Tag: brain abnormalities

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

Medial prefrontal cortex deficits correlate with unrefreshing sleep in patients with chronic fatigue syndrome

Abstract:

Unrefreshing sleep is a hallmark of chronic fatigue syndrome/myalgic encephalomyelitis (CFS). This study examined brain structure variations associated with sleep quality in patients with CFS. 38 patients with CFS (34.8 ± 10.1 years old) and 14 normal controls (NCs) (34.7 ± 8.4 years old) were recruited. All subjects completed the Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index (PSQI), and Chalder Fatigue Scale (CFQ) questionnaires. Brain MRI measures included global and regional grey and white matter volumes, magnetization transfer T1 weighted (MT-T1w) intensities, and T1 weighted (T1w) and T2 weighted spin echo signal intensities.

We performed voxel based group comparisons of these regional brain MRI measures and regressions of these measures with the PSQI and CFQ scales adjusted for age, anxiety and depression, and the appropriate global measure. In CFS patients, negative correlations were observed in the medial prefrontal cortex (mPFC) between PSQI and MT-T1w intensities (family-wise error corrected cluster, PFWE < 0.05) and between PSQI and T1w intensities (PFWE < 0.05). In the same mPFC location, both MT and T1w intensities were lower in CFS patients compared with NCs (uncorrected voxel P < 0.001).

This study is the first to report that brain structural differences are associated with unrefreshing sleep in CFS. This result refutes the suggestion that unrefreshing sleep is a misperception in CFS patients and further investigation of this symptom is warranted.

Source: Shan ZY, Kwiatek R, Burnet R, Del Fante P, Staines DR, Marshall-Gradisnik SM, Barnden LR. Medial prefrontal cortex deficits correlate with unrefreshing sleep in patients with chronic fatigue syndrome. NMR Biomed. 2017 Jun 29. doi: 10.1002/nbm.3757. [Epub ahead of print] http://onlinelibrary.wiley.com/doi/10.1002/nbm.3757/full

CNS findings in chronic fatigue syndrome and a neuropathological case report

Abstract:

Chronic fatigue syndrome (CFS) is characterized as a persistent, debilitating complex disorder of unknown etiology, whereby patients suffer from extreme fatigue, which often presents with symptoms that include chronic pain, depression, weakness, mood disturbances, and neuropsychological impairment. In this mini review and case report, we address central nervous system (CNS) involvement of CFS and present neuropathological autopsy findings from a patient who died with a prior diagnosis of CFS.

Among the most remarkable pathological features of the case are focal areas of white matter loss, neurite beading, and neuritic pathology of axons in the white matter with axonal spheroids. Atypical neurons displaying aberrant sprouting processes in response to injury are observed throughout cortical gray and white matter. Abundant amyloid deposits identical to AD plaques with accompanying intracellular granular structures are observed as well. Neurofibrillary tangles are also present in the white matter of the frontal cortex, thalamus and basal ganglia.

Taken together, these neuropathological findings warrant further studies into CNS disease associated with CFS.

 

Source: Kimberly Ferrero, Mitchell Silver, Alan Cocchetto, Eliezer Masliah, Dianne Langford. CNS findings in chronic fatigue syndrome and a neuropathological case report. Journal of Investigative Medicine. DOI: 10.1136/jim-2016-000390 Published 6 April 2017. http://jim.bmj.com/content/early/2017/04/06/jim-2016-000390

 

Brain imaging reveals clues about chronic fatigue syndrome

A brain imaging study shows that patients with chronic fatigue syndrome may have reduced responses, compared with healthy controls, in a region of the brain connected with fatigue. The findings suggest that chronic fatigue syndrome is associated with changes in the brain involving brain circuits that regulate motor activity and motivation.

Compared with healthy controls, patients with chronic fatigue syndrome had less activation of the basal ganglia, as measured by fMRI (functional magnetic resonance imaging). This reduction of basal ganglia activity was also linked with the severity of fatigue symptoms.

According to the Centers for Disease Control and Prevention, chronic fatigue syndrome is a debilitating and complex disorder characterized by intense fatigue that is not improved by bed rest and that may be worsened by exercise or mental stress.

The results are scheduled for publication in the journal PLOS One.

“We chose the basal ganglia because they are primary targets of inflammation in the brain,” says lead author Andrew Miller, MD. “Results from a number of previous studies suggest that increased inflammation may be a contributing factor to fatigue in CFS patients, and may even be the cause in some patients.”

Miller is William P. Timmie professor of psychiatry and behavioral sciences at Emory University School of Medicine. The study was a collaboration among researchers at Emory University School of Medicine, the CDC’s Chronic Viral Diseases Branch, and the University of Modena and Reggio Emilia in Italy. The study was funded by the CDC.

The basal ganglia are structures deep within the brain, thought to be responsible for control of movements and responses to rewards as well as cognitive functions. Several neurological disorders involve dysfunction of the basal ganglia, including Parkinson’s disease and Huntington’s disease, for example.

In previous published studies by Emory researchers, people taking interferon alpha as a treatment for hepatitis C, which can induce severe fatigue, also show reduced activity in the basal ganglia. Interferon alpha is a protein naturally produced by the body, as part of the inflammatory response to viral infection. Inflammation has also been linked to fatigue in other groups such as breast cancer survivors.

“A number of previous studies have suggested that responses to viruses may underlie some cases of CFS,” Miller says. “Our data supports the idea that the body’s immune response to viruses could be associated with fatigue by affecting the brain through inflammation. We are continuing to study how inflammation affects the basal ganglia and what effects that has on other brain regions and brain function. These future studies could help inform new treatments.”

Treatment implications might include the potential utility of medications to alter the body’s immune response by blocking inflammation, or providing drugs that enhance basal ganglia function, he says.

The researchers compared 18 patients diagnosed with chronic fatigue syndrome with 41 healthy volunteers. The 18 patients were recruited [not referred] based on an initial telephone survey followed by extensive clinical evaluations. The clinical evaluations, which came in two phases, were completed by hundreds of Georgia residents. People with major depression or who were taking antidepressants were excluded from the imaging study, although those with anxiety disorders were not.

For the brain imaging portion of the study, participants were told they’d win a dollar if they correctly guessed whether a preselected card was red or black. After they made a guess, the color of the card was revealed, and at that point researchers measured blood flow to the basal ganglia.

The key measurement was: how big is the difference in activity between a win or a loss? Participants’ scores on a survey gauging their levels of fatigue were tied to the difference in basal ganglia activity between winning and losing. Those with the most fatigue had the smallest changes, especially in the right caudate and the right globus pallidus, both parts of the basal ganglia.

Ongoing studies at Emory are further investigating the impact of inflammation on the basal ganglia, including studies using anti-inflammatory treatments to reduce fatigue and loss of motivation in patients with depression and other disorders with inflammation including cancer.

 

Source: Emory Health Sciences. “Brain imaging reveals clues about chronic fatigue syndrome.” ScienceDaily. ScienceDaily, 23 May 2014. https://www.sciencedaily.com/releases/2014/05/140523192427.htm

 

Brain abnormalities found in chronic fatigue patients

An imaging study by Stanford University School of Medicine investigators has found distinct differences between the brains of patients with chronic fatigue syndrome and those of healthy people.

The findings could lead to more definitive diagnoses of the syndrome and may also point to an underlying mechanism in the disease process.

It’s not uncommon for CFS patients to face several mischaracterizations of their condition, or even suspicions of hypochondria, before receiving a diagnosis of CFS. The abnormalities identified in the study, to be published Oct. 29 in Radiology, may help to resolve those ambiguities, said lead author Michael Zeineh, MD, PhD, assistant professor of radiology.

“Using a trio of sophisticated imaging methodologies, we found that CFS patients’ brains diverge from those of healthy subjects in at least three distinct ways,” Zeineh said.

CFS affects between 1 million and 4 million individuals in the United States and millions more worldwide. Coming up with a more precise number of cases is tough because it’s difficult to actually diagnose the disease. While all CFS patients share a common symptom — crushing, unremitting fatigue that persists for six months or longer — the additional symptoms can vary from one patient to the next, and they often overlap with those of other conditions.

Scientific Challenge

“CFS is one of the greatest scientific and medical challenges of our time,” said the study’s senior author, Jose Montoya, MD, professor of infectious diseases and geographic medicine. “Its symptoms often include not only overwhelming fatigue but also joint and muscle pain, incapacitating headaches, food intolerance, sore throat, enlargement of the lymph nodes, gastrointestinal problems, abnormal blood-pressure and heart-rate events, and hypersensitivity to light, noise or other sensations.”

The combination of symptoms can devastate a patient’s life for 10, 20 or even 30 years, said Montoya, who has been following 200 CFS patients for several years in an effort to identify the syndrome’s underlying mechanisms. He hopes to accelerate the development of more-effective treatments than now exist. (A new Stanford Medicine magazine story describes the study in more detail.)

“In addition to potentially providing the CFS-specific diagnostic biomarker we’ve been desperately seeking for decades, these findings hold the promise of identifying the area or areas of the brain where the disease has hijacked the central nervous system,” Montoya said.

“If you don’t understand the disease, you’re throwing darts blindfolded,” said Zeineh. “We asked ourselves whether brain imaging could turn up something concrete that differs between CFS patients’ and healthy people’s brains. And, interestingly, it did.”

The Stanford investigators compared brain images of 15 CFS patients chosen from the group Montoya has been following to those of 14 age- and sex-matched healthy volunteers with no history of fatigue or other conditions causing symptoms similar to those of CFS.

Three Key Findings

The analysis yielded three noteworthy results, the researchers said. First, an MRI showed that overall white-matter content of CFS patients’ brains, compared with that of healthy subjects’ brains, was reduced. The term “white matter” largely denotes the long, cablelike nerve tracts carrying signals among broadly dispersed concentrations of “gray matter.” The latter areas specialize in processing information, and the former in conveying the information from one part of the brain to another.

That finding wasn’t entirely unexpected, Zeineh said. CFS is thought to involve chronic inflammation, quite possibly as a protracted immunological response to an as-yet unspecified viral infection. Inflammation, meanwhile, is known to take a particular toll on white matter.

But a second finding was entirely unexpected. Using an advanced imaging technique — diffusion-tensor imaging, which is especially suited to assessing the integrity of white matter — Zeineh and his colleagues identified a consistent abnormality in a particular part of a nerve tract in the right hemisphere of CFS patients’ brains. This tract, which connects two parts of the brain called the frontal lobe and temporal lobe, is called the right arcuate fasciculus, and in CFS patients it assumed an abnormal appearance.

Furthermore, there was a fairly strong correlation between the degree of abnormality in a CFS patient’s right arcuate fasciculus and the severity of the patient’s condition, as assessed by performance on a standard psychometric test used to evaluate fatigue.

Right vs. Left

Although the right arcuate fasciculus’s function is still somewhat mysterious, its counterpart in the brain’s left hemisphere has been extensively explored. The left arcuate fasciculus connects two critical language areas of the left side of the brain termed Wernicke’s and Broca’s areas, which are gray-matter structures several centimeters apart. These two structures are important to understanding and generating speech, respectively. Right-handed people almost always have language organized in this fashion exclusively in the left side of the brain, but the precise side (left or right) and location of speech production and comprehension are not so clear-cut in left-handed people. (It’s sometimes said that every left-hander’s brain is a natural experiment.) So, pooling left- and right-handed people’s brain images can be misleading. And, sure enough, the finding of an abnormality in the right arcuate fasciculus, pronounced among right-handers, was murky until the two left-handed patients and four left-handed control subjects’ images were exempted from the analysis.

Bolstering these observations was the third finding: a thickening of the gray matter at the two areas of the brain connected by the right arcuate fasciculus in CFS patients, compared with controls. Its correspondence with the observed abnormality in the white matter joining them makes it unlikely that the two were chance findings, Zeineh said.

Although these results were quite robust, he said, they will need to be confirmed. “This study was a start,” he said. “It shows us where to look.” The Stanford scientists are in the planning stages of a substantially larger study.

 

Source: Stanford University Medical Center. “Brain abnormalities found in chronic fatigue patients.” ScienceDaily. ScienceDaily, 29 October 2014.  https://www.sciencedaily.com/releases/2014/10/141029084118.htm

 

Chronic fatigue syndrome patients had reduced activity in brain’s ‘reward center’

Chronic fatigue syndrome, a medical disorder characterized by extreme and ongoing fatigue with no other diagnosed cause, remains poorly understood despite decades of scientific study. Although researchers estimate that more than 1 million Americans are affected by this condition, the cause for chronic fatigue syndrome, a definitive way to diagnose it, and even its very existence remain in question. In a new study, researchers have found differing brain responses in people with this condition compared to healthy controls, suggesting an association between a biologic functional response and chronic fatigue syndrome.

The findings show that patients with chronic fatigue syndrome have decreased activation of an area of the brain known as the basal ganglia in response to reward. Additionally, the extent of this lowered activation was associated with each patient’s measured level of fatigue. The basal ganglia are at the base of the brain and are associated with a variety of functions, including motor activity and motivation. Diseases affecting basal ganglia are often associated with fatigue. These results shed more light on this mysterious condition, information that researchers hope may eventually lead to better treatments for chronic fatigue syndrome.

The study was conducted by Elizabeth R. Unger, James F. Jones, and Hao Tian of the Centers for Disease Control and Prevention (CDC), Andrew H. Miller and Daniel F. Drake of Emory University School of Medicine, and Giuseppe Pagnoni of the University of Modena and Reggio Emilia. An abstract of their study entitled, “Decreased Basal Ganglia Activation in Chronic Fatigue Syndrome Subjects is Associated with Increased Fatigue,” will be discussed at the meeting Experimental Biology 2012, being held April 21-25 at the San Diego Convention Center. The abstract is sponsored by the American Society for Investigative Pathology (ASIP), one of six scientific societies sponsoring the conference which last year attracted some 14,000 attendees.

More Fatigue, Less Activation

Dr. Unger says that she and her colleagues became curious about the role of the basal ganglia after previous studies by collaborators at Emory University showed that patients treated with interferon alpha, a common treatment for chronic hepatitis C and several other conditions, often experienced extreme fatigue. Further investigation into this phenomenon showed that basal ganglia activity decreased in patients who received this immune therapy. Since the fatigue induced by interferon alpha shares many characteristics with chronic fatigue syndrome, Unger and her colleagues decided to investigate whether the basal ganglia were also affected in this disorder.

The researchers recruited 18 patients with chronic fatigue syndrome, as well as 41 healthy volunteers with no symptoms of CFS. Each study participant underwent functional magnetic resonance imaging, a brain scan technique that measures activity in various parts of the brain by blood flow, while they played a simple card game meant to stimulate feelings of reward. The participants were each told that they’d win a small amount of money if they correctly guessed whether a preselected card was red or black. After making their choice, they were presented with the card while researchers measured blood flow to the basal ganglia during winning and losing hands.

The researchers showed that patients with chronic fatigue syndrome experienced significantly less change in basal ganglia blood flow between winning and losing than the healthy volunteers. When the researchers looked at scores for the Multidimensional Fatigue Inventory, a survey often used to document fatigue for chronic fatigue syndrome and various other conditions, they also found that the extent of a patient’s fatigue was tightly tied with the change in brain activity between winning and losing. Those with the most fatigue had the smallest change.

Results Suggest Role of Inflammation

Unger notes that the findings add to our understanding of biological factors that may play a role in chronic fatigue syndrome. “Many patients with chronic fatigue syndrome encounter a lot of skepticism about their illness,” she says. “They have difficulty getting their friends, colleagues, coworkers, and even some physicians to understand their illness. These results provide another clue into the biology of chronic fatigue syndrome.”

The study also suggests some areas of further research that could help scientists develop treatments for this condition in the future, she adds. Since the basal ganglia use the chemical dopamine as their major neurotransmitter, dopamine metabolism may play an important role in understanding and changing the course of this illness. Similarly, the difference in basal ganglia activation between the patients and healthy volunteers may be caused by inflammation, a factor now recognized as pivotal in a variety of conditions, ranging from heart disease to cancer.

Estimates from the CDC suggest that annual medical costs associated with chronic fatigue syndrome total about $14 billion in the United States. Annual losses to productivity because of lost work time range between $9 and $37 billion, with costs to individual households ranging between $8,000 and $20,000 per year.

 

Source: Federation of American Societies for Experimental Biology (FASEB). (2012, April 24). Chronic fatigue syndrome patients had reduced activity in brain’s ‘reward center’. ScienceDaily. Retrieved March 4, 2017 from https://www.sciencedaily.com/releases/2012/04/120424142109.htm

 

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)

 

Static and dynamic functional connectivity in patients with chronic fatigue syndrome: use of arterial spin labelling fMRI

Abstract:

Studies using arterial spin labelling (ASL) have shown that individuals with chronic fatigue syndrome (CFS) have decreased regional cerebral blood flow, which may be associated with changes in functional neural networks.

Indeed, recent studies indicate disruptions in functional connectivity (FC) at rest in chronically fatigued patients including perturbations in static FC (sFC), that is average FC at rest between several brain regions subserving neurocognitive, motor and affect-related networks.

Whereas sFC often provides information of functional network reorganization in chronic illnesses, investigations of temporal changes in functional connectivity between multiple brain areas may shed light on the dynamic characteristics of brain network activation associated with such maladies.

We used ASL fMRI in 19 patients with CFS and 15 healthy controls (HC) to examine both static and dynamic changes in FC among several a priori selected brain regions during a fatiguing cognitive task. HC showed greater increases than CFS in static FC (sFC) between insula and temporo-occipital structures and between precuneus and thalamus/striatum.

Furthermore, inferior frontal gyrus connectivity to cerebellum, occipital and temporal structures declined in HC but increased in CFS. Patients also showed lower dynamic FC (dFC) between hippocampus and right superior parietal lobule. Both sFC and dFC correlated with task-related fatigue increases.

These data provide the first evidence that perturbations in static and dynamic FC may underlie chronically fatigued patients’ report of task-induced fatigue. Further research will determine whether such changes in sFC and dFC are also characteristic for other fatigued individuals, including patients with chronic pain, cancer and multiple sclerosis.

© 2016 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

 

Source: Boissoneault J, Letzen J, Lai S, Robinson ME, Staud R. Static and dynamic functional connectivity in patients with chronic fatigue syndrome: use of arterial spin labelling fMRI. Clin Physiol Funct Imaging. 2016 Sep 28. doi: 10.1111/cpf.12393. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/27678090

 

 

Emotional conflict processing in adolescent chronic fatigue syndrome: A pilot study using functional magnetic resonance imaging

Abstract:

INTRODUCTION: Studies of neurocognition suggest that abnormalities in cognitive control contribute to the pathophysiology of chronic fatigue syndrome (CFS) in adolescents, yet these abnormalities remain poorly understood at the neurobiological level. Reports indicate that adolescents with CFS are significantly impaired in conflict processing, a primary element of cognitive control.

METHOD: In this study, we examine whether emotional conflict processing is altered on behavioral and neural levels in adolescents with CFS and a healthy comparison group. Fifteen adolescent patients with CFS and 24 healthy adolescent participants underwent functional magnetic resonance imaging (fMRI) while performing an emotional conflict task that involved categorizing facial affect while ignoring overlaid affect labeled words.

RESULTS: Adolescent CFS patients were less able to engage the left amygdala and left midposterior insula (mpINS) in response to conflict than the healthy comparison group. An association between accuracy interference and conflict-related reactivity in the amygdala was observed in CFS patients. A relationship between response time interference and conflict-related reactivity in the mpINS was also reported. Neural responses in the amygdala and mpINS were specific to fatigue severity.

CONCLUSIONS: These data demonstrate that adolescent CFS patients displayed deficits in emotional conflict processing. Our results suggest abnormalities in affective and cognitive functioning of the salience network, which might underlie the pathophysiology of adolescent CFS.

 

Source: Wortinger LA, Endestad T, Melinder AM, Øie MG, Sulheim D, Fagermoen E, Wyller VB. Emotional conflict processing in adolescent chronic fatigue syndrome: A pilot study using functional magnetic resonance imaging. J Clin Exp Neuropsychol. 2016 Sep 20:1-14. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/27647312

 

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)