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The fronto-parietal connectivity in freezing of gait: a left/right imbalance ?
Céline Tard1, Caroline Moreau2, Romain Viard3, Christine Delmaire2, David Devos2, Pierre Lenfant2, Kathy Dujardin2, Luc Defebvre2, Arnaud Delval2, and Renaud Lopes2

1Neurology Department, Lille University Hospital Center, Lille, France, 2Lille University Hospital Center, Lille, France, 3Radiology Department, Lille University Hospital Center, Lille, France

Synopsis

The multimodal MRI assessment is here used to better understand the previous known parietoprefrontal networks' abnormalities in parkinsonian patients with freezing of gait. Anatomic disconnection was observed in the right prefrontal cortex in those patients and functional disconnection was major from the left one. The imbalance between left and right networks is discussed heyard the pathophysiology of freezing.

Background

Freezing of gait in Parkinson's disease is a paroxysmal gait dysfunction, marked by the absence of the forward progression of the foot, despite the intention to walk, with a high risk of fall [1]. Concerning its pathophysiology, it seems to result from the episodic overload of motor and cognitive circuits. Parieto-frontal networks are involved in visuo-driven locomotion and could be a key structure to explain this phenomenon. Previously we demonstrated that the frontal areas of this network were hypometabolic during gait in parkinsonian patients with freezing of gait, while parietal ones were hypermetabolic [2].

Objective

Our objective was to clarify the cerebral dysfunction of the frontal premotor regions in parkinsonian freezers.

Methods

Resting-state MRI was performed in 10 freezer and 14 non-freezer patients matched for disease severity and cognitive status. Freezer patients were known to present hypometabolism of frontal areas during gait. Atrophy measures, anatomical connectivity (with ROIs in premotor and frontal eye field areas, and whole brain connectivity) and functional connectivity (from the same ROIs) were studied.

Results

We found orbitofrontal atrophy in freezers patients. Concerning white matter, the premotor areas were anatomically disconnected from the cortical and subcortical structures, namely from the right FEF (only a tendency from left PMc). Then, functional MRI studies revealed a functional disconnection of the prefrontal cortex in FoG patients, at least from the left premotor cortex. Connectivity from the right FEF was preserved in the FoG group, contrasting with anatomic results.

Conclusions

Multimodal imaging techniques helped us to better characterize the involvement of the prefrontal cortex in freezing. Atrophy was described in the orbitofrontal area, whereas white matter lesions were preponderant in the right prefrontal cortex and functional disconnection was major from the left one.

The destructuration of the right parieto-frontal network prevents the equilibrium between left and right networks. The anatomic disruption of the right parieto-frontal in freezers could enhance its dominance on the left parietofrontal network, via interhemispheric inhibitions. This imbalance between these two circuits could explain the preponderance of stimulus-driven attention on goal-driven attention in freezers [3].

Acknowledgements

No acknowledgement found.

References

[1] Nutt JG, Bloem BR, Giladi N, Hallett M, Horak FB, Nieuwboer A. Freezing of gait: moving forward on a mysterious clinical phenomenon. Lancet Neurol. 2011 Aug;10(8):734-44.

[2] Tard C, Delval A, Devos D, Lopes R, Lenfant P, Dujardin K, Hossein-Foucher C, Semah F, Duhamel A, Defebvre L, Le Jeune F, Moreau C. Brain metabolic abnormalities during gait with freezing in Parkinson's disease. Neuroscience. 2015 Oct 29;307:281-301

[3] Corbetta M, Patel G, Shulman GL. The reorienting system of the human brain: from environment to theory of mind. . Neuron. 2008 May 8;58(3):306-24

Figures

Figure 1: Box plots (median, 1st and 3rd quartiles) of fibers density and mean fractional anisotropy per fiber: *: p<0.005

Figure 2: Probabilistic tractography from the right premotor cortex of two subjects; all fibres passing through this ROI are represented. The colour scale shows the fractional anisotropy per fibre. The upper and lower rows of images show representative data from a patient in the freezing-group and a patient from the non-freezing group, respectively.

Figure 3: Results of TBSS analysis. In white, you can see the FA skeleton of white matter mapping from the mean FA from all patients in both groups. In yellow-red scale are represented significant tracts (p<0.05, TFCE corrected) where FA is higher in the non-FoG group than in the FoG group, mainly in the right cortico-spinal tract, corpus callosum and frontoparietal regions (superior longitudinal fasciculus). No voxel was significant for reduced FA in non-freezing group compared with freezing group. The significant voxels are inflated for ease of viewing. In blue are represented the rPM. Note the continuity of this gray matter ROI and the statistically anatomic hypoconnectivity of frontoparietal tract in the freezing-group, in whole brain analysis.

Figure 4: Significant functional connectivity for the right premotor cortex, in the freezing group on the first line and in the non-freezing group in the second line. In the indicated regions, the BOLD signal varied with the BOLD signal in the right premotor cortex. A p-value of 0.005 uncorrected was used for display purpose. The colour scales correspond to the T-scores. Note the more widespread functional connectivity in the freezing group between the right premotor cortex on one hand and the right insula and the right on the other.

Figure 5: Significant functional connectivity for the left premotor cortex, in the freezing group on the first line and in the non-freezing group in the second line. In the indicated regions, the BOLD signal varied with the BOLD signal in the left premotor cortex. A p-value of 0.005 uncorrected was used for display purpose. The colour scales correspond to the T-scores. Note the more widespread functional connectivity in the non-FoG group between the left premotor cortex on one hand and the cerebellum, basal ganglia, the contralateral premotor cortex and the auditory cortex on the other.

Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)
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