Category: Cognitive Dysfunction

Resting-state functional connectivity, cognition, and fatigue in response to cognitive exertion: a novel study in adolescents with chronic fatigue syndrome

Abstract:

Emerging evidence suggests that central nervous system dysfunction may underlie the core symptoms of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in adults, such as cognitive disturbance, fatigue and post-exertional malaise. Research into brain dysfunction in the pediatric CFS/ME context, however, is severely lacking. It is unclear whether the adolescent CFS/ME brain functions differently compared with healthy peers, particularly in situations where significant mental effort is required. This study used resting-state functional MRI in a novel repeated-measures design to evaluate intrinsic connectivity, cognitive function, and subjective fatigue, before and after a period of cognitive exertion in 48 adolescents (25 CFS/ME, 23 healthy controls).

Results revealed little evidence for a differential effect of cognitive exertion in CFS/ME compared with controls. Both groups demonstrated a similar rate of reduced intrinsic functional connectivity within the default mode network (DMN), reduced sustained attentional performance, slower processing speed, and increased subjective fatigue as a result of cognitive exertion.

However, CFS/ME adolescents consistently displayed higher subjective fatigue, and controls outperformed the CFS/ME group overall on cognitive measures of processing speed, sustained attention and new learning. No brain-behavior relationships were observed between DMN connectivity, cognitive function, and fatigue over time.

These findings suggest that effortful cognitive tasks may elicit similar levels of energy expenditure across all individuals in the form of reduced brain functioning and associated fatigue. However, CFS/ME may confer a lower starting threshold from which to access energy reserves and cognitive resources when cognitive effort is required.

Source: Josev EK, Malpas CB, Seal ML, Scheinberg A6, Lubitz L, Rowe K, Knight SJ. Resting-state functional connectivity, cognition, and fatigue in response to cognitive exertion: a novel study in adolescents with chronic fatigue syndrome. Brain Imaging Behav. 2019 May 17. doi: 10.1007/s11682-019-00119-2. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31102168

Impairments in cognitive performance in chronic fatigue syndrome are common, not related to co-morbid depression but do associate with autonomic dysfunction

Abstract:

OBJECTIVES: To explore cognitive performance in chronic fatigue syndrome (CFS) examining two cohorts. To establish findings associated with CFS and those related to co-morbid depression or autonomic dysfunction.

METHODS: Identification and recruitment of participants was identical in both phases, all CFS patients fulfilled Fukuda criteria. In Phase 1 (n = 48) we explored cognitive function in a heterogeneous cohort of CFS patients, investigating links with depressive symptoms (HADS). In phase 2 (n = 51 CFS & n = 20 controls) participants with co-morbid major depression were excluded (SCID). Furthermore, we investigated relationships between cognitive performance and heart rate variability (HRV).

RESULTS: Cognitive performance in unselected CFS patients is in average range on most measures. However, 0-23% of the CFS sample fell below the 5th percentile. Negative correlations occurred between depressive symptoms (HAD-S) with Digit-Symbol-Coding (r = -.507, p = .006) and TMT-A (r = -.382, p = .049). In CFS without depression, impairments of cognitive performance remained with significant differences in indices of psychomotor speed (TMT-A: p = 0.027; digit-symbol substitution: p = 0.004; digit-symbol copy: p = 0.007; scanning: p = .034) Stroop test suggested differences due to processing speed rather than inhibition. Both cohorts confirmed relationships between cognitive performance and HRV (digit-symbol copy (r = .330, p = .018), digit-symbol substitution (r = .313, p = .025), colour-naming trials Stroop task (r = .279, p = .050).

CONCLUSION: Cognitive difficulties in CFS may not be as broad as suggested and may be restricted to slowing in basic processing speed. While depressive symptoms can be associated with impairments, co-morbidity with major depression is not itself responsible for reductions in cognitive performance. Impaired autonomic control of heart-rate associates with reductions in basic processing speed.

Source: Robinson LJ, Gallagher P, Watson S, Pearce R, Finkelmeyer A, Maclachlan L, Newton JL. Impairments in cognitive performance in chronic fatigue syndrome are common, not related to co-morbid depression but do associate with autonomic dysfunction. PLoS One. 2019 Feb 5;14(2):e0210394. doi: 10.1371/journal.pone.0210394. eCollection 2019. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210394 (Full article)

Feedback on underperformance in patients with Chronic Fatigue Syndrome: The impact on subsequent neuropsychological test performance

Abstract:

Performance Validity Tests (PVTs) are used to measure the credibility of neuropsychological test results. Until now, however, a minimal amount is known about the effects of feedback upon noncredible results (i.e., underperformance) on subsequent neuropsychological test performance.

The purpose of this study was to investigate the effects of feedback on underperformance in Chronic Fatigue Syndrome (CFS) patients. A subset of these patients received feedback on Amsterdam Short-Term Memory (ASTM) failure (i.e., feedback [FB] group). After matching, the final sample consisted of two comparable groups (i.e., FB and No FB; both n = 33). At baseline and follow-up assessment, the patients completed the ASTM and two measurements of information processing speed (Complex Reaction Time [CRT] and Symbol Digit Test [SDT]).

Results indicated that the patients in the FB group improved significantly on the CRT, compared to the No FB group. Although not significant, a comparable trend-like effect was observed for the SDT. Independent of the feedback intervention there was a substantial improvement on ASTM performance at re-administration. A limited feedback intervention upon underperformance in CFS patients may result in improvement on information processing speed performance. This implies that such an intervention might be clinically relevant, since it maximizes the potential of examining the patients’ actual level of cognitive abilities.

Source: Roor JJ, Knoop H, Dandachi-FitzGerald B, Peters MJV, Bleijenberg G, Ponds RWHM. Feedback on underperformance in patients with Chronic Fatigue Syndrome: The impact on subsequent neuropsychological test performance. Appl Neuropsychol Adult. 2018 Oct 31:1-9. doi: 10.1080/23279095.2018.1519509. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30380922

A Concurrent Cognitive Task Does Not Perturb Quiet Standing in Fibromyalgia and Chronic Fatigue Syndrome

Abstract:

BACKGROUND AND OBJECTIVES: Cognitive complaints are common in fibromyalgia (FM) and chronic fatigue syndrome (CFS). Fatigue as well as pain may require greater effort to perform cognitive tasks, thereby increasing the load on processing in the central nervous system and interfering with motor control.

METHODS: The effect of a concurrent arithmetic cognitive task on postural control during quiet standing was investigated in 75 women (aged 19-49 years) and compared between FM, CFS, and matched controls (n=25/group). Quiet standing on a force plate was performed for 60 s/condition, with and without a concurrent cognitive task. The center of pressure data was decomposed into a slow component and a fast component representing postural sway and adjusting ankle torque.

RESULTS: Compared to controls, CFS and FM displayed lower frequency in the slow component (p < 0.001), and CFS displayed greater amplitude in the slow (p=0.038 and p=0.018) and fast (p=0.045) components. There were no interactions indicating different responses to the added cognitive task between any of the three groups.

CONCLUSION: Patients displayed insufficient postural control across both conditions, while the concurrent cognitive task did not perturb quiet standing. Fatigue but not pain correlated with postural control variables.

Source: Rasouli O, Fors EA, Vasseljen O, Stensdotter AK. A Concurrent Cognitive Task Does Not Perturb Quiet Standing in Fibromyalgia and Chronic Fatigue Syndrome. Pain Res Manag. 2018 Aug 7;2018:9014232. doi: 10.1155/2018/9014232. eCollection 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109464/ (Full article)

Patients with chronic fatigue syndrome do not score higher on the autism-spectrum quotient than healthy controls: Comparison with autism spectrum disorder

Abstract:

Clinically, there is an overlap of several symptoms of chronic fatigue syndrome (CFS) and autism spectrum disorder (ASD), including fatigue; brain “fog”; cognitive impairments; increased sensitivity to sound, light, and odour; increased pain and tenderness; and impaired emotional contact.

Adults with CFS (n = 59) or ASD (n = 50) and healthy controls (HC; n = 53) were assessed with the Autism-Spectrum Quotient (AQ) in a cross-sectional study. Non-parametric analysis was used to compare AQ scores among the groups. Univariate analysis of variance (ANCOVA) was used to identify if age, sex, or diagnostic group influenced the differences in scores. Patients with ASD scored significantly higher on the AQ than the CFS group and the HC group. No differences in AQ scores were found between the CFS and HC groups. AQ results were influenced by the diagnostic group but not by age or sex, according to ANCOVA. Despite clinical observations of symptom overlap between ASD and CFS, adult patients with CFS report few autistic traits in the self-report instrument, the AQ. The choice of instrument to assess autistic traits may influence the results.

Source: Bileviciute-Ljungar I, Maroti D, Bejerot S. Patients with chronic fatigue syndrome do not score higher on the autism-spectrum quotient than healthy controls: Comparison with autism spectrum disorder. Scand J Psychol. 2018 May 8. doi: 10.1111/sjop.12451. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29738079

Altered right anterior insular connectivity and loss of associated functions in adolescent chronic fatigue syndrome

Abstract:

Impairments in cognition, pain intolerance, and physical inactivity characterize adolescent chronic fatigue syndrome (CFS), yet little is known about its neurobiology. The right dorsal anterior insular (dAI) connectivity of the salience network provides a motivational context to stimuli. In this study, we examined regional functional connectivity (FC) patterns of the right dAI in adolescent CFS patients and healthy participants.

Eighteen adolescent patients with CFS and 18 aged-matched healthy adolescent control participants underwent resting-state functional magnetic resonance imaging. The right dAI region of interest was examined in a seed-to-voxel resting-state FC analysis using SPM and CONN toolbox. Relative to healthy adolescents, CFS patients demonstrated reduced FC of the right dAI to the right posterior parietal cortex (PPC) node of the central executive network. The decreased FC of the right dAI-PPC might indicate impaired cognitive control development in adolescent CFS. Immature FC of the right dAI-PPC in patients also lacked associations with three known functional domains: cognition, pain and physical activity, which were observed in the healthy group. These results suggest a distinct biological signature of adolescent CFS and might represent a fundamental role of the dAI in motivated behavior.

Source: Wortinger LA, Glenne Øie M, Endestad T, Bruun Wyller V. Altered right anterior insular connectivity and loss of associated functions in adolescent chronic fatigue syndrome. PLoS One. 2017 Sep 7;12(9):e0184325. doi: 10.1371/journal.pone.0184325. ECollection 2017. https://www.ncbi.nlm.nih.gov/pubmed/28880891

Prevalence of and risk factors for severe cognitive and sleep symptoms in ME/CFS and MS

Abstract:

BACKGROUND: There are considerable phenotypic and neuroimmune overlaps between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis (MS). While the precise aetiologies of both MS and ME/CFS are unclear, evidence suggests that deterioration in cognitive function is widely prevalent in patients with either condition. Little is known about differing risk factors or exposures, which may lead to severe cognitive or sleep symptoms. This study aims to gauge the extent of cognitive and sleep symptoms in ME/CFS and MS patients participating in the UK ME/CFS Biobank and identify the characteristics of those experiencing severe symptoms.

METHODS: This was a cross-sectional study of 395 UK ME/CFS Biobank participants, recruited from primary care and the community, using similar standardised protocols, and matched by age, sex and geographical area. Data were collected from participants using a standardized written questionnaire at clinical visits. Cognitive symptoms included problems with short-term memory, attention, and executive function. Sleep symptoms included unrefreshing sleep and poor quality or inadequate duration of sleep. All participants reported symptoms based on an ordinal severity scale. Multivariable logistic regression was carried out in the ME/CFS group to investigate socio-demographic factors associated with severe symptoms.

RESULTS: All cognitive and sleep symptoms were more prevalent in the ME/CFS group, with 'trouble concentrating' (98.3%) the most commonly reported symptom. Severe symptoms were also more commonly reported in the ME/CFS group, with 55% reporting 'severe, unrefreshing sleep'. Similarly, in the MS group, the most commonly reported severe symptoms were sleep-related. Logistic regression analysis revealed that ME/CFS patients aged over 50 years were more than three times as likely to experience severe symptoms than those younger than 30 (OR 3.23, p = 0.031). Current smoking was associated with severe symptoms, increasing the risk by approximately three times (OR 2.93, p = 0.003) and those with household incomes of more than £15,000 per year were less likely to experience severe symptoms compared to those earning less than this (OR 0.31, p = 0.017).

CONCLUSIONS:Cognitive and sleep symptoms are more common in ME/CFS patients than in MS patients and healthy controls, providing further support for existing evidence of central nervous system abnormalities in ME/CFS. Our findings suggest that people with ME/CFS who are smokers, or have a low income, are more likely to report severe cognitive and sleep symptoms. Future research should aim to develop strategies to prevent the progression of severe cognitive and sleep symptoms through early interventions that prioritise patients identified as being at highest risk.

Source: Jain V, Arunkumar A, Kingdon C, Lacerda E, Nacul L. Prevalence of and risk factors for severe cognitive and sleep symptoms in ME/CFS and MS. BMC Neurol. 2017 Jun 20;17(1):117. doi: 10.1186/s12883-017-0896-0. https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-017-0896-0 (Full article)

Chronic fatigue syndrome: System under stress

Australian researchers have discovered for the first time that reduced heart rate variability — or changes in heart beat timing — best predicts cognitive disturbances, such as concentration difficulties commonly reported by people with chronic fatigue syndrome (CFS). This adds to the growing body of evidence linking autonomic nervous system imbalance to symptoms of this poorly understood disorder.

The findings are reported in the journal PLOS ONE.

Chronic fatigue syndrome is characterised by medically unexplained, disabling fatigue and neuropsychiatric symptoms of at least six months’ duration. The disturbance underlying the symptoms in CFS is still poorly understood.

“We have studied autonomic function in CFS for some time and our findings clearly indicate a loss of integrity in stress-responsive neural and physiological systems in CFS. Patients with this condition are hyper-responsive to challenges arising both from within the body and from the environment,” says lead researcher, Associate Professor Ute Vollmer-Conna of the University of New South Wales in Sydney, Australia.

“Even when they sleep, their stress-responsive neural systems are on high alert, signalling that it is not safe to relax. I think this condition may be understood by analogy to post-traumatic stress disorder, just that in CFS the original trauma is most likely a physiological, internal one, such as a severe infection.”

In a study of 30 patients with CFS and 40 healthy individuals, UNSW researchers recorded the heart beats of participants (via ECG) and analysed cardiac responses to cognitive challenges, and associations with mental performance outcomes.

The patients with CFS performed with similar accuracy, but they took significantly longer to complete the tests than people without the condition. They also had greater heart rate reactivity; low and unresponsive heart rate variability; and prolonged heart rate-recovery after the cognitive challenge.

Resting heart rate variability (an index of vagus nerve activity) was identified as the only significant predictor of cognitive outcomes, while current levels of fatigue and other symptoms did not relate to cognitive performance.

“This is the first demonstration of an association between reduced cardiac vagal tone and cognitive impairment in CFS. Our findings confirm previous reports of a significant loss of vagal modulation, which becomes particularly apparent when dealing with challenging tasks. The current results are consistent with the notion that CFS represents a ‘system under stress’,” Associate Professor Vollmer-Conna says.

The findings could lead to new ways to improve cognitive difficulties in people with CFS, including biofeedback assisted retraining of autonomic functioning, the researchers say.

Journal Reference: Alison Beaumont, Alexander R. Burton, Jim Lemon, Barbara K. Bennett, Andrew Lloyd, Uté Vollmer-Conna. Reduced Cardiac Vagal Modulation Impacts on Cognitive Performance in Chronic Fatigue Syndrome. PLoS ONE, 2012; 7 (11): e49518 DOI: 10.1371/journal.pone.0049518

 

Source: University of New South Wales. “Chronic fatigue syndrome: System under stress.” ScienceDaily. ScienceDaily, 15 November 2012. https://www.sciencedaily.com/releases/2012/11/121115133806.htm

 

Neural Consequences of Post-Exertion Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Post exertion malaise is one of the most debilitating aspects of Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, yet the neurobiological consequences are largely unexplored. The objective of the study was to determine the neural consequences of acute exercise using functional brain imaging.

Fifteen female Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients and 15 healthy female controls completed 30 minutes of submaximal exercise (70% of peak heart rate) on a cycle ergometer. Symptom assessments (e.g. fatigue, pain, mood) and brain imaging data were collected one week prior to and 24 hours following exercise.

Functional brain images were obtained during performance of: 1) a fatiguing cognitive task – the Paced Auditory Serial Addition Task, 2) a non-fatiguing cognitive task – simple number recognition, and 3) a non-fatiguing motor task – finger tapping. Symptom and exercise data were analyzed using independent samples t-tests. Cognitive performance data were analyzed using mixed-model analysis of variance with repeated measures. Brain responses to fatiguing and non-fatiguing tasks were analyzed using linear mixed effects with cluster-wise (101-voxels) alpha of 0.05.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients reported large symptom changes compared to controls (effect size ≥0.8, p<0.05). Patients and controls had similar physiological responses to exercise (p>0.05). However, patients exercised at significantly lower Watts and reported greater exertion and leg muscle pain (p<0.05).

For cognitive performance, a significant Group by Time interaction (p<0.05), demonstrated pre- to post-exercise improvements for controls and worsening for patients. Brain responses to finger tapping did not differ between groups at either time point. During number recognition, controls exhibited greater brain activity (p<0.05) in the posterior cingulate cortex, but only for the pre-exercise scan. For the Paced Serial Auditory Addition Task, there was a significant Group by Time interaction (p<0.05) with patients exhibiting increased brain activity from pre- to post-exercise compared to controls bilaterally for inferior and superior parietal and cingulate cortices.

Changes in brain activity were significantly related to symptoms for patients (p<0.05). Acute exercise exacerbated symptoms, impaired cognitive performance and affected brain function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients.

These converging results, linking symptom exacerbation with brain function, provide objective evidence of the detrimental neurophysiological effects of post-exertion malaise.

Published by Elsevier Inc.

 

Source: Cook DB, Light AR, Light KC, Broderick G, Shields MR, Dougherty RJ, Meyer JD, VanRiper S, Stegner AJ, Ellingson LD, Vernon SD. Neural Consequences of Post-Exertion Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Brain Behav Immun. 2017 Feb 16. pii: S0889-1591(17)30051-X. doi: 10.1016/j.bbi.2017.02.009. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28216087

 

Low putamen activity associated with poor reward sensitivity in childhood chronic fatigue syndrome

Abstract:

Motivational signals influence a wide variety of cognitive processes and components of behavioral performance. Cognitive dysfunction in patients with childhood chronic fatigue syndrome (CCFS) may be closely associated with a low motivation to learn induced by impaired neural reward processing. However, the extent to which reward processing is impaired in CCFS patients is unclear.

The aim of the present functional magnetic resonance imaging (fMRI) study was to determine whether brain activity in regions related to reward sensitivity is impaired in CCFS patients. fMRI data were collected from 13 CCFS patients (mean age, 13.6 ± 1.0 years) and 13 healthy children and adolescents (HCA) (mean age, 13.7 ± 1.3 years) performing a monetary reward task. Neural activity in high- and low-monetary-reward conditions was compared between CCFS and HCA groups. Severity of fatigue and the reward obtained from learning in daily life were evaluated by questionnaires.

Activity of the putamen was lower in the CCFS group than in the HCA group in the low-reward condition, but not in the high-reward condition. Activity of the putamen in the low-reward condition in CCFS patients was negatively and positively correlated with severity of fatigue and the reward from learning in daily life, respectively.

We previously revealed that motivation to learn was correlated with striatal activity, particularly the neural activity in the putamen. This suggests that in CCFS patients low putamen activity, associated with altered dopaminergic function, decreases reward sensitivity and lowers motivation to learn.

 

Source: Mizuno K, Kawatani J, Tajima K, Sasaki AT, Yoneda T, Komi M, Hirai T, Tomoda A, Joudoi T, Watanabe Y. Low putamen activity associated with poor reward sensitivity in childhood chronic fatigue syndrome. Neuroimage Clin. 2016 Sep 26;12:600-606. eCollection 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5043413/ (Full article)