{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T07:17:41Z","timestamp":1787987861477,"version":"build-2784847793"},"reference-count":47,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson\u2019s Research (MJFF)","doi-asserted-by":"publisher","award":["MJFF-020020"],"award-info":[{"award-number":["MJFF-020020"]}],"id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Edward and Barbara Bell Family Endowed Chair","award":["MJFF-020020"],"award-info":[{"award-number":["MJFF-020020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>Freezing of gait (FOG) is a disabling symptom associated with Parkinson\u2019s disease (PD). Its understanding and effective treatment is compromised due to the difficulty in reliably triggering FOG in clinical and laboratory environments. The Cleveland Clinic-Virtual Home Environment (CC-VHE) platform was developed to address the challenges of eliciting FOG by combining an omnidirectional treadmill with immersive virtual reality (VR) environments to induce FOG under physical, emotional, and cognitive triggers. Recent developments in deep brain stimulation devices that sense neural signals from the subthalamic nucleus in real time offer the potential to understand the underlying neural mechanism(s) of FOG. This manuscript presents the coupling of the CC-VHE technology, VR paradigms, and the experimental and analytical methods for recording and analyzing synchronous cortical, subcortical, and kinematic data as an approach to begin to understand the nuanced neural pathology associated with FOG. To evaluate the utility and feasibility of coupling VR and neural sensing technology, initial data from one participant are included.<\/jats:p>","DOI":"10.3390\/s25134036","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T12:10:31Z","timestamp":1751285431000},"page":"4036","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["An Experimental Approach for Investigating Freezing of Gait in Parkinson\u2019s Disease Using Virtual Reality and Neural Sensing: A Pilot Study"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3047-8091","authenticated-orcid":false,"given":"Mandy","family":"Miller Koop","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5468-8208","authenticated-orcid":false,"given":"Anson B.","family":"Rosenfeldt","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Scelina","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan","family":"Scelina","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8598-4341","authenticated-orcid":false,"given":"Colin","family":"Waltz","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S.","family":"Bazyk","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Visar","family":"Berki","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio N.","family":"Reyes Torres","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enio","family":"Kuvliev","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Nagel","sequence":"additional","affiliation":[{"name":"Center for Neurological Restoration, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8323-6873","authenticated-orcid":false,"given":"Benjamin L.","family":"Walter","sequence":"additional","affiliation":[{"name":"Center for Neurological Restoration, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6605-9855","authenticated-orcid":false,"given":"James","family":"Liao","sequence":"additional","affiliation":[{"name":"Center for Neurological Restoration, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Escobar","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth B.","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Center for Neurological Restoration, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay L.","family":"Alberts","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Center for Neurological Restoration, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1212\/WNL.0000000000003213","article-title":"Loss of independence in early Parkinson disease: A 5-year population-based incident cohort study","volume":"87","author":"Bjornestad","year":"2016","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.parkreldis.2011.08.022","article-title":"Loss of ability to work and ability to live independently in Parkinson\u2019s disease","volume":"18","author":"Heckman","year":"2012","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1046\/j.1468-1331.2003.00611.x","article-title":"Characterization of freezing of gait subtypes and the response of each to levodopa in Parkinson\u2019s disease","volume":"10","author":"Schaafsma","year":"2003","journal-title":"Eur. J. Neurol."},{"key":"ref_4","first-page":"e5329","article-title":"Falls When Standing, Falls When Walking: Different Mechanisms, Different Outcomes in Parkinson Disease","volume":"11","author":"Lieberman","year":"2019","journal-title":"Cureus"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Palakurthi, B., and Burugupally, S.P. (2019). Postural Instability in Parkinson\u2019s Disease: A Review. Brain Sci., 9.","DOI":"10.3390\/brainsci9090239"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Cao, S.S., Yuan, X.Z., Wang, S.H., Taximaimaiti, R., and Wang, X.P. (2020). Transverse Strips Instead of Wearable Laser Lights Alleviate the Sequence Effect Toward a Destination in Parkinson\u2019s Disease Patients with Freezing of Gait. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.00838"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1093\/brain\/awz314","article-title":"Freezing of gait: Understanding the complexity of an enigmatic phenomenon","volume":"143","author":"Weiss","year":"2020","journal-title":"Brain"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1080\/17434440.2021.1909471","article-title":"Device profile of the percept PC deep brain stimulation system for the treatment of Parkinson\u2019s disease and related disorders","volume":"18","year":"2021","journal-title":"Expert. Rev. Med. Devices"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41531-022-00350-7","article-title":"Diurnal modulation of subthalamic beta oscillatory power in Parkinson\u2019s disease patients during deep brain stimulation","volume":"8","author":"Feldmann","year":"2022","journal-title":"NPJ Park. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zhang, L.L., Zhang, L., Dong, J., Zhao, Y., and Wang, X.P. (2022). Factors Contributing to Malnutrition in Parkinson\u2019s Disease Patients with Freezing of Gait. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.816315"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.gaitpost.2018.12.009","article-title":"Non-motor predictors of freezing of gait in Parkinson\u2019s disease","volume":"68","author":"Banks","year":"2019","journal-title":"Gait Posture"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1177\/1545968320912756","article-title":"Do Patients with Parkinson\u2019s Disease with Freezing of Gait Respond Differently Than Those Without to Treadmill Training Augmented by Virtual Reality?","volume":"34","author":"Bekkers","year":"2020","journal-title":"Neurorehabil. Neural Repair."},{"key":"ref_13","first-page":"459321","article-title":"Is freezing of gait in Parkinson\u2019s disease a result of multiple gait impairments? Implications for treatment","volume":"2012","author":"Plotnik","year":"2012","journal-title":"Parkinsons Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Vandenbossche, J., Deroost, N., Soetens, E., Coomans, D., Spildooren, J., Vercruysse, S., Nieuwboer, A., and Kerckhofs, E. (2012). Freezing of gait in Parkinson\u2019s disease: Disturbances in automaticity and control. Front. Hum. Neurosci., 6.","DOI":"10.3389\/fnhum.2012.00356"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.parkreldis.2008.08.006","article-title":"A pathophysiological model of freezing of gait in Parkinson\u2019s disease","volume":"15","author":"Lewis","year":"2009","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chen, C.C., Yeh, C.H., Chan, H.L., Chang, Y.J., Tu, P.H., Yeh, C.H., Lu, C.S., Fischer, P., Tinkhauser, G., and Tan, H. (2019). Subthalamic nucleus oscillations correlate with vulnerability to freezing of gait in patients with Parkinson\u2019s disease. Neurobiol. Dis., 132.","DOI":"10.1016\/j.nbd.2019.104605"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1093\/brain\/awy019","article-title":"The functional network signature of heterogeneity in freezing of gait","volume":"141","author":"Hall","year":"2018","journal-title":"Brain"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1002\/mds.20115","article-title":"Falls and freezing of gait in Parkinson\u2019s disease: A review of two interconnected, episodic phenomena","volume":"19","author":"Bloem","year":"2004","journal-title":"Mov. Disord."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.parkreldis.2017.10.013","article-title":"A prospective study of falls in relation to freezing of gait and response fluctuations in Parkinson\u2019s disease","volume":"46","author":"Okuma","year":"2018","journal-title":"Park. Relat. Disord."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"107019","DOI":"10.1016\/j.parkreldis.2024.107019","article-title":"An immersive virtual reality shopping task detects declines in instrumental activities of daily living in individuals with Parkinson\u2019s disease","volume":"125","author":"Rosenfeldt","year":"2024","journal-title":"Park. Relat. Disord."},{"key":"ref_21","first-page":"e63978","article-title":"The Immersive Cleveland Clinic Virtual Reality Shopping Platform for the Assessment of Instrumental Activities of Daily Living","volume":"185","author":"Alberts","year":"2022","journal-title":"J. Vis. Exp."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Lewis, M.M., Waltz, C., Scelina, K., Scelina, L., Owen, K., Hastilow, K., Koop, M.M., Rosenfeldt, A.B., and Alberts, J.L. (2023). Older adults exhibit declines in instrumental activities of daily living during a virtual grocery shopping task. Front. Virtual Real., 4.","DOI":"10.3389\/frvir.2023.1261096"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.3758\/s13423-022-02104-1","article-title":"The item-specific proportion congruency effect transfers to non-category members based on broad visual similarity","volume":"29","author":"Cochrane","year":"2022","journal-title":"Psychon. Bull. Rev."},{"key":"ref_24","first-page":"371","article-title":"The ten-twenty electrode system of the International Federation","volume":"10","author":"Jasper","year":"1958","journal-title":"Electroencephalogr. Clin. Neurophysiol."},{"key":"ref_25","unstructured":"Medtronic (2025, January 31). BrainSense\u2122 Whitepaper Update for A610 v3.0. Available online: https:\/\/www.medtronicacademy.com\/en-us\/document\/brainsense--whitepaper-update-for-a610-v3-0\/DBS."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1109\/TAU.1967.1161901","article-title":"The use of fast Fourier transform for the estimation of power spectra: A method based on time averaging over short, modified periodograms","volume":"15","author":"Welch","year":"1967","journal-title":"IEEE Trans. Audio Electroacoust."},{"key":"ref_27","first-page":"2184","article-title":"Real-time modeling and 3D visualization of source dynamics and connectivity using wearable EEG","volume":"2013","author":"Mullen","year":"2013","journal-title":"Annu. Int. Conf. IEEE Eng. Med. Biol. Soc."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Delorme, A., Palmer, J., Onton, J., Oostenveld, R., and Makeig, S. (2012). Independent EEG sources are dipolar. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030135"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jneumeth.2003.10.009","article-title":"EEGLAB: An open source toolbox for analysis of single-trial EEG dynamics including independent component analysis","volume":"134","author":"Delorme","year":"2004","journal-title":"J. Neurosci. Methods"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1109\/TNSRE.2021.3107106","article-title":"Identification of EEG Dynamics During Freezing of Gait and Voluntary Stopping in Patients with Parkinson\u2019s Disease","volume":"29","author":"Cao","year":"2021","journal-title":"IEEE Trans. Neural Syst. Rehabil. Eng."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1126\/science.1099745","article-title":"Neuronal oscillations in cortical networks","volume":"304","author":"Buzsaki","year":"2004","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"S468","DOI":"10.1002\/mds.22144","article-title":"Clinimetrics of freezing of gait","volume":"23","author":"Snijders","year":"2008","journal-title":"Mov. Disord."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1002\/mds.1206","article-title":"Abnormalities of the spatiotemporal characteristics of gait at the onset of freezing in Parkinson\u2019s disease","volume":"16","author":"Nieuwboer","year":"2001","journal-title":"Mov. Disord."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"O\u2019Day, J., Syrkin-Nikolau, J., Anidi, C., Kidzinski, L., Delp, S., and Bronte-Stewart, H. (2020). The turning and barrier course reveals gait parameters for detecting freezing of gait and measuring the efficacy of deep brain stimulation. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0231984"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Gilat, M., Shine, J.M., Bolitho, S.J., Matar, E., Kamsma, Y.P., Naismith, S.L., and Lewis, S.J. (2013). Variability of Stepping during a Virtual Reality Paradigm in Parkinson\u2019s Disease Patients with and without Freezing of Gait. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066718"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1109\/JBHI.2015.2479625","article-title":"Dual Motor-Cognitive Virtual Reality Training Impacts Dual-Task Performance in Freezing of Gait","volume":"19","author":"Killane","year":"2015","journal-title":"IEEE J. Biomed. Health Inform."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Janssen, S., de Ruyter van Steveninck, J., Salim, H.S., Cockx, H.M., Bloem, B.R., Heida, T., and van Wezel, R.J.A. (2020). The Effects of Augmented Reality Visual Cues on Turning in Place in Parkinson\u2019s Disease Patients with Freezing of Gait. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.00185"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Zhao, H., Feng, Z., Hao, S., Tan, H., Zhan, S., Liu, W., Lu, Y., and Cao, C. (2023, January 24\u201327). A Virtual Reality (VR) based Comprehensive Freezing of Gait (FOG) Neuro-electrophysiologic Evaluation System for People with Parkinson\u2019s Disease (PD). Proceedings of the 2023 45th Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), Sydney, Australia.","DOI":"10.1109\/EMBC40787.2023.10340628"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.clinph.2013.09.006","article-title":"Abnormal patterns of theta frequency oscillations during the temporal evolution of freezing of gait in Parkinson\u2019s disease","volume":"125","author":"Shine","year":"2014","journal-title":"Clin. Neurophysiol."},{"key":"ref_40","first-page":"6618","article-title":"An EEG study of turning freeze in Parkinson\u2019s disease patients: The alteration of brain dynamic on the motor and visual cortex","volume":"2015","author":"Handojoseno","year":"2015","journal-title":"Annu. Int. Conf. IEEE Eng. Med. Biol. Soc."},{"key":"ref_41","first-page":"3044","article-title":"Detection of turning freeze in Parkinson\u2019s disease based on S-transform decomposition of EEG signals","volume":"2017","author":"Gilat","year":"2017","journal-title":"Annu. Int. Conf. IEEE Eng. Med. Biol. Soc."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Asher, E.E., Plotnik, M., Gunther, M., Moshel, S., Levy, O., Havlin, S., Kantelhardt, J.W., and Bartsch, R.P. (2021). Connectivity of EEG synchronization networks increases for Parkinson\u2019s disease patients with freezing of gait. Commun. Biol., 4.","DOI":"10.1038\/s42003-021-02544-w"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"fcab277","DOI":"10.1093\/braincomms\/fcab277","article-title":"Movement-related EEG signatures associated with freezing of gait in Parkinson\u2019s disease: An integrative analysis","volume":"3","author":"Karimi","year":"2021","journal-title":"Brain Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1093\/brain\/awac121","article-title":"Cortical phase-amplitude coupling is key to the occurrence and treatment of freezing of gait","volume":"145","author":"Yin","year":"2022","journal-title":"Brain"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1111\/ejn.13853","article-title":"Oscillatory activity in the cortico-basal ganglia-thalamic neural circuits in Parkinson\u2019s disease","volume":"48","author":"Singh","year":"2018","journal-title":"Eur. J. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.nbd.2013.12.005","article-title":"High beta activity in the subthalamic nucleus and freezing of gait in Parkinson\u2019s disease","volume":"64","author":"Toledo","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Conde, C.I., Lang, C., Baumann, C.R., Easthope, C.A., Taylor, W.R., and Ravi, D.K. (2023). Triggers for freezing of gait in individuals with Parkinson\u2019s disease: A systematic review. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1326300"}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/25\/13\/4036\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:00:52Z","timestamp":1760032852000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/25\/13\/4036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,28]]},"references-count":47,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["s25134036"],"URL":"https:\/\/doi.org\/10.3390\/s25134036","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,28]]}}}