Brain architecture changes across the FTLD spectrum

Abstract Background To explore structural/functional MRI connectomic features of the motor neuron disease (MND) and behavioral variant of frontotemporal dementia (bvFTD) spectrum. Method 115 MND (including amyotrophic lateral sclerosis [ALS] and primary lateral sclerosis), 35 bvFTD patients and 61 controls underwent clinical/cognitive and MRI evaluations. MND patients were divided in 79 pure‐motor (MND‐motor) and 36 cognitive/behavioral impaired (MND‐ci/bi). A sub‐analysis was performed on ALS patients only (54 ALS‐motor, 21 ALS‐ci/bi and 8 ALS‐FTD). Graph analysis and connectomics assessed structural/functional topological network properties at global, lobar and regional level. Result Globally, bvFTD showed altered structural and functional network properties compared to all other groups. At lobar level, bvFTD showed altered structural and functional network properties within the frontotemporal and basal ganglia areas relative to all groups. Structural alterations in the parietal lobe discriminated bvFTD from controls and MND‐motor only. MND groups showed altered structural properties within sensorimotor and basal ganglia areas relative to controls. Regionally, bvFTD showed widespread structural damage and decreased functional connectivity relative to all groups. MND showed disrupted structural architecture and enhanced functional connectivity within sensorimotor, basal ganglia and frontotemporal areas relative to controls. Similar results have been found in ALS sub‐analysis. Conclusion The disruption of the structural architecture in MND worsens in relation with cognitive deficits. Functional changes are characterized by enhanced functional connectivity in presence of exclusive motor impairment that intensifies with the occurrence of cognitive impairment in MND. The Italian Ministry of Health (GR‐2011‐02351217; GR‐2013‐02357415; RF‐2011‐02351193), AriSLA (ConnectALS), European Research Council (StG‐2016_714388_NeuroTRACK).