Biology subjects

Sullivan, M.

Publications and source records attributed to Sullivan, M..

At least 19 recordsLinked to original sources

bioRxiv2026

First community challenge for automated virus taxonomy

The rapid rate of virus discovery renders manual curation by taxonomy experts increasingly impractical, creating a need for reliable software that can reproducibly assign viral contigs to taxa at all fifteen ranks of the virus taxonomy. We led an open community challenge for the computational taxonomic classification of viruses and assembled a dataset of virus sequences combining expert-curated and metagenomic sequences. Seventeen teams contributed a total of thirty-four automated, fully reproducible classification pipelines. Most tools correctly assigned viruses belonging to established species, genera, or families, but viruses that are unclassified at those lower ranks remain challenging. This study provides datasets, open-source software, novel approaches, and recommendations to benchmark computational taxonomic classification of viruses, and support organizing the many viruses discovered in big omics data.

microbiology↗

bioRxiv2025

Myeloid HDAC7 drives liver inflammation and systemic glucose dysregulation during diet-induced obesity

ObjectivesHistone deacetylase 7 (HDAC7), a classical HDAC family member, promotes LPS-inducible glycolysis and inflammatory mediator production in macrophages, innate immune cells that contribute to pathology in metabolic diseases. Here, we investigated myeloid HDAC7 functions in obesity-driven metabolic disease. MethodsWe used gain- and loss-of-function genetic approaches in mice to investigate myeloid HDAC7 functions in hepatic inflammation and metabolic disease, as well as associations with hepatic gene signatures characteristic of advanced chronic liver disease (CLD). ResultsTransgenic expression of Hdac7 in myeloid cells increased liver inflammation and liver mRNA levels of Ccl2 and Il1b, key inflammatory mediators linked to CLD. Liver glycogen levels were also decreased, another feature of CLD. Transgenic expression of Hdac7 in myeloid cells mimicked the hepatic inflammatory phenotype that was observed in mice fed a high fat, high cholesterol, and high sucrose (HFHCHS) diet, an obesity model that mimics some features of metabolic dysfunction-associated steatotic liver disease. In myeloid Hdac7 transgenic mice fed a HFHCHS diet, relative weight gain was increased, fasted glucose levels were elevated and glucose tolerance was dysregulated by comparison to control mice. Conversely, fasted blood glucose levels were reduced and glucose tolerance was improved in myeloid Hdac7-deleted mice on a HFHCHS diet. HDAC7 mRNA levels were also elevated in the livers of people with advanced CLD and spatial transcriptomics revealed that myeloid HDAC7 directs hepatic gene signatures characteristic of advanced CLD. ConclusionsMyeloid HDAC7 contributes to hepatic inflammation and systemic glucose dysregulation in a mouse model of obesity and liver inflammation.

immunology↗

bioRxiv2025

KCNQ1 regulates human neuronal development through mitochondrial and insulin signalling pathways

KCNQ1 encodes a voltage-gated potassium channel implicated in various peripheral and neurological disorders, yet its role during human neuronal development remains unclear. To investigate this, we generated KCNQ1 knockouts (KO) in human induced pluripotent stem cell lines and differentiated them into neural stem cells (NSCs) and cortical neurons. KCNQ1-deficient NSCs showed impaired neurite outgrowth, linked to reduced cell adhesion and disrupted neural cell adhesion molecule (NCAM) signalling. This phenotype was reproduced in wild-type and heterozygous lines by pharmacological KCNQ1 inhibition. Whole transcriptome, proteome, and follow-up analyses revealed mitochondrial dysfunction in KO NSCs, including reduced mitochondrial copy number and ATP synthase expression. Additionally, evidence was obtained for an impairment of insulin signalling in NSCs and neurons, with diminished insulin receptor gene expression and perturbation of key downstream signalling pathways (RAS-MAPK, PI3K-AKT). In neurons, KCNQ1 loss resulted in decreased synaptic activity and a more immature gene expression profile. Overall, our work reveals a novel role for KCNQ1 in human neurodevelopment by regulating cell adhesion, mitochondrial function, and insulin signalling. This work increases our understanding of KCNQ1 function in neurons and its contribution to neurological phenotypes observed in patients with KCNQ1-related diseases.

molecular biology↗

bioRxiv2025

Single-cell neural network classifiers reveal that PM21 NK cell expansion is dependent on B cell signaling

In the field drug development ML/AI methods are being applied to improve drug production speed, costs, and reliability. In allogenic NK cell therapy production, one of the biggest challenges is the inherent variability in the donors that provide the starting material for NK cell expansion. In this study we performed PM21-mediated NK cell expansion on 26 donors, and in parallel performed single-cell transcriptomics on the same donor sample prior to expansion. Canonical differential expression analysis and cell state abundance did not highlight any significant difference between donors with high and low NK cell expansion yield. Instead, training neural networks classifiers for high-yield donors enabled identifying several highly predictive models with perfect cross-validation recall. Further investigation of the most predictive models unveiled a previously unknown role for B cell in supportive NK cell expansion. Overall, this study represents a blueprint for combining deep phenotyping and machine learning methods to unveil novel biology and improve the quality and speed of delivery of cell therapeutics to patients.

systems biology↗

bioRxiv2025

High-Resolution Spatial Transcriptomics Reveals Fibroblast and Neuroimmune Microenvironments in Endometriosis Lesions

Endometriosis is a chronic, systemic, inflammatory disease characterized by the presence of endometrium-like tissue growing outside of the uterus. One of its main symptoms is chronic pain and inflammation leading to a decreased quality of life. This is a common disease, as at least one in ten female-born individuals have endometriosis. Yet the understanding of the mechanisms that drive pain symptoms and disease progression remain poorly defined. This study establishes the precise spatial transcriptomic cartography of human ovarian and peritoneal lesions, two of the most commonly found lesions. We identified shared spatial features across lesion types, including immune cell infiltration, fibroblast specific compartments surrounding epithelial glands, and distinct distributions of neuronal and macrophage subsets. We precisely defined sensory neuronal subtypes, and mapped their spatial location relative to immune cells. We further validate the epithelial-neuronal interactome, using an in vitro 3D model of peripheral sensory brain organoids co-cultured with human endometriosis epithelial and fibroblast cells. By mapping spatial cellular interactions and identifying conserved features across lesion types linked to pain, our study provides emerging insights into endometriosis pathophysiology, paving the way for the development of novel targeted therapeutic strategies.

cell biology↗

bioRxiv2025

High-throughput detection and quantification of vitamin B12 in microbiome isolates using Escherichia coli

Vitamin B12 is an essential micronutrient produced only by prokaryotes, and animals must acquire it from their diet. Vitamin B12 is critical for the synthesis of methionine and propionyl-CoA metabolism. In humans, vitamin B12 deficiency has been linked to many disorders, including infertility and developmental abnormalities. The growing trend towards plant-based diets and the ageing populations increase the risk of vitamin B12 deficiency, and therefore, there is an increasing interest in understanding vitamin B12 biology. Accurate approaches for detecting and quantifying vitamin B12 are essential in studying its complex biology, from its biogenesis in Bacteria and Archaea to its effects in complex organisms. Here, we present an approach using the commonly available E. coli methionine auxotroph strain B834 (DE3) and a multi-well spectrophotometer to detect and quantify vitamin B12 from biological samples at picomolar concentrations. We further show that our quantification method for vitamin B12 is sufficient to reveal important differences in the production of vitamin B12 from vitamin B12-synthesising bacteria commonly found in the microbiome of wild Caenorhabditis elegans isolates. Our results establish a high-throughput and simple assay platform for detecting and quantifying vitamin B12 using the E. coli B834 (DE3) strain.

microbiology↗

bioRxiv2025

Auto-methylation of the histone methyltransferase SetDB1 at its histone-mimic motifs ensures the spreading and maintenance of heterochromatin

Heterochromatin plays a critical role in nuclear organization and the regulation of gene expression by directing 3D genome organization, regulating lineage-specific gene expression, and ensuring the repression of transposable elements and endogenous retroviruses. Functionally and structurally distinct chromatin domains are defined by the so-called histone code, which consists of combinations of post-translational histone modifications deposited by "code writers" and recognized by "code readers." The primary mark of heterochromatin, trimethylation of histone H3 at lysine 9 (H3K9me3), is deposited by histone methyltransferases, such as SetDB1, and serves as a binding platform for readers, most notably HP1 family proteins. Using a reporter system to monitor the dynamics of heterochromatin establishment and maintenance, we demonstrated that transient tethering of HP1 triggers the SetDB1-dependent establishment of stable heterochromatin. This finding indicates the presence of a feedback mechanism wherein the reader of the H3K9me3 mark recruits the writer. We further discovered that the genetic interaction between SetDB1 and HP1 is mirrored by a direct physical interaction. This interaction requires the auto-methylation of two conserved histone mimic motifs located in unstructured regions of SetDB1. HP1 binds these SetDB1 motifs using the same molecular interface it employs to recognize the modified histone tail. Our findings show that SetDB1 auto-methylation is essential for the spreading and stable maintenance of heterochromatin. This includes its roles in processes such as X-chromosome inactivation and the negative feedback regulation of a large gene family encoding KRAB-ZNF transcriptional repressors. Thus, the primary heterochromatin mark is not limited to nucleosomes but is also deployed on the marks writer itself. This fosters a direct physical interaction between the writer and the reader, ensuring key features of heterochromatin: its spreading to establish extended domains and its stable maintenance through cell divisions.

genetics↗

bioRxiv2024

A rational approach for the targeted discovery and characterisation of microbiome-derived therapeutics

The human gut microbiome is intrinsically involved in health and disease, representing a wealth of untapped therapeutic potential. Here, we demonstrate the utility and potential of a metagenome guided, large cohort-based approach for the rational selection of live biotherapeutics from the human gut. We applied this approach to Inflammatory Bowel Disease (IBD), identifying several lead candidates that were significantly depleted in individuals with IBD compared to healthy controls. Their therapeutic potential was assessed in preclinical models of IBD where they improved markers of disease pathology by reducing inflammation and promoting mucosal healing and wound repair. All leads had excellent safety profiles in silico and in vitro, and several additionally presented favourable manufacturing properties, supporting their progression into clinical trials. We believe that this rational approach will be generalisable to any disease state with underlying microbiome aetiology and will expedite the development of novel microbiome-derived therapeutics to improve human health.

microbiology↗

bioRxiv2024

Generative Adversarial Networks Accurately Reconstruct Pan-Cancer Histology from Pathologic, Genomic, and Radiographic Latent Features

Artificial intelligence models have been increasingly used in the analysis of tumor histology to perform tasks ranging from routine classification to identification of novel molecular features. These approaches distill cancer histologic images into high-level features which are used in predictions, but understanding the biologic meaning of such features remains challenging. We present and validate a custom generative adversarial network - HistoXGAN - capable of reconstructing representative histology using feature vectors produced by common feature extractors. We evaluate HistoXGAN across 29 cancer subtypes and demonstrate that reconstructed images retain information regarding tumor grade, histologic subtype, and gene expression patterns. We leverage HistoXGAN to illustrate the underlying histologic features for deep learning models for actionable mutations, identify model reliance on histologic batch effect in predictions, and demonstrate accurate reconstruction of tumor histology from radiographic imaging for a virtual biopsy.

cancer biology↗

bioRxiv2024

Cellular mechanotransduction of human osteoblasts in microgravity

Astronauts experience significant and rapid bone loss as a result of an extended stay in space, making the International Space Station (ISS) the perfect laboratory for studying osteoporosis due to the accelerated nature of bone loss on the ISS. This prompts the question, how does the lack of load due to zero-gravity propagate to bone-forming cells, human fetal osteoblasts (hFOBs), altering their maturation to mineralization? Here, we aim to study the mechanotransduction mechanisms by which bone loss occurs in microgravity. Two automated experiments, 4 microfluidic chips capable of measuring single-cell mechanics of hFOBs via aspiration and cell spheroids incubated in pressure-controlled chambers, were each integrated into a CubeLab deployed to the ISS National Laboratory. For the first experiment, we report protrusion measurements of aspirated cells after exposure to microgravity at the ISS and compare these results to ground control conducted inside the CubeLab. Our analysis revealed slightly elongated protrusions for space samples compared to ground samples indicating softening of hFOB cells in microgravity. In the second experiment, we encapsulated osteoblast spheroids in collagen gel and incubated the samples in pressure-controlled chambers. We found that microgravity significantly reduced filamentous actin levels in the hFOB spheroids. When subjected to pressure, the spheroids exhibited increased pSMAD1/5/9 expression, regardless of the microgravity condition. Moreover, microgravity reduced YAP expression, while pressure increased YAP levels, thus restoring YAP expression for spheroids in microgravity. Our study provides insights into the influence of microgravity on the mechanical properties of bone cells and the impact of compressive pressure on cell behavior and signaling in space.

cell biology↗

bioRxiv2023

In vivo evolution of a Klebsiella pneumoniae capsule defect promotes complement-mediated opsono-phagocytosis and persistence during recurrent infection

Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) bloodstream infections rarely overwhelm the host but are associated with high mortality. The complement system is a key host defense against bloodstream infection. However, there are varying reports of serum resistance among KPC-Kp isolates. We assessed growth of 59 KPC-Kp clinical isolates in human serum and found increased resistance in 16/59 (27%). We identified five genetically-related bloodstream isolates with varying serum resistance profiles collected from a single patient during an extended hospitalization marked by recurrent KPC-Kp bloodstream infections. We noted a loss-of-function mutation in the capsule biosynthesis gene, wcaJ, that emerged during infection was associated with decreased polysaccharide capsule content, and resistance to complement-mediated killing. Surprisingly, disruption of wcaJ increased deposition of complement proteins on the microbial surface compared to the wild-type strain and led to increased complement-mediated opsono-phagocytosis in human whole blood. Disabling opsono-phagocytosis in the airspaces of mice impaired in vivo control of the wcaJ loss-of-function mutant in an acute lung infection model. These findings describe the rise of a capsular mutation that promotes KPC-Kp persistence within the host by enabling co-existence of increased bloodstream fitness and reduced tissue virulence. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=124 SRC="FIGDIR/small/542722v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@155736eorg.highwire.dtl.DTLVardef@10d47c0org.highwire.dtl.DTLVardef@e1ab83org.highwire.dtl.DTLVardef@1c33131_HPS_FORMAT_FIGEXP M_FIG Graphical abstract Created with BioRender.com C_FIG

microbiology↗

bioRxiv2023

Reversible expansion of tissue macrophages in response to macrophage colony-stimulating factor (CSF1) transforms systemic metabolism to fuel growth.

Background and AimMacrophages regulate metabolic homeostasis in health and disease. Macrophage colony-stimulating factor (CSF1)-dependent macrophages contribute to homeostatic control of the size of the liver. This study aimed to determine the systemic metabolic consequences of elevating circulating CSF1. Methods and ResultsAcute administration of a CSF1-Fc fusion protein led to monocytosis, increased resident tissue macrophages in the liver and all major organs, and liver growth. These effects were associated with increased hepatic glucose uptake and extensive mobilisation of body fat. The impacts of CSF1 on macrophage abundance, liver size and body composition were rapidly reversed to restore homeostasis. CSF1s effects on metabolism were independent of several known endocrine regulators and did not impact the physiological fasting response. Analysis using implantable telemetry in metabolic cages revealed progressively reduced body temperature and physical activity with no change in diurnal food intake. ConclusionThese results demonstrate the existence of a dynamic equilibrium between CSF1, the mononuclear phagocyte system, metabolic regulation and homeostatic control of liver:body weight ratio.

immunology↗

bioRxiv2023

Genetic diversity of North American popcorn germplasm and the effect of population structure on nicosulfuron response

Popcorn is an important crop in the United States; however, genetic analyses of popcorn are limited and tend to utilize relatively few markers that cannot capture the total genomic variation. To improve the genomic resources in popcorn, a panel of 362 popcorn accessions was evaluated using 417,218 single nucleotide polymorphisms generated using a genotyping-by-sequencing approach. Using this genomic data, a model-based clustering analysis identified two populations. The first comprised North American Yellow Pearl Popcorns and several accessions of the Chilean Curagua landrace. The second, the Pointed and Latin American Popcorns, included all remaining North American (pointed and early popcorns), Latin American, and global accessions. The two populations exhibited large differences in population structure and genetic diversity. The North American Yellow Pearl Popcorns constitute a highly inbred population with limited genetic diversity compared to the Pointed and Latin American Popcorns. Additionally, phenotypic differences between the two populations were observed in kernel color and nicosulfuron sensitivity. A filtered set of SNPs was curated and used for genome-wide association studies and popcorn-specific candidate genes for nicosulfuron tolerance were identified. The genomic characterization described here can be used by breeding programs to accelerate the rate of genetic gain and incorporate genetic diversity into elite popcorn germplasm. Core IdeasO_LINorth American Popcorn is composed of two distinct populations that differ genetically and phenotypically. C_LIO_LINorth American Yellow Pearl Popcorns contain limited genetic diversity and are highly inbred. C_LIO_LIPointed and Latin American Popcorns exhibit considerable genetic diversity and rapid linkage disequilibrium decay. C_LIO_LIKernel color does not affect nicosulfuron sensitivity and instead reflects differences between the populations. C_LIO_LIPopcorn-specific candidate genes for nicosulfuron tolerance are distinct from dent corn. C_LI

genetics↗

bioRxiv2022

Unraveling the viral dark matter of the rumen microbiome with a new global virome database

Like in the human gut and other environments, viruses are probably also diverse and modulate the microbiome (both population and function) in the rumen of ruminants, but it remains largely unknown. Here we mined 975 published rumen metagenomes for viral sequences, created the first rumen virome database (RVD), and perform ecogenomic meta-analyses of these data. This identified 397,180 species-level viral operational taxonomic units (vOTUs) and allowed for a 10-fold increase in classification rate of rumen viral sequences compared with other databases. Most of the classified vOTUs belong to the order Caudovirales, but distinct from those in the human gut. Rumen viruses likely have ecosystem impacts as they were predicted to infect dominant fiber degraders and methane producers, and they carry diverse auxiliary metabolic genes and antibiotic resistance genes. Together, the RVD database and these findings provide a baseline framework for future research on how viruses may impact the rumen ecosystem.

microbiology↗

bioRxiv2021

Cooperation between CYB5R3 and NOX4 via coenzyme Q mitigates endothelial inflammation

NADPH oxidase 4 (NOX4) regulates endothelial inflammation by producing reactive oxygen species. Since coenzyme Q (CoQ) mimics affect NOX4 activity, we hypothesize that cytochrome b5 reductase 3 (CYB5R3), a CoQ reductase abundant in vascular endothelial cells, modulates inflammatory activation. Mice lacking endothelial CYB5R3 (R3 KO), under lipopolysaccharides (LPS) challenge, showed exacerbated hypotension, decreased acetylcholine-induced vasodilation, and elevated vascular adhesion molecule 1 (Vcam-1) mRNA in aorta. In vitro, silencing Cyb5r3 enhanced LPS-induced VCAM-1 protein in a NOX4 dependent manner. APEX2- based electron microscopy and proximity biotinylation demonstrated CYB5R3s localization on the mitochondrial outer membrane and its interaction with NOX4, which was further confirmed by the proximity ligation assay. Notably, Cyb5r3 silenced HAECs had less total H2O2 but more mitochondrial O2*-. Using inactive or non-membrane bound active CYB5R3, we found CYB5R3 activity and membrane translocation were needed for optimal generation of H2O2 by NOX4. Lastly, CoQ deficient cells showed decreased NOX4-derived H2O2, indicating a requirement for endogenous CoQ in NOX4 activity. In conclusion, CYB5R3 mitigates endothelial inflammatory activation by assisting in NOX4-dependent H2O2 generation via CoQ. NOVELTY AND SIGNIFICANCEO_ST_ABSWhat Is Known?C_ST_ABSNADPH oxidase 4 (NOX4) reportedly produces primarily hydrogen peroxide (H2O2) and, to a lesser extent, superoxide (O2*-) and has been shown to have both beneficial and deleterious effects in the cardiovascular system. NOX4 activity can be affected by NAD(P)H quinone oxidoreductase 1 (NQO1), a CoQ reductase, and synthetic quinone compounds used to mimic CoQ. Cytochrome b5 reductase 3 (CYB5R3) is known to reduce CoQ and is highly expressed in endothelial cells. What New Information Does This Article Contribute?In vivo, the lack of endothelial CYB5R3 causes exacerbated lipopolysaccharides (LPS)-induced inflammatory signaling, endothelial dysfunction, and hypotension. Endothelial CYB5R3 mitigates inflammatory signaling by LPS and tumor necrosis factor (TNF-) in a NOX4 dependent manner. In endothelial cells, CYB5R3 and NOX4 reside in close proximity on the mitochondrial outer membrane. NOX4s ability to generate H2O2 depends on the membrane translocation and activity of CYB5R3 and the presence of endogenous CoQ. NONSTANDARD Abbreviations and Acronyms [Table 1] Protein names are abbreviated as capital letters (e.g., CYB5R3), while the corresponding gene names are annotated as in italic lower cases (e.g., Cyb5r3).

cell biology↗

bioRxiv2021

Making Strides in Doctoral-Level Career Outcomes Reporting: Surveying the Landscape of Classification and Visualization Methodologies and Creating a Crosswalk Tool

The recent movement underscoring the importance of career taxonomies has helped usher in a new era of transparency in PhD career outcomes. The convergence of discipline-specific organizational movements, interdisciplinary collaborations, and federal initiatives have all helped to increase PhD career outcomes tracking and reporting. Transparent and publicly available PhD career outcomes are being used by institutions to attract top applicants, as prospective graduate students are factoring these in when deciding on the program and institution in which to enroll for their PhD studies. Given the increasing trend to track PhD career outcomes, the number of institutional efforts and supporting offices for these studies have increased, as has the variety of methods being used to classify and report/visualize outcomes. This report identifies and summarizes currently available PhD career taxonomy tools, resources, and visualization options to help catalyze and empower institutions to develop and publish their own PhD career outcomes. Similar fields between taxonomies were mapped to create a new crosswalk tool. This work serves as an empirical review of the career outcome tracking systems available and highlights organizations, consortia, and funding agencies that are impacting policy change toward greater transparency in PhD career outcomes reporting.

scientific communication and education↗

bioRxiv2021

Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drive rapid and potent immunogenicity capable of single-dose protection

Antibodies from SARS-CoV-2 vaccines may target epitopes which reduce durability or increase the potential for escape from vaccine-induced immunity. Using a novel synthetic vaccinology pipeline, we developed rationally immune focused SARS-CoV-2 Spike-based vaccines. N-linked glycans can be employed to alter antibody responses to infection and vaccines. Utilizing computational modeling and comprehensive in vitro screening, we incorporated glycans into the Spike Receptor-Binding Domain (RBD) and assessed antigenic profiles. We developed glycan coated RBD immunogens and engineered seven multivalent configurations. Advanced DNA delivery of engineered nanoparticle vaccines rapidly elicited potent neutralizing antibodies in guinea pigs, hamsters and multiple mouse models, including human ACE2 and human B cell repertoire transgenics. RBD nanoparticles encoding wild-type and the P.1 SARS-CoV-2 variant induced high levels of cross-neutralizing antibodies. Single, low dose immunization protected against a lethal SARS-CoV-2 challenge. Single-dose coronavirus vaccines via DNA-launched nanoparticles provide a platform for rapid clinical translation of novel, potent coronavirus vaccines.

immunology↗

bioRxiv2020

Action Imagery and Observation in Neurorehabilitation for Parkinson's Disease (ACTION-PD): development and pilot randomised controlled trial of a user-informed home training intervention to improve everyday functional actions

BackgroundParkinsons disease (PD) causes difficulties with everyday manual activities, but few studies have addressed these therapeutically. Training with action observation (AO) and motor imagery (MI) can significantly improve performance in healthy individuals, particularly when these techniques are applied simultaneously (AO+MI). Both AO and MI have shown promising effects in PD, but previous studies have used these separately. This article describes the development and pilot testing of an intervention combining AO+MI and physical practice to improve functional manual actions in PD. MethodsThe home-based intervention, delivered using a tablet computer app, was iteratively designed by an interdisciplinary team including people with PD, and further developed through focus groups and initial testing. The intervention was then tested in a six-week randomised controlled trial (ISRCTN 11184024) of 10 participants with mild to moderate PD (6 intervention; 4 treatment as usual). Results and ConclusionsUsage and qualitative data provided preliminary evidence of acceptability and usability, indicating that a feasibility RCT is warranted. Exploratory analyses suggested potential improvements in manual actions. The importance of personalisation, choice, and motivation was highlighted, as well as the need to facilitate engagement in motor imagery. The findings also have broader relevance for AO+MI interventions in PD and other populations.

neuroscience↗