{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T06:56:07Z","timestamp":1773384967437,"version":"3.50.1"},"reference-count":62,"publisher":"MIT Press - Journals","issue":"2","content-domain":{"domain":["direct.mit.edu"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>During rehabilitation after stroke motor sequence learning is of particular importance because considerable effort is devoted to (re)acquiring lost motor skills. Previous studies suggest that implicit motor sequence learning is preserved in stroke patients but were restricted to the spatial dimension, although the timing of single action components is as important as their spatial order. As the left parietal cortex is known to play a critical role in implicit timing and spatiotemporal integration, in this study we applied an adapted version of the SRT task designed to assess both spatial (different stimulus locations) and temporal (different response\u2013stimulus intervals) aspects of motor learning to 24 right-handed patients with a single left-hemisphere (LH) stroke and 24 age-matched healthy controls. Implicit retrieval of sequence knowledge was tested both at Day 1 and after 24 hr (Day 2). Additionally, voxel-based lesion symptom mapping was used to investigate the neurobiological substrates of the behavioral effects. Although LH stroke patients showed a combined spatiotemporal learning effect that was comparable to that observed in controls, LH stroke patients did not show learning effects for the learning probes in which only one type of sequence information was maintained whereas the other one was randomized. Particularly on Day 2, patients showed significantly smaller learning scores for these two learning probes than controls. Voxel-based lesion symptom mapping analyses revealed for all learning probes that diminished learning scores on Day 2 were associated with lesions of the striatum. This might be attributed to its role in motor chunking and offline consolidation as group differences occurred on Day 2 only. The current results suggest that LH stroke patients rely on multimodal information (here: temporal and spatial information) when retrieving motor sequence knowledge and are very sensitive to any disruption of the learnt sequence information as they seem to build very rigid chunks preventing them from forming independent spatial and temporal sequence representations.<\/jats:p>","DOI":"10.1162\/jocn_a_00890","type":"journal-article","created":{"date-parts":[[2015,12,23]],"date-time":"2015-12-23T12:35:20Z","timestamp":1450874120000},"page":"223-236","update-policy":"https:\/\/doi.org\/10.1162\/mitpressjournals.corrections.policy","source":"Crossref","is-referenced-by-count":14,"title":["Timing Matters? Learning of Complex Spatiotemporal Sequences in Left-hemisphere Stroke Patients"],"prefix":"10.1162","volume":"28","author":[{"given":"Anna","family":"Dovern","sequence":"first","affiliation":[{"name":"1University Hospital Cologne"},{"name":"2Research Centre J\u00fclich"}]},{"given":"Gereon R.","family":"Fink","sequence":"additional","affiliation":[{"name":"1University Hospital Cologne"},{"name":"2Research Centre J\u00fclich"}]},{"given":"David C.","family":"Timpert","sequence":"additional","affiliation":[{"name":"1University Hospital Cologne"},{"name":"2Research Centre J\u00fclich"}]},{"given":"Jochen","family":"Saliger","sequence":"additional","affiliation":[{"name":"3Neurological Rehabilitation Centre Godesh\u00f6he, Bonn, Germany"}]},{"given":"Hans","family":"Karbe","sequence":"additional","affiliation":[{"name":"3Neurological Rehabilitation Centre Godesh\u00f6he, Bonn, Germany"}]},{"given":"Peter H.","family":"Weiss","sequence":"additional","affiliation":[{"name":"1University Hospital Cologne"},{"name":"2Research Centre J\u00fclich"}]},{"given":"Iring","family":"Koch","sequence":"additional","affiliation":[{"name":"4RWTH Aachen University"}]}],"member":"281","published-online":{"date-parts":[[2016,2,1]]},"reference":[{"key":"2021073020590053300_R1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.neuron.2008.02.008","article-title":"Both the hippocampus and striatum are involved in consolidation of motor sequence memory","volume":"58","author":"Albouy","year":"2008","journal-title":"Neuron"},{"key":"2021073020590053300_R2","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.neuroscience.2005.01.047","article-title":"Difficulty of perceptual spatiotemporal integration modulates the neural activity of left inferior parietal cortex","volume":"132","author":"Assmus","year":"2005","journal-title":"Neuroscience"},{"key":"2021073020590053300_R3","doi-asserted-by":"crossref","first-page":"S82","DOI":"10.1016\/j.neuroimage.2003.09.025","article-title":"Left inferior parietal cortex integrates time and space during collision judgements","volume":"20","author":"Assmus","year":"2003","journal-title":"Neuroimage"},{"key":"2021073020590053300_R4","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/nn1050","article-title":"Voxel-based lesion-symptom mapping","volume":"6","author":"Bates","year":"2003","journal-title":"Nature Neuroscience"},{"key":"2021073020590053300_R5","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1177\/1545968307300438","article-title":"Learning implicitly: Effects of task and severity after stroke","volume":"5","author":"Boyd","year":"2007","journal-title":"Neurorehabilitation and Neural Repair"},{"key":"2021073020590053300_R6","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0304-3940(00)01734-1","article-title":"Implicit motor-sequence learning in humans following unilateral stroke: The impact of practice and explicit knowledge","volume":"298","author":"Boyd","year":"2001","journal-title":"Neuroscience Letters"},{"key":"2021073020590053300_R7","first-page":"17","article-title":"Attention and structure in sequence learning","volume":"16","author":"Cohen","year":"1990","journal-title":"Journal of Experimental Psychology: Learning, Memory, and Cognition"},{"key":"2021073020590053300_R8","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/j.neuroimage.2010.09.038","article-title":"Functionally dissociating temporal and motor components of response preparation in left intraparietal sulcus","volume":"54","author":"Cotti","year":"2011","journal-title":"Neuroimage"},{"key":"2021073020590053300_R9","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.cogbrainres.2004.02.011","article-title":"fMRI studies of temporal attention: Allocating attention within, or towards, time","volume":"21","author":"Coull","year":"2004","journal-title":"Cognitive Brain Research"},{"key":"2021073020590053300_R10","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.neuropsychologia.2012.08.017","article-title":"Functional anatomy of timing differs for production versus prediction of time intervals","volume":"51","author":"Coull","year":"2013","journal-title":"Neuropsychologia"},{"key":"2021073020590053300_R11","doi-asserted-by":"crossref","first-page":"7426","DOI":"10.1523\/JNEUROSCI.18-18-07426.1998","article-title":"Where and when to pay attention: The neural systems for directing attention to spatial locations and to time intervals as revealed by both PET and fMRI","volume":"18","author":"Coull","year":"1998","journal-title":"Journal of Neuroscience"},{"key":"2021073020590053300_R12","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/S0197-4580(03)00030-7","article-title":"Similar network activated by young and old adults during the acquisition of a motor sequence","volume":"24","author":"Daselaar","year":"2003","journal-title":"Neurobiology of Aging"},{"key":"2021073020590053300_R13","doi-asserted-by":"crossref","first-page":"3318","DOI":"10.1162\/jocn_a_00030","article-title":"Orienting attention in time activates left intraparietal sulcus for both perceptual and motor task goals","volume":"23","author":"Davranche","year":"2011","journal-title":"Journal of Cognitive Neuroscience"},{"key":"2021073020590053300_R14","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/0028-3932(68)90037-7","article-title":"Ideational apraxia: A quantitative study","volume":"6","author":"De Renzi","year":"1968","journal-title":"Neuropsychologia"},{"key":"2021073020590053300_R15","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.neuroimage.2014.05.022","article-title":"Off-line consolidation of motor sequence learning results in greater integration within a cortico-striatal functional network","volume":"99","author":"Debas","year":"2014","journal-title":"Neuroimage"},{"key":"2021073020590053300_R16","doi-asserted-by":"crossref","first-page":"17839","DOI":"10.1073\/pnas.1013176107","article-title":"Brain plasticity related to the consolidation of motor sequence learning and motor adaptation","volume":"107","author":"Debas","year":"2010","journal-title":"Proceedings of the National Academy of Sciences, U.S.A."},{"key":"2021073020590053300_R17","doi-asserted-by":"crossref","first-page":"8102","DOI":"10.1523\/JNEUROSCI.6585-10.2011","article-title":"Apraxia impairs intentional retrieval of incidentally acquired motor knowledge","volume":"31","author":"Dovern","year":"2011","journal-title":"Journal of Neuroscience"},{"key":"2021073020590053300_R18","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1016\/j.neuroimage.2004.12.034","article-title":"A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data","volume":"25","author":"Eickhoff","year":"2005","journal-title":"Neuroimage"},{"key":"2021073020590053300_R19","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1136\/jnnp.61.2.176","article-title":"Defective imitation of gestures in patients with damage in the left or right hemispheres","volume":"61","author":"Goldenberg","year":"1996","journal-title":"Journal of Neurology, Neurosurgery, and Psychiatry"},{"key":"2021073020590053300_R20","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1006\/nlme.1998.3843","article-title":"The basal ganglia and chunking of action repertoires","volume":"70","author":"Graybiel","year":"1998","journal-title":"Neurobiology of Learning and Memory"},{"key":"2021073020590053300_R21","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1146\/annurev.neuro.29.051605.112851","article-title":"Habits, rituals, and the evaluative brain","volume":"31","author":"Graybiel","year":"2008","journal-title":"Annual Review of Neuroscience"},{"key":"2021073020590053300_R22","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1046\/j.1471-4159.2003.02017.x","article-title":"Marked disparity between age\u2013related changes in dopamine and other presynaptic dopaminergic markers in human striatum","volume":"87","author":"Haycock","year":"2003","journal-title":"Journal of Neurochemistry"},{"key":"2021073020590053300_R23","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1093\/brain\/120.1.123","article-title":"Attention and stimulus characteristics determine the locus of motor-sequence encoding. A PET study","volume":"120","author":"Hazeltine","year":"1997","journal-title":"Brain"},{"key":"2021073020590053300_R24","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.neuroscience.2006.03.030","article-title":"The left parietal cortex and motor intention: An event-related functional magnetic resonance imaging study","volume":"140","author":"Hesse","year":"2006","journal-title":"Neuroscience"},{"key":"2021073020590053300_R25","first-page":"161","article-title":"Implicit learning of loosely defined structures","volume-title":"Handbook of implicit learning","author":"Hoffmann","year":"1998"},{"key":"2021073020590053300_R26","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1080\/13803390490918273","article-title":"A new test battery to assess aphasic disturbances and associated cognitive dysfunctions\u2014German normative data on the aphasia check list","volume":"27","author":"Kalbe","year":"2005","journal-title":"Journal of Clinical and Experimental Neuropsychology"},{"key":"2021073020590053300_R27","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.humov.2007.01.004","article-title":"Anticipatory response control in motor sequence learning: Evidence from stimulus\u2013response compatibility","volume":"26","author":"Koch","year":"2007","journal-title":"Human Movement Science"},{"key":"2021073020590053300_R28","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/PL00008165","article-title":"Patterns, chunks, and hierarchies in serial reaction-time tasks","volume":"63","author":"Koch","year":"2000","journal-title":"Psychological Research"},{"key":"2021073020590053300_R29","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.neuropsychologia.2010.10.025","article-title":"Keeping time in your sleep: Overnight consolidation of temporal rhythm","volume":"49","author":"Lewis","year":"2011","journal-title":"Neuropsychologia"},{"key":"2021073020590053300_R30","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/S0959-4388(03)00036-9","article-title":"Distinct systems for automatic and cognitively controlled time measurement: Evidence from neuroimaging","volume":"13","author":"Lewis","year":"2003","journal-title":"Current Opinion in Neurobiology"},{"key":"2021073020590053300_R31","doi-asserted-by":"crossref","first-page":"S58","DOI":"10.1016\/j.neuroimage.2003.09.009","article-title":"Neural mechanisms associated with attention to temporal synchrony versus spatial orientation: An fMRI study","volume":"20","author":"Lux","year":"2003","journal-title":"Neuroimage"},{"key":"2021073020590053300_R32","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1097\/00004356-198112000-00001","article-title":"A performance test for assessment of upper limb function in physical rehabilitation treatment and research","volume":"4","author":"Lyle","year":"1981","journal-title":"International Journal of Rehabilitation Research"},{"key":"2021073020590053300_R33","volume-title":"Aids to examination of the peripheral nervous system: Memorandum no 45","author":"Medical Research Council of the United Kingdom","year":"1978"},{"key":"2021073020590053300_R34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0010-0285(87)90002-8","article-title":"Attentional requirements of learning: Evidence from performance measures","volume":"19","author":"Nissen","year":"1987","journal-title":"Cognitive Psychology"},{"key":"2021073020590053300_R35","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/0028-3932(71)90067-4","article-title":"The assessment and analysis of handedness: The Edinburgh inventory","volume":"9","author":"Oldfield","year":"1971","journal-title":"Neuropsychologia"},{"key":"2021073020590053300_R36","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.neuroscience.2011.01.040","article-title":"Functional neuroanatomy associated with the expression of distinct movement kinematics in motor sequence learning","volume":"179","author":"Orban","year":"2011","journal-title":"Neuroscience"},{"key":"2021073020590053300_R37","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1080\/09602010600832788","article-title":"Implicit sequence learning processes after unilateral stroke","volume":"17","author":"Orrell","year":"2007","journal-title":"Neuropsychological Rehabilitation"},{"key":"2021073020590053300_R38","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1002\/1097-0193(200008)10:4<179::AID-HBM30>3.0.CO;2-H","article-title":"Striatum forever, despite sequence learning variability: A random effect analysis of PET data","volume":"10","author":"Peigneux","year":"2000","journal-title":"Human Brain Mapping"},{"key":"2021073020590053300_R39","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.bbr.2011.09.044","article-title":"Parallel contributions of cerebellar, striatal and M1 mechanisms to motor sequence learning","volume":"226","author":"Penhune","year":"2012","journal-title":"Behavioural Brain Research"},{"key":"2021073020590053300_R40","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1191\/0269215506cr916oa","article-title":"Implicit learning of a motor skill after mild and moderate stroke","volume":"20","author":"Pohl","year":"2006","journal-title":"Clinical Rehabilitation"},{"key":"2021073020590053300_R41","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1093\/ptj\/81.11.1780","article-title":"Implicit learning of a perceptual-motor skill after stroke","volume":"81","author":"Pohl","year":"2001","journal-title":"Physical Therapy"},{"key":"2021073020590053300_R42","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1080\/00335558008248231","article-title":"Orienting of attention","volume":"32","author":"Posner","year":"1980","journal-title":"Quarterly Journal of Experimental Psychology"},{"key":"2021073020590053300_R43","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1177\/003693305700200504","article-title":"Cerebral vascular accidents in patients over the age of 60: II. Prognosis","volume":"2","author":"Rankin","year":"1957","journal-title":"Scottish Medical Journal"},{"key":"2021073020590053300_R44","first-page":"585","article-title":"Assessing implicit learning with indirect tests: Determining what is learned about sequence structure","volume":"20","author":"Reed","year":"1994","journal-title":"Journal of Experimental Psychology: Learning, Memory, and Cognition"},{"key":"2021073020590053300_R45","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1097\/01.wnr.0000175615.93312.1a","article-title":"The role of the striatum in implicit learning: A functional magnetic resonance imaging study","volume":"16","author":"Reiss","year":"2005","journal-title":"NeuroReport"},{"key":"2021073020590053300_R46","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1016\/j.neuroimage.2010.01.015","article-title":"Activation in striatum and medial temporal lobe during sequence learning in younger and older adults: Relations to performance","volume":"50","author":"Rieckmann","year":"2010","journal-title":"Neuroimage"},{"key":"2021073020590053300_R47","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1162\/jocn.2007.19.7.1081","article-title":"Improving lesion-symptom mapping","volume":"19","author":"Rorden","year":"2007","journal-title":"Journal of Cognitive Neuroscience"},{"key":"2021073020590053300_R48","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1162\/089892901750363244","article-title":"The attentional role of the left parietal cortex: The distinct lateralization and localisation of motor attention in the human brain","volume":"13","author":"Rushworth","year":"2001","journal-title":"Journal of Cognitive Neuroscience"},{"key":"2021073020590053300_R49","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s00221-003-1548-8","article-title":"Chunking during human visuomotor sequence learning","volume":"152","author":"Sakai","year":"2003","journal-title":"Experimental Brain Research"},{"key":"2021073020590053300_R50","volume-title":"Block-Tapping-Test","author":"Schellig","year":"1997"},{"key":"2021073020590053300_R51","doi-asserted-by":"crossref","first-page":"165","DOI":"10.5709\/acp-0113-1","article-title":"Generalized lessons about sequence learning from the study of the serial reaction time task","volume":"8","author":"Schwarb","year":"2012","journal-title":"Advances in Cognitive Psychology"},{"key":"2021073020590053300_R52","volume-title":"Seashore measures of musical talents","author":"Seashore","year":"1960"},{"key":"2021073020590053300_R53","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1007\/s00221-005-2284-z","article-title":"Neural correlates of encoding and expression in implicit sequence learning","volume":"165","author":"Seidler","year":"2005","journal-title":"Experimental Brain Research"},{"key":"2021073020590053300_R54","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.bandc.2004.09.015","article-title":"Multidimensional sequence learning in patients with focal basal ganglia lesions","volume":"58","author":"Shin","year":"2005","journal-title":"Brain and Cognition"},{"key":"2021073020590053300_R55","first-page":"445","article-title":"Concurrent learning of temporal and spatial sequences","volume":"28","author":"Shin","year":"2002","journal-title":"Journal of Experimental Psychology: Learning, Memory, and Cognition"},{"key":"2021073020590053300_R56","volume-title":"A compendium of neuropsychological tests","author":"Spreen","year":"1991"},{"key":"2021073020590053300_R57","doi-asserted-by":"crossref","first-page":"819","DOI":"10.3758\/BF03202749","article-title":"Implicit serial learning: Questions inspired by Hebb (1961)","volume":"21","author":"Stadler","year":"1993","journal-title":"Memory & Cognition"},{"key":"2021073020590053300_R58","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1080\/00222895.1975.10735040","article-title":"The role of timing in motor program representation","volume":"7","author":"Summers","year":"1975","journal-title":"Journal of Motor Behavior"},{"key":"2021073020590053300_R59","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1080\/00222895.1977.10735094","article-title":"The relationship between the sequencing and timing components of a skill","volume":"9","author":"Summers","year":"1977","journal-title":"Journal of Motor Behavior"},{"key":"2021073020590053300_R60","doi-asserted-by":"crossref","first-page":"9024","DOI":"10.1523\/JNEUROSCI.22-20-09024.2002","article-title":"Differential involvement of parietal and precentral regions in movement preparation and motor intention","volume":"22","author":"Thoenissen","year":"2002","journal-title":"Journal of Neuroscience"},{"key":"2021073020590053300_R61","volume-title":"K\u00f6lner Apraxie-Screening","author":"Weiss","year":"2013"},{"key":"2021073020590053300_R62","doi-asserted-by":"crossref","first-page":"3967","DOI":"10.1016\/j.neuropsychologia.2010.09.014","article-title":"Implicit timing activates the left inferior parietal cortex","volume":"48","author":"Wiener","year":"2010","journal-title":"Neuropsychologia"}],"container-title":["Journal of Cognitive Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/direct.mit.edu\/jocn\/article-pdf\/28\/2\/223\/1950527\/jocn_a_00890.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/direct.mit.edu\/jocn\/article-pdf\/28\/2\/223\/1950527\/jocn_a_00890.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T01:02:47Z","timestamp":1627693367000},"score":1,"resource":{"primary":{"URL":"https:\/\/direct.mit.edu\/jocn\/article\/28\/2\/223\/28465\/Timing-Matters-Learning-of-Complex-Spatiotemporal"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,1]]},"references-count":62,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2016,2,1]]},"published-print":{"date-parts":[[2016,2,1]]}},"URL":"https:\/\/doi.org\/10.1162\/jocn_a_00890","relation":{},"ISSN":["0898-929X","1530-8898"],"issn-type":[{"value":"0898-929X","type":"print"},{"value":"1530-8898","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2016,2]]},"published":{"date-parts":[[2016,2,1]]}}}