2016 – Page 7 – American ME and CFS Society

Do evidence based interventions for chronic fatigue syndrome improve sleep? A systematic review and narrative synthesis

Abstract:

Cognitive behavioural therapy (CBT) and graded exercise therapy (GET) are recommended evidence based treatments for chronic fatigue syndrome (CFS), with research supporting their effectiveness in reducing fatigue and functional impairment. However, little research has focussed on the effect of these treatments on sleep, despite high reported sleep disturbance in CFS.

Using a narrative synthesis approach, we aimed to 1) systematically identify and summarise the current evidence for the effectiveness of CBT and GET in improving sleep; 2) consider factors influencing treatment effectiveness, including incorporation of sleep management techniques; and 3) consider the appropriateness of sleep outcome measures used within evaluations. Studies evaluating CBT and/or GET for CFS, and including a sleep outcome were eligible for inclusion. Eight studies were identified.

We found that GET interventions can improve sleep but this effect is inconsistent across studies. For CBT the evidence is limited with only one of two evaluations demonstrating sleep-related improvements.

We conclude from existing research that we know little about the effects of including sleep management components within CBT and GET interventions. We suggest that future research should explore the effectiveness of sleep components within interventions, and sleep specific interventions, using comprehensive outcome measures that fully capture the range of sleep difficulties experienced in CFS.

Source: Russell C, Kyle SD, Wearden AJ. Do evidence based interventions for chronic fatigue syndrome improve sleep? A systematic review and narrative synthesis. Sleep Med Rev. 2016 May 13. pii: S1087-0792(16)30012-0. doi: 10.1016/j.smrv.2016.05.001. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/27524207

Enhanced psychological flexibility and improved quality of life in chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

OBJECTIVE: Psychological Flexibility (PF) is a relatively new concept in physical health. It can be defined as an overarching process of being able to accept the presence of wanted/unwanted experiences, choosing whether to change or persist in behaviour in response to those experiences. Associations between processes of PF and quality of life (QoL) have been found in long-term health conditions such as chronic pain, PF has not yet been applied to Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME).

METHODS: Changes in PF, fatigue severity and QoL were examined in one hundred and sixty-five patients with CFS/ME engaged in a six-week outpatient interdisciplinary group treatment programme. Participants were assessed using a series of self-report measures at the start of the start (T1) and end of a six-week programme (T2) and at six months follow up (T3).

RESULTS: Significant changes in PF and QoL were observed from pre-treatment (T1) to post treatment follow-up (T2 and T3); changes in fatigue severity were observed from T1 to T3 only. Controlling for fatigue severity, changes in the PF dimension of activity/occupational engagement were associated with improvement in QoL at six month follow up (T3) but not at six weeks post programme (T2).

CONCLUSION: Findings indicate an interdisciplinary group treatment approach for people with CFS/ME may be associated with improved QoL, processes of PF and fatigue severity, supporting a link between PF and long term health conditions. Results highlight links between PF and patient QoL in CFS/ME and the value of interdisciplinary treatment approaches in this patient population.

Source: Densham S, Williams D, Johnson A, Turner-Cobb JM. Enhanced psychological flexibility and improved quality of life in chronic fatigue syndrome/myalgic encephalomyelitis. J Psychosom Res. 2016 Sep;88:42-7. doi: 10.1016/j.jpsychores.2016.07.009. Epub 2016 Jul 19. https://www.ncbi.nlm.nih.gov/pubmed/27521652

A UK based review of recommendations regarding the management of chronic fatigue syndrome

Abstract:

OBJECTIVES: Chronic fatigue syndrome (CFS) is a controversial illness, with apparent disagreements between medical authorities and patient support organisations regarding safe and effective treatments. The aim of this study was to measure the extent of different views regarding treatments, comparing patient support organisations and medical authorities in the UK.

METHODS: Two independent raters analysed two groups of resources: UK patient support websites and both medical websites and textbooks. A 5-point Likert scale was developed with the question ‘With what strength does the source recommend these treatments?’ The various treatments were divided into the following four groups: complementary and alternative medicine (CAM), pharmacological, rehabilitative, and pacing therapies.

RESULTS: There were significant differences between the scores for patient support organisations and medical sources for all 4 treatment groups. The results for supporting CAM were 74% (patient group) vs 16% (medical source) (p<0.001), 71% vs 42% for pharmacological (p=0.01), 28% vs 94% for rehabilitative (p<0.001) and 91% vs 50% for pacing treatments (p=0.001).

CONCLUSIONS: There were substantially different treatment recommendations between patient support organisations and medical sources. Since expectations can determine response to treatment, these different views may reduce the engagement in and effectiveness of rehabilitative therapies recommended by national guidelines and supported by systematic reviews.

Source: Mallet M, King E, White PD. A UK based review of recommendations regarding the management of chronic fatigue syndrome. J Psychosom Res. 2016 Sep;88:33-5. doi: 10.1016/j.jpsychores.2016.07.008. Epub 2016 Jul 17. https://www.ncbi.nlm.nih.gov/pubmed/27521650

Comment

Ellen M Goudsmit 2016 Aug 16 12:55 p.m.

It should be noted that the PACE trial did not assess pacing as recommended by virtually all patient groups. This behavioural strategy is based on the observation that minimal exertion tends to exacerbate symptoms, plus the evidence that many with ME and CFS cannot gradually increase activity levels for more than a few days because of clinically significant adverse reactions [1]. It does not make any assumptions about aetiology.

The authors state that “It should be remembered that the moderate success of behavioural approaches does not imply that CFS/ME is a psychological or psychiatric disorder.” I submit that this relates to CBT and GET and not to strategies such as pacing. It might be helpful here to remind readers that the GET protocol for CFS/ME (as tested in most RCTs) is partly based on an operant conditioning theory, which is generally regarded as psychological [2]. The rehabilitative approaches promoted in the UK, i.e. CBT and GET, tend to focus on fatigue and sleep disorders, both of which may be a result of stress and psychiatric disorders e.g. depression. A review of the literature from the ‘medical authorities’ in the UK shows that almost without exception, they tend to limit the role of non-psychiatric aetiological factors to the acute phase and that somatic symptoms are usually attributed to fear of activity and the physiological effects of stress.

I informed the editor that as it read, the paper suggests that 1. patients have no sound medical source to support their preference for pacing and that 2. the data from the PACE trial provides good evidence against this strategy. I clarified that the trial actually evaluated adaptive pacing therapy (a programme including advice on stress management and a version of pacing that permits patients to operate at 70% of their estimated capability.) The editor chose not to investigate this issue in the manner one expects from an editor of a reputable journal. In light of the above issues, the information about pacing in this paper may mislead readers.

Interested scientists may find an alternative analysis of the differing views highly illuminating [3].

[1]. Goudsmit, EM., Jason, LA, Nijs, J and Wallman, KE. Pacing as a strategy to improve energy management in myalgic encephalomyelitis/chronic fatigue syndrome: A consensus document. Disability and Rehabilitation, 2012, 34, 13, 1140-1147. doi: 10.3109/09638288.2011.635746.]

[2]. Goudsmit, E. The PACE trial. Are graded activity and cognitive-behavioural therapy really effective treatments for ME? Online 18th March 2016. http://www.axfordsabode.org.uk/me/ME-PDF/PACE trial the flaws.pdf

[3]. Friedberg, F. Cognitive-behavior therapy: why is it so vilified in the chronic fatigue syndrome community? Fatigue: Biomedicine, Health & Behavior, 2016, 4, 3, 127-131. http://www.tandfonline.com/doi/full/10.1080/21641846.2016.1200884

Systemic exercise intolerance disease: What’s in a name?

Abstract:

The syndrome characterized primarily by chronic, disabling fatigue without adequate explanation has been of interest to patients, clinicians and researchers. Chronic fatigue syndrome (CFS) is a widely used term for this condition in scientific and lay literature but is not acceptable to many patients because of perceived stigma due to implied psychological causation.

CFS has recently been replaced by systemic exercise intolerance disease (SEID) by the Institute of medicine with the objectives of providing and disseminating evidence-based criteria and to provide a more acceptable name for this condition. Simultaneously, changes have taken place in DSM-5 with regards to this condition. Mental health professionals need to be aware of this change in the interests of patient care.

The need to replace CFS with SEID and the nosological changes also indicate an inability to do away with the Descartian mind-body dualism despite efforts to the contrary and a need to debate the failure of the bio-psycho-social model to ‘mainstream’ and destigmatize psychiatry.

Source: Sen MS, Sahoo S, Aggarwal S, Singh SM. Systemic exercise intolerance disease: What’s in a name?Asian J Psychiatr. 2016 Aug;22:157-8. doi: 10.1016/j.ajp.2016.06.003. Epub 2016 Jun 23. https://www.ncbi.nlm.nih.gov/pubmed/27520920

Comment

Lily Chu 2016 Sep 14 8:50 p.m.

As a member of the Institute of Medicine Committee, I talked to multiple patients, caregivers, clinicians, and researchers. The problem they have with the name “CFS” goes beyond psychological stigma. For one, fatigue is only one symptom of the disease but not even the most disabling one for patients. Post-exertional malaise and cognitive issues are. Secondly, most patients and families are concerned about psychological implications not because of stigmatization but simply because CFS is NOT a psychological or psychiatric condition. Some patients experience co-morbid depression, acknowledge its presence, and receive treatment for it. In support groups, patients discuss depression and anxiety without fear of stigma. The problem comes when clinicians or researchers conflate patients’ depression with their CFS and conclude that they can treat the latter condition with cognitive behavioral therapy or with SSRIs. An analogy would be if tomorrow, patients experiencing myocardial infarcts and major depression were told aspirin, B-blockers, cholesterol medication, etc. would no longer be the treatments for myocardial infarcts but instead SSRIs would be. Could you imagine how patients would feel in that circumstance? That is why they are concerned.

TauG-guidance of dynamic balance control during gait initiation in patients with chronic fatigue syndrome and fibromyalgia

Abstract:

BACKGROUND: Impaired postural control has been reported in static conditions in chronic fatigue syndrome and fibromyalgia, but postural control in dynamic tasks have not yet been investigated. Thus, we investigated measurements from a force plate to evaluate dynamic balance control during gait initiation in patients with chronic fatigue syndrome and fibromyalgia compared to matched healthy controls.

METHODS: Thirty female participants (10 per group) performed five trials of gait initiation. Center of pressure (CoP) trajectory of the initial weight shift onto the supporting foot in the mediolateral direction (CoPX) was analyzed using General Tau Theory. We investigated the hypothesis that tau of the CoPX motion-gap (τCoPx) is coupled onto an intrinsic tauG-guide (τG) by keeping the relation τCoPx=KτG, where K is a scaling factor that determines the relevant kinematics of a movement.

FINDINGS: Mean K values were 0.57, 0.55, and 0.50 in fibromyalgia, chronic fatigue syndrome, and healthy controls, respectively. Both patient groups showed K values significantly higher than 0.50 (P<0.05), indicating that patients showed poorer dynamic balance control, CoPX colliding with the boundaries of the base of support (K>0.5).

INTERPRETATION: The findings revealed a lower level of dynamic postural control in both fibromyalgia and chronic fatigue syndrome compared to controls.

Source: Rasouli O, Stensdotter AK, Van der Meer AL. TauG-guidance of dynamic balance control during gait initiation in patients with chronic fatigue syndrome and fibromyalgia. Clin Biomech (Bristol, Avon). 2016 Aug;37:147-52. doi: 10.1016/j.clinbiomech.2016.07.008. Epub 2016 Jul 22. https://www.ncbi.nlm.nih.gov/pubmed/27474799

Genetic variation in catechol-O-methyltransferase modifies effects of clonidine treatment in chronic fatigue syndrome

Abstract:

Clonidine, an α2-adrenergic receptor agonist, decreases circulating norepinephrine and epinephrine, attenuating sympathetic activity. Although catechol-O-methyltransferase (COMT) metabolizes catecholamines, main effectors of sympathetic function, COMT genetic variation effects on clonidine treatment are unknown. Chronic fatigue syndrome (CFS) is hypothesized to result in part from dysregulated sympathetic function.

A candidate gene analysis of COMT rs4680 effects on clinical outcomes in the Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL), a randomized double-blinded clonidine versus placebo trial, was conducted (N=104). Patients homozygous for rs4680 high-activity allele randomized to clonidine took 2500 fewer steps compared with placebo (Pinteraction=0.04).

There were no differences between clonidine and placebo among patients with COMT low-activity alleles. Similar gene-drug interactions were observed for sleep (Pinteraction=0.003) and quality of life (Pinteraction=0.018). Detrimental effects of clonidine in the subset of CFS patients homozygous for COMT high-activity allele warrant investigation of potential clonidine-COMT interaction effects in other conditions

Source: Hall KT, Kossowsky J, Oberlander TF, Kaptchuk TJ, Saul JP, Wyller VB, Fagermoen E, Sulheim D, Gjerstad J, Winger A, Mukamal KJ. Genetic variation in catechol-O-methyltransferase modifies effects of clonidine treatment in chronic fatigue syndrome. Pharmacogenomics J. 2016 Oct;16(5):454-60. doi: 10.1038/tpj.2016.53. Epub 2016 Jul 26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028250/ (Full article)

Investigating unexplained fatigue in general practice with a particular focus on CFS/ME

Abstract:

Unexplained fatigue is not infrequent in the community. It presents a number of challenges to the primary care physician and particularly if the clinical examination and routine investigations are normal. However, while fatigue is a feature of many common illnesses, it is the main problem in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). This is a poorly understood condition that is accompanied by several additional symptoms which suggest a subtle multisystem dysfunction. Not infrequently it is complicated by sleep disturbance and alterations in attention, memory and mood.

Specialised services for the diagnosis and management of CFS/ME are markedly deficient in the UK and indeed in virtually all countries around the world. However, unexplained fatigue and CFS/ME may be confidently diagnosed on the basis of specific clinical criteria combined with the normality of routine blood tests. The latter include those that assess inflammation, autoimmunity, endocrine dysfunction and gluten sensitivity. Early diagnosis and intervention in general practice will do much to reduce patient anxiety, encourage improvement and prevent expensive unnecessary investigations.

There is presently an on-going debate as to the precise criteria that best confirms CFS/ME to the exclusion of other medical and psychiatric/psychological causes of chronic fatigue. There is also some disagreement as to best means of investigating and managing this very challenging condition. Uncertainty here can contribute to patient stress which in some individuals can perpetuate and aggravate symptoms. A simple clinical scoring system and a short list of routine investigations should help discriminate CFS/ME from other causes of continued fatigue.

Source: Bansal AS. Investigating unexplained fatigue in general practice with a particular focus on CFS/ME. BMC Fam Pract. 2016 Jul 19;17:81. doi: 10.1186/s12875-016-0493-0. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950776/ (Full article)

Comments

Ellen M Goudsmit 2016 Jul 24 07:44 a.m.
I am not persuaded that ME, as described by clinicians and researchers prior to 1988, has much to do with neurasthenia. Indeed, fatigue was not a criterion for the diagnosis of ME [1]. It presents as a more neurological disorder, e.g. muscle weakness after minimal exertion. References to CFS/ME are misleading where research used criteria for chronic fatigue or CFS, rather than ME. The assumption of equivalence has been tested and the differences are of clinical significance.

A useful strategy to avoid post-exertion related exacerbations is pacing [2]. I missed a reference.

1 Goudsmit, EM, Shepherd, C., Dancey, CP and Howes, S. ME: Chronic fatigue syndrome or a distinct clinical entity? Health Psychology Update, 2009, 18, 1, 26-33. http://www.bpsshop.org.uk/Health-Psychology-Update-Vol-18-No-1-2009-P797.aspx

2 Goudsmit, EM., Jason, LA, Nijs, J and Wallman, KE. Pacing as a strategy to improve energy management in myalgic encephalomyelitis/chronic fatigue syndrome: A consensus document. Disability and Rehabilitation, 2012, 34, 13, 1140-1147. doi: 10.3109/09638288.2011.635746.
Tom Kindlon 2016 Jul 21 8:49 p.m.
Some information on an unpublished study on pupil responses:
Dr Bansal mentions he has observed unusual responses by the pupils to light. I thought I would highlight a study that was done in the late 1990s looking at this. Unfortunately the researcher passed away before it could be published. Perhaps there are better sources than these lay articles but I thought they might be of some use in the hope that the finding might be followed up again.

Eye test hope for ME sufferers

Jenny Hope

A new eye test can ‘see’ changes in the brain triggered by the crippling disease ME. The advance comes from a number of research projects that could lead to better treatments for the illness once ridiculed as ‘yuppie flu’.

It gives fresh hope to an estimated 150,000 victims of chronic fatigue syndrome, which can leave those worst affected bedridden with pain, suffering short-term memory loss and unable to walk even short distances.

Scientists at the Royal Free Hospital and the City University in London have found a way to measure changes in the eyes of ME patients which may show they lack an important brain chemical.

A study by Dr Ian James and Professor John Barbur checked the pupils of 16 ME patients and 24 healthy individuals, using a computer to measure changes identified between the two groups.

They found patients with chronic fatigue had larger pupils and also had a stronger reaction to light and other stimuli. The changes could be linked to a deficiency of the brain chemical serotonin, which is known to occur in ME and is also linked to depression.

Professor John Hughes, chairman of the Chronic Fatigue Syndrome Research Foundation, said the research should make it possible to understand changes occurring in the brain of a sufferer.

This could help those studying the effect of different drugs and possibly help doctors diagnose CFS, he added.

At present there are no reliable tests, although a checklist of symptoms developed five years ago is being used by doctors worldwide.

BREAKTHROUGH FOR ME by Geraint Jones

For years, ME has been treated with suspicion by doctors. Many believe that for every genuine sufferer there is another who simply believes himself to be ill. Experts cannot agree on whether the condition is a physical illness or a psychological disorder which exists only in the victim’s mind. One reason for this scepticism is that, as yet, no one has been able to provide an accurate diagnosis for ME, or myalgic encephalomyelitis, which is known to affect 150,000 people in Britain. There is no known cure and treatment is often based on antidepressant drugs like Prozae, with limited success.

All this may be about to change. Dr Ian James, consultant and reader in clinical pharmacology at London’s Royal Free Hospital School of Medicine, believes that he has found a way of diagnosing the chronic fatigue syndrome and hopes to use it to develop a treatment programme. The breakthrough came after months of research spearheaded by Dr James and Professor John Barbur of London’s City University. It centres round the discovery that the eyes of ME sufferers respond to light and motion stimuli in an unusual way.

“Several doctors treating ME patients noticed that they showed an abnormal pupil response”, says Dr James. “When the pupil is subjected to changes in light, or is required to alter focus from a close object to one further away, it does so by constricting and dilating. ME patients’ eyes do this as well but there is an initial period of instability when the pupil fluctuates in size”.

Using a computerised “pupilometer”, which precisely measures eye responses, Dr James embarked on a detailed study of this phenomenon on ME patients, using non-sufferers as a control. A variety of shapes were flashed on to a screen and moved across it, while a computer precisely measured pupil reflex to each of the 40 tests. Results confirmed that the pupil fluctuation was peculiar to those participants who suffered from ME.

Dr James concluded that the abnormal pupil response is a result of some kind of interference in the transfer of impulses from the brain to the eye. He believes that ME is the result of a deficiency of a neuro-transmitter called 5HT, whose job it is to pass impulses through nerves to cells. The eyes of ME sufferers treated with 5HT behave normally. “I do not yet know how the ME virus causes abnormalities in 5HT transmission but it does inhibit its function”, says Dr James.

Potential use of visible and near-infrared spectroscopy for the analysis and diagnosis of chronic fatigue syndrome (Review)

Abstract:

At present, chronic fatigue syndrome (CFS) is diagnosed on the basis of clinical symptoms. Although various psychological, endocrinological and immunological abnormalities of patients with CFS have been reported, no clear consensus exists regarding the symptoms for this disorder. Thus, an objective diagnostic method for CFS is urgently required.

The present study investigated the diagnosis and analysis of CFS using visible and near infrared (Vis NIR) spectroscopy. Previous studies have demonstrated the potential of Vis-NIR spectroscopy for diagnosing CFS by analyzing either serum samples as an invasive approach or thumbs as a non invasive approach.

Analysis of the Vis NIR spectra of blood and thumbs suggested that factors absorbing in this spectral region are altered in patients with CFS compared with healthy individuals. These findings are likely to facilitate the search for biomarkers associated with CFS and to increase our understanding of the pathophysiology of the disorder. The current review aimed to outline the latest studies and discuss the future perspectives for CFS made possible by Vis-NIR spectroscopy.

Source: Sakudo A. Potential use of visible and near-infrared spectroscopy for the analysis and diagnosis of chronic fatigue syndrome (Review). Mol Med Rep. 2016 Sep;14(3):1875-9. doi: 10.3892/mmr.2016.5476. Epub 2016 Jul 7. https://www.ncbi.nlm.nih.gov/pubmed/27430297

Neuromuscular Strain Increases Symptom Intensity in Chronic Fatigue Syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a complex, multisystem disorder that can be disabling. CFS symptoms can be provoked by increased physical or cognitive activity, and by orthostatic stress. In preliminary work, we noted that CFS symptoms also could be provoked by application of longitudinal neural and soft tissue strain to the limbs and spine of affected individuals.

In this study we measured the responses to a straight leg raise neuromuscular strain maneuver in individuals with CFS and healthy controls. We randomly assigned 60 individuals with CFS and 20 healthy controls to either a 15 minute period of passive supine straight leg raise (true neuromuscular strain) or a sham straight leg raise. The primary outcome measure was the symptom intensity difference between the scores during and 24 hours after the study maneuver compared to baseline.

Fatigue, body pain, lightheadedness, concentration difficulties, and headache scores were measured individually on a 0-10 scale, and summed to create a composite symptom score. Compared to individuals with CFS in the sham strain group, those with CFS in the true strain group reported significantly increased body pain (P = 0.04) and concentration difficulties (P = 0.02) as well as increased composite symptom scores (all P = 0.03) during the maneuver.

After 24 hours, the symptom intensity differences were significantly greater for the CFS true strain group for the individual symptom of lightheadedness (P = 0.001) and for the composite symptom score (P = 0.005). During and 24 hours after the exposure to the true strain maneuver, those with CFS had significantly higher individual and composite symptom intensity changes compared to the healthy controls.

We conclude that a longitudinal strain applied to the nerves and soft tissues of the lower limb is capable of increasing symptom intensity in individuals with CFS for up to 24 hours. These findings support our preliminary observations that increased mechanical sensitivity may be a contributor to the provocation of symptoms in this disorder.

Source: Rowe PC, Fontaine KR, Lauver M, Jasion SE, Marden CL, Moni M, Thompson CB, Violand RL. Neuromuscular Strain Increases Symptom Intensity in Chronic Fatigue Syndrome. PLoS One. 2016 Jul 18;11(7):e0159386. doi: 10.1371/journal.pone.0159386. ECollection 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948885/ (Full article)

Aberrant Resting-State Functional Connectivity in the Salience Network of Adolescent Chronic Fatigue Syndrome

Abstract:

Neural network investigations are currently absent in adolescent chronic fatigue syndrome (CFS). In this study, we examine whether the core intrinsic connectivity networks (ICNs) are altered in adolescent CFS patients.

Eighteen adolescent patients with CFS and 18 aged matched healthy adolescent control subjects underwent resting-state functional magnetic resonance imaging (rfMRI). Data was analyzed using dual-regression independent components analysis, which is a data-driven approach for the identification of independent brain networks. Intrinsic connectivity was evaluated in the default mode network (DMN), salience network (SN), and central executive network (CEN). Associations between network characteristics and symptoms of CFS were also explored.

Adolescent CFS patients displayed a significant decrease in SN functional connectivity to the right posterior insula compared to healthy comparison participants, which was related to fatigue symptoms. Additionally, there was an association between pain intensity and SN functional connectivity to the left middle insula and caudate that differed between adolescent patients and healthy comparison participants.

Our findings of insula dysfunction and its association with fatigue severity and pain intensity in adolescent CFS demonstrate an aberration of the salience network which might play a role in CFS pathophysiology.

Source: Wortinger LA, Endestad T, Melinder AM, Øie MG, Sevenius A, Bruun Wyller V. Aberrant Resting-State Functional Connectivity in the Salience Network of Adolescent Chronic Fatigue Syndrome. PLoS One. 2016 Jul 14;11(7):e0159351. doi: 10.1371/journal.pone.0159351. ECollection 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944916/ (Full article)