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

Abstract

Funding information The Judith Jane Mason FoundationUnrefreshing 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 T 1 weighted (MT-T1w) intensities, and T 1 weighted (T1w) and T 2 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, P FWE < 0.05) and between PSQI and T1w intensities (P FWE < 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. Sleep plays an important role in human health and well-being, with its recuperative, restorative, and learning consolidation properties. 4,5Unrefreshing sleep is a hallmark of ME/CFS that causes patients to wake up feeling tired even after extended periods of sleep, to experience excessive daytime sleepiness, and to have difficulty falling asleep and staying asleep. Therefore, unrefreshing sleep results at least in worsening fatigue symptoms and adds to the 'illness burden' in CFS patients. 6 Roughly 91% of CFS patients report unrefreshing sleep regardless of adequate sleep duration. 7 The effect of unrefreshing sleep is of importance in CFS aetiology because sleep disturbance can cause fatigue, myalgia, and poor attention. 8 A recent path analysis study, exploring the interrelationship of different symptoms in CFS, found that poor sleep quality directly impacted on

Poor self‐reported sleep quality and health‐related quality of life in patients with chronic fatigue syndrome/myalgic encephalomyelitis

“…Sleep disturbances have been frequently described in CSF/ME populations (Buckwald, Pascualy, Bombardier, & Kith, ; Jackson & Bruck, ; Morriss et al., ; Shan et al., ). The symptoms are particularly relevant, as the presence of unrefreshing sleep is included in all the versions of the diagnostic criteria for CFS/ME (Carruthers et al., , ; Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, ; Fukuda et al., ).…”

“…Sleep disturbances have been frequently described in CSF/ME populations (Buckwald, Pascualy, Bombardier, & Kith, 1994;Jackson & Bruck, 2012;Morriss et al, 1993;Shan et al, 2017). Various tools are available for the study of sleep disturbances, including subjective assessment questionnaires such as the DePaul Symptom Questionnaire, the Sleep Assessment Questionnaire and the PSQI.…”

Reduced heart rate variability predicts fatigue severity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis

“…Previous studies have provided strong evidence for autonomic nervous system (ANS) involvement in individuals with CFS/ME, including perturbations in the structure and function of brain (reflected by fMRI testing) [4][5][6][7][8][9][10][11]. In brief, cerebral blood flow volume changes and reduced HRV may lead to greater exacerbation of ANS symptoms in individuals with CFS/ME.…”

Transient Receptor Potential Ion Channels in the Etiology and Pathomechanism of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

“…aging results indicate that TRPM3 in the CNS participates as a Ca 2+ -permeable and sphingosine-activated channel in oligodendrocyte differentiation and CNS WM myelination [34]. Indeed, multiple and widely distributed WM abnormalities are observed in CFS/ME patients, including myelination deficits in the midbrain [25] [26], progressive WM atrophy in inferior fronto-occipital fasciculus [27], and association of disrupted sleep with WM atrophy in the medial frontal brain [28].…”

“…Interestingly, neuroimaging studies in CFS/ME patients have demonstrated changes in the brain structural connections and alterations in hemodynamic response to cognitive tasks [25] [26] [27] [28]. The consistent observations of wider regions with greater blood oxygenation level dependent activation in CFS/ME patients [29] [30] [31] could potentially be explained by disrupted neurovascular coupling, which is dependent on Ca 2+ signaling in astrocytes [32].…”