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Spatial and temporal independent component analysis of functional MRI data containing a pair of task-related waveforms.

Independent component analysis (ICA) is a technique that attempts to separate data into maximally independent groups. Achieving maximal independence in space or time yields two varieties of ICA meaningful for functional MRI (fMRI) applications: spatial ICA (SICA) and temporal ICA (TICA). SICA has so far dominated the application of ICA to fMRI. The objective of these experiments was to study ICA with two predictable components present and evaluate the importance of the underlying independence assumption in the application of ICA. Four novel visual activation paradigms were designed, each consisting of two spatiotemporal components that were either spatially dependent, temporally dependent, both spatially and temporally dependent, or spatially and temporally uncorrelated, respectively. Simulated data were generated and fMRI data from six subjects were acquired using these paradigms. Data from each paradigm were analyzed with regression analysis in order to determine if the signal was occurring as expected. Spatial and temporal ICA were then applied to these data, with the general result that ICA found components only where expected, e.g., S(T)ICA "failed" (i.e., yielded independent components unrelated to the "self-evident" components) for paradigms that were spatially (temporally) dependent, and "worked" otherwise. Regression analysis proved a useful "check" for these data, however strong hypotheses will not always be available, and a strength of ICA is that it can characterize data without making specific modeling assumptions. We report a careful examination of some of the assumptions behind ICA methodologies, provide examples of when applying ICA would provide difficult-to-interpret results, and offer suggestions for applying ICA to fMRI data especially when more than one task-related component is present in the data.

Algorithms↗

Medium-range oscillatory network and the 20-Hz sensorimotor induced potential.

Although synchronously oscillating neuronal assemblies have been the subject of many studies, a clear identification of the spatiotemporal characteristics of a medium-range oscillatory network is still lacking. Herein, we present a method for the extraction of a new waveform, namely the mean induced potential (IP), which allows the identification of the spatiotemporal characteristics of induced EEG responses. The IP calculation was applied to the 20-Hz component of the sensorimotor rhythm in order to obtain a 20-Hz sensorimotor induced potential (20-Hz SIP). The spatiotemporal characteristics of the 20-Hz bursts seen after median nerve stimulation and self-paced finger movements were extracted by means of current source density reconstruction and synchronization analysis. A cortical network including the controlateral primary motor cortex, the supplementary motor area, and the controlateral supramarginalis gyrus was found to generate the 20-Hz bursts, and the various activated areas were found to be highly synchronized. Our results demonstrate for the first time the existence of a medium-range cortical network in the human sensorimotor region whose constituents oscillate synchronously.

Adult↗

Variations on the vertical jump: individual adaptations to changing task demands.

Here we explored the coordination of joint behaviors exhibited during the vertical jump and variations of that jump. By manipulating the take-off angle, we required an adjustment to changing task demands. It was hypothesized that kinematic features of the jump would change but that spatiotemporal relationships essential to propulsion would remain invariant across all conditions. To test this hypothesis, six adult male subjects performed jumps at six different take-off angles. An analysis of cinematographic data revealed that individual subjects changed the sequence and timing of lower-extremity joint reversals. In contrast, the covariation of joint behaviors during the propulsive phase and the timing of maximum intersegmental extension velocities were extremely stable within each individual across changes in task. We argue that the flexibility to alter sequence and timing is part of a strategy that permits adaptation to the context and facilitates a continued coordination among variables associated with propulsion.

Journal Article↗

Modulation of the frequency of spontaneous sarcoplasmic reticulum Ca2+ release events (Ca2+ sparks) by myoplasmic [Mg2+] in frog skeletal muscle.

The modulation by internal free [Mg2+] of spontaneous calcium release events (Ca2+ "sparks") from the sarcoplasmic reticulum (SR) was studied in depolarized notched frog skeletal muscle fibers using a laser scanning confocal microscope in line-scan mode (x vs. t). Over the range of [Mg2+] from 0.13 to 1.86 mM, decreasing the [Mg2+] induced an increase in the frequency of calcium release events in proportion to [Mg2+]-1.6. The change of event frequency was not due to changes in [Mg-ATP] or [ATP]. Analysis of individual SR calcium release event properties showed that the variation in event frequency induced by the change of [Mg2+] was not accompanied by any changes in the spatiotemporal spread (i.e., spatial half width or temporal half duration) of Ca2+ sparks. The increase in event frequency also had no effect on the distribution of event amplitudes. Finally, the rise time of calcium sparks was independent of the [Mg2+], indicating that the open time of the SR channel or channels underlying spontaneous calcium release events was not altered by [Mg2+] over the range tested. These results suggest that in resting skeletal fibers, [Mg2+] modulates the SR calcium release channel opening frequency by modifying the average closed time of the channel without altering the open time. A kinetic reaction scheme consistent with our results and those of bilayer and SR vesicle experiments indicates that physiological levels of resting Mg2+ may inhibit channel opening by occupying the site for calcium activation of the SR calcium release channel.

Adenine Nucleotides↗

Hierarchical Bayesian inference in the visual cortex.

Traditional views of visual processing suggest that early visual neurons in areas V1 and V2 are static spatiotemporal filters that extract local features from a visual scene. The extracted information is then channeled through a feedforward chain of modules in successively higher visual areas for further analysis. Recent electrophysiological recordings from early visual neurons in awake behaving monkeys reveal that there are many levels of complexity in the information processing of the early visual cortex, as seen in the long-latency responses of its neurons. These new findings suggest that activity in the early visual cortex is tightly coupled and highly interactive with the rest of the visual system. They lead us to propose a new theoretical setting based on the mathematical framework of hierarchical Bayesian inference for reasoning about the visual system. In this framework, the recurrent feedforward/feedback loops in the cortex serve to integrate top-down contextual priors and bottom-up observations so as to implement concurrent probabilistic inference along the visual hierarchy. We suggest that the algorithms of particle filtering and Bayesian-belief propagation might model these interactive cortical computations. We review some recent neurophysiological evidences that support the plausibility of these ideas.

Animals↗

Organization and regulation of the rat Cx31 gene. Implication for a crucial role of the intron region.

The connexin31 (Cx31) gene, a member of the connexin multigene family, is expressed in a characteristic spatiotemporal pattern during placental development in rodents. To elucidate the trophoblast-specific regulation of Cx31, we have isolated the rat Cx31 gene and performed structural and functional promoter analysis. The isolated Cx31 gene contains two exons separated by an intron of 2.6 kb. The first exon of the Cx31 gene is preceded by a TATA-less promoter region. Transcription is initiated in exon 1 from two transcription start sites producting transcripts of 105 and 139 bp. The 935 bp of the 5' flanking region of exon 1 comprises five putative binding sites for the GATA transcription factors as well as a NF-kappa B element, a CAAT-box and E-box/E-box-related sequences. For functional promoter analysis, the rat choriocarcinoma cell line Rcho-1 and the mouse keratinocyte cell line Hel37, which both express Cx31, were chosen. Only constructs including exon 1 and the complete intron showed high activity in transient transfection experiments in both cell lines. All deletion fragments of the putative promoter region, but which contain the entire intron sequence, did not reveal any obvious changes in luciferase activity. However, deletion of 1.1 kb of the intron sequence downstream of the splice donor site resulted in the loss of promoter activity. The intron exhibits no enhancer activity for the gene; however, the mRNA stability was increased in the presence of the intron sequence. These results indicate that parts of the intron sequence are critical for basic promoter function of the Cx31 gene.

Animals↗

Systems analysis of PKA-mediated phosphorylation gradients in live cardiac myocytes.

Compartmentation and dynamics of cAMP and PKA signaling are important determinants of specificity among cAMP's myriad cellular roles. Both cardiac inotropy and the progression of heart disease are affected by spatiotemporal variations in cAMP/PKA signaling, yet the dynamic patterns of PKA-mediated phosphorylation that influence differential responses to agonists have not been characterized. We performed live-cell imaging and systems modeling of PKA-mediated phosphorylation in neonatal cardiac myocytes in response to G-protein coupled receptor stimuli and UV photolysis of "caged" cAMP. cAMP accumulation was rate-limiting in PKA-mediated phosphorylation downstream of the beta-adrenergic receptor. Prostaglandin E1 stimulated higher PKA activity in the cytosol than at the sarcolemma, whereas isoproterenol triggered faster sarcolemmal responses than cytosolic, likely due to restricted cAMP diffusion from submembrane compartments. Localized UV photolysis of caged cAMP triggered gradients of PKA-mediated phosphorylation, enhanced by phosphodiesterase activity and PKA-mediated buffering of cAMP. These findings indicate that combining live-cell FRET imaging and mechanistic computational models can provide quantitative understanding of spatiotemporal signaling.

Animals↗

Effects of an ankle-foot orthosis on spatiotemporal parameters and energy cost of hemiparetic gait.

OBJECTIVE: To assess the effect of an ankle-foot orthosis on the gait and energy parameters of walking in chronic hemiparetic subjects. DESIGN: With/without group comparison. SETTING: Consecutive patients recruited from the gait analysis laboratory of our rehabilitation department. SUBJECTS: A group of nine chronic hemiparetic patients, with the same gait pattern alteration, were evaluated during walking at free speed with and without the use of an orthosis. OUTCOME MEASURES: Gait analysis and study of energy cost. RESULTS AND CONCLUSION: The orthosis significantly improved self-selected speed (15.47 versus 21.39 m/min), stride cycle (2.33 versus 2.08 s), stance (1.83 versus 1.48 s) and double support (1.55 versus 1.16 s) and reduced energy cost (0.76 versus 0.49 ml O2/kg/m) of walking without affecting cardiorespiratory response. Moreover, a significant correlation was found between the improvement of double support and the reduction of energy cost.

Aged↗

Wavelet-based cluster analysis: data-driven grouping of voxel time courses with application to perfusion-weighted and pharmacological MRI of the rat brain.

MRI time series experiments produce a wealth of information contained in two or three spatial dimensions that evolve over time. Such experiments can, for example, localize brain response to pharmacological stimuli, but frequently the spatiotemporal characteristics of the cerebral response are unknown a priori and variable, and thus difficult to evaluate using hypothesis-based methods alone. Here we used features in the temporal dimension to group voxels with similar time courses based on a nonparametric discrete wavelet transform (DWT) representation of each time course. Applying the DWT to each voxel decomposes its temporal information into coefficients associated with both time and scale. Discarding scales in the DWT that are associated with high-frequency oscillations (noise) provided a straight-forward data reduction step and decreased the computational burden. Optimization-based clustering was then applied to the remaining wavelet coefficients in order to produce a finite number of voxel clusters. This wavelet-based cluster analysis (WCA) was evaluated using two representative classes of MRI neuroimaging experiments. In perfusion-weighted MRI, following occlusion of the middle cerebral artery (MCAO), WCA differentiated healthy tissue and different regions within the ischemic hemisphere. Following an acute cocaine challenge, WCA localized subtle differences in the pharmacokinetic profile of the cerebral response. We conclude that WCA provides a robust method for blind analysis of time series image data.

Animals↗

Retinal degeneration in the nervous mutant mouse. I. Light microscopic cytopathology and changes in the interphotoreceptor matrix.

Nervous is an autosomal recessive mutation in mice (gene symbol, nr) that produces a progressive cerebellar and retinal degeneration. We have examined various cytopathological features of the photoreceptor degeneration by light microscopy. An increase in the number of pyknotic photoreceptor nuclei in the outer nuclear layer (ONL) is first seen at postnatal day (P) 11. Between P13 and P19 there is a rapid loss of photoreceptors, with the ONL about 60% the thickness of littermate controls at P19. Between P19 and 2.5 months of age, photoreceptor cell loss is minimal, and there is a relatively slow loss of these cells between 3 and 7.5 months of age. At 7.5 months, the ONL consists of single row of nuclei, most of which are lost over the ensuing months, although a few photoreceptor nuclei persist at 17 months of age and older. Both rods and cones are lost at comparable rates for the first 2 months of life, but rods are somewhat preferentially lost at later ages. A very slight central-to-peripheral gradient of photoreceptor degeneration exists in the nr/nr retina, but no superior-inferior hemispheric differences are evident. The rate, spatiotemporal gradient, and hemispheric similarity in photoreceptor degeneration are the same in albino nr/nr mice reared either in cyclic light or in the dark, and in pigmented nr/nr mice. Autoradiographic analysis of rod outer segment renewal shows that outer segment membranes are synthesized in nervous homozygotes. Rhythmic outer segment disc shedding and phagocytosis by the retinal pigment epithelium occur at approximately normal rates in nr/nr mice. Histochemical and immunocytochemical study of the interphotoreceptor matrix (IPM) reveals the exclusion of stainable IPM from the outer segment zone by lamellar whorls of outer segment membrane, accumulation of stainable IPM in the basal region of the outer segment zone, and the absence of an intense band of stainable IPM at the apical surface of the retinal pigment epithelium. These changes in the IPM are similar to those seen in the Royal College of Surgeons rat. However, comparison of cytopathological changes in these two mutants reveal that the IPM defect probably is not the primary cause of photoreceptor cell death in nr/nr mice, and that similar phenotypic appearance does not necessarily signify similar pathological processes.

Animals↗

Thermally evoked parotid salivation.

Parotid salivation is known to be influenced by the temperature of liquids moved around the mouth. Here we investigated the ability of non-liquid thermal stimuli to change the rate of salivation. Unilateral parotid saliva was collected using a Lashley Cup from 12 normally hydrated subjects. Thermal stimuli were delivered through a copper tube, in which temperature-controlled water flowed, resting statically on the anterior tongue. During separate trials, the tube was 10, 22, or 44 degrees C, or the resting temperature of the tongue (or hypothenar of the hand, the control site). On each trial, the unstimulated salivation rate was first measured for 6 min while the subject remained seated with the mouth closed. Subsequently, salivation was measured for 6 min during application of the thermal stimulus. The tube was then removed for 1-2 min before the next trial. During the trials, subjects repeatedly rated the subjective temperature of the tongue (or hypothenar) and its perceived wetness/dryness. Stimulated salivation, expressed as a proportion of the previously measured unstimulated salivation, differed among body sites and temperatures (P<0.03). A significant increase in salivation was seen only for the 10 degrees C stimulus applied to the tongue. Wetness ratings and salivation rates were positively correlated, albeit weakly. These results demonstrate that temperature-evoked changes in parotid salivation do not require the unique spatiotemporal dynamics of the tongue and jaw movements in wetting the oral mucosa.

Adult↗

High-throughput single-cell proteomics and transcriptomics from same cells with a nanoliter-scale, spin-transfer approach.

Single-cell multiomic platforms provide a comprehensive snapshot of cellular states and cell types by offering critical insights into the spatiotemporal regulation of biomolecular networks at a systems level, thereby defining the basis of multicellularity. Here, we introduce nanoSPINS, an advanced platform that enables high-throughput profiling and integrative analysis of the transcriptome and proteome from the same single cells using RNA sequencing and isobaric labeling LC-MS-based proteomics, respectively. NanoSPINS can efficiently transfer mRNA-containing droplets across two microarrays via a centrifugation-based approach, while proteins are retained on the initial platform. Benchmarking of nanoSPINS on two cell lines demonstrates its ability to generate global proteomic and transcriptomic profiles that align well with previously established methodologies/platforms. The incorporation of isobaric TMTpro labeling into this single-cell multiomics platform significantly enhances the throughput of single-cell proteomic analyses. Through the high-throughput quantification of the proteome and transcriptome, nanoSPINS not only facilitates the identification of molecular features at both mRNA and protein level but also provides larger sample sizes for improved statistical power in clustering and differential abundance. Given the broad applicability of single-cell multiomics in biological research and clinical settings, we believe nanoSPINS represents a powerful platform for the characterization of heterogeneous cell populations.

Single-Cell Analysis↗

Biorthogonal decomposition techniques unveil the nature of the irregularities observed in the solar cycle.

We present a biorthogonal decomposition of the temporal and latitudinal distribution of sunspots recorded since 1874. We show that the butterfly diagrams can be interpreted as the result of approximately constant amplitudes and phases of two oscillations with periods close to 22 years. Our analysis reveals clear evidence of the absence of low-dimensional chaos, at least for the time scales that can be analyzed with this database. This result suggests that the spatiotemporal irregularities observed in the solar cycle are due to the superposition of regular structures with a stochastic background.

Journal Article↗

Changes in somatosensory evoked potentials during kindling: analogy to learning modifications.

Cortical somatosensory evoked potential (SSEP) changes were studied during kindling of the right pericruciate cortex and in the right hippocampus in 7 cats. The test electric stimuli were delivered to left and right anterior paw. The ipsi- and contralateral SSEPs were averaged before kindling and about every 35th day during kindling. Paroxysmal epileptic discharges developed in all cats. The main consistent changes in all the SSEPs involved components N2-P3-N3, i.e., those with latencies of 90--330 msec. Specifically we noted (1) a gradual decrease in the duration and latency of the N3 component (2) an increase in the slope of the P3-N3 component and (3) a decrease in the duration and latency of the p3 component. These changes were present in both hemispheres, ipsi- and contralateral to both right and left paw stimulation, though favoring the contralateral responses. The changes started to develop before the appearance of spontaneous epileptic activity and seem to be independent of the epileptogenic effect of kindling. Thus, during kindling two types of neuronal function modification seem to take place: epileptogenic and nonepileptogenic. The nonepileptogenic nature of kindling is discussed from the point of view that some forms of learning and kindling are based on similar neurophysiological processes, which lead to permanent neuronal bioelectrical changes. These plastic changes underlie the development of such processes as memory and epilepsy. The difference between these two processes may be in the disturbance of spatiotemporal distribution of coherence in neuronal ensembles.

Animals↗

Comparison between language and music.

Similarities and differences between language and music processing are examined from an evolutionary and a cognitive perspective. Language and music cannot be considered single entities; they need to be decomposed into different component operations or levels of processing. The central question concerns one of the most important claims of the generative grammar theory, that is, the specificity of language processing: do the computations performed to process language rely on specific linguistic processes or do they rely on general cognitive principles? Evidence from brain imaging results is reviewed, noting that this field is currently in need of metanalysis of the available results to precisely evaluate this claim. A series of experiments, mainly using the event-related brain potentials method, were conducted to compare different levels of processing in language and music. Overall, results favor language specificity when certain aspects of semantic processing in language are compared with certain aspects of melodic and harmonic processing in music. By contrast, results support the view that general cognitive principles are involved when aspects of syntactic processing in language are compared with aspects of harmonic processing in music. Moreover, analysis of the temporal structure led to similar effects in language and music. These tentative conclusions must be supported by other brain imaging results to shed further light on the spatiotemporal dynamics of the brain structure-function relationship.

Brain↗

Identification of 16S ribosomal DNA-defined bacterial populations at a shallow submarine hydrothermal vent near Milos Island (Greece).

In a recent publication (S. M. Sievert, T. Brinkhoff, G. Muyzer, W. Ziebis, and J. Kuever, Appl. Environ. Microbiol. 65:3834-3842, 1999) we described spatiotemporal changes in the bacterial community structure at a shallow-water hydrothermal vent in the Aegean Sea near the isle of Milos (Greece). Here we describe identification and phylogenetic analysis of the predominant bacterial populations at the vent site and their distribution at the vent site as determined by sequencing of DNA molecules (bands) excised from denaturing gradient gels. A total of 36 bands could be sequenced, and there were representatives of eight major lineages of the domain Bacteria. Cytophaga-Flavobacterium and Acidobacterium were the most frequently retrieved bacterial groups. Less than 33% of the sequences exhibited 90% or more identity with cultivated organisms. The predominance of putative heterotrophic populations in the sequences retrieved is explained by the input of allochthonous organic matter at the vent site.

Bacteria↗

Spatiotemporal characteristics of neuronal sensory integration in the barrel cortex of the rat.

In primary sensory cortices, neuronal responses to a stimulus presented as part of a rapid sequence often differ from responses to an isolated stimulus. It has been reported that sequential stimulation of two whiskers produces facilitatory modulations of barrel cortex neuronal responses. These results are at odds with the well-known suppressive interaction that has been usually described. Herein, we have examined the dependency of response modulation on the spatiotemporal pattern of stimulation by varying the spatial arrangement of the deflected vibrissae, the temporal frequency of stimulation, and the time interval between whisker deflections. Extracellular recordings were made from primary somatosensory cortex of anesthetized rats. Two contralateral whiskers were stimulated at 0.5 and 8 Hz at intervals ranging from 0 to +/-30 ms. Response interactions were assessed during stimulation of the principal and adjacent whiskers, first from the same row and second from the same arc. When tested at 0.5 Hz, 59% of single units showed a statistically significant suppressive interaction, whereas response facilitation was found in only 6% of cells. In contrast, at 8 Hz, a significant supralinear summation was observed in 19% of the cells, particularly for stimulations along an arc rather than along a row. Multi-unit recordings showed similar results. These observations indicate that most of the interactions in the barrel cortex during two-whisker stimulation are suppressive. However, facilitation can be revealed when stimuli are applied at a physiological frequency and could be the basis for internal representations of the spatiotemporal pattern of the stimulus.

Action Potentials↗

Drift-balanced random stimuli: a general basis for studying non-Fourier motion perception.

To some degree, all current models of visual motion-perception mechanisms depend on the power of the visual signal in various spatiotemporal-frequency bands. Here we show how to construct counterexamples: visual stimuli that are consistently perceived as obviously moving in a fixed direction yet for which Fourier-domain power analysis yields no systematic motion components in any given direction. We provide a general theoretical framework for investigating non-Fourier motion-perception mechanisms; central are the concepts of drift-balanced and microbalanced random stimuli. A random stimulus S is drift balanced if its expected power in the frequency domain is symmetric with respect to temporal frequency, that is, if the expected power in S of every drifting sinusoidal component is equal to the expected power of the sinusoid of the same spatial frequency, drifting at the same rate in the opposite direction. Additionally, S is microbalanced if the result WS of windowing S by any space-time-separable function W is drift balanced. We prove that (i) any space-time-separable random (or nonrandom) stimulus is microbalanced; (ii) any linear combination of pairwise independent microbalanced (respectively, drift-balanced) random stimuli is microbalanced and drift balanced if the expectation of each component is uniformly zero; (iii) the convolution of independent microbalanced and drift-balanced random stimuli is microbalanced and drift balanced; (iv) the product of independent microbalanced random stimuli is microbalanced; and (v) the expected response of any Reichardt detector to any microbalanced random stimulus is zero at every instant in time. Examples are provided of classes of microbalanced random stimuli that display consistent and compelling motion in one direction. All the results and examples from the domain of motion perception are transposable to the space-domain problem of detecting orientation in a texture pattern.

Fourier Analysis↗