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Functional reorganization of the locomotor network in Parkinson patients with freezing of gait.

Fling BW, Cohen RG, Mancini M, Carpenter SD, Fair DA, Nutt JG, Horak FB - PLoS ONE (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, School of Medicine, Oregon Health & Science University, Portland, Oregon, United States of America.

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.

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Associations between locomotor network functional connectivity and freezing severity.A) Functional connectivity strength of the lMLR – SMA loop was positively correlated with clinical rating of FoG severity during the single task turning condition (r = 0.71). B) Functional connectivity strength of the rMLR – SMA loop was also positively correlated with objective sensor measurement of FoG severity during dual-task turning (0.76).
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pone-0100291-g005: Associations between locomotor network functional connectivity and freezing severity.A) Functional connectivity strength of the lMLR – SMA loop was positively correlated with clinical rating of FoG severity during the single task turning condition (r = 0.71). B) Functional connectivity strength of the rMLR – SMA loop was also positively correlated with objective sensor measurement of FoG severity during dual-task turning (0.76).

Mentions: Seed pairings demonstrating group differences in functional connectivity strength were analyzed for relationships with metrics of freezing (see Table 2 for all relationships). Briefly, higher functional connectivity between the lMLR-SMA pair (Figure 5), as well as between the lCLR – SMA pair, was strongly correlated with higher clinical ratings of FoG and self-reported NFOGQ scores in FoG+. Similarly, the higher functional connectivity between the rMLR – SMA pair was strongly related with higher Freezing Ratio during turning under the dual task condition in FoG+ (Figure 5). It is worth noting that disease duration was not related to functional connectivity strength for any of the identified seed pairings, nor were any significant relationships between structural connectivity strength and measures of freezing found.


Functional reorganization of the locomotor network in Parkinson patients with freezing of gait.

Fling BW, Cohen RG, Mancini M, Carpenter SD, Fair DA, Nutt JG, Horak FB - PLoS ONE (2014)

Associations between locomotor network functional connectivity and freezing severity.A) Functional connectivity strength of the lMLR – SMA loop was positively correlated with clinical rating of FoG severity during the single task turning condition (r = 0.71). B) Functional connectivity strength of the rMLR – SMA loop was also positively correlated with objective sensor measurement of FoG severity during dual-task turning (0.76).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061081&req=5

pone-0100291-g005: Associations between locomotor network functional connectivity and freezing severity.A) Functional connectivity strength of the lMLR – SMA loop was positively correlated with clinical rating of FoG severity during the single task turning condition (r = 0.71). B) Functional connectivity strength of the rMLR – SMA loop was also positively correlated with objective sensor measurement of FoG severity during dual-task turning (0.76).
Mentions: Seed pairings demonstrating group differences in functional connectivity strength were analyzed for relationships with metrics of freezing (see Table 2 for all relationships). Briefly, higher functional connectivity between the lMLR-SMA pair (Figure 5), as well as between the lCLR – SMA pair, was strongly correlated with higher clinical ratings of FoG and self-reported NFOGQ scores in FoG+. Similarly, the higher functional connectivity between the rMLR – SMA pair was strongly related with higher Freezing Ratio during turning under the dual task condition in FoG+ (Figure 5). It is worth noting that disease duration was not related to functional connectivity strength for any of the identified seed pairings, nor were any significant relationships between structural connectivity strength and measures of freezing found.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, School of Medicine, Oregon Health & Science University, Portland, Oregon, United States of America.

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.

Show MeSH
Related in: MedlinePlus