under high cognitive demands, older adults tend to resort to simpler, habitual, or model-free decision strategies. This age-related shift in decision behavior has been attributed to deficits in the representation of the cognitive maps, or state spaces, necessary for more complex model-based decision-making. Yet, the neural mechanisms behind this shift remain unclear. In this study, we used a modified 2-stage Markov task in combination with computational modeling and single-trial EEG analyses to establish neural markers of age-related changes in goal-directed decision-making under different demands on the representation of state spaces. Our results reveal that the shift to simpler decision strategies in older adults is due to (i) impairments in the representation of the transition structure of the task and (ii) a diminished signaling of the reward value associated with decision options. In line with the diminished state space hypothesis of human aging, our findings suggest that deficits in goal-directed, model-based behavior in older adults result from impairments in the representation of state spaces of cognitive tasks.


Asunto(s)
Toma de Decisiones , Motivación , Humanos , Anciano , Recompensa , Envejecimiento/psicología , Simulación por Computador
2.
Cereb Cortex ; 33(23): 11247-11256, 2023 11 27.
Artículo en Inglés | MEDLINE | ID: mdl-37782941

RESUMEN

Accumulated evidence from animal studies suggests a role for the neuromodulator dopamine in memory processes, particularly under conditions of novelty or reward. Our understanding of how dopaminergic modulation impacts spatial representations and spatial memory in humans remains limited. Recent evidence suggests age-specific regulation effects of dopamine pharmacology on activity in the medial temporal lobe, a key region for spatial memory. To which degree this modulation affects spatially patterned medial temporal representations remains unclear. We reanalyzed recent data from a pharmacological dopamine challenge during functional brain imaging combined with a virtual object-location memory paradigm to assess the effect of Levodopa, a dopamine precursor, on grid-like activity in the entorhinal cortex. We found that Levodopa impaired grid cell-like representations in a sample of young adults (n = 55, age = 26-35 years) in a novel environment, accompanied by reduced spatial memory performance. We observed no such impairment when Levodopa was delivered to participants who had prior experience with the task. These results are consistent with a role of dopamine in modulating the encoding of novel spatial experiences. Our results suggest that dopamine signaling may play a larger role in shaping ongoing spatial representations than previously thought.


Asunto(s)
Levodopa , Aprendizaje Espacial , Animales , Humanos , Adulto Joven , Adulto , Levodopa/farmacología , Dopamina , Corteza Entorrinal/fisiología , Memoria Espacial
3.
Neuroimage ; 279: 120327, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37582418

RESUMEN

Selective use of new information is crucial for adaptive decision-making. Combining a gamble bidding task with assessing cortical responses using functional near-infrared spectroscopy (fNIRS), we investigated potential effects of information valence on behavioral and neural processes of belief and value updating during uncertainty reduction in young adults. By modeling changes in the participants' expressed subjective values using a Bayesian model, we dissociated processes of (i) updating beliefs about statistical properties of the gamble, (ii) updating values of a gamble based on new information about its winning probabilities, as well as (iii) expectancy violation. The results showed that participants used new information to update their beliefs and values about the gambles in a quasi-optimal manner, as reflected in the selective updating only in situations with reducible uncertainty. Furthermore, their updating was valence-dependent: information indicating an increase in winning probability was underweighted, whereas information about a decrease in winning probability was updated in good agreement with predictions of the Bayesian decision theory. Results of model-based and moderation analyses showed that this valence-dependent asymmetry was associated with a distinct contribution of expectancy violation, besides belief updating, to value updating after experiencing new positive information regarding winning probabilities. In line with the behavioral results, we replicated previous findings showing involvements of frontoparietal brain regions in the different components of updating. Furthermore, this study provided novel results suggesting a valence-dependent recruitment of brain regions. Individuals with stronger oxyhemoglobin responses during value updating was more in line with predictions of the Bayesian model while integrating new information that indicates an increase in winning probability. Taken together, this study provides first results showing expectancy violation as a contributing factor to sub-optimal valence-dependent updating during uncertainty reduction and suggests limitations of normative Bayesian decision theory.


Asunto(s)
Mapeo Encefálico , Encéfalo , Adulto Joven , Humanos , Incertidumbre , Teorema de Bayes , Encéfalo/fisiología , Probabilidad , Toma de Decisiones/fisiología
4.
Neuroimage ; 273: 120099, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37037380

RESUMEN

Aging is associated with changes in spatial navigation behavior. In addition to an overall performance decline, older adults tend to rely more on proximal location cue information than on environmental boundary information during spatial navigation compared to young adults. The fact that older adults are more susceptible to errors during spatial navigation might be partly attributed to deficient dopaminergic modulation of hippocampal and striatal functioning. Hence, elevating dopamine levels might differentially modulate spatial navigation and memory performance in young and older adults. In this work, we administered levodopa (L-DOPA) in a double-blind within-subject, placebo-controlled design and recorded functional neuroimaging while young and older adults performed a 3D spatial navigation task in which boundary geometry or the position of a location cue were systematically manipulated. An age by intervention interaction on the neural level revealed an upregulation of brain responses in older adults and a downregulation of responses in young adults within the medial temporal lobe (including hippocampus and parahippocampus) and brainstem, during memory retrieval. Behaviorally, L-DOPA had no effect on older adults' overall memory performance; however, older adults whose spatial memory improved under L-DOPA also showed a shift towards more boundary processing under L-DOPA. In young adults, L-DOPA induced a decline in spatial memory performance in task-naïve participants. These results are consistent with the inverted-U-shaped hypothesis of dopamine signaling and cognitive function and suggest that increasing dopamine availability improves hippocampus-dependent place learning in some older adults.


Asunto(s)
Dopamina , Navegación Espacial , Anciano , Humanos , Adulto Joven , Hipocampo/fisiología , Levodopa/farmacología , Memoria Espacial/fisiología , Navegación Espacial/fisiología , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/fisiología , Método Doble Ciego
5.
Neuroimage ; 264: 119670, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36243268

RESUMEN

Previous studies indicate a role of dopamine in spatial navigation. Although neural representations of direction are an important aspect of spatial cognition, it is not well understood whether dopamine directly affects these representations, or only impacts other aspects of spatial brain function. Moreover, both dopamine and spatial cognition decline sharply during age, raising the question which effect dopamine has on directional signals in the brain of older adults. To investigate these questions, we used a double-blind cross-over L-DOPA/Placebo intervention design in which 43 younger and 37 older adults navigated in a virtual spatial environment while undergoing functional magnetic resonance imaging (fMRI). We studied the effect of L-DOPA, a dopamine precursor, on fMRI activation patterns that encode spatial walking directions that have previously been shown to lose specificity with age. This was done in predefined regions of interest, including the early visual cortex, retrosplenial cortex, and hippocampus. Classification of brain activation patterns associated with different walking directions was improved across all regions following L-DOPA administration, suggesting that dopamine broadly enhances neural representations of direction. No evidence for differences between regions was found. In the hippocampus these results were found in both age groups, while in the retrosplenial cortex they were only observed in younger adults. Taken together, our study provides evidence for a link between dopamine and the specificity of neural responses during spatial navigation. SIGNIFICANCE STATEMENT: The sense of direction is an important aspect of spatial navigation, and neural representations of direction can be found throughout a large network of space-related brain regions. But what influences how well these representations track someone's true direction? Using a double-blind cross-over L-DOPA/Placebo intervention design, we find causal evidence that the neurotransmitter dopamine impacts the fidelity of direction selective neural representations in the human hippocampus and retrosplenial cortex. Interestingly, the effect of L-DOPA was either equally present or even smaller in older adults, despite the well-known age related decline of dopamine. These results provide novel insights into how dopamine shapes the neural representations that underlie spatial navigation.


Asunto(s)
Levodopa , Navegación Espacial , Humanos , Anciano , Levodopa/farmacología , Dopamina/fisiología , Navegación Espacial/fisiología , Mapeo Encefálico/métodos , Imagen por Resonancia Magnética
6.
Alcohol Clin Exp Res ; 46(4): 667-681, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35257381

RESUMEN

BACKGROUND: While drinking alcohol, one must choose between the immediate rewarding effects and the delayed reward of a healthier lifestyle. Individuals differ in their devaluation of a delayed reward based on the time required to receive it, i.e., delay discounting (DD). Previous studies have shown that adolescents discount more steeply than adults and that steeper DD is associated with heavier alcohol use in both groups. METHODS: In a large-scale longitudinal study, we investigated whether higher rates of DD are an antecedent or a consequence of alcohol use during adolescent development. As part of the IMAGEN project, 2220 adolescents completed the Monetary Choice Questionnaire as a DD measure, the Alcohol Use Disorders Identification Test, and the Timeline Follow Back interview at ages 14, 16, 18, and 22. Bivariate latent growth curve models were applied to investigate the relationship between DD and drinking. To explore the consequences of drinking, we computed the cumulative alcohol consumption and correlated it with the development of discounting. A subsample of 221 participants completed an intertemporal choice task (iTeCh) during functional magnetic resonance imaging at ages 14, 16, and 18. Repeated-measures ANOVA was used to differentiate between high-risk and low-risk drinkers on the development of neural processing during intertemporal choices. RESULTS: Overall, high rates of DD at age 14 predicted a greater increase in drinking over 8 years. In contrast, on average, moderate alcohol use did not affect DD from ages 14 to 22. Of note, we found indicators for less brain activity in top-down control areas during intertemporal choices in the participants who drank more. CONCLUSIONS: Steep DD was shown to be a predictor rather than a consequence of alcohol use in low-level drinking adolescents. Important considerations for future longitudinal studies are the sampling strategies to be used and the reliability of the assessments.


Asunto(s)
Alcoholismo , Descuento por Demora , Adolescente , Adulto , Humanos , Estudios Longitudinales , Reproducibilidad de los Resultados , Recompensa , Adulto Joven
7.
Sensors (Basel) ; 22(4)2022 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-35214306

RESUMEN

In the early 2020s, the coronavirus pandemic brought the notion of remotely connected care to the general population across the globe. Oftentimes, the timely provisioning of access to and the implementation of affordable care are drivers behind tele-healthcare initiatives. Tele-healthcare has already garnered significant momentum in research and implementations in the years preceding the worldwide challenge of 2020, supported by the emerging capabilities of communication networks. The Tactile Internet (TI) with human-in-the-loop is one of those developments, leading to the democratization of skills and expertise that will significantly impact the long-term developments of the provisioning of care. However, significant challenges remain that require today's communication networks to adapt to support the ultra-low latency required. The resulting latency challenge necessitates trans-disciplinary research efforts combining psychophysiological as well as technological solutions to achieve one millisecond and below round-trip times. The objective of this paper is to provide an overview of the benefits enabled by solving this network latency reduction challenge by employing state-of-the-art Time-Sensitive Networking (TSN) devices in a testbed, realizing the service differentiation required for the multi-modal human-machine interface. With completely new types of services and use cases resulting from the TI, we describe the potential impacts on remote surgery and remote rehabilitation as examples, with a focus on the future of tele-healthcare in rural settings.


Asunto(s)
Infecciones por Coronavirus , Telemedicina , Atención a la Salud , Humanos , Internet , Pandemias , Telemedicina/métodos , Tacto
8.
J Neurophysiol ; 125(4): 1382-1395, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33689490

RESUMEN

Performing a goal-directed movement consists of a chain of complex preparatory mechanisms. Such planning especially requires integration (or binding) of various action features, a process that has been conceptualized in the "theory of event coding." Theoretical considerations and empirical research suggest that these processes are subject to developmental effects from adolescence to adulthood. The aim of the present study was to investigate age-related modulations in action feature binding processes and to shed light on underlying neurophysiological development from preadolescence to early adulthood. We examined a group of healthy participants (n = 61) between 10 and 30 yr of age, who performed a task that requires a series of bimanual response selections in an embedded paradigm. For an in-depth analysis of the underlying neural correlates, we applied EEG signal decomposition together with source localization analyses. Behavioral results across the whole group did not show binding effects in reaction times but in intraindividual response variability. From age 10 to 30 yr, there was a decrease in reaction times and reaction time variability but no age-related effect in action file binding. The latter were corroborated by Bayesian data analyses. On the brain level, the developmental effects on response selection were associated with activation modulations in the superior parietal cortex (BA7). The results show that mechanisms of action execution and speed, but not those of action feature binding, are subject to age-related changes between the age of 10 and 30 yr.NEW & NOTEWORTHY Different aspects of an action need to be integrated to allow smooth unfolding of behavior. We examine developmental effects in these processes and show that mechanisms of action execution and speed, but not those of action feature binding, are subject to age-related changes between the age of 10 and 30 yr.


Asunto(s)
Desarrollo Humano/fisiología , Actividad Motora/fisiología , Lóbulo Parietal/fisiología , Desempeño Psicomotor/fisiología , Tiempo de Reacción/fisiología , Adolescente , Adulto , Factores de Edad , Niño , Electroencefalografía , Femenino , Humanos , Masculino , Adulto Joven
9.
J Neurophysiol ; 124(1): 207-217, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32233902

RESUMEN

Attentional control is crucial for selectively attending to relevant information when our brain is confronted with a multitude of sensory signals. Graph-theoretical measures provide a powerful tool for investigating the efficiency of brain network communication in separating and integrating information. Albeit, it has been demonstrated that anodal transcranial direct current stimulation (atDCS) can boost auditory attention in situations with high control demands, its effect on neurophysiological mechanisms of functional brain network communication in situations when attentional focus conflicts with perceptual saliency remain unclear. This study investigated the effects of atDCS on network connectivity and θ-oscillatory power under different levels of attentional-perceptual conflict. We hypothesized that the benefit of atDCS on network communication efficiency would be particularly apparent in conditions requiring high attentional control. Thirty young adults participated in a dichotic listening task with intensity manipulation, while EEG activity was recorded. In a cross-over design, participants underwent right frontal atDCS and sham stimulations in two separate sessions. Time-frequency decomposition and graph-theoretical analyses of network efficiency (using "small-world" properties) were used to quantify θ-oscillatory power and brain network efficiency, respectively. The atDCS-induced effect on task efficiency in the most demanding condition was mirrored only by an increase in network efficiency during atDCS compared with the sham stimulation. These findings are corroborated by Bayesian analyses. AtDCS-induced performance enhancement under high levels of attentional-perceptual conflicts is accompanied by an increase in network efficiency. Graph-theoretical measures can serve as a metric to quantify the effects of noninvasive brain stimulation on the separation and integration of information in the brain.NEW & NOTEWORTHY As compared with sham stimulation, application of atDCS enhances θ-oscillation-based network efficiency, but it has no impact on θ-oscillation power. Individual differences in θ-oscillation-based network efficiency correlated with performance efficiency under the sham stimulation.


Asunto(s)
Atención/fisiología , Percepción Auditiva/fisiología , Corteza Cerebral/fisiología , Conectoma , Red Nerviosa/fisiología , Ritmo Teta/fisiología , Estimulación Transcraneal de Corriente Directa , Adulto , Femenino , Humanos , Masculino , Adulto Joven
10.
Neuroimage ; 199: 217-227, 2019 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-31129304

RESUMEN

Successful action control requires the ability to attend to relevant sensory signals in the environment. This, however, can be complicated when different sensory inputs compete for the brain's limited resources. Under such conditions, sensory processes interact with top-down attention to selectively process goal-relevant stimuli, while inhibiting irrelevant or distracting sensory signals. In the current study, we set out to provide causal mechanistic insights for whether and how prefrontal regions are involved in resolving attentional-perceptual conflicts. To this end, we applied atDCS and examined neurophysiological processes of selective auditory perception. To evaluate whether atDCS differentially affects intermingled neurophysiological subprocesses involved during conflict resolution, we decomposed the EEG data using residue iteration decomposition (RIDE). We show that the right prefrontal regions are causally involved in resolving attentional-perceptual conflicts and that atDCS increases the efficacy to do so. The data show that dissociable neurophysiological signals are specifically affected by atDCS. Conflict resolution processes that involve inhibition of competing stimuli and response evaluation and are associated with right middle frontal gyrus (BA46) seem to become intensified by atDCS during the resolution of attentional-perceptual conflicts. After stimulation the early stimulus processing level was also less prone to sensory conflicts, but this alone could not explain the increased behavioral efficacy associated with atDCS. These observed effects likely reflect changes in neuronal gain control mechanisms. Taken together, results of this study may have implications for treating attentional hyperactivity disorder, for which pharmacological intervention is currently the common therapeutic approach.


Asunto(s)
Atención/fisiología , Percepción Auditiva/fisiología , Mapeo Encefálico , Conflicto Psicológico , Corteza Prefrontal/fisiología , Estimulación Transcraneal de Corriente Directa , Adulto , Electroencefalografía , Femenino , Humanos , Masculino , Adulto Joven
11.
Neuroimage ; 197: 414-424, 2019 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-31054351

RESUMEN

Older adults experience difficulties in daily situations that require flexible information selection in the presence of multiple competing sensory inputs, like for instance multi-talker situations. Modulations of rhythmic neural activity in the alpha-beta (8-30 Hz) frequency range in posterior brain areas have been established as a cross-modal neural correlate of selective attention. However, research linking compromised auditory selective attention to changes in rhythmic neural activity in aging is sparse. We tested younger (n = 25; 22-35 years) and older adults (n = 26; 63-76 years) in an attention modulated dichotic listening task. In this, two streams of highly similar auditory input were simultaneously presented to participants' both ears (i.e., dichotically) while attention had to be focused on the input to only one ear (i.e. target) and the other, distracting information had to be ignored. We here demonstrate a link between severely compromised auditory selective attention in aging and a partial reorganization of attention-related rhythmic neural responses. In particular, in old age we observed a shift from a self-initiated, preparatory modulation of lateralized alpha rhythmic activity to an externally driven response in the alpha-beta range. Critically, moment-to-moment fluctuations in the age-specific patterns of self-initiated and externally driven lateralized rhythmic activity were associated with behavioral performance. We conclude that adult age differences in spatial selective attention likely derive from a functional reorganization of rhythmic neural activity within the aging brain.


Asunto(s)
Envejecimiento/fisiología , Ritmo alfa , Atención/fisiología , Percepción Auditiva/fisiología , Lateralidad Funcional/fisiología , Estimulación Acústica , Adulto , Anciano , Pruebas de Audición Dicótica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
12.
Nature ; 504(7480): 432-6, 2013 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-24213632

RESUMEN

Myocardial infarction, a leading cause of death in the Western world, usually occurs when the fibrous cap overlying an atherosclerotic plaque in a coronary artery ruptures. The resulting exposure of blood to the atherosclerotic material then triggers thrombus formation, which occludes the artery. The importance of genetic predisposition to coronary artery disease and myocardial infarction is best documented by the predictive value of a positive family history. Next-generation sequencing in families with several affected individuals has revolutionized mutation identification. Here we report the segregation of two private, heterozygous mutations in two functionally related genes, GUCY1A3 (p.Leu163Phefs*24) and CCT7 (p.Ser525Leu), in an extended myocardial infarction family. GUCY1A3 encodes the α1 subunit of soluble guanylyl cyclase (α1-sGC), and CCT7 encodes CCTη, a member of the tailless complex polypeptide 1 ring complex, which, among other functions, stabilizes soluble guanylyl cyclase. After stimulation with nitric oxide, soluble guanylyl cyclase generates cGMP, which induces vasodilation and inhibits platelet activation. We demonstrate in vitro that mutations in both GUCY1A3 and CCT7 severely reduce α1-sGC as well as ß1-sGC protein content, and impair soluble guanylyl cyclase activity. Moreover, platelets from digenic mutation carriers contained less soluble guanylyl cyclase protein and consequently displayed reduced nitric-oxide-induced cGMP formation. Mice deficient in α1-sGC protein displayed accelerated thrombus formation in the microcirculation after local trauma. Starting with a severely affected family, we have identified a link between impaired soluble-guanylyl-cyclase-dependent nitric oxide signalling and myocardial infarction risk, possibly through accelerated thrombus formation. Reversing this defect may provide a new therapeutic target for reducing the risk of myocardial infarction.


Asunto(s)
Susceptibilidad a Enfermedades/metabolismo , Infarto del Miocardio/metabolismo , Óxido Nítrico/metabolismo , Transducción de Señal , Animales , Chaperonina con TCP-1/genética , Chaperonina con TCP-1/metabolismo , GMP Cíclico/metabolismo , Exoma/genética , Femenino , Predisposición Genética a la Enfermedad , Guanilato Ciclasa/deficiencia , Guanilato Ciclasa/genética , Guanilato Ciclasa/metabolismo , Células HEK293 , Humanos , Masculino , Ratones , Mutación/genética , Infarto del Miocardio/genética , Infarto del Miocardio/fisiopatología , Linaje , Activación Plaquetaria , Receptores Citoplasmáticos y Nucleares/deficiencia , Receptores Citoplasmáticos y Nucleares/genética , Receptores Citoplasmáticos y Nucleares/metabolismo , Reproducibilidad de los Resultados , Solubilidad , Guanilil Ciclasa Soluble , Trombosis/metabolismo , Vasodilatación
13.
Cereb Cortex ; 28(11): 3764-3774, 2018 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-29028956

RESUMEN

Older decision-makers may capitalize on their greater experiences in financial decisions and by this offset decline in cognitive abilities. However, this pattern of results should reverse in situations that place high demands on cognitive control functions. In this study, we investigated how decision conflict affects the neural mechanisms of intertemporal decision-making in younger and older adults. To individually adjust the level of decision conflict we determined the indifference point (IDP) in intertemporal decision-making for each participant. During functional magnetic resonance imaging, participants performed choice options close to their IDP (high conflict) or far away from the IDP (low conflict). In younger adults, decision conflict leads to reduced delay discounting and lower discount rates are associated with higher working memory (WM) capacity. In older adults, high decision conflict is associated with enhanced discounting, hypoactivation in the ventral striatum as well diminished ventral striatal representations of differences in subjective values. Taken together, our results show that under enhanced decision conflict, younger adults engage in a more reflective decision mode that reflects individual differences in WM capacity. In contrast, older adults get more present-oriented under high demands on cognitive control and this decision bias is associated with changes in striatal value signaling.


Asunto(s)
Encéfalo/fisiología , Conflicto Psicológico , Descuento por Demora/fisiología , Adulto , Factores de Edad , Anciano , Mapeo Encefálico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Memoria a Corto Plazo/fisiología , Recompensa , Adulto Joven
14.
Neuroimage ; 167: 384-395, 2018 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-29191478

RESUMEN

Adaptive behavior in daily life often requires the ability to acquire and represent sequential contingencies between actions and the associated outcomes. Although accumulating evidence implicates the role of dorsolateral prefrontal cortex (dlPFC) in complex value-based learning and decision-making, direct evidence for involvements of this region in integrating information across sequential decision states is still scarce. Using a 3-stage deterministic Markov decision task, here we applied offline, inhibitory low-frequency 1-Hz repetitive transcranial magnetic stimulation (rTMS) over the left dlPFC in young male adults (n = 31, mean age = 23.8 years, SD = 2.5 years) in a within-subject cross-over design to study the roles of this region in influencing value-based sequential decision-making. In two separate sessions, each participant received 1-Hz rTMS stimulation either over the left dlPFC or over the vertex. The results showed that transiently inhibiting the left dlPFC impaired choice accuracy, particularly in situations in which the acquisition of sequential transitions between decision states and temporally lagged action-outcome contingencies played a greater role. Estimating parameters of a diffusion model from behavioral choices, we found that the diffusion drift rate, which reflects the efficiency of information integration, was attenuated by the stimulation. Moreover, the effects of rTMS interacted with session: individuals who could not efficiently integrate information across sequential states in the first session due to disrupted dlPFC function also could not catch up in performance during the second session with those individuals who could learn sequential transitions with intact dlPFC function in the first session. Taken together, our findings suggest that the left dlPFC is crucially involved in the acquisition of complex sequential relations and in the potential of such learning.


Asunto(s)
Conducta de Elección/fisiología , Aprendizaje/fisiología , Corteza Prefrontal/fisiología , Desempeño Psicomotor/fisiología , Recompensa , Estimulación Magnética Transcraneal/métodos , Adulto , Estudios Cruzados , Humanos , Masculino , Inhibición Neural/fisiología , Adulto Joven
15.
Hum Brain Mapp ; 39(12): 5050-5061, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30133058

RESUMEN

The ability to selectively perceive and flexibly attend to relevant sensory signals in the environment is essential for action control. Whereas neuromodulation of sensory or attentional processing is often investigated, neuromodulation of interactive effects between perception and attention, that is, high attentional control demand when the relevant sensory information is perceptually less salient than the irrelevant one, is not well understood. To fill this gap, this pharmacological-electroencephalogram (EEG) study applied an intensity-modulated, focused-attention dichotic listening paradigm together with temporal EEG signal decomposition and source localization analyses. We used a double-blind MPH/placebo crossover design to delineate the effects of methylphenidate (MPH)-a dopamine/norepinephrine transporter blocker-on the resolution of perceptual-attentional conflicts, when perceptual saliency and attentional focus favor opposing ears, in healthy young adults. We show that MPH increased behavioral performance specifically in the condition with the most pronounced conflict between perceptual saliency and attentional focus. On the neurophysiological level, MPH effects in line with the behavioral data were observed after accounting for intraindividual variability in the signal. More specifically, MPH did not show an effect on stimulus-related processes but modulated the onset latency of processes between stimulus evaluation and responding. These modulations were further shown to be associated with activation differences in the temporoparietal junction (BA40) and the superior parietal cortex (BA7) and may reflect neuronal gain modulation principles. The findings provide mechanistic insights into the role of modulated dopamine/norepinephrine transmitter systems for the interactions between perception and attention.


Asunto(s)
Atención/efectos de los fármacos , Percepción Auditiva/efectos de los fármacos , Corteza Cerebral/efectos de los fármacos , Conflicto Psicológico , Electroencefalografía/métodos , Potenciales Evocados/fisiología , Metilfenidato/farmacología , Inhibidores de la Captación de Neurotransmisores/farmacología , Desempeño Psicomotor/efectos de los fármacos , Adulto , Estudios Cruzados , Inhibidores de Captación de Dopamina/farmacología , Método Doble Ciego , Femenino , Humanos , Masculino , Metilfenidato/administración & dosificación , Inhibidores de la Captación de Neurotransmisores/administración & dosificación , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/antagonistas & inhibidores , Adulto Joven
16.
Int J Neuropsychopharmacol ; 21(7): 649-655, 2018 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-29618012

RESUMEN

Background: Perceptual decision making is the process through which available sensory information is gathered and processed to guide our choices. However, the neuropsychopharmacological basis of this important cognitive function is largely elusive. Yet, theoretical considerations suggest that the dopaminergic system may play an important role. Methods: In a double-blind, randomized, placebo-controlled study design, we examined the effect of methylphenidate in 2 dosages (0.25 mg/kg and 0.5 mg/kg body weight) in separate groups of healthy young adults. We used a moving dots task in which the coherency of the direction of moving dots stimuli was manipulated in 3 levels (5%, 15%, and 35%). Drift diffusion modelling was applied to behavioral data to capture subprocesses of perceptual decision making. Results: The findings show that only the drift rate (v), reflecting the efficiency of sensory evidence accumulation, but not the decision criterion threshold (a) or the duration of nondecisional processes (Ter), is affected by methylphenidate vs placebo administration. Compared with placebo, administering 0.25 mg/kg methylphenidate increased v, but only in the 35% coherence condition. Administering 0.5 mg/kg methylphenidate did not induce modulations. Conclusions: The data suggest that dopamine selectively modulates the efficacy of evidence accumulation during perceptual decision making. This modulation depends on 2 factors: (1) the degree to which the dopaminergic system is modulated using methylphenidate (i.e., methylphenidate dosage) and (2) the signal-to-noise ratio of the visual information. Dopamine affects sensory evidence accumulation only when dopamine concentration is not shifted beyond an optimal level and the incoming information is less noisy.


Asunto(s)
Toma de Decisiones/efectos de los fármacos , Inhibidores de Captación de Dopamina/farmacología , Metilfenidato/farmacología , Percepción de Movimiento/efectos de los fármacos , Reconocimiento Visual de Modelos/fisiología , Desempeño Psicomotor/efectos de los fármacos , Adulto , Inhibidores de Captación de Dopamina/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Masculino , Metilfenidato/administración & dosificación , Adulto Joven
17.
PLoS Comput Biol ; 13(5): e1005418, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28486504

RESUMEN

Normative models of human cognition often appeal to Bayesian filtering, which provides optimal online estimates of unknown or hidden states of the world, based on previous observations. However, in many cases it is necessary to optimise beliefs about sequences of states rather than just the current state. Importantly, Bayesian filtering and sequential inference strategies make different predictions about beliefs and subsequent choices, rendering them behaviourally dissociable. Taking data from a probabilistic reversal task we show that subjects' choices provide strong evidence that they are representing short sequences of states. Between-subject measures of this implicit sequential inference strategy had a neurobiological underpinning and correlated with grey matter density in prefrontal and parietal cortex, as well as the hippocampus. Our findings provide, to our knowledge, the first evidence for sequential inference in human cognition, and by exploiting between-subject variation in this measure we provide pointers to its neuronal substrates.


Asunto(s)
Cognición/fisiología , Lóbulo Frontal/fisiología , Hipocampo/fisiología , Lóbulo Parietal/fisiología , Adulto , Anciano , Teorema de Bayes , Biología Computacional , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Neurológicos , Análisis y Desempeño de Tareas , Adulto Joven
18.
Proc Natl Acad Sci U S A ; 112(24): 7593-8, 2015 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-26034283

RESUMEN

Better-performing younger adults typically express greater brain signal variability relative to older, poorer performers. Mechanisms for age and performance-graded differences in brain dynamics have, however, not yet been uncovered. Given the age-related decline of the dopamine (DA) system in normal cognitive aging, DA neuromodulation is one plausible mechanism. Hence, agents that boost systemic DA [such as d-amphetamine (AMPH)] may help to restore deficient signal variability levels. Furthermore, despite the standard practice of counterbalancing drug session order (AMPH first vs. placebo first), it remains understudied how AMPH may interact with practice effects, possibly influencing whether DA up-regulation is functional. We examined the effects of AMPH on functional-MRI-based blood oxygen level-dependent (BOLD) signal variability (SD(BOLD)) in younger and older adults during a working memory task (letter n-back). Older adults expressed lower brain signal variability at placebo, but met or exceeded young adult SD(BOLD) levels in the presence of AMPH. Drug session order greatly moderated change-change relations between AMPH-driven SD(BOLD) and reaction time means (RT(mean)) and SDs (RT(SD)). Older adults who received AMPH in the first session tended to improve in RT(mean) and RT(SD) when SD(BOLD) was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SD(BOLD) decreased (for RT(mean)) or no effect at all (for RT(SD)). The present findings support the hypothesis that age differences in brain signal variability reflect aging-induced changes in dopaminergic neuromodulation. The observed interactions among AMPH, age, and session order highlight the state- and practice-dependent neurochemical basis of human brain dynamics.


Asunto(s)
Envejecimiento/fisiología , Envejecimiento/psicología , Encéfalo/efectos de los fármacos , Encéfalo/fisiología , Dextroanfetamina/farmacología , Memoria a Corto Plazo/efectos de los fármacos , Adulto , Anciano , Dopamina/fisiología , Método Doble Ciego , Femenino , Neuroimagen Funcional , Humanos , Análisis de los Mínimos Cuadrados , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Modelos Neurológicos , Modelos Psicológicos , Análisis Multivariante , Adulto Joven
19.
Cogn Affect Behav Neurosci ; 17(2): 406-421, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28050805

RESUMEN

In this study, we investigated the interplay of habitual (model-free) and goal-directed (model-based) decision processes by using a two-stage Markov decision task in combination with event-related potentials (ERPs) and computational modeling. To manipulate the demands on model-based decision making, we applied two experimental conditions with different probabilities of transitioning from the first to the second stage of the task. As we expected, when the stage transitions were more predictable, participants showed greater model-based (planning) behavior. Consistent with this result, we found that stimulus-evoked parietal (P300) activity at the second stage of the task increased with the predictability of the state transitions. However, the parietal activity also reflected model-free information about the expected values of the stimuli, indicating that at this stage of the task both types of information are integrated to guide decision making. Outcome-related ERP components only reflected reward-related processes: Specifically, a medial prefrontal ERP component (the feedback-related negativity) was sensitive to negative outcomes, whereas a component that is elicited by reward (the feedback-related positivity) increased as a function of positive prediction errors. Taken together, our data indicate that stimulus-locked parietal activity reflects the integration of model-based and model-free information during decision making, whereas feedback-related medial prefrontal signals primarily reflect reward-related decision processes.


Asunto(s)
Encéfalo/fisiología , Toma de Decisiones/fisiología , Objetivos , Hábitos , Algoritmos , Simulación por Computador , Electroencefalografía , Potenciales Evocados , Función Ejecutiva/fisiología , Retroalimentación , Femenino , Humanos , Masculino , Cadenas de Markov , Modelos Neurológicos , Pruebas Neuropsicológicas , Recompensa , Percepción Visual/fisiología , Adulto Joven
20.
Dev Sci ; 19(5): 699-709, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-26074422

RESUMEN

Observational learning is an important mechanism for cognitive and social development. However, the neurophysiological mechanisms underlying observational learning in children are not well understood. In this study, we used a probabilistic reward-based observational learning paradigm to compare behavioral and electrophysiological markers of individual and observational reinforcement learning in 8- to 10-year-old children. Specifically, we manipulated the amount of observable information as well as children's similarity in age to the observed person (same-aged child vs. adult) to examine the effects of similarity in age on the integration of observed information in children. We show that the feedback-related negativity (FRN) during individual reinforcement learning reflects the valence of outcomes of own actions. Furthermore, we found that the feedback-related negativity during observational reinforcement learning (oFRN) showed a similar distinction between outcome valences of observed actions. This suggests that the oFRN can serve as a measure of observational learning in middle childhood. Moreover, during observational learning children profited from the additional social information and imitated the choices of their own peers more than those of adults, indicating that children have a tendency to conform more with similar others (e.g. their own peers) compared to dissimilar others (adults). Taken together, our results show that children can benefit from integrating observable information and that oFRN may serve as a measure of observational learning in children.


Asunto(s)
Fenómenos Electrofisiológicos , Aprendizaje/fisiología , Influencia de los Compañeros , Recompensa , Adulto , Factores de Edad , Biorretroalimentación Psicológica , Niño , Conducta de Elección , Potenciales Evocados , Humanos , Motivación , Neurorretroalimentación , Observación , Adulto Joven
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