Abstract
Freezing of gait (FOG) is a disabling motor symptom that affects patients with Parkinson’s disease (PD). MRI-based evidence suggest that multiple brain structures are involved in the occurrence of FOG. We investigated the integrity of the neuronal networks in PD patients with FOG (PD-FOG), considering both within-network resting-state functional connectivity (rsFC) and between-network rsFC. Thirty-one PD patients (15 PD-FOG and 16 PD-nFOG) and 16 healthy subjects (HS) underwent a rsfMRI study. The data was analysed by using FSL Melodic and FSLNets software to study within- and between-network rsFC. PD-FOG displayed a higher within-network rsFC that involved a greater number of resting-state networks (RSNs) than PD-nFOG. rsFC in the basal ganglia network significantly correlated with the Timed Up and Go test. Moreover, when compared with HS, PD-FOG displayed reduced rsFC between the right fronto-parietal and executive-control RSNs, which significantly correlated with FOG severity. This study demonstrates that FOG is associated with an impaired interplay and communication between the RSNs that underpin attentive and executive abilities, especially in the right hemisphere.
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Almeida, Q. J., & Lebold, C. A. (2010). Freezing of gait in Parkinson’s disease: A perceptual cause for a motor impairment? Journal of Neurology, Neurosurgery, and Psychiatry, 81(5), 513–518. https://doi.org/10.1136/jnnp.2008.160580.
Antonini, A., Abbruzzese, G., Ferini-Strambi, L., Tilley, B., Huang, J., Stebbins, G. T., et al. (2013). Validation of the Italian version of the movement disorder society—unified Parkinson’s disease rating scale. Neurological Sciences, 34(5), 683–687. https://doi.org/10.1007/s10072-012-1112-z.
Baggio, H.-C., Segura, B., Sala-Llonch, R., Marti, M.-J., Valldeoriola, F., Compta, Y., Tolosa, E., & Junqué, C. (2015). Cognitive impairment and resting-state network connectivity in Parkinson’s disease. Human Brain Mapping, 36(1), 199–212. https://doi.org/10.1002/hbm.22622.
Bartels, A. L., & Leenders, K. L. (2008). Brain imaging in patients with freezing of gait. Movement Disorders, 23(S2), S461–S467. https://doi.org/10.1002/mds.21912.
Beckmann, C. F., & Smith, S. M. (2004). Probabilistic independent component analysis for functional magnetic resonance imaging. IEEE Transactions on Medical Imaging, 23(2), 137–152. https://doi.org/10.1109/TMI.2003.822821.
Beckmann, C. F., & Smith, S. M. (2005). Tensorial extensions of independent component analysis for multisubject FMRI analysis. NeuroImage, 25(1), 294–311. https://doi.org/10.1016/j.neuroimage.2004.10.043.
Beckmann, C. F., DeLuca, M., Devlin, J. T., & Smith, S. M. (2005). Investigations into resting-state connectivity using independent component analysis. Philosophical Transactions of the Royal Society of London B: Biological Sciences, 360(1457), 1001–1013. https://doi.org/10.1098/rstb.2005.1634.
Berardelli, A., Wenning, G. K., Antonini, A., Berg, D., Bloem, B. R., Bonifati, V., Brooks, D., Burn, D. J., Colosimo, C., Fanciulli, A., Ferreira, J., Gasser, T., Grandas, F., Kanovsky, P., Kostic, V., Kulisevsky, J., Oertel, W., Poewe, W., Reese, J. P., Relja, M., Ruzicka, E., Schrag, A., Seppi, K., Taba, P., & Vidailhet, M. (2013). EFNS/MDS-ES/ENS [corrected] recommendations for the diagnosis of Parkinson’s disease. European Journal of Neurology, 20(1), 16–34. https://doi.org/10.1111/ene.12022.
Bharti, K., Bologna, M., Upadhyay, N., Piattella, M. C., Suppa, A., Petsas, N., Giannì, C., Tona, F., Berardelli, A., & Pantano, P. (2017). Abnormal resting-state functional connectivity in progressive Supranuclear palsy and Corticobasal syndrome. Frontiers in Neurology, 8, 248. https://doi.org/10.3389/fneur.2017.00248.
Biswal, B. B. (2012). Resting state fMRI: A personal history. NeuroImage, 62(2), 938–944. https://doi.org/10.1016/j.neuroimage.2012.01.090.
Canu, E., Agosta, F., Sarasso, E., Volontè, M. A., Basaia, S., Stojkovic, T., Stefanova, E., Comi, G., Falini, A., Kostic, V. S., Gatti, R., & Filippi, M. (2015). Brain structural and functional connectivity in Parkinson’s disease with freezing of gait. Human Brain Mapping, 36(12), 5064–5078. https://doi.org/10.1002/hbm.22994.
Corbetta, M., & Shulman, G. L. (1998). Human cortical mechanisms of visual attention during orienting and search. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 353(1373), 1353–1362. https://doi.org/10.1098/rstb.1998.0289.
Desikan, R. S., Ségonne, F., Fischl, B., Quinn, B. T., Dickerson, B. C., Blacker, D., Buckner, R. L., Dale, A. M., Maguire, R. P., Hyman, B. T., Albert, M. S., & Killiany, R. J. (2006). An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. NeuroImage, 31(3), 968–980. https://doi.org/10.1016/j.neuroimage.2006.01.021.
Dirnberger, G., & Jahanshahi, M. (2013). Executive dysfunction in Parkinson’s disease: A review. Journal of Neuropsychology, 7(2), 193–224. https://doi.org/10.1111/jnp.12028.
Dubois, B., Slachevsky, A., Litvan, I., & Pillon, B. (2000). The FAB: A frontal assessment battery at bedside. Neurology, 55(11), 1621–1626.
Fling, B. W., Cohen, R. G., Mancini, M., Carpenter, S. D., Fair, D. A., Nutt, J. G., & Horak, F. B. (2014). Functional reorganization of the locomotor network in Parkinson patients with freezing of gait. PLoS One, 9(6), e100291. https://doi.org/10.1371/journal.pone.0100291.
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975). “Mini-mental state”: A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12(3), 189–198. https://doi.org/10.1016/0022-3956(75)90026-6.
Fox, M. D., Snyder, A. Z., Vincent, J. L., Corbetta, M., Van Essen, D. C., & Raichle, M. E. (2005). The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proceedings of the National Academy of Sciences of the United States of America, 102(27), 9673–9678. http://www.pnas.org/content/102/27/9673.short. Accessed 16 February 2016.
Gilat, M., Ehgoetz Martens, K. A., Miranda-Domínguez, O., Arpan, I., Shine, J. M., Mancini, M., Fair, D. A., Lewis, S. J. G., & Horak, F. B. (2018). Dysfunctional limbic circuitry underlying freezing of gait in Parkinson’s disease. Neuroscience, 374, 119–132. https://doi.org/10.1016/j.neuroscience.2018.01.044.
Hamilton, M. (1967). Development of a rating scale for primary depressive illness. The British Journal of Social and Clinical Psychology, 6(4), 278–296.
Hoehn, M. M., & Yahr, M. D. (1967). Parkinsonism: Onset, progression and mortality. Neurology, 17(5), 427–442.
Kelly, R. E., Jr., Alexopoulos, G. S., Wang, Z., Gunning, F. M., Murphy, C. F., Morimoto, S. S., et al. (2010). Visual inspection of independent components: Defining a procedure for artifact removal from fMRI data. Journal of Neuroscience Methods, 189(2), 233–245. https://doi.org/10.1016/j.jneumeth.2010.03.028.
Kostic, V. S., Agosta, F., Pievani, M., Stefanova, E., Jecmenica-Lukic, M., Scarale, A., Spica, V., & Filippi, M. (2012). Pattern of brain tissue loss associated with freezing of gait in Parkinson disease. Neurology, 78(6), 409–416. https://doi.org/10.1212/WNL.0b013e318245d23c.
Melrose, R. J., Young, S., Weissberger, G. H., Natta, L., Harwood, D., Mandelkern, M., & Sultzer, D. L. (2017). Cerebral metabolic correlates of attention networks in Alzheimer’s disease: A study of the Stroop. Neuropsychologia, 106, 383–389. https://doi.org/10.1016/j.neuropsychologia.2017.10.020.
Nichols, T. E., & Holmes, A. P. (2002). Nonparametric permutation tests for functional neuroimaging: A primer with examples. Human Brain Mapping, 15(1), 1–25. http://onlinelibrary.wiley.com/doi/10.1002/hbm.1058/full. Accessed 1 March 2016.
Nieuwboer, A., Rochester, L., Herman, T., Vandenberghe, W., Emil, G. E., Thomaes, T., & Giladi, N. (2009). Reliability of the new freezing of gait questionnaire: Agreement between patients with Parkinson’s disease and their carers. Gait & Posture, 30(4), 459–463. https://doi.org/10.1016/j.gaitpost.2009.07.108.
Nonnekes, J., Timmer, M. H. M., de Vries, N. M., Rascol, O., Helmich, R. C., & Bloem, B. R. (2016). Unmasking levodopa resistance in Parkinson’s disease. Movement Disorders: Official Journal of the Movement Disorder Society, 31(11), 1602–1609. https://doi.org/10.1002/mds.26712.
Nutt, J. G., Bloem, B. R., Giladi, N., Hallett, M., Horak, F. B., & Nieuwboer, A. (2011). Freezing of gait: Moving forward on a mysterious clinical phenomenon. The Lancet Neurology, 10(8), 734–744. https://doi.org/10.1016/S1474-4422(11)70143-0.
Onu, M., Badea, L., Roceanu, A., Tivarus, M., & Bajenaru, O. (2015). Increased connectivity between sensorimotor and attentional areas in Parkinson’s disease. Neuroradiology, 57(9), 957–968. https://doi.org/10.1007/s00234-015-1556-y.
Pietracupa, S., Suppa, A., Upadhyay, N., Giannì, C., Grillea, G., Leodori, G., Modugno, N., di Biasio, F., Zampogna, A., Colonnese, C., Berardelli, A., & Pantano, P. (2018). Freezing of gait in Parkinson’s disease: Gray and white matter abnormalities. Journal of Neurology, 265(1), 52–62. https://doi.org/10.1007/s00415-017-8654-1.
Ptak, R., Schnider, A., & Fellrath, J. (2017). The dorsal Frontoparietal network: A Core system for emulated action. Trends in Cognitive Sciences, 21(8), 589–599. https://doi.org/10.1016/j.tics.2017.05.002.
Raichle, M. E., & Snyder, A. Z. (2007). A default mode of brain function: A brief history of an evolving idea. NeuroImage, 37(4), 1083–1090. https://doi.org/10.1016/j.neuroimage.2007.02.041.
Rosazza, C., & Minati, L. (2011). Resting-state brain networks: Literature review and clinical applications. Neurological Sciences, 32(5), 773–785. https://doi.org/10.1007/s10072-011-0636-y.
Scolari, M., Seidl-Rathkopf, K. N., & Kastner, S. (2015). Functions of the human frontoparietal attention network: Evidence from neuroimaging. Current Opinion in Behavioral Sciences, 1, 32–39. https://doi.org/10.1016/j.cobeha.2014.08.003.
Smith, S. M. (2002). Fast robust automated brain extraction. Human Brain Mapping, 17(3), 143–155. https://doi.org/10.1002/hbm.10062.
Tessitore, A., Amboni, M., Cirillo, G., Corbo, D., Picillo, M., Russo, A., Vitale, C., Santangelo, G., Erro, R., Cirillo, M., Esposito, F., Barone, P., & Tedeschi, G. (2012a). Regional gray matter atrophy in patients with Parkinson disease and freezing of gait. AJNR. American Journal of Neuroradiology, 33(9), 1804–1809. https://doi.org/10.3174/ajnr.A3066.
Tessitore, A., Amboni, M., Esposito, F., Russo, A., Picillo, M., Marcuccio, L., Pellecchia, M. T., Vitale, C., Cirillo, M., Tedeschi, G., & Barone, P. (2012b). Resting-state brain connectivity in patients with Parkinson’s disease and freezing of gait. Parkinsonism & Related Disorders, 18(6), 781–787. https://doi.org/10.1016/j.parkreldis.2012.03.018.
Tessitore, A., Esposito, F., Vitale, C., Santangelo, G., Amboni, M., Russo, A., Corbo, D., Cirillo, G., Barone, P., & Tedeschi, G. (2012c). Default-mode network connectivity in cognitively unimpaired patients with Parkinson disease. Neurology, 79(23), 2226–2232. https://doi.org/10.1212/WNL.0b013e31827689d6.
Tessitore, A., Giordano, A., De Micco, R., Russo, A., & Tedeschi, G. (2014). Sensorimotor connectivity in Parkinson’s disease: The role of functional neuroimaging. Frontiers in Neurology, 5. https://doi.org/10.3389/fneur.2014.00180.
Tomlinson, C. L., Stowe, R., Patel, S., Rick, C., Gray, R., & Clarke, C. E. (2010). Systematic review of levodopa dose equivalency reporting in Parkinson’s disease. Movement Disorders: Official Journal of the Movement Disorder Society, 25(15), 2649–2653. https://doi.org/10.1002/mds.23429.
Van Dijk, K. R. A., Sabuncu, M. R., & Buckner, R. L. (2012). The influence of head motion on intrinsic functional connectivity MRI. NeuroImage, 59(1), 431–438. https://doi.org/10.1016/j.neuroimage.2011.07.044.
Wang, M., Jiang, S., Yuan, Y., Zhang, L., Ding, J., Wang, J., Zhang, J., Zhang, K., & Wang, J. (2016). Alterations of functional and structural connectivity of freezing of gait in Parkinson’s disease. Journal of Neurology, 263(8), 1583–1592. https://doi.org/10.1007/s00415-016-8174-4.
Werner, C. J., Dogan, I., Saß, C., Mirzazade, S., Schiefer, J., Shah, N. J., Schulz, J. B., & Reetz, K. (2014). Altered resting-state connectivity in Huntington’s disease. Human Brain Mapping, 35(6), 2582–2593. https://doi.org/10.1002/hbm.22351.
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Bharti, K., Suppa, A., Pietracupa, S. et al. Aberrant functional connectivity in patients with Parkinson’s disease and freezing of gait: a within- and between-network analysis. Brain Imaging and Behavior 14, 1543–1554 (2020). https://doi.org/10.1007/s11682-019-00085-9
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DOI: https://doi.org/10.1007/s11682-019-00085-9