Waiting impulsivity in progressive supranuclear palsy-Richardson's syndrome

Abstract

Background: Waiting impulsivity in progressive supranuclear palsy-Richardson's syndrome (PSP-RS) is difficult to assess, and its regulation is known to involve nucleus accumbens (NAc) subregions. We investigated waiting impulsivity using the "jumping the gun" (JTG) sign, which is defined as premature initiation of clapping before the start signal in the three-clap test and compared clinical features of PSP-RS patients with and without the sign and analyzed neural connectivity and microstructural changes in NAc subregions.

Materials and methods: A positive JTG sign was defined as the participant starting to clap before the start sign in the three-clap test. We classified participants into the JTG positive (JTG +) and JTG negative (JTG-) groups and compared their clinical features, microstructural changes, and connectivity between NAc subregions using diffusion tension imaging. The NAc was parcellated into core and shell subregions using data-driven connectivity-based methods.

Results: Seventy-seven patients with PSP-RS were recruited, and the JTG + group had worse frontal lobe battery (FAB) scores, more frequent falls, and more occurrence of the applause sign than the JTG- group. A logistic regression analysis revealed that FAB scores were associated with a positive JTG sign. The mean fiber density between the right NAc core and right medial orbitofrontal gyrus was higher in the JTG + group than the JTG- group.

Discussion: We show that the JTG sign is a surrogate marker of waiting impulsivity in PSP-RS patients. Our findings enrich the current literature by deepening our understanding of waiting impulsivity in PSP patients and introducing a novel method for its evaluation.

Keywords: diffusion tensor imaging; frontal lobe dysfunction; nucleus accumbens; progressive supranuclear palsy; waiting impulsivity.

FIGURE 1

An overview of our framework to segment the NAc into core/shell region and representative parcellation of NAc based on super-pixel clustering. A total of 77 patients with PSP-RS were enrolled in the study. We compared the demographic and clinical characteristics of the participants based on the presence of the JTG sign, with 34 classified as JTG + and 43 as JTG-. Out of the 77 participants, 44 underwent T1-weighted and DWI MRI and were included in the brain MRI analysis, with 19 classified as JTG + and 25 as JTG- (A). FreeSurfer was applied to T1-weighted MRI data to parcellate regions based on the Desikan–Killiany atlas. We used the Mrtrix3 framework to preprocess diffusion-weighted MRI data and performed anatomically constrained tractography to compute streamline density between the NAc and 14 target regions. Finally, super-pixel clustering was applied based on the streamline density with each target region to identify the core and shell regions of the left NAc and right NAc (B). In the left column of panel (C), red and green denote the core and shell subregions, respectively, of the left NAc. In the right column, blue and yellow denote the core and shell subregions, respectively, of the right NAc. The middle column shows the subregions of both the left and right NAc in an axial view (C). PSP-RS, progressive supranuclear palsy-Richardson’s syndrome; JTG, jumping the gun; AMY, amygdala; CA, caudate; CACG, caudal anterior cingulate gyrus; RACG, rostral anterior cingulate gyrus; PCG, posterior cingulate gyrus; PUT, putamen; TH, thalamus; LOFG, lateral orbitofrontal gyrus; MOFG, medial orbitofrontal gyrus; FP, frontal pole; HIP, hippocampus; IN, insula; PHG, parahippocampal gyrus; TP, temporal pole; NAc, nucleus accumbens.

FIGURE 2

The connectivity analysis showed a significant difference in the mean fiber density between the right NAc core and right MOFG in the JTG + group compared with that in the JTG- group (p = 0.001, p_FDR = 0.017). (A,C) Represent axial and sagittal images of the JTG+ group, showing the connectivity between the right NAc core and the right MOFG, as well as the right MOFG-NAc core pathway. (B,D) Display the corresponding images for the JTG- group. NAc, nucleus accumbens; MOFG, medial orbitofrontal gyrus; JTG, jumping the gun; FDR, false discovery rate.