Investigating the neural substrates of gambling disorder using multiple neuromodulation and neuroimaging approaches

Introduction : Le trouble du jeu de hasard et d'argent (GD) est caractérisé par un comportement de jeu inadapté qui interfère avec les activités personnelles ou professionnelles. Ce trouble psychiatrique est difficile à traiter avec les thérapies actuelles et les rechutes sont fréquentes. Les symptômes dépressifs et cognitifs (e.g., l'impulsivité), ainsi que le "craving" (désir intense de jouer) sont des facteurs prédictifs de rechutes. Une meilleure compréhension des substrats neuronaux et leurs significations cliniques pourraient mener au développement de nouveaux traitements. La stimulation transcrânienne à courant direct (tDCS) pourrait être l'un de ceux-ci car elle permet de cibler des circuits neuronaux spécifiques. De plus, la tDCS ciblant le cortex dorsolatéral préfrontal (DLPFC) pourrait améliorer les symptômes dépressifs et cognitifs et réduire le craving. Cependant, les effets précis de la tDCS sur la fonction cérébrale, ainsi que leurs significations cliniques, demeurent à être élucidés. Par ailleurs, étant donné que les patients avec GD présentent souvent des différences morphométriques par rapport aux individus en santé, il est possible de faire l'hypothèse que la morphométrie cérébrale influence les effets de la tDCS. Objectifs : Ce travail avait trois objectifs principaux. Le premier objectif était d'explorer s'il y avait des associations entre les substrats neuronaux et les symptômes cliniques et cognitifs. Le deuxième objectif était d'examiner les effets de la tDCS sur la fonction cérébrale. Le troisième objectif était d'explorer si la morphométrie du site de stimulation (DLPFC) pouvait influencer les effets de la tDCS sur les substrats neuronaux. Méthode : Nous avons réalisé quatre études différentes. Dans la première étude, nous avons mesuré la morphométrie cérébrale en utilisant l'imagerie par résonance magnétique (IRM) structurelle. Nous avons mesuré les corrélations entre la morphométrie et les symptômes cliniques (dépression, sévérité et durée du GD) et cognitifs (impulsivité). De plus, nous avons comparé la morphométrie des patients à celui d'une base de données normative (individus en santé) en contrôlant pour plusieurs facteurs comme l'âge. Dans la deuxième étude, nous avons mesuré la fonction cérébrale (connectivité fonctionnelle) des patients avec l'IRM fonctionnelle. Nous avons examiné s'il y avait des liens entre la connectivité fonctionnelle et les symptômes cognitifs (impulsivité et prise de risque) et cliniques (sévérité et durée du GD). Dans la troisième étude, nous avons étudié les effets de la tDCS sur la connectivité fonctionnelle et si la morphométrie du DLPFC pouvait influencer ces effets. Dernièrement, dans la quatrième étude, nous avons examiné si la morphométrie du DLPFC pouvait influencer les effets de la tDCS sur la neurochimie (avec la spectroscopie par résonance magnétique). Résultats : Nous avons démontré deux corrélations positives entre la superficie du cortex occipital et les symptômes dépressifs (étude I). Nous avons également mis en évidence une corrélation positive entre la connectivité fonctionnelle d'un réseau occipital et l'impulsivité (étude II). De plus, il y avait une corrélation positive entre la connectivité fonctionnelle de ce réseau et la sévérité du GD. Par ailleurs, il y avait des corrélations positives entre la connectivité fonctionnelle de l'opercule frontal droit et la prise de risque (étude II). En outre, la connectivité fonctionnelle d'un réseau cérébelleux était corrélée avec les symptômes dépressifs (étude II). Les patients avaient aussi plusieurs différences morphométriques par rapport aux individus en santé (cortex occipital, préfrontal, etc.). Nous avons démontré également que la tDCS appliquée sur le DLPFC a augmenté la connectivité fonctionnelle d'un réseau fronto-pariétal (étude III). Finalement, cette thèse a montré que la morphométrie du DLPFC influence les augmentations induites par la tDCS sur la connectivité fonctionnelle du réseau fronto-pariétal (étude III) et le niveau de GABA frontal (étude IV). Conclusions : Cette thèse démontre une importance clinique potentielle pour les régions occipitales, frontales et cérébelleuses, particulièrement pour les patients ayant des symptômes dépressifs ou cognitifs. De plus, elle montre que la tDCS peut renforcer le fonctionnement d'un réseau fronto-pariétal connu pour son rôle dans les fonctions exécutives. Il reste à déterminer si un plus grand nombre de sessions pourrait apporter des bénéfices cliniques additionnels afin d'aider les patients à résister le jeu. Finalement, les résultats de cette thèse suggèrent que la morphométrie des régions sous les électrodes pourrait aider à identifier les meilleurs candidats pour la tDCS et pourrait être considéré pour la sélection des cibles de stimulation.Introduction: Gambling disorder (GD) is characterised by maladaptive gambling behaviour that interferes with personal or professional activities. This psychiatric disorder is difficult to treat with currently available treatments and relapse rates are high. Several factors can predict relapse, including depressive and cognitive (e.g., impulsivity, risk taking) symptoms, in addition to craving (strong desire to gamble). A better understanding of neural substrates and their clinical significance could help develop new treatments. Transcranial direct current stimulation (tDCS) might be one of these since it can target specific neural circuits. In addition, tDCS targeting the dorsolateral prefrontal cortex (DLPFC) could improve depressive and cognitive symptoms as well as reduce craving. However, the precise effects of tDCS on brain function, as well as their clinical significance, remain to be elucidated. Furthermore, considering that patients with GD often display morphometric differences as compared to healthy individuals, it may be worth investigating whether brain morphometry influences the effects of tDCS. Objectives: This work had three main objectives. The first objective was to explore whether there were associations between neural substrates and clinical and cognitive symptoms. The second objective was to examine the effects of tDCS on brain function. The third objective was to explore whether morphometry of the stimulation site (DLPFC) influenced the effects of tDCS on neural substrates. Methods: We carried out four different studies. In the first study, we investigated brain morphometry using structural magnetic resonance imaging (MRI). We tested for correlations between morphometry and clinical symptoms (depression, GD severity, GD duration) and cognitive symptoms (impulsivity). In addition, we compared the morphometry of patients with GD to that of a normative database (healthy individuals) while controlling for several factors such as age. In a second study, we assessed brain function (functional connectivity) in patients with functional MRI (fMRI). We examined whether there were associations between brain function and cognitive symptoms (impulsivity and risk taking) as well as clinical symptoms (GD severity and duration). In the third study, we examined tDCS-induced effects on brain function and whether morphometry of the DLPFC influenced these effects. Lastly, in the fourth study, we examined whether DLPFC morphometry influenced tDCS-induced effects on neurochemistry (using magnetic resonance spectroscopy imaging). Results: Firstly, we found two positive correlations between surface area of the occipital cortex and depressive symptoms (study I). We also showed a positive correlation between functional connectivity of an occipital network and impulsivity (study II). In addition, there was a positive correlation between functional connectivity of this network and GD severity (study II). In addition, there were positive correlations between functional connectivity of the right frontal operculum and risk-taking (study II). Also, functional connectivity of a cerebellar network was positively correlated with depressive symptoms (study II). Moreover, patients with GD had several morphometric differences as compared to healthy individuals (occipital and prefrontal cortices, etc.). Furthermore, we observed that tDCS over the DLPFC increased functional connectivity of a fronto-parietal circuit during stimulation (study III). Lastly, this thesis indicated that DLPFC morphometry influenced tDCS-induced elevations on fronto-parietal functional connectivity (study III) and frontal GABA levels (study IV). Conclusions: This thesis suggests the potential clinical relevance of occipital, frontal, and cerebellar regions, particularly for those with depressive and cognitive symptoms. It also indicates that tDCS can strengthen the functioning of a fronto-parietal network known to be implicated in executive functions. It remains to be seen whether a greater number of tDCS sessions could lead to clinical benefits to help patients resist gambling. Finally, the results of this thesis suggest that morphometry of the regions under the electrodes might help predict better candidates for tDCS and could be considered to select stimulation targets

Letter from Christina Bouchard Duplissa to her cousin Amy Bouchard Morin

Letter from Christina Bouchard Duplissa to her cousin Amy Bouchard Morin, December 15, 1994. This letter contains reminiscences about Duplissa\u27s early years on French Island in Old Town, Maine, between 1939 and 1950. She recalls children\u27s games and other entertainment; and neighborhood relationships. Typed transcription, no original copy.https://digitalcommons.library.umaine.edu/mf026/1067/thumbnail.jp

Designing a Semantically Rich Visual Iinterface for Cultural Digital Libraries Using the UNESCO Multilingual Thesaurus

This paper reports on the design of a visual user interface for the UNESCO digital portal. The interface makes use of the UNESCO multilingual thesaurus to provide visualized views of terms and their relationships and the way in which spaces associated with the thesaurus, the query and the results can be integrated into a single user interface.\u

Changes in resting-state functional MRI connectivity during and after transcranial direct current stimulation in healthy adults

IntroductionTranscranial direct current stimulation (tDCS) applied over the dorsolateral prefrontal cortex (DLPFC) at rest can influence behaviors. However, its mechanisms remain poorly understood. This study examined the effect of a single session of tDCS over the bilateral DLPFC on resting-state functional connectivity using fMRI (rs-fcMRI) during and after stimulation in healthy adults. We also investigated whether baseline rs-fcMRI predicted tDCS-induced changes in rs-fcMRI.MethodsThis was a randomized, sham-controlled, double-blind, crossover study. We delivered tDCS for 30 min at 1 mA with the anode and cathode over the left and right DLPFC, respectively. We used seed-based analyses to measure tDCS-induced effects on whole-brain rs-fcMRI using a 3 (before, during, after stimulation) × 2 (active, sham stimulation) ANOVA.ResultsThere were four significant Time × Stimulation interactions on the connectivity scores with the left DLPFC seed (under the anode electrode) and no interactions for the right DLPFC seed (under the cathode electrode). tDCS changed rs-fcMRI between the left DLPFC seed and parieto-occipital, parietal, parieto-occipitotemporal, and frontal clusters during and after stimulation, as compared to sham. Furthermore, rs-fcMRI prior to stimulation predicted some of these tDCS-induced changes in rs-fcMRI during and after stimulation. For instance, rs-fcMRI of the fronto-parietooccipital network predicted changes observed after active stimulation, rs-fcMRI of the fronto-parietal network predicted changes during active stimulation, whereas rs-fcMRI of the fronto-parieto-occipitotemporal and the frontal networks predicted changes both during and after active stimulation.DiscussionOur findings reveal that tDCS modulated rs-fcMRI both during and after stimulation mainly in regions distal, but also in those proximal to the area under the anode electrode, which were predicted by rs-fcMRI prior to tDCS. It might be worth considering rs-fcMRI to optimize response to tDCS

An accurate calculation of the nucleon axial charge with lattice QCD

We report on a lattice QCD calculation of the nucleon axial charge, $g_A$, using M\"{o}bius Domain-Wall fermions solved on the dynamical $N_f=2+1+1$ HISQ ensembles after they are smeared using the gradient-flow algorithm. The calculation is performed with three pion masses, $m_\pi\sim\{310,220,130\}$ MeV. Three lattice spacings ($a\sim\{0.15,0.12,0.09\}$ fm) are used with the heaviest pion mass, while the coarsest two spacings are used on the middle pion mass and only the coarsest spacing is used with the near physical pion mass. On the $m_\pi\sim220$ MeV, $a\sim0.12$ fm point, a dedicated volume study is performed with $m_\pi L \sim \{3.22,4.29,5.36\}$. Using a new strategy motivated by the Feynman-Hellmann Theorem, we achieve a precise determination of $g_A$ with relatively low statistics, and demonstrable control over the excited state, continuum, infinite volume and chiral extrapolation systematic uncertainties, the latter of which remains the dominant uncertainty. Our final determination at 2.6\% total uncertainty is $g_A = 1.278(21)(26)$, with the first uncertainty including statistical and systematic uncertainties from fitting and the second including model selection systematics related to the chiral and continuum extrapolation. The largest reduction of the second uncertainty will come from a greater number of pion mass points as well as more precise lattice QCD results near the physical pion mass.Comment: 17 pages + 11 pages of references and appendices. 15 figures. Interested readers can download the Python analysis scripts and an hdf5 data file at https://github.com/callat-qcd/project_gA_v

Cannabinoid Receptors CB1 and CB2 Modulate the Electroretinographic Waves in Vervet Monkeys

The expression patterns of the cannabinoid receptor type 1 (CB1R) and the cannabinoid receptor type 2 (CB2R) are well documented in rodents and primates. In vervet monkeys, CB1R is present in the retinal neurons (photoreceptors, horizontal cells, bipolar cells, amacrine cells, and ganglion cells) and CB2R is exclusively found in the retinal glia (Müller cells). However, the role of these cannabinoid receptors in normal primate retinal function remains elusive. Using full-field electroretinography in adult vervet monkeys, we recorded changes in neural activity following the blockade of CB1R and CB2R by the intravitreal administration of their antagonists (AM251 and AM630, resp.) in photopic and scotopic conditions. Our results show that AM251 increases the photopic a-wave amplitude at high flash intensities, whereas AM630 increases the amplitude of both the photopic a- and b-waves. In scotopic conditions, both blockers increased the b-wave amplitude but did not change the a-wave amplitude. These findings suggest an important role of CB1R and CB2R in primate retinal function

Mobius domain-wall fermions on gradient-flowed dynamical HISQ ensembles

We report on salient features of a mixed lattice QCD action using valence Mobius domain-wall fermions solved on the dynamical N-f = 2 + 1 + 1 highly improved staggered quark sea- quark ensembles generated by the MILC Collaboration. The approximate chiral symmetry properties of the valence fermions are shown to be significantly improved by utilizing the gradient- flow scheme to first smear the highly improved staggered quark configurations. The greater numerical cost of the Mobius domain- wall inversions is mitigated by the highly efficient QUDA library optimized for NVIDIA GPU accelerated compute nodes. We have created an interface to this optimized QUDA solver in CHROMA. We provide tuned parameters of the action and performance of QUDA using ensembles with the lattice spacings a similar or equal to {0.15; 0.12; 0.09} fm and pion masses m(pi) similar or equal to {310; 220; 130} MeV. We have additionally generated two new ensembles with a similar to 0.12 fm and m(pi) similar to {400; 350} MeV. With a fixed flow time of t(gf) = 1 in lattice units, the residual chiral symmetry breaking of the valence fermions is kept below 10% of the light quark mass on all ensembles, m(res) less than or similar to 0.1 x m(l), with moderate values of the fifth dimension L-5 and a domain- wall height M-5 \u3c= 1.3. As a benchmark calculation, we perform a continuum, infinite volume, physical pion and kaon mass extrapolation of F-K +/-/F-pi +/- and demonstrate our results are independent of flow time and consistent with the FLAG determination of this quantity at the level of less than one standard deviation

Sept façons à prendre en main la mise en œuvre de la formation médicale fondée sur les compétences au niveau des programmes

Competency-based medical education (CBME) curricula are becoming increasingly common in graduate medical education. Put simply, CBME is focused on educational outcomes, is independent of methods and time, and is composed of achievable competencies.1 In spite of widespread uptake, there remains much to learn about implementing CBME at the program level. Leveraging the collective experience of program leaders at Queen’s University, where CBME simultaneously launched across 29 specialty programs in 2017, this paper leverages change management theory to provide a short summary of how program leaders can navigate the successful preparation, launch, and initial implementation of CBME within their residency programs

Chemically-Mediated Roostmate Recognition and Roost Selection by Brazilian Free-Tailed Bats (Tadarida brasiliensis)

BACKGROUND: The Brazilian free-tailed bat (Tadarida brasiliensis) is an exceptionally social and gregarious species of chiropteran known to roost in assemblages that can number in the millions. Chemical recognition of roostmates within these assemblages has not been extensively studied despite the fact that an ability to chemically recognize individuals could play an important role in forming and stabilizing complex suites of social interactions. METHODOLOGY/PRINCIPAL FINDINGS: Individual bats were given a choice between three roosting pouches: one permeated with the scent of a group of roostmates, one permeated with the scent of non-roostmates, and a clean control. Subjects rejected non-roostmate pouches with greater frequency than roostmate pouches or blank control pouches. Also, bats chose to roost in the roostmate scented pouches more often than the non-roostmate or control pouches. CONCLUSIONS/SIGNIFICANCE: We demonstrated that T. brasiliensis has the ability to chemically recognize roostmates from non-roostmates and a preference for roosting in areas occupied by roostmates. It is important to investigate these behaviors because of their potential importance in colony dynamics and roost choice