Cognitive control and emotion in hallucination-proneness : exploring audiovisual cognitive and emotional conflict

Dissertação de Mestrado Interuniversitário, Neuropsicologia Clínica e Experimental, 2021, Universidade de Lisboa, Faculdade de PsicologiaProneness to unusual experiences such as hallucinations, has been proposed to exist on a continuum. Accordingly, cognitive mechanisms that underpin hallucinations may act as markers of this continuum. Cognitive control and emotion play a key role in the production of hallucinations and in this dissertation Zinchenko and colleagues’ (2015) paradigm is replicated to test if their interaction acts as a marker of a continuum underlying proneness to unusual experiences. Emotion has been found to trigger cognitive control processes and facilitate conflict processing in both emotional and cognitive conflict. When the target dimension of a stimulus is emotional, conflict processing is sped up in both conflict types. We tested if hallucination proneness modulated this emotioncognitive control interaction. The paradigm probes emotion’s influence over cognitive control in two tasks, one for each type of conflict. In cognitive conflict, participants categorized spoken vowels and in emotional conflict their emotional valence, while visual information was congruent or incongruent. Emotion was task relevant in emotional conflict, but not in cognitive conflict type. The dissertation includes the analysis of the N100 ERP in cognitive conflict. Our results show that the early dynamic interplay between emotion and cognitive control is not a marker of a cognitive continuum underlying proneness to unusual experiences. Additionally, emotional target dimension facilitated emotional conflict processing, as shown in a reduced reaction time conflict effect. However, contrary to the literature, this was not the case for cognitive conflict.Controlo cognitivo é um mecanismo adaptativo que recruta processos de atenção e que desempenha um papel fulcral na produção de comportamento direcionado a objetivos. Trata-se de um mecanismo capaz de inibir respostas automáticas e influenciar a memória de trabalho ao recrutar processos como atenção sustentada, atenção seletiva, inibição e atualização e manutenção de informação contextual (Duggirala et al., 2019). Controlo cognitivo é responsável por resolver conflito emocional, como ironia, ou conflito cognitivo, como o teste de Stroop (Stroop, 1935). Processar conflito de estímulos com dimensões incongruentes resulta em tempos de reação mais longos, numa taxa de erro mais elevada e num N100 com maior amplitude (Ochsner et al., 2009; Zinchenko et al., 2015; Zinchenko, Obermeier, Kanske, Schröger, & Kotz, 2017; Zinchenko, Obermeier, Kanske, Schröger, Villringer, et al., 2017). Esta diferença comportamental e neurofisiológica de processamento entre estímulos congruentes e incongruentes chama-se efeito de conflito e reflete uma maior competição por recursos de atenção no processamento dos estímulos incongruentes (West, 2003). Emoção influencia controlo cognitivo em conflito emocional e cognitivo, pois estímulos emocionais captam recursos de atenção (Nesse M, 1990; Zinchenko et al., 2015). Se a dimensão alvo – a dimensão importante a focar para resolver conflito – tiver propriedades emocionais o processamento de conflito é facilitado. Se a dimensão não importante para resolver conflito tiver propriedades emocionais, o processamento de conflito é dificultado. Por outras palavras, estímulos com uma dimensão alvo emocional apresentam um conflito cognitivo menor em relação a estímulos com dimensão não alvo emocional. Apesar de não existirem diferenças entre conflito emocional e cognitivo a nível comportamental cada tipo de conflito está associado a mecanismos neuropsicológicos diferentes. Conflito cognitivo resolve conflito ao amplificar o processamento da dimensão alvo, a passo que conflito emocional resolve conflito ao predizer que dimensão terá que ser inibida (Zinchenko et al., 2015). Suscetibilidade a experiências incomuns, como por exemplo alucinações, tem sido teorizada a existir num contínuo (Kelleher et al., 2013; van Os & Reininghaus, 2016). Os mecanismos cognitivos que produzem alucinações podem ser marcadores deste contínuo (Badcock & Hugdahl, 2011), como é o caso de inibição intencional (AldersonDay et al., 2019). Alucinações auditivas são produzidas por uma interação entre sinais anormais no córtex auditivo e uma incapacidade em suprimir estes mesmos sinais devido a controlo cognitivo comprometido (Laloyaux et al., 2019). Para além de controlo cognitivo, emoção também desempenha um papel central na produção de alucinações (Waters et al., 2012). Por um lado, em indivíduos com um diagnóstico psicótico existe uma associação entre sintomas positivos de psicose, como alucinações, e hipersensibilidade em relação a estímulos negativos (Duggirala et al., 2019). Caso esta maior sensibilidade também se verifique, em menor escala, em indivíduos com predisposição para alucinar, a interação emoção-controlo cognitivo será mais significativa. Uma dimensão alvo negativa (emocional) já facilita processamento de conflito, pois a propriedade emocional ajuda a recrutar processos executivos de atenção. Uma maior sensibilidade para com estímulos negativos intensificaria este processo. Por outro lado, em indivíduos com um diagnóstico psicótico notou-se que nas fases mais avançadas da psicose a interação emoção-controlo cognitivo perde força (Duggirala et al., 2019). Se o mesmo se notar em menor escala em indivíduos com predisposição para alucinar, emoção facilitaria ou dificultaria processamento de conflito de forma menos significativa. A presente dissertação testa se a interação entre emoção e controlo cognitivo é um marcador de suscetibilidade a experiências incomuns. O objetivo é aferir se a interação entre emoção e controlo cognitivo difere entre indivíduos com e sem predisposição para alucinar. A nossa hipótese exploratória consiste em avaliar se a associação entre experienciar alucinações e hipersensibilidade em relação a estímulos negativos também se manifesta de forma mais subtil em indivíduos com predisposição para alucinar. O paradigma de Zinchenko e colegas (2015), que testa a influência de emoção sobre conflito cognitivo e emocional num contexto multissensorial, foi replicado com uma amostra de indivíduos com e sem predisposição para alucinar. Consequentemente seria esperado replicar os resultados principais de Zinchenko e colegas (2015) em conflito cognitivo e emocional, nomeadamente um efeito de conflito nos tempos de reação e taxa de erro e um efeito de interação de emoção-controlo cognitivo. Ou seja, antevimos que existisse um menor efeito de conflito quando a dimensão alvo do estímulo é emocional comparativamente a neutra. No conflito cognitivo analisámos o N100 e prevemos que este exiba um efeito de conflito quando a dimensão alvo do estímulo é emocional

Constraints on a hadronic model for unidentified off-plane galactic gamma-ray sources

Recently the H.E.S.S. collaboration announced the detection of an unidentified gamma-ray source with an off-set from the galactic plane of 3.5 degrees: HESS J1507-622. If the distance of the object is larger than about one kpc it would be physically located outside the galactic disk. The density profile of the ISM perpendicular to the galactic plane, which acts as target material for hadronic gamma-ray production, drops quite fast with increasing distance. This fact places distance dependent constraints on the energetics and properties of off-plane gamma-ray sources like HESS J1507-622 if a hadronic origin of the gamma-ray emission is assumed. For the case of this source it is found that there seems to be no simple way to link this object to the remnant of a stellar explosions.Comment: 11 pages, 4 figures, accepted for publication in AdSp

Evidence for neuroprotective properties of human umbilical cord blood cells after neuronal hypoxia in vitro

<p>Abstract</p> <p>Background</p> <p>One of the most promising options for treatment of stroke using adult stem cells are human umbilical cord blood (HUCB) cells that were already approved for therapeutic efficacy <it>in vivo</it>. However, complexity of animal models has thus far limited the understanding of beneficial cellular mechanisms. To address the influence of HUCB cells on neuronal tissue after stroke we established and employed a human <it>in vitro </it>model of neuronal hypoxia using fully differentiated vulnerable SH-SY5Y cells. These cells were incubated under an oxygen-reduced atmosphere (O₂< 1%) for 48 hours. Subsequently, HUCB mononuclear cells (MNC) were added to post-hypoxic neuronal cultures. These cultures were characterized regarding to the development of apoptosis and necrosis over three days. Based on this we investigated the therapeutic influence of HUCB MNC on the progression of apoptotic cell death. The impact of HUCB cells and hypoxia on secretion of neuroprotective and inflammatory cytokines, chemokines and expression of adhesion molecules was proved.</p> <p>Results</p> <p>Hypoxic cultivation of neurons initially induced a rate of 26% ± 13% of apoptosis. Hypoxia also caused an enhanced expression of Caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP). Necrosis was only detected in low amounts. Within the next three days rate of apoptosis in untreated hypoxic cultures cumulated to 85% ± 11% (p ≤ 0.001). Specific cytokine (VEGF) patterns also suggest anti-apoptotic strategies of neuronal cells. Remarkably, the administration of MNC showed a noticeable reduction of apoptosis rates to levels of normoxic control cultures (7% ± 3%; p ≤ 0.001). In parallel, clustering of administered MNC next to axons and somata of neuronal cells was observed. Furthermore, MNC caused a pronounced increase of chemokines (CCL5; CCL3 and CXCL10).</p> <p>Conclusion</p> <p>We established an <it>in vitro </it>model of neuronal hypoxia that affords the possibility to investigate both, apoptotic neuronal cell death and neuroprotective therapies. Here we employed the therapeutic model to study neuroprotective properties of HUCB cells.</p> <p>We hypothesize that the neuroprotective effect of MNC was due to anti-apoptotic mechanisms related to direct cell-cell contacts with injured neuronal cells and distinct changes in neuroprotective, inflammatory cytokines as well as to the upregulation of chemokines within the co-cultures.</p

The central nervous system of sea cucumbers (Echinodermata: Holothuroidea) shows positive immunostaining for a chordate glial secretion

<p>Abstract</p> <p>Background</p> <p>Echinoderms and chordates belong to the same monophyletic taxon, the Deuterostomia. In spite of significant differences in body plan organization, the two phyla may share more common traits than was thought previously. Of particular interest are the common features in the organization of the central nervous system. The present study employs two polyclonal antisera raised against bovine Reissner's substance (RS), a secretory product produced by glial cells of the subcomissural organ, to study RS-like immunoreactivity in the central nervous system of sea cucumbers.</p> <p>Results</p> <p>In the ectoneural division of the nervous system, both antisera recognize the content of secretory vacuoles in the apical cytoplasm of the radial glia-like cells of the neuroepithelium and in the flattened glial cells of the non-neural epineural roof epithelium. The secreted immunopositive material seems to form a thin layer covering the cell apices. There is no accumulation of the immunoreactive material on the apical surface of the hyponeural neuroepithelium or the hyponeural roof epithelium. Besides labelling the supporting cells and flattened glial cells of the epineural roof epithelium, both anti-RS antisera reveal a previously unknown putative glial cell type within the neural parenchyma of the holothurian nervous system.</p> <p>Conclusion</p> <p>Our results show that: a) the glial cells of the holothurian tubular nervous system produce a material similar to Reissner's substance known to be synthesized by secretory glial cells in all chordates studied so far; b) the nervous system of sea cucumbers shows a previously unrealized complexity of glial organization. Our findings also provide significant clues for interpretation of the evolution of the nervous system in the Deuterostomia. It is suggested that echinoderms and chordates might have inherited the RS-producing radial glial cell type from the central nervous system of their common ancestor, i.e., the last common ancestor of all the Deuterostomia.</p

Neuronal hypoxia in vitro: Investigation of therapeutic principles of HUCB-MNC and CD133+ stem cells

Background The therapeutic capacity of human umbilical cord blood mononuclear cells (HUCB-MNC) and stem cells derived thereof is documented in animal models of focal cerebral ischemia, while mechanisms behind the reduction of lesion size and the observed improvement of behavioral skills still remain poorly understood. Methods A human in vitro model of neuronal hypoxia was used to address the impact of total HUCB-MNC (tMNC), a stem cell enriched fraction (CD133+, 97.38% CD133-positive cells) and a stem cell depleted fraction (CD133-, 0.06% CD133-positive cells) of HUCB-MNC by either direct or indirect co-cultivation with post-hypoxic neuronal cells (differentiated SH-SY5Y). Over three days, development of apoptosis and necrosis of neuronal cells, chemotaxis of MNC and production of chemokines (CCL2, CCL3, CCL5, CXCL8, CXCL9) and growth factors (G-CSF, GM-CSF, VEGF, bFGF) were analyzed using fluorescence microscopy, FACS and cytometric bead array. Results tMNC, CD133+ and surprisingly CD133- reduced neuronal apoptosis in direct co-cultivations significantly to levels in the range of normoxic controls (7% ± 3%). Untreated post-hypoxic control cultures showed apoptosis rates of 85% ± 11%. tMNC actively migrated towards injured neuronal cells. Both co-cultivation types using tMNC or CD133- reduced apoptosis comparably. CD133- produced high concentrations of CCL3 and neuroprotective G-CSF within indirect co-cultures. Soluble factors produced by CD133+ cells were not detectable in direct co-cultures. Conclusion Our data show that heterogeneous tMNC and even CD133-depleted fractions have the capability not only to reduce apoptosis in neuronal cells but also to trigger the retaining of neuronal phenotypes

Neuronal hypoxia <it>in vitro</it>: Investigation of therapeutic principles of HUCB-MNC and CD133⁺stem cells

Abstract Background The therapeutic capacity of human umbilical cord blood mononuclear cells (HUCB-MNC) and stem cells derived thereof is documented in animal models of focal cerebral ischemia, while mechanisms behind the reduction of lesion size and the observed improvement of behavioral skills still remain poorly understood. Methods A human in vitro model of neuronal hypoxia was used to address the impact of total HUCB-MNC (tMNC), a stem cell enriched fraction (CD133+, 97.38% CD133-positive cells) and a stem cell depleted fraction (CD133-, 0.06% CD133-positive cells) of HUCB-MNC by either direct or indirect co-cultivation with post-hypoxic neuronal cells (differentiated SH-SY5Y). Over three days, development of apoptosis and necrosis of neuronal cells, chemotaxis of MNC and production of chemokines (CCL2, CCL3, CCL5, CXCL8, CXCL9) and growth factors (G-CSF, GM-CSF, VEGF, bFGF) were analyzed using fluorescence microscopy, FACS and cytometric bead array. Results tMNC, CD133+ and surprisingly CD133- reduced neuronal apoptosis in direct co-cultivations significantly to levels in the range of normoxic controls (7% ± 3%). Untreated post-hypoxic control cultures showed apoptosis rates of 85% ± 11%. tMNC actively migrated towards injured neuronal cells. Both co-cultivation types using tMNC or CD133- reduced apoptosis comparably. CD133- produced high concentrations of CCL3 and neuroprotective G-CSF within indirect co-cultures. Soluble factors produced by CD133+ cells were not detectable in direct co-cultures. Conclusion Our data show that heterogeneous tMNC and even CD133-depleted fractions have the capability not only to reduce apoptosis in neuronal cells but also to trigger the retaining of neuronal phenotypes.</p