The default mode network (DMN) is a highly cited neural network whose functional roles are not well understood. Until recently, event related fMRI experiments used to study the DMN could only be conducted in an open-loop format. The purpose of this study was to demonstrate the potential statistical advantages of real-time fMRI studies to conduct closed-loop experiments to directly test putative DMN functions. Using both fMRI simulations and large archival datasets, we demonstrate that open-loop designs are less statistically powerful than closed-loop experiments that can trigger stimuli at controlled levels of brain activity. When simulating event scheduling on resting state data, DMN levels were normally distributed, but the event timing proved to be ineffective in capturing the highest and lowest DMN values on average across subjects. Statistical differences in DMN levels collected by the Human Connectome Project-Aging (HCP-A) during a Go/NoGo task were also reported, along with the network's distributional effects across subjects. When examining DMN levels in 136 subjects more prone to commission errors the mean DMN levels were reported to be higher during and prior to incorrect NoGo responses. Exploring DMN levels in these same individuals reacting to a Go task also revealed differing measurement patterns when compared to all 711 subjects in the study. Additionally, the distribution of total DMN levels across all participants, as well as during a Go or NoGo trial, showed a shift in the mean towards deactivation. Furthermore, the peak at this location was greater and revealed that increased sampling occurred at the mean and under sampling at the tails. Overall, the cumulative findings in this study were successful in providing statistical arguments to support propositions for more powerful closed-loop experimentation in fMRI. / Master of Science / Activity in a neural network is observed through the use of functional MRI (fMRI) by tracking higher levels of oxygenated blood to that region when active and lower quantities when inactive. Neural networks vary in their responsibilities, thus fMRI tasks are designed to trigger a response based on the functional role of the network. This can be exemplified by studying the blood flow to default mode network (DMN), a network responsible for mind wandering, during a task that requires focus. Researchers can then correlate moments of high activity, which indicates a greater degree of mind wandering, or low activity to a correct or incorrect response to the task. Unfortunately, the timing in which a task is presented to the participant is predetermined prior to the subject entering the MRI making it difficult to capture a correct or incorrect response at the precise moment of activation or deactivation. This concept is known as open-loop and often collects data at moments of neutral activity, neither high nor low. In contrast, a closed-loop design allows a researcher to monitor the DMN's activation levels in real time and present the task at a desired time. This provides more useful data to the experimenter as all recorded responses to the task correlate with exact moments of high and low activation. This makes claims about the neural network's role statistically more powerful as there is a greater quantity of data at these moments rather than during a neutral activation state. The purpose of this thesis is to provide statistical arguments that support propositions for more powerful closed-loop experimentation in fMRI.

Le cerveau présente des fluctuations de son activité qui reflètent différents niveaux d’engagement avec le monde extérieur. Le traitement des stimuli externes n’est pas seulement associé avec une augmentation du métabolisme cérébrale, mais également avec une désactivation importante dans un ensemble des structures spécifiques connus sous le nom de ‘Default-Mode Network’ (DMN, réseau par défaut). Le rôle du DMN reste énigmatique en partie parce que ses corrélats électrophysiologiques et sa dynamique temporelle sont encore mal compris. En utilisant des enregistrements éléctrophysiologiques intracrânien chez le patient épileptique, nous démontrons que la population neuronale de ce réseau montre des suppressions de l’activité gamma (60-140 Hz). Plus important, nous montrons de quelle manière le profil temporale (en millisecondes) et l’amplitude de cette désactivation sont étroitement corrélés avec la difficulté de la tâche et la performance individuelle. Les résultats mettent également en évidence que pendant une tâche attentionnelle, une activation soutenue dans le temps de la bande gamma est présente dans un large réseau, alors que des activations transitoires sont spécifiques aux régions temporale et occipitale. Nos résultats révèlent ainsi un rôle essentiel des mécanismes d’activation et de désactivation des oscillations large bande gamma dans l’exécution d’un comportement orienté vers un but. / The brain displays moment-to-moment activity fluctuations that reflect various levels of engagement with the outside world. Processing external stimuli is not only associated with increased brain metabolism but also with prominent deactivation in specific structures, collectively known as the default-mode network (DMN). The role of the DMN remains enigmatic partly because its electrophysiological correlates and temporal dynamics are still poorly understood. Using unprecedented wide-spread depth recordings in epileptic patients, undergoing intracranial EEG during pre-surgical evaluation, we reveal that DMN neural populations display task-related suppressions of gamma (60-140 Hz) power and, critically, we show how millisecond temporal profile and amplitude of gamma deactivation tightly correlate with task demands and subject performance. The results show also that during an attentional task, sustained activations in the gamma band power are presented across large cortical networks, while transient activations are mostly specific to occipital and temporal regions. Our findings reveal a pivotal role for broadband gamma modulations in the interplay between activation and deactivation networks mediating efficient goal-directed behavior

Attention is a key mental function in everyday life, but unfortunately we easily get distracted. The brain correlates underlying sustained attention, the so-called sustained attention network (SAN), have been well identified, as have the brain correlates underlying mind-wandering, the so-called default mode network (DMN). Nevertheless, even though we know about the underlying brain processes, this knowledge has not yet been translated in advanced brain-based attention training protocols. Here we proposed to use a novel brain imaging technique based on real-time functional magnetic resonance imaging (fMRI) to provide individuals with information about ongoing levels of activity in the attention and the default mode networks. To the best of our knowledge, this is the first study to show that, with the help of that fMRI-neurofeedback, individuals can learn how to improve controlling of, at the same time, SAN activation and DMN deactivation. This learning process was explained mainly in terms of DMN deactivation. Behavioral effects were observed when separating a group with the best learners in an overall measure of attention and specifically in the task-switching ability, controlled by a test-retest group performing the same behavioral tests battery. Neurofeedback-induced functional connectivity changes were also observed in multiple brain regions positively and negatively related to attention. Although the behavioral effects were no longer present two months after training, participants still held the learned ability of controlling self-regulation of the concerned networks. This approach potentially provides a non-invasive and non-pharmacological tool to deliver general enhancements in the attention ability for healthy subjects and it can be potentially beneficial to many neurological and psychiatric patients. We also show in this thesis compelling evidence that brain regions definition and other experimental parameters are crucial for inducing learning of self-regulation via fMRI-neurofeedback, in a similar study also considering differential signal of attention-related competitive networks. We finally present Personode, a useful, easy to use, and open access toolbox to neuroimaging researchers, for independent component analysis maps classification into canonical resting-state networks and regions-of--interest definition in individual and group levels. We also show that the toolbox leads to better results for task-induced activation and functional connectivity analyses. / A atenção é uma função mental crucial na vida cotidiana, mas infelizmente distrai-se facilmente. Os fundamentos cerebrais que sustentam a atenção, a chamada rede de atenção, foram satisfatoriamente identificados, assim como os fundamentos cerebrais que sustentam a divagação, a chamada rede de modo padrão. Entretanto, embora tais processos sejam conhecidos, este conhecimento ainda não foi transformado em protocolos avançados de treinamento de atenção baseado na atividade cerebral. Portanto, é proposto o uso de uma nova técnica baseada em imageamento por ressonância funcional (fMRI) em tempo real para proporcionar aos indivíduos informação sobre os níveis de atividade cerebral atuais nas redes de atenção e de modo padrão. Segundo nosso conhecimento atual, esse é o primeiro estudo a mostrar que, com o auxílio do neurofeedback baseado em fMRI, indivíduos podem aprender como melhorar o controle da ativação da rede de atenção e da desativação da rede de modo padrão ao mesmo tempo. Este processo de treinamento poderia ser explicado principalmente em termos da desativação da rede de modo padrão. Efeitos comportamentais foram observados, ao separar um grupo com os melhores aprendizes, em uma medida de atenção geral e, especificamente, na habilidade de alternação de tarefas, controlado por um grupo teste-reteste realizando a mesma bateria de testes comportamentais. Alterações em conectividade funcional induzidas por neurofeedback foram também reveladas em múltiplas regiões cerebrais positiva e negativamente relacionadas à atenção. Embora os efeitos comportamentais não puderam ser constatados depois de dois meses após o treinamento, os participantes ainda mantiveram a habilidade de controlar a autorregulação das redes em questão. Esse método provê uma ferramenta não-invasiva e não-farmacológica para proporcionar melhorias gerais na habilidade de atenção para sujeitos saudáveis, o que pode ser potencialmente benéfico para muitos pacientes de desordens neurológicas e psiquiátricas. Nesta tese, são mostradas evidências convincentes de que a definição de redes cerebrais e outros parâmetros experimentais de neurofeedback baseado em fMRI são decisivos para a indução do aprendizado de autorregulação, em um estudo similar, também considerando o sinal diferencial de redes competitivas relacionadas à atenção. Finalmente, é apresentado Personode, uma ferramenta útil, de fácil utilização e de livre acesso direcionado a pesquisadores em neuroimagem, para classificação de mapas produzidos por uma análise de componentes independentes em redes de repouso canônicas e definições de regiões de interesse em níveis individuais e de grupo. É também mostrado que a ferramenta conduz a melhores resultados para análises de ativação induzida à tarefa e conectividade funcional.

The brain displays moment-to-moment activity fluctuations that reflect various levels of engagement with the outside world. Processing external stimuli is not only associated with increased brain metabolism but also with prominent deactivation in specific structures, collectively known as the default-mode network (DMN). The role of the DMN remains enigmatic partly because its electrophysiological correlates and temporal dynamics are still poorly understood. Using unprecedented wide-spread depth recordings in epileptic patients, undergoing intracranial EEG during pre-surgical evaluation, we reveal that DMN neural populations display task-related suppressions of gamma (60-140 Hz) power and, critically, we show how millisecond temporal profile and amplitude of gamma deactivation tightly correlate with task demands and subject performance. The results show also that during an attentional task, sustained activations in the gamma band power are presented across large cortical networks, while transient activations are mostly specific to occipital and temporal regions. Our findings reveal a pivotal role for broadband gamma modulations in the interplay between activation and deactivation networks mediating efficient goal-directed behavior

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common child-onset neurodevelopment disorders, affecting 5% of children in the United States (American Psychiatric Association, 2013). Treatment matching in ADHD is difficult and unsatisfactory; the same general treatment algorithm is recommended for all children. It is therefore important to consider the development of specialized treatment programs based on a variety of behavioral and neurological biomarkers. Unfortunately, due to its multi-faceted classification, the heterogeneity of this behavioral disorder is under-investigated (Costa Dias et al., 2015). Scientific research in this area is especially limited as the severity of ADHD goes undiagnosed, children tend to have difficulties remaining still in MRI scanners, and the hyperactivity-impulsivity that is associated with ADHD may cause further challenges when trying to remain motionless in the scanner. Furthermore, tasks such as Facial Emotion Perception Task (FEPT) and Theory of Mind (ToM) have not been used to analyze social and behavioral deficits in children with ADHD. More research needs to be allocated to helping uncover the neural substrates underlying the inattention and hyperactivity traits of this disorder. For this reason, we acquired functional magnetic resonance imaging (fMRI) data from five children with ADHD performing the FEPT and ToM tasks. The results showed the children have an easier and quick time correctly identifying happy emotional states, as compared to the fearful, angry, and neutral conditions. Results from the FEPT task also revealed that the participants were thinking and reasoning more (i.e., taking longer to deduce an ending) when identifying emotions than identifying animals. The ToM task showed that the default mode network (DMN) may not be fully suppressed when the children are choosing the correct cartoon ending, and therefore the children may be having lapses in attention. These findings may assist the current hypothesis that the default mode network has reduced network homogeneity in people with ADHD. Overall, the findings presented in this thesis provide a good diving board into discovering the reason(s) for the social cognition and emotion recognition impairments associated with ADHD, but further research is needed in order to one day pinpoint and ultimately correct the regions(s) of dysfunction.

Abstract Frontotemporal lobar degeneration (FTLD) is the second most common neurodegenerative disease leading to early-onset dementia with an estimated worldwide prevalence of 10 to 30 cases per 100000 individuals in the age group of 46 to 65 years. Behavioral variant frontotemporal dementia (bvFTD) is the most common FTLD subtype. It is characterized by a progressive deterioration of behavior and personality as well as executive dysfunction. In Finland, almost 50 % of familial FTLD cases are attributable to the C9ORF72 mutation. bvFTD is associated with a characteristic pattern of brain atrophy detectable in structural MRI. However, these changes are typically not visible in the early stages of the disease. Resting-state functional MRI (RS-fMRI) is being increasingly used to evaluate changes in functional connectivity within neuronal networks in the brain but only a few RS-fMRI investigations of bvFTD patients have been published with inconsistent results. The object of this thesis was to investigate functional connectivity changes detected in the salience (SLN) and default mode networks (DMN) in bvFTD. Another aim was to clarify the role of other cognitive resting-state networks in this disease. A cohort of 26 bvFTD patients was studied, with 8 of these patients carrying the C9ORF72 expansion. Connectivity changes were detected in multiple clinically relevant cognitive networks. Decreased functional connectivity was observed in the SLN, which is associated with guiding of behavior. Increased activity was present in the DMN and the dorsal attention network (DAN). In C9ORF72 associated bvFTD, there was an abnormal linkage detected between the DMN and the thalamus. Currently, fMRI is generally used as a research tool and in a group setting. Different study methods have been used in the literature and also in the studies of this thesis, the analysis procedures differed to some extent. The variety of analysis methods may explain the heterogeneity in fMRI findings in bvFTD patients. There is a need for standardization of the fMRI methodology, larger study groups and also in the future the methodology should be improved so that single patient analysis would provide results to allow a confident diagnosis of this disease. / Tiivistelmä Otsa-ohimolohkorappeuma (Frontotemporal lobar degeneration, FTLD) on toiseksi yleisin etenevä dementiaan johtava sairaus, joka ilmaantuu usein jo työikäisenä. Otsalohkodementia on otsa-ohimolohkorappeuman yleisin alamuoto, jonka oireisto painottuu persoonan ja käyttäytymisen muutoksiin sekä toiminnan ohjauksen ongelmiin. Suomessa C9ORF72-toistojaksomutaatio selittää lähes 50 % perinnöllisistä otsa-ohimolohkorappeumista. Aivojen rakenteellisella magneettikuvauksella (MK) voidaan havaita rakenteellisia muutoksia, jotka ilmaantuvat kuitenkin vasta taudin edettyä vaikeampaan vaiheeseen. Aivojen lepotilan toiminnallinen magneettikuvaus (TMK) mahdollistaa aivojen hermoverkkojen toiminnan eli konnektiviteetin kartoituksen. Aiemmin TMK:a on tutkittu esim. Alzheimerin taudissa. Otsalohkodementiassa TMK:sta on julkaistu ainoastaan yksittäisiä tutkimuksia ja tulokset ovat olleet osin ristiriitaisia. Väitöskirjatutkimuksen tarkoituksena on ollut selvittää valve-lepotilan hermoverkossa ja olennaisen tunnistavassa hermoverkossa tapahtuvia muutoksia otsalohkodementiaa sairastavilla potilailla. Toisena tavoitteena on ollut tutkia muissa kognitiivisissa hermoverkoissa tapahtuvia muutoksia. Otsalohkodementiaa sairastaville potilaille (n= 26) sekä ikä- ja sukupuolivakioiduille kontrolleille on tehty kliininen tutkimus ja rakenteellinen sekä toiminnallinen aivojen magneettikuvaus. Kahdeksalla potilaalla todettiin C9ORF72-toistojaksomutaatio. Useiden kognitiivisten hermoverkkojen toiminnassa havaittiin muutoksia, jotka korreloivat potilaiden kliinisiin oireisiin. Alentunutta konnektiviteettia todettiin olennaisen tunnistavassa hermoverkossa, joka osallistuu käyttäytymisen säätelyyn. Lisääntynyttä konnektiviteettia esiintyi valve-lepotilan hermoverkossa ja tarkkaavaisuus hermoverkossa. Potilailla, joilla on C9ORF72-mutaatio, havaittiin epänormaali yhteys valve-lepotilan hermoverkon ja talamuksen välillä. TMK:ta käytetään tällä hetkellä lähinnä tutkimustyökaluna. Analyysityökaluissa on ollut vaihtelevuutta eri julkaisuissa ja osin myös tämän väitöskirjan osatöissä. Julkaistut TMK-löydökset otsalohkodementiassa ovat osin ristiriitaisia ja se saattaa selittyä erilaisilla analyysimenetelmillä. Metodologiaa tulisi standardisoida ja lisäksi tarvitaan suurempia potilasryhmiä ja menetelmien kehittämistä, jotta TMK:n käyttö yksilötason kliinisessä diagnostiikassa olisi jatkossa mahdollista.

Young football players are hypothesized to experience damage to the brain and brain function from repeated subconcussive head acceleration events (HAEs) during practices and games. Such damage may cause delayed cognitive and mental problems. Resting state fMRI (rs-fMRI) is an effective non-invasive method to detect alterations in brain functional connectivity. Seed-based rsfMRI analysis using the central node of the default mode network (DMN) as the seed is a common approach to measuring intrinsic changes of the DMN, accepted as a key network in brain function. Seed-based rs-fMRI analysis of the DMN was used to explore how age, HAE intensity, and HAE counts influence brain connectivity in youth athletes (ages 12-18). Middle school and high school football players and peer controls were studied using rs-fMRI before and after one season of competition. An identifiability matrix was generated from the seed-based connectivity matrix, allowing measurement of similarity between pre-season and post-season functional connectivity. The consistency of seed-based brain functional connectivity we observed across the season of play for players has no statistically significant difference from controls. The identifiability matrix exhibited no relation to the number and magnitude of any subset of HAEs experienced which rejected our hypothesis. Another finding is that high school football players exhibited the largest percentage increase in identification from middle school football players in the somatomotor network over other resting-state networks.

La méditation par le ‘mindfulness’ favorise la stabilité émotionelle, mais les mécanismes neuroneux qui sous-tendent ces effets sont peu connus. Ce projet investiga l’effet du ‘mindfulness’ sur les réponses cérébrales et subjectives à des images négatives, positives et neutres chez des méditants expérimentés et des débutants au moyen de l’imagerie par résonance magnétique fonctionnelle (IRMf). Le ‘mindfulness’ atténua l’intensité émotionelle via différents mécanismes cérébraux pour chaque groupe. Comparés aux méditants, les débutants manifestèrent une déactivation de l’amygdale en réponse aux stimuli émotifs durant le ‘mindfulness’. Comparés aux débutants, les méditants exhibèrent une déactivation de régions du réseau du mode par défaut (RMD) pendant le ‘mindfulness’ pour tous stimuli (cortex médian préfrontal [CMP], cortex cingulaire postérieur [CCP]). Le RMD est constitué de régions fonctionnellement connectées, activées au repos et déactivées lors de tâches explicites. Cependant, nous ne connaissons pas les impacts de l’entraînement par la méditation sur la connectivité entre régions du RMD et si ces effets persistent au-delà d’un état méditatif. La connectivité fonctionnelle entre régions du RMD chez les méditants et débutants au repos fut investiguée au moyen de l’IRMf. Comparés aux débutants, les méditants montrèrent une connectivité affaiblie entre subdivisions du CMP, et une connectivité accrue entre le lobule pariétal inférieur et trois regions du RMD. Ces résultats reflètent que les bienfaits immédiats du ‘mindfulness’ sur la psychopathologie pourraient être dûs à une déactivation de régions limbiques impliquées dans la réactivité émotionelle. De plus, les bienfaits à long-terme de la méditation sur la stabilité émotionelle pourrait être dûs à une déactivation de régions corticales et cingulaires impliquées dans l’évaluation de la signification émotive et une connectivité altérée entre régions du RMD à l’état de repos. / Mindfulness meditation promotes emotional stability, yet little is known of the brain mechanisms through which this is achieved. The impact of mindfulness on the neural and subjective responses to negative, positive, and neutral pictures in experienced meditators and beginners was investigated using functional magnetic resonance imaging (fMRI). Mindfulness attenuated emotional intensity via distinct neural pathways for each group. For beginners, mindfulness induced a deactivation of the amygdala during emotional processing compared to meditators. For meditators (relative to beginners), mindfulness induced deactivations of areas involved in the evaluation of emotional significance and the default mode network (DMN) across all picture categories (medial prefrontal cortex [MPFC], posterior cingulate cortex). The DMN consists of functionally connected brain areas typically activated at rest and deactivated during goal-directed tasks. It remains unknown whether meditation training influences functional connectivity within DMN regions, and if so, whether these effects persist beyond a state of meditation per se. Functional connectivity within DMN regions at rest was examined using fMRI in beginners and meditators. Relative to beginners, meditators exhibited decreased connectivity between MPFC subdivisions, and increased connectivity between the right inferior parietal lobule and three other DMN regions. These findings may reflect that early beneficial effects of mindfulness on psychopathology are due to deactivations of limbic regions involved in emotional reactivity. On the other hand, long-term effects of meditation on emotional stability may occur through a down-regulation of prefrontal and cingulate regions involved in the evaluation of emotional significance, and altered functional connectivity within DMN regions at rest.

Introdução: Apesar de ser uma intervenção potencialmente promissora para melhorar a cognição em sujeitos com comprometimento cognitivo leve (CCL), os efeitos do treinamento aeróbio (TA) no metabolismo regional de glicose (MRG) no cérebro ainda são pouco conhecidos. Objetivo: Avaliar os efeitos do TA na cognição e no MRG cerebral em sujeitos com CCL, usando tomografia por emissão de pósitrons com 18F - fluordesoxiglicose (PET-18FDG). Métodos: Sessenta e cinco sujeitos com CCL realizaram um programa de TA de intensidade moderada, duas vezes por semana, durante 24 semanas. Uma avaliação cognitiva com a escala Alzheimer\'s Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) e outra do metabolismo cerebral em repouso com o PET-18FDG foram realizadas antes e depois da intervenção. A capacidade aeróbia foi comparada utilizando o consumo máximo de oxigênio (VO2 máx.) medido em mL/kg/min. Os dados de PET-18FDG foram analisados voxel por voxel com o programa SPM8 (limiar: p < 0,001 não corrigido, tamanho de agrupamento >= 50 voxels). Uma técnica de modelação de equações estruturais foi usada para criar um modelo para explorar as mudanças no MRG cerebral em repouso depois do programa de TA. Resultados: Comparações com testes t pareados revelaram melhora nos valores da escala ADAS-Cog (diferença média: -2,4 (3,5), p < 0,001) e no VO2 máx. (diferença média: 1,4 (2,3) mL/kg/min, p < 0,001). A análise metabólica do cérebro constatou uma redução bilateral do MRG em ambos os polos temporais anteriores, no giro frontal inferior esquerdo, no giro do cíngulo anterior esquerdo, no hipocampo direito, no giro frontal médio esquerdo e nos núcleos caudados bilaterais. Em contraste, houve um aumento do MRG no precuneus direito e no giro frontal inferior esquerdo. Um modelo de confirmação de fatores foi usado para criar variáveis latentes que refletem a rede de saliência (RS) e a rede de modo padrão (default mode network (DMN)) com base em regiões com mudanças no MRG encontradas depois do TA. Uma análise de caminhos foi utilizada para testar a hipótese de que o TA poderia induzir mudanças (diminuição) do MRG em regiões da RS. Essa redução pode refletir um aumento da eficiência da rede e, consequentemente, um melhor controle sobre outras redes. Em última instância, essa mudança induziria um aumento do MRG no precuneus, um importante nó da DMN. Os valores de adequação do modelo atingiram significância estatística, demonstrando que esse modelo explica a variância dos dados medidos. Conclusão: O TA melhorou a cognição e alterou o MRG em regiões da DMN e da rede de saliência em sujeitos com CCL / Background: Despite being a potentially promising intervention to improve cognition in subjects with mild cognitive impairment (MCI), the effects of aerobic training (AT) on regional brain glucose metabolism (rBGM) are not yet entirely understood. Objective: To evaluate the effects of AT on cognition and rBGM in subjects with MCI using 18FDG-PET. Methods: Sixty-five subjects with MCI performed a twice-a-week, moderate intensity, AT program for 24 weeks. Assessment with the ADAS-Cog (Alzheimer\'s Disease Assessment Scale - Cognitive Subscale) and evaluation of rBGM with 18FDG-PET were performed before and after the intervention. Aerobic capacity was compared using the relative maximal oxygen consumption (VO2 max) measured in mL/Kg/min. 18FDG-PET data were analyzed on a voxel-by-voxel basis with SPM8 (threshold: uncorrected p < 0.001, cluster size >= 50 voxels). Structural equation modeling was used to create a model to explore the changes of resting-state rBGM after the AT program. Results: Comparisons using paired t-tests revealed improvements in the ADAS-Cog (mean difference: -2.4 (3.5), p < 0.001) and VO2 max scores (mean difference: 1.4 (2.3) mL/kg/min, p < 0.001). Brain metabolic analysis revealed a bilateral reduction of rBGM in both anterior temporal poles, left inferior frontal gyrus, left anterior cingulate cortex, right hippocampus, left middle frontal gyrus and bilateral caudate nuclei. In contrast, there was an increase in rBGM in the right precuneus and left inferior frontal gyrus. Confirmatory factor analysis was used to create latent variables reflecting the salience network (SN) and default mode network (DMN) based on regions with rBGM changes found after the AT. A path model analysis was used to test the hypothesis that AT would induce rBGM changes (decrease) in regions of the SN. This decrement may reflect improved efficacy and consequently, better control over other networks. Ultimately, these changes would induce an increment in rBGM in the precuneus, an important node of the DMN. Values of model fit reached statistical significance, demonstrating that this model explain the variance of the measured data. Conclusion: AT improved cognition and changed rBGM measured with 18FDG-PET in nodes od the DMN and SN in subjects with MCI

Introdução: Apesar de ser uma intervenção potencialmente promissora para melhorar a cognição em sujeitos com comprometimento cognitivo leve (CCL), os efeitos do treinamento aeróbio (TA) no metabolismo regional de glicose (MRG) no cérebro ainda são pouco conhecidos. Objetivo: Avaliar os efeitos do TA na cognição e no MRG cerebral em sujeitos com CCL, usando tomografia por emissão de pósitrons com 18F - fluordesoxiglicose (PET-18FDG). Métodos: Sessenta e cinco sujeitos com CCL realizaram um programa de TA de intensidade moderada, duas vezes por semana, durante 24 semanas. Uma avaliação cognitiva com a escala Alzheimer\'s Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) e outra do metabolismo cerebral em repouso com o PET-18FDG foram realizadas antes e depois da intervenção. A capacidade aeróbia foi comparada utilizando o consumo máximo de oxigênio (VO2 máx.) medido em mL/kg/min. Os dados de PET-18FDG foram analisados voxel por voxel com o programa SPM8 (limiar: p < 0,001 não corrigido, tamanho de agrupamento >= 50 voxels). Uma técnica de modelação de equações estruturais foi usada para criar um modelo para explorar as mudanças no MRG cerebral em repouso depois do programa de TA. Resultados: Comparações com testes t pareados revelaram melhora nos valores da escala ADAS-Cog (diferença média: -2,4 (3,5), p < 0,001) e no VO2 máx. (diferença média: 1,4 (2,3) mL/kg/min, p < 0,001). A análise metabólica do cérebro constatou uma redução bilateral do MRG em ambos os polos temporais anteriores, no giro frontal inferior esquerdo, no giro do cíngulo anterior esquerdo, no hipocampo direito, no giro frontal médio esquerdo e nos núcleos caudados bilaterais. Em contraste, houve um aumento do MRG no precuneus direito e no giro frontal inferior esquerdo. Um modelo de confirmação de fatores foi usado para criar variáveis latentes que refletem a rede de saliência (RS) e a rede de modo padrão (default mode network (DMN)) com base em regiões com mudanças no MRG encontradas depois do TA. Uma análise de caminhos foi utilizada para testar a hipótese de que o TA poderia induzir mudanças (diminuição) do MRG em regiões da RS. Essa redução pode refletir um aumento da eficiência da rede e, consequentemente, um melhor controle sobre outras redes. Em última instância, essa mudança induziria um aumento do MRG no precuneus, um importante nó da DMN. Os valores de adequação do modelo atingiram significância estatística, demonstrando que esse modelo explica a variância dos dados medidos. Conclusão: O TA melhorou a cognição e alterou o MRG em regiões da DMN e da rede de saliência em sujeitos com CCL / Background: Despite being a potentially promising intervention to improve cognition in subjects with mild cognitive impairment (MCI), the effects of aerobic training (AT) on regional brain glucose metabolism (rBGM) are not yet entirely understood. Objective: To evaluate the effects of AT on cognition and rBGM in subjects with MCI using 18FDG-PET. Methods: Sixty-five subjects with MCI performed a twice-a-week, moderate intensity, AT program for 24 weeks. Assessment with the ADAS-Cog (Alzheimer\'s Disease Assessment Scale - Cognitive Subscale) and evaluation of rBGM with 18FDG-PET were performed before and after the intervention. Aerobic capacity was compared using the relative maximal oxygen consumption (VO2 max) measured in mL/Kg/min. 18FDG-PET data were analyzed on a voxel-by-voxel basis with SPM8 (threshold: uncorrected p < 0.001, cluster size >= 50 voxels). Structural equation modeling was used to create a model to explore the changes of resting-state rBGM after the AT program. Results: Comparisons using paired t-tests revealed improvements in the ADAS-Cog (mean difference: -2.4 (3.5), p < 0.001) and VO2 max scores (mean difference: 1.4 (2.3) mL/kg/min, p < 0.001). Brain metabolic analysis revealed a bilateral reduction of rBGM in both anterior temporal poles, left inferior frontal gyrus, left anterior cingulate cortex, right hippocampus, left middle frontal gyrus and bilateral caudate nuclei. In contrast, there was an increase in rBGM in the right precuneus and left inferior frontal gyrus. Confirmatory factor analysis was used to create latent variables reflecting the salience network (SN) and default mode network (DMN) based on regions with rBGM changes found after the AT. A path model analysis was used to test the hypothesis that AT would induce rBGM changes (decrease) in regions of the SN. This decrement may reflect improved efficacy and consequently, better control over other networks. Ultimately, these changes would induce an increment in rBGM in the precuneus, an important node of the DMN. Values of model fit reached statistical significance, demonstrating that this model explain the variance of the measured data. Conclusion: AT improved cognition and changed rBGM measured with 18FDG-PET in nodes od the DMN and SN in subjects with MCI