title: Motor loop dysfunction causes impaired cognitive sequencing in patients suffering from Parkinson's disease.
abstract: Cognitive impairment in Parkinson's disease (PD) is often attributed to dopamine deficiency in the prefrontal-basal ganglia-thalamo-cortical loops. Although recent studies point to a close interplay between motor and cognitive abilities in PD, the so-called "motor loop" connecting supplementary motor area (SMA) and putamen has been considered solely with regard to the patients' motor impairment. Our study challenges this view by testing patients with the serial prediction task (SPT), a cognitive task that requires participants to predict stimulus sequences and particularly engages premotor sites of the motor loop. We hypothesised that affection of the motor loop causes impaired SPT performance, especially when the internal sequence representation is challenged by suspension of external stimuli. As shown for motor tasks, we further expected this impairment to be compensated by hyperactivity of the lateral premotor cortex (PM). We tested 16 male PD patients ON and OFF dopaminergic medication and 16 male age-matched healthy controls in an functional Magnetic Resonance Imaging study. All subjects performed two versions of the SPT: one with on-going sequences (SPT0), and one with sequences containing non-informative wildcards (SPT+) increasing the demands on mnemonic sequence representation. Patients ON (compared to controls) revealed an impaired performance coming along with hypoactivity of SMA and putamen. Patients OFF compared to ON medication, while showing poorer performance, exhibited a significantly increased PM activity for SPT+ vs. SPT0. Furthermore, patients' performance positively co-varied with PM activity, corroborating a compensatory account. Our data reveal a contribution of the motor loop to cognitive impairment in PD, and suggest a close interplay of SMA and PM beyond motor control.
authors.affiliation: Department of Neurology, University Hospital Cologne, Kerpener Str. 62 D-50937 Cologne, Germany; Max Planck Institute for Neurological Research, Gleueler Str. 50 D-50931 Cologne, Germany.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Schönberger
authors.affiliation: Department of Neurology, University Hospital Cologne, Kerpener Str. 62 D-50937 Cologne, Germany; Department of Psychology, University of Muenster, Fliednerstr. 21 D-48149 Münster, Germany.
authors.forename: Klara
authors.initials: K
authors.lastname: Hagelweide
authors.affiliation: Department of Neurology, University Hospital Cologne, Kerpener Str. 62 D-50937 Cologne, Germany; Max Planck Institute for Neurological Research, Gleueler Str. 50 D-50931 Cologne, Germany.
authors.forename: Esther A
authors.initials: EA
authors.lastname: Pelzer
authors.affiliation: Department of Neurology, University Hospital Cologne, Kerpener Str. 62 D-50937 Cologne, Germany; Institute of Neuroscience and Medicine (INM3), Cognitive Neuroscience, Research Centre Jülich, Leo-Brandt-Straße D-52425 Jülich, Germany.
authors.forename: Gereon R
authors.initials: GR
authors.lastname: Fink
authors.affiliation: Department of Neurology, University Hospital Cologne, Kerpener Str. 62 D-50937 Cologne, Germany; Department of Psychology, University of Muenster, Fliednerstr. 21 D-48149 Münster, Germany. Electronic address: rschubotz@uni-muenster.de.
authors.forename: Ricarda I
authors.initials: RI
authors.lastname: Schubotz
mesh_terms: D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D001931:Brain Mapping; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D015259:Dopamine Agents / Q000627:therapeutic use; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology; D011930:Reaction Time / Q000187:drug effects; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D014796:Visual Perception / Q000187:drug effects / Q000502:physiology*
chemical_list: D000978:Antiparkinson Agents; D015259:Dopamine Agents
keywords: Cognitive sequencing; Lateral premotor cortex; Parkinson's disease; Serial prediction task; Supplementary motor area