@article{pmid42501784,

title = {Cortical structure and brain size in Thai transfeminine individuals with and without gender-affirming hormone use compared with cisgender heterosexual men, heterosexual women, and gay men},

author = {Malvina N Skorska and Monika Folkierska-Żukowska and Artit Rodkong and Pongpun Saokhieo and Olivier Parent and Daisy Z Hu and Diana E Peragine and Snimar Kaur and Lindsey T Thurston and Taweewat Supintham and Oranicha Kaewthip and Kittichai Wantanajittikul and Gabriel A Devenyi and M Mallar Chakravarty and Suwat Chariyalertsak and Suwit Saekho and Doug P VanderLaan},

doi = {10.1016/j.neuroscience.2026.07.051},

issn = {1873-7544},

year  = {2026},

date = {2026-07-01},

journal = {Neuroscience},

abstract = {Transfeminine individuals' cortical phenotype has been shown to resemble cisgender women's. However, prior studies lacked tests of the generalizability of this finding beyond clinic populations in Europe and the Americas, and of the specificity of this phenotype to gender identity rather than the often-confounding factor of sexual orientation. Also, in clinic-based studies, transfeminine individuals' brain size and cortical thickness have been shown to decrease following the use of gender-affirming hormones (GAH). Focusing on a Thai population, this study provides a test of cross-population generalizability and helps disentangle effects of sex, gender identity, sexual orientation, and self-regulated use of GAH-a widespread but underexamined practice. Brain size and cortical structure were examined in 140 Thai adults (aged 18-44): heterosexual and gay cisgender men, heterosexual cisgender women, and transfeminine individuals attracted to men known locally as sao praphet song ("second kind of woman") with or without histories of GAH use. Regional cortical thickness and, to a limited extent, surface area were associated with gender identity and use of GAH, but not with sexual orientation. Gay men's cortical structure aligned with heterosexual men's. Feminine gender identity-in cisgender women and GAH-naïve sao praphet song-was associated with greater frontal and parietal cortical thickness. Among sao praphet song, GAH use was associated with smaller brain size and thinner cortices. These findings support the generalizability of the previously observed cortical phenotype of transfeminine individuals, and its specificity to gender identity rather than sexual orientation, as well as inform GAH-related brain differences in the context of self-regulated GAH use.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42288478,

title = {Regional sex differences in human cortical anatomy vary in their morphometric bases and overlap with sex chromosomal and gonadal influences},

author = {Hyo M Lee and Siyuan Liu and Elisa Guma and Elizabeth Levitis and Rebecca Shafee and Gabrielle Dugan and François M Lalonde and Liv Clasen and Alex DeCasien and M Mallar Chakravarty and Jason P Lerch and Konrad Wagstyl and Angela Delaney and Armin Raznahan},

doi = {10.1038/s41467-026-74274-8},

issn = {2041-1723},

year  = {2026},

date = {2026-06-01},

journal = {Nat Commun},

volume = {17},

number = {1},

abstract = {Humans show reproducible sex differences in regional cortical volume (CV), but it remains unclear how these relate to the two biologically dissociable determinants of CV - surface area (SA) and cortical thickness (CT) - or to potentially causal sex chromosomal and gonadal effects. Here, we analyze neuroimaging data in two independent human cohorts (N = 1754) to identify and interrelate highly reproducible sex differences in regional CV, SA and CT - as well as their alignment with distinct functional networks and histomolecular signatures. Integrating neuroimaging data from clinical cohorts with sex chromosome aneuploidy and isolated gonadotropin-releasing hormone deficiency (N = 313) establishes that regions of sex-biased cortical anatomy are enriched for congruent effects of X-chromosome dosage (e.g., primary sensory and insular cortices) and gonadal hormones (e.g., dorsal parietal regions and angular gyrus). This work refines maps of sex-biased human cortical organization and helps to narrow hypotheses regarding their potential genetic and endocrine causes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42014585,

title = {Morphological and anatomical variations in subcortical anatomy between humans and chimpanzees associated with heritability patterns related to human behavioral traits},

author = {Nadia Blostein and Gabriel A Devenyi and Sejal Patel and Raihaan Patel and Stephanie Tullo and Eric Plitman and Manuela Costantino and Ross Markello and Olivier Parent and Saashi A Bedford and Chet C Sherwood and William D Hopkins and Alyssa Dai and Jakob Seidlitz and Armin Raznahan and M Mallar Chakravarty},

doi = {10.1038/s42003-026-10066-6},

issn = {2399-3642},

year  = {2026},

date = {2026-04-01},

journal = {Commun Biol},

abstract = {There has been significant research on cortical reorganization in human evolution, but much less is known about the reorganization of subcortical circuits, key partners of the cortex. Here, using advanced image analysis and comparative neuroimaging, we systematically map organizational differences in striatal, pallidal, and thalamic anatomy between humans and chimpanzees. We relate interspecies differences-proxies for evolutionary change-to genetics and behavioral correlates in humans. We show highly heritable morphological measures are expanded across species, contrasting previous cortical findings. Multivariate techniques identified morphological-cognitive latent variables linked to striatal expansion and affective variables specifically associated with conserved thalamic and pallidal regions. Our results confirm that regions tied to higher-order cognitive functions are expanded in humans, whereas regions linked to lower-order limbic functions are conserved. These findings provide new insights into subcortical architecture. Additionally, we developed tools to map neuroimaging data across species, a prerequisite for quantitatively translating animal neuroanatomy to humans.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41611013,

title = {Cortical thickness, cognition, and clinical profile in antipsychotic-naïve individuals with psychosis},

author = {Luis F Rivera-Chávez and Triana J Tello-Gerez and Matthew Danyluik and Pablo León-Ortiz and Yohan Yee and Francisco Reyes-Madrigal and Gabriel A Devenyi and M Mallar Chakravarty and Camilo de la Fuente-Sandoval},

doi = {10.1016/j.pnpbp.2026.111625},

issn = {1878-4216},

year  = {2026},

date = {2026-03-01},

journal = {Prog Neuropsychopharmacol Biol Psychiatry},

volume = {145},

pages = {111625},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41916976,

title = {Characterizing spatiotemporal white matter hyperintensity pathophysiology in vivo to disentangle vascular and neurodegenerative contributions},

author = {Olivier Parent and Zaki Alasmar and Sophia Osborne and Aurélie Bussy and Manuela Costantino and Jérémie P Fouquet and Daniela Quesada and Alexandre Pastor-Bernier and Alfonso Fajardo-Valdez and Alexa Pichet-Binette and Ann McQuarrie and Josefina Maranzano and Gabriel A Devenyi and Christopher J Steele and Sylvia Villeneuve and  and  and Mahsa Dadar and M Mallar Chakravarty},

doi = {10.1038/s41467-026-70832-2},

issn = {2041-1723},

year  = {2026},

date = {2026-03-01},

journal = {Nat Commun},

volume = {17},

number = {1},

abstract = {White matter hyperintensities (WMHs) are neuroimaging markers widely interpreted as caused by cerebral small vessel disease, yet emerging evidence suggests that a subset may have a neurodegenerative etiology. Current imaging methods have lacked the specificity to disentangle biological processes underlying WMHs in vivo. Here, we used voxel-level normative modeling and seven microstructural MRI markers with complementary biophysical sensitivities to generate single-subject high-resolution WMH pathophysiology maps in a large cohort (n = 32,526). We calculated data-driven spatial patterns of similar WMHs, revealing distinct periventricular, posterior, and anterior clusters. We identified a reproducible WMH signature linked to dementia and Alzheimer's disease, characterized by a posterior predominance and a pathophysiological pattern indicative of selective fiber degeneration. Posterior WMHs connected cortical regions vulnerable to tau pathology. Our framework helps parsing vascular and neurodegenerative contributions of WMHs in vivo, which could alter the course of treatment strategies and provide nuanced interpretations of research findings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41386393,

title = {Uncovering novel endocannabinoidome-gut microbiome-brain axis-based therapeutic targets in a Fragile X Syndrome mouse model},

author = {Antonella Campanale and Hayatte-Dounia Mir and Elizabeth Dumais and Antonio Inserra and Nicolas Flamand and Mallar Chakravarty and Ilse Gantois and Nadeem Siddiqui and Nahum Sonenberg and Gabriella Gobbi and Cristoforo Silvestri and Vincenzo Di Marzo},

doi = {10.1016/j.pnpbp.2025.111575},

issn = {1878-4216},

year  = {2026},

date = {2026-01-01},

journal = {Prog Neuropsychopharmacol Biol Psychiatry},

volume = {144},

pages = {111575},

abstract = {BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition associated with increased risk of psychiatric, gastrointestinal, and metabolic comorbidities. Recent studies highlight the bidirectional role of the gut microbiome (GM) and endocannabinoidome (eCBome)-axis in the gut-brain axis, suggesting its therapeutic potential for ASD and comorbidities.nnMETHODS: We investigated the eCBome-GM-brain axis in the Fragile X Messenger Ribonucleoprotein 1 (Fmr1) mouse model, known as a genetic model of ASD, to identify therapeutic targets. Fecal GM composition was analysed by 16S rDNA sequencing, brain eCBome profile by HPLC-MS/MS and qRT-PCR, and fecal short chain fatty acids by GC-FID.nnRESULTS: Significant eCBome-GM-brain axis dysregulation was observed in Fmr1 compared to wild-type mice. GM analyses revealed potential gut dysbiosis, increased permeability, and inflammation. Specifically, elevated Akkermansia and Eubacterium siraeum-linked to gut barrier dysfunction-and Ruminococcus and Clostridium, associated with ASD severity, were identified. Concurrently, decreased levels of the gut health biomarker Roseburia and the taxa Helicobacter and Anaeroplasma were observed. Brain region-specific eCBome alterations underscored neuroinflammation. In the HPC, reduced anti-inflammatory dihomogamma-linolenic acid (DGLA) was accompanied by elevated pro-inflammatory 12-hydroxy-heptadecatrienoic acid, a mediator of microglial activation. In the PFC, decreased DGLA, 1/2-linoleoylglycerol, and N-linoleoyl-ethanolamine suggested neuroinflammation; elevated prostaglandin D2, a marker of autophagy impairment, underscores further mechanisms of dysfunction. Upregulation of cannabinoid type 2 and PPAR-γ receptor genes in the PFC suggested a compensatory response to neuroinflammation. Correlations between eCBome and GM alterations highlighted potential links between gut dysbiosis, systemic inflammation, and neurodevelopmental atypicalities.nnCONCLUSIONS: The Fmr1 ASD mouse model harbors significant eCBome-GM-brain axis alterations. This study highlights specific GM taxa and eCBome components as potential therapeutic targets for clinical validation in Fragile X Syndrome and ASD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42529501,

title = {Experimental quality control induces changes in Allen mouse brain connectomes},

author = {Vikram Nathan and Stephanie Tullo and Lizette Herrera-Portillo and Gabriel A Devenyi and Yohan Yee and M Mallar Chakravarty},

doi = {10.1162/IMAG.a.1310},

issn = {2837-6056},

year  = {2026},

date = {2026-01-01},

journal = {Imaging Neurosci (Camb)},

volume = {4},

abstract = {The Allen Mouse Brain Connectivity Atlas (AMBCA) is widely used to represent structural connectivity in the mouse brain. The AMBCA consists of tracer injection experiments where neuronal projections axonally connected to the initial injection site are labeled. The resulting whole-brain structural connectomes, derived from a subset of these experiments in C57BL/6 mice, have been used in several studies of connectomic architectures. However, through close inspection of n = 437 distinct experiments used in a publicly-available connectome (Knox et al., 2018), we observed experiments with off-target injections, diffuse projections, unrealistically small injections and projections, and anatomical misalignments, affecting the accuracy and applicability of these connectivity experiments. We applied a combined automated and manual quality control (QC) and identified n = 56 (~13% of the original n = 437) experiments representing a wide variety of injection and projection failures across the brain. Automated QC was used to detect extreme injection and projection sizes and misalignments, while manual QC was used to detect subtle off-target tracer spreading. Using the remaining n = 381 experiments, we rebuilt two different connectomes using previously-published methods; specifically: the regionalized voxel model from Knox et al. (2018), and the homogeneous model from Oh et al. (2014). Our rebuilt connectomes show strong losses in connectivity between regions with limited evidence of structural connectivity by other methods (e.g., hippocampus-medulla, cerebellum-isocortex) and gains in connectivity between regions with strong connectivity evidence (hypothalamus-cerebellum, hypothalamus-isocortex). Finally, we analyzed the rich club and community organization to demonstrate the potential downstream impacts on the representation of the overall structural connectome architectures of our QC'd connectomes and observed subtle whole-brain organizational changes. We present our rebuilt connectomes, and particularly highlight the regionalized voxel model, as more accurate representations of structural connectivity derived from the AMBCA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41433477,

title = {Alzheimer's Imaging Consortium},

author = {Olivier Parent and Sophia Osborne and Gabriel A Devenyi and Aurelie Bussy and Manuela Costantino and Jérémie Fouquet and Daniela Quesada Rodriguez and Mahsa Dadar and Mallar M Chakravarty},

doi = {10.1002/alz70862_110231},

issn = {1552-5279},

year  = {2025},

date = {2025-12-01},

journal = {Alzheimers Dement},

volume = {21 Suppl 8},

number = {Suppl 8},

pages = {e110231},

abstract = {BACKGROUND: White matter hyperintensity (WMH) pathophysiology varies across regions and consists of various degrees of edema, inflammation, demyelination, and axonal degeneration. Notable sex differences in WMH volume have been observed, with women having a higher WMH burden than men starting from midlife, which is hypothesized to be due to the menopausal transition and the consequent reduction in the neuroprotective effects of estrogen. However, a deep characterization of the spatial pathophysiological patterns of WMHs across sexes is lacking.nnMETHOD: We estimated WMH pathophysiology in vivo at a high spatial resolution using microstructural magnetic resonance imaging (MRI). In the UK Biobank dataset (n = 32,526, 15,144 males, 17,382 females), diffusion- and susceptibility-weighted images were used to derive fluid-, fiber-, and myelin- and iron-sensitive markers. Age- and sex-specific expected values of healthy white matter microstructure were calculated at a voxel-level resolution using normative modeling and used to contrast with WMH microstructural values to derive pathophysiological estimates (Figure 1A). We derived spatial clusters of pathophysiologically similar WMHs by applying spectral clustering to group-level averages of WMH pathophysiology (Figure 1B) resulting in three regions: periventricular, posterior, and anterior (Figure 1C). The median WMH pathophysiology within each region was sampled for each subject. We characterized sex differences in our derived WMH pathophysiological patterns using linear models, controlling for non-linear age effects and correcting p-values using the false discovery rate.nnRESULT: In general, females showed higher WMH volumes and more severe WMH pathophysiology, with notable exceptions: males showed higher WMH volume and worst orientation dispersion (OD) pathophysiology in posterior WMHs (Figure 2). When investigating WMH pathophysiology for equivalent WMH volume, a clear pattern emerged, with strong effects in females mostly restricted to periventricular and posterior WMHs for most pathophysiological markers. Intriguingly, this was not the case for the OD marker which only showed a significantly higher effect in males in the PV region.nnCONCLUSION: Taken together, our results show nuanced sex-specific effects in WMHs. There are clear spatial differences, with females having more WMHs but similar pathophysiological effects in anterior WMHs, while males show higher WMH volumes but lower pathophysiological effects in posterior WMHs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41285189,

title = {Effects of prenatal cannabis exposure on offspring mental health: A focus on the role of the immune system},

author = {Haley A Vecchiarelli and Samantha L Baglot and Tallan Black and Esther Y Choi and Lani Cupo and Colby Sandberg and Léa Siron and M Mallar Chakravarty and Matthew N Hill and John G Howland and Jibran Y Khokhar and Marie-Ève Tremblay},

doi = {10.1016/j.neubiorev.2025.106488},

issn = {1873-7528},

year  = {2025},

date = {2025-11-01},

journal = {Neurosci Biobehav Rev},

volume = {181},

pages = {106488},

abstract = {Globally, there is increasing legalization, permissiveness and acceptability of medical and recreational cannabis use-including among pregnant people. Yet, we lack a full understanding of cannabis' effects, including during pregnancy and in offspring who experienced prenatal cannabis exposure (PCE), despite decades of research. In particular, the ability of PCE to impact offspring mental health has been investigated in literature. Given the emerging link between mental health and immune system functioning (both centrally and peripherally) and that cannabinoid receptors are abundantly expressed in the immune system, it may be the case that PCE alters offspring mental health by impacting the immune system. In this review, we highlight current research on the effects of PCE and discuss differences among administration methods and across species, with a particular focus on changes in the immune system-focusing both on immune processes in the central nervous system and peripherally-relevant to altered offspring mental health. While the field is too nascent for robust conclusions, some interesting findings have been reported. Particularly in the placenta, in both humans and rodents (using vaporized exposure paradigms), cannabis use during pregnancy is associated with a reduction in pro-inflammatory cytokine levels, which is linked, in humans, to increased offspring anxiety, aggression and hyperactivity behaviors. Whereas data with regards to central nervous system immune cells, i.e., microglia, is limited, PCE seems to impact T cell dynamics in various organs. However, the link between offspring immune cell changes and offspring mental health requires further establishment. We conclude by discussing important future directions and a focus on harm reduction.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41020412,

title = {The PREVENT-AD cohort: Accelerating Alzheimer's disease research and treatment in Canada and beyond},

author = {Sylvia Villeneuve and Judes Poirier and John C S Breitner and Jennifer Tremblay-Mercier and Jordana Remz and Jean-Michel Raoult and Yara Yakoub and Jonathan Gallego-Rudolf and Ting Qiu and Alfonso Fajardo Valdez and Bery Mohammediyan and Mohammadali Javanray and Amelie Metz and Safa Sanami and Valentin Ourry and Alfie Wearn and Alexandre Pastor-Bernier and Manon Edde and Julie Gonneaud and Cherie Strikwerda-Brown and Christine L Tardif and Claudine J Gauthier and Maxime Descoteaux and Mahsa Dadar and Étienne Vachon-Presseau and Andrée-Ann Baril and Simon Ducharme and Maxime Montembeault and Maiya R Geddes and Jean-Paul Soucy and Natasha Rajah and Robert Laforce and Christian Bocti and Christos Davatzikos and Lune Bellec and Pedro Rosa-Neto and Sylvain Baillet and Alan C Evans and D Louis Collins and M Mallar Chakravarty and Kaj Blennow and Henrik Zetterberg and R Nathan Spreng and Alexa Pichet Binette and },

doi = {10.1002/alz.70653},

issn = {1552-5279},

year  = {2025},

date = {2025-10-01},

journal = {Alzheimers Dement},

volume = {21},

number = {10},

pages = {e70653},

abstract = {The PResymptomatic EValuation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD) is an investigator-driven study that was created in 2011 and enrolled cognitively normal older adults with a family history of sporadic AD. Participants are deeply phenotyped and have now been followed annually for more than 12 years (median follow-up 8.0 years, SD 3.1). Multimodal magnetic resonance imaging (MRI), genetic, neurosensory, clinical, cerebrospinal fluid, and cognitive data collected until 2017 on 348 participants who agreed to open sharing with the neuroscience community were already available. We now share a new release including 6 years of additional follow-up cognitive data, and additional MRI follow-ups, clinical progression, new longitudinal behavioral and lifestyle measures (questionnaires, actigraphy), longitudinal AD plasma biomarkers, amyloid-beta and tau positron emission tomography (PET), magnetoencephalography, as well as neuroimaging analytic measures from all MRI modalities. We describe the PREVENT-AD study, the data shared with the global research community, as well as the model we created to sustain longitudinal follow-ups while also allowing new innovative data collection. HIGHLIGHTS: The PResymptomatic EValuation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD) is a single-site longitudinal study that started in 2011 with annual follow-up data collection on individuals at risk of Alzheimer's disease who were all cognitively normal at enrolment. All 387 participants were enrolled between 2011 and 2017 and 306 (79%) of these participants were still in the study as of December 2023. While the PREVENT-AD dataset was not originally planned to be shared with the global research community, 348 participants retrospectively consented for their data to be shared with researchers worldwide. The first release of data was in 2019. We now share a second release that includes 6 years of additional follow-up visits, information on clinical progression and novel cognitive, behavioral, genetic, plasma and neuroimaging (amyloid and tau positron emission tomography [PET], magnetoencephalography [MEG], and new magnetic resonance imaging [MRI] sequences) data. It also includes analytic outputs for neuroimaging modalities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40962830,

title = {Impact of prenatal delta-9-tetrahydrocannabinol exposure on mouse brain development: a fetal-to-adulthood magnetic resonance imaging study},

author = {Lani Cupo and Haley A Vecchiarelli and Daniel Gallino and Jared VanderZwaag and Katerina Bradshaw and Annie Phan and Mohammadparsa Khakpour and Benneth Ben-Azu and Elisa Guma and Jérémie P Fouquet and Shoshana Spring and Brian J Nieman and Gabriel A Devenyi and Marie-Eve Tremblay and M Mallar Chakravarty},

doi = {10.1038/s41380-025-03189-5},

issn = {1476-5578},

year  = {2025},

date = {2025-09-01},

journal = {Mol Psychiatry},

abstract = {While cannabis use during pregnancy is often perceived as harmless, little is known about its consequences on offspring neurodevelopment. There is an urgent need to map the effects of prenatal cannabis exposure on the brain through the course of the lifespan. We used magnetic resonance imaging spanning nine timepoints, behavioral assays, and electron microscopy to build a trajectory from gestation to adulthood in mice exposed prenatally to delta-9-tetrahydrocannabinol (THC). Our results demonstrate a spatio-temporal patterning, with ventriculomegaly in THC-exposed embryos followed by a deceleration of brain growth in neonates that is sustained until adulthood, especially in females. We observed consistently impacted regions in both the cortex and subcortex, aligned with sex-dependent changes to social behavior in neonates and increased anxiety-like behavior in adolescents. Our results suggest prenatal THC exposure has a sustained sex-dependent impact on neurodevelopment that may persist into early adulthood.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41040728,

title = {Tracking a decade of structural changes in preclinical and prodromal Alzheimer's disease: insights from amyloid-β pathology},

author = {Ting Qiu and Zhen-Qi Liu and Jonathan Gallego-Rudolf and Manon Edde and Alex Valcourt Caron and Yuanchao Zhang and M Mallar Chakravarty and Jean-Paul Soucy and D Louis Collins and Judes Poirier and John Breitner and Gemma Salvadó and Alexa Pichet Binette and Maxime Descoteaux and Sylvia Villeneuve},

doi = {10.1101/2025.09.25.25336640},

year  = {2025},

date = {2025-09-01},

journal = {medRxiv},

abstract = {Alzheimer's disease (AD) pathology is typically associated with reduced brain volume and cortical thickness, interpreted as neurodegeneration. However, several cross-sectional studies in cognitively unimpaired individuals have paradoxically reported larger brain volume and thicker cortex in the presence of amyloid-β (Aβ), suggesting that Aβ-brain structure associations may not follow a simple linear pattern early in the disease. We leveraged over a decade of longitudinal data from the PREVENT-AD cohort (N=367, mean follow-up 7.17 years, range 0-11.27 years) to investigate how Aβ burden related to both cross-sectional levels and longitudinal changes in brain volume, cortical thickness, and cortical tissue mean diffusivity (MD) derived from free-water corrected diffusion tensor imaging. We examined associations separately in individuals below (Aβ-) and above (Aβ+) the Aβ-positivity threshold, tested for nonlinearity across all participants, and aligned structural trajectories to the estimated years from Aβ-positivity onset. We found that higher Aβ was associated with larger brain volume, higher cortical thickness and lower MD in regions such as the fusiform gyrus, supramarginal gyrus, hippocampal volume, inferior parietal and middle temporal cortex in the Aβ- group. The opposite associations were found in the Aβ+ group. Across all participants, volume and thickness showed an inverse U-shaped relationship with Aβ, while MD followed a U-shaped pattern. Longitudinally, the rate of cortical thickness change showed an inverse U-shaped association with Aβ, whereas Aβ burden was associated with faster volume loss and greater MD increase. When structural measures were aligned to the estimated time of Aβ positivity onset, volume and thickness increased years before the expected Aβ positivity onset and declined thereafter, while MD showed no association with time relative to Aβ positivity onset. Our results help reconcile inconsistencies across prior studies and suggest that brain structural changes related to Aβ pathology start years before Aβ positivity onset and follow nonlinear trajectories. These early structural changes might be due to pathological processes such as neuroinflammatory swelling early in the course of the disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41019640,

title = {Fractionation of sex differences in human cortical anatomy},

author = {Hyo M Lee and Siyuan Liu and Elisa Guma and Elizabeth Levitis and Rebecca Shafee and Gabrielle Dugan and François M Lalonde and Liv Clasen and Alex DeCasien and M Mallar Chakravarty and Jason P Lerch and Konrad Wagstyl and Angela Delaney and Armin Raznahan},

doi = {10.1101/2025.09.10.675377},

issn = {2692-8205},

year  = {2025},

date = {2025-09-01},

journal = {bioRxiv},

abstract = {Humans show reproducible sex differences in regional cortical volume (CV), but it remains unclear how these arise from underlying sex-biases in the two biologically dissociable determinants of CV: surface area (SA) and cortical thickness (CT). Moreover, limited access to experimental methods in humans has hindered direct studies of the causal drivers of regional sex differences in the human cortex, although rodent models have argued for both chromosomal and gonadal contributions to sex-biased mammalian cortical development. Here, we first use structural neuroimaging data in two independent human cohorts (combined N=1,754; 967 females) to quantify and spatially resolve the differential contributions of SA and CT to observed sex differences in CV. These dissociable facets of sex-biased cortical organization are highly reproducible and align with distinct functional networks and histo-molecular signatures. We then leverage complementary neuroimaging data in clinical case-control cohorts (combined N=313) featuring variations in X and Y chromosome dosage (sex chromosome aneuploidies) and testicular hormone production (isolated GnRH deficiency) to establish that regions of sex-biased CV, SA and CT in humans are enriched for congruent anatomical effects of X-chromosome dosage (e.g., primary sensory and insular cortices) and gonadal hormones (e.g. dorsomedial frontal and temporo-parietal-occipital regions). Taken together, these findings substantially advance both the breadth and granularity of our understanding regarding sex-biased cortical organization in humans - disambiguating sex effects on regional CV, SA and CT and nominating their potential genetic and endocrine causes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40620111,

title = {The Neural Correlates of Delusions in Dementia: A Scoping Review},

author = {Adèle Gagnon and Bryn H Manns and Karina Atanasiu and Dominique Lumley and Mallar Chakravarty and Serge Gauthier and Ian Gold},

doi = {10.1111/psyg.70060},

issn = {1479-8301},

year  = {2025},

date = {2025-07-01},

journal = {Psychogeriatrics},

volume = {25},

number = {4},

pages = {e70060},

abstract = {Delusions are common symptoms of dementia and are clinically significant. The objective of this scoping review is to identify possible neural correlates. MEDLINE (OVID), EMBASE (OVID) and Web of Science were searched in December 2020 for the keywords 'delusions' and 'dementia'. Two informal searches were carried out subsequently. Results were limited to those in English. Intervention and study characteristics were extracted using standardised tools. Eighteen published studies, using four distinct experimental methods, were included, and 31 brain regions were identified as correlates of delusions. No region was identified consistently within included studies or found in more than four studies. Despite the range of brain regions identified, a number form part of the default mode network, the salience network or the central executive network. We explore the implications of these findings for understanding delusions in dementia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40086421,

title = {Sex and APOE4-specific links between cardiometabolic risk factors and white matter alterations in individuals with a family history of Alzheimer's disease},

author = {Stefanie A Tremblay and R Nathan Spreng and Alfie Wearn and Zaki Alasmar and Amir Pirhadi and Christine L Tardif and Mallar M Chakravarty and Sylvia Villeneuve and Ilana R Leppert and Felix Carbonell and Yasser Iturria Medina and Christopher J Steele and Claudine J Gauthier and },

doi = {10.1016/j.neurobiolaging.2025.03.003},

issn = {1558-1497},

year  = {2025},

date = {2025-06-01},

journal = {Neurobiol Aging},

volume = {150},

pages = {80--96},

abstract = {Early detection of pathological changes in Alzheimer's disease (AD) has garnered significant attention in the last few decades as interventions aiming to prevent progression will likely be most effective when initiated early. White matter (WM) alterations are among the earliest changes in AD, yet limited work has comprehensively characterized the effects of AD risk factors on WM. In older adults with a family history of AD, we investigated the sex-specific and APOE genotype-related relationships between WM microstructure and risk factors. Multiple MRI-derived metrics were integrated using a multivariate approach based on the Mahalanobis distance (D2). To uncover the specific biological underpinnings of these WM alterations, we then extracted the contribution of each MRI feature to D2 in significant clusters. Lastly, the links between WM D2 and cognition were explored. WM D2 in several regions was associated with high systolic blood pressure, BMI, and glycated hemoglobin, and low cholesterol, in both males and females. APOE4 + displayed a distinct risk pattern, with LDL-cholesterol having a detrimental effect only in carriers, and this pattern was linked to immediate memory performance. Myelination was the main mechanism underlying WM alterations. Our findings reveal that combined exposure to multiple cardiometabolic risk factors negatively impacts microstructural health, which may subsequently affect cognition. Notably, APOE4 carriers exhibited a different risk pattern, especially in the role of LDL, suggesting distinct underlying mechanisms in this group.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40585093,

title = {Characterizing spatiotemporal white matter hyperintensity pathophysiology in vivo to disentangle vascular and neurodegenerative contributions},

author = {Olivier Parent and Zaki Alasmar and Sophia Osborne and Aurélie Bussy and Manuela Costantino and Jérémie P Fouquet and Daniela Quesada and Alexandre Pastor-Bernier and Alfonso Fajardo-Valdez and Alexa Pichet-Binette and Ann McQuarrie and Josefina Maranzano and Gabriel A Devenyi and Christopher J Steele and Sylvia Villeneuve and  and  and Mahsa Dadar and M Mallar Chakravarty},

doi = {10.1101/2025.06.10.25329342},

year  = {2025},

date = {2025-06-01},

journal = {medRxiv},

abstract = {White matter hyperintensities (WMHs) are neuroimaging markers widely interpreted as caused by cerebral small vessel disease, yet emerging evidence suggests that a subset may have a neurodegenerative etiology. Current imaging methods have lacked the specificity to disentangle biological processes underlying WMHs . Here, we used voxel-level normative modeling and seven microstructural MRI markers with complementary biophysical sensitivities to generate single-subject high-resolution WMH pathophysiology maps in a large cohort (=32,526). We calculated data-driven spatial patterns of similar WMHs, revealing distinct periventricular, posterior, and anterior clusters. We identified a reproducible WMH signature linked to dementia and Alzheimer's disease, characterized by a posterior predominance and a pathophysiological pattern indicative of selective fiber degeneration. Posterior WMHs connected cortical regions vulnerable to tau pathology. Our framework distinguishes vascular and neurodegenerative contributions of WMHs , which could alter the course of treatment strategies and provide nuanced interpretations of research findings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40566800,

title = {Biomarker changes associated with fornix deep brain stimulation in Alzheimer's disease},

author = {Jürgen Germann and Robert S C Amaral and Jennifer Tomaszczyk and Kazuaki Yamamoto and Gavin J B Elias and Flavia Venetucci Gouveia and Anna Vasilevskaya and Foad Taghdiri and Gabriel A Devenyi and Tejas Sankar and Jeannie-Marie Leoutsakos and Cynthia A Munro and Paul B Rosenberg and Constantine G Lyketsos and Esther S Oh and William S Anderson and Zoltan Mari and Lisa Fosdick and Kristen E Drake and Steven D Targum and Jo Cara Pendergrass and Anna Burke and Stephen Salloway and Wael F Asaad and Francisco A Ponce and Marwan Sabbagh and David A Wolk and Gordon Baltuch and Michael S Okun and Kelly D Foote and Peter Giacobbe and Mary Pat McAndrews and David F Tang-Wai and Gwenn S Smith and M Carmela Tartaglia and M Mallar Chakravarty and Andres M Lozano and },

doi = {10.1002/alz.70394},

issn = {1552-5279},

year  = {2025},

date = {2025-06-01},

journal = {Alzheimers Dement},

volume = {21},

number = {6},

pages = {e70394},

abstract = {INTRODUCTION: Deep brain stimulation of the fornix (fx-DBS) is being investigated for treatment of Alzheimer's disease (AD). The therapy aims at alleviating memory and cognitive circuit dysfunction. In preclinical models of AD, electrical stimulation of the memory circuit has demonstrated a possible disease-modifying potential. Here we examined changes resulting from fx-DBS in hippocampal atrophy and amyloid accumulation in AD patients with fx-DBS.nnMETHODS: Repeated magnetic resonance imaging and positron emission tomography (PET) images acquired over the course of 12 months were used to assess changes in hippocampal volume in 36 ADvance trial patients compared to 40 matched untreated AD patients from the Alzheimer's Disease Neuroimaging Initiative, and in 10 separate patients with repeated flutemetamol PET and cerebrospinal fluid (CSF) markers.nnRESULTS: We observed a reduction of hippocampal atrophy and amyloid beta (Aβ) PET binding, and an increase in the CSF Aβ/total-tau ratio in DBS patients.nnDISCUSSION: These findings highlight the potential of fornix deep brain stimulation to modify AD biomarkers and possibly progression in some patients.nnHIGHLIGHTS: Fornix deep brain stimulation (fx-DBS) is being investigated to treat Alzheimer's disease (AD). Results show that fx-DBS modifies imaging and cerebrospinal fluid (CSF) markers. It reduces hippocampal atrophy and increases the amyloid beta/total-tau CSF ratio. These findings highlight the potential of fx-DBS to modify AD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39875591,

title = {fMRI data acquisition and analysis for task-free, anesthetized rats},

author = {Roël M Vrooman and Monica van den Berg and Gabriel Desrosiers-Gregoire and Wessel A van Engelenburg and Marie E Galteau and Sung-Ho Lee and Andor Veltien and David A Barrière and Diana Cash and M Mallar Chakravarty and Gabriel A Devenyi and Alessandro Gozzi and Olli Gröhn and Andreas Hess and Judith R Homberg and Ileana O Jelescu and Georgios A Keliris and Tom Scheenen and Yen-Yu Ian Shih and Marleen Verhoye and Claire Wary and Marcel Zwiers and Joanes Grandjean},

doi = {10.1038/s41596-024-01110-y},

issn = {1750-2799},

year  = {2025},

date = {2025-06-01},

journal = {Nat Protoc},

volume = {20},

number = {6},

pages = {1393--1412},

abstract = {Templates for the acquisition of large datasets such as the Human Connectome Project guide the neuroimaging community to reproducible data acquisition and scientific rigor. By contrast, small animal neuroimaging often relies on laboratory-specific protocols, which limit cross-study comparisons. The establishment of broadly validated protocols may facilitate the acquisition of large datasets, which are essential for uncovering potentially small effects often seen in functional MRI (fMRI) studies. Here, we outline a procedure for the acquisition of fMRI datasets in rats and describe animal handling, MRI sequence parameters, data conversion, preprocessing, quality control and data analysis. The procedure is designed to be generalizable across laboratories, has been validated by using datasets across 20 research centers with different scanners and field strengths ranging from 4.7 to 17.2 T and can be used in studies in which it is useful to compare functional connectivity measures across an extensive range of datasets. The MRI procedure requires 1 h per rat to complete and can be carried out by users with limited expertise in rat handling, MRI and data processing.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40320230,

title = {Longitudinal clinical outcomes based on cognitive and hippocampal clusters of first episode psychosis},

author = {Lucas A Ronat and Delphine Raucher-Chéné and Katie M Lavigne and Mallar Chakravarty and Ridha Joober and Ashok Malla and Jai Shah and Martin Lepage},

doi = {10.1016/j.pnpbp.2025.111392},

issn = {1878-4216},

year  = {2025},

date = {2025-06-01},

journal = {Prog Neuropsychopharmacol Biol Psychiatry},

volume = {139},

pages = {111392},

abstract = {BACKGROUND: In first episode psychosis (FEP), cognitive impairments are core features contributing to clinical and functional heterogeneity. Significant impairment indicates greater clinical severity throughout the course of the illness, particularly for negative symptoms. Hippocampal volume is smaller in FEP than in healthy controls (notably subfields like Cornu Ammonis 1-3 and subiculum), and is related to cognitive impairments and negative symptoms. The aim of this study was to compare the clinical and functional trajectories of FEP subgroups as a function of cognitive performance and hippocampal volumes.nnMETHODS: One hundred FEP patients and sixty healthy controls initially assessed using the CogState research battery, underwent 3 T MRI to extract hippocampal subfields and adjacent structures using the MAGeT brain algorithm. Clinical assessments were carried out for negative (Motivational and Pleasure - MAP, and diminished expression - EXP) and depressive symptoms, and global functioning. Measurements were taken at 4 time points (3, 9, 15, 21 months following program entry). Based on available first timepoint standardized cognitive and hippocampal features, using healthy controls as reference, clusters were determined by a hierarchical ascending classification. Their clinical and functional longitudinal trajectories were analyzed using linear mixed-effects models.nnRESULTS: Three baseline clusters were revealed: normal-range hippocampal volume with low attention, working and verbal memory (FEP 0), small hippocampus with low verbal memory and social cognition (FEP 1), and large hippocampus with low verbal memory (FEP 2). At baseline, the clusters did not differ on symptoms severity and global functioning. Longitudinally, MAP, EXP and depressive symptoms decreased over time in FEP 0. Global functioning improved in FEP 0 and FEP 1, while FEP 2 was clinically and functionally stable over time. Longitudinal inter-group comparisons did not yield any significant differences.nnCONCLUSION: The clusters were dissociated between hippocampus and cognition, but their trajectories suggest the importance of hippocampal integrity in the clinical and/or functional outcome. Future studies are needed to understand intervention efficiency depending on hippocampal integrity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39961166,

title = {Exploring morphological and microstructural signatures across the Alzheimer's spectrum and risk factors},

author = {Aurélie Bussy and Raihaan Patel and Olivier Parent and Alyssa Salaciak and Saashi A Bedford and Sarah Farzin and Stephanie Tullo and Cynthia Picard and Sylvia Villeneuve and Judes Poirier and John Cs Breitner and Gabriel A Devenyi and  and Christine L Tardif and M Mallar Chakravarty},

doi = {10.1016/j.neurobiolaging.2025.01.011},

issn = {1558-1497},

year  = {2025},

date = {2025-05-01},

journal = {Neurobiol Aging},

volume = {149},

pages = {1--18},

abstract = {Neural alterations, including myelin degeneration and inflammation-related iron burden, may accompany early Alzheimer's disease (AD) pathophysiology. This study aims to identify multi-modal signatures associated with MRI-derived atrophy and quantitative MRI (qMRI) measures of myelin and iron in a unique dataset of 158 participants across the AD spectrum, including those without cognitive impairment, at familial risk for AD, with mild cognitive impairment, and with AD dementia. Our results revealed a brain pattern with decreased cortical thickness, indicating increased neuronal death, and compromised hippocampal integrity due to reduced myelin content. This pattern was associated with lifestyle factors such as smoking, high blood pressure, high cholesterol, and anxiety, as well as older age, AD progression, and APOE-ɛ4 carrier status. These findings underscore the value of qMRI metrics as a non-invasive tool, offering sensitivity to lifestyle-related modifiable risk factors and medical history, even in preclinical stages of AD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}