Freezing of gait is associated with cortical thinning in mesial frontal cortex

Abstract

Aims.The relationship between freezing of gait (FOG) and regional brain atrophy has been intensively investigated, but it is still not clearly understood. The study objective was to test whether grey matter (GM) atrophy contributes to FOG in Parkinson´s disease (PD) using a surface-based algorithm. Methods. We investigated 21 patients with PD, 11 with FOG and 10 without FOG. Both groups were assessed using a FOG questionnaire and Hoehn and Yahr staging. High resolution T1-weighted brain images were acquired for each subject using a 1.5T MRI scanner. A surface-based method implemented in FreeSurfer was used to quantify the GM atrophy. A vertex-wise and region of interest (ROI) comparison of spatially normalized subject data using a general linear model and the Wilcoxon rank sum test were to assess significant group differences. Results. Higher global levels of cortical atrophy were detected in freezers, although this was not statistically significant. The vertex-wise analysis revealed significant local reduction in grey matter thickness in the left supplementary motor area, m iddle/anterior cingulate cortex, temporal pole and right frontal operculum in freezers at P<0.001, uncorrected. The ROI analysis of average thickness confirmed the regional atrophy in bilateral anterior and posterior cingulate cortices. No significant relative regional cortical atrophy was observed in non-freezers. Conclusion. FOG was associated with regional cortical atrophy, especially in mesial frontal and cingulate cortices. Our findings provide additional evidence that the development of FOG in patients with PD is associated with local structural cortical changes.

Changes in Cortical Thickness in Patients With Early Parkinson’s Disease at Different Hoehn and Yahr Stages

“… Pietracupa et al (2017) found that PD patients with FOG exhibit significant changes in WM and cortical thinning of the mesial surface of the bilateral cerebral hemispheres. Vastik et al (2017) found that FOG was associated with regional GM atrophy in the mesial frontal and cingulate cortices. Consistent with our results, the thickness of the posterior cingulate cortex and the temporal cortex were correlated with H-Y stages.…”

Neuroimaging advances in Parkinson's disease with freezing of gait: A systematic review

“…(2015)17 PD-FOG (57±7) 21 PD-nFOG (47±9)VBMGM volumeGM loss in right cerebellum, medial frontal, precentral cortex, and left middle temporal gyrusNot performedMyers et al. (2017)25 PD-FOG (67±10) 38 PD-nFOG (64±10)VBMCerebellar volumesNo GM lossNo correlationVastik et al. (2017)11 PD-FOG (71±6) 10 PD-nFOG (69±10)SBMGM thicknessGM loss in left SMA, anterior cingulate cortex, temporal pole and right frontal operculumNo correlationBharti et al.…”

“…SBM provides cortical thickness and surface area measures (Fischl, 2012). Only two recent studies (Pietracupa et al., 2018; Vastik et al., 2017) have investigated possible GM changes in PD-FOG using the SBM technique and both demonstrated prominent cortical thinning in frontoparietal regions of the medial wall in PD-FOG.…”

“…This hypothesis is consistent with the clinical observation that in PD, FOG commonly occurs in the presence of challenging environmental conditions such as passage through a narrow space (Almeida and Lebold, 2010), while turning (Spildooren et al., 2013), during a dual task, or while trying to avoid obstacles (Jacobs et al., 2009; Lewis and Barker, 2009; Snijders et al., 2010; Spildooren et al., 2010). Several neuroimaging studies in PD-FOG have reported structural and functional changes in the SMA (Fling et al., 2014; Snijders et al., 2011; Vastik et al., 2017; Vercruysse et al., 2015). The SMA is thought to play a key role in gait control since it encodes specific sequences of movement and generates anticipatory postural adjustments (APAs) (Massion, 1992).…”

“…A final comment concerns a third set of studies on PD-FOG that demonstrates structural and functional changes in brain areas included in the limbic system such as the cingulate cortex and amygdala (Gilat et al., 2018; Vastik et al., 2017). Clinical studies have disclosed that anxiety and depression are common non-motor features in PD-FOG that crucially contribute to FOG occurrence (Martens et al., 2014).…”