Abstract
Freezing of gait (FoG) is a transient inability to initiate or maintain stepping that often accompanies advanced Parkinson’s disease (PD) and significantly impairs mobility. The current study uses a multimodal neuroimaging approach to assess differences in the functional and structural locomotor neural network in PD patients with and without FoG and relates these findings to measures of FoG severity. Twenty-six PD patients and fifteen age-matched controls underwent resting-state functional magnetic resonance imaging and diffusion tensor imaging along with self-reported and clinical assessments of FoG. After stringent movement correction, fifteen PD patients and fourteen control participants were available for analysis. We assessed functional connectivity strength between the supplementary motor area (SMA) and the following locomotor hubs: 1) subthalamic nucleus (STN), 2) mesencephalic and 3) cerebellar locomotor region (MLR and CLR, respectively) within each hemisphere. Additionally, we quantified structural connectivity strength between locomotor hubs and assessed relationships with metrics of FoG. FoG+ patients showed greater functional connectivity between the SMA and bilateral MLR and between the SMA and left CLR compared to both FoG− and controls. Importantly, greater functional connectivity between the SMA and MLR was positively correlated with i) clinical, ii) self-reported and iii) objective ratings of freezing severity in FoG+, potentially reflecting a maladaptive neural compensation. The current findings demonstrate a re-organization of functional communication within the locomotor network in FoG+ patients whereby the higher-order motor cortex (SMA) responsible for gait initiation communicates with the MLR and CLR to a greater extent than in FoG− patients and controls. The observed pattern of altered connectivity in FoG+ may indicate a failed attempt by the CNS to compensate for the loss of connectivity between the STN and SMA and may reflect a loss of lower-order, automatic control of gait by the basal ganglia.
Highlights
Balance and gait are impaired in the majority of older people, especially those with age-related, neurological degeneration such as Parkinsonism
The overall pattern of these results demonstrated a reorganization of functional communication within the locomotor network in freezing of gait (FoG)+ patients whereby the supplementary motor area (SMA) communicated with the MLR and CLR to a greater extent than in control participants or FoG2 PD patients
The current findings demonstrate a reorganization of functional communication within the locomotor network in FoG+ patients whereby the higher order motor cortex (SMA) responsible for gait initiation communicates with the MLR and CLR to a greater extent than for FoG2 or controls
Summary
Balance and gait are impaired in the majority of older people, especially those with age-related, neurological degeneration such as Parkinsonism. Freezing episodes have typically been reported in relation to repetitive lower limb movements; an emerging body of literature reports upper limb freezing within these same patients [2]. Freezing of the upper and/or lower limb(s) significantly impairs mobility and limits independent function, but the neural underpinnings of freezing episodes remain poorly understood. A growing body of work suggests that these deficits in upper and lower limb movements require increased cognitive control of previously automated actions [3]. Recent work suggests that dysfunction of top-down inhibitory control may serve a critical role in disorders of movement initiation observed in AHDH, Huntington disease, schizophrenia and PD [4]
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