Looking beneath the surface: the importance of subcortical structures in frontotemporal dementia

Abstract

Whilst initial anatomical studies of frontotemporal dementia focussed on cortical involvement, the relevance of subcortical structures to the pathophysiology of frontotemporal dementia has been increasingly recognized over recent years. Key structures affected include the caudate, putamen, nucleus accumbens, and globus pallidus within the basal ganglia, the hippocampus and amygdala within the medial temporal lobe, the basal forebrain, and the diencephalon structures of the thalamus, hypothalamus and habenula. At the most posterior aspect of the brain, focal involvement of brainstem and cerebellum has recently also been shown in certain subtypes of frontotemporal dementia. Many of the neuroimaging studies on subcortical structures in frontotemporal dementia have been performed in clinically defined sporadic cases. However, investigations of genetically- and pathologically-confirmed forms of frontotemporal dementia are increasingly common and provide molecular specificity to the changes observed. Furthermore, detailed analyses of sub-nuclei and subregions within each subcortical structure are being added to the literature, allowing refinement of the patterns of subcortical involvement. This review focuses on the existing literature on structural imaging and neuropathological studies of subcortical anatomy across the spectrum of frontotemporal dementia, along with investigations of brain-behaviour correlates that examine the cognitive sequelae of specific subcortical involvement: it aims to 'look beneath the surface' and summarize the patterns of subcortical involvement have been described in frontotemporal dementia.

Keywords: MR imaging; frontotemporal dementia; subcortical structures.

Graphical Abstract

Figure 1

Subcortical structures involved in frontotemporal dementia. Structures are grouped and coloured based on their location and anatomical organization. The basal ganglia include the striatum (nucleus accumbens, caudate and putamen), the globus pallidus, substantia nigra and subthalamic nucleus. The amygdala and hippocampus are located in the medial temporal lobe, while the thalamus, hypothalamus and habenula are part of the diencephalon. Below the cerebrum, lie the cerebellum and brainstem (midbrain, pons and medulla oblongata).

Figure 2

Overview of the involvement of the subcortical structures in the clinical, genetic and pathological groups of FTD.