Aims

To explore stepwise functional connectivity (SFC) rearrangements in patients affected by frontotemporal lobar degeneration (FTLD) variants.

Methods

Patients with behavioral variant of frontotemporal dementia (bvFTD, n=26), nonfluent (nfvPPA, n=11) or semantic variant of primary progressive aphasia (svPPA, n=14) underwent clinical evaluation and 3T MRI scan. For each subgroup, cortical thickness was assessed, in order to identify the peak of atrophy (here considered as the disease epicenter), when compared with 37 age- and sex-matched healthy controls. These areas were used as seed regions for the subsequent SFC analyses.

Results

The selected seed regions were the right orbitofrontal cortex for bvFTD, left supplementary motor area for nfvPPA, and left temporal pole for svPPA. Compared with controls, all three patient groups showed decreased SFC in widespread regions with direct/intermediate connections with the respective seed regions. bvFTD and nfvPPA patients also showed increased SFC within the brain regions closest to the respective seed region and homologous contralateral cortices at one link-step. At further link-steps, SFC increase was also observed in the posterior cerebellum of bvFTD and nfvPPA patients, and the superior frontal cortex of svPPA patients.

Conclusions

Our findings indicate an increase in the short-range direct connectivity around the disease epicenters of FTLD, probably as a compensation for neurodegeneration, in contrast with widespread functional rearrangements that characterize each phenotype across different link-steps. This was the first study exploring SFC in FTLD, opening promising perspectives to understand the physiopathological underpinnings of these presentations and model disease evolution.

Supported by: European Research Council (StG-2016_714388_NeuroTRACK).