Objective.
Some neurodegenerative diseases, such as amyotrophic lateral sclerosis and Parkinson’s disease, present as diseases of one or more functionally homogeneous neural systems.
Some of the regions known to be atrophic in frontotemporal dementia (FTD) belong to the rostral limbic system (RLS), which connects the orbitofrontal, anterior cingulate, anterior insular cortex, the amygdala, the ventral striatum and the periaqueductal gray. The RLS is considered to process the motivational and emotional content of internal and external stimuli and to regulate context-dependent behaviors. The clinical manifestation of FTD is compatible with disruption of this system.
Objective of this study was to investigate whether frontotemporal dementia (FTD) might have characteristics of a disease of neural systems guiding behavior, such as the RLS.

Materials and methods.
Nine patients with FTD and 26 healthy controls underwent high resolution 3D brain magnetic resonance imaging. Statistical parametric mapping (SPM99) algorithms performed a) spatial normalization to a Talairach-based template, b) segmentation c) smoothing of the gray matter, and d) voxel by voxel comparison of gray matter concentration between cases and controls. P values were set at <0.05 corrected for multiple comparisons.

Results.
All but one (the periaqueductal gray) regions of the rostral limbic system were found to be significantly atrophic in FTD. The periaqueductal gray displayed significant atrophy at p<0.001 uncorrected. Atrophy outside the rostral limbic system was confined to small isolated regions in the frontal and temporal gyri.

Conclusions.
All regions known to belong to the rostral limbic system were atrophic in FTD. On the contrary, atrophy outside this system was confined to small isolated regions. FTD might be considered a neural system disease where the rostral limbic system is specifically damaged, leading to the observed clinical phenotype, and particularly to behavioral disturbances.