Comparative validation of automated presurgical tractography based on constrained spherical deconvolution and diffusion tensor imaging with direct electrical stimulation.

OBJECTIVES: Accurate presurgical brain mapping enables preoperative risk assessment and intraoperative guidance. This cross-sectional study investigated whether constrained spherical deconvolution (CSD) methods were more accurate than diffusion tensor imaging (DTI)-based methods for presurgical white matter mapping using intraoperative direct electrical stimulation (DES) as the ground truth. METHODS: Five different tractography methods were compared (three DTI-based and two CSD-based) in 22 preoperative neurosurgical patients undergoing surgery with DES mapping. The corticospinal tract (CST, N = 20) and arcuate fasciculus (AF, N = 7) bundles were reconstructed, then minimum distances between tractograms and DES coordinates were compared between tractography methods. Receiver-operating characteristic (ROC) curves were used for both bundles. For the CST, binary agreement, linear modeling, and posthoc testing were used to compare tractography methods while correcting for relative lesion and bundle volumes. RESULTS: Distance measures between 154 positive (functional response, pDES) and negative (no response, nDES) coordinates, and 134 tractograms resulted in 860 data points. Higher agreement was found between pDES coordinates and CSD-based compared to DTI-based tractograms. ROC curves showed overall higher sensitivity at shorter distance cutoffs for CSD (8.5 mm) compared to DTI (14.5 mm). CSD-based CST tractograms showed significantly higher agreement with pDES, which was confirmed by linear modeling and posthoc tests (PFWE < .05). CONCLUSIONS: CSD-based CST tractograms were more accurate than DTI-based ones when validated using DES-based assessment of motor and sensory function. This demonstrates the potential benefits of structural mapping using CSD in clinical practice.

Preliminary evidence for preserved synaptic density in late-life depression.

Late-life depression has been consistently associated with lower gray matter volume, the origin of which remains largely unexplained. Recent in-vivo PET findings in early-onset depression and Alzheimer's Disease suggest that synaptic deficits contribute to the pathophysiology of these disorders and may therefore contribute to lower gray matter volume in late-life depression. Here, we investigate synaptic density in vivo for the first time in late-life depression using the synaptic vesicle glycoprotein 2A receptor radioligand 11C-UCB-J. We included 24 currently depressed adults with late-life depression (73.0 ± 6.2 years, 16 female, geriatric depression scale = 19.5 ± 6.8) and 36 age- and gender-matched healthy controls (70.4 ± 6.2 years, 21 female, geriatric depression scale = 2.7 ± 2.9) that underwent simultaneous 11C-UCB-J positron emission tomography (PET) and 3D T1- and T2-FLAIR weighted magnetic resonance (MR) imaging on a 3-tesla PET-MR scanner. We used analyses of variance to test for 11C-UCB-J binding and gray matter volumes differences in regions implicated in depression. The late-life depression group showed a trend in lower gray matter volumes in the hippocampus (p = 0.04), mesial temporal (p = 0.02) and prefrontal cortex (p = 0.02) compared to healthy control group without surviving correction for multiple comparison. However, no group differences in 11C-UCB-J binding were found in these regions nor were any associations between 11C-UCB-J and depressive symptoms. Our data suggests that, in contrast to Alzheimer's Disease, lower gray matter volume in late-life depression is not associated with synaptic density changes. From a therapeutic standpoint, preserved synaptic density in late-life depression may be an encouraging finding.

Human-Prosthetic Interaction (HumanIT): A study protocol for a clinical trial evaluating brain neuroplasticity and functional performance after lower limb loss.

BACKGROUND: Lower limb amputation contributes to structural and functional brain alterations, adversely affecting gait, balance, and overall quality of life. Therefore, selecting an appropriate prosthetic ankle is critical in enhancing the well-being of these individuals. Despite the availability of various prostheses, their impact on brain neuroplasticity remains poorly understood. OBJECTIVES: The primary objective is to examine differences in the degree of brain neuroplasticity using magnetic resonance imaging (MRI) between individuals wearing a new passive ankle prosthesis with an articulated ankle joint and a standard passive prosthesis, and to examine changes in brain neuroplasticity within these two prosthetic groups. The second objective is to investigate the influence of prosthetic type on walking performance and quality of life. The final objective is to determine whether the type of prosthesis induces differences in the walking movement pattern. METHODS: Participants with a unilateral transtibial amputation will follow a 24-week protocol. Prior to rehabilitation, baseline MRI scans will be performed, followed by allocation to the intervention arms and commencement of rehabilitation. After 12 weeks, baseline functional performance tests and a quality of life questionnaire will be administered. At the end of the 24-week period, participants will undergo the same MRI scans, functional performance tests and questionnaire to evaluate any changes. A control group of able-bodied individuals will be included for comparative analysis. CONCLUSION: This study aims to unravel the differences in brain neuroplasticity and prosthesis type in patients with a unilateral transtibial amputation and provide insights into the therapeutic benefits of prosthetic devices. The findings could validate the therapeutic benefits of more advanced lower limb prostheses, potentially leading to a societal impact ultimately improving the quality of life for individuals with lower limb amputation. TRIAL REGISTRATION: NCT05818410 (Clinicaltrials.gov).

Neural correlates of transfer of learning in motor coordination tasks: role of inhibitory and excitatory neurometabolites.

We aimed to investigate transfer of learning, whereby previously acquired skills impact new task learning. While it has been debated whether such transfer may yield positive, negative, or no effects on performance, very little is known about the underlying neural mechanisms, especially concerning the role of inhibitory (GABA) and excitatory (Glu) (measured as Glu + glutamine (Glx)) neurometabolites, as measured by magnetic resonance spectroscopy (MRS). Participants practiced a bimanual coordination task across four days. The Experimental group trained a task variant with the right hand moving faster than the left (Task A) for three days and then switched to the opposite variant (Task B) on Day4. The control group trained Task B across four days. MRS data were collected before, during, and after task performance on Day4 in the somatosensory (S1) and visual (MT/V5) cortex. Results showed that both groups improved performance consistently across three days. On Day4, the Experimental group experienced performance decline due to negative task transfer while the control group continuously improved. GABA and Glx concentrations obtained during task performance showed no significant group-level changes. However, individual Glx levels during task performance correlated with better (less negative) transfer performance. These findings provide a first window into the neurochemical mechanisms underlying task transfer.

Baseline GABA+ levels in areas associated with sensorimotor control predict initial and long-term motor learning progress.

Synaptic plasticity relies on the balance between excitation and inhibition in the brain. As the primary inhibitory and excitatory neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate (Glu), play critical roles in synaptic plasticity and learning. However, the role of these neurometabolites in motor learning is still unclear. Furthermore, it remains to be investigated which neurometabolite levels from the regions composing the sensorimotor network predict future learning outcome. Here, we studied the role of baseline neurometabolite levels in four task-related brain areas during different stages of motor skill learning under two different feedback (FB) conditions. Fifty-one healthy participants were trained on a bimanual motor task over 5 days while receiving either concurrent augmented visual FB (CA-VFB group, N = 25) or terminal intrinsic visual FB (TA-VFB group, N = 26) of their performance. Additionally, MRS-measured baseline GABA+ (GABA + macromolecules) and Glx (Glu + glutamine) levels were measured in the primary motor cortex (M1), primary somatosensory cortex (S1), dorsolateral prefrontal cortex (DLPFC), and medial temporal cortex (MT/V5). Behaviorally, our results revealed that the CA-VFB group outperformed the TA-VFB group during task performance in the presence of augmented VFB, while the TA-VFB group outperformed the CA-VFB group in the absence of augmented FB. Moreover, baseline M1 GABA+ levels positively predicted and DLPFC GABA+ levels negatively predicted both initial and long-term motor learning progress in the TA-VFB group. In contrast, baseline S1 GABA+ levels positively predicted initial and long-term motor learning progress in the CA-VFB group. Glx levels did not predict learning progress. Together, these findings suggest that baseline GABA+ levels predict motor learning capability, yet depending on the FB training conditions afforded to the participants.

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.

A cross-sectional case-control study on the structural connectome in recovered hospitalized COVID-19 patients.

COVID-19 can induce neurological sequelae, negatively affecting the quality of life. Unravelling this illness's impact on structural brain connectivity, white-matter microstructure (WMM), and cognitive performance may help elucidate its implications. This cross-sectional study aimed to investigate differences in these factors between former hospitalised COVID-19 patients (COV) and healthy controls. Group differences in structural brain connectivity were explored using Welch-two sample t-tests and two-sample Mann-Whitney U tests. Multivariate linear models were constructed (one per region) to examine fixel-based group differences. Differences in cognitive performance between groups were investigated using Wilcoxon Rank Sum tests. Possible effects of bundle-specific FD measures on cognitive performance were explored using a two-group path model. No differences in whole-brain structural organisation were found. Bundle-specific metrics showed reduced fiber density (p = 0.012, Hedges' g = 0.884) and fiber density cross-section (p = 0.007, Hedges' g = 0.945) in the motor segment of the corpus callosum in COV compared to healthy controls. Cognitive performance on the motor praxis and digit symbol substitution tests was worse in COV than healthy controls (p < 0.001, r = 0.688; p = 0.013, r = 422, respectively). Associations between the cognitive performance and bundle-specific FD measures differed significantly between groups. WMM and cognitive performance differences were observed between COV and healthy controls.

Changes in leukoencephalopathy and serum neurofilament after (neo)adjuvant chemotherapy for breast cancer.

BACKGROUND: Previous case studies have provided evidence for chemotherapy-induced leukoencephalopathy in patients with breast cancer. However, prospective research is lacking. Hence, we investigated leukoencephalopathy before and after chemotherapy and its association with a serum neuroaxonal damage marker. METHODS: This prospective cohort study included 40 patients receiving chemotherapy for breast cancer, and two age- and education-matched control groups, recruited between 2018 and 2021 (31-64 years of age). The latter control groups consisted of 39 chemotherapy-naïve patients and 40 healthy women. Fluid-attenuated inversion-recovery magnetic resonance imaging was used for lesion volumetry (total, juxtacortical, periventricular, infratentorial, and deep white matter) and blood serum to measure neurofilament light chain (NfL) levels. Acquisition took place pre-chemotherapy and three months and one-year post-chemotherapy, or at corresponding intervals. Within/between group differences were compared using robust mixed-effects modeling, and associations between total lesion volume and serum-NfL with linear regression. RESULTS: Stronger increases in deep white matter lesion volumes were observed shortly post-chemotherapy, compared with healthy women (ßstandardized=0.09, pFDR<0.001). Increases in total lesion volume could mainly be attributed to enlargement of existing lesions (mean±SD, 0.12±0.16 mL), rather than development of new lesions (0.02±0.02 mL). A stronger increase in serum-NfL concentration was observed shortly post-chemotherapy compared with both control groups (ß>0.70, p<0.004), neither of which showed any changes over time, whereas a decrease was observed compared with healthy women one-year post-chemotherapy (ß=-0.54, p = 0.002). Serum-NfL concentrations were associated with lesion volume one-year post-chemotherapy (or at matched timepoint; ß=0.36, p = 0.010), whereas baseline or short-term post-therapy levels or changes were not. CONCLUSION: These results underscore the possibility of chemotherapy-induced leukoencephalopathy months post-treatment, as well as the added value of serum-NfL as a prognostic marker for peripheral/central neurotoxicity. TRANSLATIONAL RELEVANCE: Previous case studies have provided evidence of chemotherapy-induced leukoencephalopathy in patients with breast cancer. However, prospective studies to estimate longitudinal changes are currently missing. In this study, we used longitudinal fluid-attenuated inversion-recovery magnetic resonance imaging to assess white matter lesion volumes in patients treated for non-metastatic breast cancer and healthy women. Our findings demonstrate that chemotherapy-treated patients exhibit stronger increases in lesion volumes compared with healthy women, specifically in deep white matter, at three months post-chemotherapy. Increases could mainly be attributed to enlargement of existing lesions, rather than development of new lesions. Last, serum concentrations of neurofilament light chain, a neuroaxonal damage marker, increased shortly after chemotherapy and long-term post-chemotherapy levels were associated with lesion volumes. These findings highlight the potential of this non-invasive serum marker as a prognostic marker for peripheral and/or central neurotoxicity. Implementation in clinical practice could aid in therapeutic decisions, assessing disease activity, or monitoring treatment response.

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.

Maternal anxiety during pregnancy is associated with weaker prefrontal functional connectivity in adult offspring.

BACKGROUND: The connectome, constituting a unique fingerprint of a person's brain, may be influenced by its prenatal environment, potentially affecting later-life resilience and mental health. METHODS: We conducted a prospective resting-state functional Magnetic Resonance Imaging study in 28-year-old offspring (N = 49) of mothers whose anxiety was monitored during pregnancy. Two offspring anxiety subgroups were defined: "High anxiety" (n = 13) group versus "low-to-medium anxiety" (n = 36) group, based on maternal self-reported state anxiety at 12-22 weeks of gestation. To predict resting-state functional connectivity of 32 by 32 ROIs, maternal state anxiety during pregnancy was included as a predictor in general linear models for both ROI-to-ROI and graph theoretical metrics. Sex, birth weight and postnatal anxiety were included as covariates. RESULTS: Higher maternal anxiety was associated with weaker functional connectivity of medial prefrontal cortex with left inferior frontal gyrus (t = 3.45, pFDR < 0.05). Moreover, network-based statistics (NBS) confirmed our finding and revealed an additional association of weaker connectivity between left lateral prefontal cortex with left somatosensory motor gyrus in the offspring. While our results showed a general pattern of lower functional connectivity in adults prenatally exposed to maternal anxiety, we did not observe significant differences in global brain networks between groups. CONCLUSIONS: Weaker (medial) prefrontal cortex functional connectivity in the high anxiety adult offspring group suggests a long-term negative impact of prenatal exposure to high maternal anxiety, extending into adulthood. To prevent mental health problems at population level, universal primary prevention strategies should aim at lowering maternal anxiety during pregnancy.

Correction: Schroyen et al. Neuroinflammation and Its Association with Cognition, Neuronal Markers and Peripheral Inflammation after Chemotherapy for Breast Cancer. Cancers 2021, 13, 4198.

In the original publication [...].

White matter and neurochemical mechanisms underlying age-related differences in motor processing speed.

Aging is associated with changes in the central nervous system and leads to reduced life quality. Here, we investigated the age-related differences in the CNS underlying motor performance deficits using magnetic resonance spectroscopy and diffusion MRI. MRS measured N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) concentrations in the sensorimotor and occipital cortex, whereas dMRI quantified apparent fiber density (FD) in the same voxels to evaluate white matter microstructural organization. We found that aging was associated with increased reaction time and reduced FD and NAA concentration in the sensorimotor voxel. Both FD and NAA mediated the association between age and reaction time. The NAA concentration was found to mediate the association between age and FD in the sensorimotor voxel. We propose that the age-related decrease in NAA concentration may result in reduced axonal fiber density in the sensorimotor cortex which may ultimately account for the response slowness of older participants.

Brain gray matter reduction and premature brain aging after breast cancer chemotherapy: a longitudinal multicenter data pooling analysis.

Brain gray matter (GM) reductions have been reported after breast cancer chemotherapy, typically in small and/or cross-sectional cohorts, most commonly using voxel-based morphometry (VBM). There has been little examination of approaches such as deformation-based morphometry (DBM), machine-learning-based brain aging metrics, or the relationship of clinical and demographic risk factors to GM reduction. This international data pooling study begins to address these questions. Participants included breast cancer patients treated with (CT+, n = 183) and without (CT-, n = 155) chemotherapy and noncancer controls (NC, n = 145), scanned pre- and post-chemotherapy or comparable intervals. VBM and DBM examined GM volume. Estimated brain aging was compared to chronological aging. Correlation analyses examined associations between VBM, DBM, and brain age, and between neuroimaging outcomes, baseline age, and time since chemotherapy completion. CT+ showed longitudinal GM volume reductions, primarily in frontal regions, with a broader spatial extent on DBM than VBM. CT- showed smaller clusters of GM reduction using both methods. Predicted brain aging was significantly greater in CT+ than NC, and older baseline age correlated with greater brain aging. Time since chemotherapy negatively correlated with brain aging and annual GM loss. This large-scale data pooling analysis confirmed findings of frontal lobe GM reduction after breast cancer chemotherapy. Milder changes were evident in patients not receiving chemotherapy. CT+ also demonstrated premature brain aging relative to NC, particularly at older age, but showed evidence for at least partial GM recovery over time. When validated in future studies, such knowledge could assist in weighing the risks and benefits of treatment strategies.

How negative affect does and does not lead to binge eating-The importance of craving and negative urgency in bulimia nervosa.

Studies suggest that negative affect (NA) can trigger binge eating (BE) in patients with bulimia nervosa (BN). Important factors in this relation between NA and BE could be craving (an intense desire for a BE episode) and negative urgency (the tendency to act rashly when NA is high). Therefore, this study wants to firstly explore the relations between NA, craving, rash action, and BE in daily life and secondly whether craving and rash action mediate the relationship between NA and BE. A sample of 70 female patients with BN and 76 female healthy controls (HC) took part in an experience sampling study where they reported on momentary NA, craving, rash action, and eating behaviors in daily life in a burst-measurement design over a period of 12 months. Assessments occurred eight times a day on Thursdays, Fridays, and Saturdays in seven bursts of 3 weeks, all separated by 5-week periods of no assessment. First, NA predicted subsequent rash action in the whole sample but this was more pronounced in patients with BN. Second, NA predicted subsequent craving in patients with BN, but not in HC. Third, rash action and craving predicted subsequent BE in patients with BN. Fourth, NA had competing effects on eating in patients with BN, predicting subsequent BE through rash action and craving, but also predicting subsequent not eating. These results suggest that NA can lead to BE in daily life through rash action and craving, but that NA can also lead to dietary restriction. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Neuroplasticity in F16 fighter jet pilots.

Exposure to altered g-levels causes unusual sensorimotor demands that must be dealt with by the brain. This study aimed to investigate whether fighter pilots, who are exposed to frequent g-level transitions and high g-levels, show differential functional characteristics compared to matched controls, indicative of neuroplasticity. We acquired resting-state functional magnetic resonance imaging data to assess brain functional connectivity (FC) changes with increasing flight experience in pilots and to assess differences in FC between pilots and controls. We performed whole-brain exploratory and region-of-interest (ROI) analyses, with the right parietal operculum 2 (OP2) and the right angular gyrus (AG) as ROIs. Our results show positive correlations with flight experience in the left inferior and right middle frontal gyri, and in the right temporal pole. Negative correlations were observed in primary sensorimotor regions. We found decreased whole-brain functional connectivity of the left inferior frontal gyrus in fighter pilots compared to controls and this cluster showed decreased functional connectivity with the medial superior frontal gyrus. Functional connectivity increased between the right parietal operculum 2 and the left visual cortex, and between the right and left angular gyrus in pilots compared to controls. These findings suggest altered motor, vestibular, and multisensory processing in the brains of fighter pilots, possibly reflecting coping strategies to altered sensorimotor demands during flight. Altered functional connectivity in frontal areas may reflect adaptive cognitive strategies to cope with challenging conditions during flight. These findings provide novel insights into brain functional characteristics of fighter pilots, which may be of interest to humans traveling to space.

Exploring structural connectomes in children with unilateral cerebral palsy using graph theory.

We explored structural brain connectomes in children with spastic unilateral cerebral palsy (uCP) and its relation to sensory-motor function using graph theory. In 46 children with uCP (mean age = 10 years 7 months ± 2 years 9 months; Manual Ability Classification System I = 15, II = 16, III = 15) we assessed upper limb somatosensory and motor function. We collected multi-shell diffusion-weighted, T1-weighted and T2-FLAIR MRI and identified the corticospinal tract (CST) wiring pattern using transcranial magnetic stimulation. Structural connectomes were constructed using Virtual Brain Grafting-modified FreeSurfer parcellations and multi-shell multi-tissue constrained spherical deconvolution-based anatomically-constrained tractography. Graph metrics (characteristic path length, global/local efficiency and clustering coefficient) of the whole brain, the ipsilesional/contralesional hemisphere, and the full/ipsilesional/contralesional sensory-motor network were compared between lesion types (periventricular white matter (PWM) = 28, cortical and deep gray matter (CDGM) = 18) and CST-wiring patterns (ipsilateral = 14, bilateral = 14, contralateral = 12, unknown = 6) using ANCOVA with age as covariate. Using elastic-net regularized regression we investigated how graph metrics, lesion volume, lesion type, CST-wiring pattern and age predicted sensory-motor function. In both the whole brain and subnetworks, we observed a hyperconnectivity pattern in children with CDGM-lesions compared with PWM-lesions, with higher clustering coefficient (p = [<.001-.047], η p 2 =[0.09-0.27]), characteristic path length (p = .003, η p 2 =0.19) and local efficiency (p = [.001-.02], η p 2 =[0.11-0.21]), and a lower global efficiency with age (p = [.01-.04], η p 2 =[0.09-0.15]). No differences were found between CST-wiring groups. Overall, good predictions of sensory-motor function were obtained with elastic-net regression (R2  = .40-.87). CST-wiring pattern was the strongest predictor for motor function. For somatosensory function, all independent variables contributed equally to the model. In conclusion, we demonstrated the potential of structural connectomics in understanding disease severity and brain development in children with uCP.

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.

Prolonged microgravity induces reversible and persistent changes on human cerebral connectivity.

The prospect of continued manned space missions warrants an in-depth understanding of how prolonged microgravity affects the human brain. Functional magnetic resonance imaging (fMRI) can pinpoint changes reflecting adaptive neuroplasticity across time. We acquired resting-state fMRI data of cosmonauts before, shortly after, and eight months after spaceflight as a follow-up to assess global connectivity changes over time. Our results show persisting connectivity decreases in posterior cingulate cortex and thalamus and persisting increases in the right angular gyrus. Connectivity in the bilateral insular cortex decreased after spaceflight, which reversed at follow-up. No significant connectivity changes across eight months were found in a matched control group. Overall, we show that altered gravitational environments influence functional connectivity longitudinally in multimodal brain hubs, reflecting adaptations to unfamiliar and conflicting sensory input in microgravity. These results provide insights into brain functional modifications occurring during spaceflight, and their further development when back on Earth.

A paleo-neurologic investigation of the social brain hypothesis in frontotemporal dementia.

The social brain hypothesis posits that a disproportionate encephalization in primates enabled to adapt behavior to a social context. Also, it has been proposed that phylogenetically recent brain areas are disproportionally affected by neurodegeneration. Using structural and functional magnetic resonance imaging, the present study investigates brain-behavior associations and neural integrity of hyperspecialized and domain-general cortical social brain areas in behavioral variant frontotemporal dementia (bvFTD). The results revealed that both structure and function of hyperspecialized social areas in the middle portion of the superior temporal sulcus (STS) are compromised in bvFTD, while no deterioration was observed in domain general social areas in the posterior STS. While the structural findings adhered to an anterior-posterior gradient, the functional group differences only occurred in the hyperspecialized locations. Activity in specialized regions was associated with structural integrity of the amygdala and with social deficits in bvFTD. In conclusion, the results are in line with the paleo-neurology hypothesis positing that neurodegeneration primarily hits cortical areas showing increased specialization, but also with the compatible alternative explanation that anterior STS regions degenerate earlier, based on stronger connections to and trans-neuronal spreading from regions affected early in bvFTD.