Iron Deposition and Distribution Across the Hippocampus Is Associated with Pattern Separation and Pattern Completion in Older Adults at Risk for Alzheimer's Disease.

Elevated iron deposition in the brain has been observed in older adult humans and persons with Alzheimer's disease (AD), and has been associated with lower cognitive performance. We investigated the impact of iron deposition, and its topographical distribution across hippocampal subfields and segments (anterior, posterior) measured along its longitudinal axis, on episodic memory in a sample of cognitively unimpaired older adults at elevated familial risk for AD (N = 172, 120 females, 52 males; mean age = 68.8 ± 5.4 years). MRI-based quantitative susceptibility maps were acquired to derive estimates of hippocampal iron deposition. The Mnemonic Similarity Task was used to measure pattern separation and pattern completion, two hippocampally mediated episodic memory processes. Greater hippocampal iron load was associated with lower pattern separation and higher pattern completion scores, both indicators of poorer episodic memory. Examination of iron levels within hippocampal subfields across its long axis revealed topographic specificity. Among the subfields and segments investigated here, iron deposition in the posterior hippocampal CA1 was the most robustly and negatively associated with the fidelity memory representations. This association remained after controlling for hippocampal volume and was observed in the context of normal performance on standard neuropsychological memory measures. These findings reveal that the impact of iron load on episodic memory performance is not uniform across the hippocampus. Both iron deposition levels as well as its spatial distribution, must be taken into account when examining the relationship between hippocampal iron and episodic memory in older adults at elevated risk for AD.

Decreased long-range temporal correlations in the resting-state functional magnetic resonance imaging blood-oxygen-level-dependent signal reflect motor sequence learning up to 2 weeks following training.

Decreased long-range temporal correlations (LRTC) in brain signals can be used to measure cognitive effort during task execution. Here, we examined how learning a motor sequence affects long-range temporal memory within resting-state functional magnetic resonance imaging signal. Using the Hurst exponent (HE), we estimated voxel-wise LRTC and assessed changes over 5 consecutive days of training, followed by a retention scan 12 days later. The experimental group learned a complex visuomotor sequence while a complementary control group performed tightly matched movements. An interaction analysis revealed that HE decreases were specific to the complex sequence and occurred in well-known motor sequence learning associated regions including left supplementary motor area, left premotor cortex, left M1, left pars opercularis, bilateral thalamus, and right striatum. Five regions exhibited moderate to strong negative correlations with overall behavioral performance improvements. Following learning, HE values returned to pretraining levels in some regions, whereas in others, they remained decreased even 2 weeks after training. Our study presents new evidence of HE's possible relevance for functional plasticity during the resting-state and suggests that a cortical subset of sequence-specific regions may continue to represent a functional signature of learning reflected in decreased long-range temporal dependence after a period of inactivity.

Modeling venous bias in resting state functional MRI metrics.

Resting-state (rs) functional magnetic resonance imaging (fMRI) is used to detect low-frequency fluctuations in the blood oxygen-level dependent (BOLD) signal across brain regions. Correlations between temporal BOLD signal fluctuations are commonly used to infer functional connectivity. However, because BOLD is based on the dilution of deoxyhemoglobin, it is sensitive to veins of all sizes, and its amplitude is biased by draining veins. These biases affect local BOLD signal location and amplitude, and may also influence BOLD-derived connectivity measures, but the magnitude of this venous bias and its relation to vein size and proximity is unknown. Here, veins were identified using high-resolution quantitative susceptibility maps and utilized in a biophysical model to investigate systematic venous biases on common local rsfMRI-derived measures. Specifically, we studied the impact of vein diameter and distance to veins on the amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), Hurst exponent (HE), regional homogeneity (ReHo), and eigenvector centrality values in the grey matter. Values were higher across all distances in smaller veins, and decreased with increasing vein diameter. Additionally, rsfMRI values associated with larger veins decrease with increasing distance from the veins. ALFF and ReHo were the most biased by veins, while HE and fALFF exhibited the smallest bias. Across all metrics, the amplitude of the bias was limited in voxel-wise data, confirming that venous structure is not the dominant source of contrast in these rsfMRI metrics. Finally, the models presented can be used to correct this venous bias in rsfMRI metrics.

Lamina-dependent calibrated BOLD response in human primary motor cortex.

Disentangling neural activity at different cortical depths during a functional task has recently generated growing interest, since this would allow to separate feedforward and feedback activity. The majority of layer-dependent studies have, so far, relied on gradient-recalled echo (GRE) blood-oxygenation-level dependent (BOLD) acquisitions, which are weighted towards the large draining veins at the cortical surface. The current study aims to obtain quantitative brain activity responses in the primary motor cortex on a laminar scale without the contamination due to accompanying secondary vascular effects. Evoked oxidative metabolism was evaluated using the Davis model, to investigate its applicability, advantages, and limits in lamina-dependent fMRI. Average values for the calibration parameter, M, and for changes in the cerebral metabolic rate of oxygen consumption (CMRO2) during a unilateral finger-tapping task were (11±2)% and (30±7)%, respectively, with distinct variation features across the cortical depth. The results presented here showed an uncoupling between BOLD-based functional magnetic resonance imaging (fMRI) and metabolic changes across cortical depth, while the tight coupling between CMRO2 and CBV was conserved across cortical layers. We conclude that the Davis model can help to obtain estimates of lamina-dependent metabolic changes without contamination from large draining veins, with high consistency and reproducibility across participants.

Baseline oxygenation in the brain: Correlation between respiratory-calibration and susceptibility methods.

New MRI methods for noninvasive imaging of baseline oxygen extraction fraction (OEF) in the brain show great promise. Quantitative O2 imaging (QUO2) applies a biophysical model to measure OEF in tissue from BOLD, cerebral blood flow (CBF), and end-tidal O2 (ETO2) signals acquired during two or more gas manipulations. Alternatively, quantitative susceptibility mapping (QSM) maps baseline OEF along cerebral vessels based on the deoxyhemoblogin (dHb) susceptibility shift between veins and water. However, these approaches have not been carefully compared to each other or to known physiological signals. The aims of this study were to compare OEF values by QUO2 and QSM; and to see if baseline OEF relates to BOLD and CBF changes during a visual task. Simultaneous BOLD and arterial spin labeling (ASL) scans were acquired at 7T in 11 healthy subjects continuously during hypercapnia (5% CO2, 21% O2), hyperoxia (100% O2), and carbogen (5% CO2, 95% O2) for QUO2 analysis. Separate BOLD-ASL scans were acquired during a checkerboard stimulus to identify functional changes in the visual cortex. Gradient echo phase images were also collected at rest for QSM reconstruction of OEF along cerebral veins draining the visual cortex. Mean baseline OEF was (43.5±14)% for QUO2 with two gases, (42.3±17)% for QUO2 with three gases, and (29.4±3)% for QSM across volunteers. Three-gas QUO2 values of OEF correlated with QSM values of OEF (P=0.03). However, Bland-Altman analysis revealed that QUO2 tended to measure higher baseline OEF with respect to QSM, which likely results from underestimation of the hyperoxic BOLD signal and low signal-to-noise ratio of the ASL acquisitions. Across subjects, the percent CBF change during the visual task correlated with OEF measured by 3-gas QUO2 (P<0.04); and by QSM (P=0.035), providing evidence that the new methods measure true variations in brain physiology across subjects.

Cortical lamina-dependent blood volume changes in human brain at 7 T.

Cortical layer-dependent high (sub-millimeter) resolution functional magnetic resonance imaging (fMRI) in human or animal brain can be used to address questions regarding the functioning of cortical circuits, such as the effect of different afferent and efferent connectivities on activity in specific cortical layers. The sensitivity of gradient echo (GE) blood oxygenation level-dependent (BOLD) responses to large draining veins reduces its local specificity and can render the interpretation of the underlying laminar neural activity impossible. The application of the more spatially specific cerebral blood volume (CBV)-based fMRI in humans has been hindered by the low sensitivity of the noninvasive modalities available. Here, a vascular space occupancy (VASO) variant, adapted for use at high field, is further optimized to capture layer-dependent activity changes in human motor cortex at sub-millimeter resolution. Acquired activation maps and cortical profiles show that the VASO signal peaks in gray matter at 0.8-1.6mm depth, and deeper compared to the superficial and vein-dominated GE-BOLD responses. Validation of the VASO signal change versus well-established iron-oxide contrast agent based fMRI methods in animals showed the same cortical profiles of CBV change, after normalization for lamina-dependent baseline CBV. In order to evaluate its potential of revealing small lamina-dependent signal differences due to modulations of the input-output characteristics, layer-dependent VASO responses were investigated in the ipsilateral hemisphere during unilateral finger tapping. Positive activation in ipsilateral primary motor cortex and negative activation in ipsilateral primary sensory cortex were observed. This feature is only visible in high-resolution fMRI where opposing sides of a sulcus can be investigated independently because of a lack of partial volume effects. Based on the results presented here, we conclude that VASO offers good reproducibility, high sensitivity and lower sensitivity than GE-BOLD to changes in larger vessels, making it a valuable tool for layer-dependent fMRI studies in humans.

Using carbogen for calibrated fMRI at 7Tesla: comparison of direct and modelled estimation of the M parameter.

Task-evoked changes in cerebral oxygen metabolism can be measured using calibrated functional Magnetic Resonance Imaging (fMRI). This technique requires the use of breathing manipulations such as hypercapnia, hyperoxia or a combination of both to determine a calibration factor M. The M-value is usually obtained by extrapolating the BOLD signal measured during the gas manipulation to its upper theoretical physiological limit using a biophysical model. However, a recently introduced technique uses a combination of increased inspired concentrations of O2 and CO2 to saturate the BOLD signal completely. In this study, we used this BOLD saturation technique to measure M directly at 7Tesla (T). Simultaneous carbogen-7 (7% CO2 in 93% O2) inhalation and visuo-motor task performance were used to elevate venous oxygen saturation in visual and motor areas close to their maximum, and the BOLD signal measured during this manipulation was used as an estimate of M. As accurate estimation of M is crucial for estimation of valid oxidative metabolism values, these directly estimated M-values were assessed and compared with M-values obtained via extrapolation modelling using the generalized calibration model (GCM) on the same dataset. Average M-values measured using both methods were 10.4±3.9% (modelled) and 7.5±2.2% (direct) for a visual-related ROI, and 11.3±5.2% (modelled) and 8.1±2.6% (direct) for a motor-related ROI. Results from this study suggest that, for the CO2 concentration used here, modelling is necessary for the accurate estimation of the M parameter. Neither gas inhalation alone, nor gas inhalation combined with a visuo-motor task, was sufficient to completely saturate venous blood in most subjects. Calibrated fMRI studies should therefore rely on existing models for gas inhalation-based calibration of the BOLD signal.

Regional reproducibility of calibrated BOLD functional MRI: implications for the study of cognition and plasticity.

Calibrated BOLD fMRI is a promising alternative to the classic BOLD contrast due to its reduced venous sensitivity and greater physiological specificity. The delayed adoption of this technique for cognitive studies may stem partly from a lack of information on the reproducibility of these measures in the context of cognitive tasks. In this study we have explored the applicability and reproducibility of a state-of-the-art calibrated BOLD technique using a complex functional task at 7 tesla. Reproducibility measures of BOLD, CBF, CMRO2 flow-metabolism coupling n and the calibration parameter M were compared and interpreted for three ROIs. We found an averaged intra-subject variation of CMRO2 of 8% across runs and 33% across days. BOLD (46% across runs, 36% across days), CBF (33% across runs, 46% across days) and M (41% across days) showed significantly higher intra-subject variability. Inter-subject variability was found to be high for all quantities, though CMRO2 was the most consistent across brain regions. The results of this study provide evidence that calibrated BOLD may be a viable alternative for longitudinal and cognitive MRI studies.

MVComp toolbox: MultiVariate Comparisons of brain MRI features accounting for common information across metrics.

Multivariate approaches have recently gained in popularity to address the physiological unspecificity of neuroimaging metrics and to better characterize the complexity of biological processes underlying behavior. However, commonly used approaches are biased by the intrinsic associations between variables, or they are computationally expensive and may be more complicated to implement than standard univariate approaches. Here, we propose using the Mahalanobis distance (D2), an individual-level measure of deviation relative to a reference distribution that accounts for covariance between metrics. To facilitate its use, we introduce an open-source python-based tool for computing D2 relative to a reference group or within a single individual: the MultiVariate Comparison (MVComp) toolbox. The toolbox allows different levels of analysis (i.e., group- or subject-level), resolutions (e.g., voxel-wise, ROI-wise) and dimensions considered (e.g., combining MRI metrics or WM tracts). Several example cases are presented to showcase the wide range of possible applications of MVComp and to demonstrate the functionality of the toolbox. The D2 framework was applied to the assessment of white matter (WM) microstructure at 1) the group-level, where D2 can be computed between a subject and a reference group to yield an individualized measure of deviation. We observed that clustering applied to D2 in the corpus callosum yields parcellations that highly resemble known topography based on neuroanatomy, suggesting that D2 provides an integrative index that meaningfully reflects the underlying microstructure. 2) At the subject level, D2 was computed between voxels to obtain a measure of (dis)similarity. The loadings of each MRI metric (i.e., its relative contribution to D2) were then extracted in voxels of interest to showcase a useful option of the MVComp toolbox. These relative contributions can provide important insights into the physiological underpinnings of differences observed. Integrative multivariate models are crucial to expand our understanding of the complex brain-behavior relationships and the multiple factors underlying disease development and progression. Our toolbox facilitates the implementation of a useful multivariate method, making it more widely accessible.

Neuromodulatory subcortical nucleus integrity is associated with white matter microstructure, tauopathy and APOE status.

The neuromodulatory subcortical nuclei within the isodendritic core (IdC) are the earliest sites of tauopathy in Alzheimer's disease (AD). They project broadly throughout the brain's white matter. We investigated the relationship between IdC microstructure and whole-brain white matter microstructure to better understand early neuropathological changes in AD. Using multiparametric quantitative magnetic resonance imaging we observed two covariance patterns between IdC and white matter microstructure in 133 cognitively unimpaired older adults (age 67.9 ± 5.3 years) with familial risk for AD. IdC integrity related to 1) whole-brain neurite density, and 2) neurite orientation dispersion in white matter tracts known to be affected early in AD. Pattern 2 was associated with CSF concentration of phosphorylated-tau, indicating AD specificity. Apolipoprotein-E4 carriers expressed both patterns more strongly than non-carriers. IdC microstructure variation is reflected in white matter, particularly in AD-affected tracts, highlighting an early mechanism of pathological development.

A generalized procedure for calibrated MRI incorporating hyperoxia and hypercapnia.

Calibrated MRI techniques use the changes in cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) signal evoked by a respiratory manipulation to extrapolate the total BOLD signal attributable to deoxyhemoglobin at rest (M). This parameter can then be used to estimate changes in the cerebral metabolic rate of oxygen consumption (CMRO(2)) based on task-induced BOLD and CBF signals. Different approaches have been described previously, including addition of inspired CO(2) (hypercapnia) or supplemental O(2) (hyperoxia). We present here a generalized BOLD signal model that reduces under appropriate conditions to previous models derived for hypercapnia or hyperoxia alone, and is suitable for use during hybrid breathing manipulations including simultaneous hypercapnia and hyperoxia. This new approach yields robust and accurate M maps, in turn allowing more reliable estimation of CMRO(2) changes evoked during a visual task. The generalized model is valid for arbitrary flow changes during hyperoxia, thus benefiting from the larger total oxygenation changes produced by increased blood O(2) content from hyperoxia combined with increases in flow from hypercapnia. This in turn reduces the degree of extrapolation required to estimate M. The new procedure yielded M estimates that were generally higher (7.6 ± 2.6) than those obtained through hypercapnia (5.6 ± 1.8) or hyperoxia alone (4.5 ± 1.5) in visual areas. These M values and their spatial distribution represent a more accurate and robust depiction of the underlying distribution of tissue deoxyhemoglobin at rest, resulting in more accurate estimates of evoked CMRO(2) changes.

Sex-specific relationships between obesity, physical activity, and gray and white matter volume in cognitively unimpaired older adults.

Independently, obesity and physical activity (PA) influence cerebral structure in aging, yet their interaction has not been investigated. We examined sex differences in the relationships among PA, obesity, and cerebral structure in aging with 340 participants who completed magnetic resonance imaging (MRI) acquisition to quantify grey matter volume (GMV) and white matter volume (WMV). Height and weight were measured to calculate body mass index (BMI). A PA questionnaire was used to estimate weekly Metabolic Equivalents. The relationships between BMI, PA, and their interaction on GMV Regions of Interest (ROIs) and WMV ROIs were examined. Increased BMI was associated with higher GMV in females, an inverse U relationship was found between PA and GMV in females, and the interaction indicated that regardless of BMI greater PA was associated with enhanced GMV. Males demonstrated an inverse U shape between BMI and GMV, and in males with high PA and had normal weight demonstrated greater GMV than normal weight low PA revealed by the interaction. WMV ROIs had a linear relationship with moderate PA in females, whereas in males, increased BMI was associated with lower WMV as well as a positive relationship with moderate PA and WMV. Males and females have unique relationships among GMV, PA and BMI, suggesting sex-aggregated analyses may lead to biased or non-significant results. These results suggest higher BMI, and PA are associated with increased GMV in females, uniquely different from males, highlighting the importance of sex-disaggregated models. Future work should include other imaging parameters, such as perfusion, to identify if these differences co-occur in the same regions as GMV.

Cerebral blood flow in schizophrenia: A systematic review and meta-analysis of MRI-based studies.

INTRODUCTION: Schizophrenia-spectrum disorders (SSD) represent one of the leading causes of disability worldwide and are usually underpinned by neurodevelopmental brain abnormalities observed on a structural and functional level. Nuclear medicine imaging studies of cerebral blood flow (CBF) have already provided insights into the pathophysiology of these disorders. Recent developments in non-invasive MRI techniques such as arterial spin labeling (ASL) have allowed broader examination of CBF across SSD prompting us to conduct an updated literature review of MRI-based perfusion studies. In addition, we conducted a focused meta-analysis of whole brain studies to provide a complete picture of the literature on the topic. METHODS: A systematic OVID search was performed in Embase, MEDLINEOvid, and PsycINFO. Studies eligible for inclusion in the review involved: 1) individuals with SSD, first-episode psychosis or clinical-high risk for psychosis, or; 2) had healthy controls for comparison; 3) involved MRI-based perfusion imaging methods; and 4) reported CBF findings. No time span was specified for the database queries (last search: 08/2022). Information related to participants, MRI techniques, CBF analyses, and results were systematically extracted. Whole-brain studies were then selected for the meta-analysis procedure. The methodological quality of each included studies was assessed. RESULTS: For the systematic review, the initial Ovid search yielded 648 publications of which 42 articles were included, representing 3480 SSD patients and controls. The most consistent finding was that negative symptoms were linked to cortical fronto-limbic hypoperfusion while positive symptoms seemed to be associated with hyperperfusion, notably in subcortical structures. The meta-analysis integrated results from 13 whole-brain studies, across 426 patients and 401 controls, and confirmed the robustness of the hypoperfusion in the left superior and middle frontal gyri and right middle occipital gyrus while hyperperfusion was found in the left putamen. CONCLUSION: This updated review of the literature supports the implication of hemodynamic correlates in the pathophysiology of psychosis symptoms and disorders. A more systematic exploration of brain perfusion could complete the search of a multimodal biomarker of SSD.

Comparison of pulsed and pseudocontinuous arterial spin-labeling for measuring CO2 -induced cerebrovascular reactivity.

PURPOSE: To compare the performance of pulsed and pseudocontinuous arterial spin-labeling (PASL and pCASL) methods in measuring CO(2) -induced cerebrovascular reactivity (CVR). MATERIALS AND METHODS: Subjects were scanned using both ASL sequences during a controlled hypercapnia procedure and visual stimulation. CVR was computed as the percent CO(2) -induced increase in cerebral blood flow (Δ%CBF) per mmHg increase in end-tidal PCO(2) . Visually evoked responses were expressed as Δ%CBF. Resting CBF and temporal signal-to-noise ratio were also computed. Regionally averaged values for the different quantities were compared in gray matter (GM) and visual cortex (VC) using t-tests. RESULTS: Both PASL and pCASL yielded comparable respective values for resting CBF (56 ± 3 and 56 ± 4 mL/min/100g) and visually evoked responses (75 ± 5% and 81 ± 4%). Values of CVR determined using pCASL (GM 4.4 ± 0.2, VC 8 ± 1 Δ%CBF/mmHg), however, were significantly higher than those measured using PASL (GM 3.0 ± 0.6, VC 5 ± 1 Δ%CBF/mmHg) in both GM and VC. The percentage of GM voxels in which statistically significant hypercapnia responses were detected was also higher for pCASL (27 ± 5% vs. 16 ± 3% for PASL). CONCLUSION: pCASL may be less prone to underestimation of CO(2) -induced flow changes due to improved label timing control.

Motor sequences; separating the sequence from the motor. A longitudinal rsfMRI study.

In motor learning, sequence specificity, i.e. the learning of specific sequential associations, has predominantly been studied using task-based fMRI paradigms. However, offline changes in resting state functional connectivity after sequence-specific motor learning are less well understood. Previous research has established that plastic changes following motor learning can be divided into stages including fast learning, slow learning and retention. A description of how resting state functional connectivity after sequence-specific motor sequence learning (MSL) develops across these stages is missing. This study aimed to identify plastic alterations in whole-brain functional connectivity after learning a complex motor sequence by contrasting an active group who learned a complex sequence with a control group who performed a control task matched for motor execution. Resting state fMRI and behavioural performance were collected in both groups over the course of 5 consecutive training days and at follow-up after 12 days to encompass fast learning, slow learning, overall learning and retention. Between-group interaction analyses showed sequence-specific decreases in functional connectivity during overall learning in the right supplementary motor area (SMA). We found that connectivity changes in a key region of the motor network, the superior parietal cortex (SPC) were not a result of sequence-specific learning but were instead linked to motor execution. Our study confirms the sequence-specific role of SMA that has previously been identified in online task-based learning studies, and extends it to resting state network changes after sequence-specific MSL.

The Role of Cerebrovascular-Reactivity Mapping in Functional MRI: Calibrated fMRI and Resting-State fMRI.

Task and resting-state functional MRI (fMRI) is primarily based on the same blood-oxygenation level-dependent (BOLD) phenomenon that MRI-based cerebrovascular reactivity (CVR) mapping has most commonly relied upon. This technique is finding an ever-increasing role in neuroscience and clinical research as well as treatment planning. The estimation of CVR has unique applications in and associations with fMRI. In particular, CVR estimation is part of a family of techniques called calibrated BOLD fMRI, the purpose of which is to allow the mapping of cerebral oxidative metabolism (CMRO2) using a combination of BOLD and cerebral-blood flow (CBF) measurements. Moreover, CVR has recently been shown to be a major source of vascular bias in computing resting-state functional connectivity, in much the same way that it is used to neutralize the vascular contribution in calibrated fMRI. Furthermore, due to the obvious challenges in estimating CVR using gas challenges, a rapidly growing field of study is the estimation of CVR without any form of challenge, including the use of resting-state fMRI for that purpose. This review addresses all of these aspects in which CVR interacts with fMRI and the role of CVR in calibrated fMRI, provides an overview of the physiological biases and assumptions underlying hypercapnia-based CVR and calibrated fMRI, and provides a view into the future of non-invasive CVR measurement.

Comparing the effect of cognitive vs. exercise training on brain MRI outcomes in healthy older adults: A systematic review.

Aging is associated with cognitive decline. Importantly cognition and cerebral health is enhanced with interventions like cognitive (CT) and exercise training (ET). However, effects of CT and ET interventions on brain magnetic resonance imaging outcomes have never been compared systematically. Here, the primary objective was to critically and systematically compare CT to ET in healthy older adults on brain MRI outcomes. A total of 38 studies were included in the final review. Although results were mixed, patterns were identified: CT showed improvements in white matter microstructure, while ET demonstrated macrostructural enhancements, and both demonstrated changes to task-based BOLD signal changes. Importantly, beneficial effects for cognitive and cerebral outcomes were observed by almost all, regardless of intervention type. Overall, it is suggested that future work include more than one MRI outcome, and report all results including null. To better understand the MRI changes associated with CT or ET, more studies explicitly comparing interventions within the same domain (i.e. resistance vs. aerobic) and between domains (i.e. CT vs. ET) are needed.

Sex moderations in the relationship between aortic stiffness, cognition, and cerebrovascular reactivity in healthy older adults.

It is well established that sex differences exist in the manifestation of vascular diseases. Arterial stiffness (AS) has been associated with changes in cerebrovascular reactivity (CVR) and cognitive decline in aging. Specifically, older adults with increased AS show a decline on executive function (EF) tasks. Interestingly, the relationship between AS and CVR is more complex, where some studies show decreased CVR with increased AS, and others demonstrate preserved CVR despite higher AS. Here, we investigated the possible role of sex on these hemodynamic relationships. Acquisitions were completed in 48 older adults. Pseudo-continuous arterial spin labeling (pCASL) data were collected during a hypercapnia challenge. Aortic pulse wave velocity (PWV) data was acquired using cine phase contrast velocity series. Cognitive function was assessed with a comprehensive neuropsychological battery, and a composite score for EF was calculated using four cognitive tests from the neuropsychological battery. A moderation model test revealed that sex moderated the relationship between PWV and CVR and PWV and EF, but not between CVR and EF. Together, our results indicate that the relationships between central stiffness, cerebral hemodynamics and cognition are in part mediated by sex.

White matter microstructural changes in short-term learning of a continuous visuomotor sequence.

Efficient neural transmission is crucial for optimal brain function, yet the plastic potential of white matter (WM) has long been overlooked. Growing evidence now shows that modifications to axons and myelin occur not only as a result of long-term learning, but also after short training periods. Motor sequence learning (MSL), a common paradigm used to study neuroplasticity, occurs in overlapping learning stages and different neural circuits are involved in each stage. However, most studies investigating short-term WM plasticity have used a pre-post design, in which the temporal dynamics of changes across learning stages cannot be assessed. In this study, we used multiple magnetic resonance imaging (MRI) scans at 7 T to investigate changes in WM in a group learning a complex visuomotor sequence (LRN) and in a control group (SMP) performing a simple sequence, for five consecutive days. Consistent with behavioral results, where most improvements occurred between the two first days, structural changes in WM were observed only in the early phase of learning (d1-d2), and in overall learning (d1-d5). In LRNs, WM microstructure was altered in the tracts underlying the primary motor and sensorimotor cortices. Moreover, our structural findings in WM were related to changes in functional connectivity, assessed with resting-state functional MRI data in the same cohort, through analyses in regions of interest (ROIs). Significant changes in WM microstructure were found in a ROI underlying the right supplementary motor area. Together, our findings provide evidence for highly dynamic WM plasticity in the sensorimotor network during short-term MSL.

Associations Between Relative Morning Blood Pressure, Cerebral Blood Flow, and Memory in Older Adults Treated and Controlled for Hypertension.

[Figure: see text].