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)

 

Increasing orthostatic stress impairs neurocognitive functioning in chronic fatigue syndrome with postural tachycardia syndrome

Abstract:

CFS (chronic fatigue syndrome) is commonly co-morbid with POTS (postural tachycardia syndrome). Individuals with CFS/POTS experience unrelenting fatigue, tachycardia during orthostatic stress and ill-defined neurocognitive impairment, often described as ‘mental fog’. We hypothesized that orthostatic stress causes neurocognitive impairment in CFS/POTS related to decreased CBFV (cerebral blood flow velocity).

A total of 16 CFS/POTS and 20 control subjects underwent graded tilt table testing (at 0, 15, 30, 45, 60 and 75°) with continuous cardiovascular, cerebrovascular, and respiratory monitoring and neurocognitive testing using an n-back task at each angle. The n-back task tests working memory, concentration, attention and information processing. The n-back task imposes increasing cognitive challenge with escalating (0-, 1-, 2-, 3- and 4-back) difficulty levels. Subject dropout due to orthostatic presyncope at each angle was similar between groups.

There were no n-back accuracy or RT (reaction time) differences between groups while supine. CFS/POTS subjects responded less correctly during the n-back task test and had greater nRT (normalized RT) at 45, 60 and 75°. Furthermore, at 75° CFS/POTS subjects responded less correctly and had greater nRT than controls during the 2-, 3- and 4-back tests. Changes in CBFV were not different between the groups and were not associated with n-back task test scores.

Thus we conclude that increasing orthostatic stress combined with a cognitive challenge impairs the neurocognitive abilities of working memory, accuracy and information processing in CFS/POTS, but that this is not related to changes in CBFV. Individuals with CFS/POTS should be aware that orthostatic stress may impair their neurocognitive abilities.

 

Source: Ocon AJ, Messer ZR, Medow MS, Stewart JM. Increasing orthostatic stress impairs neurocognitive functioning in chronic fatigue syndrome with postural tachycardia syndrome. Clin Sci (Lond). 2012 Mar;122(5):227-38. doi: 10.1042/CS20110241. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368269/ (Full article)

 

Cognitive functioning in chronic fatigue syndrome: a meta-analysis

Abstract:

BACKGROUND: Cognitive problems are commonly reported in persons with chronic fatigue syndrome (CFS) and are one of the most disabling symptoms of this condition. A number of cognitive deficits have been identified, although the findings are inconsistent and hindered by methodological differences. The current study therefore conducted a meta-analysis of research examining cognitive functioning in persons with CFS in order to identify the pattern and magnitude of any deficits that are associated with this condition.

METHOD: A comprehensive search of the PubMed and PsycINFO databases for studies that examined cognitive functioning in CFS between 1988 and 2008 identified 50 eligible studies. Weighted Cohen’s d effect sizes, 95% confidence intervals and fail-safe Ns were calculated for each cognitive score.

RESULTS: Evidence of cognitive deficits in persons with CFS was found primarily in the domains of attention, memory and reaction time. Deficits were not apparent on tests of fine motor speed, vocabulary, reasoning and global functioning.

CONCLUSIONS: Persons with CFS demonstrate moderate to large impairments in simple and complex information processing speed and in tasks requiring working memory over a sustained period of time.

Comment in: Letter to the Editor: Plausible explanations for neurocognitive deficits in ME/CFS, aggravation of neurocognitive impairment induced by exertion. [Psychol Med. 2010]

 

Source: Cockshell SJ, Mathias JL. Cognitive functioning in chronic fatigue syndrome: a meta-analysis. Psychol Med. 2010 Aug;40(8):1253-67. doi: 10.1017/S0033291709992054. Epub 2010 Jan 5. https://www.ncbi.nlm.nih.gov/pubmed/20047703

 

Neuropsychological performance in persons with chronic fatigue syndrome: results from a population-based study

Abstract:

OBJECTIVE: To examine the neuropsychological function characterized in subjects with chronic fatigue syndrome (CFS) at the same time controlling for relevant confounding factors. CFS is associated with symptoms of neuropsychological dysfunction. Objective measures of neuropsychological performance have yielded inconsistent results possibly due to sample selection bias, diagnostic heterogeneity, comorbid psychiatric disorders, and medication usage.

METHOD: CFS subjects (n = 58) and well controls (n = 104) from a population-based sample were evaluated, using standardized symptom severity criteria. Subjects who had major psychiatric disorders or took medications known to influence cognition were excluded. Neuropsychological function was measured using the Cambridge Neuropsychological Test Automated Battery (CANTAB).

RESULTS: Compared with controls, CFS subjects exhibited significant decreases in motor speed as measured in the simple and five-choice movement segments of the CANTAB reaction time task. CFS subjects also exhibited alterations in working memory as manifested by a less efficient search strategy on the spatial working memory task, fewer % correct responses on the spatial recognition task, and prolonged latency to a correct response on the pattern recognition task. A significantly higher percentage of CFS subjects versus controls exhibited evidence of neuropsychological impairment (defined by performance 1 standard deviation below the CANTAB normative mean) in tasks of motor speed and spatial working memory. Impairment in CFS subjects versus control subjects ranged from 20% versus 4.8% in five-choice movement time (p = .002) to 27.8% versus 10.6% in search strategy on the spatial working memory task (p = .006).

CONCLUSIONS: These results confirm and quantify alterations in motor speed and working memory in CFS subjects independent of comorbid psychiatric disease and medication usage.

 

Source: Majer M, Welberg LA, Capuron L, Miller AH, Pagnoni G, Reeves WC. Neuropsychological performance in persons with chronic fatigue syndrome: results from a population-based study. Psychosom Med. 2008 Sep;70(7):829-36. doi: 10.1097/PSY.0b013e31817b9793. Epub 2008 Jul 7. https://www.ncbi.nlm.nih.gov/pubmed/18606722

 

Probing the working memory system in chronic fatigue syndrome: a functional magnetic resonance imaging study using the n-back task

Abstract:

OBJECTIVE: Up to 90% of patients with chronic fatigue syndrome (CFS) report substantial cognitive difficulties. However, objective evidence supporting these claims is inconsistent. The present functional magnetic resonance imaging study examined the neural correlates of working memory in patients with CFS compared with controls.

METHODS: Seventeen patients with CFS and 12 healthy control subjects were scanned while performing a parametric version of the n-back task (0-, 1-, 2-, and 3-back).

RESULTS: Both groups performed comparably well and activated the verbal working memory network during all task levels. However, during the 1-back condition, patients with CFS showed greater activation than control subjects in medial prefrontal regions, including the anterior cingulate gyrus. Conversely, on the more challenging conditions, patients with CFS demonstrated reduced activation in dorsolateral prefrontal and parietal cortices. Furthermore, on the 2- and 3-back conditions, patients but not control subjects significantly activated a large cluster in the right inferior/medial temporal cortex. Trend analyses of task load demonstrated statistically significant differences in brain activation between the two groups as the demands of the task increased.

CONCLUSIONS: These results suggest that patients with CFS show both quantitative and qualitative differences in activation of the working memory network compared with healthy control subjects. It remains to be determined whether these findings stay stable after successful treatment.

 

Source: Caseras X, Mataix-Cols D, Giampietro V, Rimes KA, Brammer M, Zelaya F, Chalder T, Godfrey EL. Probing the working memory system in chronic fatigue syndrome: a functional magnetic resonance imaging study using the n-back task. Psychosom Med. 2006 Nov-Dec;68(6):947-55. Epub 2006 Nov 1. https://www.ncbi.nlm.nih.gov/pubmed/17079703

 

Working memory deficits in chronic fatigue syndrome: differentiating between speed and accuracy of information processing

Abstract:

To examine the relative influence of speed of information processing versus working memory ability, CFS participants with psychiatric comorbidity (CFS-Psych) and CFS without a psychiatric history (CFS-noPsych) were examined on tests of visual and auditory processing speed and visual and auditory working memory.

Compared to healthy controls (HC) and a group of participants with rheumatoid arthritis (RA), the CFS-noPsych group displayed significantly reduced performance on tests of information processing speed, but not on tests of working memory. No significant differences were observed between the CFS-Psych group and any other group in the study. The implications of group heterogeneity on the understanding of cognitive impairment in CFS are discussed.

 

Source: Deluca J, Christodoulou C, Diamond BJ, Rosenstein ED, Kramer N, Natelson BH. Working memory deficits in chronic fatigue syndrome: differentiating between speed and accuracy of information processing. J Int Neuropsychol Soc. 2004 Jan;10(1):101-9. http://www.ncbi.nlm.nih.gov/pubmed/14751012

 

Working memory deficits associated with chronic fatigue syndrome

Abstract:

Cognitive impairments are among the most frequently reported and least investigated components of the chronic fatigue syndrome (CFS). As part of a multifaceted study of the CFS, the present study investigated the cognitive functioning of chronic fatigue patients.

The performance of 20 CFS patients was compared to that of controls (N = 20) on 4 tests of working memory (WM). Digit Span Forward was used to assess the storage capacity of WM. Multiple aspects of central executive functioning were assessed using several standard measures: Digit Span Backward, and Trails A and Trails B. More recently developed measures of WM were used to assess control of processing under temporal demands (working memory task) and resistance to interference (a sustained attention task).

Deficits were restricted to more demanding tasks, requiring resistance to interference and efficient switching between processing routines. The overall results clearly implicate deficits in the control aspects of central executive function in CFS.

 

Source: Dobbs BM, Dobbs AR, Kiss I. Working memory deficits associated with chronic fatigue syndrome. J Int Neuropsychol Soc. 2001 Mar;7(3):285-93. http://www.ncbi.nlm.nih.gov/pubmed/11311029

 

Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression

Abstract:

OBJECTIVES: Patients with chronic fatigue syndrome complain of physical and mental fatigue that is worsened by exertion. It was predicted that the cognitive and motor responses to vigorous exercise in patients with chronic fatigue syndrome would differ from those in depressed and healthy controls.

METHODS: Ten patients with chronic fatigue syndrome, 10 with depressive illness, and 10 healthy controls completed cognitive and muscle strength testing before and after a treadmill exercise test. Measures of cardiovascular functioning and perceived effort, fatigue, and mood were taken during each stage of testing.

RESULTS: Depressed patients performed worst on cognitive tests at baseline. During the treadmill test, patients with chronic fatigue syndrome had higher ratings of perceived effort and fatigue than both control groups, whereas patients with depression reported lower mood. After exertion, patients with chronic fatigue syndrome showed a greater decrease than healthy controls on everyday tests of focused (p=0.02) and sustained (p=0.001) attention, as well as greater deterioration than depressed patients on the focused attention task (p=0.03). No between group differences were found in cardiovascular or symptom measures taken during the cognitive testing.

CONCLUSIONS: Patients with chronic fatigue syndrome show a specific sensitivity to the effects of exertion on effortful cognitive functioning. This occurs despite subjective and objective evidence of effort allocation in chronic fatigue syndrome, suggesting that patients have reduced working memory capacity, or a greater demand to monitor cognitive processes, or both. Further insight into the pathophysiology of the core complaints in chronic fatigue syndrome is likely to be realised by studying the effects of exercise on other aspects of everyday functioning.

 

Source: Blackwood SK, MacHale SM, Power MJ, Goodwin GM, Lawrie SM. Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression. J Neurol Neurosurg Psychiatry. 1998 Oct;65(4):541-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170292/ (Full study)

 

Attention and verbal learning in patients with chronic fatigue syndrome

Abstract:

Former neuropsychological studies with Chronic Fatigue Syndrome (CFS) patients evaluated a broad range of cognitive functions. Several, but not all, reported subtle attentional and memory impairments suggesting possible mild cerebral involvement.

In this study, a battery of attentional tests and a verbal memory task were administered to 20 CFS patients and 22 healthy controls (HC) in order to clarify the specific nature of attention and memory impairment in these patients. The results provide evidence for attentional dysfunction in patients with CFS as compared to HC.

CFS patients performed more poorly on a span test measuring attentional capacity and working memory. Speeded attentional tasks with a more complex element of memory scanning and divided attention seem to be a sensitive measure of reduced attentional capacity in these patients.

Focused attention, defined as the ability to attend to a single stimulus while ignoring irrelevant stimuli, appears not to be impaired. CFS patients were poorer on recall of verbal information across learning trials, and poor performance on delayed recall may be due to poor initial learning and not only to a retrieval failure.

 

Source: Michiels V, Cluydts R, Fischler B. Attention and verbal learning in patients with chronic fatigue syndrome. J Int Neuropsychol Soc. 1998 Sep;4(5):456-66. http://www.ncbi.nlm.nih.gov/pubmed/9745235

 

Cognitive slowing and working memory difficulties in chronic fatigue syndrome

Abstract:

OBJECTIVE: Patients with chronic fatigue syndrome (CFS) commonly report problems with attention, memory, learning, and speed of cognitive processing. This study attempted to evaluate these complaints using objective test criteria.

METHOD: A test battery composed of six tests assessing these cognitive functions was given on two consecutive days. Twenty CFS patients were compared with 20 healthy control subjects and 14 patients with a history of major depression or dysthymia matched by age, intelligence, education level, and sex.

RESULTS: Compared with control subjects, CFS patients consistently scored lower on tests in which motor and cognitive processing speeds were a critical factor, eg, reaction-time tasks. They also had more difficulty on working-memory tests in which rapid cognitive processing speed is also an important factor. The effort made on the first day of testing did not result in a decline in cognitive function on the following day. CFS patients did not qualify as having affective disorder by several different diagnostic criteria. Nonetheless, CFS patients’ test performances did not differ from patients with a history of major depression or dysthymia.

CONCLUSIONS: It is concluded that, although CFS and major depression and dysthymia have distinct clinical features, these disorders have slowed motor and cognitive processing speed in common.

Comment in: Cognitive slowing in chronic fatigue syndrome (CFS) [Psychosom Med. 1997]

 

Source: Marshall PS, Forstot M, Callies A, Peterson PK, Schenck CH. Cognitive slowing and working memory difficulties in chronic fatigue syndrome. Psychosom Med. 1997 Jan-Feb;59(1):58-66. http://www.ncbi.nlm.nih.gov/pubmed/9021867