Zero-phase-delay connectivity increases the reliability, concordance with structure, and prognostic ability of functional connectivity metrics

Chirag Mehra; Ahmad Beyh; Petroula Laiou; Pilar Garces; Declan Murphy; Eva Loth; Flavio Dell' Acqua; Joshua B. Ewen; Mark Richardson; Jonathan O'Muircheartaigh

doi:10.1101/2025.01.04.631256

Zero-phase-delay connectivity increases the reliability, concordance with structure, and prognostic ability of functional connectivity metrics

Chirag Mehra^*, Ahmad Beyh, Petroula Laiou, Pilar Garces, Declan Murphy, Eva Loth, Flavio Dell' Acqua, Joshua B. Ewen, Mark Richardson, Jonathan O'Muircheartaigh

^*Corresponding author for this work

Research output: Working paper/Preprint › Preprint

Abstract

Zero-phase-delay synchrony between the activity of distant neural populations has been robustly observed. Nevertheless, contemporary electroencephalography and magnetencephalography functional connectivity analyses typically exclude zero-phase-delay functional connections, assuming that they are predominantly artefactual. However, the effects of excluding them on the performance of functional connectivity metrics as potential biomarkers are unknown. Here, we showed that most cortico-cortical functional connections occur with zero- or near-zero phase-delay, even where such connectivity was unlikely to be artefactual. Including, rather than excluding, zero-phase-delay connectivity increased the reliability, concordance with structural connectivity, and predictive validity (for longitudinal changes in cognition) of functional connectivity metrics. We found that excluding zero-phase-delay connections penalised functional connectivity strength between the strongest structurally connected regions: stronger structural connections led to functional connections with phase-delays closer to zero, mediated by a shorter signal propagation time. Our findings challenge generally accepted assumptions that zero-phase-exclusive methods are superior to zero-phase-inclusive methods.

Original language	English
DOIs	https://doi.org/10.1101/2025.01.04.631256
Publication status	Published - 4 Jan 2025

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10.1101/2025.01.04.631256Licence: CC BY-NC-ND

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title = "Zero-phase-delay connectivity increases the reliability, concordance with structure, and prognostic ability of functional connectivity metrics",

abstract = "Zero-phase-delay synchrony between the activity of distant neural populations has been robustly observed. Nevertheless, contemporary electroencephalography and magnetencephalography functional connectivity analyses typically exclude zero-phase-delay functional connections, assuming that they are predominantly artefactual. However, the effects of excluding them on the performance of functional connectivity metrics as potential biomarkers are unknown. Here, we showed that most cortico-cortical functional connections occur with zero- or near-zero phase-delay, even where such connectivity was unlikely to be artefactual. Including, rather than excluding, zero-phase-delay connectivity increased the reliability, concordance with structural connectivity, and predictive validity (for longitudinal changes in cognition) of functional connectivity metrics. We found that excluding zero-phase-delay connections penalised functional connectivity strength between the strongest structurally connected regions: stronger structural connections led to functional connections with phase-delays closer to zero, mediated by a shorter signal propagation time. Our findings challenge generally accepted assumptions that zero-phase-exclusive methods are superior to zero-phase-inclusive methods.",

author = "Chirag Mehra and Ahmad Beyh and Petroula Laiou and Pilar Garces and Declan Murphy and Eva Loth and {Dell' Acqua}, Flavio and Ewen, {Joshua B.} and Mark Richardson and Jonathan O'Muircheartaigh",

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AU - Mehra, Chirag

AU - Beyh, Ahmad

AU - Laiou, Petroula

AU - Garces, Pilar

AU - Murphy, Declan

AU - Loth, Eva

AU - Dell' Acqua, Flavio

AU - Ewen, Joshua B.

AU - Richardson, Mark

AU - O'Muircheartaigh, Jonathan

PY - 2025/1/4

Y1 - 2025/1/4

N2 - Zero-phase-delay synchrony between the activity of distant neural populations has been robustly observed. Nevertheless, contemporary electroencephalography and magnetencephalography functional connectivity analyses typically exclude zero-phase-delay functional connections, assuming that they are predominantly artefactual. However, the effects of excluding them on the performance of functional connectivity metrics as potential biomarkers are unknown. Here, we showed that most cortico-cortical functional connections occur with zero- or near-zero phase-delay, even where such connectivity was unlikely to be artefactual. Including, rather than excluding, zero-phase-delay connectivity increased the reliability, concordance with structural connectivity, and predictive validity (for longitudinal changes in cognition) of functional connectivity metrics. We found that excluding zero-phase-delay connections penalised functional connectivity strength between the strongest structurally connected regions: stronger structural connections led to functional connections with phase-delays closer to zero, mediated by a shorter signal propagation time. Our findings challenge generally accepted assumptions that zero-phase-exclusive methods are superior to zero-phase-inclusive methods.

AB - Zero-phase-delay synchrony between the activity of distant neural populations has been robustly observed. Nevertheless, contemporary electroencephalography and magnetencephalography functional connectivity analyses typically exclude zero-phase-delay functional connections, assuming that they are predominantly artefactual. However, the effects of excluding them on the performance of functional connectivity metrics as potential biomarkers are unknown. Here, we showed that most cortico-cortical functional connections occur with zero- or near-zero phase-delay, even where such connectivity was unlikely to be artefactual. Including, rather than excluding, zero-phase-delay connectivity increased the reliability, concordance with structural connectivity, and predictive validity (for longitudinal changes in cognition) of functional connectivity metrics. We found that excluding zero-phase-delay connections penalised functional connectivity strength between the strongest structurally connected regions: stronger structural connections led to functional connections with phase-delays closer to zero, mediated by a shorter signal propagation time. Our findings challenge generally accepted assumptions that zero-phase-exclusive methods are superior to zero-phase-inclusive methods.

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BT - Zero-phase-delay connectivity increases the reliability, concordance with structure, and prognostic ability of functional connectivity metrics

ER -

Zero-phase-delay connectivity increases the reliability, concordance with structure, and prognostic ability of functional connectivity metrics

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