Open AccessIdentifying the neural correlates of doorway freezing in Parkinson's disease
Author(s) -
Matar Elie,
Shine James M.,
Gilat Moran,
Ehgoetz Martens Kaylena A.,
Ward Philip B.,
Frank Michael J.,
Moustafa Ahmed A.,
Naismith Sharon L.,
Lewis Simon J. G.
Publication year - 2019
Publication title -
human brain mapping
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.005
H-Index - 191
eISSN - 1097-0193
pISSN - 1065-9471
DOI - 10.1002/hbm.24506
Subject(s) - functional magnetic resonance imaging , neuroscience , parkinson's disease , subthalamic nucleus , latency (audio) , gait , neural correlates of consciousness , functional connectivity , psychology , magnetic resonance imaging , task (project management) , cognition , physical medicine and rehabilitation , disease , medicine , computer science , deep brain stimulation , pathology , telecommunications , radiology , management , economics
Freezing of gait (FOG) in Parkinson's disease (PD) is frequently triggered upon passing through narrow spaces such as doorways. However, despite being common the neural mechanisms underlying this phenomenon are poorly understood. In our study, 19 patients who routinely experience FOG performed a previously validated virtual reality (VR) gait paradigm where they used foot‐pedals to navigate a series of doorways. Patients underwent testing randomised between both their “ON” and “OFF” medication states. Task performance in conjunction with blood oxygenation level dependent (BOLD) signal changes between “ON” and “OFF” states were compared within each patient. Specifically, as they passed through a doorway in the VR environment patients demonstrated significantly longer “footstep” latencies in the OFF state compared to the ON state. As seen clinically in FOG this locomotive delay was primarily triggered by narrow doorways rather than wide doorways. Functional magnetic resonance imaging revealed that footstep prolongation on passing through doorways was associated with selective hypoactivation in the presupplementary motor area (pSMA) bilaterally. Task‐based functional connectivity analyses revealed that increased latency in response to doorways was inversely correlated with the degree of functional connectivity between the pSMA and the subthalamic nucleus (STN) across both hemispheres. Furthermore, increased frequency of prolonged footstep latency was associated with increased connectivity between the bilateral STN. These findings suggest that the effect of environmental cues on triggering FOG reflects a degree of impaired processing within the pSMA and disrupted signalling between the pSMA and STN, thus implicating the “hyperdirect” pathway in the generation of this phenomenon.