Around the world Alzheimer’s Disease (AD) is on the rise. Previous studies have shown the default mode network (DMN) sees changes with AD progression as the disease erodes away cortical areas. Aerobic exercise with significant increases to cardiorespiratory fitness could show neuro-protective changes to delay AD. This study will explore if functional connectivity changes in the DMN can be seen in a young adult sample by using group independent component analysis through FSL MELODIC. The young adult sample of 19 were selected from a larger study at the Brain Plasticity and Neuroimaging Laboratory at Boston University. The participants engaged in a twelve-week exercise intervention in either a strength training or aerobic training group. They also completed pre-intervention and post-intervention resting-state fMRI scans to evaluate change in functional connectivity in the default mode network. Cardiorespiratory fitness was assessed using a modified Balke protocol with pre-intervention and post-intervention VO2 max percentiles being used. Through two repeated-measure ANOVA analyses, this study found no significant increase in mean functional connectivity or cardiorespiratory fitness in the young adult sample. While improvements in mean VO2 max percentile and functional connectivity would have been seen with a larger sample size, this study adds to the literature by suggesting if fitness does not improve significantly, neither will functional connectivity in the default mode network.

The current study explored how hot and cool executive functions (EF) could predict resting-state connectivity of the Default Mode Network (DMN) and Central Executive Network (CEN) in a mixed clinical and typically developing sample of adolescents. It was hypothesized that hot EF would predict a quadratic, inverted U-shaped, relationship between connectivity of the major regions of the DMN: the Posterior Cingulate Cortex (PCC) and the Medial Prefrontal Cortex (MPFC). It also was hypothesized that cool EF would predict a quadratic, inverted U-shaped, relationship between the connectivity of the major regions of the CEN: the right Posterior Parietal Cortex (right PPC) and the right Dorsal Lateral Prefrontal Cortex (right DLPFC). The results suggested that hot EF, specifically emotional regulation, predicted a quadratic relationship in DMN connectivity. However, this relationship was U-shaped instead of an inverted U-shaped. Thus, participants who scored well or poorly in emotional regulation generally had higher connectivity than those with average scores in emotional regulation. There were no significant results between cool EF and the CEN. Additional exploratory analysis suggested that the main hypotheses were not driven or suppressed by group differences. Further exploration observed other brain regions involved in resting-state activity that may play a role in hot or cool EF. Overall, findings support the Internal Mentation Hypothesis of DMN activity and are indicative of a relationship between emotional regulation and DMN resting-state connectivity.

A perda auditiva consiste na perda, parcial ou total, da capacidade de ouvir determinados sons e compreensão de palavras. De acordo com o Censo Demográco do ano de 2000, o Brasil apresenta aproximadamente 5.700.000 de indivíduos com surdez, sendo deste total aproximadamente 2 milhões de indivíduos possuidores de perda auditiva severa e profunda. Atualmente diversos estudos têm sido realizados a m de vericar a plasticidade neural e o processo de linguagem em indivíduos surdos, entretanto pouco se conhece acerca do funcionamento do cérebro em repouso, e.g. a rede de modo padrão. O objetivo deste estudo é observar e analisar como se manifesta a organização neuronal, tanto funcional quanto estrutural, em surdos, no estado de repouso. Foram utilizadas imagens fMRI, para a obtenção de dados a respeito do funcionamento cerebral em seu estado de repouso basal, e imagens DTI, a m de se determinar as conexões neuronais. Os dados dos mapas de conectividade funcional e estrutural foram comparados com os achados denidos para sujeitos ouvintes. Nossos achados ilustram que o indivíduo surdo têm maior suporte para a atenção dirigida à tomada de decisão, monitoramento ambiental baseado nos movimentos de objetos e também no controle motor e visual. Podemos armar que a privação auditiva não oferece barreiras intransponíveis para o convívio familiar ou social, sendo o indivíduo surdo tão produtivo e capaz quanto qualquer outro, desde que a abordagem linguística seja condizente com suas capacidades sensoriais. / Hearing loss consists of partial or total loss of the ability to hear certain sounds and comprehension of words. According to the Brazilian Demographic Census of the year 2000, there are approximately 5,700,000 deaf individuals, of which approximately 2 million of them have severe and profound hearing loss. Several studies have now been carried out to verify neural plasticity and the language process in deaf individuals, however little is known about the brain functioning at rest, e.g. the network in standard mode. The objective of this study is to observe and analyze how neuronal organization, both in terms of functional and structural brain networks, is manifested in deaf individuals at resting state. We used fMRI images to obtain data on brain functioning in its basal state of rest and DTI images in order to determine neural connections. The data from the functional and structural connectivity maps were compared with the dened ndings for hearing subjects. Our ndings illustrate that the deaf individual has greater support for attention directed to decision making, environmental monitoring based on movement of objects and also on motor and visual control. We can arm that hearing deprivation does not oer impossible barriers to family or social life, being the deaf individual as productive and capable as any other, since the linguistic approach is consistent with their sensorial capacities.

Mind-wandering was until recently not a mainstream topic of research. The aim of this literature review is to present current views on the definition of mind-wandering and how the phenomenon is experienced. Furthermore, it gives an account of the implications of mind-wandering on cognitive performance, as well as its neurological correlates. In addition, the methods used to study mind-wandering are reviewed.The study of mind-wandering reveals a highly frequent phenomenon with practical consequences on a broad scale, both disruptive and supportive to goal-related behaviour and wellbeing in general. Originating from the default network, and its regions related to representations of self, memory, Theory of Mind, empathy and creativity, mind-wandering is hypothesized to be a function for planning one’s future life. Suggested further research concerns how mind-wandering can be countered, detected from the outside and whether it alters the physical feature of the brain.

Abstract: The default mode network of the brain is a set of functionally connected regions associated with introspection and daydreaming. Recent fMRI studies have discovered that the default mode network is often perturbed in the diseased brain. For example, the default mode network is known to be modulated in dementia, ADHD, depression, and schizophrenia, among others. This has led many into believing that this network could have a role in the physiopathology of nervous system disease, or could be a useful marker of brain function. However, very few studies have yet been done which investigate how surgical lesions such as brain tumours affect the default mode network. Consequently, the goal of this project was to characterise the effect of brain tumours on the default mode network based on their location, histological type, and other parameters. / Le mode de fonctionement par défaut du cerveau est un réseau cérébral associé à la rêverie et à l’introspection. Des études récentes sur ce réseau ont découvert qu’il est perturbé dans plusieurs pathologies cérébrales. Par example, le mode de fonctionnement par défaut est modulé en démence, TDAH, dépression, schizophrénie et plusieurs autres maladies liés au cerveau. Ceci a mené à l’hypothèse que le mode de fonctionnement par défaut pourrait avoir un rôle dans la physiopathologie des maladies du système nerveux, ou pourrait être un marqueur utile du fonctionnement cérébral. Par contre, très peu d’études ont investigué l’effet de lésions chirurgicaux comme les tumeurs cérébrales sur le mode de fonctionnement par défaut. Par conséquent, le but de ce projet était de caractériser l’importance de l’histologie, de la localisation et de plusieurs autres paramètres de l’effet d’une tumeur cérébrale sur le mode de fonctionnement par défaut.

Les mutations génétiques et les conditions pathologiques affectent la connectivité functionnelle du cerveau. Nous avons combiné la mutagénèse chez la souris et l’analyse de connectivité fonctionnelle (CF) par imagerie en Resonance Magnétique Nucléaire (IRM) pour déterminer l’impact de la délétion du gène codant pour le récepteur orphelin GPR88 sur la CF du cerveau entier. En utilisant une approche non biaisée, nous avons découvert que la délétion génétique chez la souris altère fortement le Default Mode Network, une caractéristique de nombreuses maladies psychiatriques. Nous avons aussi observé des modifications importantes de la connectivité des cortex moteurs et somatosensoriels,et du striatum en accord avec le pattern d’expression du récepteur. Enfin, une analyse par régions d’intérêt montre une perturbation importante du réseau mesocorticolimbic, qui pourrait expliquer la tendance de ces animaux à consommer de fortes quantités d’alcool. La concordance entre les altérations de CF et celles du comportement des animaux GPR88 knockout positionnent ce récepteur comme une cible prometteuse pour le traitement de maladies psychiatriques. / Pathological agitations of the brain and the expression or mutation of single gene affect overall brain connectivity. Here we combined mouse mutagenesis with functional and structural MRI and explored mouse whole brain connectivity maps non-invasively in response to the inactivation of Gpr88 gene. We perceived robust modifications in the default mode network which is considered a hallmark of many psychiatric conditions, followed by sensori-motor network allied to sensorimotor gating deficiency underlying hyperactivity phenotype in Gpr88-/- mice. In addition, hippocampal and dorsal striatum functional connectivity perturbations might underlie learning deficiency and weakened amygdala connectivity with cortex and striatum might suggest triggering of risk-taking behavior previously observed in these animals. Moreover, Gpr88 deletion strongly modifies the reward network leading Gpr88-/- mice vulnerable to alcohol intake. This is the first evidence of Gpr88 involvement in reshaping the mouse brain connectome. The concordance between connectivity alterations and behavior deficits posits Gpr88 as a potential target for psychiatric disorders.

This study investigated the effects of lesion presence within larger brain networks (e.g., default mode network (DMN), salience network (SN), and mentalizing network (MN)) in the chronic phase of a pediatric traumatic brain injury (TBI) and the effect on social function. We compared children with a TBI to children with an orthopedic injury (OI) with three different aims. The first aim was to determine whether network volume differed by group (e.g., TBI vs. OI). Second, investigate if lesion presence in a sub component region of the network resulted in total network volume loss for that network. Finally, learn whether network volume would predict outcome on the Behavior Assessment System for Children, Second Edition (BASC-2). Approximately 184 participants (65% male; 70% Caucasian) between the ages of 6-17 years completed testing and a structural MRI scan in the chronic stage (at least one-year post-injury) of the injury. Injury severity included complicated mild, moderate, and severe TBI. Radiological findings were analyzed using recommendations from the Common Data Elements' core (presence or absence of a lesion) and supplementary (lesion type and location) recommendations. Volumetrics for all participants were obtained with FreeSurfer to quantify total network volumes for the DMN, SN, and MN. The parent of each participant completed a behavioral measure for externalizing and internalizing behaviors. Three sets of statistical analyses were completed, including multivariate analysis of covariance, analysis of covariance, and multiple regression, for each of the three aims of the study, respectively. There were significant differences in total DMN volume between the two groups and participants with lesions solely in the MN had lower total MN volume. Moreover, lower total MN volume was associated with worse functioning on measures of externalizing and internalizing behaviors. The larger implications, including developmental and social implications, of these findings are discussed.

Psychiatry is in a crisis. Mental health disorders are on the rise worldwide and there are currently not enough efficient treatment methods that would meet the patients’ needs. Hence, the societal and economic costs of mental health problems are enormous, as well as the suffering of individuals afflicted by mental health problems. Lysergic acid diethylamide (LSD) and psilocybin are substances that create an altered state of consciousness characterized by altered sensory perception and on some occasions, ego-dissolution, and mystical experiences. In recent studies, LSD and psilocybin have been shown to carry significant therapeutic potential in the treatment of depression and anxiety disorders in conjunction with psychotherapy. The therapeutic effects of LSD and psilocybin have also been shown to persist for between 3-12 months post-treatment. LSD and psilocybin, like other classical hallucinogens, increase serotonin availability, which has been suggested to attenuate symptoms of anxiety and depression. In addition, LSD and psilocybin alter the activity of the default mode network, which has been suggested to be overly active in depressed and anxious patients. This essay is a literature review of the neural mechanisms of LSD and psilocybin, their potential therapeutic effects in the treatment of depressive and anxiety disorders, and how insights about said neural mechanisms may be useful in understanding the possible application of psychedelics in the treatment of depressive and anxiety disorders. In sum, recent studies have provided converging and convincing evidence on therapeutic potential of LSD and psilocybin. Yet, few conclusions on the exact neural mechanisms of how LSD and psilocybin alleviate depressive and anxiety symptoms can be made. Although the future of this research field looks promising, archaic national- and international regulations continue to be a hindrance to research into psychedelic drugs. Yet, due to the psychiatric crisis and the promising results so far, more studies in this field are warranted.

Background: Methamphetamine (MA) abuse is a global crisis that exacerbates sociopolitico-economic burdens in South Africa. MA use is associated with a myriad of neural abnormalities of structure and function, with associated neurocognitive deficits, particularly executive function (EF). Working memory (WM) training has been identified as a potential adjunct to treatment of substance use disorder (SUD) to improve EF in the hope of reducing relapse rates. Neuroimaging suggests MA alters intrinsic resting state functional connectivity (rsFC), and this may contribute to neuropsychological deficits observed in methamphetamine use disorder (MUD). Methods: This nested study analysed data described in Brooks et al. (2016), in which WM training was used as an adjunct to inpatient treatment of MUD. Healthy controls (HC, N = 25) were compared to two MUD groups, one receiving treatment as usual (TAU, N = 17), and one receiving additional cognitive training (CT, N = 24) in the form of a modified version of the ‘N-back' task (C-Ya). This task was also used to assess WMA in the neural scanner, using conditions of 0-back and 1-back across groups. The current research explored these data in a novel manner through examining rsFC. Hypotheses: It was predicted that: 1) HC and MUD participants would differ on measures of WMA, but WMA would improve in MA groups at follow-up compared to baseline and this would be augmented in the CT group; 2) rsFC networks of neural regions supporting WM would be predictive of ability to perform well and improve on WM tasks; and 3) MA groups would display heightened rsFC activity within and between resting state neural networks of the default mode network (DMN) and canonical cognitive control networks (CCNs). Results: Significant differences were observed between HC and MA groups in race and level of education, but not on WMA as tested in the scanner. The CT group, who completed WMA 3-back conditions, demonstrated significant improvement on this task post- intervention. Exploratory regression models showed the WM rsFC network did not demonstrate significant relationships with any clinical, demographic, or WM variables when controlling for multiple comparisons. Heightened connectivity within and between the DMN and CCNs was observed in the MUD compared to the HC group, which provided support for hypothesis 3. Exploratory multivariate regression models demonstrated race, age, education, duration of drug use, and an interaction of group and abstinence may impact rsFC in these networks. Post-hoc analyses identified pairwise network combinations affected by these variables. Conclusions: Despite limitations of this small study, it offers tentative preliminary insights into the largely unexplored field of rsFC in MA populations. This study supports limited research demonstrating hyperconnectivity within and between CCNs and DMN of MA users. This study also offers support for recent research suggesting that easier conditions of the Nback task may not reliably test all aspects of WM function. Exploratory analyses of covariates potentially affecting rsFC provide a platform for directions of future research.

京都大学 / 0048 / 新制・課程博士 / 博士(教育学) / 甲第20127号 / 教博第204号 / 新制||教||167(附属図書館) / 京都大学大学院教育学研究科教育科学専攻 / (主査)准教授 野村 理朗, 教授 齊藤 智, 教授 Emmanuel MANALO / 学位規則第4条第1項該当 / Doctor of Philosophy (Education) / Kyoto University / DGAM