Oxytocin Affects the Connectivity of the Precuneus and the Amygdala: A Randomized, Double-Blinded, Placebo-Controlled Neuroimaging Trial

BACKGROUND: Although oxytocin is one of the most widely studied neuropeptides in recent times, the mechanistic process by which it modulates social-affective behavior in the brain is not yet clearly understood. Thus, to understand the neurophysiological basis of oxytocin effects, we used resting-state functional MRI to examine the effects of intranasal oxytocin on brain connectivity in healthy males. METHODS: Using a randomized, double-blinded, placebo-controlled, crossover design, 15 healthy male volunteers received 24 IU intranasal oxytocin or placebo prior to resting-state functional MRI acquisition at 3T. RESULTS: We found that oxytocin significantly reduced the degree centrality of the right precuneus (P<.05). Oxytocin also reduced connectivity between the bilateral amygdalae and between the right precuneus and the right and left amygdala (P<.05). Although there were no significant changes in regional homogeneity at the whole brain level, posthoc results showed a reduction involving the right precuneus (P<.05). CONCLUSIONS: These results show that oxytocin affects one of the key centers in the brain for social cognition and introspective processing, the precuneus, and enhances our understanding of how oxytocin can modulate brain networks at rest. An improved understanding of the neurophysiological effects of oxytocin can be important in terms of evaluating the mechanisms that are likely to underlie the clinical responses observed upon long-term oxytocin administration

Isolation, biochemical and molecular characterization of strains of coliforms from the water sample collected from Shivnath river

Coliform bacteria include organisms like Escherichia coli, Enterobacter sp., Klebsiella sp. and Citrobacter sp.and are gram negative, facultative anaerobic, non-sporulating and lactose fermenting organisms. E. coli is used as the indicator organism for detection of faecal contamination of water. Conventional methods for the detection of Coliforms in water include microbial culture technique in lactose containing media, Biochemical characterization, study of cell morphology, colony morphology etc. These methods are time consuming with limited specificity. DNA based molecular techniques like 16S rRNA gene sequencing is highly specific. In this research work, the16S rRNA gene sequencing technique was used to characterize the two isolates from water samples of Shivnath River after the above said preliminary tests were conducted. The two strains of coliforms identified by this technique were Escherichia coli strain GA and Enterobacter cloacae strain AB6

Quantifying the core deficit in classical schizophrenia

In the classical descriptions of schizophrenia, Kraepelin and Bleuler recognised disorganization and impoverishment of mental activity as fundamental symptoms. Their classical descriptions also included a tendency to persisting disability. The psychopathological processes underlying persisting disability in schizophrenia remain poorly understood. The delineation of a core deficit underlying persisting disability would be of value in predicting outcome and enhancing treatment. We tested the hypothesis that mental disorganization and impoverishment are associated with persisting impairments of cognition and role-function, and together reflect a latent core deficit that is discernible in cases diagnosed by modern criteria. We used Confirmatory Factor Analysis to determine whether measures of disorganisation, mental impoverishment, impaired cognition and role functioning in 40 patients with schizophrenia represent a single latent variable. Disorganization scores were computed from the variance shared between disorganization measures from three commonly used symptom scales. Mental impoverishment scores were computed similarly. A single factor model exhibited a good fit, supporting the hypothesis that these measures reflect a core deficit.Persisting brain disorders are associated with a reduction in Post Motor Beta Rebound (PMBR), the characteristic increase in electrophysiological beta amplitude that follows a motor response. Patients had significantly reduced PMBR compared with healthy controls. PMBR was negatively correlated with core deficit score.While the symptoms constituting impoverished and disorganised mental activity are dissociable in schizophrenia, nonetheless, the variance that these two symptom domains share with impaired cognition and role function, appears to reflect a pathophysiological process that might be described as the core deficit of classical schizophrenia

Glutathione and glutamate in schizophrenia: a 7T MRS study

In schizophrenia, abnormal neural metabolite concentrations may arise from cortical damage following neuroinflammatory processes implicated in acute episodes. Inflammation is associated with increased glutamate, whereas the antioxidant glutathione may protect against inflammation-induced oxidative stress. We hypothesized that patients with stable schizophrenia would exhibit a reduction in glutathione, glutamate, and/or glutamine in the cerebral cortex, consistent with a post-inflammatory response, and that this reduction would be most marked in patients with “residual schizophrenia”, in whom an early stage with positive psychotic symptoms has progressed to a late stage characterized by long-term negative symptoms and impairments. We recruited 28 patients with stable schizophrenia and 45 healthy participants matched for age, gender, and parental socio-economic status. We measured glutathione, glutamate and glutamine concentrations in the anterior cingulate cortex (ACC), left insula, and visual cortex using 7T proton magnetic resonance spectroscopy (MRS). Glutathione and glutamate were significantly correlated in all three voxels. Glutamine concentrations across the three voxels were significantly correlated with each other. Principal components analysis (PCA) produced three clear components: an ACC glutathione–glutamate component; an insula-visual glutathione–glutamate component; and a glutamine component. Patients with stable schizophrenia had significantly lower scores on the ACC glutathione–glutamate component, an effect almost entirely leveraged by the sub-group of patients with residual schizophrenia. All three metabolite concentration values in the ACC were significantly reduced in this group. These findings are consistent with the hypothesis that excitotoxicity during the acute phase of illness leads to reduced glutathione and glutamate in the residual phase of the illness

Glutathione and glutamate in schizophrenia: a 7T MRS study

In schizophrenia, abnormal neural metabolite concentrations may arise from cortical damage following neuroinflammatory processes implicated in acute episodes. Inflammation is associated with increased glutamate, whereas the antioxidant glutathione may protect against inflammation-induced oxidative stress. We hypothesized that patients with stable schizophrenia would exhibit a reduction in glutathione, glutamate and/or glutamine in the cerebral cortex, consistent with a postinflammatory response, and that this reduction would be most marked in patients with residual schizophrenia an early stage with positive psychotic symptoms has progressed to a late stage characterised by long-term negative symptoms and impairments. We recruited 28 patients with stable schizophrenia and 45 healthy participants matched for age, gender and parental socio-economic status. We measured glutathione, glutamate and glutamine concentrations in the anterior cingulate cortex (ACC), left insula, and visual cortex using 7T proton Magnetic Resonance Spectroscopy (MRS). Glutathione and glutamate were significantly correlated in all three voxels. Glutamine concentrations across the three voxels were significantly correlated with each other. Principal Components Analysis (PCA) produced three clear components: an ACC glutathione-glutamate component; an insula-visual glutathione-glutamate component; and a glutamine component. Patients with stable schizophrenia had significantly lower scores on the ACC glutathione-glutamate component, an effect almost entirely leveraged by the sub-group of patients with residual schizophrenia. All three metabolite concentration values in the ACC were significantly reduced in this group. These findings are consistent with the hypothesis that excito-toxicity during the acute phase of illness leads to reduced glutathione and glutamate in the residual phase of the illness

Multimodal Imaging of the Salience Network in Schizophrenia

Growing evidence suggests that the Salience Network, anchored on the bilateral anterior insula and dorsal anterior cingulate cortex plays a key role in the pathophysiology of schizophrenia. However, several questions regarding the exact nature of these abnormalities in schizophrenia remain unanswered. This thesis examines the neurobiological basis of Salience Network dysfunction in patients with schizophrenia. Specifically, in this work, we use multi-modal neuroimaging techniques to investigate abnormalities in the functioning, connectivity and neurochemistry of the Salience Network in schizophrenia. Chapter 1 introduces the concept of schizophrenia as a disorder of salience and the role of the Salience Network in this context. Chapter 2 describes participant recruitment, data collection and the neuroimaging techniques used in this work. Chapters 3 to 5 present the results from three research studies. In the first study, using functional Magnetic Resonance Imaging (fMRI) and Magnetoencephalography (MEG), we investigate regional brain activity in response to a task designed to engage the Salience Network. We report evidence demonstrating inefficient cerebral recruitment in patients with schizophrenia i.e. aberrant activity in task positive and task negative brain regions; along with reduced beta response to relevant stimuli in the Salience Network. These findings are reported in chapter 3. In chapter 4, we use high resolution 7T Magnetic Resonance Spectroscopy (MRS) and demonstrate that neurochemical abnormalities in schizophrenia vary between patients depending on their clinical status. Specifically, we show that glutathione and glutamate concentrations in the Anterior Cingulate Cortex are prominently reduced in patients with residual schizophrenia. We also provide evidence linking two popular neurochemical theories of schizophrenia – the NMDA receptor hypofunction hypothesis and the theory of oxidative stress. Chapter 5 explores the question of disrupted effective connectivity within the Salience Network in schizophrenia using resting-state fMRI. In this chapter, we report abnormalities in effective connectivity within the Salience Network in patients with schizophrenia. We also demonstrate that these aberrant causal interactions are related to the neurochemical abnormalities reported in chapter 4. Finally, in Chapter 6, we discuss the significance and translational potential of these findings and offer recommendations for future work. Overall, using a multimodal imaging study design and a wide range of measures, this thesis reports novel findings which further our understanding of Salience Network dysfunction in schizophrenia and provides a good foundation for future research studies in this area

Multimodal Imaging of the Salience Network in Schizophrenia

Growing evidence suggests that the Salience Network, anchored on the bilateral anterior insula and dorsal anterior cingulate cortex plays a key role in the pathophysiology of schizophrenia. However, several questions regarding the exact nature of these abnormalities in schizophrenia remain unanswered. This thesis examines the neurobiological basis of Salience Network dysfunction in patients with schizophrenia. Specifically, in this work, we use multi-modal neuroimaging techniques to investigate abnormalities in the functioning, connectivity and neurochemistry of the Salience Network in schizophrenia. Chapter 1 introduces the concept of schizophrenia as a disorder of salience and the role of the Salience Network in this context. Chapter 2 describes participant recruitment, data collection and the neuroimaging techniques used in this work. Chapters 3 to 5 present the results from three research studies. In the first study, using functional Magnetic Resonance Imaging (fMRI) and Magnetoencephalography (MEG), we investigate regional brain activity in response to a task designed to engage the Salience Network. We report evidence demonstrating inefficient cerebral recruitment in patients with schizophrenia i.e. aberrant activity in task positive and task negative brain regions; along with reduced beta response to relevant stimuli in the Salience Network. These findings are reported in chapter 3. In chapter 4, we use high resolution 7T Magnetic Resonance Spectroscopy (MRS) and demonstrate that neurochemical abnormalities in schizophrenia vary between patients depending on their clinical status. Specifically, we show that glutathione and glutamate concentrations in the Anterior Cingulate Cortex are prominently reduced in patients with residual schizophrenia. We also provide evidence linking two popular neurochemical theories of schizophrenia – the NMDA receptor hypofunction hypothesis and the theory of oxidative stress. Chapter 5 explores the question of disrupted effective connectivity within the Salience Network in schizophrenia using resting-state fMRI. In this chapter, we report abnormalities in effective connectivity within the Salience Network in patients with schizophrenia. We also demonstrate that these aberrant causal interactions are related to the neurochemical abnormalities reported in chapter 4. Finally, in Chapter 6, we discuss the significance and translational potential of these findings and offer recommendations for future work. Overall, using a multimodal imaging study design and a wide range of measures, this thesis reports novel findings which further our understanding of Salience Network dysfunction in schizophrenia and provides a good foundation for future research studies in this area

Frontal neural metabolite changes in schizophrenia and their association with cognitive control: A systematic review

A large proportion of patients with schizophrenia exhibit deficits in cognitive control functions including working memory, processing speed and inhibitory control, which have been associated with frontal brain areas. In this systematic review, we investigated differences between chronic schizophrenia patients, first-episode (FEP) patients and healthy control groups in the neurometabolite levels of GABA, glutamate, glutamine and Glx in frontal brain areas. Additionally, we reviewed correlations between cognitive control functions or negative symptoms and these neurometabolite levels. Several studies reported decreased GABA or glutamate concentrations in frontal lobe areas, particularly in chronic schizophrenia patients, while the results were mixed for FEP patients. Working memory performance and prediction errors have been associated with frontal GABA and glutamate levels, and processing speed with frontomedial GABA levels in chronic patients. The relationship between metabolites and negative symptom severity was somewhat inconsistent. Future studies should take the participants' age, medication status or responsivity, disease stage and precise anatomical location of the voxel into account when comparing neurometabolite levels between schizophrenia patients and healthy controls

Intensity and spatiotemporal variations of drought in Tumakuru district, India using drought indices

Depletion of water resources and soil moisture leading to drought is a global concern and the effective assessment and monitoring using a drought model has become essential. A detailed account of frequency, run length and temporal trend of the drought events are presented in the study from 1981 to 2019 at the 1-, 3-, 6-, 9-, 12- and 24-month timescale using the Standardized Precipitation Index and Standardized Precipitation Evapotranspiration Index. SPI recorded more drought months in the extreme category with 14 months at Gubbi station for example, while SPEI showed only 5 months. SPEI showed longer drought length in moderate and severe categories for agricultural and hydrological drought. At a 1-month timescale, both the indices reported extreme drought events where Tiptur station in May 2016 (–4.75) and Chikkanayakanahalli station in March 1992 (–2.76) were the worst-case scenarios. The study aims at providing practical results to facilitate decision-makers for drought risk management

Oxytocin modulates the effective connectivity between the precuneus and the dorsolateral prefrontal cortex

Our social activity is heavily influenced by the process of introspection, with emerging research suggesting a role for the Default Mode Network (DMN) in social cognition. We hypothesize that oxytocin, a neuropeptide with an important role in social behaviour, can effectively alter the connectivity of the DMN. We test this hypothesis using a randomized, double-blind, crossover, placebo-controlled trial where 15 healthy male participants received 24 IU oxytocin or placebo prior to a resting-state functional MRI scan. We used Granger Causality Analysis for the first time to probe the role of oxytocin on brain networks and found that oxytocin reverses the pattern of effective connectivity between the bilateral precuneus and the left dorsolateral prefrontal cortex (dlPFC), a key central executive network (CEN) region. Under placebo, the bilateral precuneus exerted a significant negative causal influence on the left dlPFC and the left dlPFC exerted a significant positive causal influence on the bilateral precuneus. However, under oxytocin, these patterns were reversed, i.e. positive causal influence from the bilateral precuneus to the left dlPFC and negative causal influence from the left dlPFC to the bilateral precuneus (with statistically significant effects for the right precuneus). We propose that these oxytocin-induced effects could be a mechanistic process by which it modulates social cognition. These results provide a measurable target for the physiological effects of oxytocin in the brain and offer oxytocin as a potential agent to enhance the cooperative role of the predominantly ‘task-inactive’ ‘default mode’ brain regions in both healthy and patient populations