{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T16:34:28Z","timestamp":1785515668426,"version":"3.56.0"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T00:00:00Z","timestamp":1608163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005362","name":"Universita degli Studi di Bari Aldo Moro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005362","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Scientific literature does not offer sufficient data on electroencephalography (EEG) functional connectivity and its correlations with clinical and cognitive features in premanifest and manifest HD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>This study tries to identify abnormal EEG patterns of functional connectivity, in conditions of \u201cbrain resting state\u201d and correlations with motor decline and cognitive variable in Huntington\u2019s disease (HD), in premanifest and manifest phase, looking for a reliable marker measuring disease progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>This was an observational cross-sectional study; 105 subjects with age \u226518 years submitted to HD genetic test. Each subject underwent a neurological, psychiatric, and cognitive assessment, EEG recording and genetic investigation for detecting the expansion of the CAG trait. EEG connectivity analysis was performed by means of exact Low Resolution Electric Tomography (eLORETA) in 18 premanifest HD (pHD), 49 manifest HD (mHD), and 38 control (C) subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>HD patients showed a Power Spectral Density reduced in the alpha range and increased in delta band compared to controls; no difference was detectable between pHD and mHD; the Global Connectivity in pHD revealed no significant differences if compared to mHD. The Current Source Density was similar among groups. No statistically significant results when comparing pHD with C group, even in comparison of mHD with Controls, and pHD with mHD. mHD compared to Controls showed a significant increase in delta, alpha1, alpha2, beta2, and beta3. Lagged Phase Synchronization in delta, alpha1, alpha2, beta2, and beta3 bands was increased in HD compared to controls (<jats:italic>t<\/jats:italic> = \u22123.921, <jats:italic>p<\/jats:italic> &amp;lt; 0.05). A significant correlation was found in Regression Analysis: statistically significant results in pHD for the \u201cSymbol Digit Modality Test and lagged phase synchronization\u201d in the Beta1 (<jats:italic>r<\/jats:italic> = \u22120.806, <jats:italic>p<\/jats:italic> &amp;lt; 0.05) in the prefrontal regions. The same correlation was found in mHD for the Stroop Word Reading Test (SWRT) in the Alpha2 band (<jats:italic>r<\/jats:italic> = \u22120.759, <jats:italic>p<\/jats:italic> &amp;lt; 0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Increased phase synchronization in main bands characterized EEG in HD patients, as compared to controls. pHD were not dissimilar from mHD as regard to this EEG pattern. Increased phase synchronization correlated to cognitive decline in HD patients, with a similar trend in pHD, suggesting that it would be a potential biomarker of early phenotypical expression.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphys.2020.612325","type":"journal-article","created":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T13:41:51Z","timestamp":1610026911000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["EEG Functional Connectivity and Cognitive Variables in Premanifest and Manifest Huntington\u2019s Disease: EEG Low-Resolution Brain Electromagnetic Tomography (LORETA) Study"],"prefix":"10.3389","volume":"11","author":[{"given":"Marianna","family":"Delussi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virgilio","family":"Nazzaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Ricci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"de Tommaso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.pscychresns.2005.06.008","article-title":"Correlation of PET and qEEG in normal subjects.","volume":"146","author":"Alper","year":"2006","journal-title":"Psychiatry Res."},{"key":"B2","article-title":"Topographic classification of EEG patterns in Huntington\u2019s disease.","volume":"2004","author":"Bellotti","year":"2004","journal-title":"Neurol. Clin. Neurophysiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"3484","DOI":"10.1016\/j.neuropsychologia.2011.08.024","article-title":"On the role of fronto-striatal neural synchronization processes for response inhibition\u2013evidence from ERP phase-synchronization analyses in pre-manifest Huntington\u2019s disease gene mutation carriers.","volume":"49","author":"Beste","year":"2011","journal-title":"Neuropsychologia"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1016\/j.neuropsychologia.2007.12.008","article-title":"Response inhibition in Huntington\u2019s disease-a study using ERPs and sLORETA.","volume":"46","author":"Beste","year":"2008","journal-title":"Neuropsychologia"},{"key":"B5","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/0028-3932(94)90001-9","article-title":"EEG power spectra in Huntington\u2019s disease: clinical and neuropsychological correlates.","volume":"32","author":"Bylsma","year":"1994","journal-title":"Neuropsychologia"},{"key":"B6","doi-asserted-by":"publisher","first-page":"3727","DOI":"10.1113\/jp270268","article-title":"Relationship between subthalamic nucleus neuronal activity and electrocorticogramis altered in the R6\/2 mouse model of Huntington\u2019s disease.","volume":"593","author":"Callahan","year":"2015","journal-title":"J. Physiol."},{"key":"B7","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-020-15352-3","article-title":"The globus pallidus orchestrates abnormal network dynamics in a model of Parkinsonism.","volume":"11","author":"Crompe","year":"2020","journal-title":"Nat. Commun."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1016\/s1388-2457(03)00074-9","article-title":"Detection of subclinical brain electrical activity changes in Huntington\u2019s disease using artificial neural networks.","volume":"114","author":"de Tommaso","year":"2003","journal-title":"Clin. Neurophysiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.jns.2007.01.011","article-title":"Abnormalities of the contingent negative variation in Huntington\u2019s disease: correlations with clinical features.","volume":"254","author":"de Tommaso","year":"2007","journal-title":"J. NeurolSci."},{"key":"B10","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"\u201cMini-mental state\u201d. A practical method for grading the cognitive state of patients for the clinician.","volume":"12","author":"Folstein","year":"1975","journal-title":"J. Psychiatr. Res."},{"key":"B11","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/jcbfm.1991.122","article-title":"Comparing functional (PET) images: the assessment of significant change.","volume":"11","author":"Friston","year":"1991","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B12","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1038\/jcbfm.2012.17","article-title":"The search for sensitive biomarkers in presymptomatic Huntington disease.","volume":"32","author":"Henry","year":"2012","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B13","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1002\/mds.20332","article-title":"Interrater agreement in the assessment of motor manifestations of Huntington\u2019s disease.","volume":"20","author":"Hogarth","year":"2005","journal-title":"Mov. Disord."},{"key":"B14","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1097\/00004647-199601000-00002","article-title":"Nonparametric analysis of statistic images from functional mapping experiments.","volume":"16","author":"Holmes","year":"1996","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B15","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1177\/1073858405277450","article-title":"Thalamic mechanisms of EEG alpha rhythms and their pathological implications.","volume":"11","author":"Hughes","year":"2005","journal-title":"Neuroscientist"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1371\/currents.RRN1192","article-title":"QEEG measures in Huntington\u2019s disease: a pilot study.","volume":"2","author":"Hunter","year":"2010","journal-title":"PLoS Curr."},{"key":"B17","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1002\/mds.870110204","article-title":"Unified Huntington\u2019s disease rating scale: reliability and consistency.","volume":"11","year":"1996","journal-title":"Mov. Disord."},{"key":"B18","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.genhosppsych.2007.11.005","article-title":"Behavioural problems in Huntington\u2019s disease using the problem behaviours assessment.","volume":"30","author":"Kingma","year":"2008","journal-title":"Gen. Hosp. Psychiatry"},{"key":"B19","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1159\/000501616","article-title":"Differential changes in functional connectivity of striatum-prefrontal and striatum-motor circuits in premanifest Huntington\u2019s disease.","volume":"19","author":"Kronenburger","year":"2019","journal-title":"Neurodegener. Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.pscychresns.2018.03.001","article-title":"Disturbed functional connectivity within the left prefrontal cortex and sensorimotor areas predicts impaired cognitive speed in patients with first-episode schizophrenia.","volume":"30","author":"Krukow","year":"2018","journal-title":"Psychiatry Res. Neuroimaging"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1002\/mds.10273","article-title":"Clinical relevance of electrophysiological tests in the assessment of patients with Huntington\u2019s disease.","volume":"17","author":"Lefaucheur","year":"2002","journal-title":"Mov. Disord."},{"key":"B22","article-title":"Dynamic network interactions among distinct brain rhythms as a hallmark of physiologic state and function.","volume":"3","author":"Lin","year":"2020","journal-title":"Commun. Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.neunet.2019.12.021","article-title":"The role of coupling connections in a model of the cortico-basal ganglia-thalamocortical neural loop for the generation of beta oscillations.","volume":"123","author":"Liu","year":"2020","journal-title":"Neural Netw."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2015.00062","article-title":"Plasticity of brain wave network interactions and evolution across physiologic states.","volume":"9","author":"Liu","year":"2015","journal-title":"Front. Neural Circuits"},{"key":"B25","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/0013-4694(80)90011-5","article-title":"Relative contribution of intracortical and thalamocortical processes in the generation alpha rhythms, revealed by partial coherence analysis.","volume":"50","author":"Lopes da Silva","year":"1980","journal-title":"Electroencephalogr. Clin. Neurophysiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1007\/s00415-020-09730-6","article-title":"Utility of the Parkinson\u2019s disease-cognitive rating scale for the screening of global cognitive status in Huntington\u2019s disease.","volume":"267","author":"Martinez-Horta","year":"2020","journal-title":"J. Neurol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1098\/rstb.2001.0915","article-title":"A probabilistic atlas and reference system for the human brain: international consortium for brain mapping (ICBM).","volume":"356","author":"Mazziotta","year":"2001","journal-title":"Philos. Trans. R Soc. Lond. B Biol. Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/hbm.1058","article-title":"Nonparametric permutation test for functional neuroimaging: a primer with examples.","volume":"15","author":"Nichols","year":"2002","journal-title":"Hum. Brain Mapp."},{"key":"B29","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1007\/s12017-015-8355-9","article-title":"Neuronal network oscillations in neurodegenerative diseases.","volume":"17","author":"Nimmrich","year":"2015","journal-title":"Neuromolecular Med."},{"key":"B30","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/B978-0-12-381328-2.00013-4","article-title":"Huntington\u2019s disease: clinical presentation and treatment.","volume":"98","author":"Novak","year":"2011","journal-title":"Inter. Rev. Neurobiol."},{"key":"B31","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1007\/s00415-010-5852-5","article-title":"EEG low-resolution brain electromagnetic tomography (LORETA) in Huntington\u2019s disease.","volume":"258","author":"Painold","year":"2011","journal-title":"J. Neurol."},{"key":"B32","first-page":"91","article-title":"Functional imaging with low-resolution brain electromagnetic tomography (LORETA): a review.","author":"Pascual-Marqui","year":"2002","journal-title":"Methods Find. Exp. Clin. Pharmacol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/s0925-4927(99)00013-x","article-title":"Low resolution brain electromagnetic tomography (LORETA) functional imaging in acute, neuroleptic- naive, first-episode, productive schizophrenia.","volume":"90","author":"Pascual-Marqui","year":"1999","journal-title":"Psychiatry Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"3768","DOI":"10.1098\/rsta.2011.0081","article-title":"Assessing interactions in the brain with exact low resolution electromagnetic tomography.","volume":"369","author":"Pascual-Marqui","year":"2011","journal-title":"Philos. Trans. A Math. Phys. Eng. Sci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/0167-8760(84)90014-x","article-title":"Low resolution electromagnetic tomography: a new method for localizing electrical activity in the brain.","volume":"18","author":"Pascual-Marqui","year":"1994","journal-title":"Int. J. Psychophysiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1006\/nimg.2002.1143","article-title":"Anatomically informed basis functions for EEG source localization: combining functional and anatomical constraints.","volume":"16","author":"Phillips","year":"","journal-title":"Neuroimage"},{"key":"B37","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1006\/nimg.2002.1175","article-title":"Systematic regularization of linear inverse solutions of the EEG source localization problem.","volume":"17","author":"Phillips","year":"","journal-title":"Neuroimage"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1016\/j.clinph.2016.11.019","article-title":"Sleep-related modifications of EEG connectivity in the sensory-motor networks in Huntington disease: an eLORETA study and review of the literature.","volume":"128","author":"Piano","year":"","journal-title":"Clin. Neurophysiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1177\/1550059416632413","article-title":"Wake and Sleep EEG in patients with Huntington disease: an eLORETA study and review of the literature.","volume":"48","author":"Piano","year":"","journal-title":"Clin. EEG Neurosci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.jns.2014.06.035","article-title":"Alpha-theta border EEG abnormalities in preclinical Huntington\u2019s disease.","volume":"344","author":"Ponomareva","year":"2014","journal-title":"J. Neurol. Sci."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1212\/01.wnl.0000204230.16619.d9","article-title":"The association of CAG repeat length with clinical progression in Huntington disease.","volume":"66","author":"Rosenblatt","year":"2006","journal-title":"Neurology"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1212\/wnl.31.10.1333","article-title":"Huntington disease: functional capacities in patients treated with neuroleptic and antidepressant drugs.","volume":"31","author":"Shoulson","year":"1981","journal-title":"Neurology"},{"key":"B43","author":"Smith","year":"2007","journal-title":"Symbol Digits Modalities Test: Manual."},{"key":"B44","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/0197-4580(90)90057-7","article-title":"Computer analysis of EEG activity in dementia of the Alzheimer\u2019s type and Huntington\u2019s disease.","volume":"11","author":"Streletz","year":"1990","journal-title":"Neurobiol. Aging"},{"key":"B45","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1037\/h0054651","article-title":"Studies of interference in serial verbal reactions.","volume":"18","author":"Stroop","year":"1935","journal-title":"J. Exp. Psychol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1016\/s1474-4422(09)70170-x","article-title":"Biological and clinical manifestation of Huntington\u2019s disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data.","volume":"8","author":"Tabrizi","year":"2009","journal-title":"Lancet Neurol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/s1474-4422(10)70276-3","article-title":"Biological and clinical changes in premanifest and early stage Huntington\u2019s disease in the TRACK-HD study: the 12-month longitudinal analysis.","volume":"10","author":"Tabrizi","year":"2011","journal-title":"Lancet Neurol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/s0887-6177(97)00095-4","article-title":"Normative data stratified by age and education for two measures of verbal fluency: FAS and animal naming.","volume":"14","author":"Tombaugh","year":"1999","journal-title":"Arch. Clin. Neuropsychol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1114\/1.1415526","article-title":"A self-coherence enhancement algorithm and its application to enhancing three-dimensional source estimation from EEGs.","volume":"29","author":"Yao","year":"2001","journal-title":"Ann. Biomed. Eng."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2020.612325\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T13:41:56Z","timestamp":1610026916000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2020.612325\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,17]]},"references-count":49,"alternative-id":["10.3389\/fphys.2020.612325"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2020.612325","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,17]]},"article-number":"612325"}}