Assessing the Role of the Left Dorsal Frontal Cortex in Working Memory Guidance: Attentional or Mnemonic? A Neurostimulation Study

Available online 17 May 2019Perceptual selection can be guided by the contents of working memory (WM). Neuroimaging and neuropsychological data point to a role of a fronto-parietal and fronto-thalamic networks in WM guidance. Here we assessed the effect of transcranial direct current stimulation of the left dorsal frontal cortex (lDFC) in a combined WM/attention paradigm. We asked the extent to which the lDFC is implicated in mnemonic and selective attention functions during WM guidance of behavior. Observers were asked to keep information in memory while searching for a visual target, while the validity of WM contents for the search task varied. We tested the effects of lDFC-tDCS on the strength of WM guidance of search, whether any tDCS effect is dependent on the amount of WM load, and whether lDFC-tDCS primarily influences how WM contents are retained, the process of selective attention in search task, or both. Consistent with prior behavioral findings, we found that (i) selection of items that matched the contents of WM was facilitated relative to non-matching items and (ii) this WM guidance effect was reduced when the level processing/cognitive load in WM was higher. Notably, across two experiments we found that lDFC-tDCS modulated WM guidance of visual selection in the context of high processing loads in WM. No effects of tDCS were observed in WM accuracy. These findings suggest that the role of the left dorsal frontal cortex in WM guidance is associated with selective attentional control rather than mnemonic processing.J.B-T. was supported by a grant from the Bial Foundation. D. S. acknowledges support from the Spanish Ministry of Economy and Competitiveness (MINECO), through the ‘Severo Ochoa’ Programme for Centres/Units of Excellence in R&D (SEV-2015-490) and project grants PSI2016-76443-P from MINECO and PI-2017-25 from the Basque Governmen

Psilocybin-assisted therapy as an option for treatment-resistant depression : a narrative review

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2021A Depressão Resistente ao Tratamento é um dos outcomes do Transtorno Depressivo Major e está associada uma baixa qualidade de vida e a um maior uso de cuidados de saúde. Evidência científica demonstrou que a psilocibina, um psicadélico clássico agonista do recetor 2A de serotonina, pode ser usado como uma opção terapêutica no tratamento de diversas doenças psiquiátricas. Este trabalho tem como propósito providenciar uma revisão integrativa da atual evidência científica sobre o uso da psilocibina como opção terapêutica no tratamento da Depressão Resistente ao Tratamento. As seguintes bases de dados foram pesquisadas de 1 de janeiro de 2010 a 1 de maio de 2021: PubMed, Multidisciplinary Association for Psychedelic Studies’ (MAPS) Psychedelic Bibliography e CochraneLibrary. Apenas estudos com o objetivo de avaliar os efeitos da psilocibina em pacientes com uma idade superior a 18 anos e com o diagnóstico de Depressão Resistente ao Tratamento foram incluídos. Estudos com placebo, placebo ativo e outros tratamentos como modelos comparativos foram incluídos. Nove estudos foram incluídos. Em linha com a evidência científica anterior, o benefício do tratamento com psilocibina não está apenas associado a uma redução dos sintomas depressivos, mas também a outros efeitos como mudanças na personalidade, perspetivas, comportamentos e um bem-estar psicológico geral. Uma análise qualitativa dos pacientes submetidos ao tratamento confirma os resultados quantitativos. A psilocibina parece atuar de uma forma diferente, mas complementar aos antidepressivos clássicos. A nível neurobiológico parece criar um mecanismo de ‘reset’. A psilocibina poderá ser usada no futuro como uma opção terapêutica no tratamento da Depressão Resistente ao Tratamento. No entanto, a confirmação através de estudos randomizados controlados com placebo utilizando uma amostra mais vasta serão necessários.Treatment-Resistant Depression is one of the outcomes of Major Depression Disorder and is associated with lower health related quality of life, greater work productivity and activity impairment and increased healthcare resources utilization. Evidence has shown that psilocybin, a classic 5-HT2AR agonist psychedelic, can be used in the treatment of several mental disorders, including Major Depressive Disorder. The purpose of this paper is to provide an integrative review and offer novel insights regarding the use of psilocybin as a treatment option for Treatment-Resistant Depression. The PubMed, Multidisciplinary Association for Psychedelic Studies’ (MAPS) Psychedelic Bibliography and CochraneLibrary online databases were searched from January 1st of 2010 to May 1st of 2021. Only clinical trials evaluating the effects of psilocybin on patients, older than 18 years old, with a diagnosis of Treatment-Resistant Depression were included. Clinical trials with placebo, active placebo and previous medications as comparison models were 2 included. Nine studies formed the review. As previous evidence has shown, the benefits of treatment with psilocybin may not be only related to a reduction in depressive symptoms, but to broader effects like changes in personality, perspectives, behaviors, and psychological wellbeing overall. A qualitative analysis of the patients that underwent this treatment confirmed the quantitative results. Psilocybin appears to act in a different but complementary way of classic antidepressants and at a neurobiological level it seems to work through a ‘reset’ mechanism. Psilocybin seems to be a possible future treatment option for Treatment-Resistant Depression. However, this needs confirmation from well-designed placebo controlled randomized trials employing a large sample size

Neural substrates supporting the influence of working memory contents on visual attention

The present thesis investigates the neural mechanisms supporting working memory (WM) guidance of visual attention, focusing on the role of the thalamus. Chapter 1 is a review of the relevant literature and sets-up the specific research aims. Chapters 2 and 3 explore the role of the thalamus on guidance of attention by WM contents. Stroke patients with focal-brain lesions performed a WM-guided search task. In valid conditions, the colour of the search target was pre-cued by the WM cue while on neutral conditions there was no cue prior to search. In invalid conditions, the WM cue specified the colour of a search distracter and the target appeared elsewhere. First, it was hypothesized that lesions to the thalamus could lead to deficits in attentional control (e.g. failing to separate irrelevant memory contents with relevant target information and leading to increased capture from WM-like distracters during invalid search conditions). An alternative hypothesis was that the thalamus may support the capture of attention by WM contents, hence thalamic patients would display little bias of attention from the WM contents, despite those contents are being maintained in memory. It was found that patients with focal-thalamic lesions especially in the ventrolateral nucleus, showed no search benefit from the valid cues on search as opposed to a control group of patients with lesions outside the thalamus and non-stroke patients. In the invalid condition, thalamic patients showed no capture by the irrelevant search item that matched the WM cue, whereas a group of healthy age-match controls exhibited the normal effect of capture by irrelevant contents held in WM. These observations suggest that lesions to the ventrolateral nucleus of the thalamus impair the capture of attention from WM contents. In Chapter 4, I aimed to establish the role of cortical structures that are known to be structurally connected with the ventrolateral nucleus of the thalamus (i.e. superior frontal gyrus) in WM guidance of attention. To do this, I investigated the effects of transcranial direct current stimulation (tDCS) of the dorsal frontal cortex in WM guidance of attention under distinct WM loads. I found that despite the effect of WM guidance of attention decreasing as WM load increased, frontal-tDCS modulated WM guidance in these conditions. We suggest that the dorsal frontal cortex forms part of a network alongside the thalamus in supporting WM guidance of attention. Finally, I conducted a functional Magnetic Resonance Imaging (fMRI) experiment (Chapter 5) with healthy volunteers to test the hypothesis that the thalamus plays a role in WM guidance when learning of abstract cue-target feature associations needs to take place for guidance of behaviour to emerge. I used four Japanese ideograms as WM cues, each associated with the colour surrounding the sought after target in the subsequent search display (valid trials). In the neutral condition, four different Japanese ideograms were presented that did not predict the colour of the target. Hence, for WM to guide attention the association between the abstract cue and the colour that surrounded the search target needed to be learned. I found that responses in the thalamus and the frontoparietal cortex displayed sensitivity to the predictiveness of the ideogram cues as WM guidance of attention emerged during learning. The findings reported in this thesis demonstrate the pivotal role of the thalamus in WM guidance of attention.Open Acces

Poem for Eavan Boland

“Poema para Eavan Boland” / “Poem for Eavan Boland”, de  José Huguenin. Tradução para o inglês por Rafael Teles da Silva. Escrito para “Eavan Boland — In Her Many Images”, ABEI Journal 23.2 (2021).“Poema para Eavan Boland” / “Poem for Eavan Boland” by  José Huguenin. English translation by Rafael Teles da Silva. Written for “Eavan Boland — In Her Many Images”, ABEI Journal 23.2 (2021)

Sobre uma filosofia milenarista da história: Uma análise estrutural da iconografia O plano divino através dos séculos

Este artigo analisa uma iconografia milenarista protestante conhecida popularmente como O plano divino através dos séculos. Afinal, que história é “relatada” nos limites de seu enquadramento? A fim de tratar dessa questão, empreendo uma leitura antropológica de inspiração estruturalista, cujo objetivo é demonstrar que a oikonomia de O plano divino opera como uma “máquina de suprimir o tempo” com predileção para uma urgência do “fim dos tempos”. O argumento central consiste, pois, em demonstrar que o esquema mítico dessa iconografia milenarista pode ser lido como uma específica filosofia da história, isto é, um sistema teleológico especulativo e variável em diferentes contextos

Sobre uma filosofia milenarista da história: Uma análise estrutural da iconografia O plano divino através dos séculos*

Este artigo analisa uma iconografia milenarista protestante conhecida popularmente como O plano divino através dos séculos. Afinal, que história é “relatada” nos limites de seu enquadramento? A fim de tratar dessa questão, empreendo uma leitura antropológica de inspiração estruturalista, cujo objetivo é demonstrar que a oikonomia de O plano divino opera como uma “máquina de suprimir o tempo” com predileção para uma urgência do “fim dos tempos”. O argumento central consiste, pois, em demonstrar que o esquema mítico dessa iconografia milenarista pode ser lido como uma específica filosofia da história, isto é, um sistema teleológico especulativo e variável em diferentes contextos.This article analyzes a protestant millenarian iconography popularly known as The divine plan through the centuries. After all, what history is “reported” within the limits of its frame? In order to deal with this issue, I undertake an anthropological reading of structuralist inspiration, whose objective is to demonstrate that the oikonomia of The divine plan operates as a “machine to suppress time” with a predilection for an urgency of the “end of times”. The central argument therefore consists in demonstrating that the mythical scheme of this millenarian iconography can be read as a specific philosophy of history, that is, a teleological system speculative and variable in different contexts