Biology subjects

Gomez, D. E. P.

Publications and source records attributed to Gomez, D. E. P..

7 recordsLinked to original sources

bioRxiv2026

A hypothalamic-brainstem activity sequence underlies arousal fluctuations during daytime drowsiness

During monotonous tasks, struggling with drowsiness leads to dynamic fluctuations in vigilance and task performance. Whether these moment-to-moment fluctuations are regulated by sleep-wake control circuitry remains unknown. Here, we used high-resolution 7T fMRI optimized for subcortical imaging to resolve activity across the human arousal regulatory system, including the hypothalamus, brainstem nuclei, basal forebrain, and thalamus, during a sustained attention task as subjects spontaneously experienced drowsiness. We identified a coordinated activity pattern locked to behavioral failures: widespread transient suppression during arousal drops and reactivation during recovery across all arousal-promoting regions, with opposite responses in the sleep-promoting hypothalamic preoptic area. These changes unfolded over [~]10-15 s in a 30 consistent sequence, led by the hypothalamic nuclei. Furthermore, suppression of brainstem nuclei preceded cortical infraslow (<0.05 Hz) oscillations, implicating a role in global neurovascular dynamics. These findings provide a temporally resolved, network-level portrait of human subcortical dynamics during drowsiness and identify a hypothalamic-led, brainstem-mediated activity sequence underlying behavioral arousal fluctuations and global cortical hemodynamics.

neuroscience↗

bioRxiv2025

Temporal evolution and spatial heterogeneity of cerebral cortical-depth profiles of the BOLD-fMRI response

Functional MRI measures brain activity by tracking the associated hemodynamic response, which is shaped by the vascular anatomy. Microscopy studies have shown that the hemodynamic response initiates within the cerebral cortex then spreads upwards to the pial surface, where the largest fMRI signal changes are seen, however responses at the cortical surface exhibit poor neuronal specificity. Motived by this, we characterized the time-evolution of the fMRI response in humans. At some cortical locations the fMRI response peaked at the pial surface but in others it peaked within the cortex, likely due to the sparsity of large pial vessels and the dense capillary bed in middle cortical layers. We observed the earliest response onset in middle cortical depths, which is also the site of thalamocortical input. Standard approaches that aggregate fMRI responses over space and time may therefore lose meaningful information, and "physiologically-informed" strategies may enhance neuronal specificity of fMRI measurements.

neuroscience↗

bioRxiv2025

Visual stimulus-evoked blood velocity responses in individual human posterior cerebral arteries measured with dynamic phase-contrast functional MR angiography

Functional MRI (fMRI) tracks brain activity through the associated hemodynamic changes via neurovascular coupling. Neurons communicate with the microvessels of the parenchyma to initiate a hemodynamic response, and these microvessels then communicate with upstream arterioles and arteries. The role of the larger feeding arteries--far upstream from the site of neuronal activity--in coordinating this response is incompletely understood, yet is important for the interpretation of fMRI. Functional Transcranial Doppler (fTCD) can noninvasively measure blood velocity changes in a subset of the largest macrovessels, albeit with poor spatial resolution, whereas existing functional MR angiography (fMRA) methods can assess blood velocity in mid-sized macrovessels but still lack the temporal resolution required to capture dynamic responses. This study aims to propose a new, quantitative fMRA method for measuring blood velocity responses in individual vessels in humans at high spatiotemporal resolution. A dynamic functional phase-contrast MRA approach was developed to quantify responses evoked by visual stimuli in the "P2" segment of the posterior cerebral artery (PCA), located [~]6 cm away from primary visual cortex. The achieved temporal resolution is comparable to that of conventional blood-oxygenation-level-dependent (BOLD) fMRI, enabling block-design stimulation paradigms similar to those used in conventional fMRI studies. The temporal and spatial properties of the blood velocity responses were evaluated using both long- and short-duration visual stimuli presented to either the full visual field or a single hemifield. Robust responses were measured on both 3T and 7T clinical MRI scanners, and an approximately 3.3 {+/-} 1.2 cm/s increase in the blood velocity in the targeted segment was observed, which is roughly a 10% increase from baseline. Visual hemifield stimulation generated a measurable blood velocity response only in the contralateral cerebral hemisphere, indicating that systemic physiological changes occurring with stimulation cannot account for the observed response, suggesting that they instead reflect neurovascular coupling initiated in the visual cortex. The observed arterial blood velocity response is consistent with a downstream reduction in microvascular resistance and may represent a passive response rather than an active vessel dilation at the targeted arterial segment. The proposed method has the potential to extend the capability of commonly used approaches, such as fTCD, in clinical applications.

neuroscience↗

bioRxiv2025

Modeling dynamic inflow effects in fMRI to quantify cerebrospinal fluid flow

Cerebrospinal fluid (CSF) flow in the brain is tightly regulated and essential for brain health, and imaging techniques are needed to quantitatively establish the properties of this flow system. Flow-sensitive fMRI has recently emerged as a tool to measure large scale CSF flow dynamics with high sensitivity and temporal resolution; however, the measured signal is not quantitative. Here, we developed a dynamic model to simulate fMRI inflow signals based on time-varying flow velocities. We validated the model in both human and phantom data, and used it to identify important properties of the fMRI inflow signal that inform how the signal should be interpreted. Additionally, we developed a physics-based deep learning framework to invert the model, which enables direct estimation of velocity using fMRI inflow data. This work allows new quantitative information to be obtained from fMRI, which will enable neuroimaging researchers to take advantage of the high sensitivity, high temporal resolution, and wide availability of fMRI to obtain flow signals that are physically interpretable.

neuroscience↗

bioRxiv2024

The temporal specificity of BOLD fMRI is systematically related to anatomical and vascular features of the human brain

The ability to detect fast responses with functional MRI depends on the speed of hemodynamic responses to neural activity, because hemodynamic responses act as a temporal low-pass filter which blurs rapid changes. However, the shape and timing of hemodynamic responses are highly variable across the brain and across stimuli. This heterogeneity of responses implies that the temporal specificity of fMRI signals, or the ability of fMRI to preserve fast information, could also vary substantially across the cortex. In this work we investigated how local differences in hemodynamic response timing affect the temporal specificity of fMRI. We used ultra-high field (7T) fMRI at high spatiotemporal resolution, studying the primary visual cortex (V1) as a model area for investigation. We used visual stimuli oscillating at slow and fast frequencies to probe the temporal specificity of individual voxels. As expected, we identified substantial variability in temporal specificity, with some voxels preserving their responses to fast neural activity more effectively than others. We investigated which voxels had the highest temporal specificity, and tested whether voxel timing was related to anatomical and vascular features. We found that low temporal specificity is only weakly explained by the presence of large veins or cerebral cortical depth. Notably, however, temporal specificity depended strongly on a voxels position along the anterior-posterior anatomical axis of V1, with voxels within the calcarine sulcus being capable of preserving close to 25% of their amplitude as the frequency of stimulation increased from 0.05Hz to 0.20Hz, and voxels nearest to the occipital pole preserving less than 18%. These results indicate that detection biases in high-resolution fMRI will depend on the anatomical and vascular features of the area being imaged, and that these biases will differ depending on the timing of the underlying neuronal activity. While we attribute this variance primarily to hemodynamic effects, neuronal nonlinearities may also influence response timing. Importantly, this spatial heterogeneity of temporal specificity suggests that it could be exploited to achieve higher specificity in some locations, and that tailored data analysis strategies may help improve the detection and interpretation of fast fMRI responses.

neuroscience↗

bioRxiv2023

Resting-state fMRI signals contain spectral signatures of local hemodynamic response timing

Functional magnetic resonance imaging (fMRI) has proven to be a powerful tool for noninvasively measuring human brain activity; yet, thus far, fMRI has been relatively limited in its temporal resolution. A key challenge is understanding the relationship between neural activity and the blood-oxygenation-level-dependent (BOLD) signal obtained from fMRI, generally modeled by the hemodynamic response function (HRF). The timing of the HRF varies across the brain and individuals, confounding our ability to make inferences about the timing of the underlying neural processes. Here we show that resting-state fMRI signals contain information about HRF temporal dynamics that can be leveraged to understand and characterize variations in HRF timing across both cortical and subcortical regions. We found that the frequency spectrum of resting-state fMRI signals significantly differs between voxels with fast versus slow HRFs in human visual cortex. These spectral differences extended to subcortex as well, revealing significantly faster hemodynamic timing in the lateral geniculate nucleus of the thalamus. Ultimately, our results demonstrate that the temporal properties of the HRF impact the spectral content of resting-state fMRI signals and enable voxel-wise characterization of relative hemodynamic response timing. Furthermore, our results show that caution should be used in studies of resting-state fMRI spectral properties, as differences can arise from purely vascular origins. This finding provides new insight into the temporal properties of fMRI signals across voxels, which is crucial for accurate fMRI analyses, and enhances the ability of fast fMRI to identify and track fast neural dynamics.

neuroscience↗

bioRxiv2021

A temporal sequence of thalamic activity unfolds at transitions in behavioral arousal state

The moment of awakening from sleep reflects a profound transformation in neural activity and behavior. The thalamus is a key controller of arousal state, but whether its diverse nuclei exhibit coordinated or distinct activity at transitions in behavioral arousal state is not known. Using fast fMRI at ultra-high field (7 Tesla), we measured sub-second activity across thalamocortical networks and within nine thalamic nuclei to delineate these dynamics during spontaneous transitions in behavioral arousal state. We discovered a stereotyped sequence of activity across thalamic nuclei that preceded behavioral arousal after a period of inactivity, followed by widespread cortical deactivation. These thalamic dynamics were linked to whether participants remained awake or fell back asleep, with unified thalamic activation reflecting subsequent maintenance of awake behavior. These results provide an outline of the complex interactions across thalamocortical circuits that orchestrate arousal state transitions, and additionally, demonstrate that fast fMRI can resolve sub-second subcortical dynamics in the human brain.

neuroscience↗