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Jakub Kopal

Alumni
Google Scholar

Publications

Quantifying associations between socio-spatial factors and cognitive development in the ABCD cohort
Nicole Osayande
Justin Marotta
Shambhavi Aggarwal
Jakub Kopal
Avram Holmes
Sarah W. Yip
Danilo Bzdok
2025-03-19
Nature Computational Science (published)
doi.org
Carriers of
<i>LRRK2</i>
pathogenic variants show a milder, anatomically distinct brain signature of Parkinson’s disease
Jakub Kopal
Andrew Vo
Qin Tao
Tanya Simuni
Lana M. Chahine
Danilo Bzdok
Alain Dagher
LRRK2 gene variants are a major genetic risk factor for both familial and sporadic Parkinson’s disease (PD), opening an … (see more)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.
2025-03-09
medRxiv (preprint)
doi.org
Inhibition of the inferior parietal lobe triggers state-dependent network adaptations
Kathleen A. Williams
Ole Numssen
Juan David Guerra
Jakub Kopal
Danilo Bzdok
Gesa Hartwigsen
The human brain comprises large-scale networks that flexibly interact to support diverse cognitive functions and adapt to variability in dai… (see more)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.
2024-10-31
Heliyon (published)
doi.org
Diversity-aware Population Models: Quantifying Associations between Socio-Spatial Factors and Cognitive Development in the ABCD Cohort
Nicole Osayande
Justin Marotta
Shambhavi Aggarwal
Jakub Kopal
Avram Holmes
Sarah W. Yip
Danilo Bzdok
Population-level analyses are inherently complex due to a myriad of latent confounding effects that underlie the interdisciplinary topics of… (see more) research interest. Despite the mounting demand for generative population models, the limited generalizability to underrepresented groups hinders their widespread adoption in downstream applications. Interpretability and reliability are essential for clinicians and policymakers, while accuracy and precision are prioritized from an engineering standpoint. Thus, in domains such as population neuroscience, the challenge lies in determining a suitable approach to model population data effectively. Notably, the traditional strata-agnostic nature of existing methods in this field reveals a pertinent gap in quantitative techniques that directly capture major sources of population stratification. The emergence of population-scale cohorts, like the Adolescent Brain Cognitive DevelopmentSM (ABCD) Study, provides unparalleled opportunities to explore and characterize neurobehavioral and sociodemographic relationships comprehensively. We propose diversity-aware population modeling, a framework poised to standardize systematic incorporation of diverse attributes, structured with respect to intrinsic population stratification to obtain holistic insights. Here, we leverage Bayesian multilevel regression and poststratification, to elucidate inter-individual differences in the relationships between socioeconomic status (SES) and cognitive development. We constructed 14 varying-intercepts and varying-slopes models to investigate 3 cognitive phenotypes and 5 sociodemographic variables (SDV), across 17 US states and 5 race subgroups. SDVs exhibited systemic socio-spatial effects that served as fundamental drivers of variation in cognitive outcomes. Low SES was disproportionately associated with cognitive development among Black and Hispanic children, while high SES was a robust predictor of cognitive development only among White and Asian children, consistent with the minorities’ diminished returns (MDRs) theory. Notably, adversity-susceptible subgroups demonstrated an expressive association with fluid cognition compared to crystallized cognition. Poststratification proved effective in correcting group attribution biases, particularly in Pennsylvania, highlighting sampling discrepancies in US states with the highest percentage of marginalized participants in the ABCD Study©. Our collective analyses underscore the inextricable link between race and geographic location within the US. We emphasize the importance of diversity-aware population models that consider the intersectional composition of society to derive precise and interpretable insights across applicable domains.
2024-07-29
Research Square (published)
doi.org
High-effect gene-coding variants impact cognition, mental well-being, and neighborhood safety substrates in brain morphology
Jakub Kopal
Guillaume Huguet
Justin Marotta
Shambhavi Aggarwal
Nicole Osayande
Kuldeep Kumar
Zohra Saci
Martineau Jean-Louis
Xiaoqian J. Chai
Tian Ge
B.T. Thomas Yeo
Paul M. Thompson
Carrie E. Bearden
Ole A. Andreassen
Sébastien Jacquemont
Danilo Bzdok
Our genetic makeup, together with environmental and social influences, shape our brain's development. Yet, the imaging genetics field has st… (see more)ruggled to integrate all these modalities to investigate the interplay between genetic blueprint, environment, human health, daily living skills and outcomes. Hence, we interrogated the Adolescent Brain Cognitive Development (ABCD) cohort to outline the effects of rare high-effect genetic variants on brain architecture and corresponding implications on cognitive, behavioral, psychosocial, and socioeconomic traits. Specifically, we designed a holistic pattern-learning algorithm that quantitatively dissects the impacts of copy number variations (CNVs) on brain structure and 962 behavioral variables spanning 20 categories in 7,657 adolescents. Our results reveal associations between genetic alterations, higher-order brain networks, and specific parameters of the family well-being (increased parental and child stress, anxiety and depression) or neighborhood dynamics (decreased safety); effects extending beyond the impairment of cognitive ability or language capacity, dominantly reported in the CNV literature. Our investigation thus spotlights a far-reaching interplay between genetic variation and subjective life quality in adolescents and their families.
2024-05-21
medRxiv (preprint)
doi.org
High-effect gene-coding variants impact cognition, mental well-being, and neighborhood safety substrates in brain morphology
Jakub Kopal
Guillaume Huguet
Justin Marotta
Shambhavi Aggarwal
Nicole Osayande
Kuldeep Kumar
Zohra Saci
Martineau Jean-Louis
Xiaoqian J. Chai
Tian Ge
B.T. Thomas Yeo
Paul M. Thompson
Carrie E. Bearden
Ole A. Andreassen
Sébastien Jacquemont
Danilo Bzdok
Our genetic makeup, together with environmental and social influences, shape our brain's development. Yet, the imaging genetics field has st… (see more)ruggled to integrate all these modalities to investigate the interplay between genetic blueprint, environment, human health, daily living skills and outcomes. Hence, we interrogated the Adolescent Brain Cognitive Development (ABCD) cohort to outline the effects of rare high-effect genetic variants on brain architecture and corresponding implications on cognitive, behavioral, psychosocial, and socioeconomic traits. Specifically, we designed a holistic pattern-learning algorithm that quantitatively dissects the impacts of copy number variations (CNVs) on brain structure and 962 behavioral variables spanning 20 categories in 7,657 adolescents. Our results reveal associations between genetic alterations, higher-order brain networks, and specific parameters of the family well-being (increased parental and child stress, anxiety and depression) or neighborhood dynamics (decreased safety); effects extending beyond the impairment of cognitive ability or language capacity, dominantly reported in the CNV literature. Our investigation thus spotlights a far-reaching interplay between genetic variation and subjective life quality in adolescents and their families.
2024-05-21
medRxiv : the preprint server for health sciences (published)
doi.org
295. Rare Variant Genetic Architecture of the Human Cortical MRI Phenotypes in General Population
Kuldeep Kumar
Sayeh Kazem
Zhijie Liao
Jakub Kopal
Guillaume Huguet
Thomas Renne
Martineau Jean‐Louis
Zhe Xie
Zohra Saci
Laura Almasy
David C. Glahn
Tomáš Paus
Guillaume Dumas
Carrie E. Bearden
Paul M. Thompson
Richard A. I. Bethlehem
Varun Warrier
Sébastien Jacquemont
2024-04-28
Biological Psychiatry (unknown)
doi.org
Harnessing population diversity: in search of tools of the trade
Danilo Bzdok
Guy Wolf
Jakub Kopal
Big neuroscience datasets are not big small datasets when it comes to quantitative data analysis. Neuroscience has now witnessed the advent … (see more)of many population cohort studies that deep-profile participants, yielding hundreds of measures, capturing dimensions of each individual’s position in the broader society. Indeed, there is a rebalancing from small, strictly selected, and thus homogenized cohorts toward always larger, more representative, and thus diverse cohorts. This shift in cohort composition is prompting the revision of incumbent modeling practices. Major sources of population stratification increasingly overshadow the subtle effects that neuroscientists are typically studying. In our opinion, as we sample individuals from always wider diversity backgrounds, we will require a new stack of quantitative tools to realize diversity-aware modeling. We here take inventory of candidate analytical frameworks. Better incorporating driving factors behind population structure will allow refining our understanding of how brain–behavior relationships depend on human subgroups.
2023-12-31
GigaScience (published)
doi.org
Harnessing population diversity: in search of tools of the trade
Danilo Bzdok
Guy Wolf
Jakub Kopal
Abstract Big neuroscience datasets are not big small datasets when it comes to quantitative data analysis. Neuroscience has now witnessed th… (see more)e advent of many population cohort studies that deep-profile participants, yielding hundreds of measures, capturing dimensions of each individual’s position in the broader society. Indeed, there is a rebalancing from small, strictly selected, and thus homogenized cohorts toward always larger, more representative, and thus diverse cohorts. This shift in cohort composition is prompting the revision of incumbent modeling practices. Major sources of population stratification increasingly overshadow the subtle effects that neuroscientists are typically studying. In our opinion, as we sample individuals from always wider diversity backgrounds, we will require a new stack of quantitative tools to realize diversity-aware modeling. We here take inventory of candidate analytical frameworks. Better incorporating driving factors behind population structure will allow refining our understanding of how brain–behavior relationships depend on human subgroups.
2023-12-31
GigaScience (published)
doi.org
F66. FROM GENE TO COGNITION: MAPPING THE EFFECTS OF GENOMIC DELETIONS AND DUPLICATIONS ON COGNITIVE ABILITY
Sayeh Kazem
Kuldeep Kumar
Guillaume Huguet
Myriam Lizotte
Thomas Renne
Jakub Kopal
Stefan Horoi
Martineau Jean-Louis
Zohra Saci
Laura Almasy
David Glahn
Guy Wolf
Guillaume Dumas
Sébastien Jacquemont
2023-09-30
European Neuropsychopharmacology (published)
doi.org
Bayesian modelling disentangles language versus executive control disruption in stroke
Gesa Hartwigsen
Jae-Sung Lim
Hee-Joon Bae
Kyung-Ho Yu
Hugo J. Kuijf
Nick A. Weaver
J. Matthijs Biesbroek
Jakub Kopal
Danilo Bzdok
Stroke is the leading cause of long-term disability worldwide. Incurred brain damage disrupts cognition, often with persisting deficits in l… (see more)anguage and executive capacities. Despite their clinical relevance, the commonalities, and differences of language versus executive control impairments remain under-specified. We tailored a Bayesian hierarchical modeling solution in a largest-of-its-kind cohort (1080 stroke patients) to deconvolve language and executive control in the brain substrates of stroke insults. Four cognitive factors distinguished left- and right-hemispheric contributions to ischemic tissue lesion. One factor delineated language and general cognitive performance and was mainly associated with damage to left-hemispheric brain regions in the frontal and temporal cortex. A factor for executive control summarized control and visual-constructional abilities. This factor was strongly related to right-hemispheric brain damage of posterior regions in the occipital cortex. The interplay of language and executive control was reflected in two factors: executive speech functions and verbal memory. Impairments on both were mainly linked to left-hemispheric lesions. These findings shed light onto the causal implications of hemispheric specialization for cognition; and make steps towards subgroup-specific treatment protocols after stroke.
2023-08-06
bioRxiv (preprint)
doi.org
The default network dominates neural responses to evolving movie stories
Enning Yang
Filip Milisav
Jakub Kopal
Avram J. Holmes
Georgios D. Mitsis
Bratislav Misic
Emily S. Finn
Danilo Bzdok
Neuroscientific studies exploring real-world dynamic perception often overlook the influence of continuous changes in narrative content. In … (see more)our research, we utilize machine learning tools for natural language processing to examine the relationship between movie narratives and neural responses. By analyzing over 50,000 brain images of participants watching Forrest Gump from the studyforrest dataset, we find distinct brain states that capture unique semantic aspects of the unfolding story. The default network, associated with semantic information integration, is the most engaged during movie watching. Furthermore, we identify two mechanisms that underlie how the default network liaises with the amygdala and hippocampus. Our findings demonstrate effective approaches to understanding neural processes in everyday situations and their relation to conscious awareness.
2023-07-13
Nature Communications (published)
doi.org