Changes In Regional Function Research Articles

Interoceptive Processing in Functional Gastrointestinal Disorders.

Functional gastrointestinal disorders (FGIDs) are characterized by chronic gastrointestinal symptoms in the absence of overt pathology and affect a significant percentage of the worldwide population. They are commonly accompanied by co-morbid psychiatric symptomatology and are associated with significant suffering and great healthcare services utilization. There is growing evidence that dysregulation of the gut-brain axis and disturbances in the processing of afferent interoceptive signals lie at the heart of these disorders. In this context, the aim of the current review was to detect and critically review original articles focusing on the role of interoception in the pathophysiology of FGIDs. Our search yielded 38 relevant studies. FGID patients displayed increased visceral sensitivity, enhanced attention to gastrointestinal interoceptive cues, and greater emotional arousal when coping with gut-derived sensations. Neuroimaging studies have shown significant structural and functional changes in regions of the interoceptive network, while molecular and genetic studies have revealed significant associations between interoceptive signaling and deficits in excitatory neurotransmission, altered endocrine and immune physiological pathways, and aberrant expression of transient receptor potential channel genes. Finally, there were emerging data suggesting that interoception-based interventions may reduce physical symptoms and improve quality of life and should be integrated into FGID clinical management practices.

Altered spontaneous regional brain activity in ventromedial prefrontal cortex and visual area of expert table tennis athletes.

Sports training may lead to functional changes in the brain, and different types of sports, including table tennis, have different influences on these changes. However, the effects of long-term table tennis practice on brain function in expert athletes are largely undefined. Here, we investigated spontaneous regional brain activity characteristics of expert table tennis athletes by using resting-state functional magnetic resonance imaging to compare differences between 25 athletes and 33 age- and sex-matched non-athletes. We analyzed four metrics-amplitude of low-frequency fluctuation (ALFF), fractional ALFF, regional homogeneity, and degree centrality-because together they identify functional changes in the brain with greater sensitivity than a single indicator and may more comprehensively describe regional functional changes. Additional statistical analysis was conducted to assess whether any correlation existed between brain activity and years of table tennis training for athletes. Results show that compared with non-athletes, table tennis athletes showed altered spontaneous regional brain activity in the ventromedial prefrontal cortex and the calcarine sulcus, a visual area. Furthermore, the functional changes in the calcarine sulcus showed a significant correlation with the number of years of expert sports training. Despite the relatively small sample size, these results indicated that the regional brain function of table tennis athletes was associated with sports training-related changes, providing insights for understanding the neural mechanisms underlying the expert performance of athletes.

Daily Cannabidiol Administration for 10 Weeks Modulates Hippocampal and Amygdalar Resting-State Functional Connectivity in Cannabis Users: A Functional Magnetic Resonance Imaging Open-Label Clinical Trial.

Introduction: Cannabis use is associated with brain functional changes in regions implicated in prominent neuroscientific theories of addiction. Emerging evidence suggests that cannabidiol (CBD) is neuroprotective and may reverse structural brain changes associated with prolonged heavy cannabis use. In this study, we examine how an ∼10-week exposure of CBD in cannabis users affected resting-state functional connectivity in brain regions functionally altered by cannabis use. Materials and Methods: Eighteen people who use cannabis took part in a ∼10 weeks open-label pragmatic trial of self-administered daily 200 mg CBD in capsules. They were not required to change their cannabis exposure patterns. Participants were assessed at baseline and post-CBD exposure with structural magnetic resonance imaging (MRI) and a functional MRI resting-state task (eyes closed). Seed-based connectivity analyses were run to examine changes in the functional connectivity of a priori regions-the hippocampus and the amygdala. We explored if connectivity changes were associated with cannabinoid exposure (i.e., cumulative cannabis dosage over trial, and plasma CBD concentrations and Δ9-tetrahydrocannabinol (THC) plasma metabolites postexposure), and mental health (i.e., severity of anxiety, depression, and positive psychotic symptom scores), accounting for cigarette exposure in the past month, alcohol standard drinks in the past month and cumulative CBD dose during the trial. Results: Functional connectivity significantly decreased pre-to-post the CBD trial between the anterior hippocampus and precentral gyrus, with a strong effect size (d=1.73). Functional connectivity increased between the amygdala and the lingual gyrus pre-to-post the CBD trial, with a strong effect size (d=1.19). There were no correlations with cannabinoids or mental health symptom scores. Discussion: Prolonged CBD exposure may restore/reduce functional connectivity differences reported in cannabis users. These new findings warrant replication in a larger sample, using robust methodologies-double-blind and placebo-controlled-and in the most vulnerable people who use cannabis, including those with more severe forms of Cannabis Use Disorder and experiencing worse mental health outcomes (e.g., psychosis, depression).

Hyperpolarized Xenon-129: A New Tool to Assess Pulmonary Physiology in Patients with Pulmonary Fibrosis.

The existing tools to quantify lung function in interstitial lung diseases have significant limitations. Lung MRI imaging using inhaled hyperpolarized xenon-129 gas (129Xe) as a contrast agent is a new technology for measuring regional lung physiology. We sought to assess the utility of the 129Xe MRI in detecting impaired lung physiology in usual interstitial pneumonia (UIP). After institutional review board approval and informed consent and in compliance with HIPAA regulations, we performed chest CT, pulmonary function tests (PFTs), and 129Xe MRI in 10 UIP subjects and 10 healthy controls. The 129Xe MRI detected highly heterogeneous abnormalities within individual UIP subjects as compared to controls. Subjects with UIP had markedly impaired ventilation (ventilation defect fraction: UIP: 30 ± 9%; healthy: 21 ± 9%; p = 0.026), a greater amount of 129Xe dissolved in the lung interstitium (tissue-to-gas ratio: UIP: 1.45 ± 0.35%; healthy: 1.10 ± 0.17%; p = 0.014), and impaired 129Xe diffusion into the blood (RBC-to-tissue ratio: UIP: 0.20 ± 0.06; healthy: 0.28 ± 0.05; p = 0.004). Most MRI variables had no correlation with the CT and PFT measurements. The elevated level of 129Xe dissolved in the lung interstitium, in particular, was detectable even in subjects with normal or mildly impaired PFTs, suggesting that this measurement may represent a new method for detecting early fibrosis. The hyperpolarized 129Xe MRI was highly sensitive to regional functional changes in subjects with UIP and may represent a new tool for understanding the pathophysiology, monitoring the progression, and assessing the effectiveness of treatment in UIP.

Depressive symptoms in cognitively unimpaired older adults are associated with decreased structural and functional integrity in the limbic network

AbstractBackgroundSubclinical depressive symptoms are prevalent in older adults. They are associated with increased risk for both clinical depression and Alzheimer’s disease (AD), and may at least partly reflect early AD manifestations. However, the brain mechanisms underlying the relationship between depressive symptoms and AD remain to be elucidated. The aim of this study was to provide a comprehensive overview of the brain substrates of subclinical depressive symptoms in cognitively unimpaired older adults using complementary multimodal neuroimaging data in two independent cohorts.MethodWe selected 135 cognitively unimpaired older adults from the baseline data of the primary cohort Age‐Well, and 252 from the replication cohort ADNI. In both cohorts, subclinical depressive symptoms were assessed using the 15‐item version of the Geriatric Depression Scale (GDS); based on this scale, participants were classified as having depressive symptoms (DepS; GDS > 0) or not (NoDepS; GDS = 0). Voxelwise between‐group comparisons were performed to highlight differences in gray matter volume and amyloid deposition (both cohorts), as well as white matter integrity, brain perfusion (Age‐Well) and glucose metabolism (ADNI). Analyses were corrected for age, sex and education (and anxiety when available i.e. in Age‐Well) and thresholded at p<0.005.ResultOlder adults with subclinical depressive symptoms had significantly lower gray matter volume, perfusion and glucose metabolism in the hippocampus compared to participants without symptoms (Fig. 1). Glucose hypometabolism extended to the amygdala, precuneus/posterior cingulate and medial prefrontal cortex, insula, and temporoparietal cortex. Older adults with subclinical depressive symptoms also showed lower white matter integrity in the fornix and the posterior parts of the cingulum and corpus callosum. Brain amyloid deposition was not associated with the presence of subclinical depressive symptoms in either cohort.ConclusionThe presence of subclinical depressive symptoms in cognitively unimpaired older adults are associated with brain structural and functional changes in regions of the limbic network known to be particularly vulnerable to AD. Structural and functional changes overlapped in the hippocampus, indicating that deterioration in this region could underlie the relationship between depressive symptoms and AD while amyloid deposition does not appear to be involved at this stage.

REGIONAL AORTIC VASCULAR DYSFUNCTION IN A RODENT MODEL OF METABOLIC SYNDROME

Objective: Obesity and diabetes constitute a hallmark of metabolic syndrome that is directly linked to vascular dysfunction and high blood pressure (BP). Accordingly, we aimed to investigate regional functional changes in thoracic and abdominal aortic responses in a rat model of high fat diet (HFD) and streptozotocin (STZ)-induced diabetes mellitus. Design and method: Five weeks old male Wistar Albino rats (n = 24) were fed with either HFD (45 kcal% fat) or control diet (10 kcal% fat) for 10 weeks. At 10 weeks of age, 40 mg/kg STZ and saline were injected intraperitoneally into the HFD and control groups, respectively. At the end of the treatment, rats were euthanized to assess vasoconstrictor and vasodilator responses of dissected aortic segments. Results: Conscious tail-cuff systolic BP was higher in the HFD relative to control (154 ± 6 mmHg vs. 110 ± 4 mmHg, p < 0.001). Oral glucose tolerance test (oGTT) generated greater AUCs in the HFD rats relative to controls (64,361 ± 383 vs. 14,169 ± 398, p < 0.001). Abdominal aortic vasoconstriction (N/g) to norepinephrine (NE, 1E-9 – 3E-5 M) and the depolarizing signals of high potassium (KCl, 5 – 120 mM) was greater (p < 0.05) in the HFD group compared with controls. Thoracic aortic vasoconstrictor responses (N/g) to NE, but not KCl, were greater (p < 0.05) in the HFD group as compared to controls. Abdominal, but not thoracic, endothelium-dependent vasorelaxation to acetylcholine (1E-10 – 1E-5 M) was blunted (p < 0.05) in the HFD group relative to controls. In contrast, thoracic and abdominal aortic responses to sodium nitroprusside (SNP)-induced endothelium-independent relaxation remained comparable between groups. Conclusions: Vascular functional responses are altered along the descending aorta in metabolic syndrome, exhibiting exaggerated vasocontractility and impaired endothelium-dependent relaxation. These vascular functional abnormalities could potentially underlie the development of hypertensive cardiovascular disease associated with the metabolic syndrome.

Intrinsic brain activity changes in temporal lobe epilepsy patients revealed by regional homogeneity analysis

PurposeTemporal lobe epilepsy is increasingly being recognized as a disorder associated with brain networks extending outside the seizure onset zone. In the current study, we aim to clarify regional functional changes using a regional homogeneity method. MethodsWe retrospectively included resting-state fMRI data from 14 left and 18 right temporal lobe epilepsy patients. Data from the control group were acquired from an open dataset. Regional homogeneity was calculated, and a two-sample t-test was performed to compare the left and right temporal lobe epilepsy groups with the control group. ResultsCompared with the healthy control group, the left temporal lobe epilepsy group showed increased regional homogeneity in the left anterior and middle cingulate cortex, and putamen; right inferior frontal gyrus; bilateral temporal lobe and precentral gyrus and decreased regional homogeneity in the left superior parietal gyrus, cuneus and inferior occipital gyrus; right inferior parietal lobule and bilateral rectus. The right temporal lobe epilepsy group showed increased regional homogeneity in the left middle cingulate cortex, precuneus, precentral and postcentral gyrus; right insula and bilateral temporal lobe and decreased regional homogeneity in the left cuneus and superior occipital gyrus; right supramarginal gyrus, fusiform gyrus, lingual gyrus, inferior occipital gyrus and putamen; and the bilateral rectus. ConclusionRegional homogeneity measurements provide evidence supporting that temporal lobe epilepsy is a complex network disease. Functional disruption of temporal lobe epilepsy at the brain region level was revealed, which may provide novel insights for any potential diagnostic and therapeutic approaches.

Brain Structural and Functional Imaging Findings in Medication-Overuse Headache.

This chapter overviews research neuroimaging findings of patients with medication-overuse headache (MOH). Results indicate; (i) correlations between neuropathology and medication-overuse; (ii) changes in brain morphology and cortical function; and (iii) brain recovery subsequent to withdrawal of medication that was overused. Results of this narrative review indicate exacerbated brain structural and functional changes in regions of the pain-matrix and in regions of the mesocortical-limbic circuit in patients with MOH compared to patients with migraine or compared to healthy controls. Modification of brain morphology as well as an association between brain recovery and medication withdrawal suggest that the MOH disease process involves state (brain modification) and trait-like (brain adaptation and recovery) neuromechanisms.

Development of Threat Expression Following Infant Maltreatment: Infant and Adult Enhancement but Adolescent Attenuation.

Early life maltreatment by the caregiver constitutes a major risk factor for the development of later-life psychopathologies, including fear-related pathologies. Here, we used an animal model of early life maltreatment induced by the Scarcity-Adversity Model of low bedding (LB) where the mother is given insufficient bedding for nest building while rat pups were postnatal days (PN) 8–12. To assess effects of maltreatment on the expression of threat-elicited defensive behaviors, animals underwent odor-shock threat conditioning at three developmental stages: late infancy (PN18), adolescence (PN45) or adulthood (>PN75) and tested the next day with odor only presentations (cue test). Results showed that in typically developing rats, the response to threat increases with maturation, although experience with maltreatment in early infancy produced enhanced responding to threat in infancy and adulthood, but a decrease in maltreated adolescents. To better understand the unique features of this decreased threat responding in adolescence, c-Fos expression was assessed within the amygdala and ventromedial prefrontal cortex (vmPFC) associated with the cued expression of threat learning. Fos counts across amygdala subregions were lower in LB rats compared to controls, while enhanced c-Fos expression was observed in the vmPFC prelimbic cortex (PL). Correlational analysis between freezing behavior and Fos revealed freezing levels were correlated with CeA in controls, although more global correlations were detected in LB-reared rats, including the BA, LA, and CeA. Functional connectivity analysis between brain regions showed that LB reared rats exhibited more diffuse interconnectivity across amygdala subnuclei, compared the more heterogeneous patterns observed in controls. In addition, functional connectivity between the IL and LA switched from positive to negative in abused adolescents. Overall, these results suggest that in adolescence, the unique developmental decrease in fear expression following trauma is associated with distinct changes in regional function and long-range connectivity, reminiscent of pathological brain function. These results suggest that early life maltreatment from the caregiver perturbs the developmental trajectory of threat-elicited behavior. Indeed, it is possible that this form of trauma, where the infant’s safety signal or “safe haven” (the caregiver) is actually the source of the threat, produces distinct outcomes across development.

MRI-derived regional flow-volume loop parameters detect early-stage chronic lung allograft dysfunction.

Chronic lung allograft dysfunction (CLAD) is a major cause for the low long-term survival rates after lung transplantation (LTx). Early detection of CLAD may enable providing medical treatment before a nonreversible graft dysfunction has occurred. MRI is advantageous to pulmonary function testing (PFT) in the ability to assess regional function changes, and thus have the potential in detecting very early stages of CLAD before changes in global forced expiratory volume during the first second (FEV1%) occur. To examine whether early stages of CLAD (diagnosed based on PFT values) could also be detected using MRI-derived parameters of regional flow-volume dynamics. Retrospective. 62 lung transplantation recipients were included in the study, 29 of which had been diagnosed with CLAD at various stages. MRI datasets were acquired with a 1.5T Siemens scanner using a spoiled gradient echo sequence. MRI datasets were retrospectively preprocessed and analyzed by a blinded radiologist according to the phase resolved functional lung MRI (PREFUL-MRI) approach, resulting in fractional ventilation (FV) maps and regional flow-volume loops (rFVL). FV- and rFVL-based parameters of regional lung ventilation were estimated. Differences between groups were compared by Mann-Whitney U-test with a Bonferroni correction for multiple comparisons (n = 2). rFVL-CC-based parameters discriminated significantly between the presence or absence of CLAD (P < 0.003). Using the contrast media-free PREFUL-MRI technique, parameters of ventilation dynamics and its regional heterogeneity were shown to be sensitive for the detection of early CLAD stages. 3 TECHNICAL EFFICACY: Stage 3 J. Magn. Reson. Imaging 2019;50:1873-1882.

Analysis of Tourism Villages Development in Indonesia: Case Studies : Three Tourism Villages

Potential tourist resources that attract many visitors are in the countryside, where natural resource potential is the main attraction. This has encouraged a number of countries to start upgrading villages to support tourism. Although physical investment is seen as accelerating tourism development, tourism sustainability in an area is not going well without the participation of the local community. This paper discusses the development of rural tourism in Indonesia. There are three tourism villages representing the Indonesian Tourism Village, namely Kampung Naga in Tasikmalaya Regency, Sinarresmi Tradisional Village in Sukabumi Regency (Ciletuh Geopark area), and Sade Village in Central Lombok Regency. The background includes the tourism component (attractions, facilities, and accessibility) and community resilience and tourism market segmentation to changes in regional functions. Methodology includes literature review and observation. The findings of this study indicate that the development of sustainable tourism in rural areas is strongly influenced by community acceptance and resilience in tourism development. As in Kampung Naga and Kampung SInarresmi consider the village is not a tourist attraction, the visit that comes not as an opportunity, but their reception as hosts and tourists as guests. Meanwhile, in Sade Village consider their area as a tourist attraction, so that tourist visits are seen as opportunities for economic growth, by commercializing traditional dances.

The Spatial Associations of Cerebral Blood Flow and Spontaneous Brain Activities with White Matter Hyperintensities-An Exploratory Study Using Multimodal Magnetic Resonance Imaging.

White matter hyperintensities (WMHs) have been reported to be correlated with functional brain changes, but the association of the specific WMHs distribution pattern with regional functional changes remains uncertain. The aim of this study is to explore the possible spatial correlation of WMH with changes in cerebral blood flow (CBF) and spontaneous brain activities in elderly using a novel approach. The WMHs, CBF, and spontaneous brain activities measured by intrinsic connectivity contrast (ICC), were quantified using multimodal magnetic resonance imaging for 69 elderly subjects. Such approach enables us to expand our search for newly identified correlated areas by drawing strengths of different modes and provides a means for triangulation as well as complementary insights. The results showed significant positive correlations between WMH volumes in the right superior corona radiata and CBF in the left supplementary motor area, as well as between WMH volumes in left anterior limb internal capsule and CBF in the right putamen. Significant correlations of regional WMH volumes and ICC were also detected between the right anterior corona radiata and the left cuneus, and the right superior occipital cortex, as well as between the right superior corona radiata and the left superior occipital cortex. These findings may suggest a regional compensatory functional enhancement accounting for the maintenance of cognitively normal status, which can be supported by the widely observed phenomenon that mild to moderate WMH load could have little effect on global cognitive performance.

Convergent and divergent intranetwork and internetwork connectivity patterns in patients with remitted late-life depression and amnestic mild cognitive impairment

IntroductionBoth remitted late-life depression (rLLD) and amnesiac mild cognitive impairment (aMCI) alter brain functions in specific regions of the brain. They are also disconnection syndromes that are associated with a high risk of developing Alzheimer's disease (AD). ObjectivesResting-state functional connectivity magnetic resonance imaging (rs-fcMRI) was performed to define the shared and distinct aberrant patterns in intranetwork and internetwork connectivity between rLLD and aMCI and to determine how knowledge of these differences might contribute to our essential understanding of the altered sequences involved in functional systems both inside and outside of resting-state networks. MethodsWe used rs-fcMRI to investigate in five functionally well-defined brain networks in two large cohorts of subjects at high risk for AD (55 rLLD and 87 aMCI) and 114 healthy controls (HC). ResultsA reduced degree of functional connectivity was observed in the bilateral inferior temporal cortex and supplemental motor area, and reduced correlations were observed within the sensory-motor network (SMN) and in the default mode network (DMN)–control network (CON) pair in the rLLD group than the HC group. The aMCI group showed only focal functional changes in regions of interest pairs, a trend toward increased correlations within the salience network and SMN, and a trend toward a reduced correlation in the DMN–CON pair. Furthermore, the rLLD group exhibited more severely altered functional connectivity than the aMCI group. Interestingly, these altered connectivities were associated with specific multi-domain cognitive and behavioral functions in both rLLD and aMCI. The degree of functional connectivity in the right primary auditory areas was negatively correlated with Hamilton Depression Scale scores in rLLD. Notably, altered connectivity between the right middle temporal cortex and the posterior cerebellum was negatively correlated with Mattis Dementia Rating Scale scores in both rLLD and aMCI. ConclusionsThese results demonstrate that rLLD and aMCI may share convergent and divergent aberrant intranetwork and internetwork connectivity patterns as a potential continuous spectrum of the same disease. They further suggest that dysfunctions in the right specific temporal-cerebellum neural circuit may contribute to the similarities observed in rLLD and aMCI conversion to AD.

"Cytoplasmic domain effects on exposure of co-receptor-binding sites of HIV-1 Env".

We defined the effects of the cytoplasmic domain (CT) of the Env glycoprotein on co-receptor usage of HIV-1 by reciprocal exchanges of regions containing V3-V5 loops between CD4-dependent and CD4-independent isolates. Primary HIV-1 isolate Env clones CD8 CXCR4-tropic 92UG046 CT84 with an 84-aa truncated CT domain, CD4 CXCR4-tropic 92UG046, and CD4 CCR5-tropic SF162 with full-length (FL) CT domains were used for comparison. The parental 92UG046 Env with CT84 was not fusogenic, but a chimeric SF162 V3-V5-CT84 with an 84-aa truncated CT domain, which demonstrated a switched co-receptor specificity, exhibited syncytium-formation activity with 3T3T4X4 cells. The wild-type (WT) SF162 Env with CT84 or full-length CT was fusogenic in 3T3T4R5 cells. By exchange of V3-V5 loops, we were able to alter WT SF162 to switch its co-receptor preference, which was not dependent on CT domain length. These results provide evidence that CT domains can induce conformational changes in functional regions of gp120 and determine receptor tropism but do not modulate HIV-1 co-receptor specificity.

Intra-network and inter-network shared connectivity patterns in patients with remitted late-life depression and amnestic mild cognitive impairment

Objectives Both remitted late-life depression (rLLD) and amnestic mild cognitive impairment (aMCI) alter brain function in individual regions. They are also disconnection syndromes associated with a high-risk of developing Alzheimer's disease (AD). Resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) was performed to define the shared and distinct aberrant patterns in intra-network and inter-network connectivity between rLLD and aMCI. Methods We investigated rs-fcMRI in five functionally well-defined brain networks in 55 rLLD, 87 aMCI, and 114 healthy controls (HC). Results Compared with HC, rLLD showed a reduced degree of functional connectivity in the bilateral inferior temporal cortex and supplemental motor area, and reduced correlations within the sensory-motor network (SMN) and in the default-mode network (DMN) – control network (CON) pair. aMCI showed only focal functional changes in regions of interest pairs, a trend toward increased correlations within the salience network and SMN, and a trend toward reduced correlation in the DMN-CON pair. Furthermore, rLLD exhibited more severely altered functional connectivity compared to aMCI. Interestingly, these altered connectivities were associated with specific multi-domain cognitive and behavioral functions in both rLLD and aMCI. Notably, altered connectivity between right middle temporal cortex and posterior cerebellum was negatively correlated with Mattis Dementia Rating Scale scores in both rLLD and aMCI. Conclusions These results demonstrate that rLLD and aMCI may share convergent and divergent aberrant intra-network and inter-network connectivity patterns. It further suggests that dysfunction in right specific temporal-cerebellum neural circuit may contribute to the similarities observed rLLD and aMCI conversion to AD.

VLP vaccines and effects of HIV-1 Env protein modifications on their antigenic properties

An ideal protective HIV-1 vaccine can elicit broadly neutralizing antibodies, capable of preventing HIV transmission. The strategies of designing vaccines include generation of soluble recombinant proteins which mimic the native Env complex and are able to enhance the immunogenicity of gp120. Recent data indicate that the cytoplasmic tail (CT) of the Env protein has multiple functions, which can affect the early steps of infection, as well as viral assembly and antigenic properties. Modifications in the CT can be used to induce conformational changes in functional regions of gp120 and to stabilize the trimeric structure, avoiding immune misdirection and induction of non-neutralizing antibody responses. Env-trimers with modified CTs in virus-like particles (VLPs) are able to induce antibodies with broad spectrum neutralizing activity and high avidity and have the potential for developing an effective vaccine against HIV.

FDG-PET Contributions to the Pathophysiology of Memory Impairment.

Measurement of synaptic activity by Positron Emission Tomography (PET) and its relation to cognitive functions such as episodic memory, working memory and executive functions in healthy humans and patients with neurocognitive disorders have been well documented. In this review, we introduce the concept of PET imaging that allows the observation of a particular biological process in vivo through the use of radio-labelled compounds, its general use to the medical world and its contributions to the understanding of memory systems. We then focus on [(18)F]-2-fluoro-2-deoxy-D-glucose (FDG-PET), the radiotracer that is used to measure local cerebral metabolic rate of glucose that is indicative of synaptic activity in the brain. FDG-PET at rest has been at the forefront of functional neuroimaging over the past 3 decades, contributing to the understanding of cognitive functions in healthy humans and how these functional patterns change with cognitive alterations. We discuss methodological considerations that are important for optimizing FDG-PET imaging data prior to analysis. We then highlight the contribution of FDG-PET to the understanding of the patterns of functional differences in non-degenerative pathologies, normal ageing, and age-related neurodegenerative disorders. Through reasonable temporal and spatial resolution, its ability to measure synaptic activity in the whole brain, independently of any specific network and disease, makes it ideal to observe regional functional changes associated with memory impairment.

The Role of MiR‐21 in Right Ventricular Remodeling Secondary to Pulmonary Arterial Pressure Overload

Pulmonary arterial hypertension (PAH) prognosis is related to the degree of right ventricular (RV) dysfunction. While the effects of pulmonary pressure overload on RV remodeling are largely unknown, microRNA‐21 (miR‐21) has been identified as a factor involved in PAH vasculature remodeling and cellular hypertrophy. The goal of this study is to characterize regional structural and functional change in RV after PAH and identify the role of miR‐21. Pulmonary arterial constriction (PAC) induced PAH in 5‐month‐old adult male sheep. Longitudinal echocardiography was used to monitor functional and structural changes. After four weeks, hearts were harvested for histological and molecular examination. Isolated neonatal rat ventricular myocytes (NRVM) were used to define the role of miR‐21 in cardiomyocytes (CM). Elevated PA pressure led to increased RV weight and thickness in PAC sheep. Decreased systolic function was most profound in the RV basal region. Following changes in regional function, miR‐21 was also differentially upregulated in the basal region as determined by RT‐PCR. Interestingly, NRVM treated with a miR‐21 mimic increased mitosis but not cytokinesis compared to controls. Congruently, RV basal CM isolated from PAC animals revealed increased elongated multinuclear cells, supporting the notion of RV pressure overload‐induced hypertrophy. We conclude that PAC led to regional alterations and contributes to adverse global functional changes. The differential upregulation of miR‐21 in basal and altered RV CM remodeling may indicate PAC‐induced regional and global structural and functional RV remodeling.

834 Neurocircuitry and Neurochemistry of Cyclic Vomiting Syndrome

structural changes in salience (which determines the relevance of internal and external information) and central autonomic networks in IBS are correlated with differences in myelopoetic processes and gene expression in PBMCs, consistent with increased SNS modulation of the peripheral immune system. 2. Regional functional changes in the salience network are correlated with expression of pro inflammatory genes, suggesting that primed monocytes migrate to the brain, inducing structural and functional changes in brain regions involved in visceral hypersensitivity and increased anxiety.

835 Maintenance Medications for Cyclic Vomiting Syndrome Affect Gray Matter Density in Brain Areas Serving Autonomic Function

structural changes in salience (which determines the relevance of internal and external information) and central autonomic networks in IBS are correlated with differences in myelopoetic processes and gene expression in PBMCs, consistent with increased SNS modulation of the peripheral immune system. 2. Regional functional changes in the salience network are correlated with expression of pro inflammatory genes, suggesting that primed monocytes migrate to the brain, inducing structural and functional changes in brain regions involved in visceral hypersensitivity and increased anxiety.