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.

The default mode network (DMN) is a system of brain regions observed on functional magnetic resonance imaging (fMRI) when an individual is resting and deactivated during performance of goal-directed cognitive tasks, and is thought to be involved in self-related information processing. While differences with age have been observed in anatomical and functional connectivity, resting activity, and task-related deactivation of the DMN, age-related differences in the interaction between resting connectivity and active processing in the DMN are not well understood. In this study, the relation between functional connectivity and cognitive activation during performance of a task known to involve key DMN regions (i.e., posterior cingulate, medial frontal, medial temporal, and parietal regions) was investigated. Statistical Parametric Mapping (SPM) was performed on fMRI scans in healthy young (n=11) and older (n=19) adults to assess functional connectivity of the DMN at rest, and activation during a self-related source memory task. Older adults were then divided based on task performance into high- and low-performing groups to assess individual differences in connectivity and activation. Though both young and older adults showed robust connectivity among DMN regions, older adults showed greater connectivity between the DMN and other areas, particularly in frontal regions; this expansion was especially evident in low performers. Activation of the DMN during encoding and retrieval of self-related versus other-related information was greater in young adults than older adults. While low-performing older adults showed no differences between self- and other-related activation at retrieval, high performers engaged regions outside the DMN during other-related retrieval. These results suggest that older adults whose self-related source memory performance is similar to young adults exhibit preservation of DMN connectivity, self-related activation in the DMN which more closely resembles that of young adults, and additional recruitment of non-DMN networks to achieve higher memory performance. Aging in low performers is associated with dedifferentiation of DMN connectivity with expansion particularly into frontal regions, and reduced ability to engage the DMN or other networks in discriminating self- from non-self-related information. Further, preservation of DMN-specific functional connectivity is directly related to greater activation differences during retrieval of self-related versus non-self-related information in older adults.

<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

Investigation of the neural correlates of the self has implicated a network of brain regions including the medial prefrontal cortex (MPFC), posterior cingulate (PCC), precuneus (pC), and inferior parietal lobule (IPL). At the same time, recent neuroimaging work has identified the Default Mode Network (DMN), a network of brain regions that are highly active at `rest' (without an active cognitive task). While the functional significance of the DMN remains unknown, converging evidence suggests that the DMN might be critical for self-referential processing (e.g., introspection). In this dissertation, I tested this hypothesis using a lesion approach. In the first experiment, I examined the critical role of the DMN hubs (MPFC, IPL) in autobiographical memory (AM) retrieval. I predicted that if the DMN hubs were critical for AM, then lesions to either the MPFC or IPL should result in AM retrieval impairments. I tested this prediction using the Iowa Autobiographical Memory Questionnaire (IAMQ), a questionnaire that assessed retrograde AM retrieval. In support of the prediction, lesions to the MPFC and IPL were associated with significant AM retrieval impairments. While not predicted, AM retrieval deficits were also associated with lesions in medial and lateral temporal cortices, regions also considered part of the DMN. In the second experiment, I tested the critical role of the DMN hubs in the self-reference effect (SRE), a well-known memory advantage conferred by self-related processing. I predicted that if the DMN hubs were critical for the SRE, then damage to the MPFC or IPL should diminish the effect. I used a standard personality trait judgment paradigm to test this prediction. In partial support of the prediction, I found that damage to the MPFC abolished the SRE with a "self" specific deficit. While IPL damage was associated with a diminished SRE, the effects were not significant. In the third experiment, I tested the hypothesis that the DMN is critical for accurate knowledge of one's personality. I predicted that if the DMN hubs are critical for accurate self-knowledge, then damage to either the MPFC or IPL should be associated with less accurate personality reports. In partial support of the prediction, MPFC and IPL groups demonstrated less accurate personality ratings. However, performance for all lesion groups was comparable and not significantly different from healthy subjects. In the fourth experiment, I sought to test the hypothesis that the DMN is critical for mind wandering (MW). I predicted that if the DMN hubs are critical for MW, then damage to the MPFC and IPL should result in decreased MW. To test this prediction, I used two approaches: 1) an experience sampling method (Sustained Attention to Response Task), and 2) a self-report measure (Imaginal Processes Inventory scale of MW). Contrary to my prediction, IPL lesions were associated with increased MW on the SART. By contrast, in support of the prediction, both MPFC and IPL lesions were associated with significant self-reported decreases in MW. Together, these experiments provide some evidence to support the hypothesis that the DMN is critical for self-referential processing. Future work might investigate the impact of DMN lesions on other self-processes (e.g., self-agency).

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

Apesar dos numerosos estudos enfocando a compreensão da esquizofrenia, sua etiologia permanece desconhecida. Atualmente, as medicações antipsicóticas disponíveis são baseadas principalmente na hipótese dopaminérgica, porém, apresentam eficácia parcial no tratamento dos sintomas. Diante disso, outros sistemas neurais têm sido investigados e, nesse contexto, a hipótese glutamatérgica conquistou grande importância. Essa hipótese postula a presença de uma hipoatividade do receptor glutamatérgico N-metil-D-aspartato na esquizofrenia e, consequentemente, de uma desregulação na neurotransmissão do óxido nítrico. Um ensaio clínico recente com a administração de nitroprussiato de sódio, um doador de óxido nítrico, mostrou resultados significativos na melhora da sintomatologia de pacientes esquizofrênicos, entretanto, nenhum estudo de neuroimagem investigou quais são os efeitos dessa droga no sistema nervoso central. No crescente campo de estudo da neuroimagem funcional as redes neurais foram descobertas, sendo a default mode network uma das mais estudadas na esquizofrenia. Os recentes estudos de neuroimagem funcional têm evidenciado alterações do funcionamento dessa rede neural nos pacientes portadores da doença, evidenciando assim, a importância da default mode network na compreensão da esquizofrenia. Nesse caminho, o presente estudo investigou os efeitos agudos da administração de nitroprussiato de sódio na conectividade funcional da rede default mode network através da ressonância magnética funcional mediada pelo contraste BOLD (blood oxygen level dependent) em pacientes portadores de esquizofrenia e em voluntários saudáveis. Os pacientes portadores de esquizofrenia foram divididos em dois grupos de acordo com a medicação antipsicótica em uso: grupo sem clozapina (n=13) e grupo com clozapina (n=13). Os voluntários saudáveis também foram divididos em grupo controle (n=14) e grupo controle com tarefa de escuta passiva (n=5). Todos os pacientes portadores de esquizofrenia e o grupo controle foram submetidos a um protocolo de infusão de nitroprussiato de sódio com aquisição simultânea de imagens funcionais. Nossos resultados mostraram um aumento da conectividade funcional da default mode network com a infusão da medicação nos pacientes portadores de esquizofrenia, especialmente no hemisfério direito, enquanto esse mesmo padrão não foi encontrado nos controles saudáveis. Além disso, o aumento na conectividade se mostrou distinto entres os grupos de pacientes avaliados, sendo mais precoce e amplo no grupo de pacientes que não estava em uso do antipsicótico clozapina. Observamos também que o efeito modulatório da droga ocorreu sobre regiões da default mode network já estudadas e fortemente implicadas na fisiopatogenia da esquizofrenia. Assim, nossa investigação neurofuncional contribuiu para a compreensão dos efeitos terapêuticos do nitroprussiato de sódio na sintomatologia de pacientes portadores de esquizofrenia. Nossos achados também reforçam a importância do nitroprussiato de sódio como uma nova ferramenta farmacológica adjuvante no tratamento da esquizofrenia / Despite numerous studies focusing on the understanding of schizophrenia, its etiology remains unknown. Currently, available antipsychotic medications are mainly based on dopamine hypothesis, however, they exhibit partial efficacy in the treatment of the symptoms. Therefore, other neural systems have been investigated and, in this context, the glutamatergic hypothesis gained great importance. This hypothesis postulates the presence of a hypoactivity of the N-methyl-D-aspartate glutamate receptor in schizophrenia and, consequently, a deregulation of nitric oxide neurotransmission. A recent clinical trial with the administration of sodium nitroprusside, a nitric oxide donor, showed significant results in improving the symptoms of schizophrenic patients, however, no neuroimaging study investigated what are the effects of this drug on the central nervous system. The neural networks were discovered from the growing field of functional neuroimaging study and the default mode network is one of the most studied in schizophrenia. The recent functional neuroimaging studies have shown alterations in the functioning of this neural network in patients with the disease, highlighting the importance of the default mode network in the understanding of schizophrenia. In this way, the present study investigated the acute effects of sodium nitroprusside administration in the functional connectivity of the default mode network using blood oxygen level dependent (BOLD) functional magnetic resonance imaging in patients with schizophrenia and healthy volunteers. Schizophrenic patients are divided into two groups according to antipsychotic medication used: group treated without clozapine (n = 13) and group treated with clozapine (n = 13). Healthy volunteers were also divided into control group (n = 14) and control group with passive listening task (n = 5). All schizophrenic patients and healthy volunteers were subjected to a sodium nitroprusside infusion protocol simultaneously to acquisition of functional images. Our results showed increased default mode network functional connectivity with the drug infusion in patients with schizophrenia, mainly in the right hemisphere, while this same pattern was not found in healthy controls. In addition, the increase in connectivity was distinct between groups of patients because it was earlier and more extensive in the group of patients that was not in use of clozapine antipsychotic. We also note that the drug modulatory effect occurred on default mode network regions already studied and strongly implicated in the schizophrenia pathogenesis. Thus, our neurofunctional research contributed to the understanding of the sodium nitroprusside therapeutic effects on the schizophrenia symptoms. Our findings also underline the importance of sodium nitroprusside as a new adjuvant pharmacological tool in the treatment of schizophrenia

Apesar dos numerosos estudos enfocando a compreensão da esquizofrenia, sua etiologia permanece desconhecida. Atualmente, as medicações antipsicóticas disponíveis são baseadas principalmente na hipótese dopaminérgica, porém, apresentam eficácia parcial no tratamento dos sintomas. Diante disso, outros sistemas neurais têm sido investigados e, nesse contexto, a hipótese glutamatérgica conquistou grande importância. Essa hipótese postula a presença de uma hipoatividade do receptor glutamatérgico N-metil-D-aspartato na esquizofrenia e, consequentemente, de uma desregulação na neurotransmissão do óxido nítrico. Um ensaio clínico recente com a administração de nitroprussiato de sódio, um doador de óxido nítrico, mostrou resultados significativos na melhora da sintomatologia de pacientes esquizofrênicos, entretanto, nenhum estudo de neuroimagem investigou quais são os efeitos dessa droga no sistema nervoso central. No crescente campo de estudo da neuroimagem funcional as redes neurais foram descobertas, sendo a default mode network uma das mais estudadas na esquizofrenia. Os recentes estudos de neuroimagem funcional têm evidenciado alterações do funcionamento dessa rede neural nos pacientes portadores da doença, evidenciando assim, a importância da default mode network na compreensão da esquizofrenia. Nesse caminho, o presente estudo investigou os efeitos agudos da administração de nitroprussiato de sódio na conectividade funcional da rede default mode network através da ressonância magnética funcional mediada pelo contraste BOLD (blood oxygen level dependent) em pacientes portadores de esquizofrenia e em voluntários saudáveis. Os pacientes portadores de esquizofrenia foram divididos em dois grupos de acordo com a medicação antipsicótica em uso: grupo sem clozapina (n=13) e grupo com clozapina (n=13). Os voluntários saudáveis também foram divididos em grupo controle (n=14) e grupo controle com tarefa de escuta passiva (n=5). Todos os pacientes portadores de esquizofrenia e o grupo controle foram submetidos a um protocolo de infusão de nitroprussiato de sódio com aquisição simultânea de imagens funcionais. Nossos resultados mostraram um aumento da conectividade funcional da default mode network com a infusão da medicação nos pacientes portadores de esquizofrenia, especialmente no hemisfério direito, enquanto esse mesmo padrão não foi encontrado nos controles saudáveis. Além disso, o aumento na conectividade se mostrou distinto entres os grupos de pacientes avaliados, sendo mais precoce e amplo no grupo de pacientes que não estava em uso do antipsicótico clozapina. Observamos também que o efeito modulatório da droga ocorreu sobre regiões da default mode network já estudadas e fortemente implicadas na fisiopatogenia da esquizofrenia. Assim, nossa investigação neurofuncional contribuiu para a compreensão dos efeitos terapêuticos do nitroprussiato de sódio na sintomatologia de pacientes portadores de esquizofrenia. Nossos achados também reforçam a importância do nitroprussiato de sódio como uma nova ferramenta farmacológica adjuvante no tratamento da esquizofrenia / Despite numerous studies focusing on the understanding of schizophrenia, its etiology remains unknown. Currently, available antipsychotic medications are mainly based on dopamine hypothesis, however, they exhibit partial efficacy in the treatment of the symptoms. Therefore, other neural systems have been investigated and, in this context, the glutamatergic hypothesis gained great importance. This hypothesis postulates the presence of a hypoactivity of the N-methyl-D-aspartate glutamate receptor in schizophrenia and, consequently, a deregulation of nitric oxide neurotransmission. A recent clinical trial with the administration of sodium nitroprusside, a nitric oxide donor, showed significant results in improving the symptoms of schizophrenic patients, however, no neuroimaging study investigated what are the effects of this drug on the central nervous system. The neural networks were discovered from the growing field of functional neuroimaging study and the default mode network is one of the most studied in schizophrenia. The recent functional neuroimaging studies have shown alterations in the functioning of this neural network in patients with the disease, highlighting the importance of the default mode network in the understanding of schizophrenia. In this way, the present study investigated the acute effects of sodium nitroprusside administration in the functional connectivity of the default mode network using blood oxygen level dependent (BOLD) functional magnetic resonance imaging in patients with schizophrenia and healthy volunteers. Schizophrenic patients are divided into two groups according to antipsychotic medication used: group treated without clozapine (n = 13) and group treated with clozapine (n = 13). Healthy volunteers were also divided into control group (n = 14) and control group with passive listening task (n = 5). All schizophrenic patients and healthy volunteers were subjected to a sodium nitroprusside infusion protocol simultaneously to acquisition of functional images. Our results showed increased default mode network functional connectivity with the drug infusion in patients with schizophrenia, mainly in the right hemisphere, while this same pattern was not found in healthy controls. In addition, the increase in connectivity was distinct between groups of patients because it was earlier and more extensive in the group of patients that was not in use of clozapine antipsychotic. We also note that the drug modulatory effect occurred on default mode network regions already studied and strongly implicated in the schizophrenia pathogenesis. Thus, our neurofunctional research contributed to the understanding of the sodium nitroprusside therapeutic effects on the schizophrenia symptoms. Our findings also underline the importance of sodium nitroprusside as a new adjuvant pharmacological tool in the treatment of schizophrenia