title: Brain activity underlying tool-related and imitative skills after major left hemisphere stroke.
abstract: Apraxia is a debilitating cognitive motor disorder that frequently occurs after left hemisphere stroke and affects tool-associated and imitative skills. However, the severity of the apraxic deficits varies even across patients with similar lesions. This variability raises the question whether regions outside the left hemisphere network typically associated with cognitive motor tasks in healthy subjects are of additional functional relevance. To investigate this hypothesis, we explored regions where functional magnetic resonance imaging activity is associated with better cognitive motor performance in patients with left hemisphere ischaemic stroke. Thirty-six patients with chronic (>6 months) large left hemisphere infarcts (age ± standard deviation, 60 ± 12 years, 29 male) and 29 control subjects (age ± standard deviation, 72 ± 7, 15 male) were first assessed behaviourally outside the scanner with tests for actual tool use, pantomime and imitation of tool-use gestures, as well as for meaningless gesture imitation. Second, functional magnetic resonance imaging activity was registered during the passive observation of videos showing tool-associated actions. Voxel-wise linear regression analyses were used to identify areas where behavioural performance was correlated with functional magnetic resonance imaging activity. Furthermore, lesions were delineated on the magnetic resonance imaging scans for voxel-based lesion-symptom mapping. The analyses revealed two sets of regions where functional magnetic resonance imaging activity was associated with better performance in the clinical tasks. First, activity in left hemisphere areas thought to mediate cognitive motor functions in healthy individuals (i.e. activity within the putative 'healthy' network) was correlated with better scores. Within this network, tool-associated tasks were mainly related to activity in supramarginal gyrus and ventral premotor cortex, while meaningless gesture imitation depended more on the anterior intraparietal sulcus and superior parietal lobule. Second, repeating the regression analyses with total left hemisphere lesion volume as additional covariate demonstrated that tool-related skills were further supported by right premotor, right inferior frontal and left anterior temporal areas, while meaningless gesture imitation was also driven by the left dorso-lateral prefrontal cortex. In summary, tool-related and imitative skills in left hemisphere stroke patients depend on the activation of spared left hemisphere regions that support these abilities in healthy individuals. In addition, cognitive motor functions rely on the activation of ipsi- and contralesional areas that are situated outside this 'healthy' network. This activity may explain why some patients perform surprisingly well despite large left brain lesions, while others are severely impaired.
authors.affiliation: Department of Neurology and Clinical Neurosciences, University Medical Centre Freiburg, Germany Freiburg Brain Imaging Centre, University of Freiburg, Germany BrainLinks-BrainTools Cluster of Excellence, University of Freiburg, Germany markus.martin@uniklinik-freiburg.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Martin
authors.affiliation: Department of Neurology and Clinical Neurosciences, University Medical Centre Freiburg, Germany Freiburg Brain Imaging Centre, University of Freiburg, Germany BrainLinks-BrainTools Cluster of Excellence, University of Freiburg, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Nitschke
authors.affiliation: Department of Neurology and Clinical Neurosciences, University Medical Centre Freiburg, Germany Freiburg Brain Imaging Centre, University of Freiburg, Germany BrainLinks-BrainTools Cluster of Excellence, University of Freiburg, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Beume
authors.affiliation: Department of Neurology and Clinical Neurosciences, University Medical Centre Freiburg, Germany Freiburg Brain Imaging Centre, University of Freiburg, Germany BrainLinks-BrainTools Cluster of Excellence, University of Freiburg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Dressing
authors.affiliation: Department of Neurology and Clinical Neurosciences, University Medical Centre Freiburg, Germany Freiburg Brain Imaging Centre, University of Freiburg, Germany.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Bühler
authors.affiliation: Department of Neurology and Clinical Neurosciences, University Medical Centre Freiburg, Germany Freiburg Brain Imaging Centre, University of Freiburg, Germany.
authors.forename: Vera M
authors.initials: VM
authors.lastname: Ludwig
authors.affiliation: Freiburg Brain Imaging Centre, University of Freiburg, Germany Department of Neuroradiology, University Medical Centre Freiburg, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Mader
authors.affiliation: Department of Neurology and Clinical Neurosciences, University Medical Centre Freiburg, Germany Freiburg Brain Imaging Centre, University of Freiburg, Germany.
authors.forename: Michel
authors.initials: M
authors.lastname: Rijntjes
authors.affiliation: Department of Neurology and Clinical Neurosciences, University Medical Centre Freiburg, Germany Freiburg Brain Imaging Centre, University of Freiburg, Germany BrainLinks-BrainTools Cluster of Excellence, University of Freiburg, Germany.
authors.forename: Christoph P
authors.initials: CP
authors.lastname: Kaller
authors.affiliation: Department of Neurology and Clinical Neurosciences, University Medical Centre Freiburg, Germany Freiburg Brain Imaging Centre, University of Freiburg, Germany BrainLinks-BrainTools Cluster of Excellence, University of Freiburg, Germany.
authors.forename: Cornelius
authors.initials: C
authors.lastname: Weiller
mesh_terms: D000368:Aged; D001931:Brain Mapping; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000502:physiology; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007100:Imitative Behavior / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000502:physiology*; D009483:Neuropsychological Tests; D010296:Parietal Lobe / Q000502:physiology*; D011597:Psychomotor Performance / Q000502:physiology*; D020521:Stroke / Q000503:physiopathology*
keywords: apraxia; functional MRI; imitation; stroke; tool use