bioRxiv Science⌕ Search

Biology subjects

In, M.-H.

Publications and source records attributed to In, M.-H..

7 recordsLinked to original sources

White matter conduction in the human brain is mostly slow, with rare high velocity connections

White matter bundles play a crucial role in cognitive functions by rapidly transmitting information between brain regions. Inter-areal conduction guides the integration of information and conduction velocity is a fundamental parameter in theories and models of brain function. However, distributions of conduction velocity remain difficult to characterize in vivo in humans. In this work, we integrated diffusion magnetic resonance imaging (dMRI) tractography with intracranial electrical stimulation during clinical stereo-electroencephalography (sEEG) monitoring in 17 subjects to measure conduction velocity within four major white matter bundles. Our findings reveal that human brain conduction is characterized by high variability both within and between bundles, reflecting a predominance of slow connections alongside rare high-speed connections. Because conduction velocity in myelinated fibers follows an approximately linear relationship with axon diameter, we derive underlying axon diameter distributions and show that these estimates are comparable to previous post-mortem studies. These findings demonstrate a heavily skewed distribution of human neural conduction velocities and show that structural heterogeneity shapes the timing and integration of information in large-scale networks.

neuroscience↗

Cerebral Oxygen Budgeting: Network-Level BOLD Dynamics During Acute Hypoxia

Hypoxia constrains cerebral oxygen availability and challenges brain function. Previous work showed that functional connectivity reorganizes early during acute hypoxia, preceding cognitive deterioration, but the functional changes accompanying more severe hypoxic stress remain incompletely understood. We examined dynamic amplitude of low-frequency fluctuations (dALFF) in blood-oxygenation-level dependent (BOLD) fMRI during normoxia, sustained mild hypoxia, and transient severe hypoxia in healthy adults performing a continuous Go/No-go task with concurrent physiological monitoring. We characterized dALFF at whole-brain and network levels using a causal sliding-window approach, principal component analysis, and Schaefer's 17-network parcellation. Severe hypoxia elicited a non-monotonic, phase-dependent dALFF response that was not observed during normoxia or sustained mild hypoxia. Relative preservation during early hypoxia was followed by late-hypoxia suppression, which we operationally defined as a decompensation phase, and by a pronounced rebound after reoxygenation. Within this global response, dALFF became increasingly differentiated across intrinsic brain networks: DefaultA showed marked suppression, whereas SomMotB exhibited relative preservation or enhancement during decompensation. These changes were neither spatially uniform nor tightly synchronized with systemic oxygenation, while broadly overlapping temporally with cognitive deterioration. Together, these findings indicate that dALFF captures a complementary aspect of the brain's response to acute hypoxic stress, characterized by reversible, phase- and network-dependent reorganization of ongoing low-frequency BOLD dynamics under constrained oxygen availability.

neuroscience↗

Brain functional connectivity initiates structured reorganization at a critical oxygen threshold during hypoxia

The human brain dynamically adapts to hypoxia, a reduction in oxygen essential for metabolism. The brains adaptive response to hypoxia, however, remains unclear. We investigated dynamic functional connectivity (FC) in healthy adults under acute hypoxia (FiO2 = 7.7%, 11.8%) using BOLD fMRI, physiological monitoring (PetO2, PetCO2, SpO2), and a Go/No-Go task. Principal component analysis identified a hypoxia-responsive FC component involving 400 cerebral parcels. This component emerged with a critical drop in PetO2 ([~]53 mmHg), preceding changes in SpO2, BOLD signals, and behavior. These FC changes were network-specific and centered on the default mode network (DMN), which selectively synchronized with other high-level cognitive networks. In contrast, visual networks remained stable and segregated from the DMN. These results suggest that the brain proactively reorganizes its functional architecture in anticipation of oxygen decline, rather than in response to it. FC-based markers may offer early indicators of vulnerability in neurological or neurodegenerative conditions.

neuroscience↗

Single pulse electrical stimulation in white matter modulates iEEG visual responses in human early visual cortex

Electrical stimulation is increasingly used to modulate brain networks for clinical purposes. The basic unit of neurostimulation, a single electrical pulse, can travel through white matter to influence connected neuronal populations. However, the mechanisms by which it influences connected populations is not well understood: stimulation may excite, inhibit, or add noise to neuronal population activity. In this study, we investigated how single pulses modulate the neuronal processing of images in a well-controlled visual paradigm. In two human subjects implanted with iEEG electrodes for clinical purposes, single pulses were delivered to electrodes in white matter tracts connected to measurement electrodes in visual cortex. Images appeared on-screen at 0, 100, or 200 ms after each pulse. Using finite impulse response modeling, we decomposed the broadband and evoked potential responses into separate components induced by electrical stimulation and by visual processing. Single pulses induced transient broadband increases followed by suppression, but they did not modulate the visual broadband responses (i.e., stimulation response was additive to visual response). In contrast, single pulses elicited prominent brain stimulation evoked potentials and they modulated the visual evoked potentials. Specifically, visual evoked potentials were larger when stimulation occurred closer to visual onset. This indicates that a single electrical pulse can increase the strength or synchrony of visual inputs. Overall, these findings suggest that the effects of electrical stimulation in the visual system are two-fold: stimulation induces additive effects on broadband power, possibly by adding noise, and it interacts with synchronous visual inputs to amplify them.

neuroscience↗

Signatures of electrical stimulation driven network interactions in the human limbic system

Stimulation-evoked signals are starting to be used as biomarkers to indicate the state and health of brain networks. The human limbic network, often targeted for brain stimulation therapy, is involved in emotion and memory processing. Previous anatomical, neurophysiological and functional studies suggest distinct subsystems within the limbic network (Rolls, 2015). Previous studies using intracranial electrical stimulation, however, have emphasized the similarities of the evoked waveforms across the limbic network. We test whether these subsystems have distinct stimulation-driven signatures. In seven patients with drug-resistant epilepsy we stimulated the limbic system with single pulse electrical stimulation (SPES). Reliable cortico-cortical evoked potentials (CCEPs) were measured between hippocampus and the posterior cingulate cortex (PCC) and between the amygdala and the anterior cingulate cortex (ACC). However, the CCEP waveform in the PCC after hippocampal stimulation showed a unique and reliable morphology, which we term the limbic H-wave. This limbic H-wave was visually distinct and separately decoded from the amygdala to ACC waveform. Diffusion MRI data show that the measured endpoints in the PCC overlap with the endpoints of the parolfactory cingulum bundle rather than the parahippocampal cingulum, suggesting that the limbic H-wave may travel through fornix, mammillary bodies and the anterior nucleus of the thalamus (ANT). This was further confirmed by stimulating the ANT, which evoked the same limbic H-wave but with a shorter latency. Limbic subsystems have unique stimulation evoked signatures that may be used in the future to help develop stimulation therapies. Significance StatementThe limbic system is often compromised in diverse clinical conditions, such as epilepsy or Alzheimers disease, and it is important to characterize its typical circuit responses. Stimulation evoked waveforms have been used in the motor system to diagnose circuit pathology. We translate this framework to limbic subsystems using human intracranial stereo EEG (sEEG) recordings that measure deeper brain areas. Our sEEG recordings describe a stimulation evoked waveform characteristic to the memory and spatial subsystem of the limbic network that we term the limbic H-wave. The limbic H-wave follows anatomical white matter pathways from hippocampus to thalamus to the posterior cingulum and shows promise as a distinct biomarker of signaling in the human brain memory and spatial limbic network.

neuroscience↗

Multivariate pattern classification on BOLD activation pattern induced by deep brain stimulation in motor, associative, and limbic brain networks

Functional magnetic resonance imaging (fMRI) concurrently conducted with the deep brain stimulation (DBS) has shown that diffuse BOLD activation occurred not only near stimulation locus, but in multiple brain networks, supporting that network-wide modulation would underlie its therapeutic effect. While the extent and pattern of activation varies depending on specific anatomical locus stimulated by DBS, some stimulation targets could induce similar activation pattern in cerebral cortex, albeit different therapeutic and adverse effects were yielded.\n\nIn order to characterize the unique network-level activation effects of three DBS targets (subthalamic nucleus, the globus pallidus internus, and the nucleus accumbens), we trained the pattern classifier with DBS-fMRI data from three stimulation groups (21 healthy swine), wherein five six seconds of electrical stimulation was conducted while gradient-echo echo planar imaging was on going. Then whole brain regions were systematically grouped into different size of network-of-interest and the classification accuracy for individual target region was quantitatively assessed. We demonstrated that the pattern classifier could successfully differentiate BOLD activation pattern of cortical and subcortical brain regions originated from each individual stimulation target. Moreover, the success rate of classification indicated that some brain regions evoked indistinguishable BOLD pattern, suggesting the presence of commonly activated regions, which was influenced by stimulating different DBS targets.\n\nOur results provide an understanding of the biomarker of BOLD pattern that is associated with clinical effectiveness as well as an adverse effect associated to the stimulation. Further, we provide the proof-of-concept for multivariate pattern analysis that is capable of disentangling the complicated BOLD activation pattern, which cannot be readily achieved by a conventional univariate analysis.

bioinformatics↗

Resting-state functional connectivity modulates the BOLD activation induced by nucleus accumbens stimulation in the swine brain

While it is known that the clinical efficacy of deep brain stimulation (DBS) alleviates motor-related symptoms, cognitive and behavioral effects of DBS and its action mechanism on brain circuits are not clearly understood. By combining functional magnetic resonance imaging (fMRI) and DBS, we investigated the pattern of blood-oxygenation-level-dependent (BOLD) signal changes induced by stimulating the nucleus accumbens and how inter-regional resting-state functional connectivity is related with the stimulation DBS effect in a healthy swine model. We found that the pattern of stimulation-induced BOLD activation was diffused across multiple functional networks including the prefrontal, limbic, and thalamic regions, altering inter-regional functional connectivity after stimulation. Furthermore, our results showed that the strength of the DBS effect is closely related to the strength of inter-regional resting-state functional connectivity including stimulation locus and remote brain regions. Our results reveal the impact of nucleus accumbens stimulation on major functional networks, highlighting functional connectivity may mediate the modulation effect of DBS via large-scale brain networks.

neuroscience↗