The Canadian Dementia Imaging Protocol: Harmonizing National Cohorts.

BACKGROUND: Harmonized protocols to collect imaging data must be devised, employed, and maintained in multicentric studies to reduce interscanner variability in subsequent analyses. PURPOSE: To present a standardized protocol for multicentric research on dementia linked to neurodegeneration in aging, harmonized on all three major vendor platforms. The protocol includes a common procedure for qualification, quality control, and quality assurance and feasibility in large-scale studies. STUDY TYPE: Prospective. SUBJECTS: The study involved a geometric phantom, a single individual volunteer, and 143 cognitively healthy, mild cognitively impaired, and Alzheimer's disease participants in a large-scale, multicentric study. FIELD STRENGTH/SEQUENCES: MRI was perform with 3T scanners (GE, Philips, Siemens) and included 3D T1 w, PD/T2 w, T2* , T2 w-FLAIR, diffusion, and BOLD resting state acquisitions. ASSESSMENT: Measures included signal- and contrast-to-noise ratios (SNR and CNR, respectively), total brain volumes, and total scan time. STATISTICAL TESTS: SNR, CNR, and scan time were compared between scanner vendors using analysis of variance (ANOVA) and Tukey tests, while brain volumes were tested using linear mixed models. RESULTS: Geometric phantom T1 w SNR was significantly (P < 0.001) higher in Philips (mean: 71.4) than Siemens (29.5), while no significant difference was observed between vendors for T2 w (32.0 and 37.2, respectively, P = 0.243). Single individual volunteer T1 w CNR was higher in subcortical regions for Siemens (P < 0.001), while Philips had higher cortical CNR (P = 0.044). No significant difference in brain volumes was observed between vendors (P = 0.310/0.582/0.055). The average scan time was 41.0 minutes (SD: 2.8) and was not significantly different between sites (P = 0.071) and cognitive groups (P = 0.853). DATA CONCLUSION: The harmonized Canadian Dementia Imaging Protocol suits the needs of studies that need to ensure quality MRI data acquisition for the measurement of brain changes across adulthood, due to aging, neurodegeneration, and other etiologies. A detailed description, exam cards, and operators' manual are freely available at the following site: www.cdip-pcid.ca. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:456-465.

fMRI and sleep correlates of the age-related impairment in motor memory consolidation.

Behavioral studies indicate that older adults exhibit normal motor sequence learning (MSL), but paradoxically, show impaired consolidation of the new memory trace. However, the neural and physiological mechanisms underlying this impairment are entirely unknown. Here, we sought to identify, through functional magnetic resonance imaging during MSL and electroencephalographic (EEG) recordings during daytime sleep, the functional correlates and physiological characteristics of this age-related motor memory deficit. As predicted, older subjects did not exhibit sleep-dependent gains in performance (i.e., behavioral changes that reflect consolidation) and had reduced sleep spindles compared with young subjects. Brain imaging analyses also revealed that changes in activity across the retention interval in the putamen and related brain regions were associated with sleep spindles. This change in striatal activity was increased in young subjects, but reduced by comparison in older subjects. These findings suggest that the deficit in sleep-dependent motor memory consolidation in elderly individuals is related to a reduction in sleep spindle oscillations and to an associated decrease of activity in the cortico-striatal network.

Measurement Variability Following MRI System Upgrade.

Major hardware/software changes to MRI platforms, either planned or unplanned, will almost invariably occur in longitudinal studies. Our objective was to assess the resulting variability on relevant imaging measurements in such context, specifically for three Siemens Healthcare Magnetom Trio upgrades to the Prismafit platform. We report data acquired on three healthy volunteers scanned before and after three different platform upgrades. We assessed differences in image signal [contrast-to-noise ratio (CNR)] on T1-weighted images (T1w) and fluid-attenuated inversion recovery images (FLAIR); brain morphometry on T1w image; and small vessel disease (white matter hyperintensities; WMH) on FLAIR image. Prismafit upgrade resulted in higher (30%) and more variable neocortical CNR and larger brain volume and thickness mainly in frontal areas. A significant relationship was observed between neocortical CNR and neocortical volume. For FLAIR images, no significant CNR difference was observed, but WMH volumes were significantly smaller (-68%) after Prismafit upgrade, when compared to results on the Magnetom Trio. Together, these results indicate that Prismafit upgrade significantly influenced image signal, brain morphometry measures and small vessel diseases measures and that these effects need to be taken into account when analyzing results from any longitudinal study undergoing similar changes.

The Canadian Dementia Imaging Protocol: Harmonization validity for morphometry measurements.

The harmonized Canadian Dementia Imaging Protocol (CDIP) has been developed to suit the needs of a number of co-occurring Canadian studies collecting data on brain changes across adulthood and neurodegeneration. In this study, we verify the impact of CDIP parameters compliance on total brain volume variance using 86 scans of the same individual acquired on various scanners. Data included planned data collection acquired within the Consortium pour l'identification précoce de la maladie Alzheimer - Québec (CIMA-Q) and Canadian Consortium on Neurodegeneration in Aging (CCNA) studies, as well as opportunistic data collection from various protocols. For images acquired from Philips scanners, lower variance in brain volumes were observed when the stated CDIP resolution was set. For images acquired from GE scanners, lower variance in brain volumes were noticed when TE/TR values were within 5% of the CDIP protocol, compared to values farther from that criteria. Together, these results suggest that a harmonized protocol like the CDIP may help to reduce neuromorphometric measurement variability in multi-centric studies.

Double-layer estimation of intra- and extracerebral hemoglobin concentration with a time-resolved system.

We present in vivo measurements of baseline physiology from five subjects with a four-wavelength (690, 750, 800, and 850 nm) time-resolved optical system. The measurements were taken at four distances: 10, 15, 25, and 30 mm. All distances were fit simultaneously with a two-layered analytical model for the absorption and reduced scattering coefficient of both layers. The thickness of the first layer, comprising the skin, scalp, and cerebrospinal fluid, was obtained from anatomical magnetic resonance images. The fitting procedure was first tested with simulations before being applied to in vivo measurements and verified that this procedure permits accurate characterization of the hemoglobin concentrations in the extra- and intracerebral tissues. Baseline oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentrations and oxygen saturation were recovered from in vivo measurements and compared to the literature. We observed a noticeable intersubject variability of the hemoglobin concentrations, but constant values for the cerebral hemoglobin oxygen saturation.

Pointing with the eyes: the role of gaze in communicating danger.

Facial expression and direction of gaze are two important sources of social information, and what message each conveys may ultimately depend on how the respective information interacts in the eye of the perceiver. Direct gaze signals an interaction with the observer but averted gaze amounts to "pointing with the eyes", and in combination with a fearful facial expression may signal the presence of environmental danger. We used fMRI to examine how gaze direction influences brain processing of facial expression of fear. The combination of fearful faces and averted gazes activated areas related to gaze shifting (STS, IPS) and fear-processing (amygdala, hypothalamus, pallidum). Additional modulation of activation was observed in motion detection areas, in premotor areas and in the somatosensory cortex, bilaterally. Our results indicate that the direction of gaze prompts a process whereby the brain combines the meaning of the facial expression with the information provided by gaze direction, and in the process computes the behavioral implications for the observer.

Quantitative spatial comparison of diffuse optical imaging with blood oxygen level-dependent and arterial spin labeling-based functional magnetic resonance imaging.

Akin to functional magnetic resonance imaging (fMRI), diffuse optical imaging (DOI) is a noninvasive method for measuring localized changes in hemoglobin levels within the brain. When combined with fMRI methods, multimodality approaches could offer an integrated perspective on the biophysics, anatomy, and physiology underlying each of the imaging modalities. Vital to the correct interpretation of such studies, control experiments to test the consistency of both modalities must be performed. Here, we compare DOI with blood oxygen level-dependent (BOLD) and arterial spin labeling fMRI-based methods in order to explore the spatial agreement of the response amplitudes recorded by these two methods. Rather than creating optical images by regularized, tomographic reconstructions, we project the fMRI image into optical measurement space using the optical forward problem. We report statistically better spatial correlation between the fMRI-BOLD response and the optically measured deoxyhemoglobin (R=0.71, p=1x10(-7)) than between the BOLD and oxyhemoglobin or total hemoglobin measures (R=0.38, p=0.04|0.37, p=0.05, respectively). Similarly, we find that the correlation between the ASL measured blood flow and optically measured total and oxyhemoglobin is stronger (R=0.73, p=5x10(-6) and R=0.71, p=9x10(-6), respectively) than the flow to deoxyhemoglobin spatial correlation (R=0.26, p=0.10).

Cyberinfrastructure for Open Science at the Montreal Neurological Institute.

Data sharing is becoming more of a requirement as technologies mature and as global research and communications diversify. As a result, researchers are looking for practical solutions, not only to enhance scientific collaborations, but also to acquire larger amounts of data, and to access specialized datasets. In many cases, the realities of data acquisition present a significant burden, therefore gaining access to public datasets allows for more robust analyses and broadly enriched data exploration. To answer this demand, the Montreal Neurological Institute has announced its commitment to Open Science, harnessing the power of making both clinical and research data available to the world (Owens, 2016a,b). As such, the LORIS and CBRAIN (Das et al., 2016) platforms have been tasked with the technical challenges specific to the institutional-level implementation of open data sharing, including: Comprehensive linking of multimodal data (phenotypic, clinical, neuroimaging, biobanking, and genomics, etc.)Secure database encryption, specifically designed for institutional and multi-project data sharing, ensuring subject confidentiality (using multi-tiered identifiers).Querying capabilities with multiple levels of single study and institutional permissions, allowing public data sharing for all consented and de-identified subject data.Configurable pipelines and flags to facilitate acquisition and analysis, as well as access to High Performance Computing clusters for rapid data processing and sharing of software tools.Robust Workflows and Quality Control mechanisms ensuring transparency and consistency in best practices.Long term storage (and web access) of data, reducing loss of institutional data assets.Enhanced web-based visualization of imaging, genomic, and phenotypic data, allowing for real-time viewing and manipulation of data from anywhere in the world.Numerous modules for data filtering, summary statistics, and personalized and configurable dashboards. Implementing the vision of Open Science at the Montreal Neurological Institute will be a concerted undertaking that seeks to facilitate data sharing for the global research community. Our goal is to utilize the years of experience in multi-site collaborative research infrastructure to implement the technical requirements to achieve this level of public data sharing in a practical yet robust manner, in support of accelerating scientific discovery.

Higher levels of cardiovascular fitness are associated with better executive function and prefrontal oxygenation in younger and older women.

AIM: Many studies have suggested that physical exercise training improves cognition and more selectively executive functions. There is a growing interest to clarify the neurophysiological mechanisms that underlie this effect. The aim of the current study was to evaluate the neurophysiological changes in cerebral oxygenation associated with physical fitness level and executive functions. METHOD: In this study, 22 younger and 36 older women underwent a maximal graded continuous test (i.e., [Formula: see text]O2max ) in order to classify them into a fitness group (higher vs. lower fit). All participants completed neuropsychological paper and pencil testing and a computerized Stroop task (which contained executive and non-executive conditions) in which the change in prefrontal cortex oxygenation was evaluated with near infrared spectroscopy (NIRS). RESULTS: Our findings revealed a Fitness × Condition interaction (p < 0.05) such that higher fit women scored better on measures of executive functions than lower fit women. In comparison to lower fit women, higher fit women had faster reaction times in the Executive condition of the computerized Stroop task. No significant effect was observed in the non-executive condition of the test and no interactions were found with age. In measures of cerebral oxygenation (ΔHbT and ΔHbO2), we found a main effect of fitness on cerebral oxygenation during the Stroop task such that only high fit women demonstrated a significant increase in the right inferior frontal gyrus. DISCUSSION/CONCLUSION: Higher fit individuals who demonstrate better cardiorespiratory functions (as measured by [Formula: see text]O2max ) show faster reaction times and greater cerebral oxygenation in the right inferior frontal gyrus than women with lower fitness levels. The lack of interaction with age, suggests that good cardiorespiratory functions can have a positive impact on cognition, regardless of age.

Changes in diffusion path length with old age in diffuse optical tomography.

Diffuse, optical near infrared imaging is increasingly being used in various neurocognitive contexts where changes in optical signals are interpreted through activation maps. Statistical population comparison of different age or clinical groups rely on the relative homogeneous distribution of measurements across subjects in order to infer changes in brain function. In the context of an increasing use of diffuse optical imaging with older adult populations, changes in tissue properties and anatomy with age adds additional confounds. Few studies investigated these changes with age. Duncan et al. measured the so-called diffusion path length factor (DPF) in a large population but did not explore beyond the age of 51 after which physiological and anatomical changes are expected to occur [Pediatr. Res. 39(5), 889-894 (1996)]. With increasing interest in studying the geriatric population with optical imaging, we studied changes in tissue properties in young and old subjects using both magnetic resonance imaging (MRI)-guided Monte-Carlo simulations and time-domain diffuse optical imaging. Our results, measured in the frontal cortex, show changes in DPF that are smaller than previously measured by Duncan et al. in a younger population. The origin of these changes are studied using simulations and experimental measures.

Body expressions of emotion do not trigger fear contagion in autism spectrum disorder.

Although there is evidence of emotion perception deficits in autism spectrum disorder (ASD), research on this topic has been mostly confined to perception of emotions in faces. Using behavioral measures and 3T functional magnetic resonance imaging (fMRI), we examined whether such deficits extend to the perception of bodily expressed emotions. We found that individuals with ASD, in contrast to neurotypical (NT) individuals, did not exhibit a differential pattern of brain activation to bodies expressing fear as compared with emotionally neutral bodies. ASD and NT individuals showed similar patterns of activation in response to bodies engaged in emotionally neutral actions, with the exception of decreased activation in the inferior frontal cortex and the anterior insula in ASD. We discuss these findings in relation to possible abnormalities in a network of cortical and subcortical mechanisms involved in social orienting and emotion contagion. Our data suggest that emotion perception deficits in ASD may be due to compromised processing of the emotional component of observed actions.

Association of a polymorphism near CREB1 with differential aversion processing in the insula of healthy participants.

CONTEXT: Previous functional neuroimaging studies have identified a network of brain regions that process aversive stimuli, including anger. A polymorphism near the cyclic adenosine monophosphate response element binding protein gene (CREB1) has recently been associated with greater self-reported effort at anger control as well as risk for antidepressant treatment-emergent suicidality in men with major depressive disorder, but its functional effects have not been studied. OBJECTIVE: To determine whether this genetic variant is associated with altered brain processing of and behavioral avoidance responses to angry facial expressions. DESIGN AND PARTICIPANTS: A total of 28 white participants (mean age, 29.2 years; 13 women) were screened using the Structured Clinical Interview for DSM-IV to exclude any lifetime Axis I psychiatric disorder and were genotyped for rs4675690, a single-nucleotide polymorphism near CREB1. MAIN OUTCOME MEASURES: Blood oxygenation level-dependent signal by functional magnetic resonance imaging in the amygdala, insula, anterior cingulate, and orbitofrontal cortex during passive viewing of photographs of faces with emotional expressions. To measure approach and avoidance responses to anger, an off-line key-press task that traded effort for viewing time assessed valuation of angry faces compared with other expressions. RESULTS: The CREB1-linked single-nucleotide polymorphism was associated with significant differential activation in an extended neural network responding to angry and other facial expressions. The CREB1-associated insular activation was coincident with activation associated with behavioral avoidance of angry faces. CONCLUSIONS: A polymorphism near CREB1 is associated with responsiveness to angry faces in a brain network implicated in processing aversion. Coincident activation in the left insula is further associated with behavioral avoidance of these stimuli.