The impact of mindfulness on working memory-related brain activation in breast cancer survivors with cognitive complaints.

PURPOSE: Cancer-related cognitive impairment (CRCI) has been associated with altered brain activation after chemotherapy in areas related to working memory. Hence, improving working memory capacity and associated brain activation might aid in the recovery of CRCI. In this study, we investigated the potential of a mindfulness-based intervention (MBI) to impact working memory-related brain activation. METHODS: Female breast cancer survivors reporting cognitive complaints (N=117) were randomized into a mindfulness (n=43; MBI), physical training (n=36; PT), or waitlist control condition (n=38; WL). Participants completed MRI scans before the intervention, immediately after, and three months post-intervention. Task-based functional MRI was used to measure differences between groups over time in working memory-related brain activation while performing a visual-verbal n-back task. RESULTS: Data of 83 participants (32/26/25 MBI/PT/WL) was included. Compared to the waitlist group, MBI participants showed reduced task-related activation in the right middle frontal and angular gyrus and increased activation in the right dorsal posterior cingulate cortex over time. Compared to the physical training group, MBI participants showed reduced brain activation in the bilateral superior parietal lobule and right dorsal anterior cingulate cortex over time. No differences between physical training and no intervention were identified. CONCLUSION: This study showed that an 8-week mindfulness-based intervention can significantly alter brain activation across brain regions involved in working memory, attentional control, and emotion processing during performance of a working memory task. This might aid in the recovery of CRCI. IMPLICATIONS FOR CANCER SURVIVORS: Mindfulness might alter brain activation patterns while performing a working memory task, which might ultimately aid in restoring higher order cognitive functions.

The Impact of Mindfulness on Functional Brain Connectivity and Peripheral Inflammation in Breast Cancer Survivors with Cognitive Complaints.

BACKGROUND: Cancer-related cognitive impairment (CRCI) has been linked to functional brain changes and inflammatory processes. Hence, interventions targeting these underlying mechanisms are needed. In this study, we investigated the effects of a mindfulness-based intervention on brain function and inflammatory profiles in breast cancer survivors with CRCI. METHODS: Female breast cancer survivors reporting cognitive complaints (n = 117) were randomly assigned to a mindfulness-based intervention (n = 43), physical training (n = 36), or waitlist control condition (n = 38). Region-of-interest (ROI) and graph theory analyses of resting state functional MRI data were performed to study longitudinal group differences in functional connectivity and organization in the default mode, dorsal attention, salience, and frontoparietal network. Additionally, bead-based immunoassays were used to investigate the differences in inflammatory profiles on serum samples. Measures were collected before, immediately after and three months post-intervention. RESULTS: No ROI-to-ROI functional connectivity changes were identified. Compared to no intervention, graph analysis showed a larger decrease in clustering coefficient after mindfulness and physical training. Additionally, a larger increase in global efficiency after physical training was identified. Furthermore, the physical training group showed a larger decrease in an inflammatory profile compared to no intervention (IL-12p70, IFN-γ, IL-1ß, and IL-8). CONCLUSION: Both mindfulness and physical training induced changes in the functional organization of networks related to attention, emotion processing, and executive functioning. While both interventions reduced functional segregation, only physical training increased functional integration of the neural network. In conclusion, physical training had the most pronounced effects on functional network organization and biomarkers of inflammation, two mechanisms that might be involved in CRCI.

The impact of mindfulness on cancer-related cognitive impairment in breast cancer survivors with cognitive complaints.

BACKGROUND: Interventions that target cancer-related cognitive impairment (CRCI) to improve the quality of life of cancer survivors are needed. In this study, the potential of a mindfulness-based intervention to reduce CRCI in breast cancer survivors, compared with physical training and a wait list control group, was investigated. METHODS: Breast cancer survivors with cognitive complaints (N = 117) were randomly allocated to a mindfulness (n = 43), physical training (n = 36), or wait list control condition (n = 38). Participants completed neuropsychological tests and questionnaires before the intervention, immediately after, and 3 months after intervention. The primary outcome measure was the change in cognitive complaints over time. Secondary outcomes were objective cognitive impairment and psychological well-being. All outcomes were compared between groups over time using linear mixed models, including participants with missing values. RESULTS: Of the 117 included participants, 96 completed the three assessments. Participants in the three groups reported decreased cognitive complaints after intervention, without group differences. There were no between-group differences in objective cognitive impairment after intervention compared with baseline. Compared with the wait list control group, participants reported increased mindfulness skills and reduced emotional distress after mindfulness and reduced emotional distress and fatigue after physical training. CONCLUSION: Contrary to the hypothesis, all groups reported an improvement in cognitive complaints over time. It is suggested that priming and acknowledgment of CRCI might alter the experience of cognitive impairment. Additionally, both mindfulness-based intervention and physical training can improve psychological well-being of breast cancer survivors with cognitive complaints.

Methylene tetrahydrofolate reductase A1298C polymorphisms influence the adult sequelae of chemotherapy in childhood-leukemia survivors.

This retrospective correlation study investigated the putative link between methylene tetrahydrofolate reductase (MTHFR) A1298C mutations and chemotherapy-related brain function changes in adult childhood-leukemia survivors. To this end, we determined the relationship between the particular MTHFR1298 genotype (AA, AC or CC) of 31 adult childhood-leukemia survivors, and (1) their CSF Tau and phosphorylated Tau (pTau) levels at the time of treatment, (2) their adult performance intelligence quotient (PIQ), and (3) their regional brain connectivity using diffusion magnetic resonance imaging (dMRI) and resting-state functional MRI (rsfMRI). We confirmed that neuropathology markers Tau and pTau significantly increased in CSF of children after intrathecal methotrexate administration. Highest concentrations of these toxicity markers were found during the induction phase of the therapy. Moreover, CSF concentrations of Tau and pTau during treatment were influenced by the children's particular MTHFR1298 genotype. CSF Tau (but not pTau) levels significantly dropped after folinic acid supplementation. At adult age (on average 13.1 years since the end of their treatment), their particular MTHFR1298 genotype (AA, AC or CC) influenced the changes in PIQ and cortical connectivity that we found to be related to their childhood exposure to chemotherapeutics. In summary, we suggest that homozygous MTHFR1298CC individuals are more vulnerable to the adult sequelae of antifolate chemotherapy.

Effects of a mindfulness-based intervention on cancer-related cognitive impairment: Results of a randomized controlled functional magnetic resonance imaging pilot study.

BACKGROUND: Many breast cancer survivors suffer from cognitive complaints after cancer treatment, affecting their quality of life. The objective of this pilot study was to investigate the effect of a blended-care mindfulness-based intervention (MBI) on chemotherapy-related cognitive impairment and functional brain changes. Furthermore, correlations between changes in cognitive functioning and self-reported behavioral factors were investigated. METHODS: Breast cancer survivors (n = 33) who reported cognitive impairment were randomly allocated to a mindfulness condition (n = 18) or a waitlist control condition (n = 15). Patients completed questionnaires on cognitive impairment, emotional distress, and fatigue; neuropsychological tests; and resting-state functional magnetic resonance imaging before the start of MBI (time 1 [T1]), immediately after the completion of an 8-week MBI program (T2), and 3 months postintervention (T3). Resting-state functional connectivity was estimated in the default mode network, the dorsal and salience attention networks, and the frontoparietal network. Mixed model repeated-measures analysis was performed to test the intervention effect. RESULTS: Patients in the mindfulness condition exhibited significantly higher connectivity between the dorsal and salience attention networks after the mindfulness intervention compared with those in the control condition. MBI participants also had reduced subjective cognitive impairment, emotional distress, and fatigue. No intervention effect was observed on neurocognitive tests. CONCLUSIONS: MBI may induce functional brain changes in networks related to attention and may have a positive effect on subjective measures of cognitive impairment in breast cancer survivors. Therefore, MBI could be a suitable intervention to improve quality of life in this population and deserves further study in this context.

A mindfulness-based intervention for breast cancer patients with cognitive impairment after chemotherapy: study protocol of a three-group randomized controlled trial.

BACKGROUND: Mindfulness has been applied to improve cancer care by enhancing psychological well-being. However, little is known about its impact on cognitive impairment experienced by cancer patients after chemotherapy. Mindfulness may be relevant in tackling cognitive impairment by decreasing emotional distress and fatigue, by decreasing inflammation, and by strengthening functional brain connectivity. The aim of the present study protocol is to evaluate the efficacy and mechanisms of a mindfulness-based intervention to reduce cognitive impairment in breast cancer patients after chemotherapy. METHODS/DESIGN: The present study is a three-arm, parallel-group, randomized controlled trial with assessments at baseline, 1 to 3 weeks after the intervention and at 3 months' follow-up. One hundred and twenty breast cancer patients who ended treatment a minimum of 6 months and a maximum of 5 years before, and who have cognitive complaints, will be enrolled. They will be randomized into one of the following three study arms: (1) a mindfulness-based intervention group (n = 40), (2) an active control condition based on physical training (n = 40), or (3) a treatment as usual (TAU) control group (n = 40). Both the mindfulness-based intervention and the active control condition consist of four group sessions (3 h for the mindfulness condition and 2 h for the physical training) spread over 8 weeks. The primary outcomes will be cognitive symptoms as measured by the Cognitive Failure Questionnaire and changes in functional brain connectivity in the attention network. Secondary outcomes will be (1) levels of emotional distress, fatigue, mindfulness, quality of life; (2) neurocognitive tests; (3) structural and functional brain changes using MR imaging and (4) measures of inflammation. DISCUSSION: The study will examine the impact of a mindfulness-based intervention on cognitive impairment in breast cancer patients. If the findings of this study confirm the effectiveness of a mindfulness-based program to reduce cognitive impairment, it will be possible to improve quality of life for ex-cancer patients. We will inform health care providers about the potential use of a mindfulness-based intervention as a non-pharmaceutical, low-threshold mental health intervention to improve cognitive impairment after cancer. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03736460. Retrospectively registered on 8 November 2018.

Characterizing the microstructural basis of "unidentified bright objects" in neurofibromatosis type 1: A combined in vivo multicomponent T2 relaxation and multi-shell diffusion MRI analysis.

INTRODUCTION: The histopathological basis of "unidentified bright objects" (UBOs) (hyperintense regions seen on T2-weighted magnetic resonance (MR) brain scans in neurofibromatosis-1 (NF1)) remains unclear. New in vivo MRI-based techniques (multi-exponential T2 relaxation (MET2) and diffusion MR imaging (dMRI)) provide measures relating to microstructural change. We combined these methods and present previously unreported data on in vivo UBO microstructure in NF1. METHODS: 3-Tesla dMRI data were acquired on 17 NF1 patients, covering 30 white matter UBOs. Diffusion tensor, kurtosis and neurite orientation and dispersion density imaging parameters were calculated within UBO sites and in contralateral normal appearing white matter (cNAWM). Analysis of MET2 parameters was performed on 24 UBO-cNAWM pairs. RESULTS: No significant alterations in the myelin water fraction and intra- and extracellular (IE) water fraction were found. Mean T2 time of IE water was significantly higher in UBOs. UBOs furthermore showed increased axial, radial and mean diffusivity, and decreased fractional anisotropy, mean kurtosis and neurite density index compared to cNAWM. Neurite orientation dispersion and isotropic fluid fraction were unaltered. CONCLUSION: Our results suggest that demyelination and axonal degeneration are unlikely to be present in UBOs, which appear to be mainly caused by a shift towards a higher T2-value of the intra- and extracellular water pool. This may arise from altered microstructural compartmentalization, and an increase in 'extracellular-like', intracellular water, possibly due to intramyelinic edema. These findings confirm the added value of combining dMRI and MET2 to characterize the microstructural basis of T2 hyperintensities in vivo.

The functional neuroanatomy of multitasking: combining dual tasking with a short term memory task.

Insight into the neural architecture of multitasking is crucial when investigating the pathophysiology of multitasking deficits in clinical populations. Presently, little is known about how the brain combines dual-tasking with a concurrent short-term memory task, despite the relevance of this mental operation in daily life and the frequency of complaints related to this process, in disease. In this study we aimed to examine how the brain responds when a memory task is added to dual-tasking. Thirty-three right-handed healthy volunteers (20 females, mean age 39.9 ± 5.8) were examined with functional brain imaging (fMRI). The paradigm consisted of two cross-modal single tasks (a visual and auditory temporal same-different task with short delay), a dual-task combining both single tasks simultaneously and a multi-task condition, combining the dual-task with an additional short-term memory task (temporal same-different visual task with long delay). Dual-tasking compared to both individual visual and auditory single tasks activated a predominantly right-sided fronto-parietal network and the cerebellum. When adding the additional short-term memory task, a larger and more bilateral frontoparietal network was recruited. We found enhanced activity during multitasking in components of the network that were already involved in dual-tasking, suggesting increased working memory demands, as well as recruitment of multitask-specific components including areas that are likely to be involved in online holding of visual stimuli in short-term memory such as occipito-temporal cortex. These results confirm concurrent neural processing of a visual short-term memory task during dual-tasking and provide evidence for an effective fMRI multitasking paradigm.