title: Long-range projections coordinate distributed brain-wide neural activity with a specific spatiotemporal profile.
abstract: One challenge in contemporary neuroscience is to achieve an integrated understanding of the large-scale brain-wide interactions, particularly the spatiotemporal patterns of neural activity that give rise to functions and behavior. At present, little is known about the spatiotemporal properties of long-range neuronal networks. We examined brain-wide neural activity patterns elicited by stimulating ventral posteromedial (VPM) thalamo-cortical excitatory neurons through combined optogenetic stimulation and functional MRI (fMRI). We detected robust optogenetically evoked fMRI activation bilaterally in primary visual, somatosensory, and auditory cortices at low (1 Hz) but not high frequencies (5-40 Hz). Subsequent electrophysiological recordings indicated interactions over long temporal windows across thalamo-cortical, cortico-cortical, and interhemispheric callosal projections at low frequencies. We further observed enhanced visually evoked fMRI activation during and after VPM stimulation in the superior colliculus, indicating that visual processing was subcortically modulated by low-frequency activity originating from VPM. Stimulating posteromedial complex thalamo-cortical excitatory neurons also evoked brain-wide blood-oxygenation-level-dependent activation, although with a distinct spatiotemporal profile. Our results directly demonstrate that low-frequency activity governs large-scale, brain-wide connectivity and interactions through long-range excitatory projections to coordinate the functional integration of remote brain regions. This low-frequency phenomenon contributes to the neural basis of long-range functional connectivity as measured by resting-state fMRI.
authors.affiliation: Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.|Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Alex T L
authors.initials: AT
authors.lastname: Leong
authors.affiliation: Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.|Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Russell W
authors.initials: RW
authors.lastname: Chan
authors.affiliation: Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.|Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Patrick P
authors.initials: PP
authors.lastname: Gao
authors.affiliation: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Ying-Shing
authors.initials: YS
authors.lastname: Chan
authors.affiliation: Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Tsia
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: Wing-Ho
authors.initials: WH
authors.lastname: Yung
authors.affiliation: Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Pokfulam, Hong Kong SAR, China; ewu@eee.hku.hk.|Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.|School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.|State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Ed X
authors.initials: EX
authors.lastname: Wu
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D001931:Brain Mapping / Q000379:methods*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D000229:Dependovirus; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net; D062308:Optogenetics; D010775:Photic Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000473:pathology; D013997:Time Factors
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: brain connectivity; fMRI; low frequency; optogenetic; thalamus