The intraparietal sulcus governs multisensory integration of audiovisual information based on task difficulty.

Object recognition benefits maximally from multimodal sensory input when stimulus presentation is noisy, or degraded. Whether this advantage can be attributed specifically to the extent of overlap in object-related information, or rather, to object-unspecific enhancement due to the mere presence of additional sensory stimulation, remains unclear. Further, the cortical processing differences driving increased multisensory integration (MSI) for degraded compared with clear information remain poorly understood. Here, two consecutive studies first compared behavioral benefits of audio-visual overlap of object-related information, relative to conditions where one channel carried information and the other carried noise. A hierarchical drift diffusion model indicated performance enhancement when auditory and visual object-related information was simultaneously present for degraded stimuli. A subsequent fMRI study revealed visual dominance on a behavioral and neural level for clear stimuli, while degraded stimulus processing was mainly characterized by activation of a frontoparietal multisensory network, including IPS. Connectivity analyses indicated that integration of degraded object-related information relied on IPS input, whereas clear stimuli were integrated through direct information exchange between visual and auditory sensory cortices. These results indicate that the inverse effectiveness observed for identification of degraded relative to clear objects in behavior and brain activation might be facilitated by selective recruitment of an executive cortical network which uses IPS as a relay mediating crossmodal sensory information exchange.

Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome.

Glucocorticoid receptor (GR) function may have aetiopathogenic significance in chronic fatigue syndrome (CFS), via its essential role in mediating inflammatory responses as well as in hypothalamic-pituitary-adrenal axis regulation. GR function can be estimated ex vivo by measuring dexamethasone (dex) modulation of cytokine response to lipopolysaccharide (LPS), and in vivo using the impact of dex on cortisol levels. This study aimed to compare the GR function between CFS (n = 48), primary Sjögren's syndrome (a disease group control) (n = 27), and sedentary healthy controls (HCs) (n = 20), and to investigate its relationship with clinical measures. In the GR ex vivo response assay, whole blood was diluted and incubated with LPS (to stimulate cytokine production), with or without 10 or 100 nanomolar concentrations of dex. Cytometric bead array (CBA) and flow cytometry enabled quantification of cytokine levels (TNFα, interleukin- (IL-) 6, and IL-10) in the supernatants. In the in vivo response assay, five plasma samples were taken for determination of total cortisol concentration using ELISA at half-hourly intervals on two consecutive mornings separated by ingestion of 0.5 mg of dex at 11 pm. The association of the data from the in vivo and ex vivo analyses with reported childhood adversity was also examined. CFS patients had reduced LPS-induced IL-6 and TNFα production compared to both control groups and reduced suppression of TNFα by the higher dose of dex compared to HCs. Cortisol levels, before or after dex, did not differ between CFS and HCs. Cortisol levels were more variable in CFS than HCs. In the combined group (CFS plus HC), cortisol concentrations positively and ex vivo GR function (determined by dex-mediated suppression of IL-10) negatively correlated with childhood adversity score. The results do not support the hypothesis that GR dysregulation is aetiopathogenic in CFS and suggest that current and future endocrine cross-sectional studies in CFS may be vulnerable to the confounding influence of childhood trauma which is likely increased by comorbid depression.

Empathy in individuals clinically at risk for psychosis: brain and behaviour.

BACKGROUND: Empathy is a basic human ability, and patients with schizophrenia show dysfunctional empathic abilities on the behavioural and neural level. AIMS: These dysfunctions may precede the onset of illness; thus, it seems mandatory to examine the empathic abilities in individuals at clinical high risk for psychosis. METHOD: Using functional magnetic resonance imaging, we measured 15 individuals at clinical high risk of psychosis (CHR group) and compared their empathy performance with 15 healthy volunteers and 15 patients with schizophrenia. RESULTS: Behavioural data analysis indicated no significant deficit in the CHR group. Functional data analysis revealed hyperactivation in a frontotemporoparietal network including the amygdala in the CHR group compared with the other two groups. CONCLUSIONS: Despite normal behavioural performance, the CHR group activated the neural empathy network differently and specifically showed hyperactivation in regions critical for emotion processing. This could suggest a compensatory mechanism reflecting emotional hypersensitivity or dysfunctional emotion regulation. Further investigations should clarify the role of these neural alterations for development and exacerbation of psychosis.

Effective connectivity of the human cerebellum during visual attention.

Insights from both lesion and neuroimaging studies increasingly substantiate the view that the human cerebellum not only serves motor control but also supports various cognitive processes. Higher cognitive functions like working memory or executive control have been associated with the phylogenetically younger parts of the cerebellum, crus I and crus II. Functional connectivity studies corroborate this notion as activation of the cerebellum correlates with activity in numerous areas of the cerebral cortex. Moreover, these cerebrocerebellar loops were shown to be topographically organized. We used an attention-to-motion paradigm to elaborate on the effective connectivity of cerebellar crus I during visual attention. Psychophysiological interaction analyses demonstrated enhanced connectivity of the cerebellum--during attention--with dorsal visual stream regions including posterior parietal cortex (PPC) and left secondary visual cortex (V5). Dynamic causal modeling revealed a modulation of the connections from V5 to PPC and from crus I to V5 by attention. Remarkably, the influence which V5 exerted on PPC was reduced during attention, resulting in a suppression of the sensitivity of PPC to bottom-up information. Moreover, the sensitivity of V5 populations to inputs from crus I was increased under attention. This might underscore the presumed role of the cerebellum as a state estimator that provides hierarchically lower regions (V5) with top-down predictions, which in turn might be based on endogenous inputs from PPC to the cerebellum. These results are in line with formulations of attention in predictive coding, where attention increases the precision or sensitivity of hierarchically lower neuronal populations that may encode prediction error.

Negative BOLD response in the hippocampus during short-term spatial memory retrieval.

A parieto-medial temporal pathway is thought to underlie spatial navigation in humans. fMRI was used to assess the role of this pathway, including the hippocampus, in the cognitive processes likely to underlie navigation based on environmental cues. Participants completed a short-term spatial memory task in virtual space, which required no navigation but involved the recognition of a target location from a foil location based on environmental landmarks. The results showed that spatial memory retrieval based on environmental landmarks was indeed associated with increased signal in regions of the parieto-medial temporal pathway, including the superior parietal cortex, the retrosplenial cortex, and the lingual gyrus. However, the hippocampus demonstrated a signal decrease below the fixation baseline during landmark-based retrieval, whereas there was no signal change from baseline during retrieval based on viewer position. In a discussion of the origins of such negative BOLD response in the hippocampus, we consider both a suppression of default activity and an increase in activity without a corresponding boost in CBF as possible mechanisms.

The differential contribution of facial expressions, prosody, and speech content to empathy.

BACKGROUND: Facial expressions, prosody, and speech content constitute channels by which information is exchanged. Little is known about the simultaneous and differential contribution of these channels to empathy when they provide emotionality or neutrality. Especially neutralised speech content has gained little attention with regards to influencing the perception of other emotional cues. METHODS: Participants were presented with video clips of actors telling short-stories. One condition conveyed emotionality in all channels while the other conditions either provided neutral speech content, facial expression, or prosody, respectively. Participants judged the emotion and intensity presented, as well as their own emotional state and intensity. Skin conductance served as a physiological measure of emotional reactivity. RESULTS: Neutralising channels significantly reduced empathic responses. Electrodermal recordings confirmed these findings. The differential effect of the communication channels on empathy prerequisites was that target emotion recognition of the other decreased mostly when the face was neutral, whereas decreased emotional responses attributed to the target emotion were especially present in neutral speech. CONCLUSION: Multichannel integration supports conscious and autonomous measures of empathy and emotional reactivity. Emotional facial expressions influence emotion recognition, whereas speech content is important for responding with an adequate own emotional state, possibly reflecting contextual emotion-appraisal.

Effects of aversive odour presentation on inhibitory control in the Stroop colour-word interference task.

BACKGROUND: Due to the unique neural projections of the olfactory system, odours have the ability to directly influence affective processes. Furthermore, it has been shown that emotional states can influence various non-emotional cognitive tasks, such as memory and planning. However, the link between emotional and cognitive processes is still not fully understood. The present study used the olfactory pathway to induce a negative emotional state in humans to investigate its effect on inhibitory control performance in a standard, single-trial manual Stroop colour-word interference task. An unpleasant (H2S) and an emotionally neutral (Eugenol) odorant were presented in two separate experimental runs, both in blocks alternating with ambient air, to 25 healthy volunteers, while they performed the cognitive task. RESULTS: Presentation of the unpleasant odorant reduced Stroop interference by reducing the reaction times for incongruent stimuli, while the presentation of the neutral odorant had no effect on task performance. CONCLUSIONS: The odour-induced negative emotional state appears to facilitate cognitive processing in the task used in the present study, possibly by increasing the amount of cognitive control that is being exerted. This stands in contrast to other findings that showed impaired cognitive performance under odour-induced negative emotional states, but is consistent with models of mood-congruent processing.

Implicit and explicit behavioral tendencies in male and female depression.

Emotional facial expressions are the most salient cues in social life. Successful social interaction is based on correct recognition, interpretation and appropriate reaction to these cues. However, social skill deficits are among the most debilitating symptoms of depression, leading to social withdrawal and aggravating the disorder in various domains. We used an implicit joystick task to measure automatic behavioral tendencies in response to evoked facial expressions (anger, fear, sadness, happiness and neutral). Additionally, we implemented a rating procedure to assess explicit approach and avoidance reactions to these social stimuli. Our sample consisted of 24 depressed patients and 24 healthy controls. Data analysis indicated that depressed patients appear to understand the expression depicted on the emotional faces but react differently to these social cues. Female patients displayed stronger avoidance tendencies in the explicit condition whereas social withdrawal was less pronounced in the implicit condition. Our data suggest that a cognitive bias negatively influences the unimpaired automatic reactions to emotional expressions in depressed patients, and this bias may result in the characteristic social withdrawal.

Predicting acute affective symptoms after deep brain stimulation surgery in Parkinson's disease.

The current study aimed to investigate predictive markers for acute symptoms of depression and mania following deep brain stimulation (DBS) surgery of the subthalamic nucleus for the treatment of motor symptoms in Parkinson's disease (PD). Fourteen patients with PD (7 males) were included in a prospective longitudinal study. Neuropsychological tests, psychopathology scales and tests of motor functions were administered at several time points prior to and after neurosurgery. Pre-existing psychopathological and motor symptoms predicted postoperative affective side effects of DBS surgery. As these can easily be assessed, they should be considered along with other selection criteria for DBS surgery.

Generalized deficit in all core components of empathy in schizophrenia.

Empathy is a multidimensional construct composed of several components such as emotion recognition, emotional perspective taking and affective responsiveness. Patients with schizophrenia demonstrate deficits in several domains of emotion processing and perspective taking, thus suggesting a dysfunctional emotional competence. We assessed empathic abilities via three paradigms measuring emotion recognition, perspective taking and affective responsiveness as well as self-report empathy questionnaires in 24 (12 females, 12 males) schizophrenia patients meeting the DSM-IV criteria for schizophrenia and 24 matched healthy volunteers. Patients were recruited from the Department of Psychiatry and Psychotherapy, RWTH Aachen University and healthy volunteers were recruited via advertisement. Groups were matched for age, gender and parental education. Data analysis indicates a significant empathic deficit in patients, reflected in worse performance in all three domains. This deficit was only partly reflected in the self-report empathy questionnaires. Comparing the different tasks, emotional perspective taking was the most difficult task for all subjects and symptomatology worsened affective responsiveness. Schizophrenia patients not only struggle to correctly identify emotions, but also have difficulties in spontaneously simulating another person's subjective world (perspective taking) and might not be able to respond adequately in terms of their own emotional experience (affective responsiveness), which are not caused by emotion perception deficits. The results suggest that all domains of empathy are affected in schizophrenia and have to be addressed independently in behavioral therapies, thereby offering a possibility to improve socio-occupational life.

Non-literal understanding and psychosis: Metaphor comprehension in individuals with a diagnosis of schizophrenia.

Previous studies suggest that understanding of non-literal expressions, and in particular metaphors, can be impaired in people with schizophrenia; although it is not clear why. We explored metaphor comprehension capacity using a novel picture selection paradigm; we compared task performance between people with schizophrenia and healthy comparator subjects and we further examined the relationships between the ability to interpret figurative expressions non-literally and performance on a number of other cognitive tasks. Eye-tracking was used to examine task strategy. We showed that even when IQ, years of education, and capacities for theory of mind and associative learning are factored in as covariates, patients are significantly more likely to interpret metaphorical expressions literally, despite eye-tracking findings suggesting that patients are following the same interpretation strategy as healthy controls. Inhibitory control deficits are likely to be one of multiple factors contributing to the poorer performance of our schizophrenia group on the metaphor trials of the picture selection task.

Impairments in cognitive performance in chronic fatigue syndrome are common, not related to co-morbid depression but do associate with autonomic dysfunction.

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.

Associations between childhood maltreatment and inflammatory markers.

BACKGROUND: Childhood maltreatment is one of the strongest predictors of adulthood depression and alterations to circulating levels of inflammatory markers is one putative mechanism mediating risk or resilience.AimsTo determine the effects of childhood maltreatment on circulating levels of 41 inflammatory markers in healthy individuals and those with a major depressive disorder (MDD) diagnosis. METHOD: We investigated the association of childhood maltreatment with levels of 41 inflammatory markers in two groups, 164 patients with MDD and 301 controls, using multiplex electrochemiluminescence methods applied to blood serum. RESULTS: Childhood maltreatment was not associated with altered inflammatory markers in either group after multiple testing correction. Body mass index (BMI) exerted strong effects on interleukin-6 and C-reactive protein levels in those with MDD. CONCLUSIONS: Childhood maltreatment did not exert effects on inflammatory marker levels in either the participants with MDD or the control group in our study. Our results instead highlight the more pertinent influence of BMI.Declaration of interestD.A.C. and H.W. work for Eli Lilly Inc. R.N. has received speaker fees from Sunovion, Jansen and Lundbeck. G.B. has received consultancy fees and funding from Eli Lilly. R.H.M.-W. has received consultancy fees or has a financial relationship with AstraZeneca, Bristol-Myers Squibb, Cyberonics, Eli Lilly, Ferrer, Janssen-Cilag, Lundbeck, MyTomorrows, Otsuka, Pfizer, Pulse, Roche, Servier, SPIMACO and Sunovian. I.M.A. has received consultancy fees or has a financial relationship with Alkermes, Lundbeck, Lundbeck/Otsuka, and Servier. S.W. has sat on an advisory board for Sunovion, Allergan and has received speaker fees from Astra Zeneca. A.H.Y. has received honoraria for speaking from Astra Zeneca, Lundbeck, Eli Lilly, Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion, Janssen; and research grant support from Janssen. A.J.C. has received honoraria for speaking from Astra Zeneca, honoraria for consulting with Allergan, Livanova and Lundbeck and research grant support from Lundbeck.

Intracranial compliance is associated with symptoms of orthostatic intolerance in chronic fatigue syndrome.

Symptoms of orthostatic intolerance (OI) are common in Chronic Fatigue Syndrome (CFS) and similar disorders. These symptoms may relate to individual differences in intracranial compliance and cerebral blood perfusion. The present study used phase-contrast, quantitative flow magnetic resonance imaging (MRI) to determine intracranial compliance based on arterial inflow, venous outflow and cerebrospinal fluid flow along the spinal canal into and out of the cranial cavity. Flow-sensitive Alternating Inversion Recovery (FAIR) Arterial Spin Labelling was used to measure cerebral blood perfusion at rest. Forty patients with CFS and 10 age and gender matched controls were scanned. Severity of symptoms of OI was determined from self-report using the Autonomic Symptom Profile. CFS patients reported significantly higher levels of OI (p < .001). Within the patient group, higher severity of OI symptoms were associated with lower intracranial compliance (r = -.346, p = .033) and higher resting perfusion (r = .337, p = .038). In both groups intracranial compliance was negatively correlated with cerebral perfusion. There were no significant differences between the groups in intracranial compliance or perfusion. In patients with CFS, low intracranial compliance and high resting cerebral perfusion appear to be associated with an increased severity of symptoms of OI. This may signify alterations in the ability of the cerebral vasculature to cope with changes to systemic blood pressure due to orthostatic stress, but this may not be specific to CFS.

Grey and white matter differences in Chronic Fatigue Syndrome - A voxel-based morphometry study.

OBJECTIVE: Investigate global and regional grey and white matter volumes in patients with Chronic Fatigue Syndrome (CFS) using magnetic resonance imaging (MRI) and recent voxel-based morphometry (VBM) methods. METHODS: Forty-two patients with CFS and thirty healthy volunteers were scanned on a 3-Tesla MRI scanner. Anatomical MRI scans were segmented, normalized and submitted to a VBM analysis using randomisation methods. Group differences were identified in overall segment volumes and voxel-wise in spatially normalized grey matter (GM) and white matter (WM) segments. RESULTS: Accounting for total intracranial volume, patients had larger GM volume and lower WM volume. The voxel-wise analysis showed increased GM volume in several structures including the amygdala and insula in the patient group. Reductions in WM volume in the patient group were seen primarily in the midbrain, pons and right temporal lobe. CONCLUSION: Elevated GM volume in CFS is seen in areas related to processing of interoceptive signals and stress. Reduced WM volume in the patient group partially supports earlier findings of WM abnormalities in regions of the midbrain and brainstem.

Are current chronic fatigue syndrome criteria diagnosing different disease phenotypes?

IMPORTANCE: Chronic fatigue syndrome (CFS) is characterised by a constellation of symptoms diagnosed with a number of different polythetic criteria. Heterogeneity across these diagnostic criteria is likely to be confounding research into the as-yet-unknown pathophysiology underlying this stigmatised and debilitating condition and may diagnose a disease spectrum with significant implications for clinical management. No studies to date have objectively investigated this possibility using a validated measure of CFS symptoms-the DePaul Symptom Questionnaire (DSQ). OBJECTIVE: To examine whether current CFS diagnostic criteria are identifying different disease phenotypes using the DSQ. DESIGN: Case control study. SETTING: Clinical Research Facility of the Royal Victoria Infirmary, Newcastle upon Tyne, UK. PARTICIPANTS: 49 CFS subjects and ten matched, sedentary community controls, excluded for co-morbid depression. MAIN OUTCOMES AND MEASURES: Self-reported autonomic and cognitive features were assessed with the Composite Autonomic Symptom Score (COMPASS) and Cognitive Failures Questionnaire (COGFAIL) respectively. Objective autonomic cardiovascular parameters were examined using the Task Force® Monitor and a battery of neuropsychological tests administered for objective cognitive assessment. RESULTS: Self-reported autonomic and cognitive symptoms were significantly greater in CFS subjects compared to controls. There were no statistically significant differences in objective autonomic measures between CFS and controls. There were clinically significant differences between DSQ subgroups on objective autonomic testing. Visuospatial memory, verbal memory and psychomotor speed were significantly different between DSQ subgroups. CONCLUSIONS AND RELEVANCE: The finding of no significant differences in objective autonomic testing between CFS and control subjects may reflect the inclusion of sedentary controls or exclusion for co-morbid depression. Consistent exclusion criteria would enable better delineation of these two conditions and their presenting symptoms. Findings across CFS subgroups suggest subjects have a different disease burden on subjective and objective measures of function, autonomic parameters and cognitive impairment when categorised using the DSQ. Different CFS criteria may at best be diagnosing a spectrum of disease severities and at worst different CFS phenotypes or even different diseases. This complicates research and disease management and may contribute to the significant stigma associated with the condition.

Elevated brain natriuretic peptide levels in chronic fatigue syndrome associate with cardiac dysfunction: a case control study.

Objectives: To explore levels of the brain natriuretic peptide (BNP) and how these associate with the cardiac abnormalities recently identified in chronic fatigue syndrome (CFS). Methods: Cardiac magnetic resonance examinations were performed using 3T Philips Intera Achieva scanner (Best, Netherlands) in CFS (Fukuda) participants and sedentary controls matched group wise for age and sex. BNP was also measured by using an enzyme immunoassay in plasma from 42 patients with CFS and 10 controls. Results: BNP levels were significantly higher in the CFS cohort compared with the matched controls (P=0.013). When we compared cardiac volumes (end-diastolic and end-systolic) between those with high BNP levels (BNP >400 pg/mL) and low BNP (<400 pg/mL), there were significantly lower cardiac volumes in those with the higher BNP levels in both end-systolic and end-diastolic volumes (P=0.05). There were no relationships between fatigue severity, length of disease and BNP levels (P=0.2) suggesting that our findings are unlikely to be related to deconditioning. Conclusion: This study confirms an association between reduced cardiac volumes and BNP in CFS. Lack of relationship between length of disease suggests that findings are not secondary to deconditioning. Further studies are needed to explore the utility of BNP to act as a stratification paradigm in CFS that directs targeted treatments. Trail registration number: Registered with NIHR Portfolio CLRN ID 97805.

Simulating social interaction to address deficits of autistic spectrum disorder in children.

Autistic spectrum disorder (ASD) is diagnosed on the basis of impairment in reciprocal social interaction and language, and rigidity of behavior. This brief paper describes the development of an experimental intervention for preschool children newly diagnosed with ASD. The rationale for this intervention is the hypothesis that failure to attend to social cues in very early life, of itself, may bear a large share of responsibility for core social and communicative deficits. The intervention, therefore, uses eye-tracking to monitor and trigger rewards for attention to facial expression and direction of gaze.

The Impact of Target Frequency on Intra-Individual Variability in Euthymic Bipolar Disorder: A Comparison of Two Sustained Attention Tasks.

Greater intra-individual variability (IIV) in reaction time (RT) on a sustained attention task has been reported in patients with bipolar disorder (BD) compared with healthy controls. However, it is unclear whether IIV is task specific, or whether it represents general cross-task impairment in BD. This study aimed to investigate whether IIV occurs in sustained attention tasks with different parameters. Twenty-two patients with BD (currently euthymic) and 17 controls completed two sustained attention tasks on different occasions: a low target frequency (~20%) Vigil continuous performance test (CPT) and a high target frequency (~70%) CPT version A-X (CPT-AX). Variability measures (individual standard deviation and coefficient of variation) were calculated per participant, and ex-Gaussian modeling was also applied. This was supplemented by Vincentile analysis to characterize RT distributions. Results indicated that participants (patients and controls) were generally slower and more variable when completing the Vigil CPT compared with CPT-AX. Significant group differences were also observed in the Vigil CPT, with euthymic BD patients being more variable than controls. This result suggests that IIV in BD demonstrates some degree of task specificity. Further research should incorporate analysis of additional RT distributional models (drift diffusion and fast Fourier transform) to fully characterize the pattern of IIV in BD, as well as its relationship to cognitive processes.

Reduced cardiac volumes in chronic fatigue syndrome associate with plasma volume but not length of disease: a cohort study.

OBJECTIVES: To explore potential mechanisms that underpin the cardiac abnormalities seen in chronic fatigue syndrome (CFS) using non-invasive cardiac impedance, red cell mass and plasma volume measurements. METHODS: Cardiac MR (MR) examinations were performed using 3 T Philips Intera Achieva scanner (Best, NL) in participants with CFS (Fukuda; n=47) and matched case-by-case controls. Total volume (TV), red cell volume (RCV) and plasma volume (PV) measurements were performed (41 CFS and 10 controls) using the indicator dilution technique using simultaneous 51-chromium labelling of red blood cells and 125-iodine labelling of serum albumin. RESULTS: The CFS group length of history (mean±SD) was 14±10 years. Patients with CFS had significantly reduced end-systolic and end-diastolic volumes together with reduced end-diastolic wall masses (all p<0.0001). Mean±SD RCV was 1565±443 mL with 26/41 (63%) having values below 95% of expected. PV was 2659±529 mL with 13/41 (32%) <95% expected. There were strong positive correlations between TV, RCV and PV and cardiac end-diastolic wall mass (all p<0.0001; r(2)=0.5). Increasing fatigue severity correlated negatively with lower PV (p=0.04; r(2)=0.2). There were no relationships between any MR or volume measurements and length of history, suggesting that deconditioning was unlikely to be the cause of these abnormalities. CONCLUSIONS: This study confirms an association between reduced cardiac volumes and blood volume in CFS. Lack of relationship between length of disease, cardiac and plasma volumes suggests findings are not secondary to deconditioning. The relationship between plasma volume and severity of fatigue symptoms suggests a potential therapeutic target in CFS.