Veronique D. Bohbot’s research while affiliated with McGill University and other places

Spatial navigation is a multi-faceted behaviour drawing on many different aspects of cognition. Visuospatial abilities, such as mental rotation and visuospatial working memory, in particular, may be key factors. A range of tests have been developed to assess visuospatial processing and memory, but how such tests relate to navigation ability remains unclear. This understanding is important to advance tests of navigation for disease monitoring in various disorders (e.g., Alzheimer’s disease) where spatial impairment is an early symptom. Here, we report the use of an established mobile gaming app, Sea Hero Quest (SHQ), as a measure of navigation ability in a sample of young, predominantly female university students (N = 78; 20; female = 74.3%; mean age = 20.33 years). We used three separate tests of navigation embedded in SHQ: wayfinding, path integration and spatial memory in a radial arm maze. In the same participants, we also collected measures of mental rotation (Mental Rotation Test), visuospatial processing (Design Organization Test) and visuospatial working memory (Digital Corsi). We found few strong correlations across our measures. Being good at wayfinding in a virtual navigation test does not mean an individual will also be good at path integration, have a superior memory in a radial arm maze, or rate themself as having a strong sense of direction. However, we observed that participants who were good in the wayfinding task of SHQ tended to perform well on the three visuospatial tasks examined here, and to also use a landmark strategy in the radial maze task. These findings help clarify the associations between different abilities involved in spatial navigation.

White matter hyperintensities (WMHs) are radiological abnormalities reflecting cerebrovascular dysfunction detectable using magnetic resonance imaging (MRI). WMHs are often present in individuals at the later stages of the lifespan and in prodromal stages in the Alzheimer’s Disease spectrum. Tissue alterations underlying WMHs may include demyelination, inflammation, and edema, but these are highly variable by neuroanatomical location and between individuals. There is a crucial need to characterize these WMH tissue alterations in vivo to improve prognosis and, potentially, treatment outcomes. How different MRI measure(s) of tissue microstructure capture clinically-relevant WMH tissue damage is currently unknown. Here, we compared six MRI signal measures sampled within WMHs and their associations with multiple clinically-relevant outcomes, consisting of global and cortical brain morphometry, cognitive function, diagnostic and demographic differences, and cardiovascular risk factors. We used cross-sectional data from 118 participants: healthy controls (n = 30), individuals at high risk for Alzheimer’s Disease due to familial history (n = 47), mild cognitive impairment (n = 32), and clinical Alzheimer’s Disease dementia (n = 9). We sampled the median signal within WMHs on weighted MRI images (T1-weighted [T1w], T2-weighted [T2w], T1w/T2w ratio, Fluid-Attenuated Inversion Recovery [FLAIR]) as well as the relaxation times from quantitative T1 (qT1) and T2* (qT2*) images. qT2* and FLAIR signals within WMHs displayed different age- and disease-related trends compared to normal-appearing white matter signals, suggesting sensitivity to WMH-specific tissue deterioration. Further, WMH qT2*, particularly in periventricular and occipital white matter regions, was consistently associated with all types of clinically-relevant outcomes in both univariate and multivariate analyses and across two parcellation schemes. qT1 and FLAIR measures showed consistent clinical relationships in multivariate but not univariate analyses, while T1w, T2w, and T1w/T2w ratio measures were not consistently associated with clinical variables. We observed that the qT2* signal was sensitive to clinically-relevant microstructural tissue alterations specific to WMHs. Our results suggest that combining volumetric and signal measures of WMH should be considered to fully characterize the severity of WMHs in vivo. These findings may have implications in determining the reversibility of WMHs and the potential efficacy of cardio- and cerebrovascular treatments.

Sex differences in navigation have been a topic of investigation for decades and has been subjected to various contradictory findings and debates. The aim of this work was to compare the spatial memory of men and women tested in various different types of spatial tasks, while controlling for navigation strategies and aging. It is generally thought that men outperform women in navigation and that women have higher scores on object location tasks. However, many studies fail to control for different factors that may bias one sex or the other. We aggregated the data of 465 participants (349 young adults, 127 older adults) who took part in various studies conducted in our laboratory, which include both published and original unpublished data, in order to investigate sex differences. In these studies, we used a number of different paradigms: virtual radial arm mazes, a virtual wayfinding task, an object location task, a virtual Morris Water Maze, and the invisible sensor task which is a real-life model of the Morris Water Maze. While our results may seem discordant at first glance, they demonstrate that several factors can impact the performance of men and women on spatial tasks, including spontaneous navigation strategies, environmental characteristics, and age. We replicated findings showing that women favor proximal landmarks compared to men who favor distal landmarks, women have better memory than men for the position of objects in the absence of reference frames, but they will have poorer scores when navigation requires specific angles, distances and polar coordinates. Moreover, we found that in aging, women who avoid the use of landmarks when navigating a radial maze show stronger reliance on these non-spatial strategies than men. On the other hand, women who rely on landmarks, do so to the same extent as men. Our findings highlight the need to carefully take into consideration these factors in order to produce a more harmonious understanding of sex differences in navigation. Finally, the interaction between spontaneous navigation strategies, sex, and age is discussed in terms of its implications for risk of Alzheimer’s disease.

Spatial navigation is a multi-faceted behaviour drawing on many different aspects of cognition. Visuospatial abilities, such as spatial working memory and mental rotation, in particular, may be key factors. A range of tests have been developed to assess visuospatial processing and memory, but how such tests relate to navigation ability remains unclear. This understanding is important to advance tests of navigation for disease monitoring in Alzheimer’s Disease, where disorientation is an early symptom. Here, we report the use of an established mobile gaming app, Sea Hero Quest, as a measure of navigation ability. We used three separate tests of navigation embedded in the game: wayfinding, path integration and spatial memory in a radial arm maze. In the same participants, we also collected measures of mental rotation (Mental Rotation Test), visuospatial processing (Design Organization Test) and visuospatial working memory (Digital Corsi). We found few strong correlations across our measures. Being good at wayfinding in a virtual navigation test does not mean an individual will rate themself as a confident navigator, be good at path integration, or have a superior memory in a radial arm maze. However, those good at wayfinding tend to perform well on the three visuospatial tasks examined here, and to also use a landmark strategy in the radial maze task. These findings help clarify the inter-relationships between different abilities supporting visuospatial and navigation skills. Highlights Three navigation tests embedded in the game Sea Hero Quest were examined in relation to three object-based visuospatial tasks, and self-ratings of navigation ability and stress during navigation. No associations were observed among performance on wayfinding, path integration and radial arm maze levels of Sea Hero Quest. Object-based visuospatial abilities were selectively correlated with performance on wayfinding levels of Sea Hero Quest. Gameplay stress and navigation strategy were not associated with performance on Sea Hero Quest navigation tasks.

Background: The extent to which digital media use by adolescents contributes to poor mental health, or vice-versa, remains unclear. The purpose of the present study is to clarify the strength and direction of associations between adolescent internet use and the development of depression symptoms using a longitudinal modeling approach. We also examine whether associations differ for boys and girls. Methods: Data are drawn from (N = 1547) participants followed for the Quebec longitudinal Study of Child Development (QLSCD 1998-2020). Youth self-reported internet use in terms of the average hours of use per week at the ages of 13, 15, and 17. Youth also self-reported depression symptoms at the same ages. Results: After testing sex-invariance, random intercepts cross-lagged panel models stratified by sex, revealed that internet use by girls was associated with significant within-person (time-varying) change in depression symptoms. Girl's internet use at age 13 was associated with increased depression symptoms at age 15 (ß = 0.12) and internet use at age 15 increased depression at age 17 (ß = 0.10). For boys, internet use was not associated with significant time varying change in depression symptoms. Conclusions: The present findings support the hypothesis that internet use by adolescents can represent a significant risk factor for the development of depressive symptoms, particularly in girls.

Humans show a remarkable capacity to navigate various environments using different navigation strategies, and we know that strategy changes across the life span. However, this observation has been based on studies of small sample sizes. To this end, we used a mobile app-based video game (Sea Hero Quest) to test virtual navigation strategies and memory performance within a distinct radial arm maze level in over 37,000 participants. Players were presented with 6 pathways (3 open and 3 closed) and were required to navigate to the 3 open pathways to collect a target. Next, all 6 pathways were made available and the player was required to visit the pathways that were previously unavailable. Both reference memory and working memory errors were calculated. Crucially, at the end of the level, the player was asked a multiple-choice question about how they found the targets (i.e., a counting-dependent strategy vs. a landmark-dependent strategy). As predicted from previous laboratory studies, we found the use of landmarks declined linearly with age. Those using landmark-based strategies also performed better on reference memory than those using a counting-based strategy. These results extend previous observations in the laboratory showing a decreased use of landmark-dependent strategies with age.

Importance: Preventive trials of anti-amyloid agents might preferably recruit persons showing earliest biologically relevant β-amyloid (Aβ) binding on positron emission tomography (PET). Objective: To investigate the timing at which Aβ-PET binding starts showing associations with other markers of Alzheimer disease. Design, setting, and participants: This longitudinal multicentric cohort study included 3 independent cohorts: Presymptomatic Evaluation of Experimental or Novel Treatments for Alzheimer Disease (PREVENT-AD) (data collected from 2012-2020), Alzheimer Disease Neuroimaging Initiative (ADNI) (data collected from 2005-2019), and Harvard Aging Brain Study (HABS) (data collected from 2011-2019). In a 3-tiered categorization of Aβ-PET binding spatial extent, individuals were assigned as having widespread Aβ deposition if they showed positive signal throughout a designated set of brain regions prone to early Aβ accumulation. Those with binding in some but not all were categorized as having regional deposition, while those who failed to show any criterion Aβ signal were considered Aβ-negative. All participants who were cognitively unimpaired at their first Aβ PET scan. Main outcomes and measures: Differences in cerebrospinal fluid (CSF), genetics, tau-PET burden, and cognitive decline. Results: A total of 817 participants were included, including 129 from the PREVENT-AD cohort (mean [SD] age, 63.5 [4.7] years; 33 [26%] male; 126 [98%] White), 400 from ADNI (mean [SD] age, 73.6 [5.8] years; 190 [47%] male; 10 [5%] Hispanic, 338 [91%] White), and 288 from HABS (mean [SD] age, 73.7 [6.2] years; 117 [40%] male; 234 [81%] White). Compared with Aβ-negative persons, those with regional Aβ binding showed proportionately more APOE ε4 carriers (18 [64%] vs 22 [27%] in PREVENT-AD and 34 [31%] vs 38 [19%] in ADNI), reduced CSF Aβ1-42 levels (F = 24 and 71), and greater longitudinal Aβ-PET accumulation (significant β = 0.019 to 0.056). Participants with widespread amyloid binding further exhibited notable cognitive decline (significant β = -0.014 to -0.08), greater CSF phosphorylated tau181 (F = 5 and 27), and tau-PET binding (all F > 7.55). Using each cohort's specified dichotomous threshold for Aβ positivity or a visual read classification, most participants (56% to 100%, depending on classification method and cohort) with regional Aβ would have been classified Aβ-negative. Conclusions and relevance: Regional Aβ binding appears to be biologically relevant and participants at this stage remain relatively free from CSF phosphorylated tau181, tau-PET binding, and related cognitive decline, making them ideal targets for anti-amyloid agents. Most of these individuals would be classified as negative based on classical thresholds of Aβ positivity.

Importance: National Institute on Aging-Alzheimer's Association (NIA-AA) workgroups have proposed biological research criteria intended to identify individuals with preclinical Alzheimer disease (AD). Objective: To assess the clinical value of these biological criteria to identify older individuals without cognitive impairment who are at near-term risk of developing symptomatic AD. Design, setting, and participants: This longitudinal cohort study used data from 4 independent population-based cohorts (PREVENT-AD, HABS, AIBL, and Knight ADRC) collected between 2003 and 2021. Participants were older adults without cognitive impairment with 1 year or more of clinical observation after amyloid β and tau positron emission tomography (PET). Median clinical follow-up after PET ranged from 1.94 to 3.66 years. Exposures: Based on binary assessment of global amyloid burden (A) and a composite temporal region of tau PET uptake (T), participants were stratified into 4 groups (A+T+, A+T-, A-T+, A-T-). Presence (+) or absence (-) of neurodegeneration (N) was assessed using temporal cortical thickness. Main outcomes and measures: Each cohort was analyzed separately. Primary outcome was clinical progression to mild cognitive impairment (MCI), identified by a Clinical Dementia Rating score of 0.5 or greater in Knight ADRC and by consensus committee review in the other cohorts. Clinical raters were blind to imaging, genetic, and fluid biomarker data. A secondary outcome was cognitive decline, based on a slope greater than 1.5 SD below the mean of an independent subsample of individuals without cognitive impairment. Outcomes were compared across the biomarker groups. Results: Among 580 participants (PREVENT-AD, 128; HABS, 153; AIBL, 48; Knight ADRC, 251), mean (SD) age ranged from 67 (5) to 76 (6) years across cohorts, with between 55% (137/251) and 74% (95/128) female participants. Across cohorts, 33% to 83% of A+T+ participants progressed to MCI during follow-up (mean progression time, 2-2.72 years), compared with less than 20% of participants in other biomarker groups. Progression further increased to 43% to 100% when restricted to A+T+(N+) individuals. Cox proportional hazard ratios for progression to MCI in the A+T+ group vs other biomarker groups were all 5 or greater. Many A+T+ nonprogressors also showed longitudinal cognitive decline, while cognitive trajectories in other groups remained predominantly stable. Conclusions and relevance: The clinical prognostic value of NIA-AA research criteria was confirmed in 4 independent cohorts, with most A+T+(N+) older individuals without cognitive impairment developing AD symptoms within 2 to 3 years.

Objective: We aim to investigate the direction of causality of the association between adolescent video game playing and later development of ADHD symptoms using a population-based sample of Canadian Youth. Method: The present study is based on longitudinal cohort data (N = 1,467). Youth self-reported weekly hours of video game playing as well as ADHD symptoms at both 12 and 13 years of age. Results: Cross-lagged panel model were estimated to examine how adolescent video game playing prospectively contributes to ADHD symptoms while simultaneously considering how adolescent ADHD symptoms may prospectively contribute to videogame playing. Analyses revealed a significant positive association between adolescent video games playing at age 12 and ADHD symptoms at age 13. Youth ADHD symptoms at age 12 did not predict video game use at age 13. Conclusion: Our results help clarify the direction of causality of the association between video game playing and ADHD symptoms and provide evidence that video game playing can represent a risk factor for the development of attention problems in early adolescence.