TY - JOUR
T1 - Freezing of gait in Parkinson's disease is related to imbalanced stopping-related cortical activity
AU - Cockx, Helena M.
AU - Oostenveld, Robert
AU - Flórez R, Yuli A.
AU - Bloem, Bastiaan R.
AU - Cameron, Ian G.M.
AU - van Wezel, Richard J.A.
N1 - Funding Information:
First and foremost, we are grateful to all research participants who dedicated time and energy to make this study possible. We also thank patient-researchers Jan Gouman and Marc Bontjer who critically appraised the study design and results. We extend a thank you to Freek Nieuwhof for his valuable assistance during the initiation of the study, to David Mehler for his precious feedback on the performed statistics and to Liucija Svinkunaite from Artinis Medical Systems and G\u00FCnther Windau for their technical assistance with the experimental set-up. Finally, we are grateful to Ecaterina Savenco, Merel Tabor, Arne van Setten, Ren\u00E9e Jobse, Paula Koenders, Lennard van den Berg and all other students for their assistance with the measurements. This work was supported by the European Regional Development Fund (ERDF) under PROJ-00872, the 'PROMPT' project (Personalised-care and Research On Motoric-dysfunctioning for Patient-specific Treatments). The PROMPT project is a collaborative grant between two universities (Radboud University and the University of Twente), and three companies (Artinis Medical Systems, ANT Neuro and Orikami). The Radboudumc Center of Expertise for Parkinson & Movement Disorders was supported by a centre of excellence grant of the Parkinson's Foundation. The funders or companies played no role in study design, data collection, analysis and interpretation of data, or the writing of this manuscript.
Funding Information:
This work was supported by the European Regional Development Fund (ERDF) under PROJ-00872, the \u2018PROMPT\u2019 project (Personalised-care and Research On Motoric-dysfunctioning for Patient-specific Treatments). The PROMPT project is a collaborative grant between two universities (Radboud University and the University of Twente), and three companies (Artinis Medical Systems, ANT Neuro and Orikami). The Radboudumc Center of Expertise for Parkinson & Movement Disorders was supported by a centre of excellence grant of the Parkinson\u2019s Foundation. The funders or companies played no role in study design, data collection, analysis and interpretation of data, or the writing of this manuscript.
Publisher Copyright:
© The Author(s) 2024.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - Freezing of gait, characterized by involuntary interruptions of walking, is a debilitating motor symptom of Parkinson's disease that restricts people's autonomy. Previous brain imaging studies investigating the mechanisms underlying freezing were restricted to scan people in supine positions and yielded conflicting theories regarding the role of the supplementary motor area and other cortical regions. We used functional near-infrared spectroscopy to investigate cortical haemodynamics related to freezing in freely moving people. We measured functional near-infrared spectroscopy activity over multiple motor-related cortical areas in 23 persons with Parkinson's disease who experienced daily freezing ('freezers') and 22 age-matched controls during freezing-provoking tasks including turning and doorway passing, voluntary stops and actual freezing. Crucially, we corrected the measured signals for confounds of walking. We first compared cortical activity between freezers and controls during freezing-provoking tasks without freezing (i.e. turning and doorway passing) and during stops. Secondly, within the freezers, we compared cortical activity between freezing, stopping and freezing-provoking tasks without freezing. First, we show that turning and doorway passing (without freezing) resemble cortical activity during stopping in both groups involving activation of the supplementary motor area and prefrontal cortex, areas known for their role in inhibiting actions. During these freezing-provoking tasks, the freezers displayed higher activity in the premotor areas than controls. Secondly, we show that, during actual freezing events, activity in the prefrontal cortex was lower than during voluntary stopping. The cortical relation between the freezing-provoking tasks (turning and doorway passing) and stopping may explain their susceptibility to trigger freezing by activating a stopping mechanism. Besides, the stopping-related activity of the supplementary motor area and prefrontal cortex seems to be out of balance in freezers. In this paper, we postulate that freezing results from a paroxysmal imbalance between the supplementary motor area and prefrontal cortex, thereby extending upon the current role of the supplementary motor area in freezing pathophysiology.
AB - Freezing of gait, characterized by involuntary interruptions of walking, is a debilitating motor symptom of Parkinson's disease that restricts people's autonomy. Previous brain imaging studies investigating the mechanisms underlying freezing were restricted to scan people in supine positions and yielded conflicting theories regarding the role of the supplementary motor area and other cortical regions. We used functional near-infrared spectroscopy to investigate cortical haemodynamics related to freezing in freely moving people. We measured functional near-infrared spectroscopy activity over multiple motor-related cortical areas in 23 persons with Parkinson's disease who experienced daily freezing ('freezers') and 22 age-matched controls during freezing-provoking tasks including turning and doorway passing, voluntary stops and actual freezing. Crucially, we corrected the measured signals for confounds of walking. We first compared cortical activity between freezers and controls during freezing-provoking tasks without freezing (i.e. turning and doorway passing) and during stops. Secondly, within the freezers, we compared cortical activity between freezing, stopping and freezing-provoking tasks without freezing. First, we show that turning and doorway passing (without freezing) resemble cortical activity during stopping in both groups involving activation of the supplementary motor area and prefrontal cortex, areas known for their role in inhibiting actions. During these freezing-provoking tasks, the freezers displayed higher activity in the premotor areas than controls. Secondly, we show that, during actual freezing events, activity in the prefrontal cortex was lower than during voluntary stopping. The cortical relation between the freezing-provoking tasks (turning and doorway passing) and stopping may explain their susceptibility to trigger freezing by activating a stopping mechanism. Besides, the stopping-related activity of the supplementary motor area and prefrontal cortex seems to be out of balance in freezers. In this paper, we postulate that freezing results from a paroxysmal imbalance between the supplementary motor area and prefrontal cortex, thereby extending upon the current role of the supplementary motor area in freezing pathophysiology.
KW - cortical activity
KW - freezing of gait
KW - functional near-infrared spectroscopy (fNIRS)
KW - Parkinson's disease
KW - stopping
U2 - 10.1093/braincomms/fcae259
DO - 10.1093/braincomms/fcae259
M3 - Article
SN - 2632-1297
VL - 6
JO - Brain Communications
JF - Brain Communications
IS - 5
M1 - fcae259
ER -