Frontotemporal dementia: A unique window on the functional role of the temporal lobes

Abstract

Frontotemporal dementia (FTD) is an umbrella term covering a plethora of progressive changes in executive functions, motor abilities, behavior, and/or language. Different clinical syndromes have been described in relation to localized atrophy, informing on the functional networks that underlie these specific cognitive, emotional, and behavioral processes. These functional declines are linked with the underlying neurodegeneration of frontal and/or temporal lobes due to diverse molecular pathologies. Initially, the accumulation of misfolded proteins targets specifically susceptible cell assemblies, leading to relatively focal neurodegeneration that later spreads throughout large-scale cortical networks. Here, we discuss the most recent clinical, neuropathological, imaging, and genetics findings in FTD-spectrum syndromes affecting the temporal lobe. We focus on the semantic variant of primary progressive aphasia and its mirror image, the right temporal variant of FTD. Incipient focal atrophy of the left anterior temporal lobe (ATL) manifests with predominant naming, word comprehension, reading, and object semantic deficits, while cases of predominantly right ATL atrophy present with impairments of socioemotional, nonverbal semantic, and person-specific knowledge. Overall, the observations in FTD allow for crucial clinical-anatomic inferences, shedding light on the role of the temporal lobes in both cognition and complex behaviors. The concerted activity of both ATLs is critical to ensure that percepts are translated into concepts, yet important hemispheric differences should be acknowledged. On one hand, the left ATL attributes meaning to linguistic, external stimuli, thus supporting goal-oriented, action-related behaviors (e.g., integrating sounds and letters into words). On the other hand, the right ATL assigns meaning to emotional, visceral stimuli, thus guiding socially relevant behaviors (e.g., integrating body sensations into feelings of familiarity).

Keywords: Behavioral variant frontotemporal dementia; Right temporal lobe neurodegeneration; Semantic dementia; Semantic variant primary progressive aphasia.

Fig. 24.1.

Patterns of neurodegeneration in frontotemporal dementias. Example of atrophy maps in one single patient for each variant of frontotemporal dementia (FTD): (A) semantic variant of primary progressive aphasia (svPPA); (B) right temporal variant of FTD; (C) behavioral variant of FTD; and (D) nonfluent variant of primary progressive aphasia (nfvPPA). The color scale indicates W-values: i.e., deviations from controls, with values below −1.5 indicating clinically abnormal regions (below the seventh percentile compared to healthy controls).

Fig. 24.2.

(A) Binary map showing significant atrophy in TDP-43-C driven ATL neurodegeneration with predominantly left (top row) vs. right (bottom row) distribution. (B) Binary map showing atrophy progression in a case of predominantly R temporal atrophy. (C) Example of the key differences between L and R ATLs functions: regions associated with famous face recognition performance (yellow) and naming performance (purple). Panel (A) Adapted from the data published in Borghesani V, Battistella G, Mandelli ML et al. (2020a). Regional and hemispheric susceptibility of the temporal lobe to FTLD-TDP type C pathology. NeuroImage Clin 28: 102369. Panel (B) Adapted from the data published in Vonk JM, Borghesani V, Battistella G et al. (2020). Verbal semantics and the left dorsolateral anterior temporal lobe: a longitudinal case of bilateral temporal degeneration. Aphasiology 34: 865–885. Panel (C) Adapted from the data published in Borghesani V, Narvid J, Battistella G et al. (2019). “Looks familiar, but I do not know who she is”: the role of the anterior right temporal lobe in famous face recognition. Cortex 115: 72–85.

Fig. 24.3.

(A) MEG evidence of svPPA over-recruitment of dorsal cortices to read irregular words. (B) MEG evidence of svPPA over-recruitment of occipital cortices to perform semantic categorization. (C) MEG evidence of how perceptual processing (i.e., word processing in vwfa) is unaltered in svPPA patients as compared with healthy controls (left), while higher level of linguistic processing (i.e., irregular words reading in IPL) show marked deviation (right). Panel (A) Adapted from the data published in Borghesani V, Hinkley LB, Ranasinghe KG et al. (2020b). Taking the sublexical route: brain dynamics of reading in the semantic variant of primary progressive aphasia. Brain 143: 2545–2560. Panel (B) Adapted from the data published in Borghesani V, Dale CL, Lukic S, et al. (2021). Neural dynamics of semantic categorization in semantic variant of Primary Progressive Aphasia. eLife 10: e63905. Panel (C) Unpublished data from Borghesani V, Hinkley LB, Ranasinghe KG et al. (2020b). Taking the sublexical route: brain dynamics of reading in the semantic variant of primary progressive aphasia. Brain 143: 2545–2560.

Fig. 24.4.

The left ATL assigns meaning to verbal, linguistic, external inputs: it integrates sounds and letters into words, supporting and enabling goal-oriented, action-related behaviors. The right ATL assigns meaning to nonverbal, social, visceral inputs: it integrates feelings and sensations into emotions, attributing values to personally and socially relevant behaviors.