Frequency modulation of entorhinal cortex neuronal activity drives distinct frequency-dependent states of brain-wide dynamics
Piergiorgio Salvan,
Alberto Lazari,
Diego Vidaurre,
Francesca Mandino,
Heidi Johansen-Berg,
Joanes Grandjean
Affiliations
Piergiorgio Salvan
Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK; Corresponding author
Alberto Lazari
Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK
Diego Vidaurre
Wellcome Centre for Integrative Neuroimaging, OHBA, Department of Psychiatry, University of Oxford, Oxford OX3 7JX, UK; Department of Clinical Medicine, Center for Functionally Integrative Neuroscience, Aarhus University, Aarhus 8000, Denmark
Francesca Mandino
Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06520, USA
Heidi Johansen-Berg
Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK
Joanes Grandjean
Department of Medical Imaging and Donders Institute for Brain, Cognition, and Behaviour, Donders Institute, Radboud University Medical Centre, PO Box 9101, 6500HB Nijmegen, the Netherlands; Corresponding author
Summary: Human neuroimaging studies have shown that, during cognitive processing, the brain undergoes dynamic transitions between multiple, frequency-tuned states of activity. Although different states may emerge from distinct sources of neural activity, it remains unclear whether single-area neuronal spiking can also drive multiple dynamic states. In mice, we ask whether frequency modulation of the entorhinal cortex activity causes dynamic states to emerge and whether these states respond to distinct stimulation frequencies. Using hidden Markov modeling, we perform unsupervised detection of transient states in mouse brain-wide fMRI fluctuations induced via optogenetic frequency modulation of excitatory neurons. We unveil the existence of multiple, frequency-dependent dynamic states, invisible through standard static fMRI analyses. These states are linked to different anatomical circuits and disrupted in a frequency-dependent fashion in a transgenic model of cognitive disease directly related to entorhinal cortex dysfunction. These findings provide cross-scale insight into basic neuronal mechanisms that may underpin flexibility in brain-wide dynamics.