Neuroimaging of Freezing of Gait

Abstract

Functional brain imaging techniques appear ideally suited to explore the pathophysiology of freezing of gait (FOG). In the last two decades, techniques based on magnetic resonance or nuclear medicine imaging have found a number of structural changes and functional disconnections between subcortical and cortical regions of the locomotor network in patients with FOG. FOG seems to be related in part to disruptions in the "executive-attention" network along with regional tissue loss including the premotor area, inferior frontal gyrus, precentral gyrus, the parietal and occipital areas involved in visuospatial functions of the right hemisphere. Several subcortical structures have been also involved in the etiology of FOG, principally the caudate nucleus and the locomotor centers in the brainstem. Maladaptive neural compensation may present transiently in the presence of acute conflicting motor, cognitive or emotional stimulus processing, thus causing acute network overload and resulting in episodic impairment of stepping.In this review we will summarize the state of the art of neuroimaging research for FOG. We will also discuss the limitations of current approaches and delineate the next steps of neuroimaging research to unravel the pathophysiology of this mysterious motor phenomenon.

Keywords: Freezing of gait; Parkinson’s disease; magnetic resonance imaging; positron emission tomography; single photon emission computed tomography.

Fig.1

Proportion of freezers in subgroups of patients with absence, single or combined presence of cortical amyloidopathy and/or cholinopathy (reproduced with permission from [16]).

Fig.2

Areas of gray matter atrophy derived from a voxel-based morphometric direct comparison between PD patients with FOG (n = 22) and PD patients without FOG (n = 22). The GM maps were analyzed using analysis of variance (ANOVA) as implemented in SPM5. The model was adjusted for age and disease duration. The results are superimposed in representative sagittal and axial sections of a customized gray matter template, at a threshold of p <  0.005, uncorrected cluster size >50.  ^*indicates p <  0.05, cluster level corrected. Note that if we applied FWE correction on the contrasts maps, the group differences were no longer significant. Significantly lower values of GM in the freezers compared to the non-freezers were observed in the precuneus, frontal gyrus/supplementary motor area, cerebellum declive and middle temporal gyrus (p <  0.005, uncorrected). In addition, in the left IPL and the right angular gyrus, significant differences were found when correcting for multiple comparisons (p <  0.015, cluster level corrected). IFG = inferior frontal gyrus; SMA = supplementary motor area; IPL = inferior parietal lobe; MTG = middle temporal gyrus.