Temporal Fidelity Research Articles

The Emotional Cerebellum

Great attention has been given so far to cerebellar control of posture and of skilled movements despite the well-demonstrated interconnections between the cerebellum and the autonomic nervous system. Here is a review of the link between these two structures and a report on the recently acquired evidence for its involvement in the world of emotions. In rodents, the reversible inactivation of the vermis during the consolidation or the reconsolidation period hampers the retention of the fear memory trace. In this region, there is a long-term potentiation of both the excitatory synapses between the parallel fibres and the Purkinje cells and of the feed-forward inhibition mediated by molecular layer interneurons. This concomitant potentiation ensures the temporal fidelity of the system. Additional contacts between mossy fibre terminals and Golgi cells provide morphological evidence of the potentiation of another feed-forward inhibition in the granular layer. Imaging experiments show that also in humans the cerebellum is activated during mental recall of emotional personal episodes and during learning of a conditioned or unconditioned association involving emotions. The vermis participates in fear learning and memory mechanisms related to the expression of autonomic and motor responses of emotions. In humans, the cerebellar hemispheres are also involved at a higher emotional level. The importance of these findings is evident when considering the cerebellar malfunctioning in psychiatric diseases like autism and schizophrenia which are characterized behaviourally by emotion processing impairments.

Translational control of chronic pain.

Pain is a crucial physiological response to injury and pathologies. The development and maintenance of pain requires the expression of novel genes. The expression of such genes occurs in highly regulated and orchestrated manner where protein translation provides an exquisite temporal and spatial fidelity within the axons and dendrites of neurons. Signaling pathways that regulate local translation are activated by cytokines, neurotrophic factors, or neurotransmitters, which are released either due to tissue damage or neuronal activity. In recent years, the ERK and mTOR pathways have been demonstrated to be central in regulating local translation in neurons of both the peripheral and central nervous systems in diverse models of chronic pain. The ERK and mTOR pathways converge onto the cap-dependent translational machinery that regulates genes essential for the development of nociceptive sensitization. Moreover, inhibition of these pathways has proved to be effective in normalizing the biochemical changes and the associated pain in various preclinical models.

Patch based reconstruction of undersampled data (PROUD) for high signal-to-noise ratio and high frame rate contrast enhanced liver imaging.

High spatial-temporal four-dimensional imaging with large volume coverage is necessary to accurately capture and characterize liver lesions. Traditionally, parallel imaging and adapted sampling are used toward this goal, but they typically result in a loss of signal to noise. Furthermore, residual under-sampling artifacts can be temporally varying and complicate the quantitative analysis of contrast enhancement curves needed for pharmacokinetic modeling. We propose to overcome these problems using a novel patch-based regularization approach called Patch-based Reconstruction Of Under-sampled Data (PROUD). PROUD produces high frame rate image reconstructions by exploiting the strong similarities in spatial patches between successive time frames to overcome the severe k-space under-sampling. To validate PROUD, a numerical liver perfusion phantom was developed to characterize contrast-to-noise ratio (CNR) performance compared with a previously proposed method, TRACER. A second numerical phantom was constructed to evaluate the temporal footprint and lag of PROUD and TRACER reconstructions. Finally, PROUD and TRACER were evaluated in a cohort of five liver donors. In the CNR phantom, PROUD, compared with TRACER, improved peak CNR by 3.66 times while maintaining or improving temporal fidelity. In vivo, PROUD demonstrated an average increase in CNR of 60% compared with TRACER. The results presented in this work demonstrate the feasibility of using a combination of patch based image constraints with temporal regularization to provide high SNR, high temporal frame rate and spatial resolution four dimensional imaging.

Single-trial imaging of spikes and synaptic potentials in single neurons in brain slices with genetically encoded hybrid voltage sensor.

Genetically encoded voltage sensors expand the optogenetics toolkit into the important realm of electrical recording, enabling researchers to study the dynamic activity of complex neural circuits in real time. However, these probes have thus far performed poorly when tested in intact neural circuits. Hybrid voltage sensors (hVOS) enable the imaging of voltage by harnessing the resonant energy transfer that occurs between a genetically encoded component, a membrane-tethered fluorescent protein that serves as a donor, and a small charged molecule, dipicrylamine, which serves as an acceptor. hVOS generates optical signals as a result of voltage-induced changes in donor-acceptor distance. We expressed the hVOS probe in mouse brain by in utero electroporation and in transgenic mice with a neuronal promoter. Under conditions favoring sparse labeling we could visualize single-labeled neurons. hVOS imaging reported electrically evoked fluorescence changes from individual neurons in slices from entorhinal cortex, somatosensory cortex, and hippocampus. These fluorescence signals tracked action potentials in individual neurons in a single trial with excellent temporal fidelity, producing changes that exceeded background noise by as much as 16-fold. Subthreshold synaptic potentials were detected in single trials in multiple distinct cells simultaneously. We followed signal propagation between different cells within one field of view and between dendrites and somata of the same cell. hVOS imaging thus provides a tool for high-resolution recording of electrical activity from genetically targeted cells in intact neuronal circuits.

Reconstruction of dynamic image series from undersampled MRI data using data-driven model consistency condition (MOCCO).

To accelerate dynamic MR imaging through development of a novel image reconstruction technique using low-rank temporal signal models preestimated from training data. We introduce the model consistency condition (MOCCO) technique, which utilizes temporal models to regularize reconstruction without constraining the solution to be low-rank, as is performed in related techniques. This is achieved by using a data-driven model to design a transform for compressed sensing-type regularization. The enforcement of general compliance with the model without excessively penalizing deviating signal allows recovery of a full-rank solution. Our method was compared with a standard low-rank approach utilizing model-based dimensionality reduction in phantoms and patient examinations for time-resolved contrast-enhanced angiography (CE-MRA) and cardiac CINE imaging. We studied the sensitivity of all methods to rank reduction and temporal subspace modeling errors. MOCCO demonstrated reduced sensitivity to modeling errors compared with the standard approach. Full-rank MOCCO solutions showed significantly improved preservation of temporal fidelity and aliasing/noise suppression in highly accelerated CE-MRA (acceleration up to 27) and cardiac CINE (acceleration up to 15) data. MOCCO overcomes several important deficiencies of previously proposed methods based on pre-estimated temporal models and allows high quality image restoration from highly undersampled CE-MRA and cardiac CINE data.

Perceptual Training Restores Impaired Cortical Temporal Processing Due to Lead Exposure.

Low-level lead exposure is a risk factor for cognitive and learning disabilities in children and has been specifically associated with deficits in auditory temporal processing that impair aural language and reading abilities. Here, we show that rats exposed to low levels of lead in early life display a significant behavioral impairment in an auditory temporal rate discrimination task. Lead exposure also results in a degradation of the neuronal repetition-rate following capacity and response synchronization in primary auditory cortex. A modified go/no-go repetition-rate discrimination task applied in adult animals for ∼50 days nearly restores to normal these lead-induced deficits in cortical temporal fidelity. Cortical expressions of parvalbumin, brain-derived neurotrophic factor, and NMDA receptor subunits NR2a and NR2b, which are down-regulated in lead-exposed animals, are also partially reversed with training. These studies in an animal model identify the primary auditory cortex as a novel target for low-level lead exposure and demonstrate that perceptual training can ameliorate lead-induced deficits in cortical discrimination between sound sequences.

The Decoupled Mind: Mind-wandering Disrupts Cortical Phase-locking to Perceptual Events

The mind flows in a "stream of consciousness," which often neglects immediate sensory input in favor of focusing on intrinsic, self-generated thoughts or images. Although considerable research has documented the disruptive influences of task-unrelated thought for perceptual processing and task performance, the brain dynamics associated with these phenomena are not well understood. Here we investigate the possibility, suggested by several convergent lines of research, that task-unrelated thought is associated with a reduction in the trial-to-trial phase consistency of the oscillatory neural signal in response to perceptual input. Using an experience sampling paradigm coupled with continuous high-density electroencephalography, we observed that task-unrelated thought was associated with a reduction of the P1 ERP, replicating prior observations that mind-wandering is accompanied by a reduction of the brain-evoked response to sensory input. Time-frequency analysis of the oscillatory neural response revealed a decrease in theta-band cortical phase-locking, which peaked over parietal scalp regions. Furthermore, we observed that task-unrelated thought impacted the oscillatory mode of the brain during the initiation of a task-relevant action, such that more cortical processing was required to meet task demands. Together, these findings document that the attenuation of perceptual processing that occurs during task-unrelated thought is associated with a reduction in the temporal fidelity with which the brain responds to a stimulus and suggest that increased neural processing may be required to recouple attention to a task. More generally, these data provide novel confirmatory evidence for the mechanisms through which attentional states facilitate the neural processing of sensory input.

Bioclimatic variables derived from remote sensing: assessment and application for species distribution modelling

Summary Remote sensing techniques offer an opportunity to improve biodiversity modelling and prediction world‐wide. Yet, to date, the weather station‐based WorldClim data set has been the primary source of temperature and precipitation information used in correlative species distribution models. WorldClim consists of grids interpolated from in situ station data recorded primarily from 1960 to 1990. Those data sets suffer from uneven geographic coverage, with many areas of Earth poorly represented. Here, we compare two remote sensing data sources for the purposes of biodiversity prediction: MERRA climate reanalysis data and AMSR‐E, a pure remote sensing data source. We use these data to generate novel temperature‐based bioclimatic information and to model the distributions of 20 species of vertebrates endemic to four regions of South America: Amazonia, the Atlantic Forest, the Cerrado and Patagonia. We compare the bioclimatic data sets derived from MERRA and AMSR‐E information with in situ station data and contrast species distribution models based on these two products to models built with WorldClim. Surface temperature estimates provided by MERRA and AMSR‐E showed warm temperature biases relative to the in situ data fields, but the reliability of these data sets varied in geographic space. Species distribution models derived from the MERRA data performed equally well (in Cerrado, Amazonia and Patagonia) or better (Atlantic Forest) than models built with the WorldClim data. In contrast, the performance of models constructed with the AMSR‐E data was similar to (Amazonia, Atlantic Forest, Cerrado) or worse than (Patagonia) that of models built with WorldClim data. Whereas this initial comparison assessed only temperature fields, efforts to estimate precipitation from remote sensing information hold great promise; furthermore, other environmental data sets with higher spatial and temporal fidelity may improve upon these results.

A fine balance: Regulation of hippocampal Arc/Arg3.1 transcription, translation and degradation in a rat model of normal cognitive aging

Memory decline is a common feature of aging. Expression of the immediate-early gene Arc is necessary for normal long-term memory, and although experience dependent Arc transcription is reportedly reduced in the aged rat hippocampus, it has not been clear whether this effect is an invariant consequence of growing older, or a finding linked specifically to age-related memory impairment. Here we show that experience dependent Arc mRNA expression in the hippocampus fails selectively among aged rats with spatial memory deficits. While these findings are consistent with the possibility that blunted Arc transcription contributes to cognitive aging, we also found increased basal ARC protein levels in the CA1 field of the hippocampus in aged rats with memory impairment, together with a loss of the experience dependent increase observed in young and unimpaired aged rats. Follow-up analysis revealed that increased basal translation and blunted ubiquitin mediated degradation may contribute to increased basal ARC protein levels noted in memory impaired aged rats. These findings indicate that Arc expression is regulated at multiple levels, and that several of these mechanisms are altered in cognitively impaired aged rats. Defining the influence of these alterations on the spatial and temporal fidelity of synapse specific, memory-related plasticity in the aged hippocampus is an important challenge.

Eye movement measurement in diagnostic assessment of disorders of consciousness.

We review the literature to appraise the evidence supporting or disputing the use of eye movement measurement in disorders of consciousness (DOC) with low levels of arousal or awareness, such as minimally conscious state (MCS), vegetative state (VS), and coma for diagnostic and prognostic purposes. We will focus on the effectiveness of each technique in the diagnostic classification of these patients and the gradual trend in research from manual to computerized tracking methods. New tools have become available at clinicians’ disposal to assess eye movements with high spatial and temporal fidelity. The close relationship between eye movement generation and organic dysfunction in the brain allows these tools to be applied to the assessment of severe DOC as a unique supplementary toolset. We posit that eye tracking can improve clinical diagnostic precision for DOC, a key component of assessment that often dictates the course of clinical care in DOC patients. We see the emergence of long-term eye-tracking studies with seamless integration of technology in the future to improve the performance of clinical assessment in DOC.

Improved Calibration of Voltammetric Sensors for Studying Pharmacological Effects on Dopamine Transporter Kinetics in Vivo.

The distribution and density of neurons within the brain poses many challenges when making quantitative measurements of neurotransmission in the extracellular space. A volume neurotransmitter is released into the synapse during chemical communication and must diffuse through the extracellular space to an implanted sensor for real-time in situ detection. Fast-scan cyclic voltammetry is an excellent technique for measuring biologically relevant concentration changes in vivo; however, the sensitivity is limited by mass-transport-limited adsorption. Due to the resistance to mass transfer in the brain, the response time of voltammetric sensors is increased, which decreases the sensitivity and the temporal fidelity of the measurement. Here, experimental results reveal how the tortuosity of the extracellular space affects the response of the electrode. Additionally, a model of mass-transport-limited adsorption is utilized to account for both the strength of adsorption and the magnitude of the diffusion coefficient to calculate the response time of the electrode. The response time is then used to determine the concentration of dopamine released in response to salient stimuli. We present the method of kinetic calibration of in vivo voltammetric data and apply the method to discern changes in the KM for the murine dopamine transporter. The KM increased from 0.32 ± 0.08 μM (n = 3 animals) prior to drug administration to 2.72 ± 0.37 μM (n = 3 animals) after treatment with GBR-12909.

A g-factor metric for k-t-GRAPPA- and PEAK-GRAPPA-based parallel imaging.

The aim of this work is to derive a theoretical framework for quantitative noise and temporal fidelity analysis of time-resolved k-space-based parallel imaging methods. An analytical formalism of noise distribution is derived extending the existing g-factor formulation for nontime-resolved generalized autocalibrating partially parallel acquisition (GRAPPA) to time-resolved k-space-based methods. The noise analysis considers temporal noise correlations and is further accompanied by a temporal filtering analysis. All methods are derived and presented for k-t-GRAPPA and PEAK-GRAPPA. A sliding window reconstruction and nontime-resolved GRAPPA are taken as a reference. Statistical validation is based on series of pseudoreplica images. The analysis is demonstrated on a short-axis cardiac CINE dataset. The superior signal-to-noise performance of time-resolved over nontime-resolved parallel imaging methods at the expense of temporal frequency filtering is analytically confirmed. Further, different temporal frequency filter characteristics of k-t-GRAPPA, PEAK-GRAPPA, and sliding window are revealed. The proposed analysis of noise behavior and temporal fidelity establishes a theoretical basis for a quantitative evaluation of time-resolved reconstruction methods. Therefore, the presented theory allows for comparison between time-resolved parallel imaging methods and also nontime-resolved methods. Magn Reson Med 74:125-135, 2015. © 2014 Wiley Periodicals, Inc.

Abstracts fromThe 32nd AnnualNational Neurotrauma SymposiumJune 29–July 2, 2014San Francisco, California

Abstracts fromThe 32^nd AnnualNational Neurotrauma SymposiumJune 29–July 2, 2014San Francisco, California

The RNA exosome affects iron response and sensitivity to oxidative stress.

RNA degradation plays important roles for maintaining temporal control and fidelity of gene expression, as well as processing of transcripts. In Saccharomyces cerevisiae the RNA exosome is a major 3'-to-5' exoribonuclease and also has an endonuclease domain of unknown function. Here we report a physiological role for the exosome in response to a stimulus. We show that inactivating the exoribonuclease active site of Rrp44 up-regulates the iron uptake regulon. This up-regulation is caused by increased levels of reactive oxygen species (ROS) in the mutant. Elevated ROS also causes hypersensitivity to H2O2, which can be reduced by the addition of iron to H2O2 stressed cells. Finally, we show that the previously characterized slow growth phenotype of rrp44-exo(-) is largely ameliorated during fermentative growth. While the molecular functions of Rrp44 and the RNA exosome have been extensively characterized, our studies characterize how this molecular function affects the physiology of the organism.

Stacked space-time densities: a geovisualisation approach to explore dynamics of space use over time

Recent developments and ubiquitous use of global positioning devices have revolutionised movement ecology. Scientists are able to collect increasingly larger movement datasets at increasingly smaller spatial and temporal resolutions. These data consist of trajectories in space and time, represented as time series of measured locations for each tagged animal. Such data are analysed and visualised using methods for estimation of home range or utilisation distribution, which are often based on 2D kernel density in geographic space. These methods have been developed for much sparser and smaller datasets obtained through very high frequency (VHF) radio telemetry. They focus on the spatial distribution of measurement locations and ignore time and sequentiality of measurements. We present an alternative geovisualisation method for spatio-temporal aggregation of trajectories of tagged animals: stacked space-time densities. The method was developed to visually portray temporal changes in animal use of space using a volumetric display in a space-time cube. We describe the algorithm for calculation of stacked densities using four different decay functions, normally used in space use studies: linear decay, bisquare decay, Gaussian decay and Brownian decay. We present a case study, where we visualise trajectories of lesser black backed gulls, collected over 30 days. We demonstrate how the method can be used to evaluate temporal site fidelity of each bird through identification of two different temporal movement patterns in the stacked density volume: spatio-temporal hot spots and spatial-only hot spots.

On the Temporal Fidelity of Nonlinear Inverse Reconstructions for Real- Time MRI – The Motion Challenge

Purpose: To evaluate the temporal accuracy of a self-consistent nonlinear inverse reconstruction method (NLINV) for real-time MRI using highly undersampled radial gradient-echo sequences and to present an open source framework for the motion assessment of real-time MRI methods. Methods: Serial image reconstructions by NLINV combine a joint estimation of individual frames and corresponding coil sensitivities with temporal regularization to a preceding frame. The temporal fidelity of the method was determined with a phantom consisting of water-filled tubes rotating at defined angular velocity. The conditions tested correspond to real-time cardiac MRI using SSFP contrast at 1.5 T (40 ms resolution) and T1 contrast at 3.0 T (33 ms and 18 ms resolution). In addition, the performance of a post-processing temporal median filter was evaluated. Results: NLINV reconstructions without temporal filtering yield accurate estimations as long as the speed of a small moving object corresponds to a spatial displacement during the acquisition of a single frame which is smaller than the object itself. Faster movements may lead to geometric distortions. For small objects moving at high velocity, a median filter may severely compromise the spatiotemporal accuracy. Conclusion: NLINV reconstructions offer excellent temporal fidelity as long as the image acquisition time is short enough to adequately sample (“freeze”) the object movement. Temporal filtering should be applied with caution. The motion framework emerges as a valuable tool for the evaluation of real-time MRI methods.

The spatial and temporal fidelity in real-time MRI in patients with sinus rhythm and arrhythmias

Background Irregularly irregular arrhythmia is difficult to image with conventional cine CMR because arrhythmia rejection and registration-based reconstruction result in cardiac motion artifacts or unachievable breath-hold durations. Undersampled radial trajectories, combined with a suitable non-Cartesian reconstruction algorithm, have the potential to overcome these problems by sampling a small number of radial projections without loss of temporal fidelity associated with temporal regularization. Despite the large number of available real-time reconstruction algorithms and sampling trajectories, there are very few reports regarding optimal values for basic reconstruction parameters such as image exposure time (radial projections per image frame) and temporal resolution (view sharing). Our goal was to address the problem of spatial and temporal fidelity in real-time MRI using automatic active contour segmentation in subjects with sinus rhythm and also patients with irregularly irregular arrhythmias.

Fast pediatric 3D free-breathing abdominal dynamic contrast enhanced MRI with high spatiotemporal resolution.

To develop a method for fast pediatric 3D free-breathing abdominal dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) and investigate its clinical feasibility. A combined locally low rank parallel imaging method with soft gating is proposed for free-breathing DCE MRI acquisition. With Institutional Review Board (IRB) approval and informed consent/assent, 23 consecutive pediatric patients were recruited for this study. Free-breathing DCE MRI with ∼1 mm(3) spatial resolution and a 6.5-sec frame rate was acquired on a 3T scanner. Undersampled data were reconstructed with a compressed sensing method without motion correction (FB-CS) and the proposed method (FB-LR). A follow-up respiratory-triggered acquisition (RT-CS) was performed as a reference standard. The reconstructed images were evaluated independently by two radiologists. Wilcoxon tests were performed to test the hypothesis that there was no significant difference between different reconstructions. Quantitative evaluation of contrast dynamics was also performed. The mean score of overall image quality of FB-LR was 4.0 on a 5-point scale, significantly better (P < 0.05) than FB-CS reconstruction (mean score 2.9), and similar to RT-CS (mean score 4.1). FB-LR also matched the temporal fidelity of contrast dynamics with a root mean square error less than 5%. Fast 3D free-breathing DCE MRI with high scan efficiency and image quality similar to respiratory-triggered acquisition is feasible in a pediatric clinical setting.

Noncontrast enhanced four‐dimensional dynamic MRA with golden angle radial acquisition and k‐space weighted image contrast (KWIC) reconstruction

To explore the feasibility of 2D and 3D golden-angle radial acquisition strategies in conjunction with k-space weighted image contrast (KWIC) temporal filtering to achieve noncontrast enhanced dynamic MRA (dMRA) with high spatial resolution, low streaking artifacts and high temporal fidelity. Simulations and in vivo examinations in eight normal volunteers and an arteriovenous malformation patient were carried out. Both 2D and 3D golden angle radial sequences, preceded by spin tagging, were used for dMRA of the brain. The radial dMRA data were temporally filtered using the KWIC strategy and compared with matched standard Cartesian techniques. The 2D and 3D dynamic MRA image series acquired with the proposed radial techniques demonstrated excellent image quality without discernible temporal blurring compared with standard Cartesian based approaches. The image quality of radial dMRA was equivalent to or higher than that of Cartesian dMRA by visual inspection. A reduction factor of up to 10 and 3 in scan time was achieved for 2D and 3D radial dMRA compared with the Cartesian-based counterparts. The proposed 2D and 3D radial dMRA techniques demonstrated image quality comparable or even superior to those obtained with standard Cartesian methods, but within a fraction of the scan time.

Evaluation of highly accelerated real‐time cardiac cine MRI in tachycardia

Electrocardiogram (ECG)-gated breath-hold cine MRI is considered to be the gold standard test for the assessment of cardiac function. However, it may fail in patients with arrhythmia, impaired breath-hold capacity and poor ECG gating. Although ungated real-time cine MRI may mitigate these problems, commercially available real-time cine MRI pulse sequences using parallel imaging typically yield relatively poor spatiotemporal resolution because of their low image acquisition efficiency. As an extension of our previous work, the purpose of this study was to evaluate the diagnostic quality and accuracy of eight-fold-accelerated real-time cine MRI with compressed sensing (CS) for the quantification of cardiac function in tachycardia, where it is challenging for real-time cine MRI to provide sufficient spatiotemporal resolution. We evaluated the performances of eight-fold-accelerated cine MRI with CS, three-fold-accelerated real-time cine MRI with temporal generalized autocalibrating partially parallel acquisitions (TGRAPPA) and ECG-gated breath-hold cine MRI in 21 large animals with tachycardia (mean heart rate, 104 beats per minute) at 3T. For each cine MRI method, two expert readers evaluated the diagnostic quality in four categories (image quality, temporal fidelity of wall motion, artifacts and apparent noise) using a Likert scale (1-5, worst to best). One reader evaluated the left ventricular functional parameters. The diagnostic quality scores were significantly different between the three cine pulse sequences, except for the artifact level between CS and TGRAPPA real-time cine MRI. Both ECG-gated breath-hold cine MRI and eight-fold accelerated real-time cine MRI yielded all four scores of ≥ 3.0 (acceptable), whereas three-fold-accelerated real-time cine MRI yielded all scores below 3.0, except for artifact (3.0). The left ventricular ejection fraction (LVEF) measurements agreed better between ECG-gated cine MRI and eight-fold-accelerated real-time cine MRI (mean difference, -1.6%) than between ECG-gated cine MRI and three-fold-accelerated real-time cine MRI (mean difference, -5.7%). Eight-fold-accelerated real-time cine MRI with CS yields acceptable diagnostic quality and relatively accurate LVEF measurements in the challenging setting of tachycardia.