Biology subjects

Glover, G. H.

Publications and source records attributed to Glover, G. H..

9 recordsLinked to original sources

bioRxiv2026

Dose-dependent ultrasound neuromodulation of the human brain

Transcranial ultrasound stimulation (TUS) can noninvasively modulate deep brain structures, but the relationship between delivered dose and neuromodulatory response remains poorly characterized in humans. Here, we show that ultrasound-induced tissue displacement measured in vivo predicts local and downstream functional neuromodulation. In 24 healthy adults, we combined magnetic resonance acoustic radiation force imaging (MR-ARFI) with concurrent TUS-fMRI in a double-blind, counterbalanced, within-subject design. Relative to active control stimulation, targeting the lateral geniculate nucleus (LGN) increased visually evoked BOLD responses in the LGN and ipsilateral primary visual cortex, localized to the retinotopic projection zone of the stimulated LGN site. Displacement predicted effect magnitude in both regions across participants and covaried with voxelwise responses within participants. Simulated in situ intensity showed no significant association with displacement or neuromodulatory response. These findings link in vivo mechanical displacement to functional modulation of a human thalamocortical circuit, providing an empirical basis for individualized dosing in causal neuroscience and clinical intervention.

neuroscience↗

bioRxiv2026

MR-ARFI and Beyond: Characterizing the Temporal Dynamics of Acoustic Radiation Force in Human Brain

Purpose: Magnetic Resonance Acoustic Radiation Force Imaging (MR-ARFI) encodes focused ultrasound (FUS)-induced tissue displacements to MR phase shifts. Because these phase shifts are small, optimizing displacement sensitivity and minimizing motion artifacts requires characterization of the temporal dynamics of acoustic radiation force (ARF). Beyond sequence design, such characterization enables MR-ARFI to serve as a probe of brain viscoelastic behavior and can inform the design of therapeutic ultrasound pulsing schemes by quantifying how rapidly tissue deforms and relaxes. Methods: We developed a dynamic model assuming a gamma-variate impulse response for ARF(t), with time constant ({tau}) to be estimated. A single-shot spin echo ARFI acquisition with a bipolar motion encoding gradient (MEG) was implemented, incorporating retrospective corrections for head motion and physiological noise. A 500 kHz FUS pulse was applied in on/off blocks while systematically varying the timing between the MEG and sonication. The resulting phase time series were fit to the model to estimate time constant in five human participants. To assess sensitivity to tissue stiffness, {tau} was additionally measured in two customized gelatin phantoms of differing stiffness, characterized independently by MR elastography (MRE). Results: The average measured time constant in human participants was {tau} 3.7 {+/-} 0.27 ms. Comparing the two phantoms, the stiffer phantom exhibited a shorter {tau} (3.0-3.5 ms) than the softer phantom (4.0-4.5 ms), which tracked the MRE-derived Kelvin-Voigt viscoelastic time constants. In addition, the peak ARFI displacement was lower in the stiffer phantom (0.17 vs 0.74 m for the less stiff phantom), and a broader displacement focal spot size (FWHM 22 mm vs 15 mm). Conclusion: This time series approach with motion and physiological noise corrections validates an MR-based technique capable of characterizing the brain's temporal response to sonication-induced mechanical forces, providing a foundation for optimizing the design of ultrasound pulsing schemes for ARFI, as well as for future studies of brain biomechanics.

bioengineering↗

bioRxiv2025

Differential encoding of noxious heat and self-reported pain along corticospinal networks: a simultaneous spinal cord-brain fMRI study

Chronic pain poses a substantial public health burden. Elucidating how the healthy central nervous system (CNS) differentially encodes objective stimulus intensity and subjective experiences of pain perception may offer key insights into the central mechanisms contributing to chronic pain. Functional MRI (fMRI) combined with controlled noxious stimulation provides a powerful means to explore neural representations of nociception and pain perception. Here, we applied noxious heat at three intensities (46 {degrees}C, 47 {degrees}C, 48 {degrees}C, 8 trials each randomized) to the right forearm of 28 healthy women during simultaneous spinal cord-brain fMRI to investigate how distributed corticospinal activity and connectivity encode stimulus intensity and subjective pain. Activity increased with stimulus temperature across regions involved in pain processing--including somatosensory, motor, prefrontal, insular, and subcortical areas--as well as in the ipsilateral dorsal and ventral spinal cord. Spinal- brain functional connectivity was observed between the right dorsal horn and pain-related brain regions such as primary and secondary somatosensory cortex, insula, anterior cingulate cortex, thalamus, and periaqueductal gray, and was positively associated with individual pain ratings. Using representational similarity analysis (RSA), we found that multivoxel activation patterns in the brain and spinal cord, as well as corticospinal connectivity patterns, reliably tracked stimulus temperature, while only subsets of cortical regions (e.g., insula, sensorimotor, and frontal cortices) encoded subjective pain. Notably, spinal cord representations were primarily organized by stimulus temperature rather than perceived pain intensity. These findings demonstrate that simultaneous spinal cord-brain fMRI combined with multivariate modeling can identify sensory and perceptual components of nociceptive processing across the neuroaxis. Such approaches advance mechanistic understanding of pain and may inform the development of CNS-based biomarkers for chronic pain assessment and intervention.

neuroscience↗

bioRxiv2025

Mapping Hand Function with Simultaneous Brain-Spinal Cord Functional MRI

INTRODUCTIONHand motor control depends on intricate brain-spinal cord interactions that regulate muscle activity. Hand function can be disrupted by injury to the brain, spinal cord, and peripheral nerves leading to weakness and impaired coordination. Functional MRI (fMRI) can map motor-related neural activity and potentially characterize the mechanisms underlying hand weakness and diminished coordination. Although brain motor control has been extensively studied, spinal cord mechanisms remain less explored. Here we use simultaneous brain-spinal cord fMRI to map neural activity related to hand strength and dexterity across the central nervous system using force matching and finger tapping tasks. This study pioneers the use of simultaneous brain-spinal cord fMRI to comprehensively map hand function, offering novel insights into coordinated motor processing across the central nervous system. METHODSWe performed simultaneous brain-spinal cord fMRI in 28 right-handed healthy volunteers (age: 40.0 {+/-} 13.8 years, 14 females, 14 males) using a 3T GE SIGNA Premier scanner equipped with a 21-channel head-neck coil. Participants performed a force-matching task at 10%, 20%, and 30% of maximum voluntary contraction using a hand dynamometer. For the finger tapping task, participants completed button-presses at 1 Hz with a 5-button response pad for three task levels: single-digit response with the second digit only (low), single-digit response with all digits in a sequential order (medium), single-digit response with all digits in a random order (high). Visual cues and feedback were provided during the tasks. Brain and spinal cord images were processed separately using FSL and the Spinal Cord Toolbox, with motion correction, physiological noise filtering, and spatial normalization to standard templates. Subject level activity maps were generated and entered into group level analyses to explore both activations and deactivations. For the brain, we used a mixed effect design with a voxelwise threshold of Z score > 3.10 and cluster threshold of p < 0.05. For the spinal cord, we used a fixed effect design with a voxelwise threshold of Z score > 1.64 and cluster threshold of p < 0.05. Region of interest (ROI) analyses were conducted to examine localized changes in activation across task levels RESULTSBoth tasks elicited activation in motor and sensory regions of the brain and spinal cord, with graded responses in the left primary motor (M1), left primary sensory (S1) cortex, and right spinal cord gray matter across task levels. Deactivation of the right M1 and S1 was also present for both tasks. Deactivation of the left spinal cord gray matter was present in the high task level of the force matching task. The ROI analysis findings complemented the group level activity maps. DISCUSSIONOur study provides a detailed map of brain-spinal cord interactions in hand function, revealing graded neural activation and inhibition patterns across motor and sensory regions. Interhemispheric inhibition, reflected in right M1 deactivation, likely restricts extraneous motor output during unilateral tasks. For force matching, the deactivation of the left ventral and dorsal horns of the spinal cord, provides the first evidence that the inhibition of motor areas during a unilateral motor task extends to the spinal cord. Whether this inhibition results from direct descending modulation from the brain or interneuronal inhibition in the cord remains to be interrogated. These findings expand our understanding of central motor control mechanisms and could inform rehabilitation strategies for individuals with motor impairments. CONCLUSIONSOur simultaneous brain-spinal cord fMRI approach provides novel insights into the neural coordination of hand function, enhancing our understanding of motor control and its modulation. This approach may offer a foundation for studying motor dysfunction in conditions such as stroke, spinal cord injury, and neurodegenerative diseases.

neuroscience↗

bioRxiv2025

EPISeg: Automated segmentation of the spinal cord on echo planar images using open-access multi-center data

Functional magnetic resonance imaging (fMRI) of the spinal cord is relevant for studying sensation, movement, and autonomic function. Preprocessing of spinal cord fMRI data involves segmentation of the spinal cord on gradient-echo echo planar imaging (EPI) images. Current automated segmentation methods do not work well on these data, due to the low spatial resolution, susceptibility artifacts causing distortions and signal drop-out, ghosting, and motion-related artifacts. Consequently, this segmentation task demands a considerable amount of manual effort which takes time and is prone to user bias. In this work, we (i) gathered a multi-center dataset of spinal cord gradient-echo EPI with ground-truth segmentations and shared it on OpenNeuro https://openneuro.org/datasets/ds005143/versions/1.3.0, and (ii) developed a deep learning-based model, EPISeg, for the automatic segmentation of the spinal cord on gradient-echo EPI data. We observe a significant improvement in terms of segmentation quality compared to other available spinal cord segmentation models. Our model is resilient to different acquisition protocols as well as commonly observed artifacts in fMRI data. The training code is available at https://github.com/sct-pipeline/fmri-segmentation/, and the model has been integrated into the Spinal Cord Toolbox as a command-line tool.

neuroscience↗

bioRxiv2024

Optimization of MR-ARFI for Human Transcranial Focused Ultrasound

Magnetic resonance acoustic radiation force imaging (MR-ARFI) is an exceptionally promising technique to non-invasively confirm targeting accuracy and estimate exposure of low-intensity transcranial focused ultrasound stimulation. MR-ARFI uses magnetic field motion encoding gradients to visualize the MR phase changes generated by microscopic displacements at the ultrasound focus. Implementing MR-ARFI in the human central nervous system has been hindered by 1) phase distortion caused by subject motion, and 2) insufficient signal-to-noise ratio at low (<1.0 MPa) ultrasound pressures. The purpose of this study was to optimize human MR-ARFI to allow reduced ultrasound exposure while at the same time being robust to bulk and physiological motion. We demonstrate that a time series of single-shot spiral acquisitions, while triggering ultrasound on and off in blocks, provides ARFI maps that with correction are largely immune to bulk and pulsatile brain motion. Furthermore, the time series approach allows for a reduction in ultrasound exposure per slice while improving motion robustness with reduced scan time. The focused ultrasound beam can be visualized in an 80 second scan with our protocol, enabling iteration for image-guided targeting. We demonstrated robust ARFI signals at the expected target in 4 participants. Our results provide persuasive proof-of-principle that MR-ARFI can be used as a tool to guide ultrasound-based precision neural circuit therapeutics.

biophysics↗

bioRxiv2021

Transcranial Focused Ultrasound Neuromodulation of the Thalamic Visual Pathway in a Large Animal Model

BackgroundNeuromodulation of deep brain structures via transcranial ultrasound stimulation (TUS) is a promising, but still elusive approach to non-invasive treatment of brain disorders. ObjectiveThe purpose of this study was to determine whether MR-guided TUS of the lateral geniculate nucleus (LGN) can modulate visual evoked potentials (VEPs) and cortical brain oscillations in a large animal model. MethodsThe lateral geniculate nucleus (LGN) on one side was identified with T2-weighted MRI in sheep (all male, n=9). MR acoustic radiation force imaging (MR-ARFI) was used to confirm a tight sonication focus. Electroencephalographic (EEG) signals were recorded, and the visual evoked potential (VEP) peak-to-peak amplitude (N70 and P100) was calculated for each trial. Time-frequency spectral analysis was performed to elucidate the effect of TUS on cortical brain dynamics. ResultsThe VEP peak-to-peak amplitude was reversibly suppressed relative to baseline during TUS. Dynamic spectral analysis demonstrated a change in cortical oscillations when TUS is paired with visual sensory input, but not when TUS is applied by itself. ConclusionTUS non-invasively delivered to LGN can neuromodulate visual activity and oscillatory dynamics in large mammalian brains.

neuroscience↗

bioRxiv2019

Decoupling of Dopamine Release and Neural Activity in Major Depressive Disorder during Reward Processing Assessed by Simultaneous fPET-fMRI

The interaction of the midbrain dopaminergic system and the striatum is implicated in reward processing; it is still unknown, however, how this interaction is altered in Major Depressive Disorder (MDD). In the current study, we related the dopamine release/binding inferred by [11C] Raclopride functional Positron Emission Tomography (fPET) to neural activity monitored by blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in adults diagnosed with MDD and healthy controls (CTL). Participants completed a monetary incentive delay (MID) task during simultaneous [11C] Raclopride fPET and fMRI. Instead of the usual kinetic modeling method for analyzing dynamic PET time activity curves (TACs), we used a simpler general linear model (GLM) approach, which includes introducing a fPET dopamine activation response function to model changes in the TAC associated with the MID task. In addition, using simulations, we show that the GLM approach has several advantages over kinetic modeling. This is achieved without invoking erroneous steady-state assumptions or selecting a suitable reference region. Our results include the observation of both decreased fMRI activation and dopamine release/binding in the striatum in the MDD cohort, implying a reduced reward processing capacity in MDD. Furthermore, in the MDD group, individuals with lower fMRI activations in the right middle putamen and ventral medial prefrontal cortex (vmPFC) had higher reflection rumination scores, and individuals with lower dopamine release/binding in the left putamen and the right nucleus accumbens (NAcc) also had higher reflection rumination scores. Significant cross-modal inter-subject and intra-subject correlations of dopamine release/binding and fMRI activation were observed in the CTL group, but not in the MDD group. The intra-subject correlation of the two modalities was negatively associated with reflection rumination scores in the CTL group, indicating that decoupling of the dopaminergic system and striatum may be important in the pathophysiology of MDD.

neuroscience↗

bioRxiv2019

Histologic safety of transcranial focused ultrasound neuromodulation and magnetic resonance acoustic radiation force imaging in rhesus macaques and sheep

BackgroundNeuromodulation by transcranial focused ultrasound (FUS) offers the potential to non-invasively treat specific brain regions, with treatment location verified by magnetic resonance acoustic radiation force imaging (MR-ARFI).\n\nObjectiveTo investigate the safety of these methods prior to widespread clinical use, we report histologic findings in two large animal models following FUS neuromodulation and MR-ARFI.\n\nMethodsTwo rhesus macaques and thirteen Dorset sheep were studied. FUS neuromodulation was targeted to the primary visual cortex in rhesus macaques and to subcortical locations, verified by MR-ARFI, in eleven sheep. Both rhesus macaques and five sheep received a single FUS session, whereas six sheep received repeated sessions three to six days apart. The remaining two control sheep did not receive ultrasound but otherwise underwent the same anesthetic and MRI procedures as the eleven experimental sheep. Hematoxylin and eosin-stained sections of brain tissue (harvested zero to eleven days following FUS) were evaluated for tissue damage at FUS and control locations as well as tissue within the path of the FUS beam. TUNEL staining was used to evaluate for the presence of apoptosis in sheep receiving high dose FUS.\n\nResultsNo FUS-related pre-mortem histologic findings were observed in the rhesus macaques or in any of the examined sheep. Extravascular red blood cells (RBCs) were present within the meninges of all sheep, regardless of treatment group. Similarly, small aggregates of perivascular RBCs were rarely noted in non-target regions of neural parenchyma of FUS-treated (8/11) and untreated (2/2) sheep. However, no concurrent histologic abnormalities were observed, consistent with RBC extravasation occurring as post-mortem artifact following brain extraction. Sheep within the high dose FUS group were TUNEL-negative at the targeted site of FUS.\n\nConclusionsThe absence of FUS-related histologic findings suggests that the neuromodulation and MR-ARFI protocols evaluated do not cause tissue damage.

bioengineering↗