bioRxiv Science⌕ Search

Biology subjects

Emir, U. E.

Publications and source records attributed to Emir, U. E..

10 recordsLinked to original sources

SORDINO for Silent, Sensitive, Specific, and Artifact-Resisting fMRI in awake behaving mice

Blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has revolutionized our understanding of the brain activity landscape, bridging circuit neuroscience in animal models with noninvasive brain mapping in humans. This immensely utilized technique, however, faces challenges such as acoustic noise, electromagnetic interference, motion artifacts, magnetic-field inhomogeneity, and limitations in sensitivity and specificity. Here, we introduce Steady-state On-the-Ramp Detection of INduction-decay with Oversampling (SORDINO), a transformative fMRI technique that addresses these challenges by maintaining a constant total gradient amplitude while acquiring data during continuously changing gradient direction. When benchmarked against conventional fMRI on a 9.4T system, SORDINO is silent, sensitive, specific, and resistant to motion and susceptibility artifacts. SORDINO offers superior compatibility with multimodal experiments and carries novel contrast mechanisms distinct from BOLD. It also enables brain-wide activity and connectivity mapping in awake, behaving mice, overcoming stress- and motion-related confounds that are among the most challenging barriers in current animal fMRI studies.

neuroscience↗

Dissecting the chain of information processing and its interplay with neurochemicals and fluid intelligence across development

Previous research has highlighted the role of glutamate and gamma-aminobutyric acid (GABA) in perceptual, cognitive, and motor tasks. However, the exact involvement of these neurochemical mechanisms in the chain of information processing, and across human development, are unclear. In a cross-sectional longitudinal design, we used a computational approach to dissociate cognitive, decision, and visuomotor processing in 293 individuals spanning early childhood to adulthood. We found that glutamate and GABA within the intraparietal sulcus (IPS) explained unique variance in visuomotor processing, with higher glutamate predicting poorer visuomotor processing in younger participants but better visuomotor processing in mature participants, while GABA showed the opposite pattern. These findings were functionally, neuroanatomically, and neurochemically specific, and were replicated ~1.5 years later and were generalized in two further different behavioral tasks. Using resting fMRI, we revealed that the relationship between IPS neurochemicals and visuomotor processing is mediated by functional connectivity in the visuomotor network. We then extended our findings to high-level cognitive behavior by predicting fluid intelligence performance. We showed that fluid intelligence performance is explained by IPS GABA and glutamate and is mediated by visuomotor processing, and moderated by the developmental stage. These results provide an integrative biological and psychological mechanistic explanation that links cognitive processes and neurotransmitters across human development and establishes their involvement in intelligent behavior.

neuroscience↗

NIfTI-MRS: A standard format for magnetic resonance spectroscopic data

PurposeThe use of multiple data formats in the MRS community currently hinders data sharing and integration. NIfTI-MRS is proposed as a standard MR spectroscopy data format, which is implemented as an extension to the neuroimaging informatics technology initiative (NIfTI) format. Using this standardised format will facilitate data sharing, ease algorithm development, and encourage the integration of MRS analysis with other imaging modalities. MethodsA file format based on the NIfTI header extension framework was designed to incorporate essential spectroscopic metadata and additional encoding dimensions. A detailed description of the specification is provided. An open-source command-line conversion program is implemented to enable conversion of single-voxel and spectroscopic imaging data to NIfTI-MRS. To provide visualisation of data in NIfTI-MRS, a dedicated plugin is implemented for FSLeyes, the FSL image viewer. ResultsAlongside online documentation, ten example datasets are provided in the proposed format. In addition, minimal examples of NIfTI-MRS readers have been implemented. The conversion software, spec2nii, currently converts fourteen formats to NIfTI-MRS, including DICOM and vendor proprietary formats. ConclusionThe proposed format aims to solve the issue of multiple data formats being used in the MRS community. By providing a single conversion point, it aims to simplify the processing and analysis of MRS data, thereby lowering the barrier to use of MRS. Furthermore, it can serve as the basis for open data sharing, collaboration, and interoperability of analysis programs. It also opens possibility of greater standardisation and harmonisation. By aligning with the dominant format in neuroimaging, NIfTI-MRS enables the use of mature tools present in the imaging community, demonstrated in this work by using a dedicated imaging tool, FSLeyes, as a viewer.

neuroscience↗

Brain stimulation boosts perceptual learning by altering sensory GABAergic plasticity and functional connectivity

Interpreting cluttered scenes --a key skill for successfully interacting with our environment-- relies on our ability to select relevant sensory signals while filtering out noise. Training is known to improve our ability to make these perceptual judgements by altering local processing in sensory brain areas. Yet, the brain-wide network mechanisms that mediate our ability for perceptual learning remain largely unknown. Here, we combine transcranial direct current stimulation (tDCS) with multi-modal brain measures to modulate cortical excitability during training on a signal-in-noise task (i.e. detection of visual patterns in noise) and test directly the link between processing in visual cortex and its interactions with decision-related areas (i.e. posterior parietal cortex). We test whether brain stimulation alters inhibitory processing in visual cortex, as measured by magnetic resonance spectroscopy (MRS) of GABA and functional connectivity between visual and posterior parietal cortex, as measured by resting state functional magnetic resonance imaging (rs-fMRI). We show that anodal tDCS during training results in faster learning and decreased GABA+ during training, before these changes occur for training without stimulation (i.e. sham). Further, anodal tDCS decreases occipito-parietal interactions and time-varying connectivity across the visual cortex. Our findings demonstrate that tDCS boosts learning by accelerating visual GABAergic plasticity and altering interactions between visual and decision-related areas, suggesting that training optimises gain control mechanisms (i.e. GABAergic inhibition) and functional inter-areal interactions to support perceptual learning.

neuroscience↗

A mechanism for hippocampal memory recall based on excitatory-inhibitory fluctuations in neocortex

The brain has a remarkable capacity to acquire and store memories that can later be selectively recalled. These processes are supported by the hippocampus which is thought to index memory recall by reinstating information stored across distributed neocortical circuits. However, the mechanism that supports this interaction remains unclear. Here, in humans, we show that recall of a visual cue from a paired associate is accompanied by a transient increase in the ratio between glutamate and GABA in visual cortex. Moreover, these excitatory-inhibitory fluctuations are predicted by activity in the hippocampus. These data suggest the hippocampus gates memory recall by indexing information stored across neocortical circuits using a disinhibitory mechanism.

neuroscience↗

GABAergic inhibition in the human visual cortex relates to eye dominance

Our binocular world is seamlessly assembled from two retinal images that remain segregated until the cerebral cortex. Despite the coherence of this input, there is often an imbalance between the strength of these connections in the brain. Eye dominance provides a measure of the perceptual dominance of one eye over the other. Theoretical models suggest that eye dominance is related to reciprocal inhibition between monocular units in the primary visual cortex, the first location where the binocular input is combined. As the specific inhibitory interactions in the binocular visual system critically depend on the presence of visual input, we sought to test the role of inhibition by measuring the concentrations of inhibitory (GABA) neurotransmitters during monocular visual stimulation of the dominant and the non-dominant eye. GABA-levels were acquired in V1 using a combined functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) sequence on a 7-Tesla MRI scanner. Individuals with stronger eye dominance had a greater difference in GABAergic inhibition between the eyes. This relationship was present only when the visual system was actively processing sensory input and was not present at rest. We provide the first evidence that imbalances in GABA levels during ongoing sensory processing are related to eye dominance in the human visual cortex. This provides strong support to the view that intracortical inhibition underlies normal eye dominance. SIGNIFICANCE STATEMENTWhat we see is shaped by excitation and inhibition in our brain. We investigated how eye dominance, the perceptual preference of one eyes input over the other, is related to levels of inhibitory neurotransmitter GABA during monocular visual stimulation. GABAergic inhibition is related to eye dominance, but only when the visual system is actively processing sensory input. This provides key support for the view that imbalances in visual competition that are observed in the normal visual system arise from an inability of GABA signalling to suppress the stronger sensory representation.

neuroscience↗

Fast in vivo 23Na imaging and T2* mapping using accelerated 2D-FID magnetic resonance spectroscopic imaging at 3 T: Proof of concept and reliability study

PurposeTo implement an accelerated MR-acquisition method allowing to map sodium T2* relaxation and absolute concentration within skeletal muscles at 3T. MethodsA fast-2D density-weighted concentric-ring-trajectory 23Na-MRSI technique was used to acquire 64 time-points of FID with a spectral bandwidth of 312.5 Hz from a 2.5 x 2.5 mm2 in-plane resolution within about 15 minutes. The fast relaxing 23Na signal was localized with a single-shot, inversion-recovery based, non-echo (SIRENE) OVS method. The sequence was verified using simulation and phantom studies before implementing it in human calf muscles. Within two same-day sessions, 2D-SIRENE-MRSI (UTE = 0.55 ms) and 3D-MRI (UTE = 0.3 ms) data were acquired. The T2* values were fitted voxel-by-voxel using a bi-exponential model for the 2D-MRSI data. Within-subject coefficients of variation were estimated for both acquisition methods. ResultsThe MRSI-FID data allowed for fast and slow T2* mapping of the calf muscles in vivo with minimal sensitivity reduction. The spatial-distributions of 23Na concentration for both in vivo MRSI and 3D-MRI acquisitions were significantly correlated (r = 0.7, P<0.001). The test-retest results rendered high reliability for both MRSI (CV = 5%) and 3D MRI (CV = 6%). The mean [Formula] in calf muscles was 0.7 {+/-} 0.1 (contribution fraction = 37%), while [Formula] was 13.2 {+/-} 0.2 ms (63%). The mean absolute muscle 23Na concentration calculated from the T2*-corrected data was 28.6 {+/-} 3.3 mM. ConclusionThe proposed MRSI technique is a reliable technique to map sodiums absolute concentration and T2* within a clinically acceptable scan time at 3T.

biophysics↗

Musculoskeletal fat imaging and quantification by high-resolution metabolite cycling magnetic resonance spectroscopic imaging at 3 T: A fast method to generate separate distribution maps of lipid components

PurposeTo provide a rapid, non-invasive fat quantification technique capable of producing separate lipid component maps.\n\nMethodsThe calf muscles in 5 healthy adolescents (age 12-16 years; BMI = 20 {+/-} 3 Kg/m2) were scanned by two different fat fraction (FF) quantification methods. A high-resolution, density-weighted concentric ring trajectory (DW-CRT) metabolite cycling (MC) magnetic resonance spectroscopic imaging (MRSI) technique was implemented to collect data with 0.25 mL resolution within 3 minutes and 16 seconds. For comparative purposes, the standard Dixon technique was performed. The two techniques were compared using structural similarity (SSIM) analysis. Additionally, the difference in the distribution of each lipid over the adolescent calf muscles was assessed based on the MRSI data.\n\nResultsThe proposed MRSI technique provided individual FF maps for eight musculoskeletal lipids identified by LCModel analysis (L09, L11, L13, L15, L21, L23, L53, and L55) with mean SSIM indices of 0.19, 0.04, 0.03, 0.50, 0.45, 0.04, 0.07, and 0.12, respectively compared to that of Dixons FF map. Further analysis of voxels with zero SSIM demonstrated an increased sensitivity of FF lipid maps from data acquired using this MRSI technique over the standard Dixon technique. The trend of lipid spatial distribution over calf muscles was consistent with previously published findings in adults.\n\nConclusionThe advantages of this MRSI technique make it a useful tool when individual lipid FF maps are desired within a short scanning time.

biochemistry↗

The hippocampus and neocortical inhibitory engrams protect against memory interference

Our experiences often overlap with each other, sharing features, stimuli or higher-order information. But despite this overlap, we are able to selectively recall individual memories to guide our decisions and future actions. The neural mechanisms that support such precise memory recall, however, remain unclear. Here, using ultra-high field 7T MRI we reveal two distinct mechanisms that protect memories from interference. The first mechanism involves the hippocampus, where the BOLD signal predicts behavioural measures of memory interference, and contextual representations that aid separation of overlapping memories are organised using a relational code. The second mechanism involves neocortical inhibition: when we reduce the concentration of neocortical GABA using trans-cranial direct current stimulation (tDCS) neocortical memory interference increases in proportion to the reduction in GABA, which in turn predicts behavioural performance. Together these findings suggest that memory interference is mediated by both the hippocampus and neocortex, where the hippocampus aids separation of memories by coding context-dependent relational information, while neocortical inhibition prevents unwanted co-activation between overlapping memories.

neuroscience↗

The dynamics of cortical GABA in human motor learning

The ability to learn novel motor skills is both a central part of our daily lives and can provide a model for rehabilitation after a stroke. However, there are still fundamental gaps in our understanding of the physiological mechanisms that underpin human motor plasticity. The acquisition of new motor skills is dependent on changes in local circuitry within the primary motor cortex (M1). This reorganisation has been hypothesised to be facilitated by a decrease in local inhibition via modulation of the neurotransmitter GABA, but this link has not been conclusively demonstrated in humans. Here, we used 7T MR Spectroscopy to investigate the dynamics of GABA concentrations in human M1 during the learning of an explicit, serial reaction time task. We observed a significant reduction in GABA concentration during motor learning that was not seen in an equivalent motor task lacking a learnable sequence, nor during a passive resting task of the same duration. No change in glutamate was observed in any group. Furthermore, baseline M1 GABA was strongly predictive of the degree of subsequent learning, such that greater inhibition was associated with poorer subsequent learning. This result suggests that higher levels of cortical inhibition may present a barrier that must be surmounted in order achieve an increase in M1 excitability, and hence encoding of a new motor skill. These results provide strong support for the mechanistic role of GABAergic inhibition in motor plasticity, raising questions regarding the link between population variability in motor learning and GABA metabolism in the brain.\n\nFunding informationJ.K.:Wellcome Trust Sir Henry Wellcome Postdoctoral Fellowship (204696/Z/16/Z). C.J.S.: Wellcome Trust/Royal Society Henry Dale Fellowships (102584/Z/13/Z).

neuroscience↗