Publications by authors named "Gianluca Baldassarre"

58 Publications

Internal manipulation of perceptual representations in human flexible cognition: A computational model.

Neural Netw 2021 Jul 15;143:572-594. Epub 2021 Jul 15.

Laboratory of Computational Embodied Neuroscience, Institute of Cognitive Sciences and Technologies, National Research Council of Italy, Rome, Italy. Electronic address:

Executive functions represent a set of processes in goal-directed cognition that depend on integrated cortical-basal ganglia brain systems and form the basis of flexible human behaviour. Several computational models have been proposed for studying cognitive flexibility as a key executive function and the Wisconsin card sorting test (WCST) that represents an important neuropsychological tool to investigate it. These models clarify important aspects that underlie cognitive flexibility, particularly decision-making, motor response, and feedback-dependent learning processes. However, several studies suggest that the categorisation processes involved in the solution of the WCST include an additional computational stage of category representation that supports the other processes. Surprisingly, all models of the WCST ignore this fundamental stage and they assume that decision making directly triggers actions. Thus, we propose a novel hypothesis where the key mechanisms of cognitive flexibility and goal-directed behaviour rely on the acquisition of suitable representations of percepts and their top-down internal manipulation. Moreover, we propose a neuro-inspired computational model to operationalise this hypothesis. The capacity of the model to support cognitive flexibility was validated by systematically reproducing and interpreting the behaviour exhibited in the WCST by young and old healthy adults, and by frontal and Parkinson patients. The results corroborate and further articulate the hypothesis that the internal manipulation of representations is a core process in goal-directed flexible cognition.
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http://dx.doi.org/10.1016/j.neunet.2021.07.013DOI Listing
July 2021

Low Levels of Gastrin 17 are Related with Endoscopic Findings of Esophagitis and Typical Symptoms of GERD.

J Gastrointestin Liver Dis 2021 Feb 12;30(1):25-29. Epub 2021 Feb 12.

Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.

Background And Aims: In clinical practice, most patients with symptoms suggestive of gastroesophageal reflux disease (GERD) undergo esophago-gastro-duodenoscopy (EGD), despite its low sensitivity in detecting reflux stigmata. Gastrin 17 (G-17) has been proposed to be related with GERD, due to the negative feedback between acid secretion and this hormone. We assessed the clinical usefulness of fasting G-17 serum determination for a non-invasive diagnosis of GERD in patients with typical symptoms.

Methods: We consecutively enrolled patients complaining of typical GERD symptoms in two different settings: a single referral center and a primary care setting. Control groups consisted of dyspeptic patients. All subjects underwent assessment of serum levels of G-17 and EGD.

Results: At the academic hospital, 100 GERD patients (n=89 with erosive esophagitis and 11 with Barrett's esophagus) had statistically significant low levels of G-17 as compared with 184 dyspeptic patients (1.7±1.2 pg/L vs 8.9±5.7 pg/L p<0.0001). Similarly, in the primary care setting, 163 GERD patients had statistically significant low levels of G-17 as compared with 132 dyspeptic patients (0.5±0.2 pg/L vs. 4.0±2.6 pg/L, p<0.0001). Moreover, in the primary care setting, no statistically significant differences were found for G-17 levels between patients with erosive and non-erosive reflux pattern (0.4±0.2 vs 0.7±0.3; p=0.08). In primary care, the accuracy of G-17 less than 1 pg/L to diagnose non-invasively GERD was 94.3%.

Conclusions: Low levels of G-17 were detected in patients with erosive esophagitis and Barrett's esophagus in a referral center and in patients with typical GERD symptoms in a sample of patients from a primary care setting.
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http://dx.doi.org/10.15403/jgld-2952DOI Listing
February 2021

A computational model of language functions in flexible goal-directed behaviour.

Sci Rep 2020 12 10;10(1):21623. Epub 2020 Dec 10.

Laboratory of Computational Embodied Neuroscience, Institute of Cognitive Sciences and Technologies, National Research Council of Italy, Rome, Italy.

The function of language in high-order goal-directed human cognition is an important topic at the centre of current debates. Experimental evidence shows that inner speech, representing a self-directed form of language, empowers cognitive processes such as working memory, perception, categorization, and executive functions. Here we study the relations between inner speech and processes like feedback processing and cognitive flexibility. To this aim we propose a computational model that controls an artificial agent who uses inner speech to internally manipulate its representations. The agent is able to reproduce human behavioural data collected during the solution of the Wisconsin Card Sorting test, a neuropsychological test measuring cognitive flexibility, both in the basic condition and when a verbal shadowing protocol is used. The components of the model were systematically lesioned to clarify the specific impact of inner speech on the agent's behaviour. The results indicate that inner speech improves the efficiency of internal representation manipulation. Specifically, it makes the representations linked to specific visual features more disentangled, thus improving the agent's capacity to engage/disengage attention on stimulus features after positive/negative action outcomes. Overall, the model shows how inner speech could improve goal-directed internal manipulation of representations and enhance behavioural flexibility.
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http://dx.doi.org/10.1038/s41598-020-78252-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729881PMC
December 2020

A generative spiking neural-network model of goal-directed behaviour and one-step planning.

PLoS Comput Biol 2020 12 8;16(12):e1007579. Epub 2020 Dec 8.

Institute of Cognitive Sciences and Technologies, National Research Council, Rome, Italy.

In mammals, goal-directed and planning processes support flexible behaviour used to face new situations that cannot be tackled through more efficient but rigid habitual behaviours. Within the Bayesian modelling approach of brain and behaviour, models have been proposed to perform planning as probabilistic inference but this approach encounters a crucial problem: explaining how such inference might be implemented in brain spiking networks. Recently, the literature has proposed some models that face this problem through recurrent spiking neural networks able to internally simulate state trajectories, the core function at the basis of planning. However, the proposed models have relevant limitations that make them biologically implausible, namely their world model is trained 'off-line' before solving the target tasks, and they are trained with supervised learning procedures that are biologically and ecologically not plausible. Here we propose two novel hypotheses on how brain might overcome these problems, and operationalise them in a novel architecture pivoting on a spiking recurrent neural network. The first hypothesis allows the architecture to learn the world model in parallel with its use for planning: to this purpose, a new arbitration mechanism decides when to explore, for learning the world model, or when to exploit it, for planning, based on the entropy of the world model itself. The second hypothesis allows the architecture to use an unsupervised learning process to learn the world model by observing the effects of actions. The architecture is validated by reproducing and accounting for the learning profiles and reaction times of human participants learning to solve a visuomotor learning task that is new for them. Overall, the architecture represents the first instance of a model bridging probabilistic planning and spiking-processes that has a degree of autonomy analogous to the one of real organisms.
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http://dx.doi.org/10.1371/journal.pcbi.1007579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748287PMC
December 2020

A Computational Model Integrating Multiple Phenomena on Cued Fear Conditioning, Extinction, and Reinstatement.

Front Syst Neurosci 2020 29;14:569108. Epub 2020 Sep 29.

Institute of Cognitive Sciences and Technologies, National Research Council, Rome, Italy.

Conditioning, extinction, and reinstatement are fundamental learning processes of animal adaptation, also strongly involved in human pathologies such as post-traumatic stress disorder, anxiety, depression, and dependencies. Cued fear conditioning, extinction, restatement, and systematic manipulations of the underlying brain amygdala and medial prefrontal cortex, represent key experimental paradigms to study such processes. Numerous empirical studies have revealed several aspects and the neural systems and plasticity underlying them, but at the moment we lack a comprehensive view. Here we propose a computational model based on firing rate leaky units that contributes to such integration by accounting for 25 different experiments on fear conditioning, extinction, and restatement, on the basis of a single neural architecture having a structure and plasticity grounded in known brain biology. This allows the model to furnish three novel contributions to understand these open issues: (a) the functioning of the central and lateral amygdala system supporting conditioning; (b) the role played by the endocannabinoids system in within- and between-session extinction; (c) the formation of three important types of neurons underlying fear processing, namely fear, extinction, and persistent neurons. The model integration of the results on fear conditioning goes substantially beyond what was done in previous models.
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http://dx.doi.org/10.3389/fnsys.2020.569108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550679PMC
September 2020

Functional Dyspesia.

Acta Biomed 2020 07 9;91(3):e2020069. Epub 2020 Jul 9.

Department of Medicine and Surgery, University of Parma, Parma, Italy.

Dyspepsia is a functional GI disorder consisting in a wide range of symptoms. The main diagnostic challenge has been whether to perform an EGD or an abdominal US in order not to miss organic lesions, but to avoid unnecessary and sometimes invasive tests. Pepsinogen serology has been proposed as an useful non-invasive test to explore the status of the gastric mucosa, suggesting this strategy as an adequate approach in management of dyspepsia. In a primary care setting, 266 dyspeptic patients were investigated to establish the proper diagnosis. The workup included upper GI endoscopy with biopsies, a structured questionnaire including type and severity of symptoms, serological determination of serum pepsinogens, gastrin 17 and IgG against Hp. Inclusion criteria were dyspeptic symptoms (epigastric pain, nausea and/or vomiting, post prandial fullness, early satiation) lasting more than 1 year and the association between symptoms and food ingestion.. Helicobacter pylori infection was present in 114 subjects, characterized by high levels of pepsinogen II and IgG against Hp. Twenty subjects were classified according with the diagnosis of chronic body atrophic gastritis. Nausea and post prandial fullness were the most frequent symptoms (48% and 41%, respectively) in the studied population, followed by epigastric pain and early satiation (37% and 26% respectively). A diagnosis of normality by serological diagnosis was found in half of patients experiencing epigastric pain and in about 60% of subjects with the three other symptoms (nausea, post prandial fullness, and early satiation). In conclusion, this experience confirms the clinical usefulness of serology in dyspepsia, contributing to correctly diagnosing CAG and H.p. infection in such patients and providing a good correlation with the clinical picture.
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http://dx.doi.org/10.23750/abm.v91i3.10150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716988PMC
July 2020

Computational Modeling of Catecholamines Dysfunction in Alzheimer's Disease at Pre-Plaque Stage.

J Alzheimers Dis 2020 ;77(1):275-290

Laboratory of Computational Embodied Neuroscience (LOCEN), Institute of Cognitive Sciences and Technologies, National Research Council, Rome, Italy.

Background: Alzheimer's disease (AD) etiopathogenesis remains partially unexplained. The main conceptual framework used to study AD is the Amyloid Cascade Hypothesis, although the failure of recent clinical experimentation seems to reduce its potential in AD research.

Objective: A possible explanation for the failure of clinical trials is that they are set too late in AD progression. Recent studies suggest that the ventral tegmental area (VTA) degeneration could be one of the first events occurring in AD progression (pre-plaque stage).

Methods: Here we investigate this hypothesis through a computational model and computer simulations validated with behavioral and neural data from patients.

Results: We show that VTA degeneration might lead to system-level adjustments of catecholamine release, triggering a sequence of events leading to relevant clinical and pathological signs of AD. These changes consist first in a midfrontal-driven compensatory hyperactivation of both VTA and locus coeruleus (norepinephrine) followed, with the progression of the VTA impairment, by a downregulation of catecholamine release. These processes could then trigger the neural degeneration at the cortical and hippocampal levels, due to the chronic loss of the neuroprotective role of norepinephrine.

Conclusion: Our novel hypothesis might contribute to the formulation of a wider system-level view of AD which might help to devise early diagnostic and therapeutic interventions.
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http://dx.doi.org/10.3233/JAD-200276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592658PMC
September 2021

Acceptability of the Transitional Wearable Companion "+" in Children With Autism Spectrum Disorder: A Comparative Pilot Study.

Front Psychol 2020 28;11:951. Epub 2020 May 28.

Institute of Cognitive Sciences and Technologies, ISTC-CNR, Rome, Italy.

+ is an experimental interactive soft toy, looking like a panda, developed for young children. When touched on the paws or head (inputs), the toy can emit attractive responses such as colored lights and amusing sounds (outputs). + is wirelessly connected to a control tablet through which an adult caregiver can modify its input-output contingencies so as to produce different, rewarding response patterns using the same device. Given these features, we propose + as a potential novel tool to support the therapy of Autism Spectrum Disorder (ASD). The allure of the device could be exploited to capture the attention and encourage the social interaction of toddlers during play activities with therapists. In this pilot study, + was tested on two small groups of children aged 30-48 months, one group diagnosed with ASD and the second with Communication Disorder, a condition that often presents-especially at an early age-overlapping symptoms with ASD. The proposed play activities aimed to foster simple imitative behaviors and stimulate the engagement of the children. The results were compared with those of a previous test run on Typically Developed children. Preliminary observations, based on the analysis of video recordings, suggest that, on average, + is able to encourage a positive engagement and that different groups tend to manifest some different behaviors.
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http://dx.doi.org/10.3389/fpsyg.2020.00951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270338PMC
May 2020

Risk factors for endoscopic severity of diverticular disease of the colon and its outcome: a real-life case-control study.

Eur J Gastroenterol Hepatol 2020 09;32(9):1123-1129

Department of Medicine and Surgery, Gastroenterology Unit, University of Parma, Parma.

Background: Diverticular disease is an increasing global problem.

Aims: To assess the factors associated with the severity of diverticular disease and its outcome, analyzing a real-life population.

Methods: A cohort of patients, submitted to colonoscopy from 1 January 2012 to 30 April 2018 was revised. The endoscopic severity of diverticular disease was scored according to the Diverticular Inflammation and Complications Assessment (DICA) classification.

Results: A cohort of 11 086 patients was identified during the study period, 5635 with diverticulitis and 5451 without diverticulosis. Blood hypertension, diabetes and angiotensin receptor blocker users occurred more frequently in the study group, while the prevalence of colorectal cancer (CRC) was significantly lower. Age >70 years, BMI >30 and blood hypertension were factors independently related to the presence of diverticulosis, while diabetes and CRC were significantly associated with the absence of diverticulosis. Female sex, age, smoke, appendectomy, proton-pump inhibitors and acetyl-salicylic acid use were directly related to the severity of diverticular disease, while CRC and colonic polyp occurrence were inversely related to the severity of diverticular disease, significantly. Female sex, age >70 years and smoke were significantly related to the severity of diverticular disease. CRC and colonic polyps were significantly less in DICA 3 patients. DICA 3 patients were more often symptomatic, at higher risk of hospital admission, longer hospital stay and higher mean costs.

Conclusions: Several factors are associated with the severity of diverticular disease according to the DICA classification. The DICA classification is also predictive of the outcome of the disease in terms of hospital admission, stay and costs.
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http://dx.doi.org/10.1097/MEG.0000000000001787DOI Listing
September 2020

Editorial: Intrinsically Motivated Open-Ended Learning in Autonomous Robots.

Front Neurorobot 2019 17;13:115. Epub 2020 Jan 17.

Istituto di Scienze e Tecnologie della Cognizione, Consiglio Nazionale delle Ricerche, Rome, Italy.

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http://dx.doi.org/10.3389/fnbot.2019.00115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978885PMC
January 2020

Sensorimotor Contingencies as a Key Drive of Development: From Babies to Robots.

Front Neurorobot 2019 4;13:98. Epub 2019 Dec 4.

Integrative Neuroscience and Cognition Center, UMR 8002, CNRS, Université Paris Descartes, Paris, France.

Much current work in robotics focuses on the development of robots capable of autonomous unsupervised learning. An essential prerequisite for such learning to be possible is that the agent should be sensitive to the link between its actions and the consequences of its actions, called sensorimotor contingencies. This sensitivity, and more particularly its role as a key drive of development, has been widely studied by developmental psychologists. However, the results of these studies may not necessarily be accessible or intelligible to roboticians. In this paper, we review the main experimental data demonstrating the role of sensitivity to sensorimotor contingencies in infants' acquisition of four fundamental motor and cognitive abilities: body knowledge, memory, generalization, and goal-directedness. We relate this data from developmental psychology to work in robotics, highlighting the links between these two domains of research. In the last part of the article we present a blueprint architecture demonstrating how exploitation of sensitivity to sensorimotor contingencies, combined with the notion of "goal," allows an agent to develop new sensorimotor skills. This architecture can be used to guide the design of specific computational models, and also to possibly envisage new empirical experiments.
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http://dx.doi.org/10.3389/fnbot.2019.00098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904889PMC
December 2019

An Embodied Agent Learning Affordances With Intrinsic Motivations and Solving Extrinsic Tasks With Attention and One-Step Planning.

Front Neurorobot 2019 26;13:45. Epub 2019 Jul 26.

Laboratory of Computational Embodied Neuroscience, Institute of Cognitive Sciences and Technologies, National Research Council of Italy, Rome, Italy.

We propose an architecture for the open-ended learning and control of embodied agents. The architecture learns action affordances and forward models based on intrinsic motivations and can later use the acquired knowledge to solve extrinsic tasks by decomposing them into sub-tasks, each solved with one-step planning. An affordance is here operationalized as the agent's estimate of the probability of success of an action performed on a given object. The focus of the work is on the overall architecture while single sensorimotor components are simplified. A key element of the architecture is the use of "active vision" that plays two functions, namely to focus on single objects and to factorize visual information into the object appearance and object position. These processes serve both the acquisition and use of object-related affordances, and the decomposition of extrinsic goals (tasks) into multiple sub-goals (sub-tasks). The architecture gives novel contributions on three problems: (a) the learning of affordances based on intrinsic motivations; (b) the use of active vision to decompose complex extrinsic tasks; (c) the possible role of affordances within planning systems endowed with models of the world. The architecture is tested in a simulated stylized 2D scenario in which objects need to be moved or "manipulated" in order to accomplish new desired overall configurations of the objects (extrinsic goals). The results show the utility of using intrinsic motivations to support affordance learning; the utility of active vision to solve composite tasks; and the possible utility of affordances for solving utility-based planning problems.
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http://dx.doi.org/10.3389/fnbot.2019.00045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676802PMC
July 2019

Different Dopaminergic Dysfunctions Underlying Parkinsonian Akinesia and Tremor.

Front Neurosci 2019 29;13:550. Epub 2019 May 29.

National Research Council, Institute of Cognitive Sciences and Technologies, Rome, Italy.

Although the occurrence of Parkinsonian akinesia and tremor is traditionally associated to dopaminergic degeneration, the multifaceted neural processes that cause these impairments are not fully understood. As a consequence, current dopamine medications cannot be tailored to the specific dysfunctions of patients with the result that generic drug therapies produce different effects on akinesia and tremor. This article proposes a computational model focusing on the role of dopamine impairments in the occurrence of akinesia and resting tremor. The model has three key features, to date never integrated in a single computational system: (a) an architecture constrained on the basis of the relevant known system-level anatomy of the basal ganglia-thalamo-cortical loops; (b) spiking neurons with physiologically-constrained parameters; (c) a detailed simulation of the effects of both phasic and tonic dopamine release. The model exhibits a neural dynamics compatible with that recorded in the brain of primates and humans. Moreover, it suggests that akinesia might involve both tonic and phasic dopamine dysregulations whereas resting tremor might be primarily caused by impairments involving tonic dopamine release and the responsiveness of dopamine receptors. These results could lead to develop new therapies based on a system-level view of the Parkinson's disease and targeting phasic and tonic dopamine in differential ways.
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http://dx.doi.org/10.3389/fnins.2019.00550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549580PMC
May 2019

Action Observation With Dual Task for Improving Cognitive Abilities in Parkinson's Disease: A Pilot Study.

Front Syst Neurosci 2019 11;13. Epub 2019 Feb 11.

Institute of Cognitive Sciences and Technologies, Italian National Research Council, Rome, Italy.

Action observation therapy (AOT) has been recently proposed as a new rehabilitation approach for treatment of motor deficits in Parkinson's disease. To date, this approach has never been used to deal with cognitive deficits (e.g., deficits in working memory, attention), which are impairments that are increasingly recognized in Parkinsonian patients. Typically, patients affected by these dysfunctions have difficulty filtering out irrelevant information and tend to lose track of the task goal. In this paper, we propose that AOT may also be used to improve cognitive abilities of Parkinsonian patients if it is used within a dual task framework. We articulate our hypothesis by pivoting on recent findings and on preliminary results that were obtained through a pilot study that was designed to test the efficacy of a long-term rehabilitation program that, for the first time, uses AOT within a dual task framework for treating cognitive deficits in patients with Parkinson's disease. Ten Parkinson's disease patients underwent a 45-min treatment that consisted in watching a video of an actor performing a daily-life activity and then executing it while performing distractive tasks (AOT with dual task). The treatment was repeated three times per week for a total of 4 weeks. Patients' cognitive/motor features were evaluated through standard tests four times: 1 month before treatment, the first and the last day of treatment and 1 month after treatment. The results show that this approach may provide relevant improvements in cognitive aspects related to working memory (verbal and visuospatial memory) and attention. We discuss these results by pivoting on literature on action observation and recent literature demonstrating that the dual task method can be used to stimulate cognition and concentration. In particular, we propose that using AOT together with a dual task may train the brain systems supporting executive functions through two mechanisms: (i) stimulation of goal setting within the mirror neuron system through action observation and (ii) working memory and persistent goal maintenance through dual task stimuli.
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http://dx.doi.org/10.3389/fnsys.2019.00007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378302PMC
February 2019

Acceptability of the Transitional Wearable Companion "+me" in Typical Children: A Pilot Study.

Front Psychol 2019 8;10:125. Epub 2019 Feb 8.

Istituto di Scienze e Tecnologie della Cognizione, Consiglio Nazionale delle Ricerche (ISTC-CNR), Rome, Italy.

This work presents the results of the first experimentation of +-the first prototype of -run on 15 typically developed (TD) children with ages between 8 and 34 months. + is an interactive device that looks like a teddy bear that can be worn around the neck, has touch sensors, can emit appealing lights and sounds, and has input-output contingencies that can be regulated with a tablet via Bluetooth. The participants were engaged in social play activities involving both the device and an adult experimenter. + was designed with the objective of exploiting its intrinsic allure as an attractive toy to stimulate social interactions (e.g., eye contact, turn taking, imitation, social smiles), an aspect potentially helpful in the therapy of Autism Spectrum Disorders (ASD) and other Pervasive Developmental Disorders (PDD). The main purpose of this preliminary study is to evaluate the general acceptability of the toy by TD children, observing the elicited behaviors in preparation for future experiments involving children with ASD and other PDD. First observations, based on video recording and scoring, show that + stimulates good social engagement in TD children, especially when their age is higher than 24 months.
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http://dx.doi.org/10.3389/fpsyg.2019.00125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375895PMC
February 2019

The super-learning hypothesis: Integrating learning processes across cortex, cerebellum and basal ganglia.

Neurosci Biobehav Rev 2019 05 18;100:19-34. Epub 2019 Feb 18.

Institute of Cognitive Sciences and Technologies, National Research Council, Via San Martino della Battaglia 44, 00185 Rome, Italy.

Despite wide evidence suggesting anatomical and functional interactions between cortex, cerebellum and basal ganglia, the learning processes operating within them --often viewed as respectively unsupervised, supervised and reinforcement learning-- are studied in isolation, neglecting their strong interdependence. We discuss how those brain areas form a highly integrated system combining different learning mechanisms into an effective super-learning process supporting the acquisition of flexible motor behaviour. The term "super-learning" does not indicate a new learning paradigm. Rather, it refers to the fact that different learning mechanisms act in synergy as they: (a) affect neural structures often relying on the widespread action of neuromodulators; (b) act within various stages of cortical/subcortical pathways that are organised in pipeline to support multiple sensation-to-action mappings operating at different levels of abstraction; (c) interact through the reciprocal influence of the output compartments of different brain structures, most notably in the cerebello-cortical and basal ganglia-cortical loops. Here we articulate this new hypothesis and discuss empirical evidence supporting it by specifically referring to motor adaptation and sequence learning.
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http://dx.doi.org/10.1016/j.neubiorev.2019.02.008DOI Listing
May 2019

General differential Hebbian learning: Capturing temporal relations between events in neural networks and the brain.

PLoS Comput Biol 2018 08 28;14(8):e1006227. Epub 2018 Aug 28.

Laboratory of Computational Embodied Neuroscience, Institute of Cognitive Sciences and Technologies, National Research Council of Italy (LOCEN-ISTC-CNR), Roma, Italy.

Learning in biologically relevant neural-network models usually relies on Hebb learning rules. The typical implementations of these rules change the synaptic strength on the basis of the co-occurrence of the neural events taking place at a certain time in the pre- and post-synaptic neurons. Differential Hebbian learning (DHL) rules, instead, are able to update the synapse by taking into account the temporal relation, captured with derivatives, between the neural events happening in the recent past. The few DHL rules proposed so far can update the synaptic weights only in few ways: this is a limitation for the study of dynamical neurons and neural-network models. Moreover, empirical evidence on brain spike-timing-dependent plasticity (STDP) shows that different neurons express a surprisingly rich repertoire of different learning processes going far beyond existing DHL rules. This opens up a second problem of how capturing such processes with DHL rules. Here we propose a general DHL (G-DHL) rule generating the existing rules and many others. The rule has a high expressiveness as it combines in different ways the pre- and post-synaptic neuron signals and derivatives. The rule flexibility is shown by applying it to various signals of artificial neurons and by fitting several different STDP experimental data sets. To these purposes, we propose techniques to pre-process the neural signals and capture the temporal relations between the neural events of interest. We also propose a procedure to automatically identify the rule components and parameters that best fit different STDP data sets, and show how the identified components might be used to heuristically guide the search of the biophysical mechanisms underlying STDP. Overall, the results show that the G-DHL rule represents a useful means to study time-sensitive learning processes in both artificial neural networks and brain.
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http://dx.doi.org/10.1371/journal.pcbi.1006227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130884PMC
August 2018

Know Your Body Through Intrinsic Goals.

Front Neurorobot 2018 3;12:30. Epub 2018 Jul 3.

Institute of Cognitive Sciences and Technologies, National Research Council - CNR, Rome, Italy.

The first "object" that newborn children play with is their own body. This activity allows them to autonomously form a sensorimotor map of their own body and a repertoire of actions supporting future cognitive and motor development. Here we propose the theoretical hypothesis, operationalized as a computational model, that this acquisition of body knowledge is not guided by random motor-babbling, but rather by autonomously generated goals formed on the basis of intrinsic motivations. Motor exploration leads the agent to discover and form representations of the possible sensory events it can cause with its own actions. When the agent realizes the possibility of improving the competence to re-activate those representations, it is intrinsically motivated to select and pursue them as goals. The model is based on four components: (1) a self-organizing neural network, modulated by competence-based intrinsic motivations, that acquires abstract representations of experienced sensory (touch) changes; (2) a selector that selects the goal to pursue, and the motor resources to train to pursue it, on the basis of competence improvement; (3) an echo-state neural network that controls and learns, through goal-accomplishment and competence, the agent's motor skills; (4) a predictor of the accomplishment of the selected goals generating the competence-based intrinsic motivation signals. The model is tested as the controller of a simulated simple planar robot composed of a torso and two kinematic 3-DoF 2D arms. The robot explores its body covered by touch sensors by moving its arms. The results, which might be used to guide future empirical experiments, show how the system converges to goals and motor skills allowing it to touch the different parts of own body and how the morphology of the body affects the formed goals. The convergence is strongly dependent on competence-based intrinsic motivations affecting not only skill learning and the selection of formed goals, but also the formation of the goal representations themselves.
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http://dx.doi.org/10.3389/fnbot.2018.00030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6037791PMC
July 2018

Effectiveness and Safety of Pylera® in Patients Infected by Helicobacter Pylori: A Multicenter, Retrospective, Real Life Study.

Dig Dis 2018 17;36(4):264-268. Epub 2018 Apr 17.

Department of Clinical and Experimental Medicine, Gastroenterology Unit, University of Parma, Parma, Italy.

Background: Our aims were to assess the real life effectiveness and safety of the new bismuth-containing quadruple therapy in a large population of patients infected by Helicobacter pylori.

Methods: Consecutive dyspeptic H. pylori-positive patients were enrolled, both naïve for treatment and already unsuccessfully treated. Patients were treated with Pylera® 3 capsules 4 times/daily plus omeprazole 20 mg or esomeprazole 40 mg 2 times/daily for 10 days. Eradication was confirmed using a urea-breath test (at least 30 days after the end of the treatment). Efficacy and safety were assessed.

Results: A total of 349 patients were treated. H. pylori eradication was achieved in 316 (90.5%, 95% CIs 80.8-1.0) patients in the intention-to-treat population, and in 93.5% (95% CIs 83.5-1.0) in the per-protocol population. No difference in the eradication rate was found between naïve and previously treated patients (91.3 vs. 90.0%, p = 0.901). Adverse events occurred in 55 patients (15.8%, 95% CIs 11.9-20.1). Five patients discontinued treatment: 2 patients suffered from severe abdominal pain, one patient from headache, one patient from diarrhea, and one patient from diffuse urticarial rush.

Conclusions: Pylera® achieved a remarkable eradication rate in real life both as first treatment and as a rescue therapy, with a good safety profile.
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http://dx.doi.org/10.1159/000487391DOI Listing
August 2018

The architecture challenge: Future artificial-intelligence systems will require sophisticated architectures, and knowledge of the brain might guide their construction.

Behav Brain Sci 2017 01;40:e254

Laboratory of Computational Embodied Neuroscience,Institute of Cognitive Sciences and Technologies,National Research Council of

In this commentary, we highlight a crucial challenge posed by the proposal of Lake et al. to introduce key elements of human cognition into deep neural networks and future artificial-intelligence systems: the need to design effective sophisticated architectures. We propose that looking at the brain is an important means of facing this great challenge.
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http://dx.doi.org/10.1017/S0140525X17000036DOI Listing
January 2017

Interplay of prefrontal cortex and amygdala during extinction of drug seeking.

Brain Struct Funct 2018 Apr 28;223(3):1071-1089. Epub 2017 Oct 28.

Laboratory of Computational Embodied Neuroscience, Institute of Cognitive Sciences and Technologies, National Research Council, Rome, Italy.

Extinction of Pavlovian conditioning is a complex process that involves brain regions such as the medial prefrontal cortex (mPFC), the amygdala and the locus coeruleus. In particular, noradrenaline (NA) coming from the locus coeruleus has been recently shown to play a different role in two subregions of the mPFC, the prelimbic (PL) and the infralimbic (IL) regions. How these regions interact in conditioning and subsequent extinction is an open issue. We studied these processes using two approaches: computational modelling and NA manipulation in a conditioned place preference paradigm (CPP) in mice. In the computational model, NA in PL and IL causes inputs arriving to these regions to be amplified, thus allowing them to modulate learning processes in amygdala. The model reproduces results from studies involving depletion of NA from PL, IL, or both in CPP. In addition, we simulated new experiments of NA manipulations in mPFC, making predictions on the possible results. We searched the parameters of the model and tested the robustness of the predictions by performing a sensitivity analysis. We also present an empirical experiment where, in accord with the model, a double depletion of NA from both PL and IL in CPP with amphetamine impairs extinction. Overall the proposed model, supported by anatomical, physiological, and behavioural data, explains the differential role of NA in PL and IL and opens up the possibility to understand extinction mechanisms more in depth and hence to aid the development of treatments for disorders such as addiction.
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http://dx.doi.org/10.1007/s00429-017-1533-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869906PMC
April 2018

Parkinson's disease as a system-level disorder.

NPJ Parkinsons Dis 2016 1;2:16025. Epub 2016 Dec 1.

Laboratory of Computational Embodied Neuroscience (LOCEN), Istituto di Scienze e Tecnologie della Cognizione, Consiglio Nazionale delle Ricerche (ISTC-CNR), Roma, Italy.

Traditionally, the basal ganglia have been considered the main brain region implicated in Parkinson's disease. This single area perspective gives a restricted clinical picture and limits therapeutic approaches because it ignores the influence of altered interactions between the basal ganglia and other cerebral components on Parkinsonian symptoms. In particular, the basal ganglia work closely in concert with cortex and cerebellum to support motor and cognitive functions. This article proposes a theoretical framework for understanding Parkinson's disease as caused by the dysfunction of the entire basal ganglia-cortex-cerebellum system rather than by the basal ganglia in isolation. In particular, building on recent evidence, we propose that the three key symptoms of tremor, freezing, and impairments in action sequencing may be explained by considering partially overlapping neural circuits including basal ganglia, cortical and cerebellar areas. Studying the involvement of this system in Parkinson's disease is a crucial step for devising innovative therapeutic approaches targeting it rather than only the basal ganglia. Possible future therapies based on this different view of the disease are discussed.
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http://dx.doi.org/10.1038/npjparkd.2016.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516580PMC
December 2016

Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome.

PLoS Comput Biol 2017 03 30;13(3):e1005395. Epub 2017 Mar 30.

Laboratory of Computational Embodied Neuroscience, Institute of Cognitive Sciences and Technologies, National Research Council (CNR-ISTC-LOCEN), Roma, Italy.

Motor tics are a cardinal feature of Tourette syndrome and are traditionally associated with an excess of striatal dopamine in the basal ganglia. Recent evidence increasingly supports a more articulated view where cerebellum and cortex, working closely in concert with basal ganglia, are also involved in tic production. Building on such evidence, this article proposes a computational model of the basal ganglia-cerebellar-thalamo-cortical system to study how motor tics are generated in Tourette syndrome. In particular, the model: (i) reproduces the main results of recent experiments about the involvement of the basal ganglia-cerebellar-thalamo-cortical system in tic generation; (ii) suggests an explanation of the system-level mechanisms underlying motor tic production: in this respect, the model predicts that the interplay between dopaminergic signal and cortical activity contributes to triggering the tic event and that the recently discovered basal ganglia-cerebellar anatomical pathway may support the involvement of the cerebellum in tic production; (iii) furnishes predictions on the amount of tics generated when striatal dopamine increases and when the cortex is externally stimulated. These predictions could be important in identifying new brain target areas for future therapies. Finally, the model represents the first computational attempt to study the role of the recently discovered basal ganglia-cerebellar anatomical links. Studying this non-cortex-mediated basal ganglia-cerebellar interaction could radically change our perspective about how these areas interact with each other and with the cortex. Overall, the model also shows the utility of casting Tourette syndrome within a system-level perspective rather than viewing it as related to the dysfunction of a single brain area.
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http://dx.doi.org/10.1371/journal.pcbi.1005395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5373520PMC
March 2017

New bismuth-containing quadruple therapy in patients infected with Helicobacter pylori: A first Italian experience in clinical practice.

Helicobacter 2017 Jun 26;22(3). Epub 2017 Jan 26.

Division of Surgery, "P. Colombo" Hospital, ASL RM6, Velletri (Rome), Italy.

Background: Rising antibiotic resistance requires the evaluation of new and effective therapies.

Aims: To test the efficacy and safety of the new bismuth-containing quadruple therapy in patients infected with Helicobacter pylori.

Material And Methods: Consecutive H. pylori-positive dyspeptic patients were enrolled, either naïve or with previous failure treatment. Patients were treated with Pylera (three-in-one capsules containing bismuth subcitrate potassium 140 mg, metronidazole 125 mg, and tetracycline 125 mg) three capsules q.i.d. plus omeprazole 20 mg or esomeprazole 40 mg b.i.d. for 10 days. Eradication was confirmed using an urea breath test (at least 30 days after the end of treatment). Efficacy was assessed by UBT and safety by means of treatment-emergent adverse events.

Results: One hundred and thirty-one patients were included in the study: 42% of patients were naïve, and 58%, with previous failure treatment. H. pylori eradication was achieved in 124 patients (94.7%, 95% confidence intervals (CIs) 89.3-97.8) in ITT population. In the PP population, the percentage was 97.6% (95%, CIs 93.3-99.2). No difference in eradication rate was found either between naïve and previously treated patients (92.7% vs 96.0%, P=.383), or smoking and nonsmoking ones, or in patients taking omeprazole or esomeprazole. Treatment-emergent adverse events occurred in 35 patients (26.7%, 95% CIs 19.9-34.9). They were mild in all cases except in four, who discontinued the study due to diarrhea (three patients) and diffuse urticarial rush (one patient).

Conclusions: Pylera achieved a remarkable eradication rate in clinical practice, irrespective if it was used as first treatment or as a rescue therapy. Treatment-emergent adverse events were uncommon generally mild.
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http://dx.doi.org/10.1111/hel.12371DOI Listing
June 2017

Action observation and motor imagery for rehabilitation in Parkinson's disease: A systematic review and an integrative hypothesis.

Neurosci Biobehav Rev 2017 Jan 16;72:210-222. Epub 2016 Nov 16.

Istituto di Scienze e Tecnologie della Cognizione, Consiglio Nazionale delle Ricerche (ISTC-CNR), Via San Martino della Battaglia 44, I-00185 Roma, Italy. Electronic address:

This article discusses recent evidence supporting the use of action observation therapy and motor imagery practice for rehabilitation of Parkinson's disease. A main question that emerges from the review regards the different effectiveness of these approaches and the possibility of integrating them into a single method to enhance motor behaviour in subjects with Parkinson's disease. In particular, the reviewed studies suggest that action observation therapy can have a positive effect on motor facilitation of patients and that a long-term rehabilitation program based on action observation therapy or motor imagery practice can bring some benefit on their motor recovery. Moreover, the paper discusses how the research on the combined use of action observation and motor imagery for motor improvements in healthy subjects may encourage the combined use of action observation therapy and motor imagery practice for therapeutic aims in Parkinson's disease. To date, this hypothesis has never been experimented.
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http://dx.doi.org/10.1016/j.neubiorev.2016.11.005DOI Listing
January 2017

Goal-Directed Behavior and Instrumental Devaluation: A Neural System-Level Computational Model.

Front Behav Neurosci 2016 18;10:181. Epub 2016 Oct 18.

Laboratory of Computational Embodied Neuroscience, Institute of Cognitive Sciences and Technologies, National Research Council of Italy Rome, Italy.

Devaluation is the key experimental paradigm used to demonstrate the presence of instrumental behaviors guided by goals in mammals. We propose a neural system-level computational model to address the question of which brain mechanisms allow the current value of rewards to control instrumental actions. The model pivots on and shows the computational soundness of the hypothesis for which the internal representation of instrumental manipulanda (e.g., levers) activate the representation of rewards (or "action-outcomes", e.g., foods) while attributing to them a value which depends on the current internal state of the animal (e.g., satiation for some but not all foods). The model also proposes an initial hypothesis of the integrated system of key brain components supporting this process and allowing the recalled outcomes to bias action selection: (a) the sub-system formed by the basolateral amygdala and insular cortex acquiring the manipulanda-outcomes associations and attributing the current value to the outcomes; (b) three basal ganglia-cortical loops selecting respectively goals, associative sensory representations, and actions; (c) the cortico-cortical and striato-nigro-striatal neural pathways supporting the selection, and selection learning, of actions based on habits and goals. The model reproduces and explains the results of several devaluation experiments carried out with control rats and rats with pre- and post-training lesions of the basolateral amygdala, the nucleus accumbens core, the prelimbic cortex, and the dorso-medial striatum. The results support the soundness of the hypotheses of the model and show its capacity to integrate, at the system-level, the operations of the key brain structures underlying devaluation. Based on its hypotheses and predictions, the model also represents an operational framework to support the design and analysis of new experiments on the motivational aspects of goal-directed behavior.
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http://dx.doi.org/10.3389/fnbeh.2016.00181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067467PMC
October 2016

Appetitive Pavlovian-instrumental Transfer: A review.

Neurosci Biobehav Rev 2016 Dec 28;71:829-848. Epub 2016 Sep 28.

Laboratory of Computational Embodied Neuroscience, Institute of Cognitive Sciences and Technologies, National Research Council of Italy, Rome, Italy.

Reward-related cues are an important part of our daily life as they often influence and guide our actions. This paper reviews one of the experimental paradigms used to study the effects of cues, the Pavlovian to Instrumental Transfer paradigm. In this paradigm, cues associated with rewards through Pavlovian conditioning alter motivation and choice of instrumental actions. The first transfer experiments date back to the 1940s, but only in the last decade has it been fully recognised that there are two types of transfer, specific and general. This paper presents a systematic review of both the neural substrates and the behavioral factors affecting both types of transfer. It also examines the recent application of the paradigm to study the effect of cues on human participants, both in normal and pathological conditions, and the interactions of transfer with drugs of abuse. Finally, the paper analyses the theoretical aspects of transfer to build an overall picture of the phenomenon, from early theories to recent hierarchical accounts.
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http://dx.doi.org/10.1016/j.neubiorev.2016.09.020DOI Listing
December 2016

Consensus Paper: Towards a Systems-Level View of Cerebellar Function: the Interplay Between Cerebellum, Basal Ganglia, and Cortex.

Cerebellum 2017 02;16(1):203-229

Department of Information and Communication Technologies, Universitat Pompeu Fabra, Barcelona, Spain.

Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders. Although starting from different backgrounds and dealing with different topics, all the contributors agree that viewing the cerebellum, basal ganglia, and cortex as an integrated system enables us to understand the function of these areas in radically different ways. In addition, there is unanimous consensus between the authors that future experimental and computational work is needed to understand the function of cerebellar-basal ganglia circuitry in both motor and non-motor functions. The paper reports the most advanced perspectives on the role of the cerebellum within the cerebello-basal ganglia-thalamo-cortical system and illustrates other elements of consensus as well as disagreements and open questions in the field.
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http://dx.doi.org/10.1007/s12311-016-0763-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5243918PMC
February 2017

Comparison between different colon cleansing products for screening colonoscopy. A noninferiority trial in population-based screening programs in Italy.

Endoscopy 2016 Mar 13;48(3):223-31. Epub 2016 Jan 13.

Gastroenterologia ed Endoscopia, Azienda Ospedaliero Universitaria "Ospedali Riuniti," Trieste, Italy.

Background And Study Aims: The high volume and poor palatability of 4 L of polyethylene glycol (PEG)-based bowel cleansing preparation required before a colonoscopy represent a major obstacle for patients. The aim of this study was to compare two low volume PEG-based preparations with standard 4 L PEG in individuals with a positive fecal immunochemical test (FIT) within organized screening programs in Italy.

Patients And Methods: A total of 3660 patients with a positive FIT result were randomized to receive, in a split-dose regimen, 4 L PEG or 2 L PEG plus ascorbate (PEG-A) or 2 L PEG with citrate and simethicone plus bisacodyl (PEG-CS). The noninferiority of the low volume preparations vs. 4 L PEG was tested through the difference in proportions of adequate cleansing.

Results: A total of 2802 patients were included in the study. Adequate bowel cleansing was achieved in 868 of 926 cases (93.7 %) in the 4 L PEG group, in 872 out of 911 cases in the PEG-A group (95.7 %, difference in proportions  + 1.9 %, 95 % confidence interval [CI]  - 0.1 to 3.9), and in 862 out of 921 cases in the PEG-CS group (93.6 %, difference in proportions  - 0.2 %, 95 %CI  - 2.4 to 2.0). Bowel cleansing was adequate in 95.5 % of cases when the preparation-to-colonoscopy interval was between 120 and 239 minutes, whereas it dropped to 83.3 % with longer intervals. Better cleansing was observed in patients with regular bowel movements (95.6 %) compared with those with diarrhea (92.4 %) or constipation (90.8 %).

Conclusion: Low volume PEG-based preparations administered in a split-dose regimen guarantee noninferior bowel cleansing compared with 4 L PEG. Constipated patients require a personalized preparation.

Trial Registration: EudraCT 2012 - 003958 - 82.
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http://dx.doi.org/10.1055/s-0035-1569574DOI Listing
March 2016

The Relationship Between Specific Pavlovian Instrumental Transfer and Instrumental Reward Probability.

Front Psychol 2015 17;6:1697. Epub 2015 Nov 17.

Laboratory of Computational Embodied Neuroscience, Institute of Cognitive Sciences and Technologies, National Research Council of Italy Rome, Italy.

Goal-directed behavior is influenced by environmental cues: in particular, cues associated with a reward can bias action choice toward actions directed to that same reward. This effect is studied experimentally as specific Pavlovian-instrumental transfer (specific PIT). We have investigated the hypothesis that cues associated to an outcome elicit specific PIT by rising the estimates of reward probability of actions associated to that same outcome. In other words, cues reduce the uncertainty on the efficacy of instrumental actions. We used a human PIT experimental paradigm to test the effects of two different instrumental contingencies: one group of participants had a 33% chance of being rewarded for each button press, while another had a 100% chance. The group trained with 33% reward probability showed a stronger PIT effect than the 100% group, in line with the hypothesis that Pavlovian cues linked to an outcome work by reducing the uncertainty of receiving it. The 100% group also showed a significant specific PIT effect, highlighting additional factors that could contribute to specific PIT beyond the instrumental training contingency. We hypothesize that the uncertainty about reward delivery due to testing in extinction might be one of these factors. These results add knowledge on how goal-directed behavior is influenced by the presence of environmental cues associated with a reward: such influence depends on the probability that we have to reach a reward, namely when there is less chance of getting a reward we are more influenced by cues associated with it, and vice versa.
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http://dx.doi.org/10.3389/fpsyg.2015.01697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648073PMC
December 2015
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