Mesoscale Mapping of Mouse Cortex Reveals Frequency-Dependent Cycling between Distinct Macroscale Functional Modules

Abstract

Connectivity mapping based on resting-state activity in mice has revealed functional motifs of correlated activity. However, the rules by which motifs organize into larger functional modules that lead to hemisphere wide spatial-temporal activity sequences is not clear. We explore cortical activity parcellation in head-fixed, quiet awake GCaMP6 mice from both sexes by using mesoscopic calcium imaging. Spectral decomposition of spontaneous cortical activity revealed the presence of two dominant frequency modes (Ͻ1 and ϳ3 Hz), each of them associated with a unique spatial signature of cortical macro-parcellation not predicted by classical cytoarchitectonic definitions of cortical areas. Based on assessment of 0.1-1 Hz activity, we define two macro-organizing principles: the first being a rotating polymodal-association pinwheel structure around which activity flows sequentially from visual to barrel then to hindlimb somatosensory; the second principle is correlated activity symmetry planes that exist on many levels within a single domain such as intrahemispheric reflections of sensory and motor cortices. In contrast, higher frequency activity Ͼ1 Hz yielded two larger clusters of coactivated areas with an enlarged default mode network-like posterior region. We suggest that the apparent constrained structure for intra-areal cortical activity flow could be exploited in future efforts to normalize activity in diseases of the nervous system.

Entrainment of Arteriole Vasomotor Fluctuations by Neural Activity Is a Basis of Blood-Oxygenation-Level-Dependent “Resting-State” Connectivity

“…The local field potential (LFP) from the superficial layers is measured across the windowed region of cortex (Figure 2A). We choose to use the LFP as an aggregate measure of neuronal activity, as opposed to intracellular calcium signals (Du et al, 2014; Ma et al, 2016; Vanni et al, 2017), as a means to identify different frequency bands of neuronal activation and to connect our work with past neurovascular studies (Keller et al, 2013; Lachaux et al, 2007; Niessing et al, 2005; Nir et al, 2007; Nir et al, 2008; Thompson et al, 2013). We also were cautious of potential ictal events in mice bred to express intracellular calcium reporters (Steinmetz et al, 2017).…”

“…Of interest, one psychophysical study points to variations in perceptual performance of human subjects that occurs in phase with ultra-slow electrical activity in the brain (Monto et al, 2008), while a second study points to changes in motor output based on the phase of the ultra-slow BOLD signal (Fox et al, 2007). A second unknown, implicit to the notion of functional connectivity, is how the brain can maintain a pattern of coherent arteriole vasomotor oscillations across multiple functionally linked regions, but simultaneously support incoherent oscillations between arterioles in unrelated regions as suggested from large-scale measurements of the BOLD signal (Ma et al, 2016; Mitra et al, 1997; Vanni et al, 2017). A final unknown concerns the precise mechanism by which neurons drive the endothelial cells (Attwell and Iadecola, 2002; Cauli and Hamel, 2010).…”

“…Surprisingly, these fluctuations are correlated across distant regions of the brain, as seen by fMRI (Biswal et al, 1995; Fox and Raichle, 2007; Wolf et al, 2011) and optical (Chan et al, 2015; Ma et al, 2016; Vanni et al, 2017) techniques in awake animals and humans. Many of these regions are known to interact via long-range and commissural connections (Cordes et al, 2000; Magnuson et al, 2014).…”

Localized semi-nonnegative matrix factorization (LocaNMF) of widefield calcium imaging data

“…Non-negative matrix factorization (NMF) is a decomposition approach that optimizes a similar cost function as SVD, without orthogonality constraints but with additional non-negativity constraints on the spatial and/or temporal components (21; 6); unfortunately, as we discuss below, many of the same criticisms of PCA also apply to NMF. Finally, seed-pixel correlation maps (7) provide a useful exploratory approach for visualizing the correlation structure in the data, but do not provide a meaningful decomposition of the full video into interpretable signals per se.…”

Simultaneous mesoscopic Ca2+ imaging and fMRI: Neuroimaging spanning spatiotemporal scales

“…[5][6][7][8] Recently, approaches for carrying out wide-field "mesoscopic" imaging of the entire mouse neocortical surface have significantly broadened our understanding of coordinated signaling between distant areas. [9][10][11][12] These signals are thought to largely reflect Ca 2+ influx resulting from somatic action potentials, thereby providing high spatiotemporal resolution measurements of neural activity. [13][14] These indicators can be targeted to genetically specified cell types, but necessarily require invasive manipulation of the nervous system and are limited to non-human models.…”