resting state brain connectivity – American ME and CFS Society

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

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.

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

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)

Intrinsic Functional Hypoconnectivity in Core Neurocognitive Networks Suggests Central Nervous System Pathology in Patients with Myalgic Encephalomyelitis: A Pilot Study

Abstract:

Exact low resolution electromagnetic tomography (eLORETA) was recorded from nineteen EEG channels in nine patients with myalgic encephalomyelitis (ME) and 9 healthy controls to assess current source density and functional connectivity, a physiological measure of similarity between pairs of distributed regions of interest, between groups. Current source density and functional connectivity were measured using eLORETA software.

We found significantly decreased eLORETA source analysis oscillations in the occipital, parietal, posterior cingulate, and posterior temporal lobes in Alpha and Alpha-2. For connectivity analysis, we assessed functional connectivity within Menon triple network model of neuropathology.

We found support for all three networks of the triple network model, namely the central executive network (CEN), salience network (SN), and the default mode network (DMN) indicating hypo-connectivity in the Delta, Alpha, and Alpha-2 frequency bands in patients with ME compared to controls.

In addition to the current source density resting state dysfunction in the occipital, parietal, posterior temporal and posterior cingulate, the disrupted connectivity of the CEN, SN, and DMN appears to be involved in cognitive impairment for patients with ME. This research suggests that disruptions in these regions and networks could be a neurobiological feature of the disorder, representing underlying neural dysfunction.

Source: Zinn ML, Zinn MA, Jason LA. Intrinsic Functional Hypoconnectivity in Core Neurocognitive Networks Suggests Central Nervous System Pathology in Patients with Myalgic Encephalomyelitis: A Pilot Study. Appl Psychophysiol Biofeedback. 2016 Sep;41(3):283-300. doi: 10.1007/s10484-016-9331-3. https://www.ncbi.nlm.nih.gov/pubmed/26869373

Abnormal resting state functional connectivity in patients with chronic fatigue syndrome: an arterial spin-labeling fMRI study

Abstract:

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder characterized by severe fatigue and neurocognitive dysfunction. Recent work from our laboratory and others utilizing arterial spin labeling functional magnetic resonance imaging (ASL) indicated that ME/CFS patients have lower resting state regional cerebral blood flow (rCBF) in several brain areas associated with memory, cognitive, affective, and motor function. This hypoperfusion may underlie ME/CFS pathogenesis and may result in alterations of functional relationships between brain regions. The current report used ASL to compare functional connectivity of regions implicated in ME/CFS between patients and healthy controls (HC).

METHODS: Participants were 17 ME/CFS patients (Mage=48.88years, SD=12) fulfilling the 1994 CDC criteria and 17 age/sex matched HC (Mage=49.82years, SD=11.32). All participants underwent T1-weighted structural MRI as well as a 6-min pseudo-continuous arterial spin labeling (pCASL) sequence, which quantifies CBF by magnetically labeling blood as it enters the brain. Imaging data were preprocessed using SPM 12 and ASL tbx, and seed-to-voxel functional connectivity analysis was conducted using the CONN toolbox. All effects noted below are significant at p<0.05 with cluster-wise FDR correction for multiple comparisons.

RESULTS: ME/CFS patients demonstrated greater functional connectivity relative to HC in bilateral superior frontal gyrus, ACC, precuneus, and right angular gyrus to regions including precuneus, right postcentral gyrus, supplementary motor area, posterior cingulate gyrus, and thalamus. In contrast, HC patients had greater functional connectivity than ME/CFS in ACC, left parahippocampal gyrus, and bilateral pallidum to regions including right insula, right precentral gyrus, and hippocampus. Connectivity of the left parahippocampal gyrus correlated strongly with overall clinical fatigue of ME/CFS patients.

CONCLUSION: This is the first ASL based connectivity analysis of patients with ME/CFS. Our results demonstrate altered functional connectivity of several regions associated with cognitive, affective, memory, and higher cognitive function in ME/CFS patients. Connectivity to memory related brain areas (parahippocampal gyrus) was correlated with clinical fatigue ratings, providing supporting evidence that brain network abnormalities may contribute to ME/CFS pathogenesis.

Source: Boissoneault J, Letzen J, Lai S, O’Shea A, Craggs J, Robinson ME, Staud R. Abnormal resting state functional connectivity in patients with chronic fatigue syndrome: an arterial spin-labeling fMRI study. Magn Reson Imaging. 2016 May;34(4):603-8. doi: 10.1016/j.mri.2015.12.008. Epub 2015 Dec 18. https://www.ncbi.nlm.nih.gov/pubmed/26708036

Altered resting-state functional connectivity in women with chronic fatigue syndrome

Abstract:

The biological underpinnings of the psychological factors characterizing chronic fatigue syndrome (CFS) have not been extensively studied. Our aim was to evaluate alterations of resting-state functional connectivity in CFS patients.

Participants comprised 18 women with CFS and 18 age-matched female healthy controls who were recruited from the local community. Structural and functional magnetic resonance images were acquired during a 6-min passive-viewing block scan.

Posterior cingulate cortex seeded resting-state functional connectivity was evaluated, and correlation analyses of connectivity strength were performed. Graph theory analysis of 90 nodes of the brain was conducted to compare the global and local efficiency of connectivity networks in CFS patients with that in healthy controls.

The posterior cingulate cortex in CFS patients showed increased resting-state functional connectivity with the dorsal and rostral anterior cingulate cortex. Connectivity strength of the posterior cingulate cortex to the dorsal anterior cingulate cortex significantly correlated with the Chalder Fatigue Scale score, while the Beck Depression Inventory (BDI) score was controlled. Connectivity strength to the rostral anterior cingulate cortex significantly correlated with the Chalder Fatigue Scale score. Global efficiency of the posterior cingulate cortex was significantly lower in CFS patients, while local efficiency showed no difference from findings in healthy controls.

The findings suggest that CFS patients show inefficient increments in resting-state functional connectivity that are linked to the psychological factors observed in the syndrome.

Source: Kim BH, Namkoong K, Kim JJ, Lee S, Yoon KJ, Choi M, Jung YC. Altered resting-state functional connectivity in women with chronic fatigue syndrome. Psychiatry Res. 2015 Dec 30;234(3):292-7. doi: 10.1016/j.pscychresns.2015.10.014. Epub 2015 Oct 23. https://www.ncbi.nlm.nih.gov/pubmed/26602611

Abnormal Resting-State Functional Connectivity in Patients with Chronic Fatigue Syndrome: Results of Seed and Data-Driven Analyses

Abstract:

Although altered resting-state functional connectivity (FC) is a characteristic of many chronic pain conditions, it has not yet been evaluated in patients with chronic fatigue. Our objective was to investigate the association between fatigue and altered resting-state FC in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Thirty-six female subjects, 19 ME/CFS and 17 healthy controls, completed a fatigue inventory before undergoing functional magnetic resonance imaging. Two methods, (1) data driven and (2) model based, were used to estimate and compare the intraregional FC between both groups during the resting state (RS).

The first approach using independent component analysis was applied to investigate five RS networks: the default mode network, salience network (SN), left frontoparietal networks (LFPN) and right frontoparietal networks, and the sensory motor network (SMN).

The second approach used a priori selected seed regions demonstrating abnormal regional cerebral blood flow (rCBF) in ME/CFS patients at rest. In ME/CFS patients, Method-1 identified decreased intrinsic connectivity among regions within the LFPN. Furthermore, the FC of the left anterior midcingulate with the SMN and the connectivity of the left posterior cingulate cortex with the SN were significantly decreased.

For Method-2, five distinct clusters within the right parahippocampus and occipital lobes, demonstrating significant rCBF reductions in ME/CFS patients, were used as seeds. The parahippocampal seed and three occipital lobe seeds showed altered FC with other brain regions. The degree of abnormal connectivity correlated with the level of self-reported fatigue.

Our results confirm altered RS FC in patients with ME/CFS, which was significantly correlated with the severity of their chronic fatigue.

Source: Gay CW, Robinson ME, Lai S, O’Shea A, Craggs JG, Price DD, Staud R. Abnormal Resting-State Functional Connectivity in Patients with Chronic Fatigue Syndrome: Results of Seed and Data-Driven Analyses. Brain Connect. 2016 Feb;6(1):48-56. doi: 10.1089/brain.2015.0366. Epub 2015 Nov 10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744887/ (Full article)