Diffusion tensor imaging analysis along the perivascular space in the UK biobank.

BACKGROUND: The recently discovered glymphatic system may support the removal of neurotoxic proteins, mainly during sleep, that are associated with neurodegenerative diseases such as Alzheimer's and Parkinson's Disease. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) has been suggested as a method to index the health of glymphatic system (with higher values indicating a more intact glymphatic system). Indeed, in small-scale studies the DTI-ALPS index has been shown to correlate with age, cognitive health, and sleep, and is higher in females than males. OBJECTIVE: To determine whether these relationships are stable we replicated previous findings associating the DTI-ALPS index with demographic, sleep-related, and cognitive markers in a large sample of participants from the UK Biobank. METHODS: We calculated the DTI-ALPS index in UK Biobank participants (n = 17723). Using Bayesian and Frequentist analysis approaches, we replicate previously reported relationships between the DTI-ALPS index. RESULTS: We found the predicted associations between the DTI-ALPS index and age, longest uninterrupted sleep window (LUSWT) on a typical night, cognitive performance, and sex. However, these effects were substantially smaller than those found in previous studies. Parameter estimates from this study may be used as priors in subsequent studies using a Bayesian approach. These results suggest that the DTI-ALPS index is consistently, and therefore predictably, associated with demographics, LUWST, and cognition. CONCLUSION: We propose that the metric, calculated for the first time in a large-scale, population-based cohort, is a stable measure, but one for which stronger links to glymphatic system function are needed before it can be used to understand the relationships between glymphatic system function and health outcomes reported in the UK Biobank.

Test-retest reliability of Bayesian estimations of the effects of stimulation, prior information and individual traits on pain perception.

BACKGROUND: There is inter-individual variability in the influence of different components (e.g. nociception and expectations) on pain perception. Identifying the individual effect of these components could serve for patient stratification, but only if these influences are stable in time. METHODS: In this study, 30 healthy participants underwent a cognitive pain paradigm in which they rated pain after viewing a probabilistic cue informing of forthcoming pain intensity and then receiving electrical stimulation. The trial information was then used in a Bayesian probability model to compute the relative weight each participant put on stimulation, cue, cue uncertainty and trait-like bias. The same procedure was repeated 2 weeks later. Relative and absolute test-retest reliability of all measures was assessed. RESULTS: Intraclass correlation results showed good reliability for the effect of the stimulation (0.83), the effect of the cue (0.75) and the trait-like bias (0.75 and 0.75), and a moderate reliability for the effect of the cue uncertainty (0.55). Absolute reliability measures also supported the temporal stability of the results and indicated that a change in parameters corresponding to a difference in pain ratings ranging between 0.47 and 1.45 (depending on the parameters) would be needed to consider differences in outcomes significant. The comparison of these measures with the closest clinical data we possess supports the reliability of our results. CONCLUSIONS: These findings support the hypothesis that inter-individual differences in the weight placed on different pain factors are stable in time and could therefore be a possible target for patient stratification. SIGNIFICANCE: Our results demonstrate the temporal stability of the weight healthy individuals place on the different factors leading to the pain response. These findings give validity to the idea of using Bayesian estimations of the influence of different factors on pain as a way to stratify patients for treatment personalization.

Are We Any Closer to Understanding How Chronic Pain Develops? A Systematic Search and Critical Narrative Review of Existing Chronic Pain Vulnerability Models.

Identifying biopsychosocial factors underlying chronic pain vulnerability is essential for the design of preventative efforts. Multiple chronic pain vulnerability models exist, however, there is a lack of comprehensive evaluation of these models in the literature, potentially due to the lack of guidelines that specify the criteria by which these types of work should be assessed. In this work, we created evaluation criteria (based on the general goals of conceptual models), and we then used them to critically review the chronic pain vulnerability models available in the current peer-reviewed literature (identified through a systematic search). Particularly, we evaluated the models on the basis of conceptual clarity/specificity of measures, depth of description of aetiological and mechanistic factors, use of a whole system approach, and quality of the evidence associated with the models. We found nine conceptual models that have been explored in detail (eg, fear avoidance model, diathesis-stress model). These models excel at clarity and are supported mostly by self-report evidence of a psychological nature (anxiety sensitivity, pain catastrophizing, etc.), but provide little explanation of mechanistic and aetiological factors. In the future, models could be improved by complementing them with proposals from other models and exploring potential causal factors and mechanisms maintaining the condition. This task could be carried out through prospective cohort studies, and computational approaches, amongst others.

Trauma in childhood is associated with greater pain catastrophizing but not anxiety sensitivity: a cross-sectional study.

Introduction: Adverse life experiences have been identified as a possible vulnerability factor for chronic pain. This association could result from the effect of trauma on the psychological state of individuals. Previous studies found childhood trauma to be associated with pain catastrophizing and anxiety sensitivity, both of which have been associated with an increased risk of chronic pain. However, it is unknown whether trauma in adulthood affects these variables and whether the effect on pain catastrophizing is independent of confounds such as depression and anxiety. Objectives: To test the effect of childhood and adulthood trauma on pain catastrophizing and anxiety sensitivity whilst controlling for depression and anxiety. Methods: In the current study, we conducted an online survey in the United Kingdom in a chronic pain sample (N = 138; 123 women; age range 19-78). We analysed whether there is an association between different types of trauma (both in childhood and through the lifespan), pain catastrophizing, and anxiety sensitivity while controlling for anxiety and depression. Results: We found that childhood trauma (particularly emotional abuse) significantly predicts pain catastrophizing, even when controlling for depression and anxiety, whereas it did not have a significant effect on anxiety sensitivity. Trauma through the lifespan (not childhood) did not have a significant effect on anxiety sensitivity nor did it have a significant effect on pain catastrophizing. Conclusions: Our results show that the life stage in which trauma occurs is key in its psychological effects on patients with chronic pain. Furthermore, it shows that trauma affects some psychological variables but not others.

Frontal alpha asymmetry: A potential biomarker of approach-withdrawal motivation towards pain.

Pain-related catastrophising is a maladaptive coping strategy known to have a strong influence on clinical pain outcomes and treatment efficacy. Notwithstanding, little is known about its neurophysiological correlates. There is evidence to suggest catastrophising is associated with resting-state EEG frontal alpha asymmetry (FAA) patterns reflective of greater relative right frontal activity, which is known to be linked to withdrawal motivation and avoidance of aversive stimuli. The present study aims to investigate whether such a relationship occurs in the situational context of experimental pain. A placebo intervention was also included to evaluate effects of a potential pain-relieving intervention on FAA. 35 participants, including both chronic pain patients and healthy subjects, completed the Pain Catastrophising Scale (PCS) questionnaire followed by EEG recordings during cold pressor test (CPT)-induced tonic pain with or without prior application of placebo cream. There was a negative correlation between FAA and PCS-subscale helplessness scores, but not rumination or magnification, during the pre-placebo CPT condition. Moreover, FAA scores were shown to increase significantly in response to pain, indicative of greater relative left frontal activity that relates to approach-oriented behaviours. Placebo treatment elicited a decrease in FAA in low helplessness scorers, but no significant effects in individuals scoring above the mean on PCS-helplessness. These findings suggest that, during painful events, FAA may reflect the motivational drive to obtain reward of pain relief, which may be diminished in individuals who are prone to feel helpless about their pain. This study provides valuable insights into biomarkers of pain-related catastrophising and prospects of identifying promising targets of brain-based therapies for chronic pain management.

Does It Feel Right or Wrong? The Neuroscience of Moral Judgement.

Moral judgement has been a topic of great interest through the history of philosophy and psychology, but the neural basis of this behavior remains elusive. Greene et al.'s (2001) paper is a pioneering one that opened doors to studying the neuroscience of moral judgement. Greene and colleagues used functional Magnetic Resonance Imaging (fMRI) to measure brain activity in humans as they grappled with moral decisions. The researchers found higher activation in brain areas associated with emotion when subjects were processing dilemmas in which an individual was directly hurt, and higher activation of areas associated with working memory when subjects processed dilemmas in which individuals were hurt as a consequence of an indirect action. The paper has received some criticism, but overall, is still quite relevant in the field. This work generated the field of moral neuroscience and has sparked further research and controversy. This paper's impact at the intersection of psychology and neuroscience and its engaging topic make it valuable for teaching. Furthermore, criticism of the paper also has pedagogic value as it can serve as a tool to promote students' critical evaluation skills. The presentation of this research would be best suited for Neuroscience and Psychology students being introduced to Cognitive Neuroscience.