Building bridges: simultaneous multimodal neuroimaging approaches for exploring the organization of brain networks

Lake, Evelyn; Higley, Michael J.

doi:10.1117/1.nph.9.3.032202

Cited by 6 publications

(4 citation statements)

References 117 publications

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“…In the endeavor to uncover clinically actionable biomarkers of brain functional organization, BOLD-fMRI is critically positioned given its primacy in human studies and applicability in animal models. To this end, there is a burgeoning field of simultaneous implementations of fMRI and optical imaging methods (see review, ( Lake and Higley, 2022 )). These studies have revealed a strong concordance between hemodynamic measures, the BOLD signal, and cellular activity ( Wang et al, 2019 ) and are poised to reveal much more.…”

Section: Discussionmentioning

confidence: 99%

Functional network properties derived from wide-field calcium imaging differ with wakefulness and across cell type

et al. 2022

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Section: Discussionmentioning

confidence: 99%

Functional network properties derived from wide-field calcium imaging differ with wakefulness and across cell type

et al. 2022

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“…To address this gap, multimodal imaging in mice is emerging as a promising approach because a wide array of neuroimaging techniques are available for animal models (but inaccessible to humans) [40][41][42][43]. Despite the challenges of simultaneous multimodal acquisition, obtaining a more specific measure of neural activity, such as signals from fluorescent calcium-indicators (Ca 2+ ) simultaneously with fMRI-BOLD (or another hemodynamic signal) enables the quantification and/or validation of the neural contribution to BOLD [40,[44][45][46][47][48].…”

Section: Introductionmentioning

confidence: 99%

Multimodal measures of spontaneous brain activity reveals both common and divergent patterns of cortical functional organization

Vafaii

Mandino

Desrosiers-Grégoire

et al. 2022

Preprint

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Understanding the organization of large-scale brain networks remains a central problem in neuroscience. Work in both humans and rodents shows that the brain can be decomposed in terms of several networks (e.g., "default network"). Whereas the bulk of what we know is based on the blood-oxygenation level-dependent (BOLD) signal, the relationship between BOLD and neuronal activity is complex, which poses several challenges to interpreting networks revealed by this technique. To resolve these challenges, here we employed wide-field Ca2+imaging simultaneously recorded with fMRI-BOLD in a highly-sampled group of GCaMP6f-expressing mice. This allowed us to determine the relationship between networks discovered by BOLD and Ca2+signals both at the group level and in individual animals. Network partition used a mixed-membership stochastic blockmodel algorithm, which allows networks to be overlapping, such that a brain region may be assigned to multiple networks with varying strengths. Here, we tested the hypothesis that functional networks of the mouse brain are organized in an overlapping manner for both BOLD and Ca2+data. Our findings demonstrate that BOLD large-scale networks can be detected via Ca2+signals. In addition: (1) Overlapping networks were reliably estimated at the group level via random-effects statistical analysis. (2) Functional organization was generally similar for BOLD and Ca2+; e.g., with seven networks, cosine similarity was very high in five instances (values between 0.82-0.90; max possible value of 1), moderate in one case (0.73) and different in one case (0.26). (3) We discovered overlapping network organization in both data modalities, which was quantified in multiple ways; e.g., the proportion of regions that belonged to multiple networks was 75\% for BOLD and 60\% for Ca2+. (4) The large-scale functional organization of the mouse cortex as determined by Ca2+signals is considerably more similar to that with BOLD when both signal modalities are considered in the low temporal frequency range (0.01 to 0.5 Hz). (5) Although many similarities were observed between data modalities, finer characterization uncovered key differences related to functional hubs believed to play important roles in the integration and/or segregation of signals. In particular, the spatial distribution of membership diversity (i.e., the extent to which a region affiliates with multiple networks), differed for the two types of signals. In conclusion, Ca2+mesoscale signals revealed that the mouse cortex is functionally organized in terms of large-scale networks in a manner that reflects many of the properties observed using BOLD. Despite many similarities, important differences were also uncovered, suggesting that mesoscale Ca2+has a strong potential to uncover additional properties of the large-scale organization of the mouse brain.

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“…The focus of this minireview is not to describe in detail diverse Ca 2+ imaging techniques as excellent, comprehensive reviews are already available ( Werner et al, 2019 ; Broussard and Petreanu, 2021 ; Wang et al, 2021 ; Grienberger et al, 2022 ; Kim and Schnitzer, 2022 ; Lake and Higley, 2022 ). Instead, we discuss studies using some of these techniques to monitor the activity of neurons, astrocytes, and mitochondria in HD models ( Table 1 ).…”

Section: Introductionmentioning

confidence: 99%

Calcium imaging: A versatile tool to examine Huntington’s disease mechanisms and progression

Barry

Peng²,

Levine³

et al. 2022

Front. Neurosci.

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Huntington’s disease (HD) is a fatal, hereditary neurodegenerative disorder that causes chorea, cognitive deficits, and psychiatric symptoms. It is characterized by accumulation of mutant Htt protein, which primarily impacts striatal medium-sized spiny neurons (MSNs), as well as cortical pyramidal neurons (CPNs), causing synapse loss and eventually cell death. Perturbed Ca2+ homeostasis is believed to play a major role in HD, as altered Ca2+ homeostasis often precedes striatal dysfunction and manifestation of HD symptoms. In addition, dysregulation of Ca2+ can cause morphological and functional changes in MSNs and CPNs. Therefore, Ca2+ imaging techniques have the potential of visualizing changes in Ca2+ dynamics and neuronal activity in HD animal models. This minireview focuses on studies using diverse Ca2+ imaging techniques, including two-photon microscopy, fiber photometry, and miniscopes, in combination of Ca2+ indicators to monitor activity of neurons in HD models as the disease progresses. We then discuss the future applications of Ca2+ imaging to visualize disease mechanisms and alterations associated with HD, as well as studies showing how, as a proof-of-concept, Ca2+imaging using miniscopes in freely-behaving animals can help elucidate the differential role of direct and indirect pathway MSNs in HD symptoms.

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Building bridges: simultaneous multimodal neuroimaging approaches for exploring the organization of brain networks

Cited by 6 publications

References 117 publications

Functional network properties derived from wide-field calcium imaging differ with wakefulness and across cell type

Functional network properties derived from wide-field calcium imaging differ with wakefulness and across cell type

Multimodal measures of spontaneous brain activity reveals both common and divergent patterns of cortical functional organization

Calcium imaging: A versatile tool to examine Huntington’s disease mechanisms and progression

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