Katharine S. Baker

Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology

BackgroundChronic fatigue syndrome (CFS) is a debilitating disorder characterized by persistent fatigue that is not alleviated by rest. The lack of a clearly identified underlying mechanism has hindered the development of effective treatments. Studies have demonstrated elevated levels of inflammatory factors in patients with CFS, but findings are contradictory across studies and no biomarkers have been consistently supported. Single time-point approaches potentially overlook important features of CFS, such as fluctuations in fatigue severity. We have observed that individuals with CFS demonstrate significant day-to-day variability in their fatigue severity.MethodsTherefore, to complement previous studies, we implemented a novel longitudinal study design to investigate the role of cytokines in CFS pathophysiology. Ten women meeting the Fukuda diagnostic criteria for CFS and ten healthy age- and body mass index (BMI)-matched women underwent 25 consecutive days of blood draws and self-reporting of symptom severity. A 51-plex cytokine panel via Luminex was performed for each of the 500 serum samples collected. Our primary hypothesis was that daily fatigue severity would be significantly correlated with the inflammatory adipokine leptin, in the women with CFS and not in the healthy control women. As a post-hoc analysis, a machine learning algorithm using all 51 cytokines was implemented to determine whether immune factors could distinguish high from low fatigue days.ResultsSelf-reported fatigue severity was significantly correlated with leptin levels in six of the participants with CFS and one healthy control, supporting our primary hypothesis. The machine learning algorithm distinguished high from low fatigue days in the CFS group with 78.3% accuracy.ConclusionsOur results support the role of cytokines in the pathophysiology of CFS.

Meta-analytic evidence for decreased heart rate variability in chronic pain implicating parasympathetic nervous system dysregulation.

Abstract Both sympathetic and parasympathetic nervous systems are involved in regulating pain states. The activity of these systems seems to become disturbed in states of chronic pain. This disruption in autonomic balance can be measured through the assessment of heart rate variability (HRV), that is, the variability of the interval between consecutive heart beats. However, there is yet to be a systematic evaluation of the body of literature concerning HRV across several chronic pain conditions. Moreover, modern meta-analytical techniques have never been used to validate and consolidate the extent to which HRV may be decreased in chronic pain. Following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement guidelines, this study systematically evaluated and critically appraised the literature concerning HRV in people living with chronic pain. After screening 17,350 sources, 51 studies evaluating HRV in a chronic pain group met the inclusion criteria. Twenty-six moderate–high quality studies were included in quantitative meta-analyses. On average, the quality of studies was moderate. There were 6 frequency-domain and time-domain measures of HRV across a broad range of chronic pain conditions. High heterogeneity aside, pooled results from the meta-analyses reflected a consistent, moderate-to-large effect of decreased high-frequency HRV in chronic pain, implicating a decrease in parasympathetic activation. These effects were heavily influenced by fibromyalgia studies. Future research would benefit from wider use of standardised definitions of measurement, and also investigating the synergistic changes in pain state and HRV throughout the development and implementation of mechanism-based treatments for chronic pain.

Neural activity in readiness for incidental and explicitly timed actions

Voluntary, self-initiated actions are preceded by slowly increasing neural activity in pre-motor regions of the brain, beginning up to 2s before the onset of muscle movement. This activity is commonly seen in the scalp-recorded readiness potential, and is an index of movement preparation involving both motor programming and non-motor or cognitive processes such as attention. The specific contribution of cognitive processes, thought to occur during the earliest stage of planning, remains somewhat unclear. We suggest that attention to the timing of movement is a key voluntary process contributing to early-stage cortical activity. As a novel approach to examining this, we recorded EEG throughout a time reproduction task in which participants replicated the interval between two tones with two button-press actions. The first action, i.e. the beginning of the reproduced interval, was somewhat incidental to the task of time reproduction and required minimal attention to the time of initiation, while the second action required explicit attention to the time of initiation. Pre-movement neural activity preceding the first, relatively unattended movement was greatly reduced in amplitude and almost absent in the early stage, in contrast with readiness potentials typically seen prior to voluntary movement. Neural activity preceding explicitly timed movements was significantly larger, with effects emerging in the early component of pre-movement activity over frontal and right frontal scalp regions. We propose that attention to movement timing, i.e. the process of orienting attention in time towards the moment of movement initiation, is a key component of voluntary action preparation that is reflected in the early-stage neural activity we typically see prior to voluntary movement.

Attention and the readiness for action

The initiation of voluntary action is preceded by up to 2s of preparatory neural activity, originating in premotor and supplementary motor regions of the brain. The function of this extended period of pre-movement activity is unclear. Although recent studies have suggested that pre-movement activity is influenced by attention to action, little is understood about the specific processes that are involved in this preparatory period prior to voluntary action. We recorded readiness potentials averaged from EEG activity as participants made voluntary self-paced finger movements. We manipulated the processing resources available for action preparation using concurrent perceptual load and cognitive working memory load tasks. Results showed that pre-movement activity was significantly reduced only under conditions of high working memory load, when resources for planning action were limited by the concurrent cognitive load task. In contrast, limiting attentional resources in the perceptual load task had no effect on pre-movement readiness activity. This suggests that movement preparatory processes involve mechanisms of cognitive control that are also required for working memory, and not more general engagement of selective attentional resources. We propose that the extended period of pre-movement neural activity preceding voluntary action reflects the engagement of cognitive control mechanisms for endogenously orienting attention in time, in readiness for the initiation of voluntary action.

Everyday Executive Functioning in Chronic Pain: Specific Deficits in Working Memory and Emotion Control, Predicted by Mood, Medications, and Pain Interference.

Objectives:People with chronic pain may experience impairments in high-level cognitive skills, particularly executive functions. Such impairments are not adequately measured in most clinical pain management settings yet could be a key influence on everyday functioning. We administered a well-validated, well-normed self-report measure to determine which aspects of executive functioning are compromised in the daily experience of patients with chronic pain, and whether these are associated with pain severity, medications, and mood. Materials and Methods:Sixty-three patients attending a multidisciplinary pain management clinic, and 66 pain-free age-matched and sex-matched controls, completed the Behavior Rating Inventory of Executive Function, Adult version (BRIEF-A). The BRIEF-A measures 9 aspects of executive function: Inhibit, Shift, Emotional Control, Initiate, Self-Monitor, Working Memory, Plan/Organize, Task Monitor, and Organization of Materials. Patients completed a battery of mood and pain-related measures. Results:Profile analysis revealed that patients with chronic pain reported significantly greater overall executive function impairments than controls. The patients showed greatest impairments on Working Memory and Emotional Control subscales, with more than half scoring in the clinically elevated range. A significant proportion of the variance in these scores was explained by total medication detriment (but not opioids alone), negative emotional states, and pain interference. Pain intensity and duration were not strong predictors of reported executive dysfunction. Discussion:Multiple factors impact on self-reported executive problems in this population. Specific deficits in Working Memory and Emotional Control have implications for patient engagement with treatment, and retention of information provided in therapy. A screening tool like the BRIEF-A may be useful in pain management settings.

One Month of Oral Morphine Decreases Gray Matter Volume in the Right Amygdala of Individuals with Low Back Pain: Confirmation of Previously Reported Magnetic Resonance Imaging Results

Objective. Prolonged exposure to opioids is known to produce neuroplastic changes in animals; however, few studies have investigated the effects of short-term prescription opioid use in humans. A previous study from our laboratory demonstrated a dosage-correlated volumetric decrease in the right amygdala of participants administered oral morphine daily for 1 month. The purpose of this current study was to replicate and extend the initial findings. Methods. Twenty-one participants with chronic low back pain were enrolled in this double-blind, placebo-controlled study. Participants were randomized to receive daily morphine (n = 11) or a matched placebo (n = 10) for 1 month. High-resolution anatomical images were acquired immediately before and after the treatment administration period. Morphological gray matter changes were investigated using tensor-based morphometry, and significant regions were subsequently tested for correlation with morphine dosage. Results. Decreased gray matter volume was observed in several reward- and pain-related regions in the morphine group, including the bilateral amygdala, left inferior orbitofrontal cortex, and bilateral pre-supplementary motor areas. Morphine administration was also associated with significant gray matter increases in cingulate regions, including the mid cingulate, dorsal anterior cingulate, and ventral posterior cingulate. Conclusions. Many of the volumetric increases and decreases overlapped spatially with the previously reported changes. Individuals taking placebo for 1 month showed neither gray matter increases nor decreases. The results corroborate previous reports that rapid alterations occur in reward-related networks following short-term prescription opioid use.

Visualising conversations between care home staff and residents with dementia

ABSTRACT People with dementia living in residential care often face the dual disadvantage of increasing difficulty with communication and reduced opportunities for conversation. Social interaction is central to wellbeing of residents with dementia, so it is important that care staff have the skills to engage in conversation with them. We studied conversations in 20 care staff–resident dyads, to examine conversation structure and content, patterns of engagement within conversations, including the topics around which engagement occurred, and communication behaviours by care staff that appeared to facilitate (or impede) participation by residents. The transcripts were analysed using Discursis, a computational information visualisation tool that allows interactive visual inspection, in context, of the contributions by each speaker, the turn-taking dynamics, and the content recurring within and between speakers. We present case examples (a) where care staff did most of the talking, initiated topics and were responsible for most recurrence of content; (b) where talk was more evenly shared between partners, with some topics initiated and/or elaborated by participants with dementia; and (c) where participants with dementia talked most, with care staff supporting the conversation. We identified accommodative strategies used by care staff, such as reflecting back the other persons responses to sustain engagement. We also noted care staff behaviours that impeded communication, such as not listening attentively and not allowing sufficient time for responses. The results from this study highlight aspects of social communication within the aged care context and suggest ways in which rewarding interactions between staff and residents with dementia might be encouraged.

Optimising Cognitive Function in Persons with Chronic Pain.

Objectives: Cognitive functioning is commonly disrupted in people living with chronic pain, yet it is an aspect of pain that is often not routinely assessed in pain management settings, and there is a paucity of research on treatments or strategies to alleviate the problem. The purpose of this review is to outline recent research on cognitive deficits seen in chronic pain, to give an overview of the mechanisms involved, advocate cognitive functioning as an important target for treatment in pain populations, and discuss ways in which it may be assessed and potentially remediated. Methods: A narrative review. Results: There are several options for remediation, including compensatory, restorative, and neuromodulatory approaches to directly modify cognitive functioning, as well as physical, psychological, and medication optimization methods to target secondary factors (mood, sleep, and medications) that may interfere with cognition. Discussion: We highlight the potential to enhance cognitive functions and identify the major gaps in the research literature.

Visual–Motor Interactions during Action Observation Are Shaped by Cognitive Context

Interactions between the visual system and the motor system during action observation are important for functions such as imitation and action understanding. Here, we asked whether such processes might be influenced by the cognitive context in which actions are performed. We recorded ERPs in a delayed go/no-go task known to induce bidirectional interference between the motor system and the visual system (visuomotor interference). Static images of hand gestures were presented as go stimuli after participants had planned either a matching (congruent) or nonmatching (incongruent) action. Participants performed the identical task in two different cognitive contexts: In one, they focused on the visual image of the hand gesture shown as the go stimulus (image context), whereas in the other, they focused on the hand gesture they performed (action context). We analyzed the N170 elicited by the go stimulus to test the influence of action plans on action observation (motor-to-visual priming). We also analyzed movement-related activity following the go stimulus to examine the influence of action observation on action planning (visual-to-motor priming). Strikingly, the context manipulation reversed the direction of the priming effects: We found stronger motor-to-visual priming in the action context compared with the image context and stronger visual-to-motor priming in the image context compared with the action context. Taken together, our findings indicate that neural interactions between motor and visual processes for executed and observed actions can change depending on task demands and are sensitive to top–down control according to the context.

Associations between compensable injury, perceived fault and pain and disability 1 year after injury: a registry-based Australian cohort study

Objectives Compensable injury increases the likelihood of having persistent pain after injury. Three-quarters of patients report chronic pain after traumatic injury, which is disabling for about one-third of patients. It is important to understand why these patients report disabling pain, in order to develop targeted preventative interventions. This study examined the experience of pain and disability, and investigated their sequential interrelationships with, catastrophising, kinesiophobia and self-efficacy 1 year after compensable and non-compensable injury. Design Observational registry-based cohort study. Setting Metropolitan Trauma Service in Melbourne, Victoria, Australia. Participants Participants were recruited from the Victorian State Trauma Registry and Victorian Orthopaedic Trauma Outcomes Registry. 732 patients were referred to the study, 82 could not be contacted or were ineligible, 217 declined and 433 participated (66.6% response rate). Outcome measures The Brief Pain Inventory, Glasgow Outcome Scale, EuroQol Five Dimensions questionnaire, Pain Catastrophising Scale, Pain Self-Efficacy Questionnaire, Injustice Experience Questionnaire and the Tampa Scale of Kinesiophobia. Methods Direct and indirect relationships (via psychological appraisals of pain/injury) between baseline characteristics (compensation, fault and injury characteristics) and pain severity, pain interference, health status and disability were examined with ordinal, linear and logistic regression, and mediation analyses. Results Injury severity, compensable injury and external fault attribution were consistently associated with moderate-to-severe pain, higher pain interference, poorer health status and moderate-to-severe disability. The association between compensable injury, or external fault attribution, and disability and health outcomes was mediated via pain self-efficacy and perceived injustice. Conclusions Given that the associations between compensable injury, pain and disability was attributable to lower self-efficacy and higher perceptions of injustice, interventions targeting the psychological impacts of pain and injury may be especially necessary to improve long-term injury outcomes.