Dane B. Cook

Functional neuroimaging correlates of mental fatigue induced by cognition among chronic fatigue syndrome patients and controls.

The neural mechanisms underlying feelings of fatigue are poorly understood. The primary purpose of the study was to use functional magnetic resonance imaging (fMRI) to determine the association between feelings of mental fatigue and blood oxygen level dependent (BOLD) brain responses during a mentally fatiguing cognitive task. Healthy, non-fatigued controls and chronic fatigue syndrome (CFS) patients were included to determine the influence of chronic levels of fatigue on brain responses. We hypothesized that mental fatigue would be significantly related to brain activity during a fatiguing cognitive task but not during either a non-fatiguing motor (finger tapping) or cognitive (auditory monitoring) task. Patients (n=9) and controls (n=11) completed a finger tapping task, a simple auditory monitoring task and a challenging working memory task, designed to induce mental fatigue, while undergoing fMRI. Fatigue was measured prior to scanning and following each task during fMRI data collection. Results showed that mental fatigue was significantly related to brain activity during the fatiguing cognitive task but not the finger tapping or simple auditory monitoring tasks. Significant (p< or =0.005) positive relationships were found for cerebellar, temporal, cingulate and frontal regions. A significant (p=0.001) negative relationship was found for the left posterior parietal cortex. CFS participants did not differ from controls for either finger tapping or auditory monitoring tasks, but exhibited significantly greater activity in several cortical and subcortical regions during the fatiguing cognitive task. Our results suggest an association between subjective feelings of mental fatigue and brain responses during fatiguing cognition.

Objective evidence of cognitive complaints in Chronic Fatigue Syndrome: A BOLD fMRI study of verbal working memory

Individuals with Chronic Fatigue Syndrome (CFS) often have difficulties with complex auditory information processing. In a series of two Blood Oxygen Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) studies, we compared BOLD signal changes between Controls and individuals with CFS who had documented difficulties in complex auditory information processing (Study 1) and those who did not (Study 2) in response to performance on a simple auditory monitoring and a complex auditory information processing task (mPASAT). We hypothesized that under conditions of cognitive challenge: (1) individuals with CFS who have auditory information processing difficulties will utilize frontal and parietal brain regions to a greater extent than Controls and (2) these differences will be maintained even when objective difficulties in this domain are controlled for. Using blocked design fMRI paradigms in both studies, we first presented the auditory monitoring task followed by the mPASAT. Within and between regions of interest (ROI), group analyses were performed for both studies with statistical parametric mapping (SPM99). Findings showed that individuals with CFS are able to process challenging auditory information as accurately as Controls but utilize more extensive regions of the network associated with the verbal WM system. Individuals with CFS appear to have to exert greater effort to process auditory information as effectively as demographically similar healthy adults. Our findings provide objective evidence for the subjective experience of cognitive difficulties in individuals with CFS.

Are Women with Fibromyalgia Less Physically Active than Healthy Women

PURPOSE The primary purpose was to quantify and compare physical activity in fibromyalgia (FM) patients to age-matched healthy controls using both objective and self-report measures. Secondary purposes were to compare self-reported and objective measurement of physical activity and to evaluate the relationship between physical activity and pain and mood. METHOD Patients with FM (n=39) and healthy controls (n=40) completed the International Physical Activity Questionnaire and wore an accelerometer at the hip for 7 d. Pain and mood were measured using the McGill Pain Questionnaire, Pain Catastrophizing Scale, Beck Depression Inventory, State-Trait Anxiety Inventory, Profile of Mood States, and Fibromyalgia Impact Questionnaire. RESULTS FM patients had significantly lower physical activity than controls measured by both the International Physical Activity Questionnaire and accelerometer (P<0.05). Both groups self-reported significantly greater moderate and vigorous physical activities than were measured by the accelerometer (P < 0.05). Self-reported and objective measures of time spent in different intensities of activity showed significant correlations in healthy controls (r=0.41-0.51, ρ=0.41, P<0.05). No significant correlations between measures were found in FM patients (P>0.05). Finally, physical activity levels were negatively related (r=-0.37, P<0.05) to depressed mood for FM patients and positively related (r=-0.41, P<0.05) to self-reported vigor for healthy controls. CONCLUSIONS This controlled study objectively demonstrates that FM patients are less physically active than healthy controls, thus extending on two earlier investigations that did not show differences in total physical activity levels using wrist-mounted actigraphy methods. Physical activity levels were not predictive of pain in FM but were significantly related to depressed mood. FM patients may also have a greater variability in their manner of self-report than healthy controls. Therefore, physical activity measurement in FM patients should not be limited solely to self-report measures.

Mechanisms of Exercise-Induced Hypoalgesia

UNLABELLED The purpose of this study was to examine opioid and endocannabinoid mechanisms of exercise-induced hypoalgesia (EIH). Fifty-eight men and women (mean age = 21 years) completed 3 sessions. During the first session, participants were familiarized with the temporal summation of heat pain and pressure pain protocols. In the exercise sessions, following double-blind administration of either an opioid antagonist (50 mg naltrexone) or placebo, participants rated the intensity of heat pulses and indicated their pressure pain thresholds and pressure pain ratings before and after 3 minutes of submaximal isometric exercise. Blood was drawn before and after exercise. Results indicated that circulating concentrations of 2 endocannabinoids, N-arachidonylethanolamine and 2-arachidonoylglycerol, as well as related lipids oleoylethanolamide, palmitoylethanolamide, N-docosahexaenoylethanolamine, and 2-oleoylglycerol, increased significantly (P < .05) following exercise. Pressure pain thresholds increased significantly (P < .05), whereas pressure pain ratings decreased significantly (P < .05) following exercise. Also, temporal summation ratings were significantly lower (P < .05) following exercise. These changes in pain responses did not differ between the placebo and naltrexone conditions (P > .05). A significant association was found between EIH and docosahexaenoylethanolamine. These results suggest involvement of a nonopioid mechanism in EIH following isometric exercise. PERSPECTIVE Currently, the mechanisms responsible for EIH are unknown. This study provides support for a potential endocannabinoid mechanism of EIH following isometric exercise.

Physical Activity, Sustained Sedentary Behavior, and Pain Modulation in Women With Fibromyalgia

UNLABELLED Fibromyalgia (FM) has been conceptualized as a disorder of the central nervous system, characterized by augmented sensory processing and an inability to effectively modulate pain. We previously reported that physical activity is related to brain processing of pain, providing evidence for a potential mechanism of pain management. The purpose of this study was to extend our work by manipulating pain modulation and determining relationships to both physical activity and sustained sedentary behavior. Eleven women with FM completed accelerometer measures of physical activity and underwent functional magnetic resonance imaging of painful heat, administered alone and during distracting cognitive tasks. Results showed that physical activity was significantly (P < .005) and positively related to brain responses during distraction from pain in regions implicated in pain modulation including the dorsolateral prefrontal cortex (DLPFC), the dorsal posterior cingulate, and the periaqueductal grey. A significant negative relationship occurred in the left anterior insula. For sedentary time, significant negative relationships were observed in areas involved in both pain modulation and the sensory-discriminative aspects of pain including the DLPFC, thalamus, and superior frontal and pre- and post-central gyri. These results suggest that physical activity and sedentary behaviors are related to central nervous system regulation of pain in FM. PERSPECTIVE Our results support a promising benefit of physical activity and highlight the potentially deleterious effects of sustained sedentary behavior for pain regulation in FM. Studies aimed at increasing physical activity or reducing sedentary behavior and determining the impact of these on pain regulation are warranted.

The relationship between physical activity and brain responses to pain in fibromyalgia.

UNLABELLED The relationship between physical activity and central nervous system mechanisms of pain in fibromyalgia (FM) is unknown. This study determined whether physical activity was predictive of brain responses to experimental pain in FM using functional magnetic resonance imaging (fMRI). Thirty-four participants (n = 16 FM; n = 18 Control) completed self-report and accelerometer measures of physical activity and underwent fMRI of painful heat stimuli. In FM patients, positive relationships (P < .005) between physical activity and brain responses to pain were observed in the dorsolateral prefrontal cortex, posterior cingulate cortex, and the posterior insula, regions implicated in pain regulation. Negative relationships (P < .005) were found for the primary sensory and superior parietal cortices, regions implicated in the sensory aspects of pain. Greater physical activity was significantly (P < .05) associated with decreased pain ratings to repeated heat stimuli for FM patients. A similar nonsignificant trend was observed in controls. In addition, brain responses to pain were significantly (P < .005) different between FM patients categorized as low active and those categorized as high active. In controls, positive relationships (P < .005) were observed in the lateral prefrontal, anterior cingulate, and superior temporal cortices and the posterior insula. Our results suggest an association between measures of physical activity and central nervous system processing of pain. PERSPECTIVE Our data suggest that brain responses to pain represent a dynamic process where perception and modulation co-occur and that physical activity plays a role in balancing these processes. Physically active FM patients appear to maintain their ability to modulate pain while those who are less active do not.

Physical Activity Is Related to Pain Sensitivity in Healthy Women.

UNLABELLED There are many benefits associated with meeting current physical activity recommendations. At present, it is unknown whether a reduced sensitivity to pain is included among these benefits. PURPOSE The studys purpose was to assess the relationship between pain sensitivity and physical activity and sedentary behaviors in a sample of healthy women. METHODS Self-reported and accelerometer measures of physical activity and sedentary behavior were collected and compared with pain intensity and unpleasantness ratings to noxious thermal stimuli in a sample of 21 healthy women (age = 30.0 ± 5.8 yr). On the basis of accelerometer data, participants were classified into two groups: meets recommendations (n = 12) and insufficiently active (n = 9). Independent-samples t-tests were conducted to compare pain ratings and physical activity behaviors between groups, and correlation coefficients (Spearman ρ) were calculated between average minutes per day spent in moderate, vigorous, and sedentary behaviors, and average intensity and unpleasantness ratings. RESULTS Participants meeting physical activity recommendations had significantly lower unpleasantness ratings than their insufficiently active peers. Correlational analyses demonstrated a significant relationship between minutes spent in vigorous physical activity and both pain intensity and pain unpleasantness ratings. Relationships were not significant for moderate activity or sedentary behavior. CONCLUSIONS These results provide preliminary evidence that meeting current physical activity recommendations may be beneficial for pain in women. Moreover, participation in vigorous activity seems to account for the decreased pain sensitivity. In our sample, sedentary behavior did not seem to have a deleterious effect on pain. Results from this study have many potential applications including aiding our understanding of why exercise functions as a treatment for those with chronic pain conditions and providing a rationale for including physical activity assessment in pain research.

Exercise alters pain sensitivity in Gulf War veterans with chronic musculoskeletal pain.

UNLABELLED Since returning from the Persian Gulf, nearly 100,000 veterans of the first Gulf War (GVs) have reported numerous symptoms with no apparent medical explanation. A primary complaint of these individuals is chronic musculoskeletal pain (CMP). CMP symptoms in GVs are similar to those reported by patients with fibromyalgia (FM), but have not received equivalent scientific attention. Exercise research in CMP patients suggests that acute exercise may exacerbate pain while chronic exercise can reduce pain and improve other symptoms. However, the influence of exercise on GVs with CMP is largely unexplored. This study examined the impact of an acute bout of exercise on pain sensitivity in GVs with CMP. Thirty-two GVs (CMP, n = 15; Control, n = 17) were recruited to complete a series of psychophysical assessments to determine pain sensitivity to heat and pressure stimuli before and after exercise. In response to heat-pain stimuli, GVs with CMP reported higher pain intensity and affect ratings than healthy GVs and exhibited a significant increase in ratings following exercise. GVs with CMP rated exercise as more painful and effortful and were generally more sensitive to heat-pain stimuli than healthy GVs. These results are similar to what has been reported for acute exercise in patients with FM. PERSPECTIVE Gulf War veterans with CMP perceive exercise as more painful and effortful than healthy GVs and experience increased pain sensitivity following exercise. These results suggest that similar abnormalities in central nervous system processing of nociceptive information documented in FM may also be occurring in GVs with CMP.

Does exercise induce hypoalgesia through conditioned pain modulation

Pain sensitivity decreases with exercise. The mechanisms that underlie this exercise-induced hypoalgesia (EIH) are unclear. Our purpose was to investigate conditioned pain modulation (CPM) as a potential mechanism of EIH. Sixteen women completed pain testing during three sessions: painful exercise, nonpainful exercise, and quiet rest. Intensity and unpleasantness ratings to noxious heat stimuli were assessed at baseline and during and following each session. Results showed that pain sensitivity decreased significantly during both exercise sessions (p < .05), but not during quiet rest. Effect size calculations showed that the size of the hypoalgesic response was greater following painful exercise than nonpainful exercise. Our results suggest that exercise-induced muscle pain may contribute to the magnitude of EIH. However, as pain sensitivity also decreased following nonpainful exercise, CPM is not likely the primary mechanism of EIH.

A real-time assessment of the effect of exercise in chronic fatigue syndrome

Patients with chronic fatigue syndrome (CFS) report substantial symptom worsening after exercise. However, the time course over which this develops has not been explored. Therefore, the objective of this study was to investigate the influence of exercise on subjective symptoms and on cognitive function in CFS patients in natural settings using a computerized ecological momentary assessment method, which allowed us to track the effects of exercise within and across days. Subjects were 9 female patients with CFS and 9 healthy women. A watch-type computer was used to collect real-time data on physical and psychological symptoms and cognitive function for 1week before and 2weeks after a maximal exercise test. For each variable, we investigated temporal changes after exercise using multilevel modeling. Following exercise, physical symptoms did get worse but not until a five-day delay in CFS patients. Despite this, there was no difference in the temporal pattern of changes in psychological symptoms or in cognitive function after exercise between CFS patients and controls. In conclusion, physical symptoms worsened after several days delay in patients with CFS following exercise while psychological symptoms or cognitive function did not change after exercise.