| 1. |
- Barausse, Enrico, et al.
(författare)
-
Prospects for fundamental physics with LISA
- 2020
-
Ingår i: General Relativity and Gravitation. - : SPRINGER/PLENUM PUBLISHERS. - 0001-7701 .- 1572-9532. ; 52:8
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this paper, which is of programmatic rather than quantitative nature, we aim to further delineate and sharpen the future potential of the LISA mission in the area of fundamental physics. Given the very broad range of topics that might be relevant to LISA,we present here a sample of what we view as particularly promising fundamental physics directions. We organize these directions through a "science-first" approach that allows us to classify how LISA data can inform theoretical physics in a variety of areas. For each of these theoretical physics classes, we identify the sources that are currently expected to provide the principal contribution to our knowledge, and the areas that need further development. The classification presented here should not be thought of as cast in stone, but rather as a fluid framework that is amenable to change with the flow of new insights in theoretical physics.
|
|
| 2. |
- Guitart-Masip, Marc, et al.
(författare)
-
Differential, but not opponent, effects of L-DOPA and citalopram on action learning with reward and punishment
- 2014
-
Ingår i: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 231:5, s. 955-966
-
Tidskriftsartikel (refereegranskat)abstract
- Decision-making involves two fundamental axes of control namely valence, spanning reward and punishment, and action, spanning invigoration and inhibition. We recently exploited a go/no-go task whose contingencies explicitly decouple valence and action to show that these axes are inextricably coupled during learning. This results in a disadvantage in learning to go to avoid punishment and in learning to no-go to obtain a reward. The neuromodulators dopamine and serotonin are likely to play a role in these asymmetries: Dopamine signals anticipation of future rewards and is also involved in an invigoration of motor responses leading to reward, but it also arbitrates between different forms of control. Conversely, serotonin is implicated in motor inhibition and punishment processing. To investigate the role of dopamine and serotonin in the interaction between action and valence during learning. We combined computational modeling with pharmacological manipulation in 90 healthy human volunteers, using levodopa and citalopram to affect dopamine and serotonin, respectively. We found that, after administration of levodopa, action learning was less affected by outcome valence when compared with the placebo and citalopram groups. This highlights in this context a predominant effect of levodopa in controlling the balance between different forms of control. Citalopram had distinct effects, increasing participants' tendency to perform active responses independent of outcome valence, consistent with a role in decreasing motor inhibition. Our findings highlight the rich complexities of the roles played by dopamine and serotonin during instrumental learning.
|
|
| 3. |
- Deserno, Lorenz, et al.
(författare)
-
Ventral striatal dopamine reflects behavioral and neural signatures of model-based control during sequential decision making
- 2015
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:5, s. 1595-1600
-
Tidskriftsartikel (refereegranskat)abstract
- Whether humans make choices based on a deliberative “model-based” or a reflexive “model-free” system of behavioral control remains an ongoing topic of research. Dopamine is implicated in motivational drive as well as in planning future actions. Here, we demonstrate that higher presynaptic dopamine in human ventral striatum is associated with more pronounced model-based behavioral control, as well as an enhanced coding of model-based signatures in lateral prefrontal cortex and diminished coding of model-free learning signals in ventral striatum. Our study links ventral striatal presynaptic dopamine to a balance between two distinct modes of behavioral control in humans. The findings have implications for neuropsychiatric diseases associated with alterations of dopamine neurotransmission and a disrupted balance of behavioral control.Dual system theories suggest that behavioral control is parsed between a deliberative “model-based” and a more reflexive “model-free” system. A balance of control exerted by these systems is thought to be related to dopamine neurotransmission. However, in the absence of direct measures of human dopamine, it remains unknown whether this reflects a quantitative relation with dopamine either in the striatum or other brain areas. Using a sequential decision task performed during functional magnetic resonance imaging, combined with striatal measures of dopamine using [18F]DOPA positron emission tomography, we show that higher presynaptic ventral striatal dopamine levels were associated with a behavioral bias toward more model-based control. Higher presynaptic dopamine in ventral striatum was associated with greater coding of model-based signatures in lateral prefrontal cortex and diminished coding of model-free prediction errors in ventral striatum. Thus, interindividual variability in ventral striatal presynaptic dopamine reflects a balance in the behavioral expression and the neural signatures of model-free and model-based control. Our data provide a novel perspective on how alterations in presynaptic dopamine levels might be accompanied by a disruption of behavioral control as observed in aging or neuropsychiatric diseases such as schizophrenia and addiction.
|
|
| 4. |
- Bach, Dominik R., et al.
(författare)
-
Human Hippocampus Arbitrates Approach-Avoidance Conflict
- 2014
-
Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 24:5, s. 541-547
-
Tidskriftsartikel (refereegranskat)abstract
- Animal models of human anxiety often invoke a conflict between approach and avoidance [1, 2]. In these, a key behavioral assay comprises passive avoidance of potential threat and inhibition, both thought to be controlled by ventral hippocampus [2-6]. Efforts to translate these approaches to clinical contexts [7, 8] are hampered by the fact that it is not known whether humans manifest analogous approach-avoidance dispositions and, if so, whether they share a homologous neurobiological substrate [9]. Here, we developed a paradigm to investigate the role of human hippocampus in arbitrating an approach-avoidance conflict under varying levels of potential threat. Across four experiments, subjects showed analogous behavior by adapting both passive avoidance behavior and behavioral inhibition to threat level. Using functional magnetic resonance imaging (fMRI), we observe that threat level engages the anterior hippocampus, the human homolog of rodent ventral hippocampus [10]. Testing patients with selective hippocampal lesions, we demonstrate a causal role for the hippocampus with patients showing reduced passive avoidance behavior and inhibition across all threat levels. Our data provide the first human assay for approach-avoidance conflict akin to that of animal anxiety models. The findings bridge rodent and human research on passive avoidance and behavioral inhibition and furnish a framework for addressing the neuronal underpinnings of human anxiety disorders, where our data indicate a major role for the hippocampus.
|
|
| 5. |
- Chowdhury, Rumana, et al.
(författare)
-
Dopamine restores reward prediction errors in old age
- 2013
-
Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 16:5, s. 648-653
-
Tidskriftsartikel (refereegranskat)abstract
- Senescence affects the ability to utilize information about the likelihood of rewards for optimal decision-making. Using functional magnetic resonance imaging in humans, we found that healthy older adults had an abnormal signature of expected value, resulting in an incomplete reward prediction error (RPE) signal in the nucleus accumbens, a brain region that receives rich input projections from substantia nigra/ventral tegmental area (SN/VTA) dopaminergic neurons. Structural connectivity between SN/VTA and striatum, measured by diffusion tensor imaging, was tightly coupled to inter-individual differences in the expression of this expected reward value signal. The dopamine precursor levodopa (L-DOPA) increased the task-based learning rate and task performance in some older adults to the level of young adults. This drug effect was linked to restoration of a canonical neural RPE. Our results identify a neurochemical signature underlying abnormal reward processing in older adults and indicate that this can be modulated by L-DOPA.
|
|
| 6. |
- Critchley, Hugo D, et al.
(författare)
-
Neural systems supporting interoceptive awareness.
- 2004
-
Ingår i: Nat Neurosci. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 7:2, s. 189-95
-
Tidskriftsartikel (refereegranskat)abstract
- Influential theories of human emotion argue that subjective feeling states involve representation of bodily responses elicited by emotional events. Within this framework, individual differences in intensity of emotional experience reflect variation in sensitivity to internal bodily responses. We measured regional brain activity by functional magnetic resonance imaging (fMRI) during an interoceptive task wherein subjects judged the timing of their own heartbeats. We observed enhanced activity in insula, somatomotor and cingulate cortices. In right anterior insular/opercular cortex, neural activity predicted subjects' accuracy in the heartbeat detection task. Furthermore, local gray matter volume in the same region correlated with both interoceptive accuracy and subjective ratings of visceral awareness. Indices of negative emotional experience correlated with interoceptive accuracy across subjects. These findings indicate that right anterior insula supports a representation of visceral responses accessible to awareness, providing a substrate for subjective feeling states.
|
|
| 7. |
- de Boer, Lieke, et al.
(författare)
-
Dorsal striatal dopamine D1 receptor availability predicts an instrumental bias in action learning
- 2019
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:1, s. 261-270
-
Tidskriftsartikel (refereegranskat)abstract
- Learning to act to obtain reward and inhibit to avoid punishment is easier compared with learning the opposite contingencies. This coupling of action and valence is often thought of as a Pavlovian bias, although recent research has shown it may also emerge through instrumental mechanisms. We measured this learning bias with a rewarded go/no-go task in 60 adults of different ages. Using computational modeling, we characterized the bias as being instrumental. To assess the role of endogenous dopamine (DA) in the expression of this bias, we quantified DA D1 receptor availability using positron emission tomography (PET) with the radioligand [11C]SCH23390. Using principal-component analysis on the binding potentials in a number of cortical and striatal regions of interest, we demonstrated that cortical, dorsal striatal, and ventral striatal areas provide independent sources of variance in DA D1 receptor availability. Interindividual variation in the dorsal striatal component was related to the strength of the instrumental bias during learning. These data suggest at least three anatomical sources of variance in DA D1 receptor availability separable using PET in humans, and we provide evidence that human dorsal striatal DA D1 receptors are involved in the modulation of instrumental learning biases.
|
|
| 8. |
- Economides, Marcos, et al.
(författare)
-
Anterior Cingulate Cortex Instigates Adaptive Switches in Choice by Integrating Immediate and Delayed Components of Value in Ventromedial Prefrontal Cortex
- 2014
-
Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 34:9, s. 3340-3349
-
Tidskriftsartikel (refereegranskat)abstract
- Actions can lead to an immediate reward or punishment and a complex set of delayed outcomes. Adaptive choice necessitates the brain track and integrate both of these potential consequences. Here, we designed a sequential task whereby the decision to exploit or forego an available offer was contingent on comparing immediate value and a state-dependent future cost of expending a limited resource. Crucially, the dynamics of the task demanded frequent switches in policy based on an online computation of changing delayed consequences. We found that human subjects choose on the basis of a near-optimal integration of immediate reward and delayed consequences, with the latter computed in a prefrontal network. Within this network, anterior cingulate cortex (ACC) was dynamically coupled to ventromedial prefrontal cortex (vmPFC) when adaptive switches in choice were required. Our results suggest a choice architecture whereby interactions between ACC and vmPFC underpin an integration of immediate and delayed components of value to support flexible policy switching that accommodates the potential delayed consequences of an action.
|
|
| 9. |
- Ereira, Sam, et al.
(författare)
-
Overcoming Pavlovian bias in semantic space
- 2021
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Action is invigorated in the presence of reward-predicting stimuli and inhibited in the presence of punishment-predicting stimuli. Although valuable as a heuristic, this Pavlovian bias can also lead to maladaptive behaviour and is implicated in addiction. Here we explore whether Pavlovian bias can be overcome through training. Across five experiments, we find that Pavlovian bias is resistant to unlearning under most task configurations. However, we demonstrate that when subjects engage in instrumental learning in a verbal semantic space, as opposed to a motoric space, not only do they exhibit the typical Pavlovian bias, but this Pavlovian bias diminishes with training. Our results suggest that learning within the semantic space is necessary, but not sufficient, for subjects to unlearn their Pavlovian bias, and that other task features, such as gamification and spaced stimulus presentation may also be necessary. In summary, we show that Pavlovian bias, whilst robust, is susceptible to change with experience, but only under specific environmental conditions.
|
|
| 10. |
- Koster, Raphael, et al.
(författare)
-
Basal Ganglia Activity Mirrors a Benefit of Action and Reward on Long-Lasting Event Memory
- 2015
-
Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 25:12, s. 4908-4917
-
Tidskriftsartikel (refereegranskat)abstract
- The expectation of reward is known to enhance a consolidation of long-term memory for events. We tested whether this effect is driven by positive valence or action requirements tied to expected reward. Using a functional magnetic resonance imaging (fMRI) paradigm in young adults, novel images predicted gain or loss outcomes, which in turn were either obtained or avoided by action or inaction. After 24 h, memory for these images reflected a benefit of action as well as a congruence of action requirements and valence, namely, action for reward and inaction for avoidance. fMRI responses in the hippocampus, a region known to be critical for long-term memory function, reflected the anticipation of inaction. In contrast, activity in the putamen mirrored the congruence of action requirement and valence, whereas other basal ganglia regions mirrored overall action benefits on long-lasting memory. The findings indicate a novel type of functional division between the hippocampus and the basal ganglia in the motivational regulation of long-term memory consolidation, which favors remembering events that are worth acting for.
|
|
