Biology subjects

Uludag, K.

Publications and source records attributed to Uludag, K..

15 recordsLinked to original sources

bioRxiv2026

Relating layer fMRI signals to acoustics and intracranial neuronal activity in the human auditory cortex in a naturalistic design

Naturalistic auditory perception engages feedforward and feedback dynamics across cortical depths, yet how these are organized in the human auditory cortex has been difficult to verify noninvasively. Here, we examine depth-dependent coupling between neuronal activity and fMRI during passive music listening. Depth-specific fMRI responses were modeled using neuronal oscillation envelopes elicited by the same naturalistic stimuli from a separate group of patients under intracranial EEG monitoring. From deep toward superficial depths, the relationship between oscillatory power and fMRI responses systematically changed: alpha/beta activity (8-30 Hz) was increasingly associated with negative fMRI responses, mapping top-down feedback, while gamma band (>30 Hz) oscillations showed increasingly positive associations. Relative to a purely acoustical fMRI baseline, broadband high-frequency activity (>70 Hz), a proxy for neuronal firing, showed the strongest coupling to BOLD signals at intermediate cortical depths receiving feedforward inputs from earlier auditory pathways. Our findings reveal a spectrolaminar organization of neurovascular coupling in the human auditory cortex.

neuroscience↗

bioRxiv2025

Multiscale characterisation of the human claustrum from histology to MRI

Though linked to an unusually broad array of functions, the human claustrums complex morphology has hindered in vivo study, resulting in a small MRI literature marked by implausibly large discrepancies in reported characteristics. We constructed the first three-dimensional histological "gold standard" claustrum model, and systematically evaluated in vivo 7-Tesla MRI datasets against it and downsampled derivatives. MRI showed resolution-dependent differences rather than contrast limitations, transforming the claustrums intricate sheet into an artefactually thickened ribbon. However, submillimetre MRI reliably recovered the dorsal "core" that contains most claustral volume and density and houses major corticoclaustral connectivity. At 0.5mm resolution, extension into the temporal lobe, including irregular ventral "puddles", was partially recovered, with uncertainty reflecting boundary imprecision rather than anatomical loss. Our results refute the view that the claustrum is inaccessible in the living human brain, define practical measurement limits, and provide a foundation for future functional investigations.

neuroscience↗

bioRxiv2025

Evaluating the quality of brainstem ROI registration using structural and diffusion MRI

Accurate registration of regions of interest (ROIs) from standard atlases to participants native spaces is a critical step in fMRI studies, as it directly affects the reliability of sampled BOLD signals. While T1-weighted (T1w) image-based ROI registration is well validated and widely adopted in cortical fMRI, its performance degrades in brainstem studies due to the small size, dense packing, and poor visibility of brainstem nuclei on T1w contrast. We hypothesized that incorporating diffusion MR images, containing more information about internal brainstem architecture, should improve ROI registration accuracy. To test this, we developed four registration pipelines that either included or excluded diffusion-based alignment components and evaluated their performance using data from n=20 healthy participants. Registration accuracy was assessed using Dice coefficient for the red nucleus (RN) and the substantia nigra (SN), and mis-registration fraction--a metric developed for nuclei that cannot be manually delineated--for the dorsal raphe nucleus (DRN). The results showed that diffusion-based pipelines, using fractional anisotropy (FA) images, non-diffusion-weighted (b0) images, and multivariate combination, outperformed the T1w-only baseline. Probabilistic maps derived from inverse-transformed native ROIs further supported improved sensitivity to inter-individual anatomical variability in the diffusion-augmented pipelines. In addition, analysis of gradient magnitude maps from the Jacobian determinants revealed associations between localized deformation and image modality-specific landmarks. These findings demonstrate the potential of diffusion-augmented pipelines for improving brainstem ROI registration, which could enhance the robustness of fMRI studies on brainstem disorders characterized by functional dysregulation.

neuroscience↗

bioRxiv2025

Predictive acoustical processing in human cortical layers

In our dynamic environments, predictive processing is vital for auditory perception and its associated behaviors. Predictive coding formalizes inferential processes by implementing them as information exchange across cortical layers and areas. With laminar-specific blood oxygenation level dependent we measured responses to a cascading oddball paradigm, to ground predictive auditory processes on the mesoscopic human cortical architecture. We show that the violation of predictions are potentially hierarchically organized and associated with responses in superficial layers of the planum polare and middle layers of the lateral temporal cortex. Moreover, we relate the updating of the brains internal model to changes in deep layers. Using a modeling approach, we derive putative changes in neural dynamics while accounting for draining effects. Our results support the role of temporal cortical architecture in the implementation of predictive coding and highlight the ability of laminar fMRI to investigate mesoscopic processes in a large extent of temporal areas.

neuroscience↗

bioRxiv2023

Non-Invasive Perfusion Imaging of the Human Brain via Breath-Holding: A DSC MRI Study

Dynamic susceptibility contrast (DSC) MRI plays a pivotal role in the accurate diagnosis and prognosis of several neurovascular diseases, but is limited by its reliance on gadolinium, an intravascularly injected chelated metal. Here, we determined the feasibility of measuring perfusion using a DSC analysis of breath-hold-induced gradient-echo-MRI signal changes. We acquired data at both 3T and 7T from ten healthy participants who engaged in eight consecutive breath-holds. By pairing a novel arterial input function strategy with a standard DSC MRI analysis, we measured the cerebral blood volume, flow, and transit delay, and found values to agree with those documented in the literature using gadolinium. We also observed voxel-wise agreement between breath-hold and arterial spin labeling measures of cerebral blood flow. Breath-holding resulted in significantly higher contrast-to-noise (6.2 at 3T vs 8.5 at 7T) and gray matter-to-white matter contrast at higher field strength. Finally, using a simulation framework to assess the effect of dynamic vasodilation on perfusion estimation, we found global perfusion underestimation of 20-40%. For the first time, we have assessed the feasibility of and limitations associated with using breath-holds for perfusion estimation with DSC. We hope that the methods and results presented in this study will help pave the way toward contrast-free perfusion imaging, in both basic and clinical research.

biophysics↗

bioRxiv2023

Feasibility of high-resolution perfusion imaging using Arterial Spin Labelling MRI at 3 Tesla

Cerebral blood flow (CBF) is a critical physiological parameter of brain health and it can be non-invasively measured with arterial spin labelling (ASL) MRI. In this study, we evaluated and optimised whole-brain, high-resolution ASL as an alternative to the low-resolution ASL employed in the routine assessment of CBF in both healthy participants and patients. Two high-resolution protocols (i.e., pCASL and FAIR-Q2TIPS (PASL) with 2 mm isotropic voxels) were compared to a default clinical pCASL protocol (3.4 x 3.4 x 4 mm3), all of whom had an acquistion time of {approx} 5 min. We assessed the impact of high-resolution acquisition on reducing partial voluming and improving sensitivity to the perfusion signal, and evaluated the effectiveness of z-deblurring on the ASL data. We compared the quality of whole-brain ASL acquired using three available head coils with differing number of receive channels (i.e., 20, 32 and 64 ch). We found using higher coil counts (32 and 64 ch coils as compared to 20 ch) offer improved SNR and improved acceleration capabilities that are beneficial for ASL imaging at 3T. The inherent reduction in partial voluming effects with higher resolution acquisitions improves the resolving power of perfusion without impacting sensitivity. In conclusion, our results suggest that high-resolution ASL (2 - 2.5 mm isotropic) has the potential to become a new standard for perfusion imaging at 3 T and increase its adoption into clinical research and cognitive neuroscience applications.

neuroscience↗

bioRxiv2022

Perfusion Quantification in the Human Brain Using DSC MRI - Simulations and Validations at 3T

Gadolinium (Gd) and deoxyhemoglobin (dOHb) are paramagnetic contrast agents capable of inducing changes in T2*-weighted MRI signal, utilized in dynamic susceptibility contrast (DSC) MRI. With multiple contrast agents and analysis choices, there are a variety of questions as to its capability to accurately quantify perfusion values. To address these questions, we developed a novel signal model for DSC MRI that incorporates signal contributions from intravascular and extravascular water proton spins at 3T for arterial, venous, and cerebral tissue voxels. This framework allowed us to model the MRI signal in response to changes in Gd and dOHb concentrations, and the effects that various experimental and tissue parameters have on perfusion quantification. We compared the predictions of the numerical simulations with those obtained from experimental data at 3T on six healthy human subjects using Gd and dOHb boluses as contrast agents. Using standard DSC analysis, we identified perfusion quantification dependencies in the experimental results that were in close agreement with the simulations. We found that a reduced baseline oxygen saturation (base-SaO2), greater susceptibility of applied contrast agent (Gd vs dOHb), and larger magnitude of the hypoxic drop ({Delta}SaO2) reduces overestimation of the cerebral blood volume (rCBV) and flow (rCBF). Furthermore, shortening the bolus duration increases the accuracy and reduces the calculated values of mean transit time (MTT). This study demonstrates that changes in Gd and dOHb can be described by the same unifying theoretical framework, as validated by the experimental results. Based on our work, we suggest practices in DSC MRI that increase accuracy and reduce inter- and intra-subject variability. In uncovering a wide array of quantification dependencies, we argue that caution must be exercised when comparing perfusion values obtained from a standard DSC MRI analysis when employing different experimental paradigms.

biophysics↗

bioRxiv2021

Cerebral perfusion imaging: Hypoxia-induced deoxyhemoglobin or gadolinium?

Assessment of resting cerebrovascular perfusion measures (mean transit time, cerebral blood flow and cerebral blood volume) with magnetic resonance imaging currently requires the intravascular injection of the dynamic susceptibility contrast agent gadolinium. An initial comparison between hypoxia-induced deoxyhemoglobin and gadolinium was made for these measures in six healthy participants. A bolus of deoxyhemoglobin is generated in the lung via transient hypoxia induced by an available computer-controlled gas blender technology employing sequential gas delivery (RespirAct). We hypothesised and confirmed perfusion measures from both susceptibility contrast agents would yield similar spatial patterns of cerebrovascular perfusion measures. We conclude that hypoxia-induced deoxyhemoglobin, an endogenously, non-invasively generated, non-allergenic, non-toxic, recyclable, environmentally innocuous molecule, may be suitable to become the first new magnetic resonance imaging susceptibility contrast agent introduction since gadolinium.

neuroscience↗

bioRxiv2021

Neurodegenerative and functional signatures of the cerebellar cortex in m.3243A>G patients

Mutations of the mitochondrial DNA are an important cause of inherited diseases that can severely affect the tissues homeostasis and integrity. The m.3243A>G mutation is the most commonly observed across mitochondrial disorders and is linked to multisystemic complications, including cognitive deficits. In line with in vitro experiments demonstrating the m.3243A>Gs negative impact on neuronal energy production and integrity, m.3243A>G patients show cerebral gray matter tissue changes. However, its impact on the most neuron-dense, and therefore energy-consuming brain structure - the cerebellum - remains elusive. In this work, we used high resolution structural and functional data acquired using 7 Tesla MRI to characterize the neurodegenerative and functional signatures of the cerebellar cortex in m.3243A>G patients. Our results reveal altered tissue integrity within distinct clusters across the cerebellar cortex, apparent by their significantly reduced volume and longitudinal relaxation rate compared to healthy controls, indicating macroscopic atrophy and microstructural pathology. Spatial characterization reveals that these changes occur especially in regions related to the frontoparietal brain network that is involved in information processing and selective attention. In addition, based on resting-state fMRI data, these clusters exhibit reduced functional connectivity to frontal and parietal cortical regions, especially in patients characterized by (i) a severe disease phenotype and (ii) reduced information processing speed and attention control. Combined with our previous work, these results provide insight into the neuropathological changes and a solid base to guide longitudinal studies aimed to track disease progression.

neuroscience↗

bioRxiv2020

Non-invasive brain perfusion MRI using endogenous deoxyhemoglobin as a contrast agent: preliminary data

BackgroundThe paramagnetic properties of deoxyhemoglobin shorten T2* as do gadolinium based contrast agents. Induction of abrupt changes in arterial deoxyhemoglobin concentration ([dOHb]) can simulate intra-vascular injections of gadolinium for perfusion imaging. AimTo demonstrate the feasibility of making rapid changes in pulmonary venous hemoglobin saturation and employing the resulting changes in T2* to calculate flow metrics in the brain. MethodsA gas blender with a sequential gas delivery breathing circuit and software enabling prospective arterial blood gas targeting was used to implement rapid isocapnic lung changes in the partial pressure of blood oxygen (PaO2). Lung PO2 was initially lowered to induce a low baseline [dOHb]. PaO2 was then rapidly raised to PaO2 [~] 100 mmHg for 10 seconds and then rapidly returned to baseline. Blood oxygenation level dependent (BOLD) MRI signal changes were measured over time. ResultsArrival delay, signal amplitude and change in BOLD discriminated between large arteries, tissue and veins. The median half-time of BOLD signal in the middle cerebral artery was 1.7 s, indicating minimal dispersion confirming effective rapid modulation of pulmonary venous PO2. The contrast-to-noise ratio in the cortex was 3. Calculations of arrival delay, cerebral blood volume, mean transit time and cerebral blood flow were within normal ranges from published literature values. ConclusionNon-invasive induction of abrupt changes in [OHb] may function as a novel non-invasive vascular contrast agent for use in perfusion imaging.

neuroscience↗

bioRxiv2020

Sub-millimetre resolution laminar fMRI using Arterial Spin Labelling in humans at 7T

Laminar fMRI at ultra-high magnetic field strength is typically carried out using the Blood Oxygenation Level-Dependent (BOLD) contrast. Despite its unrivalled sensitivity to detecting activation, the BOLD contrast is limited in its spatial specificity due to signals stemming from intra-cortical ascending and pial veins. Alternatively, regional changes in perfusion (i.e., cerebral blood flow through tissue) are colocalised to neuronal activation, which can be non-invasively measured using arterial spin labelling (ASL) MRI. In addition, ASL provides a quantitative marker of neuronal activation in terms of perfusion signal, which is simultaneously acquired along with the BOLD signal. However, ASL for laminar imaging is challenging due to the lower SNR of the perfusion signal and higher RF power deposition i.e., specific absorption rate (SAR) of ASL sequences. In the present study, we present for the first time in humans, isotropic sub-millimetre spatial resolution functional perfusion images using Flow-sensitive Alternating Inversion Recovery (FAIR) ASL with a 3D-EPI readout at 7T. We show that robust statistical activation maps can be obtained with perfusion-weighting in a single session. We observed the characteristic BOLD amplitude increase towards the superficial laminae, and, in apparent discrepancy, the relative perfusion profile shows a decrease of the amplitude and the absolute perfusion profile a much smaller increase towards the cortical surface. Considering the draining vein effect on the BOLD signal using model-based spatial convolution, we show that the empirically measured perfusion and BOLD profiles are, in fact, consistent with each other. This study demonstrates that laminar perfusion fMRI in humans is feasible at 7T and that caution must be exercised when interpreting BOLD signal laminar profiles as direct representation of the cortical distribution of neuronal activity.

neuroscience↗

bioRxiv2020

Direct visualization and characterization of the human zona incerta and surrounding structures

The zona incerta (ZI) is a small gray matter region of the deep brain first identified in the 19th century, yet direct in vivo visualization and characterization has remained elusive. Noninvasive detection of the ZI and surrounding region could be critical to further our understanding of this widely connected but poorly understood deep brain region and could contribute to the development and optimization of neuromodulatory therapies. We demonstrate that high resolution (submillimetric) longitudinal (T1) relaxometry measurements at high magnetic field strength (7 Tesla) can be used to delineate the ZI from surrounding white matter structures, specifically the fasciculus cerebellothalamicus, fields of Forel (fasciculus lenticularis, fasciculus thalamicus, field H), and medial lemniscus. Using this approach, we successfully derived in vivo estimates of the size, shape, location, and tissue characteristics of substructures in the ZI region, confirming observations only previously possible through histological evaluation that this region is not just a space between structures but contains distinct morphological entities that should be considered separately. Our findings pave the way for increasingly detailed in vivo study and provide a structural foundation for precise functional and neuromodulatory investigation.

neuroscience↗

bioRxiv2020

Effects of MP2RAGE B1+ sensitivity on inter-site T1 reproducibility and morphometry at 7T

Most neuroanatomical studies are based on MR images, whose intensity profiles are not solely determined by the tissues longitudinal relaxation times (T1) but also affected by varying non-T1 contributions, hampering data reproducibility. In contrast, quantitative imaging using the MP2RAGE sequence, for example, allows direct characterization of the brain based on the tissue property of interest. Combined with 7 Tesla (7T) MRI, this offers unique opportunities to obtain robust high-resolution brain data characterized by a high reproducibility, sensitivity and specificity. However, specific MP2RAGE parameters choices - e.g., to emphasize intracortical myelin-dependent contrast variations - can substantially impact image quality and cortical analyses through remnants of B1+-related intensity variations, as illustrated in our previous work. To follow up on this: we (1) validate this protocol effect using a dataset acquired with a particularly B1+ insensitive set of MP2RAGE parameters combined with parallel transmission excitation; and (2) extend our analyses to evaluate the effects on hippocampal and subcortical morphometry. The latter remained unexplored initially but will provide important insights related to generalizability and reproducibility of neurodegenerative research using 7T MRI. We confirm that B1+ inhomogeneities have a considerably variable effect on cortical T1 and thickness estimates, as well as on hippocampal and subcortical morphometry depending on MP2RAGE setup. While T1 differed substantially across datasets initially, we show inter-site T1 comparability improves after correcting for the spatially varying B1+ field using a separately acquired Sa2RAGE B1+ map. Finally, as for cortical thickness, removal of B1+ residuals affects hippocampal and subcortical volumetry and boundary definitions, particularly near structures characterized by strong intensity changes (e.g. cerebral spinal fluid and arteries). Taken together, we show that the choice of MP2RAGE parameters can impact T1 comparability across sites and present evidence that hippocampal and subcortical segmentation results are modulated by B1+ inhomogeneities. This calls for careful (1) consideration of sequence parameters when setting acquisition protocols; as well as (2) interpretation of results focused on neuroanatomical changes due to disease. HighlightsO_LIPreviously observed effects of B1+ inhomogeneities on cortical T1 and thickness depend strongly on MP2RAGE parameters C_LIO_LIInter-site comparability of cortical T1 and thickness greatly improves after removal of B1+ residuals C_LIO_LIPost-hoc MP2RAGE B1+ correction affects hippocampal (and subcortical) size and shape analyses C_LIO_LINeuroradiological research would benefit from careful examination of imaging protocols and their impact on results, especially when B1+ maps are not acquired C_LI

neuroscience↗

bioRxiv2019

Depth-resolved ultra-high field fMRI reveals feedback contributions to surface motion perception

Human visual surface perception has neural correlates in early visual cortex, but the extent to which feedback contributes to this activity is not well known. Feedback projections preferentially enter superficial and deep anatomical layers, while avoiding the middle layer, which provides a hypothesis for the cortical depth distribution of fMRI activity related to feedback in early visual cortex. Here, we presented human participants uniform surfaces on a dark, textured background. The grey surface in the left hemifield was either perceived as static or moving based on a manipulation in the right hemifield. Physically, the surface was identical in the left visual hemifield, so any difference in percept likely was related to feedback. Using ultra-high field fMRI, we report the first evidence for a depth distribution of activation in line with feedback during the (illusory) perception of surface motion. Our results fit with a signal re-entering in superficial depths of V1, followed by a feedforward sweep of the re-entered information through V2 and V3, as suggested by activity centred in the middle-depth levels of the latter areas. This positive modulation of the BOLD signal due to illusory surface motion was on top of a strong negative BOLD response in the cortical representation of the surface stimuli, which depended on the presence of texture in the background. Hence, the magnitude and sign of the BOLD response to the surface strongly depended on background properties, and was additionally modulated by the presence or absence of illusory motion perception in a manner compatible with feedback. In summary, the present study demonstrates the potential of depth resolved fMRI in tackling biomechanical questions on perception that so far were only within reach of invasive animal experimentation.

neuroscience↗

bioRxiv2019

A dynamical model of the laminar BOLD response

High-resolution functional magnetic resonance imaging (fMRI) using blood oxygenation dependent level-dependent (BOLD) signal is an increasingly popular tool to non-invasively examine neuronal processes at the mesoscopic level. However, as the BOLD signal stems from hemodynamic changes, its temporal and spatial properties do not match those of the underlying neuronal activity. In particular, the laminar BOLD response (LBR), commonly measured with gradient-echo (GE) MRI sequence, is confounded by non-local changes in deoxygenated hemoglobin and cerebral blood volume propagated within intracortical ascending veins, leading to a unidirectional blurring of the neuronal activity distribution towards the cortical surface. Here, we present a new cortical depth-dependent model of the BOLD response based on the principle of mass conservation, which takes the effect of ascending (and pial) veins on the cortical BOLD responses explicitly into account. It can be used to dynamically model cortical depth profiles of the BOLD signal as a function of various baseline- and activity-related physiological parameters for any spatiotemporal distribution of neuronal changes. We demonstrate that the commonly observed spatial increase of LBR is mainly due to baseline blood volume increase towards the surface. In contrast, an occasionally observed local maximum in the LBR (i.e. the so-called \"bump\") is mainly due to spatially inhomogeneous neuronal changes rather than locally higher baseline blood volume. In addition, we show that the GE-BOLD signal laminar point-spread functions, representing the signal leakage towards the surface, depend on several physiological parameters and on the level of neuronal activity. Furthermore, even in the case of simultaneous neuronal changes at each depth, inter-laminar delays of LBR transients are present due to the ascending vein. In summary, the model provides a conceptual framework for the biophysical interpretation of common experimental observations in high-resolution fMRI data. In the future, the model will allow for deconvolution of the spatiotemporal hemodynamic bias of the LBR and provide an estimate of the underlying laminar excitatory and inhibitory neuronal activity.

neuroscience↗