title: Neuromuscular correlates of subthalamic stimulation and upper limb freezing in Parkinson's disease.
abstract: OBJECTIVE
  The pathophysiology of deep brain stimulation mechanisms and resistant freezing phenomena in idiopathic Parkinson's disease (iPD) remains incompletely understood. Further studies on the neuromuscular substrates are needed.
  
  
  METHODS
  We analyzed 16 patients with advanced iPD and bilateral subthalamic nucleus stimulation, and 13 age- and gender-matched healthy controls. Patients were tested after overnight withdrawal of medication with 'stimulation off' (StimOff) and 'stimulation on' (StimOn). Subjects performed continuous tapping of the right index finger with simultaneous recordings of biomechanical registration, EMG of finger flexors and extensors, and EEG. First, we analyzed EEG and EMG spectral measures comparing StimOff with healthy controls and StimOff with StimOn (irrespective of freezing). Second, we contrasted 'regular (unimpaired) tapping' and 'freezing' resistant to subthalamic neurostimulation as obtained in StimOn.
  
  
  RESULTS
  iPD showed increased intermuscular coherence around 8Hz in StimOff that was reduced in StimOn. This 8Hz muscular activity was not coherent to cortical activity. 'Freezing' episodes showed increased muscle activity of finger flexors and extensors at 6-9Hz, and increased cortical activity at 7-11Hz. During transition from regular tapping to 'freezing' the cortical activity first increased over the left sensorimotor area followed by a spread to the left frontal and right parietal areas.
  
  
  CONCLUSIONS
  We identified neuromuscular motor network features of subthalamic neurostimulation therapy and resistant upper limb freezing that point to increased low-frequency muscular and cortical activity.
  
  
  CONCLUSIONS
  Together, our findings demonstrate several motor network abnormalities associated with upper limb freezing that may translate into future research on freezing of gait in iPD.
authors: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research (HIH), University of Tuebingen, Germany; German Centre of Neurodegenerative Diseases (DZNE), University of Tuebingen, Tuebingen, Germany; Centre for Integrative Neuroscience (CIN), University of Tuebingen, Tuebingen, Germany; Graduate School of Neural & Behavioural Sciences, International Max Planck Research School, University of Tuebingen, Tuebingen, Germany. Electronic address: marlieke.scholten@uni-tuebingen.de.
authors: Marlieke
authors: M
authors: Scholten
authors: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research (HIH), University of Tuebingen, Germany; German Centre of Neurodegenerative Diseases (DZNE), University of Tuebingen, Tuebingen, Germany; Centre for Integrative Neuroscience (CIN), University of Tuebingen, Tuebingen, Germany.
authors: Rosa
authors: R
authors: Klotz
authors: Centre for Integrative Neuroscience (CIN), University of Tuebingen, Tuebingen, Germany; Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany.
authors: Christian
authors: C
authors: Plewnia
authors: Centre of Rehabilitation, Bad Gögging, Passauer Wolf, Germany.
authors: Tobias
authors: T
authors: Wächter
authors: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research (HIH), University of Tuebingen, Germany; German Centre of Neurodegenerative Diseases (DZNE), University of Tuebingen, Tuebingen, Germany; Centre for Integrative Neuroscience (CIN), University of Tuebingen, Tuebingen, Germany.
authors: Carina
authors: C
authors: Mielke
authors: Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behavior, Department of Neurology, Nijmegen, The Netherlands.
authors: Bastiaan R
authors: BR
authors: Bloem
authors: Centre for Integrative Neuroscience (CIN), University of Tuebingen, Tuebingen, Germany; MEG Center, University of Tuebingen, Tuebingen, Germany; CIMeC, Center of Mind/Brain Sciences, University of Trento, Italy.
authors: Christoph
authors: C
authors: Braun
authors: Centre for Integrative Neuroscience (CIN), University of Tuebingen, Tuebingen, Germany; Department of Neurology and Stroke, and Hertie Institute for Clinical Brain Research (HIH), University of Tuebingen, Tuebingen, Germany.
authors: Ulf
authors: U
authors: Ziemann
authors: Division of Fetal and Transitional Medicine, Children's National Medical Center, Washington, DC, USA.
authors: Rathinaswamy B
authors: RB
authors: Govindan
authors: Centre for Integrative Neuroscience (CIN), University of Tuebingen, Tuebingen, Germany; Division of Functional and Restorative Neurosurgery, Department of Neurosurgery, University of Tuebingen, Tuebingen, Germany.
authors: Alireza
authors: A
authors: Gharabaghi
authors: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research (HIH), University of Tuebingen, Germany; German Centre of Neurodegenerative Diseases (DZNE), University of Tuebingen, Tuebingen, Germany; Centre for Integrative Neuroscience (CIN), University of Tuebingen, Tuebingen, Germany; Clinical and Experimental Neuroscience, Luxembourg Center for Systems Biomedicine (LCSB), University of Luxembourg and Centre Hospitalier de Luxembourg (CHL), Luxembourg.
authors: Rejko
authors: R
authors: Krüger
authors: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research (HIH), University of Tuebingen, Germany; German Centre of Neurodegenerative Diseases (DZNE), University of Tuebingen, Tuebingen, Germany; Centre for Integrative Neuroscience (CIN), University of Tuebingen, Tuebingen, Germany. Electronic address: daniel.weiss@uni-tuebingen.de.
authors: Daniel
authors: D
authors: Weiss
mesh_terms: D000328:Adult; D000368:Aged; D046690:Deep Brain Stimulation / Q000379:methods*; D004569:Electroencephalography / Q000379:methods; D004576:Electromyography / Q000379:methods; D005260:Female; D005385:Fingers / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy*; D011597:Psychomotor Performance / Q000502:physiology*; D020531:Subthalamic Nucleus / Q000502:physiology*; D034941:Upper Extremity / Q000503:physiopathology*
keywords: Deep brain stimulation; EEG; Freezing of gait; Parkinson’s disease; Subthalamic nucleus; Upper limb freezing