An Imperfect Dopaminergic Error Signal Can Drive Temporal-Difference Learning

An open problem in the field of computational neuroscience is how to link synaptic plasticity to system-level learning. A promising framework in this context is temporal-difference (TD) learning. Experimental evidence that supports the hypothesis that the mammalian brain performs temporal-difference learning includes the resemblance of the phasic activity of the midbrain dopaminergic neurons to the TD error and the discovery that cortico-striatal synaptic plasticity is modulated by dopamine. However, as the phasic dopaminergic signal does not reproduce all the properties of the theoretical TD error, it is unclear whether it is capable of driving behavior adaptation in complex tasks. Here, we present a spiking temporal-difference learning model based on the actor-critic architecture. The model dynamically generates a dopaminergic signal with realistic firing rates and exploits this signal to modulate the plasticity of synapses as a third factor. The predictions of our proposed plasticity dynamics are in good agreement with experimental results with respect to dopamine, pre- and post-synaptic activity. An analytical mapping from the parameters of our proposed plasticity dynamics to those of the classical discrete-time TD algorithm reveals that the biological constraints of the dopaminergic signal entail a modified TD algorithm with self-adapting learning parameters and an adapting offset. We show that the neuronal network is able to learn a task with sparse positive rewards as fast as the corresponding classical discrete-time TD algorithm. However, the performance of the neuronal network is impaired with respect to the traditional algorithm on a task with both positive and negative rewards and breaks down entirely on a task with purely negative rewards. Our model demonstrates that the asymmetry of a realistic dopaminergic signal enables TD learning when learning is driven by positive rewards but not when driven by negative rewards

The Protective Action Encoding of Serotonin Transients in the Human Brain

The role of serotonin in human brain function remains elusive due, at least in part, to our inability to measure rapidly the local concentration of this neurotransmitter. We used fast-scan cyclic voltammetry to infer serotonergic signaling from the striatum of fourteen brains of human patients with Parkinson's disease. Here we report these novel measurements and show that they correlate with outcomes and decisions in a sequential investment game. We find that serotonergic concentrations transiently increase as a whole following negative reward prediction errors, while reversing when counterfactual losses predominate. This provides initial evidence that the serotonergic system acts as an opponent to dopamine signaling, as anticipated by theoretical models. Serotonin transients on one trial were also associated with actions on the next trial in a manner that correlated with decreased exposure to poor outcomes. Thus, the fluctuations observed for serotonin appear to correlate with the inhibition of over-reactions and promote persistence of ongoing strategies in the face of short-term environmental changes. Together these findings elucidate a role for serotonin in the striatum, suggesting it encodes a protective action strategy that mitigates risk and modulates choice selection particularly following negative environmental events

Training and workforce: an expert panel presents a new approach to epilepsy in the tropics

Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

Anleitung („instruction manual“) zur Anwendung der operationalen Klassifikation von Anfallsformen der ILAE 2017 // Instruction manual for the ILAE 2017 operational classification of seizure types

Dieser Begleittext zur Einführung der Klassifikation von Anfallsformen durch die Internationale Liga gegen Epilepsie (ILAE) bietet eine Anleitung, wie diese Klassifikation anzuwenden ist. Die Klassifikation wird anhand von Tabellen, einem Glossar wichtiger Fachbegriffe, einer tabellarischen Zuordnung alter und neuer Fachbegriffe, empfohlenen Abkürzungen und anhand von Beispielen verdeutlicht. Abhängig von der gewünschten Detailgenauigkeit kann eine einfache und eine ausführliche Version der Klassifikation benutzt werden. Die semiologischen Hauptsymptome werden als Grundlage zur Kategorisierung von Anfällen verwendet, die einen fokalen, generalisierten oder unbekannten Ursprung haben können. Alle fokalen Anfälle können zusätzlich hinsichtlich der erhaltenen oder gestörten Bewusstheit als bewusst oder nicht bewusst erlebt charakterisiert werden. Hierbei bedingt eine Beeinträchtigung in irgendeinem Abschnitt des Anfalls eine Klassifikation als Anfall mit Bewusstseinsstörung. Fokale Anfälle können ferner optional durch die ersten motorischen Zeichen als atonisch, mit Automatismen, klonisch, als epileptische Spasmen, hyperkinetisch, myoklonisch oder tonisch charakterisiert werden. Anfälle mit nichtmotorischem Beginn können sich als autonom, mit Innehalten (Verhaltensarrest), kognitiv, emotional oder sensorisch manifestieren. Die erste prominente Manifestation definiert die Anfallsform, die sich dann zu anderen Symptomen weiterentwickeln kann. Fokale Anfälle können sich zu bilateral tonisch-klonischen Anfällen entwickeln. Generalisierte Anfälle beinhalten eine frühe Involvierung bilateraler Netzwerke von Anfang an. Generalisierte motorische Anfallscharakteristika umfassen atonische, klonische, myoklonische, myoklonisch-atonische, myoklonisch-tonisch-klonische, tonische, tonisch-klonische Manifestationen oder epileptische Spasmen. Nichtmotorische Anfälle (Absencen) sind typisch oder atypisch, oder Anfälle mit prominenter myoklonischer Aktivität oder Lidmyoklonien. Anfälle unbekannten Ursprungs können Eigenschaften haben, die immerhin als motorisch, nichtmotorisch, tonisch-klonisch, epileptische Spasmen oder als Innehalten klassifiziert werden können. Diese Anleitung zur Anfallsklassifikation der ILAE 2017 kann die Akzeptanz der neuen Systematik unterstützen

Astrocitoma subependimário de células gigantes em pacientes com esclerose tuberosa: achados em ressonância magnética de dez casos Subependymal giant cell astrocytoma in patients with tuberous sclerosis: magnetic resonance imaging findings in ten cases

OBJETIVO: Relatar os achados de ressonância magnética (RM) em 10 casos de astrocitoma subependimário de células gigantes (ASCG) em pacientes com esclerose tuberosa (ET). MÉTODO: Foram estudados de forma retrospectiva 10 pacientes com ET e diagnóstico histológico comprovado de ASCG. Quatro pacientes eram do sexo masculino e seis do feminino, com idade média de 15,7 anos. Todos os pacientes foram investigados com RM, sendo os exames revisados por dois radiologistas, havendo decisão por consenso sobre os achados de imagem. Foram analisados os seguintes achados: localização, dimensões, intensidade de sinal em T1/T2, realce pós-contraste e outros achados associados. RESULTADOS: Todos os pacientes apresentaram lesão única sugestiva de ASCG, medindo entre 1,5 cm e 8 cm em seu maior diâmetro. Oito lesões foram encontradas junto ao forame de Monro (80%) e duas adjacentes ao corpo do ventrículo lateral (20%). Os tumores apresentavam nas imagens pesadas em T1 médio sinal (70%) e em T2 alto sinal (100%), com realce intenso após a administração do gadolínio (100%). CONCLUSÃO: Os astrocitomas subependimários de células gigantes em pacientes com ET em geral apresentam-se como lesão única próxima ao forame de Monro, com médio sinal nas imagens ponderadas em T1, alto sinal em T2 e realce intenso após a administração de contraste.<br>OBJECTIVE: To report the magnetic resonance imaging (MRI) findings in 10 patients with subependimal giant cell astrocytoma (SGCA) and tuberous sclerosis (TS). METHOD: Ten patients were retrospectively studied, presenting TS and histologically proven SGCA. Four patients were male and six female, with mean age 15.7 years. All patients underwent MRI, which was analyzed by two radiologists, final diagnosis was reached by consensus. The following findings were studied: topography, size, signal intensity on T1/T2-weighted images, contrast enhancement and associated findings. RESULTS: All patients presented a single lesion suggestive of SGCA, measuring between 1.5 cm and e 8 cm in the largest diameter. Eight lesions were found near the foramen of Monro and two in the body of the lateral ventricles. The tumors showed preferentially intermediate signal on T1 (70%), high signal on T2-weighted images (100%), with intense enhancement after contrast administration (100%). CONCLUSION: SGCA in patients with TS usually presents as a single lesion near the foramen of Monro, with intermediate signal on T1, high signal on T2-weighted images and intense contrast enhancement

Which terms should be used to describe medications used in the treatment of seizure disorders? An ILAE position paper

A variety of terms, such as "antiepileptic," "anticonvulsant," and "antiseizure" have been historically applied to medications for the treatment of seizure disorders. Terminology is important because using terms that do not accurately reflect the action of specific treatments may result in a misunderstanding of their effects and inappropriate use. The present International League Against Epilepsy (ILAE) position paper used a Delphi approach to develop recommendations on English-language terminology applicable to pharmacological agents currently approved for treating seizure disorders. There was consensus that these medications should be collectively named "antiseizure medications". This term accurately reflects their primarily symptomatic effect against seizures and reduces the possibility of health care practitioners, patients, or caregivers having undue expectations or an incorrect understanding of the real action of these medications. The term "antiseizure" to describe these agents does not exclude the possibility of beneficial effects on the course of the disease and comorbidities that result from the downstream effects of seizures, whenever these beneficial effects can be explained solely by the suppression of seizure activity. It is acknowledged that other treatments, mostly under development, can exert direct favorable actions on the underlying disease or its progression, by having "antiepileptogenic" or "disease-modifying" effects. A more-refined terminology to describe precisely these actions needs to be developed