Anatomical correlates of reward-seeking behaviours in behavioural variant frontotemporal dementia

Abstract

Behavioural variant frontotemporal dementia is characterized by abnormal responses to primary reward stimuli such as food, sex and intoxicants, suggesting abnormal functioning of brain circuitry mediating reward processing. The goal of this analysis was to determine whether abnormalities in reward-seeking behaviour in behavioural variant frontotemporal dementia are correlated with atrophy in regions known to mediate reward processing. Review of case histories in 103 patients with behavioural variant frontotemporal dementia identified overeating or increased sweet food preference in 80 (78%), new or increased alcohol or drug use in 27 (26%), and hypersexuality in 17 (17%). For each patient, a primary reward-seeking score of 0-3 was created with 1 point given for each target behaviour (increased seeking of food, drugs, or sex). Voxel-based morphometry performed in 91 patients with available imaging revealed that right ventral putamen and pallidum atrophy correlated with higher reward-seeking scores. Each of the reward-related behaviours involved partially overlapping right hemisphere reward circuit regions including putamen, globus pallidus, insula and thalamus. These findings indicate that in some patients with behavioural variant frontotemporal dementia, low volume of subcortical reward-related structures is associated with increased pursuit of primary rewards, which may be a product of increased thalamocortical feedback.

Keywords: alcohol; frontotemporal dementia; hypersexuality; overeating; reward processing.

Figure 1

Co-occurrence of reward seeking behaviours. Diagram shows the overlap in pursuit of the primary reward seeking behaviours overeating, drug or alcohol use, and hypersexuality. Numbers reflect number of patients exhibiting behaviours out of total n = 103.

Figure 2

Voxel-based morphometry of primary reward seeking score and of individual component behaviours. (A) T map thresholded at P_FWE < 0.05 and overlaid on MNI template brain showing single area of decreased volume in the right ventral pallidum associated with higher primary reward-seeking score, which is a composite of the presence of overeating, drug use, and hypersexuality. (B) Axial and coronal slices of T map thresholded at P < 0.001 uncorrected for multiple comparisons overlaid on MNI template brain showing—in red—areas of volume loss associated with higher primary reward seeking score. (C) Axial and coronal slices of T map thresholded at P < 0.01 uncorrected for multiple comparisons overlaid on MNI template brain showing areas of volume loss associated with the presence of individual primary reward-seeking behaviours. Blue shows hypersexuality. Green shows alcohol or drug seeking. Yellow/orange shows overeating and sweet food preference. The right side of axial and coronal images corresponds to the right side of the brain.

Figure 3

Schematic diagram of potential reward circuit abnormalities in behavioural variant FTD. Green arrows depict the direct pathway. Red arrows depict the indirect pathway. The dashed line indicates that additional synaptic connections exist between these structures but are not illustrated for simplicity. (A) Normal reward circuit connections at baseline. (B) The effect of a ventral striatal lesion on the direct pathway. (C) The effect of a ventral striatal lesion on the indirect pathway. (D) The effect of a ventral pallidum lesion.