Resting state functional brain networks associated with emotion processing in frontotemporal lobar degeneration

Abstract

This study investigated the relationship between emotion processing and resting-state functional connectivity (rs-FC) of the brain networks in frontotemporal lobar degeneration (FTLD). Eighty FTLD patients (including cases with behavioral variant of frontotemporal dementia, primary progressive aphasia, progressive supranuclear palsy syndrome, motor neuron disease) and 65 healthy controls underwent rs-functional MRI. Emotion processing was tested using the Comprehensive Affect Testing System (CATS). In patients and controls, correlations were investigated between each emotion construct and rs-FC changes within critical networks. Mean rs-FC of the clusters significantly associated with CATS scoring were compared among FTLD groups. FTLD patients had pathological CATS scores compared with controls. In controls, increased rs-FC of the cerebellar and visuo-associative networks correlated with better scores in emotion-matching and discrimination tasks, respectively; while decreased rs-FC of the visuo-spatial network was related with better performance in the affect-matching and naming. In FTLD, the associations between rs-FC and CATS scores involved more brain regions, such as orbitofrontal and middle frontal gyri within anterior networks (i.e., salience and default-mode), parietal and somatosensory regions within visuo-spatial and sensorimotor networks, caudate and thalamus within basal-ganglia network. Rs-FC changes associated with CATS were similar among all FTLD groups. In FTLD compared to controls, the pattern of rs-FC associated with emotional processing involves a larger number of brain regions, likely due to functional specificity loss and compensatory attempts. These associations were similar across all FTLD groups, suggesting a common physiopathological mechanism of emotion processing breakdown, regardless the clinical presentation and pattern of atrophy.

Fig. 1. Independent component analysis.

Relationship between resting state functional connectivity and CATS scores in healthy controls. Positive and negative relationships are shown in cold and warm colors, respectively. Results are overlaid on the Montreal Neurological Institute (MNI) standard brain and displayed at p < 0.05 Family-wise error corrected for multiple comparisons. Age at MRI, sex, education and gray matter density were included in the model as nuisance variables. rs-FC resting state functional connectivity, L Left. Color bar represents p values.

Fig. 2. Independent component analysis.

Positive relationship between resting state functional connectivity and CATS scores in FTLD patients. Positive relationships are shown in cold colors. Results are overlaid on the Montreal Neurological Institute (MNI) standard brain and displayed at p < 0.05 Family-wise error corrected for multiple comparisons. Age at MRI, sex and education were included in the model as nuisance variables. rs-FC resting state functional connectivity, L Left. Color bar represents p values.

Fig. 3. Independent component analysis.

Negative relationship between resting state functional connectivity and CATS scores in FTLD patients. Negative relationships are shown in warm colors. Results are overlaid on the Montreal Neurological Institute (MNI) standard brain and displayed at p < 0.05 Family-wise error corrected for multiple comparisons. Age at MRI, sex and education were included in the model as nuisance variables. rs-FC resting state functional connectivity, L Left. Color bar represents p values.

Fig. 4. Post-hoc functional connectivity analysis (cluster-based).

Mean rs-FC values within the basal ganglia-matching, basal ganglia-discrimination clusters and visuo-associative-naming clusters in FTLD groups. rs-FC resting state functional connectivity, VIS-ASS visuo-associative network, bvFTD behavioral variant of frontotemporal dementia, g-bvFTD behavioral variant of frontotemporal dementia with known genetic mutations, g-MND motor neuron disorders with known genetic mutations, MND Motor Neuron Disorders, PPA primary progressive aphasia, PSP progressive supranuclear palsy.