Neurotransmitter imbalance dysregulates brain dynamic fluidity in frontotemporal degeneration

Alberto Benussi, Enrico Premi, Stefano Gazzina, Valentina Cantoni, Maria Sofia Cotelli, Marcello Giunta, Roberto Gasparotti, Vince D. Calhoun, Barbara Borroni

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Frontotemporal degeneration (FTD) is characterized by reduced global brain flexibility along with GABAergic/glutamatergic neurotransmitter deficits. We aimed to assess the relationship between dynamical properties of time-varying whole-brain network connectivity as well as static large-scale networks and neurotransmitter imbalance using resting-state functional MRI and transcranial magnetic stimulation (TMS) in sixty-six patients with FTD. We assessed GABAergic and glutamatergic neurotransmission by TMS, considering short- and long-interval intracortical inhibition and intracortical facilitation, and large-scale networks connectivity as well as four indexes of meta-state dynamic fluidity: (1) number of distinct meta-states, (2) number of switches from one meta-state to another, (3) span of the realized meta-states, and (4) total distance traveled in the state space. No significant correlations between TMS parameters and large-scale networks connectivity were observed. However, we observed a significant correlation between short-interval intracortical inhibition–intracortical facilitation and four meta-states (all indexes p < 0.02, false discovery rate-corrected). This study suggests that neurotransmitter imbalance dysregulates brain dynamic fluidity, linking microscopic and macroscopic changes in FTD.

Original languageEnglish (US)
Pages (from-to)176-184
Number of pages9
JournalNeurobiology of aging
StatePublished - Oct 2020


  • Chronnectome
  • Frontotemporal degeneration
  • Frontotemporal dementia
  • GABA
  • Glutamate
  • Large-scale functional connectivity networks
  • MRI
  • Transcranial magnetic stimulation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Clinical Neurology
  • Geriatrics and Gerontology


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