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Vertex-files for the paper "High spatial overlap but diverging age-related trajectories of cortical magnetic resonance imaging markers aiming to represent intracortical myelin and microstructure" published in Human Brain Mapping by Parent and colleagues (2023). https://doi.org/10.1002/hbm.26259 Anonymized vertex-wise files for each subject for the following cortical markers: Boundary Sharpness Coefficient (BSC) Grey-white Matter Contrast (GWC) Cortical thickness (CT) T1-weighted/T2-weighted (T1w/T2w) ratio sampled at 25% of CT in grey matter, 50% of CT in grey matter, and 25% of CT translated in the direction of superficial white matter (SWM) Each vertex file is either surface-smoothed with a 5 mm full-width half-max (FWHM) heat kernel (supplementary analyses) or a 20 mm FWHM heat kernel (main analyses). Markers are further either in raw form or residualized for mean curvature at the vertex level.

Age-related changes of intracortical myelin in bipolar disorder (BD) have been observed to deviate from the quadratic age curve observed in healthy controls (HC), but it is unclear if this holds at varying cortical depths. From BD (n = 44; age range = 17.6–45.5 years) and HC (n = 60; age range = 17.1–45.8 years) participants, we collected 3T T1-weighted (T1w) images with strong intracortical contrast. Signal values were sampled from 3 equivolume cortical depths. Linear mixed models were used to compare age-related changes in the T1w signal between depths and between groups at each depth. In HC, the age-related changes were significantly different between the superficial one-fourth depth and the deeper depths in the right ventral somatosensory (t = −4.63; FDRp = 0.00025), left dorsomedial somatosensory (t = −3.16; FDRp = 0.028), left rostral ventral premotor (t = −3.16; FDRp = 0.028), and right ventral inferior parietal cortex (t = −3.29; FDRp = 0.028). BD participants exhibited no differences in the age-related T1w signal between depths. Illness duration was negatively correlated with the T1w signal at the one-fourth depth in the right anterior cingulate cortex (rACC; rho = −0.50; FDRp = 0.029). Physiological age-related and depth-specific variation in the T1w signal were not observed in BD. The T1w signal in the rACC may reflect lifetime disease burden in the disorder.

The common marmoset has emerged as a popular model in neuroscience research, in part due to its reproductive efficiency, genetic and neuroanatomical similarities to humans and the successful generation of transgenic lines. Stereotaxic procedures in marmosets are guided by 2D stereotaxic atlases, which are constructed with a limited number of animals and fail to account for inter-individual variability in skull and brain size. Here, we developed a frameless imaging-guided stereotaxic system that improves upon traditional approaches by using subject-specific registration of computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) data to identify a surgical target, namely the putamen, in two marmosets. The skull surface was laser-scanned with to create a point cloud that was registered to the 3D reconstruction of the skull from CT. Reconstruction of the skull, as well as of the brain from MR images, was crucial for surgical planning. Localisation and injection into the putamen was done using a 6-axis robotic arm controlled by a surgical navigation software (BrainsightTM). Integration of subject-specific registration and frameless stereotaxic navigation allowed target localisation specific to each animal. Injection of alpha-synuclein fibrils into the putamen triggered progressive neurodegeneration of the nigro-striatal system, a key feature of Parkinson’s disease. Four months post-surgery, a PET scan found evidence of nigro-striatal denervation, supporting accurate targeting of the putamen during co-registration and subsequent surgery. Our results suggest that this approach, coupled with frameless stereotaxic neuronavigation, is accurate in localising surgical targets and can be used to assess endpoints for longitudinal studies.

The integrity and function of catecholamine neurotransmitter systems can be assessed using neuromelanin-sensitive MRI (NM-MRI). The relevance of this method to neurodegenerative and psychiatric disorders is becoming increasingly evident, and it has potential as a clinical biomarker.To support future application of NM-MRI as a clinical biomarker by defining the normative range of NM-MRI signal and volume metrics in cognitively normal older adults.Prospective.A total of 152 cognitively normal older adults aged 53-86 years old, including 41 participants who had follow-up NM-MRI data collected 9-16 months later.A 3.0 T; NM-MRI turbo spin echo and T1-weighted magnetization-prepared rapid acquisition with gradient echo sequences.NM-MRI images were processed to yield summary measures of volume and signal (contrast-to-noise ratio, CNR) for the substantia nigra (SN) and locus coeruleus (LC) using a recently developed software employing a fully automated algorithm. Change in these metrics over time was also assessed.Mean and standard deviation of NM-MRI metrics were calculated; change over time was tested for significance using 1-sample t-tests. P values 0.05 were considered statistically significant.At baseline SN signal (CNR) was 10.02% (left) and 10.28% (right) and LC signal was 24.71% (left) and 20.42% (right). Baseline SN volume was 576 mmWe report normative values for NM-MRI signal and volume in the SN and LC of cognitively normal older adults and explore their change over time. These values may help future efforts to use NM-MRI as a clinical biomarker by facilitating identification of patients with extreme NM-MRI values.1.

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.

PURPOSE In this work, we propose that Δ B1+ -induced errors in magnetization transfer (MT) saturation (MTsat ) maps can be corrected with use of an R1 and B1+ map and through numerical simulations of the sequence. THEORY AND METHODS One healthy subject was scanned at 3.0T using a partial quantitative MT protocol to estimate the relationship between observed R1 (R1,obs ) and apparent bound pool size ( M0,appB ) in the brain. MTsat values were simulated for a range of B1+ , R1,obs , and M0,appB . An equation was fit to the simulated MTsat , then a linear relationship between R1,obs and M0,appB was generated. These results were used to generate correction factor maps for the MTsat acquired from single-point data. The proposed correction was compared to an empirical correction factor with different MT-preparation schemes. RESULTS M0,appB was highly correlated with R1,obs (r > 0.96), permitting the use of R1,obs to estimate M0,appB for B1+ correction. All B1+ corrected MTsat maps displayed a decreased correlation with B1+ compared to uncorrected MTsat and MTsat corrected with an empirical factor in the corpus callosum. There was good agreement between the proposed approach and the empirical correction with radiofrequency saturation at 2 kHz, with larger deviations seen when using saturation pulses further off-resonance and in inhomogeneous (ih) MTsat maps. CONCLUSION The proposed correction decreases the dependence of MTsat on B1+ inhomogeneities. Furthermore, this flexible framework permits the use of different saturation protocols, making it useful for correcting B1+ inhomogeneities in ihMT.

Purpose Most voxels in white matter contain multiple fiber populations with different orientations and levels of myelination. Conventional T1 mapping measures 1 T1 value per voxel, representing a weighted average of the multiple tract T1 times. Inversion-recovery diffusion-weighted imaging (IR-DWI) allows the T1 times of multiple tracts in a voxel to be disentangled, but the scan time is prohibitively long. Recently, slice-shuffled IR-DWI implementations have been proposed to significantly reduce scan time. In this work, we demonstrate that we can measure tract-specific T1 values in the whole brain using simultaneous multi-slice slice-shuffled IR-DWI at 3T. Methods We perform simulations to evaluate the accuracy and precision of our crossing fiber IR-DWI signal model for various fiber parameters. The proposed sequence and signal model are tested in a phantom consisting of crossing asparagus pieces doped with gadolinium to vary T1 , and in 2 human subjects. Results Our simulations show that tract-specific T1 times can be estimated within 5% of the nominal fiber T1 values. Tract-specific T1 values were resolved in subvoxel 2 fiber crossings in the asparagus phantom. Tract-specific T1 times were resolved in 2 different tract crossings in the human brain where myelination differences have previously been reported; the crossing of the cingulum and genu of the corpus callosum and the crossing of the corticospinal tract and pontine fibers. Conclusion Whole-brain tract-specific T1 mapping is feasible using slice-shuffled IR-DWI at 3T. This technique has the potential to improve the microstructural characterization of specific tracts implicated in neurodevelopment, aging, and demyelinating disorders.

BackgroundThe integrity and function of catecholamine neurotransmitter systems can be assessed using MRI sequences often referred to as neuromelanin-sensitive MRI (NM-MRI). The relevance of this method to neurodegenerative and psychiatric disorders is becoming increasingly evident, and it has potential as a clinical biomarker. To support such future applications, we report here the normative range of NM-MRI signal and volume metrics in cognitively normal older adults.Methods3 Tesla NM-MRI images and demographic and cognitive data were available from 152 cognitively normal older adults aged 53-86 years old at baseline; a subsample of 68 participants also had follow-up NM-MRI data collected around one-year later. NM-MRI images were processed to yield summary measures of volume and signal (contrast-to-noise ratio, CNR) for the substantia nigra (SN) and locus coeruleus (LC) using a recently developed software employing a fully automated algorithm. The extent of annual change in these metrics was quantified and tested for significance using 1-sample t-tests.ResultsBaseline SN signal (CNR) was 10.02% (left SN) and 10.28% (right) and baseline LC signal was 24.71% (left) and 20.42% (right). The only NM-MRI metric to show a significant annual change was a decrease in left SN volume.ConclusionWe report normative values for NM-MRI signal and volume in the SN and LC of cognitively normal older adults and normative values for their change over time. These values may help future efforts to use NM-MRI as a clinical biomarker for adults in this age range by facilitating identification of patients with extreme NM-MRI values.

Cortical thickness (CT), gray-white matter contrast (GWC), boundary sharpness coefficient (BSC), and T1-weighted/T2-weighted ratio (T1w/T2w) are cortical metrics derived from standard T1- and T2-weighted magnetic resonance imaging (MRI) images that are often interpreted as representing or being influenced by intracortical myelin content. However, there is little empirical evidence to justify these interpretations nor have the homologies or differences between these measures been examined. We examined differences and similarities in group mean and age-related trends with the underlying hypothesis that different measures sensitive to similar changes in underlying myelo- and microstructural processes should be highly related. We further probe their sensitivity to cellular organization using the BigBrain, a high-resolution digitized volume stemming from a whole human brain histologically stained for cell bodies with the Merker stain.The measures were generated on both the MRI-derived images of 127 healthy subjects, aged 18 to 81, and on the BigBrain volume using cortical surfaces that were generated with the CIVET 2.1.0 pipeline. Comparing MRI markers between themselves, our results revealed generally high overlap in spatial distribution (i.e., group mean), but mostly divergent age trajectories in the shape, direction, and spatial distribution of the linear age effect. Significant spatial relationships were found between the BSC and GWC and their BigBrain equivalent, as well as a correlation approaching significance between the BigBrain intensities and the T1w/T2w ratio in gray matter (GM) both sampled at half cortical depth.We conclude that the microstructural properties at the source of spatial distributions of MRI cortical markers (e.g. GM myelin) can be different from microstructural changes that affect these markers in aging. While our findings highlight a discrepancy in the interpretation of the biological underpinnings of the cortical markers, they also highlight their potential complementarity, as they are largely independent in aging. Our BigBrain results indicate a general trend of GM T1w signal and myelin being spatially related to the density of cells, which is possibly more pronounced in superficial cortical layers.Highlights–Different MRI cortical markers aim to represent myelin and microstructure–These markers show high spatial overlap, but mostly divergent age trajectories–It is unlikely that myelin changes are the source of the age effect for all markers–Trend of MRI signal being related to cell density in more superficial cortical layers

In this work, we propose that ΔOne healthy subject was scanned at 3.0T using a partial quantitative MT protocol to estimate the relationship between observed RThe proposed correction decreases the dependence of MT

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 increases in functional connectivity during fast learning in the sensorimotor territory of the internal segment of right globus pallidus (GPi), and sequence-specific decreases in right supplementary motor area (SMA) in overall learning. We found that connectivity changes in key regions of the motor network including the superior parietal cortex (SPC) and primary motor cortex (M1) were not a result of sequence-specific learning but were instead linked to motor execution. Our study confirms the sequence-specific role of SMA and GPi that has previously been identified in online task-based learning studies in humans and primates, and extends it to resting state network changes after sequence-specific MSL. Finally, our results shed light on a timing-specific plasticity mechanism between GPi and SMA following MSL.

Highlights • PREVENT-AD is openly releasing datasets to the neuroscience community. • PREVENT-AD is a longitudinal study of older adults at-risk of Alzheimer disease. • Data include imaging, genetics, fluid biochemistry, neurosensory, cognition and more. • Data collection methods and data sharing plans for open science are described., To move Alzheimer Disease (AD) research forward it is essential to collect data from large cohorts, but also make such data available to the global research community. We describe the creation of an open science dataset from the PREVENT-AD (PResymptomatic EValuation of Experimental or Novel Treatments for AD) cohort, composed of cognitively unimpaired older individuals with a parental or multiple-sibling history of AD. From 2011 to 2017, 386 participants were enrolled (mean age 63 years old ± 5) for sustained investigation among whom 349 have retrospectively agreed to share their data openly. Repositories are findable through the unified interface of the Canadian Open Neuroscience Platform and contain up to five years of longitudinal imaging data, cerebral fluid biochemistry, neurosensory capacities, cognitive, genetic, and medical information. Imaging data can be accessed openly at https://openpreventad.loris.ca while most of the other information, sensitive by nature, is accessible by qualified researchers at https://registeredpreventad.loris.ca. In addition to being a living resource for continued data acquisition, PREVENT-AD offers opportunities to facilitate understanding of AD pathogenesis.

Most voxels in white matter contain multiple fiber populations with different orientations and levels of myelination. Conventional TWe perform simulations to evaluate the accuracy and precision of our crossing fiber IR-DWI signal model for various fiber parameters. The proposed sequence and signal model are tested in a phantom consisting of crossing asparagus pieces doped with gadolinium to vary TOur simulations show that tract-specific TWhole-brain tract-specific T

The study of the hippocampus across the healthy adult lifespan has rendered inconsistent findings. While volumetric measurements have often been a popular technique for analysis, more advanced morphometric techniques have demonstrated compelling results that highlight the importance and improved specificity of shape-based measures. Here, the MAGeT Brain algorithm was applied on 134 healthy individuals aged 18-81 years old to extract hippocampal subfield volumes and hippocampal shape measurements, notably: local surface area (SA) and displacement. We used linear, second or third order natural splines to examine the relationships between hippocampal measures and age. In addition, partial least squares analyses were performed to relate measurements with cognitive and demographic information. Volumetric results indicated a relative preservation of the right cornus ammonis 1 with age and a global volume reduction linked with older age, female sex, lower levels of education and cognitive performance. Vertex-wise analysis demonstrated an SA preservation in the anterior hippocampus with a peak during the sixth decade, while the posterior hippocampal SA gradually decreased across lifespan. Overall, SA decrease was linked to older age, female sex and, to a lesser extent lower levels of education and cognitive performance. Outward displacement in the lateral hippocampus and inward displacement in the medial hippocampus were enlarged with older age, lower levels of cognition and education, indicating an accentuation of the hippocampal “C” shape with age. Taken together, our findings suggest that vertex-wise analyses have higher spatial specifity and that sex, education and cognition are implicated in the differential impact of age on hippocampal subregions throughout its antero-posterior and medial-lateral axes.

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.

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 Tesla 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 5 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.

Many magnetic resonance imaging (MRI) indices are being studied longitudinally to explore topics such as biomarker detection and clinical staging. A pertinent concern to longitudinal work is MRI scanner upgrades. When upgrades occur during the course of a longitudinal MRI neuroimaging investigation, there may be an impact on the compatibility of pre- and post-upgrade measures. Similarly, subject motion is another issue that may be detrimental to longitudinal MRI work; however, embedding volumetric navigators (vNavs) within acquisition sequences has emerged as a technique that allows for prospective motion correction. Our research group recently implemented an upgrade from a Siemens MAGNETOM 3T Trio system to a Siemens MAGNETOM 3T Prisma Fit system. The goals of the current work were to: 1) investigate the impact of this upgrade on commonly used structural imaging measures and proton magnetic resonance spectroscopy indices (“Prisma Upgrade protocol”) and 2) examine structural imaging measures in a sequence with vNavs alongside a standard acquisition sequence (“vNav protocol”). In both protocols, while high reliability was observed for most of the investigated MRI outputs, suboptimal reliability was observed for certain indices. Across the scanner upgrade, increases in frontal, temporal, and cingulate cortical thickness (CT) and thalamus volume, along with decreases in parietal CT, amygdala, globus pallidus, hippocampus, and striatum volumes were observed across the Prisma upgrade, and were linked to increases in signal-to-noise ratios. No significant impact of the upgrade was found in 1H-MRS analyses. Further, CT estimates were found to be larger in MPRAGE acquisitions compared to vNav-MPRAGE acquisitions mainly within temporal areas, while the opposite was found mostly in parietal brain regions. The results from this work should be considered in longitudinal study designs and comparable prospective motion correction investigations are warranted in cases of marked head movement.

MRI-histology correlation studies of the ex vivo brain mostly employ fresh, extracted (ex situ) specimens, aldehyde fixed by immersion. This method entails manipulation of the fresh brain during extraction, introducing several disadvantages: deformation of the specimen prior to MRI acquisition; introduction of air bubbles in the sulci, creating artifacts; and uneven or poor fixation of the deeper regions of the brain.We propose a new paradigm to scan the ex vivo brain, exploiting a technique used by anatomists: fixation by whole body perfusion, which implies fixation of the brain in situ. This allows scanning the brain surrounded by fluids, meninges, and skull, thus preserving the structural relationships of the brain in vivo and avoiding the disadvantages of ex situ scanning. Our aims were: 1) to assess whether months of in situ fixation resulted in a loss of fluid around the brain; 2) to evaluate whether in situ fixation modified antigenicity for myelin and neuron specific marker; 3) to assess whether in situ fixation improved the register of ex vivo brain images to standard neuroanatomical templates in pseudo-Talairach space for morphometry studies.Five head specimens fixed with a saturated sodium chloride solution (a non-standard fixative used in our anatomy laboratory for neurosurgical simulation) were employed. We acquired 3D T1-weighted (MPRAGE), 2D fluid-attenuated inversion recovery T2-weighted turbo spin echo (T2w-FLAIR), and 3D gradient-echo (3D-GRE) pulse sequences of all brains on a 1.5T MRI. After brain extraction, sections were processed for binding with myelin basic protein (MBP) and neuronal nuclei (NeuN) primary antibodies by immunofluorescence.This study showed that all but one specimen retained fluids in the subarachnoid and ventricular spaces. The specimen that lost fluid was the oldest one, with the longest interval between the time of death and the MRI scanning day being 403 days. All T1-weighted images were successfully processed through a validated pipeline used with in vivo MRIs. The pipeline did not require any modification to run on the ex vivo-in situ scans. All scans were successfully registered to the brain template, more accurately than an ex vivo-ex situ scan and exhibited positive antigenicity for MBP and NeuN.MRI and histology study of the ex vivo-in situ brain fixed by perfusion is feasible and allows for in situ MRI imaging for of at least 10 months post-mortem prior to histology analyses. Fluids around and inside the brain specimens and antigenicity for myelin and neurons were all well preserved.

To move Alzheimer Disease (AD) research forward it is essential to collect data from large cohorts, but also make such data available to the global research community. We describe the creation of an open science dataset from the PREVENT-AD (PResymptomatic EValuation of Experimental or Novel Treatments for AD) cohort, composed of cognitively unimpaired older individuals with a parental or multiple-sibling history of AD. From 2011 to 2017, 386 participants were enrolled (mean age 63 years old ± 5) for sustained investigation among whom 349 have retrospectively agreed to share their data openly. Repositories are findable through the unified interface of the Canadian Open Neuroscience Platform (https://portal.conp.ca/) and contain up to five years of longitudinal imaging data, cerebral fluid biochemistry, neurosensory capacities, cognitive, genetic, and medical information. Imaging data can be accessed openly at https://openpreventad.loris.ca while most of the other information, sensitive by nature, is accessible by qualified researchers at https://registeredpreventad.loris.ca. In addition to being a living resource for continued data acquisition, PREVENT-AD offers opportunities to facilitate understanding of AD pathogenesis.

Physical exercise has been suggested to improve cognitive performance through various neurobiological mechanisms, mediated by growth factors such as BDNF, IGF-I, and VEGF. Moreover, animal research has demonstrated that combined physical and cognitive stimulation leads to increased adult neurogenesis as compared to either experimental condition alone. In the present study, we therefore investigated whether a sequential combination of physical and spatial training in young, healthy adults elicits an additive effect on training and transfer gains. To this end, we compared the effects of (i) eight 20-minute sessions of cycling, (ii) sixteen 30-minute sessions of spatial training, (iii) a combination of both, and included (iv) a passive control cohort. We assessed longitudinal changes in cognitive performance, growth factor levels, and T1 relaxation of hippocampal subfields (acquired with 7 T MRI). While substantial physical and spatial training gains were elicited in all trained groups, longitudinal transfer changes did not differ between these groups. Notably, we found no evidence for an additive effect of sequential physical and spatial training. These results challenge the extrapolation from the findings reported in animals to young, healthy adults.

Many magnetic resonance imaging (MRI) measures are being studied longitudinally to explore topics such as biomarker detection and clinical staging. A pertinent concern to longitudinal work is MRI scanner upgrades. When upgrades occur during the course of a longitudinal MRI neuroimaging investigation, there may be an impact on the compatibility of pre- and post-upgrade measures. Similarly, subject motion is another issue that may be detrimental to MRI work and embedding volumetric navigators (vNavs) within acquisition sequences has emerged as a technique that allows for prospective motion correction. Our research group recently underwent an upgrade from a Siemens MAGNETOM 3T Tim Trio system to a Siemens MAGNETOM 3T Prisma Fit system. The goals of the current work were to: 1) investigate the impact of this upgrade on commonly used structural imaging measures and proton magnetic resonance spectroscopy indices (“Prisma Upgrade protocol”) and 2) examine structural imaging measures in a sequence with vNavs alongside a standard acquisition sequence (“vNav protocol”). While high reliability was observed for most of the investigated MRI outputs, suboptimal reliability was observed for certain indices. Across the scanner upgrade, increases in frontal, temporal, and cingulate cortical thickness (CT) and thalamus volume, along with decreases in parietal CT, amygdala, globus pallidus, hippocampus, and striatum volumes were observed across the upgrade. No significant impact of the upgrade was found in 1H-MRS analyses. Further, CT estimates were found to be larger in MPRAGE acquisitions compared to vNav-MPRAGE acquisitions mainly within temporal areas, while the opposite was found mostly in parietal brain regions. The results from this work should be considered in longitudinal study designs and comparable prospective motion correction investigations are warranted in cases of marked head movement.

Neuropathological and in vivo brain imaging studies agree that the cornu ammonis 1 and subiculum subfields of the hippocampus are most vulnerable to atrophy in the prodromal phases of Alzheimer's disease (AD). However, there has been limited investigation of the structural integrity of the components of the hippocampal circuit, including subfields and extra-hippocampal white matter structure, in relation to the progression of well-accepted cerebrospinal fluid (CSF) biomarkers of AD, amyloid-β 1-42 (Aβ) and total-tau (tau). We investigated these relationships in 88 aging asymptomatic individuals with a parental or multiple-sibling familial history of AD. Apolipoprotein (APOE) ɛ4 risk allele carriers were identified, and all participants underwent cognitive testing, structural magnetic resonance imaging, and lumbar puncture for CSF assays of tau, phosphorylated-tau (p-tau) and Aβ. Individuals with a reduction in CSF Aβ levels (an indicator of amyloid accretion into neuritic plaques) as well as evident tau pathology (believed to be linked to neurodegeneration) exhibited lower subiculum volume, lower fornix microstructural integrity, and a trend towards lower cognitive score than individuals who showed only reduction in CSF Aβ. In contrast, persons with normal levels of tau showed an increase in structural MR markers in relation to declining levels of CSF Aβ. These results suggest that hippocampal subfield volume and extra-hippocampal white matter microstructure demonstrate a complex pattern where an initial volume increase is followed by decline among asymptomatic individuals who, in some instances, may be a decade or more away from onset of cognitive or functional impairment.

PURPOSE B1 mapping is important for many quantitative imaging protocols, particularly those that include whole-brain T1 mapping using the variable flip angle (VFA) technique. However, B1 mapping sequences are not typically available on many magnetic resonance imaging (MRI) scanners. The aim of this work was to demonstrate that B1 mapping implemented using standard scanner product pulse sequences can produce B1 (and VFA T1 ) maps comparable in quality and acquisition time to advanced techniques. MATERIALS AND METHODS Six healthy subjects were scanned at 3.0T. An interleaved multislice spin-echo echo planar imaging double-angle (EPI-DA) B1 mapping protocol, using a standard product pulse sequence, was compared to two alternative methods (actual flip angle imaging, AFI, and Bloch-Siegert shift, BS). Single-slice spin-echo DA B1 maps were used as a reference for comparison (Ref. DA). VFA flip angles were scaled using each B1 map prior to fitting T1 ; the nominal flip angle case was also compared. RESULTS The pooled-subject voxelwise correlation (ρ) for B1 maps (BS/AFI/EPI-DA) relative to the reference B1 scan (Ref. DA) were ρ = 0.92/0.95/0.98. VFA T1 correlations using these maps were ρ = 0.86/0.88/0.96, much better than without B1 correction (ρ = 0.53). The relative error for each B1 map (BS/AFI/EPI-DA/Nominal) had 95th percentiles of 5/4/3/13%. CONCLUSION Our findings show that B1 mapping implemented using product pulse sequences can provide excellent quality B1 (and VFA T1 ) maps, comparable to other custom techniques. This fast whole-brain measurement (∼2 min) can serve as an excellent alternative for researchers without access to advanced B1 pulse sequences. LEVEL OF EVIDENCE 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1673-1682.

Research in the macaque monkey suggests that cortical areas with similar microstructure are more likely to be connected. Here, we examine this link in the human cerebral cortex using 2 magnetic resonance imaging (MRI) measures: quantitative T1 maps, which are sensitive to intracortical myelin content and provide an in vivo proxy for cortical microstructure, and resting-state functional connectivity. Using ultrahigh-resolution MRI at 7 T and dedicated image processing tools, we demonstrate a systematic relationship between T1-based intracortical myelin content and functional connectivity. This effect is independent of the proximity of areas. We employ nonlinear dimensionality reduction to characterize connectivity components and identify specific aspects of functional connectivity that are linked to myelin content. Our results reveal a consistent spatial pattern throughout different analytic approaches. While functional connectivity and myelin content are closely linked in unimodal areas, the correspondence is lower in transmodal areas, especially in posteromedial cortex and the angular gyrus. Our findings are in agreement with comprehensive reports linking histologically assessed microstructure and connectivity in different mammalian species and extend them to the human cerebral cortex in vivo.

While numerous studies have used magnetic resonance imaging (MRI) to elucidate normative age‐related trajectories in subcortical structures across the human lifespan, there exists substantial heterogeneity among different studies. Here, we investigated the normative relationships between age and morphology (i.e., volume and shape), and microstructure (using the T1‐weighted/T2‐weighted [T1w/T2w] signal ratio as a putative index of myelin and microstructure) of the striatum, globus pallidus, and thalamus across the adult lifespan using a dataset carefully quality controlled, yielding a final sample of 178 for the morphological analyses, and 162 for the T1w/T2w analyses from an initial dataset of 253 healthy subjects, aged 18–83. In accordance with previous cross‐sectional studies of adults, we observed age‐related volume decrease that followed a quadratic relationship between age and bilateral striatal and thalamic volumes, and a linear relationship in the globus pallidus. Our shape indices consistently demonstrated age‐related posterior and medial areal contraction bilaterally across all three structures. Beyond morphology, we observed a quadratic inverted U‐shaped relationship between T1w/T2w signal ratio and age, with a peak value occurring in middle age (at around 50 years old). After permutation testing, the Akaike information criterion determined age relationships remained significant for the bilateral globus pallidus and thalamus, for both the volumetric and T1w/T2w analyses. Our findings serve to strengthen and expand upon previous volumetric analyses by providing a normative baseline of morphology and microstructure of these structures to which future studies investigating patients with various disorders can be compared.

The hippocampus has been extensively studied in various neuropsychiatric disorders throughout the lifespan. However, inconsistent results have been reported with respect to which subfield volumes are most related to age. Here, we investigate whether these discrepancies may be explained by experimental design differences that exist between studies. Multiple datasets were used to collect 1690 magnetic resonance scans from healthy individuals aged 18-95 years old. Standard T1-weighted (T1w; MPRAGE sequence, 1 mm3 voxels), high-resolution T2-weighted (T2w; SPACE sequence, 0.64 mm3 voxels) and slab T2-weighted (Slab; 2D turbo spin echo, 0.4 x 0.4 x 2 mm3 voxels) images were acquired. The MAGeT Brain algorithm was used for segmentation of the hippocampal grey matter (GM) subfields and peri-hippocampal white matter (WM) subregions. Linear mixed-effect models and Akaike information criterion were used to examine linear, second or third order natural splines relationship between hippocampal volumes and age. We demonstrated that stratum radiatum/lacunosum/moleculare and fornix subregions expressed the highest relative volumetric decrease, while the cornus ammonis 1 presented a relative volumetric preservation of its volume with age. We also found that volumes extracted from slab images were often underestimated and demonstrated different age-related relationships compared to volumes extracted from T1w and T2w images. The current work suggests that although T1w, T2w and slab derived subfield volumetric outputs are largely homologous, modality choice plays a meaningful role in the volumetric estimation of the hippocampal subfields.

Over the last two decades, numerous human MRI studies of neuroplasticity have shown compelling evidence for extensive and rapid experience-induced brain plasticity in vivo. To date, most of these studies have consisted of simply detecting a difference in structural or functional images with little concern for their lack of biological specificity. Recent reviews and public debates have stressed the need for advanced imaging techniques to gain a better understanding of the nature of these differences - characterizing their extent in time and space, their underlying biological and network dynamics. The purpose of this article is to give an overview of advanced imaging techniques for an audience of cognitive neuroscientists that can assist them in the design and interpretation of future MRI studies of neuroplasticity. The review encompasses MRI methods that probe the morphology, microstructure, function, and connectivity of the brain with improved specificity. We underline the possible physiological underpinnings of these techniques and their recent applications within the framework of learning- and experience-induced plasticity in healthy adults. Finally, we discuss the advantages of a multi-modal approach to gain a more nuanced and comprehensive description of the process of learning.

Background MRI-histology correlation studies of the ex vivo brain mostly employ fresh, extracted (ex situ) specimens, aldehyde fixed by immersion, which has several disadvantages for MRI scanning (e.g. deformation of the organ). A minority of studies are done ex vivo-in situ (unfixed brain), requiring an MRI scanner readily available within a few hours of the time of death. New Method We propose a new technique, exploited by anatomists, for scanning the ex vivo brain: fixation by whole body perfusion, which implies fixation of the brain in situ. This allows scanning the brain surrounded by fluids, meninges, and skull, preserving the structural relationships of the brain in vivo. To evaluate the proposed method, five heads perfused-fixed with a saturated sodium chloride solution were employed. Three sequences were acquired on a 1.5 T MRI scanner: T1weighted, T2weighted-FLAIR, and Gradient-echo. Histology analysis included immunofluorescence for myelin basic protein and neuronal nuclei. Results All MRIs were successfully processed through a validated pipeline used with in vivo MRIs. All cases exhibited positive antigenicity for myelin and neuronal nuclei. Comparison with existing methods All scans registered to a standard neuroanatomical template in pseudo-Talairach space more accurately than an ex vivo-ex situ scan. The time interval to scan the ex vivo brain in situ was increased to at least 10 months. Conclusions MRI and histology study of the ex vivo-in situ brain fixed by perfusion is an alternative approach that has important procedural and practical advantages over the two standard methods to study the ex vivo brain.

BACKGROUND: The hippocampus and associated circuitry are integral to the manifestation of psychosis and associated symptoms. There is evidence for the hippocampus as a key hub in healthy brain networks, which situates the hippocampus as an important target in the emerging view of psychosis as a disorder of altered connectome development. Here, we test the hypothesis that longitudinal changes in the hippocampus and surrounding white matter in relation to coordinated changes within intracortical (IC) and superficial white matter (SWM) microstructure in first episode psychosis (FEP) patients is altered compared to controls. We also examine whether such alterations are associated with changes in negative symptoms and verbal memory, two significant predictors of functional outcome. METHODS: Longitudinal MRI scans (3T; 2–4 visits over 3–21 months) were acquired for 23 FEP and 26 HC. MP2RAGE quantitative T1 (qT1) maps, sensitive to myelin content, were used to sample microstructure of the hippocampus, IC and SWM regions. Mean qT1 for hippocampal subfields and output circuitry (fimbria, alveus, fornix, mammillary bodies) were calculated based on labels extracted from high-resolution T2-weighted scans (0.64 mm3) with MAGeT-Brain. IC qT1 was defined as the average qT1 at 35/45/55/65% cortical depths, and SWM qT1 was sampled 1mm below the grey-white matter boundary, across 81924 points of the brain surface, in relation to grey and white matter surfaces generated by CIVET. Cortical regions were then parcellated based on the Desikan-Killiany-Tourville atlas. Relationships between pair-wise regional trajectories were calculated for each subject, defined as the theta angle of separation between the qT1 rates of change of any two brain regions between timepoints. Parcellations of brain regions were defined a priori, where hippocampal subfields and surrounding white matter formed one parcel, and cortical regions were assigned to 7 parcels based on known functional networks. Graph theory was used to calculate participation coefficient (PC), to measure the distribution of connections between the hippocampal parcel to IC and SWM of the 7 cortical parcels. Mean PC of the hippocampal module was compared between FEP and controls, then correlated to changes in negative symptoms and Logical Memory from the Weschler Memory Scale in FEP. RESULTS: The PC of the hippocampal parcel in relation to IC networks was significantly reduced in FEP compared to HC (F1,45=9.85, p=0.003), and nominally reduced in relation to SWM (F1,45=4.67, p=0.036). Post-hoc analyses of individual subregions were restricted to hippocampal-IC networks, where CA1 and alveus bilaterally, left molecular layer, fornix, mammillary body and right fimbria significantly contributed to reduced hippocampal PC (p

Magnetic resonance imaging at ultra high field opens the door to quantitative brain imaging at sub-millimeter isotropic resolutions. However, novel image processing tools to analyze these new rich datasets are lacking. In this article, we introduce the Open Science CBS Neuroimaging Repository: a unique repository of high-resolution and quantitative images acquired at 7 T. The motivation for this project is to increase interest for high-resolution and quantitative imaging and stimulate the development of image processing tools developed specifically for high-field data. Our growing repository currently includes datasets from MP2RAGE and multi-echo FLASH sequences from 28 and 20 healthy subjects respectively. These datasets represent the current state-of-the-art in in-vivo relaxometry at 7 T, and are now fully available to the entire neuroimaging community.

The position of cortical areas can be approximately predicted from cortical surface folding patterns. However, there is extensive inter-subject variability in cortical folding patterns, prohibiting a one-to-one mapping of cortical folds in certain areas. In addition, the relationship between cortical area boundaries and the shape of the cortex is variable, and weaker for higher-order cortical areas. Current surface registration techniques align cortical folding patterns using sulcal landmarks or cortical curvature, for instance. The alignment of cortical areas by these techniques is thus inherently limited by the sole use of geometric similarity metrics. Magnetic resonance imaging T1 maps show intra-cortical contrast that reflects myelin content, and thus can be used to improve the alignment of cortical areas. In this article, we present a new symmetric diffeomorphic multi-contrast multi-scale surface registration (MMSR) technique that works with partially inflated surfaces in the level-set framework. MMSR generates a more precise alignment of cortical surface curvature in comparison to two widely recognized surface registration algorithms. The resulting overlap in gyrus labels is comparable to FreeSurfer. Most importantly, MMSR improves the alignment of cortical areas further by including T1 maps. As a first application, we present a group average T1 map at a uniquely high-resolution and multiple cortical depths, which reflects the myeloarchitecture of the cortex. MMSR can also be applied to other MR contrasts, such as functional and connectivity data.

Purpose There are many T1 mapping methods available, each of them validated in phantoms and reporting excellent agreement with literature. However, values in literature vary greatly, with T1 in white matter ranging from 690 to 1100 ms at 3 Tesla. This brings into question the accuracy of one of the most fundamental measurements in quantitative MRI. Our goal was to explain these variations and look into ways of mitigating them. Theory and Methods We evaluated the three most common T1 mapping methods (inversion recovery, Look-Locker, and variable flip angle) through Bloch simulations, a white matter phantom and the brains of 10 healthy subjects (single-slice). We pooled the T1 histograms of the subjects to determine whether there is a sequence-dependent bias and whether it is reproducible across subjects. Results We found good agreement between the three methods in phantoms, but poor agreement in vivo, with the white matter T1 histogram peak in healthy subjects varying by more than 30% depending on the method used. We also found that the pooled brain histograms displayed three distinct white matter peaks, with Look-Locker consistently underestimating, and variable flip angle overestimating the inversion recovery T1 values. The Bloch simulations indicated that incomplete spoiling and inaccurate B1 mapping could account for the observed differences. Conclusion We conclude that the three most common T1 mapping protocols produce stable T1 values in phantoms, but not in vivo. To improve the accuracy of T1 mapping, we recommend that sites perform in vivo validation of their T1 mapping method against the inversion recovery reference method, as the first step toward developing a robust calibration scheme. Magn Reson Med 73:514–522, 2015. © 2014 Wiley Periodicals, Inc.

Computational anatomy studies typically use T1-weighted magnetic resonance imaging contrast to look at local differences in cortical thickness or grey matter volume across time or subjects. This type of analysis is a powerful and non-invasive tool to probe anatomical changes associated with neurodevelopment, aging, disease or experience-induced plasticity. However, these comparisons could suffer from biases arising from vascular and metabolic subject- or time-dependent differences. Differences in blood flow and volume could be caused by vasodilation or differences in vascular density, and result in a larger signal contribution of the blood compartment within grey matter voxels. Metabolic changes could lead to differences in dissolved oxygen in brain tissue, leading to T1 shortening. Here, we analyze T1 maps and T1-weighted images acquired during different breathing conditions (ambient air, hypercapnia (increased CO2) and hyperoxia (increased O2)) to evaluate the effect size that can be expected from changes in blood flow, volume and dissolved O2 concentration in computational anatomy studies. Results show that increased blood volume from vasodilation during hypercapnia is associated with an overestimation of cortical thickness (1.85%) and grey matter volume (3.32%), and that both changes in O2 concentration and blood volume lead to changes in the T1 value of tissue. These results should be taken into consideration when interpreting existing morphometry studies and in future study design. Furthermore, this study highlights the overlap in structural and physiological MRI, which are conventionally interpreted as two independent modalities.

Background Integrity of hippocampal subfield structure and associated limbic circuitry subserves various memory processes, a domain that is impaired in psychosis and an important predictor of functional outcome. We use a novel atlas that encapsulates both hippocampal subfields and surrounding white matter (WM), forming the ‘memory circuit’, to assess volumes with high-resolution MRI, and microstructure with quantitative T1 (qT1). Our aims were to examine 1) group by time interactions on memory measures and the memory circuit, and 2) explore the relationships between the chosen memory measures and limbic structures, informed by results from 1), in a longitudinal sample of first episode of psychosis (FEP) patients. Methods Nineteen FEP and 20 controls with baseline and 3-month follow-up data were included. Logical Memory and Visual Reproduction Subscales of the Weschler Memory Scale, and MRI scans on a 3T scanner were collected. High-resolution T2-weighted images (0.64 mm3) were input to the MAGeT Brain algorithm to obtain volumes of hippocampal subfields and surrounding WM, defined by fimbria, alveus, fornix, and mammillary bodies. Mean qT1 values for each hippocampal subfield and WM structure were sampled from MP2RAGE (1 mm3) qT1 maps. Linear mixed models were used to assess group by time interactions on memory measures, volumes and qT1. To begin, total hippocampal volumes and WM structure for each hemisphere were examined using a Bonferroni correction for multiple comparisons, followed by post-hoc tests of individual subfields and WM structures. Linear models were then used to assess relationships between baseline memory and change in anatomical measures of interest in FEP. Models controlled for sex, education, age, and brain volume. Results Significant group by time interactions emerged on bilateral mean WM qT1 (left: F1,65=9.3, p=.003; right: F1,65=10.6, p=.002), where it was found that within the FEP group, qT1 (relaxation time in ms) increased over the 3-month follow-up period. Looking at WM structures separately, the interaction was driven by qT1 changes in fimbria, fornix, and mammillary bodies bilaterally (p’s