{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T16:46:59Z","timestamp":1759682819595,"version":"3.37.3"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neural Transm"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Deep brain stimulation of the pedunculopontine nucleus is a promising surgical procedure for the treatment of Parkinsonian gait and balance dysfunction. It has, however, produced mixed clinical results that are poorly understood. We used tractography with the aim to rationalise this heterogeneity. A cohort of eight patients with postural instability and gait disturbance (Parkinson\u2019s disease subtype) underwent pre-operative structural and diffusion MRI, then progressed to deep brain stimulation targeting the pedunculopontine nucleus. Pre-operative and follow-up assessments were carried out using the Gait and Falls Questionnaire, and Freezing of Gait Questionnaire. Probabilistic diffusion tensor tractography was carried out between the stimulating electrodes and both cortical and cerebellar regions of a priori interest. Cortical surface reconstructions were carried out to measure cortical thickness in relevant areas. Structural connectivity between stimulating electrode and precentral gyrus (<jats:italic>r<\/jats:italic>\u2009=\u20090.81, <jats:italic>p<\/jats:italic>\u2009=\u20090.01), Brodmann areas 1 (<jats:italic>r<\/jats:italic>\u2009=\u20090.78, <jats:italic>p<\/jats:italic>\u2009=\u20090.02) and 2 (<jats:italic>r<\/jats:italic>\u2009=\u20090.76, <jats:italic>p<\/jats:italic>\u2009=\u20090.03) were correlated with clinical improvement. A negative correlation was also observed for the superior cerebellar peduncle (<jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.76, <jats:italic>p<\/jats:italic>\u2009=\u20090.03). Lower cortical thickness of the left parietal lobe and bilateral premotor cortices were associated with greater pre-operative severity of symptoms. Both motor and sensory structural connectivity of the stimulated surgical target characterises the clinical benefit, or lack thereof, from surgery. In what is a challenging region of brainstem to effectively target, these results provide insights into how this can be better achieved. The mechanisms of action are likely to have both motor and sensory components, commensurate with the probable nature of the underlying dysfunction.<\/jats:p>","DOI":"10.1007\/s00702-021-02327-x","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T12:02:31Z","timestamp":1617019351000},"page":"659-670","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Tractography patterns of pedunculopontine nucleus deep brain stimulation"],"prefix":"10.1007","volume":"128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3866-3833","authenticated-orcid":false,"given":"Ashley L. B.","family":"Raghu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tariq","family":"Parker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amir P. Divanbeighi","family":"Zand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Payne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesper","family":"Andersson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Stein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tipu Z.","family":"Aziz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander L.","family":"Green","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,29]]},"reference":[{"key":"2327_CR1","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1016\/j.neuroimage.2015.10.019","volume":"125","author":"JLR Andersson","year":"2016","unstructured":"Andersson JLR, Sotiropoulos SN (2016) An integrated approach to correction for off-resonance effects and subject movement in diffusion MR imaging. Neuroimage 125:1063\u20131078","journal-title":"Neuroimage"},{"key":"2327_CR2","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1016\/S1053-8119(03)00336-7","volume":"20","author":"JLR Andersson","year":"2003","unstructured":"Andersson JLR, Skare S, Ashburner J (2003) How to correct susceptibility distortions in spin-echo echo-planar images: application to diffusion tensor imaging. Neuroimage 20:870\u2013888","journal-title":"Neuroimage"},{"key":"2327_CR3","unstructured":"Andersson JL, Jenkinson M, Smith S (2007) Non-linear registration aka Spatial normalisation FMRIB Technical Report TR07JA2. FMRIB Anal Group Univ Oxf 1\u201322"},{"key":"2327_CR4","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.neuroimage.2016.06.058","volume":"141","author":"JLR Andersson","year":"2016","unstructured":"Andersson JLR, Graham MS, Zsoldos E, Sotiropoulos SN (2016) Incorporating outlier detection and replacement into a non-parametric framework for movement and distortion correction of diffusion MR images. Neuroimage 141:556\u2013572","journal-title":"Neuroimage"},{"key":"2327_CR5","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1016\/j.neuroimage.2007.05.050","volume":"37","author":"BR Aravamuthan","year":"2007","unstructured":"Aravamuthan BR, Muthusamy KA, Stein JF, Aziz TZ, Johansen-Berg H (2007) Topography of cortical and subcortical connections of the human pedunculopontine and subthalamic nuclei. Neuroimage 37:694\u2013705","journal-title":"Neuroimage"},{"key":"2327_CR6","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1002\/mrm.10609","volume":"50","author":"TEJ Behrens","year":"2003","unstructured":"Behrens TEJ, Woolrich MW, Jenkinson M, Johansen-Berg H, Nunes RG, Clare S et al (2003) Characterization and propagation of uncertainty in diffusion-weighted MR imaging. Magn Reson Med 50:1077\u20131088","journal-title":"Magn Reson Med"},{"key":"2327_CR7","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.neuroimage.2017.04.070","volume":"170","author":"M Bianciardi","year":"2018","unstructured":"Bianciardi M, Strong C, Toschi N, Edlow BL, Fischl B, Brown EN et al (2018) A probabilistic template of human mesopontine tegmental nuclei from in vivo 7 T MRI. Neuroimage 170:222\u2013230","journal-title":"Neuroimage"},{"key":"2327_CR8","doi-asserted-by":"publisher","first-page":"1670","DOI":"10.1212\/WNL.0b013e3181c1ded6","volume":"73","author":"NI Bohnen","year":"2009","unstructured":"Bohnen NI, Muller MLTM, Koeppe RA, Studenski SA, Kilbourn MA, Frey KA et al (2009) History of falls in Parkinson disease is associated with reduced cholinergic activity. Neurology 73:1670\u20131676","journal-title":"Neurology"},{"key":"2327_CR9","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1038\/nature25448","volume":"553","author":"V Caggiano","year":"2018","unstructured":"Caggiano V, Leiras R, Go\u00f1i-Erro H, Masini D, Bellardita C, Bouvier J et al (2018) Midbrain circuits that set locomotor speed and gait selection. Nature 553:455\u2013460","journal-title":"Nature"},{"key":"2327_CR10","doi-asserted-by":"publisher","first-page":"3882","DOI":"10.1007\/s00330-017-5299-5","volume":"28","author":"F Cong","year":"2018","unstructured":"Cong F, Wang J-W, Wang B, Yang Z, An J, Zuo Z et al (2018) Direct localisation of the human pedunculopontine nucleus using MRI: a coordinate and fibre-tracking study. Eur Radiol 28:3882\u20133892","journal-title":"Eur Radiol"},{"key":"2327_CR11","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1016\/j.neuroimage.2006.01.021","volume":"31","author":"RS Desikan","year":"2006","unstructured":"Desikan RS, S\u00e9gonne F, Fischl B, Quinn BT, Dickerson BC, Blacker D et al (2006) An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage 31:968\u2013980","journal-title":"Neuroimage"},{"key":"2327_CR12","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1093\/brain\/awp229","volume":"133","author":"MU Ferraye","year":"2010","unstructured":"Ferraye MU, Debu B, Fraix V, Goetz L, Ardouin C, Yelnik J et al (2010) Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson\u2019s disease. Brain 133:205\u2013214","journal-title":"Brain"},{"key":"2327_CR13","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1016\/j.neuroimage.2012.01.021","volume":"62","author":"B Fischl","year":"2012","unstructured":"Fischl B (2012) FreeSurfer. Neuroimage 62:774\u2013781","journal-title":"Neuroimage"},{"key":"2327_CR14","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/0361-9230(87)90208-5","volume":"18","author":"E Garcia-Rill","year":"1987","unstructured":"Garcia-Rill E, Houser CR, Skinner RD, Smith W, Woodward DJ (1987) Locomotion-inducing sites in the vicinity of the pedunculopontine nucleus. Brain Res Bull 18:731\u2013738","journal-title":"Brain Res Bull"},{"key":"2327_CR15","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/S1353-8020(99)00062-0","volume":"6","author":"N Giladi","year":"2000","unstructured":"Giladi N, Shabtai H, Simon ES, Biran S, Tal J, Korczyn AD (2000) Construction of freezing of gait questionnaire for patients with Parkinsonism. Parkinsonism Relat Disord 6:165\u2013170","journal-title":"Parkinsonism Relat Disord"},{"key":"2327_CR16","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1212\/WNL.0b013e3181dc1a55","volume":"74","author":"S Gilman","year":"2010","unstructured":"Gilman S, Koeppe RA, Nan B, Wang CN, Wang X, Junck L et al (2010) Cerebral cortical and subcortical cholinergic deficits in Parkinsonian syndromes. Neurology 74:1416\u20131423","journal-title":"Neurology"},{"key":"2327_CR17","doi-asserted-by":"publisher","first-page":"4792","DOI":"10.1523\/JNEUROSCI.3646-14.2015","volume":"35","author":"NK Gut","year":"2015","unstructured":"Gut NK, Winn P (2015) Deep brain stimulation of different pedunculopontine targets in a novel rodent model of Parkinsonism. J Neurosci 35:4792\u20134803","journal-title":"J Neurosci"},{"key":"2327_CR18","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1159\/000449010","volume":"94","author":"C Hamani","year":"2016","unstructured":"Hamani C, Aziz T, Bloem BR, Brown P, Chabardes S, Coyne T et al (2016) Pedunculopontine nucleus region deep brain stimulation in Parkinson disease: surgical anatomy and terminology. Stereotact Funct Neurosurg 94:298\u2013306","journal-title":"Stereotact Funct Neurosurg"},{"key":"2327_CR19","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/0006-8993(92)91216-2","volume":"585","author":"L-N Hazrati","year":"1992","unstructured":"Hazrati L-N, Parent A (1992) Projection from the deep cerebellar nuclei to the pedunculopontine nucleus in the squirrel monkey. Brain Res 585:267\u2013271","journal-title":"Brain Res"},{"key":"2327_CR20","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1007\/s00276-018-2120-3","volume":"41","author":"DJHA Henssen","year":"2019","unstructured":"Henssen DJHA, Kuppens D, Meijer FJA, van Cappellen van Walsum AM, Temel Y, Kurt E (2019) Identification of the pedunculopontine nucleus and surrounding white matter tracts on 7T diffusion tensor imaging, combined with histological validation. Surg Radiol Anat 41:187\u2013196","journal-title":"Surg Radiol Anat"},{"key":"2327_CR21","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1002\/mds.25697","volume":"29","author":"T Herman","year":"2014","unstructured":"Herman T, Rosenberg-Katz K, Jacob Y, Giladi N, Hausdorff JM (2014) Gray matter atrophy and freezing of gait in Parkinson\u2019s disease: Is the evidence black-on-white?: gray matter atrophy and freezing of gait in PD. Mov Disord 29:134\u2013139","journal-title":"Mov Disord"},{"key":"2327_CR22","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.neuroimage.2018.08.068","volume":"184","author":"A Horn","year":"2019","unstructured":"Horn A, Li N, Dembek TA, Kappel A, Boulay C, Ewert S et al (2019) Lead-DBS v2: towards a comprehensive pipeline for deep brain stimulation imaging. Neuroimage 184:293\u2013316","journal-title":"Neuroimage"},{"key":"2327_CR23","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1002\/mds.23589","volume":"26","author":"A Insola","year":"2011","unstructured":"Insola A, Padua L, Scarnati E, Valeriani M (2011) Where are the somatosensory evoked potentials recorded from DBS leads implanted in the human pedunculopontine tegmental nucleus generated? Mov Disord 26:1573\u20131574","journal-title":"Mov Disord"},{"key":"2327_CR24","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1227\/NEU.0b013e318249c726","volume":"71","author":"A Insola","year":"2012","unstructured":"Insola A, Valeriani M, Mazzone P (2012) Targeting the pedunculopontine nucleus. Oper Neurosurg 71:96\u2013103","journal-title":"Oper Neurosurg"},{"key":"2327_CR25","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1002\/ana.410320608","volume":"32","author":"IH Jenkins","year":"1992","unstructured":"Jenkins IH, Fernandez W, Playford ED, Lees AJ, Frackowiak RSJ, Passingham RE et al (1992) Impaired activation of the supplementary motor area in Parkinson\u2019s disease is reversed when akinesia is treated with apomorphine. Ann Neurol 32:749\u2013757","journal-title":"Ann Neurol"},{"key":"2327_CR26","doi-asserted-by":"publisher","first-page":"2621","DOI":"10.1097\/00001756-200412030-00012","volume":"15","author":"N Jenkinson","year":"2004","unstructured":"Jenkinson N, Nandi D, Miall RC, Stein JF, Aziz TZ (2004) Pedunculopontine nucleus stimulation improves akinesia in a Parkinsonian monkey. NeuroReport 15:2621\u20132624","journal-title":"NeuroReport"},{"key":"2327_CR27","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1097\/00001756-200604240-00016","volume":"17","author":"N Jenkinson","year":"2006","unstructured":"Jenkinson N, Nandi D, Oram R, Stein JF, Aziz TZ (2006) Pedunculopontine nucleus electric stimulation alleviates akinesia independently of dopaminergic mechanisms. NeuroReport 17:639\u2013641","journal-title":"NeuroReport"},{"key":"2327_CR28","doi-asserted-by":"publisher","first-page":"9396","DOI":"10.1523\/JNEUROSCI.0509-12.2012","volume":"32","author":"C Karachi","year":"2012","unstructured":"Karachi C, Andre A, Bertasi E, Bardinet E, Lehericy S, Bernard FA (2012) Functional parcellation of the lateral mesencephalus. J Neurosci 32:9396\u20139401","journal-title":"J Neurosci"},{"key":"2327_CR29","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nrn2833","volume":"11","author":"C Keysers","year":"2010","unstructured":"Keysers C, Kaas JH, Gazzola V (2010) Somatosensation in social perception. Nat Rev Neurosci 11:417\u2013428","journal-title":"Nat Rev Neurosci"},{"key":"2327_CR30","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1002\/cne.902190403","volume":"219","author":"HP Killackey","year":"1983","unstructured":"Killackey HP, Gould HJ, Cusick CG, Pons TP, Kaas JH (1983) The relation of corpus callosum connections to architectonic fields and body surface maps in sensorimotor cortex of new and old world monkeys. J Comp Neurol 219:384\u2013419","journal-title":"J Comp Neurol"},{"key":"2327_CR31","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1002\/cne.903440205","volume":"344","author":"B Lavoie","year":"1994","unstructured":"Lavoie B, Parent A (1994) Pedunculopontine nucleus in the squirrel monkey: cholinergic and glutamatergic projections to the substantia nigra. J Comp Neurol 344:232\u2013241","journal-title":"J Comp Neurol"},{"key":"2327_CR32","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.3174\/ajnr.A2906","volume":"33","author":"B M\u00e4dler","year":"2012","unstructured":"M\u00e4dler B, Coenen VA (2012) Explaining clinical effects of deep brain stimulation through simplified target-specific modeling of the volume of activated tissue. Am J Neuroradiol 33:1072\u20131080","journal-title":"Am J Neuroradiol"},{"key":"2327_CR33","doi-asserted-by":"publisher","first-page":"22","DOI":"10.3389\/fnana.2011.00022","volume":"5","author":"C Martinez-Gonzalez","year":"2011","unstructured":"Martinez-Gonzalez C, Bolam JP, Mena-Segovia J (2011) Topographical organization of the pedunculopontine nucleus. Front Neuroanat 5:22","journal-title":"Front Neuroanat"},{"key":"2327_CR34","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/S0306-4522(00)00099-3","volume":"98","author":"M Matsumura","year":"2000","unstructured":"Matsumura M, Nambu A, Yamaji Y, Watanabe K, Imai H, Inase M et al (2000) Organization of somatic motor inputs from the frontal lobe to the pedunculopontine tegmental nucleus in the macaque monkey. Neuroscience 98:97\u2013110","journal-title":"Neuroscience"},{"key":"2327_CR35","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1007\/s00702-011-0593-x","volume":"118","author":"P Mazzone","year":"2011","unstructured":"Mazzone P, Sposato S, Insola A, Scarnati E (2011) The deep brain stimulation of the pedunculopontine tegmental nucleus: towards a new stereotactic neurosurgery. J Neural Transm 118:1431\u20131451","journal-title":"J Neural Transm"},{"key":"2327_CR36","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1007\/s00702-016-1518-5","volume":"123","author":"P Mazzone","year":"2016","unstructured":"Mazzone P, Vilela Filho O, Viselli F, Insola A, Sposato S, Vitale F et al (2016) Our first decade of experience in deep brain stimulation of the brainstem: elucidating the mechanism of action of stimulation of the ventrolateral pontine tegmentum. J Neural Transm 123:751\u2013767","journal-title":"J Neural Transm"},{"key":"2327_CR57","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/BF00238343","volume":"34","author":"KH Monakow","year":"1979","unstructured":"Monakow KH, Akert K, K\u00fcnzle H (1979) Projections of precentral and premotor cortex to the red nucleus and other midbrain areas in macaca fascicularis. Exp Brain Res 34:91\u2013105","journal-title":"Exp Brain Res"},{"key":"2327_CR37","doi-asserted-by":"publisher","first-page":"814","DOI":"10.3171\/JNS-07\/10\/0814","volume":"107","author":"KA Muthusamy","year":"2007","unstructured":"Muthusamy KA, Aravamuthan BR, Kringelbach ML, Jenkinson N, Voets NL, Johansen-Berg H et al (2007) Connectivity of the human pedunculopontine nucleus region and diffusion tensor imaging in surgical targeting. J Neurosurg 107:814\u2013820","journal-title":"J Neurosurg"},{"key":"2327_CR38","doi-asserted-by":"publisher","first-page":"2418","DOI":"10.1093\/brain\/awf259","volume":"125","author":"D Nandi","year":"2002","unstructured":"Nandi D, Aziz TZ, Giladi N, Winter J, Stein JF (2002) Reversal of akinesia in experimental parkinsonism by GABA antagonist microinjections in the pedunculopontine nucleus. Brain 125:2418\u20132430","journal-title":"Brain"},{"key":"2327_CR39","volume-title":"Atlas of the human brainstem","author":"G Paxinos","year":"1995","unstructured":"Paxinos G, Huang X (1995) Atlas of the human brainstem. Academic Press, San Diego"},{"key":"2327_CR40","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/B978-0-12-374236-0.10008-2","volume-title":"The human nervous system","author":"G Paxinos","year":"2012","unstructured":"Paxinos G, Huang X, Sengul G, Watson C (2012) Chapter 8\u2014Organization of brainstem nuclei. In: Mai JK, Paxinos G (eds) The human nervous system, 3rd edn. Academic Press, San Diego, pp 260\u2013327","edition":"3"},{"key":"2327_CR41","doi-asserted-by":"publisher","first-page":"3009","DOI":"10.1093\/brain\/awy216","volume":"141","author":"T Perera","year":"2018","unstructured":"Perera T, Tan JL, Cole MH, Yohanandan SAC, Silberstein P, Cook R et al (2018) Balance control systems in Parkinson\u2019s disease and the impact of pedunculopontine area stimulation. Brain 141:3009\u20133022","journal-title":"Brain"},{"key":"2327_CR42","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/BF00230016","volume":"91","author":"LL Porter","year":"1992","unstructured":"Porter LL (1992) Patterns of projections from area 2 of the sensory cortex to area 3a and to the motor cortex in cats. Exp Brain Res 91:85\u201393","journal-title":"Exp Brain Res"},{"key":"2327_CR43","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.parkreldis.2008.01.006","volume":"14","author":"JO Rinne","year":"2008","unstructured":"Rinne JO, Ma SY, Lee MS, Collan Y, R\u00f6ytt\u00e4 M (2008) Loss of cholinergic neurons in the pedunculopontine nucleus in Parkinson\u2019s disease is related to disability of the patients. Parkinsonism Relat Disord 14:553\u2013557","journal-title":"Parkinsonism Relat Disord"},{"key":"2327_CR44","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1002\/mds.27299","volume":"33","author":"O Samotus","year":"2018","unstructured":"Samotus O, Parrent A, Jog M (2018) Spinal cord stimulation therapy for gait dysfunction in advanced Parkinson\u2019s disease patients: spinal. Mov Disord 33:783\u2013792","journal-title":"Mov Disord"},{"key":"2327_CR45","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1097\/WNR.0b013e32833ce5f1","volume":"21","author":"PM Schweder","year":"2010","unstructured":"Schweder PM, Hansen PC, Green AL, Quaghebeur G, Stein J, Aziz TZ (2010) Connectivity of the pedunculopontine nucleus in Parkinsonian freezing of gait. NeuroReport 21:914\u2013916","journal-title":"NeuroReport"},{"key":"2327_CR46","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1097\/00001756-199011000-00001","volume":"1","author":"RD Skinner","year":"1990","unstructured":"Skinner RD, Kinjo N, Henderson V, Garcia-Rill E (1990) Locomotor projections from the pedunculopontine nucleus to the spinal cord. NeuroReport 1:183\u2013186","journal-title":"NeuroReport"},{"key":"2327_CR47","doi-asserted-by":"publisher","first-page":"S208","DOI":"10.1016\/j.neuroimage.2004.07.051","volume":"23","author":"SM Smith","year":"2004","unstructured":"Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TEJ, Johansen-Berg H et al (2004) Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 23:S208\u2013S219","journal-title":"Neuroimage"},{"key":"2327_CR48","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1002\/cne.902830103","volume":"283","author":"BM Spann","year":"1989","unstructured":"Spann BM, Grofova I (1989) Origin of ascending and spinal pathways from the nucleus tegmenti pedunculopontinus in the rat. J Comp Neurol 283:13\u201327","journal-title":"J Comp Neurol"},{"key":"2327_CR49","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1038\/nn.3642","volume":"17","author":"TL Tattersall","year":"2014","unstructured":"Tattersall TL, Stratton PG, Coyne TJ, Cook R, Silberstein P, Silburn PA et al (2014) Imagined gait modulates neuronal network dynamics in the human pedunculopontine nucleus. Nat Neurosci 17:449\u2013454","journal-title":"Nat Neurosci"},{"key":"2327_CR50","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1227\/NEU.0b013e31822b6f71","volume":"69","author":"W Thevathasan","year":"2011","unstructured":"Thevathasan W, Coyne TJ, Hyam JA, Kerr G, Jenkinson N, Aziz TZ et al (2011a) Pedunculopontine nucleus stimulation improves gait freezing in Parkinson disease. Neurosurgery 69:1248\u20131254","journal-title":"Neurosurgery"},{"key":"2327_CR51","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1093\/brain\/awr131","volume":"134","author":"W Thevathasan","year":"2011","unstructured":"Thevathasan W, Pogosyan A, Hyam JA, Jenkinson N, Bogdanovic M, Coyne TJ et al (2011b) A block to pre-prepared movement in gait freezing, relieved by pedunculopontine nucleus stimulation. Brain 134:2085\u20132095","journal-title":"Brain"},{"key":"2327_CR52","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.1093\/brain\/aws039","volume":"135","author":"W Thevathasan","year":"2012","unstructured":"Thevathasan W, Cole MH, Graepel CL, Hyam JA, Jenkinson N, Brittain J-S et al (2012) A spatiotemporal analysis of gait freezing and the impact of pedunculopontine nucleus stimulation. Brain 135:1446\u20131454","journal-title":"Brain"},{"key":"2327_CR53","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1212\/WNL.0b013e3181f25b35","volume":"75","author":"EW Tsang","year":"2010","unstructured":"Tsang EW, Hamani C, Moro E, Mazzella F, Poon YY, Lozano AM et al (2010) Involvement of the human pedunculopontine nucleus region in voluntary movements. Neurology 75:950\u2013959","journal-title":"Neurology"},{"key":"2327_CR54","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.parkreldis.2018.02.006","volume":"50","author":"C Uribe","year":"2018","unstructured":"Uribe C, Segura B, Baggio HC, Abos A, Garcia-Diaz AI, Campabadal A et al (2018) Cortical atrophy patterns in early Parkinson\u2019s disease patients using hierarchical cluster analysis. Parkinsonism Relat Disord 50:3\u20139","journal-title":"Parkinsonism Relat Disord"},{"key":"2327_CR55","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1152\/jn.00555.2013","volume":"111","author":"M Valencia","year":"2014","unstructured":"Valencia M, Chavez M, Artieda J, Bolam JP, Mena-Segovia J (2014) Abnormal functional connectivity between motor cortex and pedunculopontine nucleus following chronic dopamine depletion. J Neurophysiol 111:434\u2013440","journal-title":"J Neurophysiol"},{"key":"2327_CR56","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1093\/brain\/aww020","volume":"139","author":"N Vanegas-Arroyave","year":"2016","unstructured":"Vanegas-Arroyave N, Lauro PM, Huang L, Hallett M, Horovitz SG, Zaghloul KA et al (2016) Tractography patterns of subthalamic nucleus deep brain stimulation. Brain 139:1200\u20131210","journal-title":"Brain"},{"key":"2327_CR58","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1007\/s00415-015-7744-1","volume":"262","author":"M-L Welter","year":"2015","unstructured":"Welter M-L, Demain A, Ewenczyk C, Czernecki V, Lau B, El Helou A et al (2015) PPNa-DBS for gait and balance disorders in Parkinson\u2019s disease: a double-blind, randomised study. J Neurol 262:1515\u20131525","journal-title":"J Neurol"},{"key":"2327_CR59","doi-asserted-by":"publisher","first-page":"S194","DOI":"10.1016\/j.parkreldis.2008.04.030","volume":"14","author":"P Winn","year":"2008","unstructured":"Winn P (2008) Experimental studies of pedunculopontine functions: Are they motor, sensory or integrative? Parkinsonism Relat Disord 14:S194\u2013S198","journal-title":"Parkinsonism Relat Disord"},{"key":"2327_CR60","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1111\/cns.12504","volume":"22","author":"L Zhang","year":"2016","unstructured":"Zhang L, Li T-N, Yuan Y-S, Jiang S-M, Tong Q, Wang M et al (2016) The neural basis of postural instability gait disorder subtype of Parkinson\u2019s disease: a PET and fMRI study. CNS Neurosci Ther 22:360\u2013367","journal-title":"CNS Neurosci Ther"}],"container-title":["Journal of Neural Transmission"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00702-021-02327-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00702-021-02327-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00702-021-02327-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T16:29:53Z","timestamp":1675096193000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00702-021-02327-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,29]]},"references-count":60,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["2327"],"URL":"https:\/\/doi.org\/10.1007\/s00702-021-02327-x","relation":{},"ISSN":["0300-9564","1435-1463"],"issn-type":[{"type":"print","value":"0300-9564"},{"type":"electronic","value":"1435-1463"}],"subject":[],"published":{"date-parts":[[2021,3,29]]},"assertion":[{"value":"25 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 March 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"T. Z. Aziz has received travel grants from Medtronic, Abbott Laboratories and Boston Scientific. A. L. Green reports he is on Abbott Laboratories\u2019 movement disorder executive advisory board, and is faculty for their SCS and DRGS neuromodulation courses, for which he receives personal fees. He is also a data monitoring safety board committee member for a Herantis Pharma trial for PDGF in PD, and also does consultancy with InBrain as an executive advisor.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}