Direct and indirect stimulation of the brain have produced a range of perceptual, motor, and cognitive experiences, including experiences historically ascribed to religious or spiritual domains. Weak intensity, extremely low frequency electromagnetic fields patterned after physiological processes have been the subject of much research and controversy. The current study examined the Shiva technology, a unique method of field production that utilizes the same fields used in previous research. Quantitative changes in brain activity were measured using quantitative electroencephalograph and subjective reports of experiences were examined. The investigation included two different configurations of the Shiva technology. Results indicated that individuals exposed to specific patterned fields exhibited different patterns of neural activity and greater reports of unusual experiences compared to a sham condition. The importance of particular enhancement of power in regions of the brain due to the sequence of different patterns of magnetic fields was a key discovery. Personality characteristics, particularly those involved with the Default Mode Network, and their relation to baseline electroencephalographic data were also examined.

<p>It has been suggested that primate brains are inherently biased towards gathering and processing the social information present in the world. In fact, the neural network that mediates our engagement with the external world - the default mode network (DMN) ¬- is strongly convergent with the neural circuitry for social cognition. The posterior cingulate (PCC) is believed to be a key node in both the DMN and in social cognition. Human and non-human primate studies have demonstrated a role for the PCC in outcome monitoring: it tracks rewards, subjective values of choices, task engagement and global choice strategies. It is also implicated in social cognition. Human studies show that PCC activity varies with the recall of autobiographical memories and exposure to social stimuli. While several electrophysiological studies explicate the response of PCC neurons to non-social outcome monitoring and valuation, there is a lack of similar studies for social valuation. This thesis is concerned with characterizing the neuronal responses in the PCC to social stimuli and determining whether social valuation occurs in the PCC in a manner similar to that previously described for non-social outcomes. I recorded the single unit activity of neurons in the PCC of rhesus macaques while they performed behavioral tasks that required attending to the faces of high-status or low-status individuals. Monkeys valued the faces of high-status individuals more than low-status individuals, though they were equally likely to identity and overtly attend to faces of both social classes. This differential valuation of face stimuli was represented in the firing activity of PCC neurons, with higher neuronal activity seen in response to subordinate faces as compared to dominant ones. Cells in the PCC did not track the individual identity of the presented faces. Furthermore, neuronal activity in the PCC predominantly tracked social value, and not non-social reward delivery as previously reported. Neuronal activity also predicted task engagement, with higher firing rates being predictive of a decrease in task engagement. To summarize, the PCC is biased towards social information processing, and neuronal activity in the PCC tracks social category information and the level of task engagement.</p> / Dissertation

No description available.

INTRODUCTION: 3 in 100 people in the United States will experience psychosis in their lifetime. Psychosis is a disease state that occurs in several psychiatric illness, including schizophrenia and bipolar disorder. Psychosis is characterized by the heterogeneity of its symptoms, clinical manifestations, and underlying biology. The Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium was established to identify more homogenous subtypes of psychosis. Recent studies have investigated inflammatory subtypes of psychosis and elucidated the cognitive deficits and structural effects associated with elevated inflammation. Previous studies using fMRI have also elucidated the decreased connectivity of the Default Mode Network (DMN) in psychosis. In this thesis, the functional and cognitive effects of inflammatory subtypes of psychosis are further investigated by incorporating resting state fMRI functional connectivity analysis. METHODS: Blood samples and fMRI data were collected from individuals with psychosis and healthy participants recruited at the Chicago site of the B-SNIP study. Blood sample peripheral marker assays were performed for IL1β, IL6, IL8, IL10, IL12/IL23p40, interferon gamma (IFNγ), TNFα, TNFβ, CRP, Fms Related Receptor Tyrosine Kinase 1 (Flt-1), VEGF, VEGFD and Complement 4 (C4a). Principal component analysis and hierarchical clustering of peripheral marker data resulted in a two cluster solution of high and low inflammatory subtypes. Resting state networks were adapted from the literature. Network connectivity was investigated using group independent component analysis and inter-network connectivity was determined through Fisher z transformation of network loading coefficients. Mediation analysis of the DMNa on the effects of inflammation and cognition was performed using a statistical model. RESULTS: 32% (n= 30) of psychosis probands were included in the high inflammation subtype. The Proband High inflammation subtype had higher levels of TNFα, C4a, IL8, IL10 and IFNγ than the Proband Low subtype. The Proband high group had decreased activity in the DMNa compared to the Proband Low group. Inter-network connectivity analysis found a decreased connectivity between the DMNa and the Right Attentional Working Memory Network in Proband High compared to Proband Low. Mediation analysis across the whole sample revealed the DMNa has a mediating effect on inflammation and the following cognitive measures: BACS composite score, BACS verbal memory and tower subscores, Percent Correct and Weschler Memory Scale. The DMNa was also validated as a mediating variable of CRP, IL1β, IL6 separatedly for the indicated cognitive measures above.Mediation analysis across the proband sample revealed DMNa mediated inflammation and BACS composite, BACS tower subscore, and Percent Correct. CONCLUSION: Inflammatory subtypes of psychosis have proved to identify homogenous subsets of patients with unique characteristics. The high inflammation proband group had decreased DMNa activity and inter-network connectivity between the DMNa and several other resting state networks. Mediation analysis has proved that the DMNa, which is affected by inflammation, mediates cognition.

Alcohol use disorder is common, and treatments are currently inadequate. Some of the acute effects of alcohol on the brain, such as altering the decision-making and future thinking capacities, mirror the effects of chronic alcohol use. Therefore, interventions that can address these shortcomings may be useful for reducing the negative effects of alcohol use disorder in combination with other therapies. The signature of those interventions may also be evident in the signature of large-scale, dynamic brain networks, which can show whether an intervention is effective. One such intervention is episodic future thinking, which has been shown to reduce delay discounting and orient people toward pro-social, long-term outcomes. To better understand decision making in high-risk individuals, we examined delay discounting in an adolescent population. When the decision-making faculties were challenged with difficult choices, adolescents made decisions inconsistent with their predicted preference, complemented by increased brain activity in the central executive network and salience network. Using these results and the hypothesis that the default mode network would be implicated in future thinking and intertemporal choice, we examined the neural effects of a brief behavioral intervention, episodic future thinking, that seeks to address these impairments. We showed that episodic future thinking has both acute and longer-lasting effects on consequential brain networks at rest and during delay discounting compared to a control episodic thinking condition in alcohol use disorder. Our failure to show group differences in default mode network prompted us to scrutinize it more carefully, from a position where we could measure the ability to self-regulate the network rather than its resting-state tendency. We implemented a real-time fMRI experiment to test the degree to which people along the alcohol use severity spectrum can self-regulate this network. Our results showed that default mode network suppression is impaired as alcohol use disorder severity increases. In the process, we showed that direct examination of resting-state networks with these methods will provide more information than measuring them at rest alone. We also characterized the default mode network along the real-time fMRI pipeline to show the whole-brain spatial pattern of regions associated and unassociated with the network. Our results indicate that resting-state brain networks are important markers for outcomes in alcohol use disorder and that they can be manipulated under experimental conditions, potentially to the benefit of the afflicted individual. / Doctor of Philosophy / Alcohol is the most widely-used mind-altering substance in the United States. Even though most people do not develop a problem with alcohol use, many people will at some point develop drinking patterns that classify as an alcohol use disorder. Brain damage from drinking can come from the toxicity of alcohol, but also as a result of behaviors associated with drinking too much, including injury, violence, accidents, and other health-related issues. Interventions at the behavioral level can be effective at curbing drinking patterns before damage accrues, and a better understanding of those interventions at the level of the brain may make them more effective. This work investigated the decision-making processes and the ability to think clearly about the future, two faculties that begin to become diminished in alcohol use disorder. In our first set of studies, we tested a brief behavioral intervention called episodic future thinking, which helps people orient themselves away from short-term rewards like alcohol and toward long-term goals that could happen if they stopped drinking as much. We showed that one hour-long, intensive session produced changes in the connectivity between the prefrontal cortex and the lower brain. We also generated data in a long-term experiment suggesting repeated reminders of the episodic future thinking intervention produce changes in large-scale brain networks that are disrupted in substance use disorders. In a separate set of experiments, we showed that people can gain control over one of these networks, called the default mode network, to the point of being able to control a brain-machine interface just by following simple instructions. However, we demonstrated that the degree to which someone can control this brain activity was associated with their drinking severity. In other words, the more people drank, in terms of volume and frequency, the less control they had over their own brain activity. This finding is important because many researchers have shown that activity in this brain region is related to many psychopathologies, including substance use disorders. Other researchers have been developing ways in which the ability to control this brain activity can be trained. While we did not find evidence of a training effect in a small group of healthy people (5), it may be the case that people impaired by alcohol use disorder can improve through practice or through cutting back on drinking. Ultimately, we hope that the research presented here will help to guide the development of treatments for alcohol use disorder to be more effective.

Made available in DSpace on 2014-12-17T15:28:50Z (GMT). No. of bitstreams: 1 FernandaPXF_DISSERT.pdf: 1956112 bytes, checksum: 765e57e876596c2a3922bb6f98c28b64 (MD5) Previous issue date: 2012-05-25 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Ayahuasca is psychotropic beverage that has been used for ages by indigenous populations in South America, notably in the Amazon region, for religious and medicinal purposes. The tea is obtained by the decoction of leaves from the Psychotria viridis with the bark and stalk of a shrub, the Banisteriopsis caapi. The first is rich in N-N-dimethyltryptamine (DMT), which has an important and well-known hallucinogenic effect due to its agonistic action in serotonin receptors, specifically 5-HT2A. On the other hand, &#946;-carbolines present in B. caapi, particularly harmine and harmaline, are potent monoamine oxidase inhibitors (MAOi). In addition, the tetrahydroharmine (THH), also present in B. caapi, acts as mild selective serotonin reuptake inhibitor and a weak MAOi. This unique composition induces a number of affective, sensitive, perceptual and cognitive changes in individuals under the effect of Ayahuasca. On the other hand, there is growing interest in the Default Mode Network (DMN), which has been consistently observed in functional neuroimaging studies. The key components of this network include structures in the brain midline, as the anterior medial frontal cortex, ventral medial frontal cortex, posterior cingulate cortex, precuneus, and some regions within the inferior parietal lobe and middle temporal gyrus. It has been argued that DMN participate in tasks involving self-judgments, autobiographical memory retrieval, mental simulations, thinking in perspective, meditative states, and others. In general, these tasks require an internal focus of attention, hence the conclusion that the DMN is associated with introspective mental activity. Therefore, this study aimed to evaluate by functional magnetic resonance imaging (fMRI) changes in DMN caused via the ingestion of Ayahuasca by 10 healthy subjects while submitted to two fMRI protocols: a verbal fluency task and a resting state acquisition. In general, it was observed that Ayahuasca causes a reduction in the fMRI signal in central nodes of DMN, such as the anterior cingulate cortex, the medial prefrontal cortex, the posterior cingulate cortex, precuneus and inferior parietal lobe. Furthermore, changes in connectivity patterns of the DMN were observed, especially a decrease in the functional connectivity of the precuneus. Together, these findings indicate an association between the altered state of consciousness experienced by individuals under the effect of Ayahuasca, and changes in the stream of spontaneous thoughts leading to an increased introspective mental activity / A Ayahusca ? uma bebida psicotr?pica que tem sido utilizada h? s?culos por popula??es originais da Am?rica do Sul, notadamente da regi?o Amaz?nica, com fins religiosos e medicinais. O ch? ? obtido pela decoc??o de folhas da Psychotria viridis com a casca e tronco de um arbusto, a Banisteriopsis caapi. A primeira ? rica em N,N-dimetiltriptamina (DMT), que tem importante e bem conhecido efeito alucin?geno devido a sua atua??o agonista nos receptores de serotonina, especificamente 5-HT2A. Por outro lado, as &#946;-carbolinas presentes na B. caapi, particularmente a harmina e a harmalina, s?o potentes inibidores da monoamina oxidase (iMAO). Al?m disso, a tetrahidroharmina (THH), tamb?m presente na B. caapi, atua como leve inibidor seletivo da recapta??o de serotonina e um fraco inibidor de MAO. Essa composi??o ?nica provoca uma s?rie de altera??es afetivas, sensoriais, perceptuais e cognitivas em indiv?duos sob o efeito da Ayahuasca. Por outro lado, existe um interesse crescente na rede de modo padr?o, do ingl?s Default Mode Network (DMN), que tem sido consistentemente observada em estudos de neuroimagem funcional. As principais componentes dessa rede incluem estruturas da linha m?dia do c?rtex cerebral, como o c?rtex frontomedial anterior, c?rtex frontomedial ventral, o giro cingulado posterior, o pr?-cuneus e algumas regi?es do lobo parietal inferior e do giro temporal m?dio. Acredita-se que a DMN participe de tarefas que envolvem autojulgamentos, evoca??o de mem?rias autobiogr?ficas, realiza??o de simula??es mentais, pensar em perspectiva, estados meditativos, entre outros. De maneira geral, essas tarefas requerem um foco de aten??o interno, da? a conclus?o de que a DMN estaria associada ? atividade mental introspectiva. Assim, este estudo teve como objetivo avaliar, por meio de resson?ncia magn?tica funcional (fMRI), as poss?veis mudan?as da DMN causadas pela ingest?o da Ayahuasca em 10 volunt?rios saud?veis investigados enquanto se submeteram a dois protocolos: uma tarefa de flu?ncia verbal e a aquisi??o de dados cont?nuos durante estado de repouso. De maneira geral, observa-se que a Ayahuasca provoca redu??o na amplitude do sinal de fMRI nos nodos centrais da DMN, tais como o c?ngulo anterior, o c?rtex pr?-frontal medial, o c?ngulo posterior, o pr?-cuneus e o lobo parietal inferior. Al?m disso, tamb?m foram observadas altera??es no padr?o de conectividade da DMN, em particular, diminui??o da conectividade funcional no pr?-cuneus. Juntos, esses achados indicam a poss?vel associa??o entre o estado alterado de consci?ncia experimentado pelos indiv?duos sob efeito da Ayahuasca, e mudan?as no fluxo de pensamentos espont?neos ligados ao aumento da introspec??o

BACKGROUND: Schizophrenia manifests as a constellation of both psychotic symptoms (eg. hallucinations, delusions) and so-called negative symptoms. The latter includes anhedonia, avolition, amotivation and they are the strongest predictors of disability. Resting state fMRI (rsfMRI) has demonstrated that the brain is organized into low-dimensional number (7-17) brain networks and this allowed visualization of the relationship between symptom severity and large-scale brain network organization. Traditional rsfMRI analyses have assumed that the spatial organization of these networks are spatially invariant between individuals. This dogma has recently been overturned with the observation that the spatial organization of these brain networks shows significant variation between individuals. We sought to determine if previously observed relationships between symptom severity and network connectivity are actually due to individual differences in spatial organization. METHODS: 44 participants diagnosed with schizophrenia underwent rsfMRI scans and clinical assessment. A multivariate pattern analysis was used to examine how each participant’s whole brain functional connectivity correlates with ‘negative’ symptom severity. RESULTS: Brain connectivity to a region of the right dorso-lateral pre-frontal cortex (r DLPFC) correlates with symptom severity. The result is explained by the individual differences in the topographic distribution of two brain networks: the default mode network (DMN) and the task positive network (TPN). Both networks demonstrate strong (r~0.49) and significant (p<0.001) relationships between topography and symptom severity. For individuals with low symptom severity, this critical region is a part of the DMN. In highly symptomatic individuals, this region is a part of the TPN. CONCLUSIONS: Previously overlooked individual variation in brain organization is tightly linked to individual variation in schizophrenia symptom severity. The recognition of critical links between network topology and pathological symptomology may serve as a guide for future interventions aimed at establishing causal relationships between certain critical regions of the brain and cognitive and behavioral phenotypes. Thus, fMRI and network topology may be translated to a clinical setting as a viable, individual-centered treatment option. / 2020-06-17T00:00:00Z

Individuals who speak more than one language have been found to enjoy a number of benefits not directly associated with the use of the languages themselves. One of these benefits is that bilingual individuals appear to develop symptoms of dementia 4-5 years later than comparable individuals who speak just one language. Studies on this topic, however, do not consistently account for factors including if the individual learned their second language as a child or later in life, or their language proficiency. In an attempt to more carefully examine these variables, this study looks at structural and resting-state functional MRI scans of the default mode network, English and Spanish (where applicable) proficiency, language background, and demographics of young healthy adults who fall into one of three groups: early bilinguals, late bilinguals, and monolinguals. Of the three groups, late bilinguals were found to have a small but statistically significantly higher level of connectivity compared with early bilinguals in the region of the medial prefrontal cortex; patterns found examining number of languages and language proficiency in relation to functional connectivity and research group also supported this finding. These results indicate studying a language after adolescence could provide neuroprotective benefits of a nature that could potentially help delay symptoms of dementia. Age, gender, ethnicity, level of education, English language proficiency, and Spanish language use did not result in statistically significant findings, the latter of which challenges using frequency of language use to define bilingualism.

Previous work has linked the onset and progression of Alzheimer’s Disease (AD) to changes in the Default Mode Network (DMN), including greater atrophy within the hippocampus (HC) as well as diminished functional connectivity and effective connectivity between anatomical DMN structures. Animal models have described the HC as a primary region of interest in studying the effects of exercise on adult neurogenesis and memory performance. Human studies have demonstrated that aerobic exercise leads to greater cardiorespiratory fitness and improved functional connectivity in the DMN for healthy adults. The goal of this study is to go beyond the predictions of human and animal studies to investigate how cardiorespiratory fitness may be used to estimate effective connectivity between the HC and the other DMN structures for young adults using resting state fMRI. Due to the data driven nature of this study, no hypothesis has been formulated. To investigate, data from 25 sedentary young adults was analyzed. Data included a resting state fMRI procedure and a cardiorespiratory fitness test, each taken from part of a larger ongoing clinical trial in the Brain Plasticity and Neuroimaging (BPN) Lab at Boston University (BU). We utilized group independent component analysis (GICA) to identify the regions that define the DMN and Conditional Granger Causality Analysis (CGCA) to determine effective connectivity between these regions. GICA indicated 9 structural regions in the DMN, consistent with previous work. This resulted in 72 possible instances of effective connectivity. The difference of causal influence between regions was calculated for each pair of DMN regions for CGCA, resulting in 36 possible instances of causal connectivity. Linear regression models were created to analyze the effect of cardiorespiratory fitness on effective connectivity between DMN regions and found 11 linear models which exhibited a significant (p > 0.05) relationship. Eight of eleven models involved the left or right hippocampus, showing that greater cardiorespiratory fitness is correlated with changes effective connectivity between the HC and the PCC, MPFC, or LTC. These results provide proof of concept that cardiorespiratory fitness in young adults is associated with changes DMN effective connectivity, particularly involving the hippocampus. This adds to the literature suggesting extended aerobic exercise, which is known to increase cardiorespiratory fitness and has been shown to increase the volume of the HC in older adults, may be neuroprotective of the HC across the lifespan. Further investigation is required to explore how effective connectivity in the DMN changes following an aerobic exercise intervention.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23069号 / 医博第4696号 / 新制||医||1049(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 髙橋 良輔, 教授 林 康紀, 教授 渡邉 大 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM