Investigation of different ML approaches in classification of emotions induced by acute stress.

Background: Machine learning is becoming a common tool in monitoring emotion. However, methodological studies of the processing pipeline are scarce, especially ones using subjective appraisals as ground truth. New method: A novel protocol was used to induce cognitive load and physical discomfort, and emotional dimensions (arousal, valence, and dominance) were reported after each task. The performance of five common ML models with a versatile set of features (physiological features, task performance data, and personality trait) was compared in binary classification of subjectively assessed emotions. Results: The psychophysiological responses proved the protocol was successful in changing the mental state from baseline, also the cognitive and physical tasks were different. The optimization and performance of ML models used for emotion detection were evaluated. Additionally, methods to account for imbalanced classes were applied and shown to improve the classification performance. Comparison with existing methods: Classification of human emotional states often assumes the states are determined by the stimuli. However, individual appraisals vary. None of the past studies have classified subjective emotional dimensions with a set of features including biosignals, personality and behavior. Conclusion: Our data represent a typical setup in affective computing utilizing psychophysiological monitoring: N is low compared to number of features, inter-individual variability is high, and class imbalance cannot be avoided. Our observations are a) if possible, include features representing physiology, behavior and personality, b) use simple models and limited number of features to improve interpretability, c) address the possible imbalance, d) if the data size allows, use nested cross-validation.

Assessment of skin pigmentation-related bias in pulse oximetry readings among adults.

PURPOSE: Recent reports that pulse oximeters may overestimate oxygen saturation in individuals with darker skin pigmentation have prompted concerns from regulatory authorities regarding racial bias. We investigated the performance of TruSignal SpO2 sensors (GE Healthcare, Helsinki, Finland) in adults with varying skin pigmentation. METHODS: A retrospective study was conducted using a set of pooled assessments of SpO2/SaO2 measurements from nine studies to assess bias, accuracy (Arms), and precision of TruSignal sensors in healthy adults under induced hypoxia. Subgroup analyses were performed based on oxygen saturation levels (band 1, ≥ 70 and ≤ 80%; band 2, > 80 and ≤ 90%; band 3, > 90 and ≤ 100%). RESULTS: Of the 10,800 data points from 131 individuals, 8,202 (75.9%) and 2,598 (24.1%) were assigned to the light and dark pigment groups, respectively. Bias was 0.14% overall and less than 1% across oxygenation bands. The difference in bias between dark and light pigment groups was statistically significant at the low oxygenation band with SpO2 ≥ 70 and ≤ 80% (+ 0.58% and + 0.30% respectively; p = 0.0035). Throughout the saturation range, Arms was 1.64% in the light and 1.71% in the dark pigment group, within device specifications and regulatory requirements. Oxygenation was the dominating factor in stepwise ANOVA modeling. The mixed model also showed that bias was strongly affected by the oxygenation range. CONCLUSION: TruSignal sensors demonstrated higher bias at lower oxygen saturation, with less than 0.5% difference between pigment groups. These findings raise new questions, such as ways to improve pulse oximetry measurements during challenging clinical conditions, including low perfusion.

Explainable stress type classification captures physiologically relevant responses in the Maastricht Acute Stress Test.

Introduction: Current stress detection methods concentrate on identification of stress and non-stress states despite the existence of various stress types. The present study performs a more specific, explainable stress classification, which could provide valuable information on the physiological stress reactions. Methods: Physiological responses were measured in the Maastricht Acute Stress Test (MAST), comprising alternating trials of cold pressor (inducing physiological stress and pain) and mental arithmetics (eliciting cognitive and social-evaluative stress). The responses in these subtasks were compared to each other and to the baseline through mixed model analysis. Subsequently, stress type detection was conducted with a comprehensive analysis of several machine learning components affecting classification. Finally, explainable artificial intelligence (XAI) methods were applied to analyze the influence of physiological features on model behavior. Results: Most of the investigated physiological reactions were specific to the stressors, and the subtasks could be distinguished from baseline with up to 86.5% balanced accuracy. The choice of the physiological signals to measure (up to 25%-point difference in balanced accuracy) and the selection of features (up to 7%-point difference) were the two key components in classification. Reflection of the XAI analysis to mixed model results and human physiology revealed that the stress detection model concentrated on physiological features relevant for the two stressors. Discussion: The findings confirm that multimodal machine learning classification can detect different types of stress reactions from baseline while focusing on physiologically sensible changes. Since the measured signals and feature selection affected classification performance the most, data analytic choices left limited input information uncompensated.

A measure for assessment of beneficial and harmful fortitude: development and initial validation of the Sisu Scale.

Sisu is a Finnish cultural concept that denotes determination and resoluteness in the face of adversity. We propose that sisu will supplement the English-language based research on mental fortitude traits. Sisu has not been the focus of systematic research until very recently. We created a new questionnaire measuring sisu (the Sisu Scale), sought to validate the sisu construct and its sub-factor structure as postulated in a recent qualitative study. We investigated associations of sisu with other measures of mental fortitude and well-being. More generally we aimed to enrichen the cross-cultural understanding of human experience of overcoming adversity across life's challenges. We describe and validate a questionnaire that effectively measures both beneficial and harmful sisu, each comprising three sub-factors. Beneficial sisu was associated with other measures of fortitude, but less with personality dimensions. We also confirmed the existence of an independent harmful sisu factor. Beneficial sisu was associated with higher well-being and lower depressive symptoms, and harmful sisu with lower well-being and higher levels of general stress, work stress and depressive symptoms. Together the two factors were superior compared to pre-existing measures when predicting well-being-related variables. Results suggest that the new Sisu Scale we developed may provide a valuable addition to research on mental fortitude, resilience and their consequences for well-being.

Sensory Appeal and Routines Beat Health Messages and Visibility Enhancements: Mixed-Methods Analysis of a Choice-Architecture Intervention in a Workplace Cafeteria.

Easier recognition and enhanced visibility of healthy options supposedly increase healthy choices, but real-world evidence remains scarce. Addressing this knowledge gap, we promoted nutritionally favourable foods in a workplace cafeteria with three choice-architectural strategies-priming posters, point-of-choice nutrition labels, and improved product placement-and assessed their effects on visual attention, food choices, and food consumption. Additionally, we developed a method for analysing real-world eye-tracking data. The study followed a pretest-posttest design whereby control and intervention condition lasted five days each. We monitored visual attention (i.e., total number and duration of fixations) and food choices with eye tracking, interviewed customers about perceived influences on food choices, and measured cafeteria-level food consumption (g). Individual-level data represents 22 control and 19 intervention participants recruited at the cafeteria entrance. Cafeteria-level data represents food consumption during the trial (556/589 meals sold). Results indicated that the posters and labels captured participants' visual attention (~13% of fixations on defined areas of interest before food choices), but the intervention had insignificant effects on visual attention to foods, on food choices, and on food consumption. Interviews revealed 17 perceived influences on food choices, the most common being sensory appeal, healthiness, and familiarity. To conclude, the intervention appeared capable of attracting visual attention, yet ineffective in increasing healthier eating. The developed method enabled a rigorous analysis of visual attention and food choices in a natural choice setting. We discuss ways to boost the impact of the intervention on behaviour, considering target groups' motives. The work contributes with a unique, mixed-methods approach and a real-world setting that enabled a multi-dimensional effects evaluation with high external validity.

Effects of overnight military training and acute battle stress on the cognitive performance of soldiers in simulated urban combat.

Understanding the effect of stress, fatigue, and sleep deprivation on the ability to maintain an alert and attentive state in an ecologically valid setting is of importance as lapsing attention can, in many safety-critical professions, have devastating consequences. Here we studied the effect of close-quarters battle (CQ battle) exercise combined with overnight military training with sleep deprivation on cognitive performance, namely sustained attention and response inhibition. In addition, the effect of the CQ battle and overnight training on cardiac activity [heart rate and root mean square of the successive differences (RMSSD)] during the cognitive testing and the relationship between cardiac activity and cognitive performance were examined. Cognitive performance was measured with the psychomotor vigilance task (PVT) and the sustained attention to response task (SART). Altogether 45 conscripts participated in the study. The conscripts were divided into control (CON) and experimental (EXP) groups. The CON completed the training day after a night of sleep and the EXP after the overnight military training with no sleep. Results showed that the effect of the overnight training on cognitive performance and the between-group difference in heart rate (HR) and heart rate variability (HRV) depended on the cognitive test. Surprisingly, the cognitive performance was not largely affected by the CQ battle. However, as expected, the CQ battle resulted in a significant decrease in RMSSD and an increase in HR measured during the cognitive testing. Similarly, the HR parameters were related to cognitive performance, but the relationship was found only with the PVT. In conclusion, fatigue due to the overnight training impaired the ability to maintain sufficient alertness level. However, this impairment in arousal upregulation was counteracted by the arousing nature of the SART. Hence, the conscripts' cognitive performance was mainly preserved when performing a stimulating task, despite the fatigue from the sleep loss of the preceding night and physical activity.

Pasta Structure Affects Mastication, Bolus Properties, and Postprandial Glucose and Insulin Metabolism in Healthy Adults.

BACKGROUND: Structure and protein-starch interactions in pasta products can be responsible for lower postprandial glycemic responses compared with other cereal foods. OBJECTIVES: We tested the effect on postprandial glucose metabolism induced by 2 pasta products, couscous, and bread, through their structural changes during mastication and simulated gastric digestion. METHODS: Two randomized controlled trials (n = 30/trial) in healthy, normal-weight adults (mean BMI of 23.9 kg/m2 (study 1) and 23.0 kg/m2 (study 2)) evaluated postprandial glucose metabolism modulation to portions of durum wheat semolina spaghetti, penne, couscous, and bread each containing 50 g available carbohydrate. A mastication trial involving 26 normal-weight adults was conducted to investigate mastication processes and changes in particle size distribution and microstructure (light microscopy) of boluses after mastication and in vitro gastric digestion. RESULTS: Both pasta products resulted in lower areas under the 2-h curve for blood glucose (-40% for spaghetti and -22% for penne compared with couscous; -41% for spaghetti and -30% for penne compared with bread), compared with the other grain products (P < 0.05). Pasta products required more chews (spaghetti: 34 ± 18; penne: 38 ± 20; bread: 27 ± 13; couscous: 24 ± 17) and longer oral processing (spaghetti: 21 ± 13 s; penne: 23 ± 14 s; bread: 18 ± 9 s; couscous: 14 ± 10 s) compared with bread or couscous (P < 0.01). Pastas contained more large particles (46-67% of total particle area) compared with bread (0-30%) and couscous (1%) after mastication and in vitro gastric digestion. After in vitro gastric digestion, pasta samples still contained large areas of nonhydrolyzed starch embedded within the protein network; the protein in bread and couscous was almost entirely digested, and the starch was hydrolyzed. CONCLUSIONS: Preservation of the pasta structure during mastication and gastric digestion explains slower starch hydrolysis and, consequently, lower postprandial glycemia compared with bread or couscous prepared from the same durum wheat semolina flour in healthy adults. The postprandial in vivo trials were registered at clinicaltrials.gov as NCT03098017 and NCT03104686.

Pasta Structure Affects Mastication, Bolus Properties, and Postprandial Glucose and Insulin Metabolism in Healthy Adults.

BACKGROUND: Structure and protein-starch interactions in pasta products can be responsible for lower postprandial glycemic responses compared with other cereal foods. OBJECTIVES: We tested the effect on postprandial glucose metabolism induced by 2 pasta products, couscous, and bread, through their structural changes during mastication and simulated gastric digestion. METHODS: Two randomized controlled trials (n = 30/trial) in healthy, normal-weight adults (mean BMI of 23.9 kg/m2 (study 1) and 23.0 kg/m2 (study 2)) evaluated postprandial glucose metabolism modulation to portions of durum wheat semolina spaghetti, penne, couscous, and bread each containing 50 g available carbohydrate. A mastication trial involving 26 normal-weight adults was conducted to investigate mastication processes and changes in particle size distribution and microstructure (light microscopy) of boluses after mastication and in vitro gastric digestion. RESULTS: Both pasta products resulted in lower areas under the 2-h curve for blood glucose (-40% for spaghetti and -22% for penne compared with couscous; -41% for spaghetti and -30% for penne compared with bread), compared with the other grain products (P < 0.05). Pasta products required more chews (spaghetti: 34 ± 18; penne: 38 ± 20; bread: 27 ± 13; couscous: 24 ± 17) and longer oral processing (spaghetti: 21 ± 13 s; penne: 23 ± 14 s; bread: 18 ± 9 s; couscous: 14 ± 10 s) compared with bread or couscous (P < 0.01). Pastas contained more large particles (46-67% of total particle area) compared with bread (0-30%) and couscous (1%) after mastication and in vitro gastric digestion. After in vitro gastric digestion, pasta samples still contained large areas of nonhydrolyzed starch embedded within the protein network; the protein in bread and couscous was almost entirely digested, and the starch was hydrolyzed. CONCLUSIONS: Preservation of the pasta structure during mastication and gastric digestion explains slower starch hydrolysis and, consequently, lower postprandial glycemia compared with bread or couscous prepared from the same durum wheat semolina flour in healthy adults.The postprandial in vivo trials were registered at clinicaltrials.gov as NCT03098017 and NCT03104686.

Evidence for a Behaviourally Measurable Perseverance Trait in Humans.

The aim was to create and study a possible behavioural measure for trait(s) in humans that reflect the ability and motivation to continue an unpleasant behaviour, i.e., behavioural perseverance or persistence (BP). We utilised six different tasks with 54 subjects to measure the possible BP trait(s): cold pressor task, hand grip endurance task, impossible anagram task, impossible verbal reasoning task, thread and needle task, and boring video task. The task performances formed two BP factors. Together, the two-factor solution is responsible for the common variance constituting 37.3% of the total variance in the performances i.e., performance times. Excluding the impossible anagram task, the performance in any given task was better explained by performances in the other tasks (i.e., "trait", η2 range = 0.131-0.253) than by the rank order variable ("depletion", i.e., getting tired from the previous tasks, η2 range = 0-0.096).

Lentivirus vector­mediated genetic manipulation of oncogenic pathways induces tumor formation in rabbit brain.

Translation of promising experimental therapies from rodent models to clinical success has been complicated as the novel therapies often fail in clinical trials. Existing rodent glioma models generally do not allow for preclinical evaluation of the efficiency of novel therapies in combination with surgical resection. Therefore, the aim of the present study was to develop a larger animal model utilizing lentivirus vector­mediated oncogenic transformation in the rabbit brain. Lentiviruses carrying constitutively active AKT and H­Ras oncogenes, and p53 small interfering (si)RNA were introduced into newborn rabbit neural stem cells (NSCs) and intracranially implanted into rabbits' brains to initiate tumor formation. In one of the ten rabbits a tumor was detected 48 days after the implantation of transduced NSCs. Histological features of the tumor mimic was similar to a benign Grade II ganglioglioma. Immunostaining demonstrated that the tissues were positive for AKT and H­Ras. Strong expression of GFAP and Ki­67 was also detected. Additionally, p53 expression was notably lower in the tumor area. The implantation of AKT, H­Ras and p53 siRNA transduced NSCs for tumor induction resulted in ganglioglioma formation. Despite the low frequency of tumor formation, this preliminary data provided a proof of principle that lentivirus vectors carrying oncogenes can be used for the generation of brain tumors in rabbits. Moreover, these results offer noteworthy insights into the pathogenesis of a rare brain tumor, ganglioglioma.

Effect of metabolic state on implicit and explicit responses to food in young healthy females.

Recent neuroscience research has delineated key psychological components of reward: wanting, liking and learning. Each component is further divided into explicit and implicit processes. While explicit processes are consciously experienced, implicit processes are not always directly accessible to conscious inspection. In the present study, we investigated the effect of metabolic state on implicit and explicit responses and their relationship in food context, especially when foods and visually matched non-food items are contrasted, and when foods in a sole food context but differing in energy content (high-energy - low-energy) or taste (sweet - savoury) were contrasted. Sixty healthy non-obese females participated in the study in fasted and fed states. Three Implicit Association Tests were used to assess implicit associations. Explicit liking and wanting ratings were assessed by visual analogue scales. In the implicit food-non-food context, food was preferred over non-food items both in fasted and fed states, though the strength of implicit associations declined significantly from fasted to fed state. However, the direction or strength of implicit associations was not significantly different between the metabolic states when comparing concepts within food context only, differing in energy content or taste. Instead, explicit responses reflected the change in the metabolic state in a manner consistent with alliesthesia and sensory-specific satiety. The results of the present study suggest that implicit associations are relatively resistant to acute change in the metabolic condition compared to explicit ratings, which shift more readily according to the fasted-fed continuum. The shift in the prevailing metabolic state was, however, reflected in the strength of implicit responses towards food in relation to non-food items, yet in the sole food contexts implicit associations were comparable between the fasted and fed states.

Metabolic state as a modulator of neural event-related potentials for food stimuli in an implicit association test.

The Implicit Association Test (IAT) has become a ubiquitous measure of implicit associations or preferences in several fields of research, including research related to food choices. The neural dynamics of the IAT have been explored in several contexts, but in a food-related IAT with stimuli of natural motivational value they are yet to be studied. Additionally, the effect of metabolic state on them is poorly known. The present study examined the event-related potentials (ERP) in healthy non-obese females (n = 32) while they performed a food-related IAT in two sessions, in a fasted state and after a meal. The results showed differences in the ERP components N400, P3 and LPP by congruence categories. Additionally, the individual N400 and LPP deflections correlated strongly with individual IAT effects. ERP deflections were weaker in the fasted state than after the meal despite greater implicit hedonic motivation towards food in the fasted state. In conclusion, the results suggest that ERPs reflect the IAT effect. The N400, P3 and LPP components were evoked in a food-related IAT in a similar way observed in IAT tests in other contexts, reflecting a difference in meaning and motivation between congruence categories. The strong correlations of individual IAT effect with individual N400 and LPP deflections further suggests that the food-related IAT effect strength reflects the size of implicit food bias seen in neural deflections. Moreover, fasting increased implicit hedonic motivation towards food, but likely reduced cognitive resources at the same time. This could have made it harder to determine the value of novel, task-relevant stimuli, whereas it became easier postprandially and with practice.

The effect of structure and texture on the breakdown pattern during mastication and impacts on in vitro starch digestibility of high fibre rye extrudates.

The snack product category is lacking palatable, high dietary fiber containing products. This study explored how the addition of native or fermented rye bran influences the texture and sensory properties of endosperm rye flour based extrudates. In addition, mastication and bolus properties (n = 26), and in vitro starch digestibility were assessed. Three high fiber extrudates based on endosperm rye flour (EF) were produced with addition of either 40% native rye bran (NBE) or 40% fermented rye bran (FBE), and with no added bran (EFE) to achieve two pairs of extrudates to compare. EFE and FBE had different composition but resembled each other regarding macrostructure and the second pair (NBE vs. FBE) had similar core composition but different structure due to bran fermentation. The fermentation of bran was performed using exopolysaccharide (EPS)-producing strain Weissella confusa, which led to 3% (3 g per 100 g bran; dry weight) in situ dextran production. The compositionally similar extrudates (NBE vs. FBE) varied in both structure and instrumental texture: FBE were less dense, less hard and crispier than NBE. The extrudates with different composition (EFE vs. FBE) varied regarding instrumental texture: FBE were less hard and crispier than EFE. There were also subtle structural differences FBE being somewhat denser than EFE. NBE and FBE differed regarding sensory texture while textures of EFE and FBE were perceived similar. Mastication properties of the different products did not exhibit remarkable differences. There was a large number of smaller particles in both NBE and FBE bolus samples. The fragile structure of FBE, and its lower bolus viscosity, led to high in vitro starch digestibility. The results demonstrate that the structural attributes of the extrudates, rather than the core composition, dictate the breakdown pattern during mastication and in vitro starch digestibility. The extrudates with similar composition may be digested at different rates depending on their structural attributes. Although FBE had higher in vitro starch digestibility, its high DF content, palatable texture and improved sensory properties were important determinants underlying eating quality and therefore it could be a promising product to snack food category.

Effects of structural and textural properties of brittle cereal foams on mechanisms of oral breakdown and in vitro starch digestibility.

Structural and textural properties as well as the dietary fibre content of solid cereal foams influence the oral breakdown of structure, bolus formation and digestibility. The aim of this study was to investigate how structural differences of solid cereal foams (puffs vs. flakes) affect in vivo chewing and in vitro starch digestion. Four extruded puffs and flakes were produced from endosperm rye flour by extrusion processing without or with 10% rye bran (RB) addition. Extruded puffs and flakes were masticated by fifteen healthy females and the process was monitored using electromyography. Extruded puffs were more porous than flakes (97% vs 35%). The two products were also significantly different (p<0.05) in their structural and textural properties such as expansion, hardness, density and crispiness. A negative correlation was observed between hardness and crispiness index (p<0.05, r=-0.950) and density and porosity (p<0.05, r=-0.964). Addition of 10% RB had a significant effect on structural, textural and mastication properties both for puffs and flakes. Mastication of puffs required less total work than flakes (204 vs. 456%) and they were degraded to smaller particles than flakes during mastication. Irrespectively of the considerable differences in structure, texture and oral disintegration process, no significant (p<0.05) differences were observed between puffs and flakes (86.4 vs. 85.1) in terms of starch hydrolysis index. RB addition increased the hydrolysis index of puffs and flakes to 89.7 and 94.5, respectively, which was probably attributable to the increased number of particles in the bolus.

Comparison of seven different anesthesia protocols for nicotine pharmacologic magnetic resonance imaging in rat.

Pharmacologic MRI (phMRI) is a non-invasive in vivo imaging method, which can evaluate the drug effects on the brain and provide complementary information to ex vivo techniques. The preclinical phMRI studies usually require anesthesia to reduce the motion and stress of the animals. The anesthesia, however, is a crucial part of the experimental design, as it may modulate the neural drug-induced (de)activation and hemodynamic coupling. Therefore, the aim of the present study was to address this methodologic question by performing phMRI experiments with five anesthetics (α-chloralose, isoflurane, medetomidine, thiobutabarbital, and urethane) and seven anesthesia protocols. Nicotine, a widely studied psychostimulant, was administered to rats while measuring blood oxygenation level-dependent (BOLD) signals. Notably different responses were observed depending on the anesthetic used. The highest responses were measured in urethane-anesthetized rats whereas the responses were hardly noticeable in α-chloralose group. As urethane is not commonly used in phMRI, hemodynamic coupling under urethane anesthesia was investigated with functional cerebral blood flow (CBF) and volume-weighted (CBVw) imaging, and simultaneous electrophysiologic and BOLD measurements. The BOLD, CBF, and CBVw measurements in response to nicotine were highly correlated (R(2) ≥ 0.70, p<0.001). BOLD values correlated well (R(2)=0.43, p<10(-6)) with local field potential (LFP) spectral power (13-70Hz) during pharmacologic stimulation. These findings indicate that urethane anesthesia combined with BOLD contrast provides a robust protocol for nicotine phMRI studies. As urethane has mild effects to individual receptor systems, and coupling between electrophysiologic activity and hemodynamic response is maintained, this anesthetic may also be suitable for other phMRI studies.

Heart rate reactivity associated to positive and negative food and non-food visual stimuli.

Using food as a stimuli is known to cause multiple psychophysiological reactions. Heart rate variability (HRV) is common tool for assessing physiological reactions in autonomic nervous system. However, the findings in HRV related to food stimuli have not been consistent. In this paper the quick changes in HRV related to positive and negative food and non-food visual stimuli are investigated. Electrocardiogram (ECG) was measured from 18 healthy females while being stimulated with the pictures. Subjects also filled Three-Factor Eating Questionnaire to determine their eating behavior. The inter-beat-interval time series and the HRV parameters were extracted from the ECG. The quick change in HRV parameters were studied by calculating the change from baseline value (10 s window before stimulus) to value after the onset of the stimulus (10 s window during stimulus). The paired t-test showed significant difference between positive and negative food pictures but not between positive and negative non-food pictures. All the HRV parameters decreased for positive food pictures while they stayed the same or increased a little for negative food pictures. The eating behavior characteristic cognitive restraint was negatively correlated with HRV parameters that describe decreasing of heart rate.

Brain Amyloidosis and BDNF Deficiency Have Opposite Effects on Brain Volumes in AßPP/PS1 Mice Both in vivo and ex vivo.

Magnetic resonance imaging (MRI) volumetry is widely used in Alzheimer's disease (AD) research and diagnostics alongside clinical assessment. Yet few MRI volumetry studies have been conducted in AD model mice with mixed results. We performed in vivo and ex vivo MRI and extensive postmortem histological analysis in transgenic mice derived from crossing amyloid plaque producing AßPP/PS1 mice with brain-derived neurotrophic factor (BDNF) +/- mice. This allowed us to compare developmental volumetric changes due to BDNF deficiency with progressive changes due to amyloid accumulation. We found decreased whole brain volume at 3 months and decreased cortical volume at both 3 and 8 months in vivo in BDNF +/- Tg mice but increased whole brain and cortical volumes at 8 months in AßPP/PS1 mice. Consistent with this, the postmortem histological analysis showed decreased brain parenchymal area in BDNF +/- mice but an increase in AßPP/PS1 mice. BDNF gene deficiency did not affect brain amyloid load or astrogliosis, but led to decreased dentate gyrus length, whereas AßPP/PS1 mice had significantly increased amyloid load, astrogliosis, and decreased neurogenesis. Distinct and layer-specific effects were found in the hippocampus of AßPP/PS1 and BDNF +/- mice. In contrast to human AD patients, brain atrophy in amyloid producing mice appears to be masked by volume increase due to amyloid accumulation and especially accompanying astrogliosis. Our results indicate that cortical MRI volumetry can be used to some extent as a proxy to progressive brain amyloidosis in preclinical studies.

Ultrasound imaging with bolus delivered contrast agent for the detection of angiogenesis and blood flow irregularities.

Highly increased blood flow and vascularity after angiogenic gene therapy have raised concerns of shunting and hemangioma-like blood pool formation that might decrease effective perfusion and ruin the beneficial effects of the therapy. Contrast enhanced ultrasound is a promising noninvasive tool for studying skeletal muscle perfusion. The objectives of the present study were to test bolus and infusion administrations of ultrasound microbubble contrast media in imaging vascular growth in skeletal muscle and assess the functionality of vessels grown with angiogenic gene therapy. Contrast enhanced ultrasound was used to study changes in skeletal muscle perfusion in normal and gene-transduced rabbit hindlimbs 6 days after gene transfer. Adenoviral gene transfer of VEGF (10e(9)-10e(11) viral particles) or ß-galactosidase control gene (10e(11) viral particles) was done under anesthesia and induced up to 16-fold increases in relative tissue perfusion. Contrast intensity versus time curves were plotted and analyzed for contrast kinetics. Bolus administration of the contrast media was highly feasible in analyzing skeletal muscle blood flow and its kinetics. Maximal signal intensity of the bolus signal reflected relative changes in both blood flow and volume equally to the infusion method. Flow irregularities were detected after angiogenic gene therapy. In conclusion, bolus delivery of ultrasound contrast agent is highly feasible for the relative analysis of both quantity and quality of blood flow after angiogenic gene therapy. The kinetics of blood flow can and should be studied more extensively in both preclinical and clinical trials of angiogenic gene therapy since there is increasing evidence of flow irregularities in angiogenic vessels.

Relaxation along a fictitious field (RAFF) and Z-spectroscopy using alternating-phase irradiation (ZAPI) in permanent focal cerebral ischemia in rat.

Cerebral ischemia alters the molecular dynamics and content of water in brain tissue, which is reflected in NMR relaxation, diffusion and magnetization transfer (MT) parameters. In this study, the behavior of two new MRI contrasts, Relaxation Along a Fictitious Field (RAFF) and Z-spectroscopy using Alternating-Phase Irradiation (ZAPI), were quantified together with conventional relaxation parameters (T1, T2 and T1ρ) and MT ratios in acute cerebral ischemia in rat. The right middle cerebral artery was permanently occluded and quantitative MRI data was acquired sequentially for the above parameters for up to 6 hours. The following conclusions were drawn: 1) Time-dependent changes in RAFF and T1ρ relaxation are not coupled to those in MT. 2) RAFF relaxation evolves more like transverse, rather than longitudinal relaxation. 3) MT measured with ZAPI is less sensitive to ischemia than conventional MT. 4) ZAPI data suggest alterations in the T2 distribution of macromolecules in acute cerebral ischemia. It was shown that both RAFF and ZAPI provide complementary MRI information from acute ischemic brain tissue. The presented multiparametric MRI data may aid in the assessment of brain tissue status early in ischemic stroke.

Rats bred for low aerobic capacity become promptly fatigued and have slow metabolic recovery after stimulated, maximal muscle contractions.

AIM: Muscular fatigue is a complex phenomenon affected by muscle fiber type and several metabolic and ionic changes within myocytes. Mitochondria are the main determinants of muscle oxidative capacity which is also one determinant of muscle fatigability. By measuring the concentrations of intracellular stores of high-energy phosphates it is possible to estimate the energy production efficiency and metabolic recovery of the muscle. Low intrinsic aerobic capacity is known to be associated with reduced mitochondrial function. Whether low intrinsic aerobic capacity also results in slower metabolic recovery of skeletal muscle is not known. Here we studied the influence of intrinsic aerobic capacity on in vivo muscle metabolism during maximal, fatiguing electrical stimulation. METHODS: Animal subjects were genetically heterogeneous rats selectively bred to differ for non-trained treadmill running endurance, low capacity runners (LCRs) and high capacity runners (HCRs) (n = 15-19). We measured the concentrations of major phosphorus compounds and force parameters in a contracting triceps surae muscle complex using (31)P-Magnetic resonance spectroscopy ((31)P-MRS) combined with muscle force measurement from repeated isometric twitches. RESULTS: Our results demonstrated that phosphocreatine re-synthesis after maximal muscle stimulation was significantly slower in LCRs (p<0.05). LCR rats also became promptly fatigued and maintained the intramuscular pH poorly compared to HCRs. Half relaxation time (HRT) of the triceps surae was significantly longer in LCRs throughout the stimulation protocol (p≤0.05) and maximal rate of torque development (MRTD) was significantly lower in LCRs compared to HCRs from 2 min 30 s onwards (p≤0.05). CONCLUSION: We observed that LCRs are more sensitive to fatigue and have slower metabolic recovery compared to HCRs after maximal muscle contractions. These new findings are associated with reduced running capacity and with previously found lower mitochondrial content, increased body mass and higher complex disease risk of LCRs.