Lesions in different prefrontal sectors are associated with different types of acquired personality disturbances

Abstract

"Frontal lobe syndrome" is a term often used to describe a diverse array of personality disturbances following frontal lobe damage. This study's guiding premise was that greater neuroanatomical specificity could be achieved by evaluating specific types of personality disturbances following acquired frontal lobe lesions. We hypothesized that three acquired personality disturbances would be associated with lesion involvement of distinct sectors of the prefrontal cortex (PFC): 1) emotional-social disturbance and ventromedial PFC, 2) hypoemotional disturbance and dorsomedial PFC, and 3) dysexecutive and dorsolateral PFC. In addition, we hypothesized that distressed personality disturbance would not be associated with focal PFC lesions in any sector. Each hypothesis was pre-registered and tested in 182 participants with adult-onset, chronic, focal brain lesions studied with an observational, cross-sectional design. Pre- and postmorbid personality was assessed by informant-rating with the Iowa Scales of Personality Change, completed by a spouse or family member. Two complementary analytic approaches were employed: 1) a hypothesis-driven region-of-interest (ROI) regression analysis examining the associations of lesions in specific PFC sectors with acquired personality disturbances; 2) a data-driven multivariate lesion-behavior mapping analysis, which was not limited to pre-specified regions. Each hypothesis received some support: (i) Emotional/social personality disturbance was most strongly associated with ventromedial PFC lesions in both statistical approaches. (ii) Hypoemotional disturbance was associated with dorsomedial PFC lesions in the ROI analyses, without any significant lesion-symptom mapping associations. (iii) Dysexecutive personality disturbance was associated with bilateral dorsolateral PFC lesions and ventromedial PFC lesions; lesion-symptom mapping showed maximal association of executive dysfunction with damage of the right middle frontal gyrus within the dorsolateral PFC. (iv) Distressed personality disturbance was not associated with lesions in any PFC sector. Altogether, the findings can be interpreted to indicate that damage to different prefrontal sectors may disrupt different anatomical-functional systems and result in distinct personality disturbances.

Keywords: Acquired personality disturbance; Hypoemotionality; Lesion mapping; Multivariate lesion-symptom mapping; Real-life functioning.

Figure 1.. Prefrontal Regions of Interest.

Prefrontal cortex was divided into three a priori ROIs prior to conducting analyses. The ventromedial PFC sector most likely includes cytoarchitectonic areas 12, 13, 14 and 25, and inferior aspects of 10, 11, 24 and 32. The dorsomedial PFC sector most likely includes medial aspects of 6, 8, 9 and 10, and superior aspects of 24 and 32. The dorsolateral PFC sector most likely includes 44, 45, 46, 47, lateral aspects of 6, 8 and 9, and superior aspects of 10 and 11. The ROIs required some manual modification to include underlying white matter, with pre-registration of the final ROIs.

Figure 2.. Lesion overlap maps.

The distribution of brain lesions from 182 participants in the analysis is displayed on a color-coded scale, with greater lesion overlap shown in yellow and red colors. Regions with the highest coverage include the prefrontal cortex and temporal lobes bilaterally.

Figure 3.. Lesion-symptom maps.

Panel A shows a region of the white matter deep to the left ventromedial PFC with the strongest association to emotional/social personality disturbance (p = 2.28 ×10⁻⁵, peak MNI coordinate −23, 49, −2). B shows a region in the right middle frontal gyrus of the dorsolateral prefrontal cortex that, when lesioned, is significantly associated with dysexecutive personality disturbance (p = 0.03, peak voxel 38, 49, 19). The color scale reflects the strength of association of anatomical regions with the respective personality disturbance score, with voxel weights distributed on a unit-less scale of 0–1 generated by the LESYMAP program to display the strength of regional associations within significant maps, which we thresholded at 0.5 to display the strongest findings within those maps. Panel C shows the distribution of lesions that intersect with the statistically significant region for dysexecutive personality disturbance (Panel B), thus contributing to that association.