Decoding cerebro-spinal signatures of human behavior: Application to motor sequence learning.

Mapping the neural patterns that drive human behavior is a key challenge in neuroscience. Even the simplest of our everyday actions stem from the dynamic and complex interplay of multiple neural structures across the central nervous system (CNS). Yet, most neuroimaging research has focused on investigating cerebral mechanisms, while the way the spinal cord accompanies the brain in shaping human behavior has been largely overlooked. Although the recent advent of functional magnetic resonance imaging (fMRI) sequences that can simultaneously target the brain and spinal cord has opened up new avenues for studying these mechanisms at multiple levels of the CNS, research to date has been limited to inferential univariate techniques that cannot fully unveil the intricacies of the underlying neural states. To address this, we propose to go beyond traditional analyses and instead use a data-driven multivariate approach leveraging the dynamic content of cerebro-spinal signals using innovation-driven coactivation patterns (iCAPs). We demonstrate the relevance of this approach in a simultaneous brain-spinal cord fMRI dataset acquired during motor sequence learning (MSL), to highlight how large-scale CNS plasticity underpins rapid improvements in early skill acquisition and slower consolidation after extended practice. Specifically, we uncovered cortical, subcortical and spinal functional networks, which were used to decode the different stages of learning with a high accuracy and, thus, delineate meaningful cerebro-spinal signatures of learning progression. Our results provide compelling evidence that the dynamics of neural signals, paired with a data-driven approach, can be used to disentangle the modular organization of the CNS. While we outline the potential of this framework to probe the neural correlates of motor learning, its versatility makes it broadly applicable to explore the functioning of cerebro-spinal networks in other experimental or pathological conditions.

Acetoacetate enhancement of glucose mediated DNA glycation.

Acetoacetate (AA) is a ketone body, which generates reactive oxygen species (ROS). ROS production is impacted by the formation of covalent bonds between amino groups of biomacromolecules and reducing sugars (glycation). Glycation can damage DNA by causing strand breaks, mutations, and changes in gene expression. DNA damage could contribute to the pathogenesis of various diseases, including neurological disorders, complications of diabetes, and aging. Here we studied the enhancement of glucose-mediated DNA glycation by AA for the first time. The effect of AA on the structural changes, Amadori and advanced glycation end products (AGEs) formation of DNA incubated with glucose for 4 weeks were investigated using various techniques. These included UV-Vis, circular dichroism (CD) and fluorescence spectroscopy, and agarose gel electrophoresis. The results of UV-Vis and fluorescence spectroscopy confirmed that AA increased the DNA-AGE formation. The NBT test showed that AA also increased Amadori product formation of glycated DNA. Based on the CD and agarose gel electrophoresis results, the structural changes of glycated DNA was increased in the presence of AA. The chemiluminescence results indicated that AA increased ROS formation. Thus AA has an activator role in DNA glycation, which could enhance the adverse effects of glycation under high glucose conditions.

The effect of threat on cognitive biases and pain outcomes: An eye-tracking study.

BACKGROUND: Theoretical accounts of attentional and interpretation biases in pain suggest that these biases are interrelated and are both influenced by perceived threat. A laboratory-based study was conducted to test whether these biases are influenced by threat and their interrelationship and whether attention or interpretation biases predict pain outcomes. METHODS: Healthy participants (n = 87) received either threatening or reassuring pain information and then completed questionnaires, interpretation and attentional bias tasks (with eye-tracking) and a pain task (the cold pressor). RESULTS: There was an interaction effect for threat group and stimuli type on mean dwell time for face stimuli, such that there was an attentional bias towards happy faces in the low- but not high-threat group. Further, high threat was also associated with shorter pain tolerance, increased pain and distress. In correlational analyses, avoidance of affective pain words was associated with increased pain. However, no relationship was found between attention and interpretation biases, and interpretation biases were not influenced by threat or associated with pain. CONCLUSIONS: These findings provide partial support for the threat interpretation model and the importance of threat and affective pain biases, yet no relationship between cognitive processing biases was found, which may only occur in clinical pain samples. WHAT DOES THIS STUDY ADD?: In healthy participants, no relationship between attention and interpretation biases was found. Eye tracking revealed an association between later attentional processes and pain. Threat influenced attentional biases and pain outcomes, partially supporting theoretical accounts.

Interpretation biases in chronic pain patients: an incidental learning task.

BACKGROUND: The aim of this study was to investigate the impact of chronic pain on interpretation bias for ambiguous faces, using a recently developed paradigm with ecologically valid stimuli. METHODS: Fifty patients with chronic pain and 25 healthy controls were trained to respond to probes following the presentation of happy or painful faces, using an incidental learning task. During a test phase, ambiguous faces were presented. The degree to which participants were faster to respond to probes presented where painful (rather than happy) faces had previously been presented was taken as an indication of the interpretation bias towards painful faces. RESULTS: All participants had learnt the originally presented contingency. As predicted, chronic pain patients showed a greater bias towards interpreting ambiguous faces as painful than control participants. Further, there were correlations between fear of pain and catastrophizing and interpretation bias, indicating that participants with higher fear of pain and higher scores on a measure of catastrophizing were more likely to interpret ambiguous faces as painful. Severity of pain was inversely associated with increased interpretation bias for pain. CONCLUSION: These results show clear evidence that chronic pain patients do demonstrate an interpretation bias towards painful faces and that this bias is greater for those who catastrophize more and have higher levels of fear of pain, but experienced less pain in the preceding week. Given the recent potential shown for interventions that modify cognitive biases, this paradigm would seem to be well suited to future efforts to modify interpretation biases in pain.

Catastrophizing mediates the relationship between fear of pain and preference for elective caesarean section.

BACKGROUND: Fear of childbirth is associated with preference for an elective caesarean section (ECS); however, the role of fear of pain and pain catastrophizing (the tendency to predict the worst case scenario) have not been investigated. The aim of current study was to investigate whether fear of pain and catastrophizing were independent predictors of preference for ECS. We hypothesized that pain catastrophizing and negative affectivity would mediate the relationship between fear of pain and preference for ECS. METHODS: Three hundred pregnant women between 4 and 36 weeks of gestation were asked to indicate whether they would prefer to deliver their baby through an ECS or a vaginal delivery. They were also asked to complete a battery of questionnaires assessing demographic details, mood, fear of childbirth, fear of pain and catastrophizing. Consistent with cultural norms, more than half of the women preferred an ECS (58%). RESULTS: Women who chose ECS were more likely to seek private obstetric care, have had a previous caesarean section and have higher levels of fear of childbirth, fear of pain, more catastrophic cognitions and lower mood. Catastrophizing, but not negative affectivity, mediated the relationship between fear of pain and preference for ECS, as predicted. CONCLUSIONS: Fear of both childbirth and pain were both independent predictors of preference for ECS. Catastrophizing mediated the relationship between fear of pain and preference for ECS. Interventions that target these factors may reduce the trend towards increasing numbers of ECS internationally.

Administration of heparanase-III improves the survival and angiogenesis of rat skin autografts.

AIM: Heparanase, a glycohydrolase enzyme, cleaves heparan sulfate in the tissue matrix. Heparan sulfate degradation causes the release of angiogenic and growth factors, leading to angiogenesis. The aim of this paper was to evaluate the angiogenic effect of heparinase-III administration on skin autograft healing in rat. METHODS: Four groups of 14 adult male Charles River rats were enrolled. Full thickness skin autografts (15 mm in diameter) were made on the interscapular region of each rat. After 24 hours, 0.1 cc of heparanase, at the three concentrations of 0.1, 0.2, and 0.4 units, were injected intradermally into the grafts of each of the three case groups. The control group received an equal volume of the vehicle (buffered phosphate solution). After 5 days, biopsy specimens from skin grafts of 5 randomly selected rats of each group were submitted for histological studies. RESULTS: The concentration of vessels (with 5-50 mm in diameter) in the grafts of the groups receiving 0.2 and 0.4 units of heparanase-III was significantly more than that of the control group (100.43+/-11.24 and 95.85+/-12.44 vs 71.42+/-5.22 vessels/mm(2), P<0.05). The graft survival time of the group that received 0.2 U heparanase-III was significantly longer than that of the control group (15.43+/-0.72 vs 13.23+/-0.69 days; P<0.05). CONCLUSIONS: Heparanase-III administration improves the healing of rat skin autografts through induction of angiogenesis.

Could androgens protect middle-aged women from cardiovascular events? A population-based study of Swedish women: The Women's Health in the Lund Area (WHILA) Study.

OBJECTIVE: The aim of this analysis was to delineate perceived associations between androgens and cardiovascular events in perimenopausal women. DESIGN: A cross-sectional, population-based study of 6440 perimenopausal women aged 50-59 years, living in Southern Sweden. In all, 461 (7.1%) women were premenopausal (PM), 3328 (51.7%) postmenopausal without hormone therapy (HT) (PM0) and 2651 (41.2%) postmenopausal with HT (PMT). For further comparisons, 104 women (1.6%) who reported cardiovascular disease (CVD) were studied in detail; 49 had had a myocardial infarction, 49 a stroke and six women both events. For each woman with CVD, two matched controls were selected (n=208). RESULTS: In the matched controlled series, androstenedione levels were lower (p<0.005) in cases. Cases with hormone therapy had also lower testosterone levels than matched controls (p=0.05). In the total cohort, by using multiple logistic regression analyses, testosterone was positively associated with low density lipoprotein cholesterol (p<0.001) and high density lipoprotein cholesterol (HDL-C) (p<0.001) in all women, but negatively associated with levels of triglycerides in both the PM0 (p<0.001) and PMT (p<0.001) groups. Androstenedione levels were positively associated with HDL-C (p<0.05) and negatively with triglycerides (p<0.05) in the PM group. CONCLUSION: Women with cardiovascular disease had lower serum androgen levels, particularly women using hormone replacement therapy, even when controlled for lipids and other potential risk factors.

Role of small intestine in caloric compensations to oil premeals in rats.

We postulated that dose-responsive satiety after oil premeals varies with the number of gut sensors stimulated by lipolytic products along intestine. These experiments in fasted rats on satiety after oil premeals were performed to 1) determine whether satiety was induced by lipolytic products but not triglycerides; 2) confirm that oil empties from the stomach at rates that vary with oil loads; 3) ascertain that increasing rates of oil entry into duodenum extend the length of gut contacted by lipolytic products; and 4) judge whether length of gut contacted correlated with dose-responsive satieties to dietary oils. 5) Using specific antagonists, we attempted to define how satiety was signalled by gut sensors. Timing and degrees of satiety did not correlate with timing and extent of gastric distensions but, rather, with the timing and extent of spread of lipolytic products along small bowel. Satiety after the highest premeal load of oil was blocked by Pluronic L-81, an inhibitor of intestinal secretion of apolipoprotein A-IV, but was unaffected by MK-329 (a specific antagonist of cholecystokinin) or by capsaicin blockade of chemosensory nerves.

Saudi folk medicine: phytochemical and antimicrobial screening.

Plants of 25 families, encompassing 30 species were selected on the basis of their folklore uses and literature data for the present screening. Besides phytochemical screening the plant extracts were prepared and tested for their antimicrobial activity. The result of the testing showed that about 77% of these plants exhibited some level of antibacterial activity. The most common chemical constituents found in these plants were sterols and/or triterpenes, falvonoids, alkaloids and tannins. Volatile oils, volatile bases, saponins, coumarins, anthraquinones and cardiac glycosides were also detected.