Skip to content
DraconiticResearch
Search Sources API
203,948 studies31 sourcesUpdated 15 min ago
Peer-reviewedCC BY 4.0The European Journal of Neuroscience

Time to Move Upstream? A Framework for Expanding the Focus of Freezing of Gait to Prodromal, Subclinical, and Pre‐FOG Stages

  • Jeffrey M. Hausdorff1,2,3,4
  • Kaylena A. Ehgoetz Martens5
  • Moran Gilat6
  • Jorik Nonnekes7
  • Martina Mancini8
  • J. Lucas McKay9
  • Pieter Ginis6,10
  • Jamie L. Adams11
  • Jennifer R. Mammen12
  • Erika E. Howe5
  • Simon J. G. Lewis13
  • Fay Horak9
1 more authors
  • Alice Nieuwboer6
13 affiliations
  1. 1Center for the Study of Movement, Cognition, and Mobility Tel Aviv Sourasky University Medical Center ‐ Ichilov Tel Aviv Israel
  2. 2Department of Physical Therapy, Gray Faculty of Medical & Health Sciences, and Sagol School of Neuroscience Tel Aviv University Tel Aviv Israel
  3. 3Rush Alzheimer's Disease Center, Rush University Medical Center, and Department of Orthopaedic Surgery Rush Medical College Chicago Illinois USA
  4. 4School of Biomedical Engineering Tel Aviv University Tel Aviv Israel
  5. 5Department of Kinesiology and Health Sciences University of Waterloo Waterloo Canada
  6. 6Department of Rehabilitation Sciences Research Group for Neurorehabilitation (eNRGy), KU Leuven Leuven Belgium
  7. 7Department of Rehabilitation, Center of Expertise for Parkinson and Movement Disorders, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center Nijmegen the Netherlands
  8. 8Department of Neurology Oregon Health and Science University Portland Oregon USA
  9. 9Department of Biomedical Informatics and Department of Neurology Emory University School of Medicine Atlanta Georgia USA
  10. 10Clario, Part of Thermo Fisher Scientific Philadelphia Pennsylvania USA
  11. 11Department of Neurology University of Rochester Rochester New York USA
  12. 12University of Massachusetts Dartmouth College of Nursing and Health Sciences Dartmouth Massachusetts USA
  13. 13Parkinson’s Disease Research Clinic Macquarie University Brain Institute and Clinic Sydney Australia
Read full textPDFDOICite

Abstract

Freezing of gait (FOG) is one of the most disabling motor symptoms of Parkinson's disease, yet a fundamental question remains unresolved: why does FOG occur at any given moment? Most research has focused on studying FOG once it is already manifest. The present work aims to synthesize recent observations and propose a conceptual framework in which FOG reflects a dynamic process unfolding across multiple stages and time scales. Subtle changes in gait dynamics and physiology can precede episodes by several seconds (Stage −1), and experimental paradigms show that individuals without clinically recognized freezing may exhibit brief episodes under sufficiently sensitive conditions (Stage −2). At longer time scales, prospective studies indicate that vulnerability to freezing may be detectable years before onset (Stage −3). This framework reflects the idea that FOG emerges from progressive instability across interacting motor, cognitive, autonomic, and environmental systems, rather than as an isolated event. The proposed framework includes a prodromal stage, a subclinical stage, an immediate prefreezing state, and the freezing episode itself (Stage 0). This framework integrates findings from wearable sensing, physiology, and clinical studies and emphasizes that FOG remains latent in Stage −3, may be elicited only under specific conditions in Stage −2, and becomes manifest as instability evolves toward imminent and overt freezing (Stages −1 and 0, respectively). Reframing FOG as a multistage process that includes an upstream phase raises new questions regarding mechanisms, classification, and intervention, and may, ultimately, inform strategies aimed at predicting and preventing freezing rather than simply reacting to it.

Related

  1. Enhancement of gut-microbiome-based classification of prodromal Parkinson's Disease cases by hyperparameter tuning, integration of multimodal data, and meta-analysis.
    S. Gogoi, P. R. Somvanshi, V. Thakur
    bioRxivPreprintAll rights reservedFull textBioinformatics & computational biologybioRxiv
  2. Modelling prodromal Parkinson's disease- gastrointestinal pathology and early motor deficits in mice after transient rotenone exposure
    S. Selvaraji, J. Mosberger, K. K. L. Pang +5
    bioRxivPreprintAll rights reservedFull textNeurosciencebioRxiv
  3. Neuroinflammation is an early pathological process in a mouse model of prodromal Parkinsons disease
    Gabriela Mercado, Lucas Stetzik, Emily Schulz +8
    bioRxivPreprintAll rights reservedFull textNeurosciencebioRxivPMC
  4. Charting vulnerability of brainstem functional pathways in aging and prodromal synucleinopathy
    Lin Hua, Kavita Singh, Maria Guadalupe Garcia-Gomar +7
    bioRxivPreprintCC BY-NCFull textNeurosciencebioRxivPMC
  5. Adolescent prodromal phenotypes of psychiatric disorders: insights from a novel DISC1-perturbed monkey model
    Z. Lan, H. Onoe, T. Tsukiyama +28
    bioRxivPreprintCC BYFull textNeurosciencebioRxiv

Cite

BibTeXRIS
BibTeX
@article{hausdorff2026time,
  title = {{Time to Move Upstream? A Framework for Expanding the Focus of Freezing of Gait to Prodromal, Subclinical, and Pre‐FOG Stages}},
  author = {Jeffrey M. Hausdorff and Kaylena A. Ehgoetz Martens and Moran Gilat and Jorik Nonnekes and Martina Mancini and J. Lucas McKay and Pieter Ginis and Jamie L. Adams and Jennifer R. Mammen and Erika E. Howe and Simon J. G. Lewis and Fay Horak and Alice Nieuwboer},
  journal = {The European Journal of Neuroscience},
  year = {2026},
  month = nov,
  doi = {10.1111/ejn.70721},
  url = {https://doi.org/10.1111/ejn.70721},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Time to Move Upstream? A Framework for Expanding the Focus of Freezing of Gait to Prodromal, Subclinical, and Pre‐FOG Stages
AU  - Jeffrey M. Hausdorff
AU  - Kaylena A. Ehgoetz Martens
AU  - Moran Gilat
AU  - Jorik Nonnekes
AU  - Martina Mancini
AU  - J. Lucas McKay
AU  - Pieter Ginis
AU  - Jamie L. Adams
AU  - Jennifer R. Mammen
AU  - Erika E. Howe
AU  - Simon J. G. Lewis
AU  - Fay Horak
AU  - Alice Nieuwboer
PY  - 2026
DA  - 2026/11/04
JO  - The European Journal of Neuroscience
DO  - 10.1111/ejn.70721
UR  - https://doi.org/10.1111/ejn.70721
AB  - Freezing of gait (FOG) is one of the most disabling motor symptoms of Parkinson's disease, yet a fundamental question remains unresolved: why does FOG occur at any given moment? Most research has focused on studying FOG once it is already manifest. The present work aims to synthesize recent observations and propose a conceptual framework in which FOG reflects a dynamic process unfolding across multiple stages and time scales. Subtle changes in gait dynamics and physiology can precede episodes by several seconds (Stage −1), and experimental paradigms show that individuals without clinically recognized freezing may exhibit brief episodes under sufficiently sensitive conditions (Stage −2). At longer time scales, prospective studies indicate that vulnerability to freezing may be detectable years before onset (Stage −3). This framework reflects the idea that FOG emerges from progressive instability across interacting motor, cognitive, autonomic, and environmental systems, rather than as an isolated event. The proposed framework includes a prodromal stage, a subclinical stage, an immediate prefreezing state, and the freezing episode itself (Stage 0). This framework integrates findings from wearable sensing, physiology, and clinical studies and emphasizes that FOG remains latent in Stage −3, may be elicited only under specific conditions in Stage −2, and becomes manifest as instability evolves toward imminent and overt freezing (Stages −1 and 0, respectively). Reframing FOG as a multistage process that includes an upstream phase raises new questions regarding mechanisms, classification, and intervention, and may, ultimately, inform strategies aimed at predicting and preventing freezing rather than simply reacting to it.
SN  - 0953-816X
SN  - 1460-9568
ER  -