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DTI Analysis of Cerebro-Ponto-Cerebellar Pathways in Pseudobulbar Affect

Rohan Katipally Photo

Brown University (Rhode Island)


Pseudobulbar affect (PBA) is a disorder described by laughter or crying that is often exaggerated or incongruent to the patient’s true emotional state. While PBA is common in many neurological disorders, the precise neural circuits that cause it are still unknown. Studies have suggested that lesions in the cerebellum and basis pontis may be involved. In a recent hypothesis, Parvizi et al. proposed that disruptions to cerebro-ponto-cerebellar pathways lead to PBA because the cerebellum normally modulates emotional expression. The purpose of this study is to compare the integrity of the cerebro-ponto-cerebellar pathways in patients with and without PBA. Diffusion tensor imaging (DTI) is an advanced neuroimaging technique that allows us to evaluate white matter integrity.


From our pool of PLS/ALS patients and healthy volunteers, 3T MRIs and DTI for 22 patients with PBA, 25 patients without PBA, and 28 age-matched controls were selected. Tensor calculation, skull stripping, and DTI processing were performed in MRIStudio and Tortoise. Mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), and fractional anisotropy (FA) maps were created for each patient.

Voxel-wise comparison of white matter via tract-based spatial statistics (TBSS) was performed in FSL. Statistics were computed with Randomise (10000 permutations) with threshold-free cluster enhancement (TFCE) and family-wise error rate correction, adjusting for age. Atlas-based analysis was performed after segmentation in ROIEditor with the White Matter Parcellation Map Type II. The mean DTI metrics were compared between groups with statistical software, adjusting for age with post-hoc Tukey correction for multiple comparisons. 


White matter differences were observed between patients with and without PBA. After TBSS analysis, patients with PBA demonstrated greater MD (TFCE + FWE corrected) and RD (TFCE) in the cerebellum, transverse pontine fibers, middle cerebellar peduncle (MCP), anterior limb of the internal capsule (ALIC), cingulum, and frontal areas. Patients with PBA also exhibited greater AD (TFCE) in the MCP. Negligible changes in FA (TFCE) were observed between patient groups in cerebro-ponto-cerebellar pathways. Limbic areas, e.g. the fornix, showed greater MD and the ALIC displayed greater AD in patients with PBA compared to controls, while they did not in patients without PBA compared to controls.

In atlas-based analysis, the superior longitudinal fasciculus (SLF), an association tract, displayed reduced FA in PBA patients compared to controls, while it did not in non-PBA patients compared to controls. Additionally, the MD in the SLF, RD in the ALIC, and the AD in the pontine crossing tract exhibited more significant increases in PBA patients versus controls than in non-PBA patients versus controls.


DTI findings in our study may reveal white matter damage, such as deafferentation of cerebro-ponto-cerebellar pathways in PBA, particularly at the MCP, transverse pontine fibers, and cerebellum. The cerebellum has been implicated in emotional processing and shown to receive afferents from telencephalic regions, such as limbic and frontal areas. While the cerebellum has largely been associated with motor function, it also appears to influence emotional processing and modulation.

Last Modified November 26, 2013