Intrinsic connectivity network disruption in progressive supranuclear palsy
Raquel C Gardner, Adam L Boxer, Andrew Trujillo, Jacob B Mirsky, Christine C Guo, Efstathios D Gennatas, Hilary W Heuer, Eric Fine, Juan Zhou, Joel H Kramer, Bruce L Miller, William W Seeley, Raquel C Gardner, Adam L Boxer, Andrew Trujillo, Jacob B Mirsky, Christine C Guo, Efstathios D Gennatas, Hilary W Heuer, Eric Fine, Juan Zhou, Joel H Kramer, Bruce L Miller, William W Seeley
Abstract
Objective: Progressive supranuclear palsy (PSP) has been conceptualized as a large-scale network disruption, but the specific network targeted has not been fully characterized. We sought to delineate the affected network in patients with clinical PSP.
Methods: Using task-free functional magnetic resonance imaging, we mapped intrinsic connectivity to the dorsal midbrain tegmentum (dMT), a region that shows focal atrophy in PSP. Two healthy control groups (1 young, 1 older) were used to define and replicate the normal connectivity pattern, and patients with PSP were compared to an independent matched healthy control group on measures of network connectivity.
Results: Healthy young and older subjects showed a convergent pattern of connectivity to the dMT, including brainstem, cerebellar, diencephalic, basal ganglia, and cortical regions involved in skeletomotor, oculomotor, and executive control. Patients with PSP showed significant connectivity disruptions within this network, particularly within corticosubcortical and cortico-brainstem interactions. Patients with more severe functional impairment showed lower mean dMT network connectivity scores.
Interpretation: This study defines a PSP-related intrinsic connectivity network in the healthy brain and demonstrates the sensitivity of network-based imaging methods to PSP-related physiological and clinical changes.
Copyright © 2012 American Neurological Association.
Figures
![Figure 1. The dMT-associated ICN](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3732833/bin/nihms433109f1.jpg)
Figure 2. Network connectivity reductions in PSP
Figure 2. Network connectivity reductions in PSP
Examining the same dMT-associated ICN shown in Figure…
Figure 3. The broader PSP-related network in…
Figure 3. The broader PSP-related network in health and disease
Regions showing intrinsic connectivity to…
Figure 4. The matrix-derived dMT-associated ICN architecture…
Figure 4. The matrix-derived dMT-associated ICN architecture and connectivity reductions in PSP
An edge-weighted force-directed…
Figure 5. Clinical Correlations to dMT-associated ICN…
Figure 5. Clinical Correlations to dMT-associated ICN Score
Scatterplots represent the relationships between mean network…
Figure 6. Effect size comparison of dMT…
Figure 6. Effect size comparison of dMT associated ICN reductions versus grey matter atrophy in…
- Advancing functional dysconnectivity and atrophy in progressive supranuclear palsy.Brown JA, Hua AY, Trujllo A, Attygalle S, Binney RJ, Spina S, Lee SE, Kramer JH, Miller BL, Rosen HJ, Boxer AL, Seeley WW. Brown JA, et al. Neuroimage Clin. 2017 Sep 12;16:564-574. doi: 10.1016/j.nicl.2017.09.008. eCollection 2017. Neuroimage Clin. 2017. PMID: 28951832 Free PMC article.
- Tau burden and the functional connectome in Alzheimer's disease and progressive supranuclear palsy.Cope TE, Rittman T, Borchert RJ, Jones PS, Vatansever D, Allinson K, Passamonti L, Vazquez Rodriguez P, Bevan-Jones WR, O'Brien JT, Rowe JB. Cope TE, et al. Brain. 2018 Feb 1;141(2):550-567. doi: 10.1093/brain/awx347. Brain. 2018. PMID: 29293892 Free PMC article.
- Disrupted resting-state functional connectivity in progressive supranuclear palsy.Piattella MC, Tona F, Bologna M, Sbardella E, Formica A, Petsas N, Filippini N, Berardelli A, Pantano P. Piattella MC, et al. AJNR Am J Neuroradiol. 2015 May;36(5):915-21. doi: 10.3174/ajnr.A4229. Epub 2015 Feb 5. AJNR Am J Neuroradiol. 2015. PMID: 25655870 Free PMC article.
- The value of novel MRI techniques in Parkinson-plus syndromes: diffusion tensor imaging and anatomical connectivity studies.Tir M, Delmaire C, Besson P, Defebvre L. Tir M, et al. Rev Neurol (Paris). 2014 Apr;170(4):266-76. doi: 10.1016/j.neurol.2013.10.013. Epub 2014 Mar 20. Rev Neurol (Paris). 2014. PMID: 24656811 Review.
- Voxelwise meta-analysis of white matter abnormalities in progressive supranuclear palsy.Yang J, Shao N, Li J, Shang H. Yang J, et al. Neurol Sci. 2014 Jan;35(1):7-14. doi: 10.1007/s10072-013-1512-8. Epub 2013 Aug 3. Neurol Sci. 2014. PMID: 23912687 Review.
- Pathomechanisms of cognitive impairment in progressive supranuclear palsy.Jellinger KA. Jellinger KA. J Neural Transm (Vienna). 2023 Apr;130(4):481-493. doi: 10.1007/s00702-023-02613-w. Epub 2023 Mar 2. J Neural Transm (Vienna). 2023. PMID: 36862189 Review.
- Interplay of tau and functional network connectivity in progressive supranuclear palsy: a [18F]PI-2620 PET/MRI study.Aghakhanyan G, Rullmann M, Rumpf J, Schroeter ML, Scherlach C, Patt M, Brendel M, Koglin N, Stephens AW, Classen J, Hoffmann KT, Sabri O, Barthel H. Aghakhanyan G, et al. Eur J Nucl Med Mol Imaging. 2022 Dec;50(1):103-114. doi: 10.1007/s00259-022-05952-0. Epub 2022 Sep 1. Eur J Nucl Med Mol Imaging. 2022. PMID: 36048259
- Progressive supranuclear palsy and corticobasal degeneration: novel clinical concepts and advances in biomarkers.Parmera JB, Oliveira MCB, Rodrigues RD, Coutinho AM. Parmera JB, et al. Arq Neuropsiquiatr. 2022 May;80(5 Suppl 1):126-136. doi: 10.1590/0004-282X-ANP-2022-S134. Arq Neuropsiquiatr. 2022. PMID: 35976324 Free PMC article. Review.
- Global slowness and increased intra-individual variability are key features of attentional deficits and cognitive fluctuations in post COVID-19 patients.Ortelli P, Benso F, Ferrazzoli D, Scarano I, Saltuari L, Sebastianelli L, Versace V, Maestri R. Ortelli P, et al. Sci Rep. 2022 Jul 30;12(1):13123. doi: 10.1038/s41598-022-17463-x. Sci Rep. 2022. PMID: 35907947 Free PMC article.
- Default Mode Network quantitative diffusion and resting-state functional magnetic resonance imaging correlates in sporadic Creutzfeldt-Jakob disease.Paoletti M, Caverzasi E, Mandelli ML, Brown JA, Henry RG, Miller BL, Rosen HJ, DeArmond SJ, Bastianello S, Seeley WW, Geschwind MD. Paoletti M, et al. Hum Brain Mapp. 2022 Sep;43(13):4158-4173. doi: 10.1002/hbm.25945. Epub 2022 Jun 6. Hum Brain Mapp. 2022. PMID: 35662331 Free PMC article.
- Multicenter Study
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Aged
- Brain / blood supply
- Brain / pathology*
- Brain / physiopathology*
- Brain Mapping
- Female
- Humans
- Image Processing, Computer-Assisted
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Nerve Net / pathology*
- Nerve Net / physiopathology
- Neural Pathways / blood supply
- Neural Pathways / pathology*
- Oxygen / blood
- Severity of Illness Index
- Statistics as Topic
- Supranuclear Palsy, Progressive / pathology*
- Oxygen
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 2. Network connectivity reductions in PSP](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3732833/bin/nihms433109f2.jpg)
Figure 3. The broader PSP-related network in…
Figure 3. The broader PSP-related network in health and disease
Regions showing intrinsic connectivity to…
Figure 4. The matrix-derived dMT-associated ICN architecture…
Figure 4. The matrix-derived dMT-associated ICN architecture and connectivity reductions in PSP
An edge-weighted force-directed…
Figure 5. Clinical Correlations to dMT-associated ICN…
Figure 5. Clinical Correlations to dMT-associated ICN Score
Scatterplots represent the relationships between mean network…
Figure 6. Effect size comparison of dMT…
Figure 6. Effect size comparison of dMT associated ICN reductions versus grey matter atrophy in…
- Advancing functional dysconnectivity and atrophy in progressive supranuclear palsy.Brown JA, Hua AY, Trujllo A, Attygalle S, Binney RJ, Spina S, Lee SE, Kramer JH, Miller BL, Rosen HJ, Boxer AL, Seeley WW. Brown JA, et al. Neuroimage Clin. 2017 Sep 12;16:564-574. doi: 10.1016/j.nicl.2017.09.008. eCollection 2017. Neuroimage Clin. 2017. PMID: 28951832 Free PMC article.
- Tau burden and the functional connectome in Alzheimer's disease and progressive supranuclear palsy.Cope TE, Rittman T, Borchert RJ, Jones PS, Vatansever D, Allinson K, Passamonti L, Vazquez Rodriguez P, Bevan-Jones WR, O'Brien JT, Rowe JB. Cope TE, et al. Brain. 2018 Feb 1;141(2):550-567. doi: 10.1093/brain/awx347. Brain. 2018. PMID: 29293892 Free PMC article.
- Disrupted resting-state functional connectivity in progressive supranuclear palsy.Piattella MC, Tona F, Bologna M, Sbardella E, Formica A, Petsas N, Filippini N, Berardelli A, Pantano P. Piattella MC, et al. AJNR Am J Neuroradiol. 2015 May;36(5):915-21. doi: 10.3174/ajnr.A4229. Epub 2015 Feb 5. AJNR Am J Neuroradiol. 2015. PMID: 25655870 Free PMC article.
- The value of novel MRI techniques in Parkinson-plus syndromes: diffusion tensor imaging and anatomical connectivity studies.Tir M, Delmaire C, Besson P, Defebvre L. Tir M, et al. Rev Neurol (Paris). 2014 Apr;170(4):266-76. doi: 10.1016/j.neurol.2013.10.013. Epub 2014 Mar 20. Rev Neurol (Paris). 2014. PMID: 24656811 Review.
- Voxelwise meta-analysis of white matter abnormalities in progressive supranuclear palsy.Yang J, Shao N, Li J, Shang H. Yang J, et al. Neurol Sci. 2014 Jan;35(1):7-14. doi: 10.1007/s10072-013-1512-8. Epub 2013 Aug 3. Neurol Sci. 2014. PMID: 23912687 Review.
- Pathomechanisms of cognitive impairment in progressive supranuclear palsy.Jellinger KA. Jellinger KA. J Neural Transm (Vienna). 2023 Apr;130(4):481-493. doi: 10.1007/s00702-023-02613-w. Epub 2023 Mar 2. J Neural Transm (Vienna). 2023. PMID: 36862189 Review.
- Interplay of tau and functional network connectivity in progressive supranuclear palsy: a [18F]PI-2620 PET/MRI study.Aghakhanyan G, Rullmann M, Rumpf J, Schroeter ML, Scherlach C, Patt M, Brendel M, Koglin N, Stephens AW, Classen J, Hoffmann KT, Sabri O, Barthel H. Aghakhanyan G, et al. Eur J Nucl Med Mol Imaging. 2022 Dec;50(1):103-114. doi: 10.1007/s00259-022-05952-0. Epub 2022 Sep 1. Eur J Nucl Med Mol Imaging. 2022. PMID: 36048259
- Progressive supranuclear palsy and corticobasal degeneration: novel clinical concepts and advances in biomarkers.Parmera JB, Oliveira MCB, Rodrigues RD, Coutinho AM. Parmera JB, et al. Arq Neuropsiquiatr. 2022 May;80(5 Suppl 1):126-136. doi: 10.1590/0004-282X-ANP-2022-S134. Arq Neuropsiquiatr. 2022. PMID: 35976324 Free PMC article. Review.
- Global slowness and increased intra-individual variability are key features of attentional deficits and cognitive fluctuations in post COVID-19 patients.Ortelli P, Benso F, Ferrazzoli D, Scarano I, Saltuari L, Sebastianelli L, Versace V, Maestri R. Ortelli P, et al. Sci Rep. 2022 Jul 30;12(1):13123. doi: 10.1038/s41598-022-17463-x. Sci Rep. 2022. PMID: 35907947 Free PMC article.
- Default Mode Network quantitative diffusion and resting-state functional magnetic resonance imaging correlates in sporadic Creutzfeldt-Jakob disease.Paoletti M, Caverzasi E, Mandelli ML, Brown JA, Henry RG, Miller BL, Rosen HJ, DeArmond SJ, Bastianello S, Seeley WW, Geschwind MD. Paoletti M, et al. Hum Brain Mapp. 2022 Sep;43(13):4158-4173. doi: 10.1002/hbm.25945. Epub 2022 Jun 6. Hum Brain Mapp. 2022. PMID: 35662331 Free PMC article.
- Multicenter Study
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Aged
- Brain / blood supply
- Brain / pathology*
- Brain / physiopathology*
- Brain Mapping
- Female
- Humans
- Image Processing, Computer-Assisted
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Nerve Net / pathology*
- Nerve Net / physiopathology
- Neural Pathways / blood supply
- Neural Pathways / pathology*
- Oxygen / blood
- Severity of Illness Index
- Statistics as Topic
- Supranuclear Palsy, Progressive / pathology*
- Oxygen
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 3. The broader PSP-related network in…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3732833/bin/nihms433109f3.jpg)
![Figure 4. The matrix-derived dMT-associated ICN architecture…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3732833/bin/nihms433109f4.jpg)
Figure 5. Clinical Correlations to dMT-associated ICN…
Figure 5. Clinical Correlations to dMT-associated ICN Score
Scatterplots represent the relationships between mean network…
Figure 6. Effect size comparison of dMT…
Figure 6. Effect size comparison of dMT associated ICN reductions versus grey matter atrophy in…
- Advancing functional dysconnectivity and atrophy in progressive supranuclear palsy.Brown JA, Hua AY, Trujllo A, Attygalle S, Binney RJ, Spina S, Lee SE, Kramer JH, Miller BL, Rosen HJ, Boxer AL, Seeley WW. Brown JA, et al. Neuroimage Clin. 2017 Sep 12;16:564-574. doi: 10.1016/j.nicl.2017.09.008. eCollection 2017. Neuroimage Clin. 2017. PMID: 28951832 Free PMC article.
- Tau burden and the functional connectome in Alzheimer's disease and progressive supranuclear palsy.Cope TE, Rittman T, Borchert RJ, Jones PS, Vatansever D, Allinson K, Passamonti L, Vazquez Rodriguez P, Bevan-Jones WR, O'Brien JT, Rowe JB. Cope TE, et al. Brain. 2018 Feb 1;141(2):550-567. doi: 10.1093/brain/awx347. Brain. 2018. PMID: 29293892 Free PMC article.
- Disrupted resting-state functional connectivity in progressive supranuclear palsy.Piattella MC, Tona F, Bologna M, Sbardella E, Formica A, Petsas N, Filippini N, Berardelli A, Pantano P. Piattella MC, et al. AJNR Am J Neuroradiol. 2015 May;36(5):915-21. doi: 10.3174/ajnr.A4229. Epub 2015 Feb 5. AJNR Am J Neuroradiol. 2015. PMID: 25655870 Free PMC article.
- The value of novel MRI techniques in Parkinson-plus syndromes: diffusion tensor imaging and anatomical connectivity studies.Tir M, Delmaire C, Besson P, Defebvre L. Tir M, et al. Rev Neurol (Paris). 2014 Apr;170(4):266-76. doi: 10.1016/j.neurol.2013.10.013. Epub 2014 Mar 20. Rev Neurol (Paris). 2014. PMID: 24656811 Review.
- Voxelwise meta-analysis of white matter abnormalities in progressive supranuclear palsy.Yang J, Shao N, Li J, Shang H. Yang J, et al. Neurol Sci. 2014 Jan;35(1):7-14. doi: 10.1007/s10072-013-1512-8. Epub 2013 Aug 3. Neurol Sci. 2014. PMID: 23912687 Review.
- Pathomechanisms of cognitive impairment in progressive supranuclear palsy.Jellinger KA. Jellinger KA. J Neural Transm (Vienna). 2023 Apr;130(4):481-493. doi: 10.1007/s00702-023-02613-w. Epub 2023 Mar 2. J Neural Transm (Vienna). 2023. PMID: 36862189 Review.
- Interplay of tau and functional network connectivity in progressive supranuclear palsy: a [18F]PI-2620 PET/MRI study.Aghakhanyan G, Rullmann M, Rumpf J, Schroeter ML, Scherlach C, Patt M, Brendel M, Koglin N, Stephens AW, Classen J, Hoffmann KT, Sabri O, Barthel H. Aghakhanyan G, et al. Eur J Nucl Med Mol Imaging. 2022 Dec;50(1):103-114. doi: 10.1007/s00259-022-05952-0. Epub 2022 Sep 1. Eur J Nucl Med Mol Imaging. 2022. PMID: 36048259
- Progressive supranuclear palsy and corticobasal degeneration: novel clinical concepts and advances in biomarkers.Parmera JB, Oliveira MCB, Rodrigues RD, Coutinho AM. Parmera JB, et al. Arq Neuropsiquiatr. 2022 May;80(5 Suppl 1):126-136. doi: 10.1590/0004-282X-ANP-2022-S134. Arq Neuropsiquiatr. 2022. PMID: 35976324 Free PMC article. Review.
- Global slowness and increased intra-individual variability are key features of attentional deficits and cognitive fluctuations in post COVID-19 patients.Ortelli P, Benso F, Ferrazzoli D, Scarano I, Saltuari L, Sebastianelli L, Versace V, Maestri R. Ortelli P, et al. Sci Rep. 2022 Jul 30;12(1):13123. doi: 10.1038/s41598-022-17463-x. Sci Rep. 2022. PMID: 35907947 Free PMC article.
- Default Mode Network quantitative diffusion and resting-state functional magnetic resonance imaging correlates in sporadic Creutzfeldt-Jakob disease.Paoletti M, Caverzasi E, Mandelli ML, Brown JA, Henry RG, Miller BL, Rosen HJ, DeArmond SJ, Bastianello S, Seeley WW, Geschwind MD. Paoletti M, et al. Hum Brain Mapp. 2022 Sep;43(13):4158-4173. doi: 10.1002/hbm.25945. Epub 2022 Jun 6. Hum Brain Mapp. 2022. PMID: 35662331 Free PMC article.
- Multicenter Study
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Aged
- Brain / blood supply
- Brain / pathology*
- Brain / physiopathology*
- Brain Mapping
- Female
- Humans
- Image Processing, Computer-Assisted
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Nerve Net / pathology*
- Nerve Net / physiopathology
- Neural Pathways / blood supply
- Neural Pathways / pathology*
- Oxygen / blood
- Severity of Illness Index
- Statistics as Topic
- Supranuclear Palsy, Progressive / pathology*
- Oxygen
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
![Figure 5. Clinical Correlations to dMT-associated ICN…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3732833/bin/nihms433109f5.jpg)
![Figure 6. Effect size comparison of dMT…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3732833/bin/nihms433109f6.jpg)
Source: PubMed