scholarly journals Dissociable mechanisms of reward learning co-mature during human adolescence as predicted by macaque lesion models

Author(s):  
Marco K. Wittmann ◽  
Maximilian Scheuplein ◽  
Sophie G. Gibbons ◽  
MaryAnn P. Noonan

AbstractReward-guided learning and decision-making is a fundamental adaptive ability and depends on a number of component processes. We investigate how such component processes mature during human adolescence. Our approach was guided by analyses of the effects of lateral orbitofrontal lesions in macaque monkeys, as this part of the brain shows clear developmental maturation in humans during adolescence. Using matched tasks and analyses in humans (n=388, 11-35yrs), we observe developmental changes in two key learning mechanisms as predicted from the monkey data. First, choice-reward credit assignment – the ability to link a specific outcome to a specific choice – is reduced in adolescents. Second, the effects of the global reward state – how good the environment is overall recently − exerts a distinctive pattern of influence on learning in humans compared to other primates and across adolescence this pattern becomes more pronounced. Both mechanisms were correlated across participants suggesting that associative learning of correct reward assignments and GRS based learning constitute two complementary mechanisms of reward-learning that co-mature during adolescence.

Polymers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1000
Author(s):  
Sylwia Łukasiewicz

Clozapine, the second generation antipsychotic drug, is one of the prominent compounds used for treatment of schizophrenia. Unfortunately, use of this drug is still limited due to serious side effects connected to its unspecific and non-selective action. Nevertheless, clozapine still remains the first-choice drug for the situation of drug-resistance schizophrenia. Development of the new strategy of clozapine delivery into well-defined parts of the brain has been a great challenge for modern science. In the present paper we focus on the presentation of a new nanocarrier for clozapine and its use for targeted transport, enabling its interaction with the dopamine D2 and serotonin 5-HT1A heteromers (D2-5-HT1A) in the brain tissue. Clozapine polymeric nanocapsules (CLO-NCs) were prepared using anionic surfactant AOT (sodium docusate) as an emulsifier, and bio-compatible polyelectrolytes such as: poly-L-glutamic acid (PGA) and poly-L-lysine (PLL). Outer layer of the carrier was grafted by polyethylene glycol (PEG). Several variants of nanocarriers containing the antipsychotic varying in physicochemical parameters were tested. This kind of approach may enable the availability and safety of the drug, improve the selectivity of its action, and finally increase effectiveness of schizophrenia therapy. Moreover, the purpose of the manuscript is to cover a wide scope of the issues, which should be considered while designing a novel means for drug delivery. It is important to determine the interactions of a new nanocarrier with many cell components on various cellular levels in order to be sure that the new nanocarrier will be safe and won’t cause undesired effects for a patient.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Björn Lindström ◽  
Martin Bellander ◽  
David T. Schultner ◽  
Allen Chang ◽  
Philippe N. Tobler ◽  
...  

AbstractSocial media has become a modern arena for human life, with billions of daily users worldwide. The intense popularity of social media is often attributed to a psychological need for social rewards (likes), portraying the online world as a Skinner Box for the modern human. Yet despite such portrayals, empirical evidence for social media engagement as reward-based behavior remains scant. Here, we apply a computational approach to directly test whether reward learning mechanisms contribute to social media behavior. We analyze over one million posts from over 4000 individuals on multiple social media platforms, using computational models based on reinforcement learning theory. Our results consistently show that human behavior on social media conforms qualitatively and quantitatively to the principles of reward learning. Specifically, social media users spaced their posts to maximize the average rate of accrued social rewards, in a manner subject to both the effort cost of posting and the opportunity cost of inaction. Results further reveal meaningful individual difference profiles in social reward learning on social media. Finally, an online experiment (n = 176), mimicking key aspects of social media, verifies that social rewards causally influence behavior as posited by our computational account. Together, these findings support a reward learning account of social media engagement and offer new insights into this emergent mode of modern human behavior.


2019 ◽  
pp. 53-66
Author(s):  
Risto Näätänen ◽  
Teija Kujala ◽  
Gregory Light

The brain can detect sound changes very early on, even prenatally. Both positively and negatively displaced responses to deviant stimuli have been found in infancy, with the majority of studies reporting, however, positive mismatch responses (MMR) in infants within the first few months of life. Besides neural development, stimulation parameters may influence polarity. The positively displaced MMR develops towards the adult-like MMN between the ages of 3 and 9 months, there being a wide inter-individual variation in this development. From school age onwards, sound changes elicit MMNs with negative polarities fairly systematically. The MMN peak latency becomes shorter with development, similar to other event-related potential components, which is consistent with the development of myelination. MMN/MMR studies have illuminated auditory abilities and learning mechanisms in infants, suggesting, for example, that the infant brain can extract information on the regularities of sound input and foetuses can form long-lasting memory traces.


2019 ◽  
Vol 121 (4) ◽  
pp. 1561-1574 ◽  
Author(s):  
Dimitrios J. Palidis ◽  
Joshua G. A. Cashaback ◽  
Paul L. Gribble

At least two distinct processes have been identified by which motor commands are adapted according to movement-related feedback: reward-based learning and sensory error-based learning. In sensory error-based learning, mappings between sensory targets and motor commands are recalibrated according to sensory error feedback. In reward-based learning, motor commands are associated with subjective value, such that successful actions are reinforced. We designed two tasks to isolate reward- and sensory error-based motor adaptation, and we used electroencephalography in humans to identify and dissociate the neural correlates of reward and sensory error feedback processing. We designed a visuomotor rotation task to isolate sensory error-based learning that was induced by altered visual feedback of hand position. In a reward learning task, we isolated reward-based learning induced by binary reward feedback that was decoupled from the visual target. A fronto-central event-related potential called the feedback-related negativity (FRN) was elicited specifically by binary reward feedback but not sensory error feedback. A more posterior component called the P300 was evoked by feedback in both tasks. In the visuomotor rotation task, P300 amplitude was increased by sensory error induced by perturbed visual feedback and was correlated with learning rate. In the reward learning task, P300 amplitude was increased by reward relative to nonreward and by surprise regardless of feedback valence. We propose that during motor adaptation the FRN specifically reflects a reward-based learning signal whereas the P300 reflects feedback processing that is related to adaptation more generally. NEW & NOTEWORTHY We studied the event-related potentials evoked by feedback stimuli during motor adaptation tasks that isolate reward- and sensory error-based learning mechanisms. We found that the feedback-related negativity was specifically elicited by binary reward feedback, whereas the P300 was observed in both tasks. These results reveal neural processes associated with different learning mechanisms and elucidate which classes of errors, from a computational standpoint, elicit the feedback-related negativity and P300.


2020 ◽  
Vol 30 (10) ◽  
pp. 5270-5280
Author(s):  
Lieke de Boer ◽  
Benjamín Garzón ◽  
Jan Axelsson ◽  
Katrine Riklund ◽  
Lars Nyberg ◽  
...  

Abstract Probabilistic reward learning reflects the ability to adapt choices based on probabilistic feedback. The dopaminergically innervated corticostriatal circuit in the brain plays an important role in supporting successful probabilistic reward learning. Several components of the corticostriatal circuit deteriorate with age, as it does probabilistic reward learning. We showed previously that D1 receptor availability in NAcc predicts the strength of anticipatory value signaling in vmPFC, a neural correlate of probabilistic learning that is attenuated in older participants and predicts probabilistic reward learning performance. We investigated how white matter integrity in the pathway between nucleus accumbens (NAcc) and ventromedial prefrontal cortex (vmPFC) relates to the strength of anticipatory value signaling in vmPFC in younger and older participants. We found that in a sample of 22 old and 23 young participants, fractional anisotropy in the pathway between NAcc and vmPFC predicted the strength of value signaling in vmPFC independently from D1 receptor availability in NAcc. These findings provide tentative evidence that integrity in the dopaminergic and white matter pathways of corticostriatal circuitry supports the expression of value signaling in vmPFC which supports reward learning, however, the limited sample size calls for independent replication. These and future findings could add to the improved understanding of how corticostriatal integrity contributes to reward learning ability.


2006 ◽  
Vol 18 (2) ◽  
pp. 283-328 ◽  
Author(s):  
Randall C. O'Reilly ◽  
Michael J. Frank

The prefrontal cortex has long been thought to subserve both working memory (the holding of information online for processing) and executive functions (deciding how to manipulate working memory and perform processing). Although many computational models of working memory have been developed, the mechanistic basis of executive function remains elusive, often amounting to a homunculus. This article presents an attempt to deconstruct this homunculus through powerful learning mechanisms that allow a computational model of the prefrontal cortex to control both itself and other brain areas in a strategic, task-appropriate manner. These learning mechanisms are based on subcortical structures in the midbrain, basal ganglia, and amygdala, which together form an actor-critic architecture. The critic system learns which prefrontal representations are task relevant and trains the actor, which in turn provides a dynamic gating mechanism for controlling working memory updating. Computationally, the learning mechanism is designed to simultaneously solve the temporal and structural credit assignment problems. The model's performance compares favorably with standard backpropagation-based temporal learning mechanisms on the challenging 1-2-AX working memory task and other benchmark working memory tasks.


2016 ◽  
Vol 28 (2) ◽  
pp. 295-307 ◽  
Author(s):  
Alexander Schlegel ◽  
Prescott Alexander ◽  
Peter U. Tse

The brain is a complex, interconnected information processing network. In humans, this network supports a mental workspace that enables high-level abilities such as scientific and artistic creativity. Do the component processes underlying these abilities occur in discrete anatomical modules, or are they distributed widely throughout the brain? How does the flow of information within this network support specific cognitive functions? Current approaches have limited ability to answer such questions. Here, we report novel multivariate methods to analyze information flow within the mental workspace during visual imagery manipulation. We find that mental imagery entails distributed information flow and shared representations throughout the cortex. These findings challenge existing, anatomically modular models of the neural basis of higher-order mental functions, suggesting that such processes may occur at least in part at a fundamentally distributed level of organization. The novel methods we report may be useful in studying other similarly complex, high-level informational processes.


1996 ◽  
Vol 7 (4) ◽  
pp. 258-264 ◽  
Author(s):  
R B S Laing ◽  
P J Flegg ◽  
R P Brettle ◽  
C L S Leen ◽  
S M Burns

Nineteen cases of cerebral toxoplasmosis (CTOX) are reported from a group of Edinburgh AIDS patients. All patients were severely immunodeficient at the time of presentation with CD4 count <50 cells/mm 3. Thirteen patients had suffered a previous AIDS-defining illness. In Edinburgh, CTOX has developed in 48% of patients who are seropositive for toxoplasma and have a CD4 count <50 cells/mm3. It is estimated that at least half of the toxoplasma seropositive patients will develop CTOX if they survive for 21 months after reaching a time in their illness when the CD4 count=50 cells/mm 3. The incidence of CTOX in toxoplasmaseronegative patients with a CD4 count <50 cells/mm 3 is 1.3%. All patients showed improvement on treatment and there was no correlation between clinical or radiological features and patient survival. Those patients unable to tolerate first choice anti-toxoplasma therapy had a significantly shorter survival than the remainder but there was no single therapeutic regimen which conferred a survival advantage. Eighteen patients had died at the time of study and the median survival following diagnosis of cerebral toxoplasmosis was 10 months (range 3-38 months). Postmortem examination of the brain was available in 8, 4 of whom had concomitant cerebral lymphoma. The survival from AIDS or CD4 count=50 cells/mm 3 did not differ significantly between those with treated CTOX and a control group who had no toxoplasma infection, suggesting that treatment is reasonably effective. CTOX is a disease associated with severe HIV-related immunodeficiency and, in those with a CD4 count <50 cells/mm 3, occurs more than 35 times as frequently in toxoplasma-seropositive than toxoplasma-seronegative patients. Treatment is effective but the outcome of treated disease cannot be predicted from presenting clinical or radiological features. Concomitant space-occupying cerebral pathology is evident in 50% of post-mortem examinations.


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