Biology subjects

Daley, L.

Publications and source records attributed to Daley, L..

8 recordsLinked to original sources

bioRxiv2026

Connectomes across temporal scales with simultaneous wide-field optical imaging and resting-state functional MRI

Resting-state functional MRI (rs-fMRI) is a cornerstone of human brain research, yet its interpretation is complicated by its sensitivity to the slow hemodynamic response that obscures the organization of neural activity across faster time scales. Here we use simultaneous wide-field optical imaging (WOI) and rs-fMRI to directly examine the relationship between neural and hemodynamic functional connectomes across time scales. We show that much of the large-scale spatial structure is preserved across modalities, across time scales, and across frequencies. Although rs-fMRI robustly captures time-averaged neural activity, time-resolved rs-fMRI estimates of functional connectivity exhibit significantly greater variability, which partially reflects sensitivity limitations. Hemodynamic WOI signals maintain greater similarity to neural activity than rs-fMRI, although their fidelity is reduced at high frequencies. Together, our findings demonstrate that the time-averaged spatial structure of neural activity is faithfully represented in hemodynamics and rs-fMRI; provide insight into the reliability of time-resolved rs-fMRI across temporal scales; and establish a multimodal framework for validating features of dynamic brain activity. TeaserSpatial patterns of neural activity present across time scales are largely preserved in hemodynamics measured with optical imaging and rs-fMRI.

neuroscience↗

bioRxiv2026

An integrated platform for simultaneous wide-field voltage/calcium imaging and fMRI (EPI & ZTE) reveals neuronal infraslow dynamics underlying functional connectivity

Wide-field optical imaging acquired simultaneously with functional MRI (fMRI) has the ability to provide unprecedented insight into the neural origins of time-varying whole-brain activity. Simultaneously linking cellular-scale activity to whole-brain fMRI remains challenging due to optical access, RF coil placement, and transmission constraints in the MRI environment. We present an integrated platform that combines a long-distance tube-lens optical path (>98% transmission), a chronically stable optically-fused cranial window, and a subject-conformal RF surface coil compatible with both echo planar imaging (EPI) and zero-echo-time (ZTE) fMRI. The system supports concurrent wide-field imaging of genetically encoded voltage or calcium indicators concurrently with intrinsic hemoglobin signals. In individual mice, wide-field optical and fMRI measures yield concordant functional connectivity, and cross-modal timing analyses demonstrate that neuronal infraslow dynamics (<0.1 Hz) underlie the majority of fMRI connectivity, after removing hemodynamic crosstalk. The platform's sensitivity, chronic stability, and sequence flexibility broaden access to cellular-to-whole-brain investigations across basic and translational neuroimaging.

neuroscience↗

bioRxiv2026

Fidelity of Spatiotemporal Patterns of Brain Activity Across Sampling Rate, Scan Duration, and Frequency Content

Intrinsic brain activity is characterized by large-scale spatiotemporal patterns that underpin functional connectivity and cognition. Quasi-periodic patterns (QPPs) and complex principal component analysis (cPCA) have emerged as reproducible methods for capturing spatiotem-poral network interactions in resting-state functional magnetic resonance imaging (rs-fMRI). However, these methods remain sensitive to methodological factors such as scan duration, repetition time (TR), and frequency band selection. This study systematically evaluates how these parameters influence the stability and reliability of QPP- and cPCA-derived functional connectivity patterns across multiple datasets. Using five independent rs-fMRI datasets, we evaluate the impact of scan length on pattern reliability, explore the effects of TR on spatiotemporal patterns, and compare the sensitivity of different frequency bands (Slow-5, Slow-4, infraslow) in capturing network dynamics. Our findings reveal that while both QPPs and cPCA detect intrinsic network activity, their reliability varies with acquisition parameters. QPPs exhibit greater stability in shorter scans, making them suitable for individual-level analyses, whereas cPCA provides a broader representation of phase-coherent fluctuations but shows greater between-subject variability and benefits more from longer, group-level acquisi-tions. Additionally, frequency band selection significantly influences the temporal structure of extracted patterns: in our analyses, Slow-5 (0.01-0.027 Hz) tended to emphasize more recurrent, synchronized network configurations, whereas Slow-4 (0.027-0.073 Hz) more often revealed transitions between connectivity states. These results provide critical insights into optimizing methodological choices for dynamic functional connectivity analysis, enhancing the interpretability of spatiotemporal patterns in both basic and clinical neuroimaging research.

neuroscience↗

bioRxiv2024

Altered functional connectivity and spatiotemporal dynamics in individuals with sleep disorders

Idiopathic hypersomnia (IH) is a sleep disorder characterized by highly disruptive symptoms. Like narcolepsy type 1, a well-characterized sleep disorder, individuals with IH suffer from excessive daytime sleepiness, though there is little overlap in metabolic or neural biomarkers across these two disorders. This lack of common pathophysiology, combined with the clear overlap in symptoms presents an ideal paradigm for better understanding the impact of IH on an individuals functional activity and organization, and potentially, the underlying pathophysiology. This study examines the observed functional connectivity in patients with IH, and patients with narcolepsy type 1 (NT1) against healthy control individuals. Static functional connectivity is compared, as are quasi-periodic patterns, acquired from the BOLD timecourse, for all groups. In addition to baseline data comparison, the study also included a post-nap condition, where the individuals included in this analysis napped for at least 10 minutes prior to the scanning session, to explore why individuals with IH do not feel "refreshed" after a nap like individuals with NT1 do. Assessing the groups spatiotemporal patterns revealed key differences across both disorders and conditions: static connectivity revealed at baseline higher subcortical connectivity in the NT1 group. There was also observably less connectivity in the IH group both at baseline and post-nap, though none of these static analyses survived multiple comparisons correction to reach significance. The QPP results however found significant differences in the IH group in key networks, particularly the DAN/FPCN correlation is significantly different at baseline vs. post-nap, a trend not observed in either the control or NT1 groups. The DAN and FPCN are drastically altered both at baseline and post-nap when compared to the other groups, and may likely be a disorder-specific result. This study demonstrates that key networks for arousal are more heavily disrupted in IH patients, who are less affected by a nap, confirmed through both subject reporting and functional evidence through spatiotemporal patterns.

pathology↗

bioRxiv2024

Variation in the Distribution of Large-scale Spatiotemporal Patterns of Activity Across Brain States

A few large-scale spatiotemporal patterns of brain activity (quasiperiodic patterns or QPPs) account for most of the spatial structure observed in resting state functional magnetic resonance imaging (rs-fMRI). The QPPs capture well-known features such as the evolution of the global signal and the alternating dominance of the default mode and task positive networks. These widespread patterns of activity have plausible ties to neuromodulatory input that mediates changes in nonlocalized processes, including arousal and attention. To determine whether QPPs exhibit variations across brain conditions, the relative magnitude and distribution of the three strongest QPPs were examined in two scenarios. First, in data from the Human Connectome Project, the relative incidence and magnitude of the QPPs was examined over the course of the scan, under the hypothesis that increasing drowsiness would shift the expression of the QPPs over time. Second, using rs-fMRI in rats obtained with a novel approach that minimizes noise, the relative incidence and magnitude of the QPPs was examined under three different anesthetic conditions expected to create distinct types of brain activity. The results indicate that both the distribution of QPPs and their magnitude changes with brain state, evidence of the sensitivity of these large-scale patterns to widespread changes linked to alterations in brain conditions.

neuroscience↗

bioRxiv2024

Infraslow dynamic patterns in human cortical networks track a spectrum of external to internal attention

Early efforts to understand the human cerebral cortex focused on localization of function, assigning functional roles to specific brain regions. More recent evidence depicts the cortex as a dynamic system, organized into flexible networks with patterns of spatiotemporal activity corresponding to attentional demands. In functional MRI (fMRI), dynamic analysis of such spatiotemporal patterns is highly promising for providing non-invasive biomarkers of neurodegenerative diseases and neural disorders. However, there is no established neurotypical spectrum to interpret the burgeoning literature of dynamic functional connectivity from fMRI across attentional states. In the present study, we apply dynamic analysis of network-scale spatiotemporal patterns in a range of fMRI datasets across numerous tasks including a left-right moving dot task, visual working memory tasks, congruence tasks, multiple resting state datasets, mindfulness meditators, and subjects watching TV. We find that cortical networks show shifts in dynamic functional connectivity across a spectrum that tracks the level of external to internal attention demanded by these tasks. Dynamics of networks often grouped into a single task positive network show divergent responses along this axis of attention, consistent with evidence that definitions of a single task positive network are misleading. Additionally, somatosensory and visual networks exhibit strong phase shifting along this spectrum of attention. Results were robust on a group and individual level, further establishing network dynamics as a potential individual biomarker. To our knowledge, this represents the first study of its kind to generate a spectrum of dynamic network relationships across such an axis of attention. Significance StatementThis study provides significant insight into how cortical dynamics shift along a spectrum of external vs internal attention. Association and sensory networks show shifts in their relationship with the default mode network (DMN) along this spectrum. Notably, the constituent networks of the task positive network (TPN), such as the DAN, frontoparietal network (FPN), and ventral attention network (VAN) show divergent responses along this spectrum, indicating that definitions of a single "task positive" network are misleading. This is one of the first studies of large-scale spatiotemporal dynamics across such a breadth of tasks. These results provide a neurotypical reference spanning an axis of attention to interpret the growing functional dynamics literature and to help characterize functional dynamics as a potential biomarker.

neuroscience↗

bioRxiv2024

Creative tempo: Spatiotemporal dynamics of the default mode network in improvisational musicians

The intrinsic dynamics of human brain activity display a recurring pattern of anti-correlated activity between the default mode network (DMN), associated with internal processing and mentation, and task positive regions, associated with externally directed attention. In human functional magnetic resonance imaging (fMRI) data, this anti-correlated pattern is detectable on the infraslow timescale (<0.1 Hz) as a quasi-periodic pattern (QPP). While the DMN is implicated in creativity and musicality in traditional time-averaged functional connectivity studies, no one has yet explored how creative training may alter dynamic spatiotemporal patterns involving the DMN such as QPPs. In the present study, we compare the outputs of two QPP detection approaches, sliding window algorithm and complex principal components analysis (cPCA). We apply both methods to an existing dataset of musicians captured with resting state fMRI, grouped as either classical, improvisational, or minimally trained non-musicians. The original time-averaged functional connectivity (FC) analysis of this dataset used improvisation as a proxy for creative thinking and found that the DMN and visual networks (VIS) display higher connectivity in improvisational musicians. We expand upon this datasets original study and find that QPP analysis detects convergent results at the group level with both methods. In improvisational musicians, dynamic functional correlation in the group-averaged QPP was found to be increased between the DMN-VIS and DMN-FPN for both the QPP algorithm and complex principal components analysis (cPCA) methods. Additionally, we found an unexpected increase in FC in the group-averaged QPP between the dorsal attention network and amygdala in improvisational musicians; this result was not reported in the original seed-based study of this dataset. The current study represents a novel application of two dynamic FC detection methods with results that replicate and expand upon previous seed-based FC findings. The results show the robustness of both the QPP phenomenon and its detection methods. This study also demonstrates the value of dynamic FC methods in reproducing seed-based findings and their promise in detecting group-wise or individual differences that may be missed by traditional seed-based resting state fMRI studies.

neuroscience↗

bioRxiv2019

Highly efficient and specific genome editing in human cells with paired CRISPR-Cas9 nickase ribonucleoproteins

CRISPR technology has opened up many diverse genome editing possibilities in human somatic cells, but has been limited in the therapeutic realm by both potential off-target effects and low genome modification efficiencies. Recent advancements to combat these limitations include delivering Cas9 nucleases directly to cells as highly purified ribonucleoproteins (RNPs) instead of the conventional plasmid DNA and RNA-based approaches. Here, we extend RNP-based delivery in cell culture to a less characterized CRISPR format which implements paired Cas9 nickases. The use of paired nickase Cas9 RNP system, combined with a GMP-compliant non-viral delivery technology, enables editing in human cells with high specificity and high efficiency, a development that opens up the technology for further exploration into a more therapeutic role.

molecular biology↗