Brain representations of affective valence and intensity in sustained pleasure and pain.

Pleasure and pain are two fundamental, intertwined aspects of human emotions. Pleasurable sensations can reduce subjective feelings of pain and vice versa, and we often perceive the termination of pain as pleasant and the absence of pleasure as unpleasant. This implies the existence of brain systems that integrate them into modality-general representations of affective experiences. Here, we examined representations of affective valence and intensity in an functional MRI (fMRI) study (n = 58) of sustained pleasure and pain. We found that the distinct subpopulations of voxels within the ventromedial and lateral prefrontal cortices, the orbitofrontal cortex, the anterior insula, and the amygdala were involved in decoding affective valence versus intensity. Affective valence and intensity predictive models showed significant decoding performance in an independent test dataset (n = 62). These models were differentially connected to distinct large-scale brain networks-the intensity model to the ventral attention network and the valence model to the limbic and default mode networks. Overall, this study identified the brain representations of affective valence and intensity across pleasure and pain, promoting a systems-level understanding of human affective experiences.

Functional brain reconfiguration during sustained pain.

Pain is constructed through complex interactions among multiple brain systems, but it remains unclear how functional brain networks are reconfigured over time while experiencing pain. Here, we investigated the time-varying changes in the functional brain networks during 20 min capsaicin-induced sustained orofacial pain. In the early stage, the orofacial areas of the primary somatomotor cortex were separated from other areas of the somatosensory cortex and integrated with subcortical and frontoparietal regions, constituting an extended brain network of sustained pain. As pain decreased over time, the subcortical and frontoparietal regions were separated from this brain network and connected to multiple cerebellar regions. Machine-learning models based on these network features showed significant predictions of changes in pain experience across two independent datasets (n = 48 and 74). This study provides new insights into how multiple brain systems dynamically interact to construct and modulate pain experience, advancing our mechanistic understanding of sustained pain.

Post-Stroke Cognitive Impairment: Pathophysiological Insights into Brain Disconnectome from Advanced Neuroimaging Analysis Techniques.

The neurological symptoms of stroke have traditionally provided the foundation for functional mapping of the brain. However, there are many unresolved aspects in our understanding of cerebral activity, especially regarding high-level cognitive functions. This review provides a comprehensive look at the pathophysiology of post-stroke cognitive impairment in light of recent findings from advanced imaging techniques. Combining network neuroscience and clinical neurology, our research focuses on how changes in brain networks correlate with post-stroke cognitive prognosis. More specifically, we first discuss the general consequences of stroke lesions due to damage of canonical resting-state large-scale networks or changes in the composition of the entire brain. We also review emerging methods, such as lesion-network mapping and gradient analysis, used to study the aforementioned events caused by stroke lesions. Lastly, we examine other patient vulnerabilities, such as superimposed amyloid pathology and blood-brain barrier leakage, which potentially lead to different outcomes for the brain network compositions even in the presence of similar stroke lesions. This knowledge will allow a better understanding of the pathophysiology of post-stroke cognitive impairment and provide a theoretical basis for the development of new treatments, such as neuromodulation.

A neuroimaging biomarker for sustained experimental and clinical pain.

Sustained pain is a major characteristic of clinical pain disorders, but it is difficult to assess in isolation from co-occurring cognitive and emotional features in patients. In this study, we developed a functional magnetic resonance imaging signature based on whole-brain functional connectivity that tracks experimentally induced tonic pain intensity and tested its sensitivity, specificity and generalizability to clinical pain across six studies (total n = 334). The signature displayed high sensitivity and specificity to tonic pain across three independent studies of orofacial tonic pain and aversive taste. It also predicted clinical pain severity and classified patients versus controls in two independent studies of clinical low back pain. Tonic and clinical pain showed similar network-level representations, particularly in somatomotor, frontoparietal and dorsal attention networks. These patterns were distinct from representations of experimental phasic pain. This study identified a brain biomarker for sustained pain with high potential for clinical translation.

A neuroimaging marker for predicting longitudinal changes in pain intensity of subacute back pain based on large-scale brain network interactions.

Identification of predictive neuroimaging markers of pain intensity changes is a crucial issue to better understand macroscopic neural mechanisms of pain. Although a single connection between the medial prefrontal cortex and nucleus accumbens has been suggested as a powerful marker, how the complex interactions on a large-scale brain network can serve as the markers is underexplored. Here, we aimed to identify a set of functional connections predictive of longitudinal changes in pain intensity using large-scale brain networks. We re-analyzed previously published resting-state functional magnetic resonance imaging data of 49 subacute back pain (SBP) patients. We built a network-level model that predicts changes in pain intensity over one year by combining independent component analysis and a penalized regression framework. Connections involving top-down pain modulation, multisensory integration, and mesocorticolimbic circuits were identified as predictive markers for pain intensity changes. Pearson's correlations between actual and predicted pain scores were r = 0.33-0.72, and group classification results between SBP patients with persisting pain and recovering patients, in terms of area under the curve (AUC), were 0.89/0.75/0.75 for visits four/three/two, thus outperforming the previous work (AUC 0.83/0.73/0.67). This study identified functional connections important for longitudinal changes in pain intensity in SBP patients, providing provisional markers to predict future pain using large-scale brain networks.

A computer vision approach for classifying isometric grip force exertion levels.

Exposure to high and/or repetitive force exertions can lead to musculoskeletal injuries. However, measuring worker force exertion levels is challenging, and existing techniques can be intrusive, interfere with human-machine interface, and/or limited by subjectivity. In this work, computer vision techniques are developed to detect isometric grip exertions using facial videos and wearable photoplethysmogram. Eighteen participants (19-24 years) performed isometric grip exertions at varying levels of maximum voluntary contraction. Novel features that predict forces were identified and extracted from video and photoplethysmogram data. Two experiments with two (High/Low) and three (0%MVC/50%MVC/100%MVC) labels were performed to classify exertions. The Deep Neural Network classifier performed the best with 96% and 87% accuracy for two- and three-level classifications, respectively. This approach was robust to leave subjects out during cross-validation (86% accuracy when 3-subjects were left out) and robust to noise (i.e. 89% accuracy for correctly classifying talking activities as low force exertions). Practitioner summary: Forceful exertions are contributing factors to musculoskeletal injuries, yet it remains difficult to measure in work environments. This paper presents an approach to estimate force exertion levels, which is less distracting to workers, easier to implement by practitioners, and could potentially be used in a wide variety of workplaces. Abbreviations: MSD: musculoskeletal disorders; ACGIH: American Conference of Governmental Industrial Hygienists; HAL: hand activity level; MVC: maximum voluntary contraction; PPG: photoplethysmogram; DNN: deep neural networks; LOSO: leave-one-subject-out; ROC: receiver operating characteristic; AUC: area under curve.

Individual-Level Lesion-Network Mapping to Visualize the Effects of a Stroke Lesion on the Brain Network: Connectograms in Stroke Syndromes.

BACKGROUND AND PURPOSE: Similar-sized stroke lesions at similar locations can have different prognoses in clinical practice. Lesion-network mapping elucidates network-level effects of lesions that cause specific neurologic symptoms and signs, and also provides a group-level understanding. This study visualized the effects of stroke lesions on the functional brain networks of individual patients. METHODS: We enrolled patients with ischemic stroke who were hospitalized within 1 week of the stroke occurrence. Resting-state functional magnetic resonance imaging was performed 3 months after the index stroke. For image preprocessing, acute stroke lesions were visually delineated based on diffusion-weighted images obtained at admission, and the lesion mask was drawn using MRIcron software. Correlation matrices were calculated from 280 brain regions using the Brainnetome Atlas, and connectograms were visualized using in-house MATLAB code. RESULTS: We found characteristic differences in connectograms between pairs of patients who had comparable splenial, frontal cortical, cerebellar, and thalamocapsular lesions. Two representative patients with bilateral thalamic infarctions showed significant differences in their reconstructed connectograms. The cognitive function had recovered well at 3 months after stroke occurrence in patients with well-maintained interhemispheric and intrahemispheric connectivities. CONCLUSIONS: This pilot study has visualized the effects of stroke lesions on the functional brain networks of individual patients. Consideration of the neurobiologic mechanisms underlying the differences between their connectograms has yielded new hypotheses about differences in the effects of stroke lesions.

Smartphone-based lateral flow imaging system for detection of food-borne bacteria E.coli O157:H7.

We report an application for the smartphone as an accurate and unbiased reading platform of a lateral flow immunoassays for food safety application. In particular, this report focuses on detection of food-borne bacteria in samples extracted from food matrices such as ground beef and spinach. The lateral flow assay is a widely accepted methodology owing to its on-site results, low-cost analysis, and ease of use with minimum user inputs, even though sensitivity is not quite equivalent to that of standard laboratory equipment. An antibody-antigen relationship is transduced into a color change on a nitrocellulose pad while visual interpretation of this color change can result in uncertainty, particularly near the detection limit of the assay. Employing the high resolution integrated camera, constant illumination from light source, and computing power of a smartphone, we provide an objective and accurate method to determine the bacterial cell concentration in a food matrix based on the regression model from the color intensity of test lines. A 3D-printed sample holder was designed for representative commercial lateral flow assays and an in-house application was developed in Android Studio to solve the inverse problem to provide cell concentration information from the color intensity. Test results with E.coli O157:H7 as a model organism suggests that smartphone-based reader can detect 104-105 CFU/ml from ground beef and spinach food matrices.

The Nutritional Status and the Clinical Outcomes of Patients With a Spinal Cord Injury Using Nutritional Screening Tools.

OBJECTIVE: To assess the nutritional status of Korean patients with spinal cord injury (SCI), identify the predictors of undernutrition, and investigate the relationship between undernutrition and clinical outcomes. METHODS: A retrospective study design was used to determine the nutritional status of 130 patients over 19 years old admitted to the rehabilitation hospital of Yonsei University Health System between June 2015 and February 2017. The nutritional status was assessed using the malnutrition universal screening tool (MUST) and the spinal nutrition screening tool (SNST). The relationship between undernutrition and clinical outcomes was examined by comparing a low-risk group with an at-risk group using a t-test. RESULTS: Among the SCI patients, 70 (50.8%) were confirmed with undernutrition based on the MUST scores, while 60 (46.2%) had undernutrition based on the SNST scores. It was found that undernutrition has an effect on functional outcomes. CONCLUSION: We assessed the undernutrition risk in Korean SCI patients, and found that approximately 50% of the patients were at risk of undernutrition. We also found that undernutrition can affect functional recovery.

Effect of Patient Education on Reducing Medication in Spinal Cord Injury Patients With Neuropathic Pain.

OBJECTIVE: To determine whether providing education about the disease pathophysiology and drug mechanisms and side effects, would be effective for reducing the use of pain medication while appropriately managing neurogenic pain in spinal cord injury (SCI) patients. METHODS: In this prospective study, 109 patients with an SCI and neuropathic pain, participated in an educational pain management program. This comprehensive program was specifically created, for patients with an SCI and neuropathic pain. It consisted of 6 sessions, including educational training, over a 6-week period. RESULTS: Of 109 patients, 79 (72.5%) initially took more than two types of pain medication, and this decreased to 36 (33.0%) after the educational pain management program was completed. The mean pain scale score and the number of pain medications decreased, compared to the baseline values. Compared to the non-response group, the response group had a shorter duration of pain onset (p=0.004), and a higher initial number of different medications (p<0.001) and certain types of medications. CONCLUSION: This study results imply that an educational pain management program, can be a valuable complement to the treatment of spinal cord injured patients with neuropathic pain. Early intervention is important, to prevent patients from developing chronic SCI-related pain.

Impact of Diltiazem Alone versus Diltiazem with Nitrate on Five-Year Clinical Outcomes in Patients with Significant Coronary Artery Spasm.

PURPOSE: Calcium channel blockers diltiazem and nitrate have been used as selective coronary vasodilators for patients with significant coronary artery spasm (CAS). However, no study has compared the efficacy of diltiazem alone versus diltiazem with nitrate for long-term clinical outcomes in patients with CAS. MATERIALS AND METHODS: A total of 2741 consecutive patients without significant coronary artery disease with positive CAS by acetylcholine (Ach) provocation test between November 2004 and May 2014 were enrolled. Significant CAS was defined as a narrowing of >70% by incremental intracoronary injection of 20, 50, and 100 µg of Ach into the left coronary artery. Patients were assigned to either the diltiazem group (n=842) or the dual group (diltiazem with nitrate, n=1899) at physician discretion. To adjust for potential confounders, a propensity score matching (PSM) analysis was performed using the logistic regression model. After PSM analysis, two well-balanced groups (811 pairs, n=1622, C-statistic=0.708) were generated. RESULTS: At 5 years, there were similar incidences in primary endpoints, including mortality, myocardial infarction, revascularization, and recurrent angina requiring repeat coronary angiography between the two groups. Diltiazem alone was not an independent predictor for major adverse cardiovascular events or recurrent angina requiring repeat coronary angiography. CONCLUSION: Despite the expected improvement of endothelial function and the relief of CAS, the combination of diltiazem and nitrate treatment was not superior to diltiazem alone in reducing mortality and cardiovascular events up to 5 years in patients with significant CAS.

Impact of Renin-Angiotensin System Inhibitors on Long-Term Clinical Outcomes of Patients With Coronary Artery Spasm.

BACKGROUND: Coronary artery spasm (CAS) is a well-known endothelial dysfunction, and a major cause of vasospastic angina (VSA). The renin-angiotensin system (RAS) is known to be closely associated with endothelial function. However, there are only a few studies that investigated the impact of RAS inhibitor on long-term clinical outcomes in VSA patients. METHODS AND RESULTS: A total of 3349 patients with no significant coronary artery disease, diagnosed with CAS by acetylcholine provocation test were enrolled for this study. Significant CAS was defined as having ≥70% narrowing of the artery after incremental injections of 20, 50, and 100 µg of acetylcholine into the left coronary artery. Patients were divided into 2 groups according to whether the prescription included RAS inhibitor or not (RAS inhibitor group: n=666, non-RAS inhibitor group; n=2683). To adjust for any potential confounders that could cause bias, propensity score matching (PSM) analysis was performed using a logistic regression model. After PSM analysis, 2 matched groups (524 pairs, n=1048 patients, C-statistic=0.845) were generated and their baseline characteristics were balanced. During the 5-year clinical follow-up, the RAS inhibitor group showed a lower incidence of recurrent angina (8.7% versus 14.1%, P=0.027), total death (0.0% versus 1.3%, P=0.045), and total major adverse cardiovascular events (1.0% versus 4.1%, P=0.026) than the non-RAS inhibitor group. CONCLUSIONS: Chronic RAS inhibitor therapy was associated with lower incidence of cardiovascular events in VSA patients in the 5-year clinical follow-up.

Characterization of lipid-rich plaques using spectroscopic optical coherence tomography.

Intravascular optical coherence tomography (IV-OCT) is a high-resolution imaging method used to visualize the internal structures of walls of coronary arteries in vivo. However, accurate characterization of atherosclerotic plaques with gray-scale IV-OCT images is often limited by various intrinsic artifacts. In this study, we present an algorithm for characterizing lipid-rich plaques with a spectroscopic OCT technique based on a Gaussian center of mass (GCOM) metric. The GCOM metric, which reflects the absorbance properties of lipids, was validated using a lipid phantom. In addition, the proposed characterization method was successfully demonstrated in vivo using an atherosclerotic rabbit model and was found to have a sensitivity and specificity of 94.3% and 76.7% for lipid classification, respectively.

Automated detection of vessel lumen and stent struts in intravascular optical coherence tomography to evaluate stent apposition and neointimal coverage.

PURPOSE: Intravascular optical coherence tomography (IV-OCT) is a high-resolution imaging method used to visualize the microstructure of arterial walls in vivo. IV-OCT enables the clinician to clearly observe and accurately measure stent apposition and neointimal coverage of coronary stents, which are associated with side effects such as in-stent thrombosis. In this study, the authors present an algorithm for quantifying stent apposition and neointimal coverage by automatically detecting lumen contours and stent struts in IV-OCT images. METHODS: The algorithm utilizes OCT intensity images and their first and second gradient images along the axial direction to detect lumen contours and stent strut candidates. These stent strut candidates are classified into true and false stent struts based on their features, using an artificial neural network with one hidden layer and ten nodes. After segmentation, either the protrusion distance (PD) or neointimal thickness (NT) for each strut is measured automatically. In randomly selected image sets covering a large variety of clinical scenarios, the results of the algorithm were compared to those of manual segmentation by IV-OCT readers. RESULTS: Stent strut detection showed a 96.5% positive predictive value and a 92.9% true positive rate. In addition, case-by-case validation also showed comparable accuracy for most cases. High correlation coefficients (R > 0.99) were observed for PD and NT between the algorithmic and the manual results, showing little bias (0.20 and 0.46 µm, respectively) and a narrow range of limits of agreement (36 and 54 µm, respectively). In addition, the algorithm worked well in various clinical scenarios and even in cases with a low level of stent malapposition and neointimal coverage. CONCLUSIONS: The presented automatic algorithm enables robust and fast detection of lumen contours and stent struts and provides quantitative measurements of PD and NT. In addition, the algorithm was validated using various clinical cases to demonstrate its reliability. Therefore, this technique can be effectively utilized for clinical trials on stent-related side effects, including in-stent thrombosis and in-stent restenosis.

Intravascular optical imaging of high-risk plaques in vivo by targeting macrophage mannose receptors.

Macrophages mediate atheroma expansion and disruption, and denote high-risk arterial plaques. Therefore, they are substantially gaining importance as a diagnostic imaging target for the detection of rupture-prone plaques. Here, we developed an injectable near-infrared fluorescence (NIRF) probe by chemically conjugating thiolated glycol chitosan with cholesteryl chloroformate, NIRF dye (cyanine 5.5 or 7), and maleimide-polyethylene glycol-mannose as mannose receptor binding ligands to specifically target a subset of macrophages abundant in high-risk plaques. This probe showed high affinity to mannose receptors, low toxicity, and allowed the direct visualization of plaque macrophages in murine carotid atheroma. After the scale-up of the MMR-NIRF probe, the administration of the probe facilitated in vivo intravascular imaging of plaque inflammation in coronary-sized vessels of atheromatous rabbits using a custom-built dual-modal optical coherence tomography (OCT)-NIRF catheter-based imaging system. This novel imaging approach represents a potential imaging strategy enabling the identification of high-risk plaques in vivo and holds promise for future clinical implications.

Impact of Statin Use on Development of New-Onset Diabetes Mellitus in Asian Population.

There have been several reports showing that the statin use is associated with new-onset diabetes mellitus (DM). The aim of the present study was to evaluate the impact of chronic statin use on development of new-onset DM in a series of Asian population. The patients were retrospectively enrolled using the electronic database of Korea University Guro Hospital from January 2004 to February 2010. A total of 10,994 patients without a history of diabetes were analyzed. Baseline lipid profiles, fasting glucose, Hemoglobin (Hb) A1c, and glucose tolerance tests were measured in all patients before statin treatment. Included patients had HbA1c ≤ 5.7% and fasting glucose level ≤ 100 (mg/dl). The patients were divided into 2 groups according to the use of statins (the statin group, n = 2,324 patients and the nonstatin group, n = 8,670 patients). To adjust baseline potential confounders, a propensity score-matched analysis was performed using logistic regression model. After propensity score matching, 2 propensity-matched groups (1,699 pairs, n = 3,398, C statistic = 0.859) were generated and analyzed. After propensity score matching, baseline characteristics of both groups were balanced except that the statin group was older and had higher rate of coronary artery disease compared with the nonstatin group. During a 3-year follow-up, the statin group had higher incidence of new-onset DM compared with the nonstatin group (hazard ratio 1.99, 95% CI 1.36 to 2.92, p <0.001), but the statin group showed lower incidence of major adverse cerebral-cardiovascular events compared with the nonstatin group (hazard ratio 0.40, 95% CI 0.19 to 0.85, p <0.001). In the present study, although the use of statins was associated with higher rate of new-onset DM, it markedly improved 3-year cardiovascular outcomes in Asian population.

Prevalence of Gastrointestinal Diseases and Treatment Status in Noncardiac Chest Pain Patients.

BACKGROUND AND OBJECTIVES: We evaluated the prevalence of gastroesophageal reflux diseases (GERD) in noncardiac chest pain (NCCP) patients, risk factors for GERD, and status of prescriptions for GERD in Korean population. SUBJECTS AND METHODS: This was a retrospective non-interventional observational nation-wide 45-center study. Patients with a normal coronary angiogram (CAG) and upper gastroendoscopy within 2 years after CAG were enrolled. The prevalence of GERD was examined. Other gastrointestinal diseases including peptic ulcer diseases or gastritis were also examined. Risk factors for GERD were compared between the GERD group and non-GERD group. The ratio of patients medicated for gastrointestinal diseases (antacids or proton-pump inhibitor) was also examined. RESULTS: Nine hundred four patients were enrolled. Among the NCCP patients, GERD was present in 436 (48.2%), peptic ulcer disease in 154 patients (17.0%), and gastritis in 659 (72.9%). There was no difference in risk factors for GERD between the GERD and non-GERD patients. Medications for GERD and other gastrointestinal diseases were prescribed in 742 (82.1%) patients. CONCLUSION: GERD was common (42.8%) in Korean NCCP patients and most (82.1%) received the prescription of gastrointestinal medications. No differences were evident in risk factors between GERD and non-GERD patients.

Comparison of diabetic and non-diabetic patients undergoing endovascular revascularization for peripheral arterial disease.

OBJECTIVE: Peripheral arterial disease (PAD) is associated with poor outcomes. We assessed the clinical outcomes of diabetic versus non-diabetic patients with PAD who underwent peripheral transluminal angioplasty (PTA). METHODS: The outcomes of 239 consecutive patients with symptomatic PAD who underwent PTA were analyzed. Restenosis and clinical outcomes were assessed at a follow-up of 2 years. RESULTS: Diabetic patients had a higher percentage of wound as the initial diagnosis for PTA (72.7% vs. 14.2%; P<.001), chronic kidney disease (26.7% vs. 6.3%; P<.01), need for dialysis (19.3% vs. 3.1%; P<.01), and coronary artery disease (67.6% vs. 50.7%; P=.02). Infrapopliteal PTA was more commonly performed in the diabetic group (70.4% vs. 25.3%; P<.001). Diabetic patients had lower rates of angiographic follow-up at 8 months (38.6% vs. 60.3%; P<.01). Diabetic patients had higher binary restenosis (54.4% vs. 31.5%; P=.02) and had a trend toward a higher incidence of total occlusion (34.0% vs. 19.5%; P=.08). At 2-year follow-up, the amputation rate was higher in the diabetic group (24.4% vs. 1.5%; P<.001) despite PTA. CONCLUSION: Diabetic patients more frequently presented with critical limb ischemia compared with non-diabetic patients and had higher rates of restenosis and amputation at 2 years following standard PTA. Improved therapies are needed for this high-risk group of patients.

Impact of low dose atorvastatin on development of new-onset diabetes mellitus in Asian population: Three-year clinical outcomes.

BACKGROUND: High dose atorvastatin is known to be associated with new onset diabetes mellitus (NODM) in patients with high risk for developing diabetes mellitus (DM). However, low dose atorvastatin is more commonly used as compared with high dose atorvastatin. The aim of this study is to investigate the impact of low dose atorvastatin (LDA, 10mg or 20mg) on the development of NODM up to three years in Asian patients. METHODS: From January 2004 to September 2009, we investigated a total of 3566 patients who did not have DM. To adjust for potential confounders, a propensity score matching (PSM) analysis was performed using the logistic regression model. After PSM (C-statistics: 0.851), a total of 818 patients (LDA group, n=409 patients and control group, n=409 patients) were enrolled for analysis. RESULTS: Before PSM, the cumulative incidence of NODM (5.8% vs. 2.1%, p<0.001), myocardial infarction (0.5% vs. 0.1%, p-value=0.007), and major adverse cardio-cerebral event (MACCE, 1.8% vs. 0.7%, p-value=0.012) at three-years were higher in the LAD group. However, after PSM, there was a trend toward higher incidence of NODM (5.9% vs. 3.2%, p=0.064) in the LDA group, but the incidence of MACCE (1.2% vs. 1.5%, p-value=1.000) was similar between the two groups. In multivariable analysis, the LDA administration was tended to be an independent predictor of NODM (OR: 1.99, 95% CI: 1.00-3.98, p-value 0.050). CONCLUSIONS: In this study, the use of LDA tended to be a risk factor for NODM in Asian patients and reduced clinical events similar to the control group. However, large-scale randomized controlled trials will be needed to get the final conclusion.