Portrait de Danilo Bzdok

Danilo Bzdok

Membre académique principal
Chaire en IA Canada-CIFAR
Professeur agrégé, McGill University, Département de génie biomédicale
Sujets de recherche
Apprentissage profond
Biologie computationnelle
Grands modèles de langage (LLM)
Traitement du langage naturel

Biographie

Danilo Bzdok est informaticien et médecin de formation. Il possède une double formation unique en neurosciences systémiques et en algorithmes d'apprentissage automatique. Après une formation à l'Université d'Aix-la-Chapelle (RWTH) (Allemagne), à l'Université de Lausanne (Suisse) et à la Harvard Medical School (États-Unis), il a obtenu un doctorat en neurosciences du Centre de recherche de Jülich (Allemagne) et un doctorat en informatique dans le domaine des statistiques d'apprentissage automatique à l'INRIA Saclay et à NeuroSpin (Paris, France). Il est actuellement professeur agrégé à la Faculté de médecine de l'Université McGill et titulaire d’une chaire en IA Canada-CIFAR à Mila – Institut québécois d'intelligence artificielle. Son activité de recherche interdisciplinaire est centrée sur la réduction des lacunes dans la connaissance des bases cérébrales des types de pensée qui définissent l'être humain, afin de découvrir les principes clés de conception computationnelle qui sous-tendent l'intelligence humaine.

Étudiants actuels

Doctorat - McGill
Doctorat - McGill
Maîtrise recherche - HEC
Co-superviseur⋅e :
Doctorat - McGill
Collaborateur·rice de recherche - CentraleSupélec
Doctorat - McGill
Collaborateur·rice de recherche - École Polytechnique
Doctorat - McGill
Postdoctorat - McGill
Maîtrise recherche - McGill
Visiteur de recherche indépendant - McGill
Doctorat - McGill
Doctorat - McGill
Doctorat - McGill
Doctorat - McGill

Publications

Quantifying associations between socio-spatial factors and cognitive development in the ABCD cohort
Quantifying associations between socio-spatial factors and cognitive development in the ABCD cohort.
Carriers of
<i>LRRK2</i>
pathogenic variants show a milder, anatomically distinct brain signature of Parkinson’s disease
Andrew Vo
Tanya Simuni
Tanya Simuni
Lana M. Chahine
Alain Dagher
LRRK2 gene variants are a major genetic risk factor for both familial and sporadic Parkinson’s disease (PD), opening an … (voir plus)unattended window on the disease’s mechanisms and potential therapies. Investigating the influence of pathogenic variants in LRRK2 gene on brain structure is a crucial step toward enabling early diagnosis and personalized treatment. Yet, despite its significance, the ways in which LRRK2 genotype affects brain structure remain largely unexplored. Work in this domain is plagued by small sample sizes and differences in cohort composition, which can obscure genuine distinctions among clinical subgroups. In this study, we overcome such important limitations by combining explicit modeling of population background variation and pattern matching. Specifically, we leveraged a large cohort of 641 participants (including 364 with a PD diagnosis) to examine MRI-detectable cortical atrophy patterns associated with the LRRK2 pathogenic variants in people with PD and non-manifesting individuals. LRRK2 PD patients exhibited milder cortical thinning compared to sporadic PD, with notable preservation in temporal and occipital regions, suggesting a distinct pattern of neurodegeneration. Non-manifesting LRRK2 carriers showed no significant cortical atrophy, indicating no structural signs of subclinical PD. We further analyzed the relationship between aggregated alpha-synuclein in cerebrospinal fluid and atrophy. We found that those with evidence of aggregated alpha-synuclein experienced pronounced neurodegeneration and increased cortical thinning, possibly defining another aggressive PD subtype. Our findings highlight avenues for distinguishing PD subtypes, which could lead to more targeted treatment approaches and a more complete understanding of Parkinson’s disease progression.
Large language models deconstruct the clinical intuition behind diagnosing autism
Emmett Rabot
Laurent Mottron
Cell type transcriptomics reveal shared genetic mechanisms in Alzheimer’s and Parkinson’s disease
Edward A. Fon
Alain Dagher
Yasser Iturria-Medina
Jo Anne Stratton
David A Bennett
Historically, Alzheimer’s disease (AD) and Parkinson’s disease (PD) have been investigated as two distinct disorders of the brain. Howev… (voir plus)er, a few similarities in neuropathology and clinical symptoms have been documented over the years. Traditional single gene-centric genetic studies, including GWAS and differential gene expression analyses, have struggled to unravel the molecular links between AD and PD. To address this, we tailor a pattern-learning framework to analyze synchronous gene co-expression at sub-cell-type resolution. Utilizing recently published single-nucleus AD (70,634 nuclei) and PD (340,902 nuclei) datasets from postmortem human brains, we systematically extract and juxtapose disease-critical gene modules. Our findings reveal extensive molecular similarities between AD and PD gene cliques. In neurons, disrupted cytoskeletal dynamics and mitochondrial stress highlight convergence in key processes; glial modules share roles in T-cell activation, myelin synthesis, and synapse pruning. This multi-module sub-cell-type approach offers insights into the molecular basis of shared neuropathology in AD and PD.
Cell type transcriptomics reveal shared genetic mechanisms in Alzheimer’s and Parkinson’s disease
Edward A. Fon
Alain Dagher
Yasser Iturria-Medina
Jo Anne Stratton
David A Bennett
Historically, Alzheimer’s disease (AD) and Parkinson’s disease (PD) have been investigated as two distinct disorders of the brain. Howev… (voir plus)er, a few similarities in neuropathology and clinical symptoms have been documented over the years. Traditional single gene-centric genetic studies, including GWAS and differential gene expression analyses, have struggled to unravel the molecular links between AD and PD. To address this, we tailor a pattern-learning framework to analyze synchronous gene co-expression at sub-cell-type resolution. Utilizing recently published single-nucleus AD (70,634 nuclei) and PD (340,902 nuclei) datasets from postmortem human brains, we systematically extract and juxtapose disease-critical gene modules. Our findings reveal extensive molecular similarities between AD and PD gene cliques. In neurons, disrupted cytoskeletal dynamics and mitochondrial stress highlight convergence in key processes; glial modules share roles in T-cell activation, myelin synthesis, and synapse pruning. This multi-module sub-cell-type approach offers insights into the molecular basis of shared neuropathology in AD and PD.
A hierarchical Bayesian brain parcellation framework for fusion of functional imaging datasets
Da Zhi
Caroline Nettekoven
Ana Lúısa Pinho
Jörn Diedrichsen
Inhibition of the inferior parietal lobe triggers state-dependent network adaptations
Kathleen A. Williams
Ole Numssen
Juan David Guerra
Gesa Hartwigsen
The human brain comprises large-scale networks that flexibly interact to support diverse cognitive functions and adapt to variability in dai… (voir plus)ly life. The inferior parietal lobe (IPL) is a hub of multiple brain networks that sustain various cognitive domains. It remains unclear how networks respond to acute regional perturbations to maintain normal function. To provoke network-level adaptive responses to local inhibition, we combined offline transcranial magnetic stimulation (TMS) over left or right IPL with neuroimaging during attention, semantic and social cognition tasks, and rest. Across tasks, TMS specifically affected task-active network activity with inhibition and facilitation. Network interaction responses differed between rest and tasks. After TMS over both IPL regions, large-scale network interactions were exclusively facilitated at rest, but mainly inhibited during tasks. Overall, responses to TMS primarily occurred in and between domain-general default mode and frontoparietal subnetworks. These findings elucidate short-term adaptive plasticity in response to network node inhibition.
Genetic Interplay Between White Matter Hyperintensities and Alzheimer's Disease: A Brain-Body Perspective
Manpreet Singh
Kimia Shafighi
Flavie E. Detcheverry
Fanta Dabo
Ikrame Housni
Sridar Narayanan
Sarah A. Gagliano Taliun
AmanPreet Badhwar
MRI-detected white matter hyperintensities (WMH) are often recognized as markers of cerebrovascular abnormalities and an index of vascular b… (voir plus)rain injury, and are frequently present in individuals with Alzheimer’s disease (AD). Given the emerging bidirectional communication between the brain-body axis in both WMHs and AD, it is important to understand their genetic underpinnings across the whole body. However, literature on this is scarce. We investigated the brain-body axis by breaking down heritability estimates of these phenotypes across the whole body, – i.e., partitioning heritability. Our aims were to identify genetic underpinnings specific to WMHs, and common between WMHs and AD, by assessing (a) the partitioned heritability of WMHs and AD across the brain-body axis with tissue-specific annotations, (b) the partitioned heritability of WMHs and AD across the brain-body axis with cell-specific annotations, and (c) the genes associated with WMHs and AD, and verifying their expression levels across the whole body. Our tissue-specific analysis revealed that WMH-associated SNPs were significantly enriched in tissues beyond the brain, namely liver, cardiovascular, and kidney – with liver being a common tissue enriched for both WMHs and AD. Our cell-specific analysis showed enrichment of vascular endothelial cells across the tissue types enriched for WMHs, highlighting their central role in the development of WMHs. Additionally, our gene-level analysis highlighted overlapping patterns of tissue enrichment for both WMHs and AD, and showed interactions between WMH and AD associated genes. Our findings provide new insights into the systemic influences potentially contributing to WMH pathology, in particular, multi-system endothelial disorder. We hope that our multisystemic genetic findings will stimulate future WMH-research into specific pathways across the brain-body axis.
Large language models auto-profile conscious awareness changes under psychedelic drug effects
Robin Carhart-Harris
Steven Laureys
Abstract

Psychedelic experiences open a colorful view into drug-induced changes in conscious awareness. Small-samp… (voir plus)le studies on psychedelic drug action have gained traction in recent years. Yet, today’s means for measuring changes in subjective experience are mostly limited to legacy questionnaires of pre-assumed relevance, which could be complemented by bottom-up explorations of semantic facets that underlie experience reports. Here, we show how to harness large language models (LLMs) to i) design from scratch, ii) annotate at scale, and iii) evaluate with rigor a vast portfolio of experience dimensions during psychoactive drug influence, yielding > 2 million automatic dimension ratings that would otherwise have been done by hand. Investigator-independent LLM scoring of these drug effects on the human mind alone allowed to robustly discriminate the unique mental effects of 30 psychoactive substances. Successful knowledge integration of how psychedelics mediate shifts in subjective awareness will be an unavoidable milestone towards charting the full drug design space.

Nonlinear latent representations of high-dimensional task-fMRI data: Unveiling cognitive and behavioral insights in heterogeneous spatial maps
Mariam Zabihi
Seyed Mostafa Kia
Thomas Wolfers
Stijn de Boer
Charlotte Fraza
Richard Dinga
Alberto Llera Arenas
Christian F. Beckmann
Andre Marquand
Finding an interpretable and compact representation of complex neuroimaging data is extremely useful for understanding brain behavioral mapp… (voir plus)ing and hence for explaining the biological underpinnings of mental disorders. However, hand-crafted representations, as well as linear transformations, may inadequately capture the considerable variability across individuals. Here, we implemented a data-driven approach using a three-dimensional autoencoder on two large-scale datasets. This approach provides a latent representation of high-dimensional task-fMRI data which can account for demographic characteristics whilst also being readily interpretable both in the latent space learned by the autoencoder and in the original voxel space. This was achieved by addressing a joint optimization problem that simultaneously reconstructs the data and predicts clinical or demographic variables. We then applied normative modeling to the latent variables to define summary statistics (‘latent indices’) and establish a multivariate mapping to non-imaging measures. Our model, trained with multi-task fMRI data from the Human Connectome Project (HCP) and UK biobank task-fMRI data, demonstrated high performance in age and sex predictions and successfully captured complex behavioral characteristics while preserving individual variability through a latent representation. Our model also performed competitively with respect to various baseline models including several variants of principal components analysis, independent components analysis and classical regions of interest, both in terms of reconstruction accuracy and strength of association with behavioral variables.
Contributions of network structure, chemoarchitecture and diagnostic categories to transitions between cognitive topographies
Andrea I. Luppi
S. Parker Singleton
Justine Y. Hansen
Keith W. Jamison
Amy Kuceyeski
Richard F. Betzel
Bratislav Misic
The mechanisms linking the brain’s network structure to cognitively relevant activation patterns remain largely unknown. Here, by leveragi… (voir plus)ng principles of network control, we show how the architecture of the human connectome shapes transitions between 123 experimentally defined cognitive activation maps (cognitive topographies) from the NeuroSynth meta-analytic database. Specifically, we systematically integrated large-scale multimodal neuroimaging data from functional magnetic resonance imaging, diffusion tractography, cortical morphometry and positron emission tomography to simulate how anatomically guided transitions between cognitive states can be reshaped by neurotransmitter engagement or by changes in cortical thickness. Our model incorporates neurotransmitter-receptor density maps (18 receptors and transporters) and maps of cortical thickness pertaining to a wide range of mental health, neurodegenerative, psychiatric and neurodevelopmental diagnostic categories (17,000 patients and 22,000 controls). The results provide a comprehensive look-up table charting how brain network organization and chemoarchitecture interact to manifest different cognitive topographies, and establish a principled foundation for the systematic identification of ways to promote selective transitions between cognitive topographies.