Neurophysiological Correlates of Positive and Negative Symptoms in Frontotemporal Dementia

BACKGROUND: The neural correlates of behavioral symptoms in frontotemporal dementia (FTD) are still to be elucidated. Neurotransmitter abnormalities could be correlated to the pathophysiology of negative and positive symptoms in FTD. OBJECTIVE: To evaluate if the imbalance between inhibitory and excitatory cortical circuits, evaluated with transcranial magnetic stimulation (TMS), correlate with the magnitude of negative and positive symptoms, as measured by Frontal Behavioral Inventory (FBI) scores, in patients with FTD. METHODS: Paired-pulse TMS was used to investigate the activity of different intracortical circuits in 186 FTD patients (130 bvFTD, 35 avPPA, 21 svPPA). We applied short interval intracortical inhibition (SICI - GABAAergic transmission), intracortical facilitation (ICF - glutamatergic transmission), long interval intracortical inhibition (LICI - GABABergic transmission), and short latency afferent inhibition (SAI - cholinergic transmission). Linear and stepwise multiple regression analysis were used to determine the contribution of each neurophysiological measures to the total variance of FBI scores. RESULTS: At the stepwise multivariate analysis, we observed a significant negative correlation between FBI-A scores (negative symptoms) and ICF (β = -0.57, p < 0.001, adjusted R2 = 0.32). For FBI-B scores (positive symptoms), we observed a significant positive correlation for SICI (β = 0.84, p < 0.001, adjusted R2 = 0.56). Significant correlations were observed for single items of the FBI-A score with ICF and FBI-B scores with SICI, with a medium-large size effect for several items. CONCLUSIONS: The present study shows that the imbalance between inhibitory and excitatory intracortical circuits, evaluated with TMS, correlated with the magnitude of negative and positive symptoms in FTD, respectively.