Altered brain connectivity in Long Covid during cognitive exertion: a pilot study

Abstract:

Introduction: Debilitating Long-Covid symptoms occur frequently after SARS-COVID-19 infection.

Methods: Functional MRI was acquired in 10 Long Covid (LCov) and 13 healthy controls (HC) with a 7 Tesla scanner during a cognitive (Stroop color-word) task. BOLD time series were computed for 7 salience and 4 default-mode network hubs, 2 hippocampus and 7 brainstem regions (ROIs). Connectivity was characterized by the correlation coefficient between each pair of ROI BOLD time series. We tested for HC versus LCov differences in connectivity between each pair of the 20 regions (ROI-to-ROI) and between each ROI and the rest of the brain (ROI-to-voxel). For LCov, we also performed regressions of ROI-to-ROI connectivity with clinical scores.

Results: Two ROI-to-ROI connectivities differed between HC and LCov. Both involved the brainstem rostral medulla, one connection to the midbrain, another to a DM network hub. Both were stronger in LCov than HC. ROI-to-voxel analysis detected multiple other regions where LCov connectivity differed from HC located in all major lobes. Most, but not all connections, were weaker in LCov than HC. LCov, but not HC connectivity, was correlated with clinical scores for disability and autonomic function and involved brainstem ROI.

Discussion: Multiple connectivity differences and clinical correlations involved brainstem ROIs. Stronger connectivity in LCov between the medulla and midbrain may reflect a compensatory response. This brainstem circuit regulates cortical arousal, autonomic function and the sleep-wake cycle. In contrast, this circuit exhibited weaker connectivity in ME/CFS. LCov connectivity regressions with disability and autonomic scores were consistent with altered brainstem connectivity in LCov.

Source: Barnden L, Thapaliya K, Eaton-Fitch N, Barth M, Marshall-Gradisnik S. Altered brain connectivity in Long Covid during cognitive exertion: a pilot study. Front Neurosci. 2023 Jun 22;17:1182607. doi: 10.3389/fnins.2023.1182607. PMID: 37425014; PMCID: PMC10323677. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10323677/ (Full text)

Cognitive functioning in postural orthostatic tachycardia syndrome among different body positions: a prospective pilot study (POTSKog study)

Abstract:

Purpose: Approximately 96% of patients with postural orthostatic tachycardia syndrome (PoTS) report cognitive complaints. We investigated whether cognitive function is impaired during sitting and active standing in 30 patients with PoTS compared with 30 healthy controls (HCs) and whether it will improve with the counter manoeuvre of leg crossing.

Methods: In this prospective pilot study, patients with PoTS were compared to HCs matched for age, sex, and educational level. Baseline data included norepinephrine plasma levels, autonomic testing and baseline cognitive function in a seated position [the Montreal Cognitive Assessment, the Leistungsprüfsystem (LPS) subtests 1 and 2, and the Test of Attentional Performance (TAP)]. Cognitive functioning was examined in a randomized order in supine, upright and upright legs crossed position. The primary outcomes were the cognitive test scores between HCs and patients with PoTS at baseline testing, and among the different body positions.

Results: Patients with PoTS had impaired attention (TAP median reaction time) in the seated position and impaired executive functioning (Stroop) while standing compared with HC. Stroop was influenced by position (supine versus upright versus upright legs crossed) only in the PoTS group. Leg crossing did not result in an improvement in executive function. In patients with PoTS, there was a negative correlation of Stroop with norepinephrine plasma levels while standing.

Conclusion: Compared with HCs, PoTS participants showed impaired cognitive attention and executive function in the upright position that did not improve in the legs crossed position. Data provide further evidence for orthostatic cognitive deterioration in patients with PoTS.

Trial Registration Information: The study was registered at ClinicalTrials.gov (NCT03681080).

Source: Maier, A., Schopen, L., Thiel, J.C. et al. Cognitive functioning in postural orthostatic tachycardia syndrome among different body positions: a prospective pilot study (POTSKog study). Clin Auton Res (2023). https://doi.org/10.1007/s10286-023-00950-0 https://link.springer.com/article/10.1007/s10286-023-00950-0 (Full text)

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)

Reduced cardiac vagal modulation impacts on cognitive performance in chronic fatigue syndrome

Abstract:

BACKGROUND: Cognitive difficulties and autonomic dysfunction have been reported separately in patients with chronic fatigue syndrome (CFS). A role for heart rate variability (HRV) in cognitive flexibility has been demonstrated in healthy individuals, but this relationship has not as yet been examined in CFS. The objective of this study was to examine the relationship between HRV and cognitive performance in patients with CFS.

METHODS: Participants were 30 patients with CFS and 40 healthy controls; the groups were matched for age, sex, education, body mass index, and hours of moderate exercise/week. Questionnaires were used to obtain relevant medical and demographic information, and assess current symptoms and functional impairment. Electrocardiograms, perceived fatigue/effort and performance data were recorded during cognitive tasks. Between-group differences in autonomic reactivity and associations with cognitive performance were analysed.

RESULTS: Patients with CFS showed no deficits in performance accuracy, but were significantly slower than healthy controls. CFS was further characterized by low and unresponsive HRV; greater heart rate (HR) reactivity and prolonged HR-recovery after cognitive challenge. Fatigue levels, perceived effort and distress did not affect cognitive performance. HRV was consistently associated with performance indices and significantly predicted variance in cognitive outcomes.

CONCLUSIONS: These findings reveal for the first time an association between reduced cardiac vagal tone and cognitive impairment in CFS and confirm previous reports of diminished vagal activity.

 

Source: Beaumont A, Burton AR, Lemon J, Bennett BK, Lloyd A, Vollmer-Conna U. Reduced cardiac vagal modulation impacts on cognitive performance in chronic fatigue syndrome. PLoS One. 2012;7(11):e49518. doi: 10.1371/journal.pone.0049518. Epub 2012 Nov 14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498107/ (Full article)

 

Experimental evidence for interpretive but not attention biases towards somatic information in patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: This study tested whether CFS patients have an attentional information processing bias for illness-related information and a tendency to interpret ambiguous information in a somatic fashion.

DESIGN: 25 patients meeting research criteria for a diagnosis of CFS were compared to 24 healthy matched controls on a modified Stroop task and an ambiguous cues task.

METHOD: In the modified Stroop task, participants colour named a series of somatic, depressed and neutral words in order to ascertain whether the somatic words were more distracting to the CFS patients than the depressed and neutral words when compared to controls. In the ambiguous cues task, participants were presented with a tape-recorded list of 30 words including 15 ambiguous illness words (e.g., vein/vain) and 15 unambiguous words. For each word, they were asked to write down the first word that came into their head. A somatic bias score was obtained for each subject by summing the number of somatic responses to the ambiguous word cues.

RESULTS: Although CFS patients were significantly slower in colour naming all of the Stroop word categories than controls, there was no evidence for illness or depressed words creating greater interference than neutral words. However, on the ambiguous cues task, CFS patients made significantly more somatic interpretations than controls and this bias was significantly associated with the extent to which they currently reported symptoms.

CONCLUSION: CFS patients have an interpretive bias for somatic information which may play a part in the maintenance of the disorder by heightening patients’ experience of physical symptoms and helping to maintain their negative illness schemas. Although patients did not show an attentional bias in this study, this may be related to the methodology employed.

 

Source: Moss-Morris R, Petrie KJ. Experimental evidence for interpretive but not attention biases towards somatic information in patients with chronic fatigue syndrome. Br J Health Psychol. 2003 May;8(Pt 2):195-208. http://www.ncbi.nlm.nih.gov/pubmed/12804333

 

Underlying self-esteem in chronic fatigue syndrome

Abstract:

OBJECTIVE: It has been suggested that people with chronic fatigue syndrome (CFS) have low self-esteem; however, this is not necessarily apparent when self-esteem is measured overtly. This study is the first to investigate underlying self-esteem using information-processing measures and overtly administered measures of self-esteem with this population.

METHODS: The study comprised 68 participants (24 CFS, 24 healthy volunteers, and 20 chronic illness volunteers). A Self-Statements Questionnaire (SSQ) and an Emotional Stroop Test (EST) using neutral, positive, and negative trait words were administered.

RESULTS: Participants with CFS reported lower self-esteem than the two comparison groups on overt measures. Overt responses, however, did not fully account for the full extent of the interference effect from the negative word Stroop compared to the positive word Stroop.

CONCLUSION: In contrast to previous studies, participants with CFS reported lower levels of self-esteem on overt measures than two comparison groups. It is suggested, however, that the extent to which participants reported low self-esteem did not fully reflect their underlying low self-esteem and that this may result from the use of rigidly held defence mechanisms. Further use of information-processing measures, in contrast to relying only on self-report measures, is advocated for future research.

Copyright 2002 Elsevier Science Inc

 

Source: Creswell C, Chalder T. Underlying self-esteem in chronic fatigue syndrome. J Psychosom Res. 2002 Sep;53(3):755-61. http://www.ncbi.nlm.nih.gov/pubmed/12217449

 

Perception of cognitive performance in patients with chronic fatigue syndrome

Abstract:

This study examined discrepancies between perceived and actual performance by patients with chronic fatigue syndrome (CFS) confronted with a challenging cognitive task. Before and after completing a modified version of the Stroop task, 40 patients and 40 healthy control participants estimated their own performance and the performance that would normally be achieved by someone of equal age and education level. After correcting for differences between the groups in depression, we found no differences in actual performance on the Stroop. However, patients with CFS consistently underestimated their performance relative to normal performance. This difference was observed for both depressed and nondepressed subgroups of patients, persisted after adjusting the results for depression, and correlated with patients’ ratings of the mental effort and fatigue evoked by the task. The results are discussed in light of cognitive models of CFS that suggest the setting of impossibly high standards of personal performance may contribute to the dynamism of this disease.

 

Source: Metzger FA, Denney DR. Perception of cognitive performance in patients with chronic fatigue syndrome. Ann Behav Med. 2002 Spring;24(2):106-12. http://www.ncbi.nlm.nih.gov/pubmed/12054315

 

Quality of attention in chronic fatigue syndrome: subjective reports of everyday attention and cognitive difficulty, and performance on tasks of focused attention

Abstract:

Patients with chronic fatigue syndrome (also known as post-viral fatigue syndrome or myalgic encephalomyelitis) commonly report cognitive difficulties concerning attention, concentration and memory. In this study, patients were compared with matched controls on two questionnaires which assess subjective difficulties with attention and general cognitive functioning, and on two tasks requiring focused attention.

Patients reported significantly greater difficulty with attention on the Everyday Attention Questionnaire and more cognitive symptoms on the Profile of Fatigue-Related Symptoms. The objective tests did not clearly indicate a deficit in patients’ focused attention; patients tended to perform less well on the Embedded Figures Test and the Stroop Colour-Word Interference Test, but these differences were not significant.

There was, however, evidence of psychomotor retardation, with patients having longer response times for word reading and colour naming in the Stroop test. Difficulties in interpreting findings for both subjective and objective cognitive measures are discussed.

 

Source: Ray C, Phillips L, Weir WR. Quality of attention in chronic fatigue syndrome: subjective reports of everyday attention and cognitive difficulty, and performance on tasks of focused attention. Br J Clin Psychol. 1993 Sep;32 ( Pt 3):357-64. http://www.ncbi.nlm.nih.gov/pubmed/8251968