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Low-frequency signal changes reflect differences in functional connectivity between good readers and dyslexics during continuous phoneme mapping.

The current fMRI study investigated correlations of low-frequency signal changes in the left inferior frontal gyrus, right inferior frontal gyrus and cerebellum in 13 adult dyslexic and 10 normal readers to examine functional networks associated with these regions. The extent of these networks to regions associated with phonological processing (frontal gyrus, occipital gyrus, angular gyrus, inferior temporal gyrus, fusiform gyrus, supramarginal gyrus and cerebellum) was compared between good and dyslexic readers. Analysis of correlations in low-frequency range showed that regions known to activate during an "on-off" phoneme-mapping task exhibit synchronous signal changes when the task is administered continuously (without any "off" periods). Results showed that three functional networks, which were defined on the basis of documented structural deficits in dyslexics and included regions associated with phonological processing, differed significantly in spatial extent between good readers and dyslexics. The methodological, theoretical and clinical significance of the findings for advancing fMRI research and knowledge of dyslexia are discussed.

Adult↗

Corticofugal modulation of functional connectivity within the auditory thalamus of rat, guinea pig and cat revealed by cooling deactivation.

Microelectrode recordings were simultaneously performed at multiple sites in the medial geniculate body (MGB) of anesthetized cats, rats and guinea pigs. We studied the effect of cortical deactivation on the association of neural activity within the thalamus during spontaneous activity. The corticofugal influence was suppressed by temporary cooling of the auditory cortex. Pairs of spike trains recorded from the same electrode were distinguished from cases where units were in MGB but recorded with different electrodes. Time domain analyses included crosscorrelations and search for precise repetition of complex spatiotemporal firing patterns of reverberating thalamic circuits. As a complementary approach we performed bispectral analyses of simultaneously recorded local field potentials in order to uncover the frequency components of their power spectra which are non linearly coupled. All results suggest that new functional neuronal circuits might appear at the thalamic level in the absence of input from the cortex. The newly active intrathalamic connections would provide the necessary input to sustain the reverberating activity of thalamic cell assemblies and generate low frequency non-linear interactions. The dynamic control exerted by the cortex over the functional segregation of information processing carried out in the thalamus conforms with theoretical neural network studies and with the functional selectivity-adaptive filtering theory of thalamic neuronal assemblies. Although this general conclusion remains valid across species, specific differences are discussed in the frame of known differences of the microcircuitry elements.

Animals↗

Functional connections among cortical regions: topography of EEG coherence.

The covariance among EEG signals can be examined with coherence analysis. Evidence that the right hemisphere has a more diffuse receptotopic organization than the left, together with evidence that it may have a higher proportion of white to gray matter, suggests a high degree of functional connectedness among right hemisphere regions. To determine whether this is reflected in greater EEG coherence among right than left hemisphere locations, we constructed a matrix of cross-spectra among all unique pairs of EEG channels in an 8-channel montage, then statistically de-structured this matrix to examine multiple coherences and both inter- and intra-hemispheric partial multiple coherences. Analyses on data from the resting EEGs of 14 right-handed men examined weekly for several months showed higher coherences for right hemisphere locations. For the inter-hemispheric partial multiple coherences the frontal lobe values were also higher on the right, but the occipital inter-hemispheric coherences were higher on the left. These asymmetries have interesting parallels with anatomical asymmetries of the human cortex and may have functional implications.

Adult↗

Brain activation and hypothalamic functional connectivity during human non-rapid eye movement sleep: an EEG/fMRI study.

Regional differences in sleep EEG dynamics indicate that sleep-related brain activity involves local brain processes with sleep stage specific activity patterns of neuronal populations. Macroscopically, it is not fully understood which cerebral brain regions are involved in the successive discontinuation of wakefulness. We simultaneously used EEG and functional MRI on 9 subjects (6 female: mean = 24.1 years, 3 male: mean = 26.0 years) and analyzed local blood oxygenation level dependent signal changes linked to the transition from wakefulness to different non-rapid eye movement (NREM) sleep stages (according to Rechtschaffen and Kales) of the first sleep cycles after 36 h of total sleep deprivation. Several brain regions throughout the cortex, the limbic lobe, the thalamus, the caudate nucleus, as well as midbrain structures, such as the mammillary body/hypothalamus, showed reduced activity during NREM sleep across all sleep stages. Additionally, we found deactivation patterns specific to NREM sleep stages compared with wakefulness suggesting that a synchronized sleeping state can be established only if these regions interact in a well-balanced way. Sleep stage 2, which is usually linked to the loss of self-conscious awareness, is associated with signal decreases comprising thalamic and hypothalamic regions, the cingulate cortex, the right insula and adjacent regions of the temporal lobe, the inferior parietal lobule and the inferior/middle frontal gyri. The hypothalamic region known to be of particular importance in the regulation of the sleep-wake cycle shows specific temporally correlated network activity with the cortex while the system is in the sleeping state, but not during wakefulness. We describe a specific pattern of decreased brain activity during sleep and suggest that this pattern must be synchronized for establishing and maintaining sleep.

Adult↗

[The types of the structural-functional connections of the coronary circulation and the state of the myocardium in patients with isolated and combined forms of ischemic heart disease and arterial hypertension].

The analysis of evidence obtained at coronaroangiography, myocardial scintigraphy, echocardiography, severity of coronary and heart insufficiency in patients with isolated and combined forms of ischemic heart disease and arterial hypertension has identified three types of structural-functional relations between characteristics of coronary circulation and myocardial status: myocardio-perfusional (concentric myocardial hypertrophy with diastolic dysfunction leading to perfusional defects), coronaro-myocardial (affection of coronary arteries resulting in myocardial lesion with primarily systolic dysfunction), coronaro-perfusional (disturbed coronary circulation in involvement of coronary and myocardial factors).

Angiography, Digital Subtraction↗

Analyzing functional connectivity using a network likelihood model of ensemble neural spiking activity.

Analyzing the dependencies between spike trains is an important step in understanding how neurons work in concert to represent biological signals. Usually this is done for pairs of neurons at a time using correlation-based techniques. Chornoboy, Schramm, and Karr (1988) proposed maximum likelihood methods for the simultaneous analysis of multiple pair-wise interactions among an ensemble of neurons. One of these methods is an iterative, continuous-time estimation algorithm for a network likelihood model formulated in terms of multiplicative conditional intensity functions. We devised a discrete-time version of this algorithm that includes a new, efficient computational strategy, a principled method to compute starting values, and a principled stopping criterion. In an analysis of simulated neural spike trains from ensembles of interacting neurons, the algorithm recovered the correct connectivity matrices and interaction parameters. In the analysis of spike trains from an ensemble of rat hippocampal place cells, the algorithm identified a connectivity matrix and interaction parameters consistent with the pattern of conjoined firing predicted by the overlap of the neurons' spatial receptive fields. These results suggest that the network likelihood model can be an efficient tool for the analysis of ensemble spiking activity.

Action Potentials↗

Functional connectivity in single and multislice echoplanar imaging using resting-state fluctuations.

A previous report of correlations in low-frequency resting-state fluctuations between right and left hemisphere motor cortices in rapidly sampled single-slice echoplanar data is confirmed using a whole-body echoplanar MRI scanner at 1.5 T. These correlations are extended to lower sampling rate multislice echoplanar acquisitions and other right/left hemisphere-symmetric functional cortices. The specificity of the correlations in the lower sampling-rate acquisitions is lower due to cardiac and respiratory-cycle effects which are aliased into the pass-band of the low-pass filter. Data are combined for three normal right-handed male subjects. Correlations to left hemisphere motor cortex, visual cortex, and amygdala are measured in long resting-state scans.

Adult↗

Anatomical and functional connectivity of the transected ulnar nerve after intercostal neurotization in cats.

OBJECT: Acute transfer of three intercostal nerves to the ulnar nerve was performed in cats for histological and clinical evaluation of a distal muscle reinnervation. METHODS: Infraclavicular intercostal-ulnar communications were created after dividing the motor branches of the upper intercostal nerves in 14 adult cats. Reinnervation of distal forelimb muscles in the ulnar territory was assessed by electromyographic (EMG) studies and motor function rating each month until 18 months postsurgery. In five of these treated animals, and in tour controls, horseradish peroxidase (HRP) was applied to the ulnar or intercostal nerves to study the amount and distribution of retrograde motor neuron labeling in the spinal cord. Also, samples of reinnervated muscles and neurotized ulnar nerves were processed to assess regeneration. Simple ulnar transection without reconstruction led to permanent atrophy of ulnar muscles, lack of recovery according to EMG or clinical studies, and disappearance of the ulnar motor neuron pool. In contrast, ulnar neurotization with the intercostal nerves led to a high rate of functional recovery, which began 5 months postsurgery, and progressed from muscle activity synchronized with ventilatory movements to spontaneous movements that were independent of respiration. This recovery was accompanied by substantial retrograde labeling of intercostal motor neurons after HRP application in the ulnar nerve. Cell counts showed that practically the whole motor neuron pool of the involved intercostal nerves contributed to reinnervation of the transected ulnar nerve. CONCLUSIONS: These findings demonstrate that the use of intercostal nerves to neurotize long brachial plexus nerves can achieve long-lasting and successful reinnervation of distal forelimb muscles.

Animals↗

Presenilin function: connections to Alzheimer's disease and signal transduction.

Missense mutations in presenilin 1 (PS1) and presenilin 2 (PS2) are associated with early-onset familial Alzheimer's disease which displays an accelerated deposition of amyloid plaques and neurofibrillary tangles. Presenilins are multi-spanning transmembrane proteins which localize primarily to the endoplasmic reticulum and the Golgi compartments. We have previously demonstrated that PS1 exists as a high-molecular-mass complex that is likely to contain several functional ligands. Potential binding proteins were screened by the yeast two-hybrid system using the cytoplasmically orientated PS1 loop domain which was shown to interact strongly with members of the armadillo family of proteins, including beta-catenin, p0071 and a novel neuron-specific plakophilin-related armadillo protein (NPRAP). Armadillo proteins can have dual functions that encompass the stabilization of cellular junctions/synapses and the mediation of signal transduction pathways. Our observations suggest that PS1 may contribute to both aspects of armadillo-related pathways involving neurite outgrowth and nuclear translocation of beta-catenin upon activation of the wingless (Wnt) pathway. Alzheimer's disease (AD)-related presenilin mutations exhibit a dominant gain of aberrant function resulting in the prevention of beta-catenin translocation following Wnt signalling. These findings indicate a functional role for PS1 in signalling and suggest that mistrafficking of selected presenilin ligands may be a potential mechanism in the genesis of AD.

Alzheimer Disease↗

Functional connections between mediator components and general transcription factors of Saccharomyces cerevisiae.

The yeast Gal11 protein is an important component of the Mediator complex in RNA polymerase II-directed transcription. Gal11 and the general transcription factor (TF) IIE are involved in regulation of the protein kinase activity of TFIIH that phosphorylates the carboxyl-terminal domain of RNA polymerase II. We have previously shown that Gal11 binds the small and large subunits of TFIIE at two Gal11 domains, A and B, respectively, which are important for normal function of Gal11 in vivo. Here we demonstrate that Gal11 binds directly to TFIIH through domain A in vitro. A null mutation in GAL11 caused lethality of cells when combined with temperature-sensitive mutations in the genes encoding TFIIE or the carboxyl-terminal domain kinase, indicating the presence of genetic interactions between Gal11 and these proteins. Mutational depletion of Gal11 or TFIIE caused inefficient opening of the transcription initiation region, but had no significant effect on TATA-binding protein occupancy of the TATA sequence in vivo. These results suggest that the functions of Gal11 and TFIIE are necessary after recruitment of TATA-binding protein to the TATA box presumably at the step of stable preinitiation complex formation and/or promoter melting. We illustrate genetic interactions between Gal11 and other Mediator components such as Med2 and Pgd1/Hrs1/Med3.

Base Sequence↗

The size of corpus callosum and functional connectivities of cortical regions in finger and shoulder movements.

The correlations between the size of corpus callosum and the inter- and intra-hemispheric EEG coherence and the spatial EEG synchronization during finger and shoulder movements were analyzed in nine right-handed men. The cross-sectional surface areas of corpus callosum (CC) and of seven callosal regions were measured from the mid-sagittal slice of the anatomical MRI. Movement-related coherence between pairs of EEG electrodes overlying the central and parietal regions of both hemispheres was computed after spatially filtering EEG data by the Laplacian operator method. The spatial EEG synchronization was evaluated using omega-complexity, a novel measure which quantifies the number of independent sources of spontaneous EEG oscillations. The amplitude of coherence between the left and right S1/M1 areas after movement onset in the lower alpha band (7.8-9.8 Hz) correlated with the size of the callosal body in both types of movement. The size of the callosal body also correlated with the C3-Cz coherence in the 15.6-19.5 Hz band in finger movement, and in the 15.6-23.5 Hz band in shoulder movements. The size of the rostral, anterior intermediate and posterior intermediate truncus of CC correlated with omega-complexity in both types of movements indicating more foci of synchronized EEG oscillations in subjects with a large callosal truncus. The results suggest that the size of callosal truncus which is known to connect the primary sensorimotor and the supplementary motor areas of both hemispheres contributes to the coupling of EEG oscillations during voluntary finger and shoulder movements.

Adult↗

[The functional connections of the supraoptic and suprachiasmatic nuclei of the anterior hypothalamus with the superior colliculi].

Interrelation of single hypothalamic (supraoptic--SO and suprachiasmatic--SCH nuclei) and light stimuli at the level of superior colliculus (SC) were studied during chronic experiments in waking rabbits. Short-term inhibitory and the subsequent facilitatory effects of the hypothalamic stimuli on SC responses induced by light flashes were established. The foregoing light stimulus caused inhibitory effect on formation of hypothalamo-collicular responses induced by SO and SCH nuclei stimulation. The final result of the anterior hypothalamic effect on SC function is the vector value of the mechanism of interrelation between the hypothalamic inputs in this structure.

Animals↗

[An assessment of the manifestation of the functional connections between brain structures].

Responses of hypothalamic neurons to single (1/s, 20 impulses) stimulation of the prefrontal (area 8), cingulum (area 24), periamygdaloideus (RPA) cortex and hippocampus (field CA3) were studied on experimental cats anesthetized with ketamine. The routine elaborated for IBM PC/AT 386 provided: 1) selection of such neurone reaction with the latent period variation less than its length per the set value (5-20%); 2) selection of repeated neurone reactions with the same variability of latent periods from 20 cortical stimuli; 3) ranging of neurone reactions according to these indices. Quantitative estimation of the priority ranges made it possible to determine the profundity of the functional relations between the cerebral structures.

Animals↗

p68 DEAD box RNA helicase expression in keratinocytes. Regulation, nucleolar localization, and functional connection to proliferation and vascular endothelial growth factor gene expression.

Nitric oxide (NO) represents a short lived mediator that pivotally drives keratinocyte movements during cutaneous wound healing. In this study, we have identified p68 DEAD box RNA helicase (p68) from an NO-induced differential keratinocyte cDNA library. Subsequently, we have analyzed regulation of p68 by wound-associated mediators in human and murine keratinocytes. NO, serum, growth factors, and pro-inflammatory cytokines were potent inducers of p68 expression in the cells. p68 was constitutively expressed in the epithelial compartment of murine skin. Upon injury, we found a transient down-regulation of overall p68 protein in wound tissue. However, p68 did not completely disappear during early wound repair, as we found an expression of p68 protein in isolated wound margin tissue 24 h after wounding. Moreover, immunohistochemistry and cell fractionation analysis revealed a restricted localization of p68 in keratinocyte nuclei of the developing epithelium. Accordingly, cultured keratinocytes also showed a nuclear localization of the helicase. Moreover, confocal microscopy revealed a strong localization of p68 protein within the nucleoli of the cells. Functional analyses demonstrated that p68 strongly participated in keratinocyte proliferation and gene expression. Keratinocytes that constitutively overexpressed p68 protein were characterized by a marked increase in serum-induced proliferation and vascular endothelial growth factor expression, whereas down-regulation of endogenous p68 using small interfering RNA markedly attenuated serum-induced proliferation and vascular endothelial growth factor expression. Altogether, our results suggest a tightly controlled expression and nucleolar localization of p68 in keratinocytes in vitro and during skin repair in vivo that functionally contributes to keratinocyte proliferation and gene expression.

Animals↗

Functional connectivity between trigeminal and occipital nerves revealed by occipital nerve blockade and nociceptive blink reflexes.

Headache syndromes often suggest occipital and neck involvement, although it is still unknown to what extent branches of segment C1-C3 contribute actively to primary headache. Pain within the occipital area may be referred to the trigeminal territory. However, a modulation of trigeminal transmission by affecting cervical input in humans has not been elucidated so far. A convergence of cervical and trigeminal input at the level of the caudal part of the trigeminal nucleus in the brainstem has been suggested due to anatomical and neurophysiological studies in animals. We examined the R2 components of the nociceptive blink reflex responses in 15 healthy subjects before and after unilateral nerve blockade of the greater occipital nerve with 5 ml prilocain (1%). R2 response areas (AUC) decreased and the R2 latencies increased significantly after the nerve blockade only on the side of injection. AUC and latencies on the non-injection side remained stable. Thresholds for sensory or pain perception did not differ significantly between the repeated measurements on both sides. Our findings extend previous results related to anatomical and functional convergence of trigeminal and cervical afferent pathways in animals and suggest that the modulation of this pathway is of potential benefit in primary headache disorders.

Adult↗

Characterization of CAF4 and CAF16 reveals a functional connection between the CCR4-NOT complex and a subset of SRB proteins of the RNA polymerase II holoenzyme.

The CCR4-NOT transcriptional regulatory complex affects transcription both positively and negatively and consists of the following two complexes: a core 1 x 10(6) dalton (1 MDa) complex consisting of CCR4, CAF1, and the five NOT proteins and a larger, less defined 1.9-MDa complex. We report here the identification of two new factors that associate with the CCR4-NOT proteins as follows: CAF4, a WD40-containing protein, and CAF16, a putative ABC ATPase. Whereas neither CAF4 nor CAF16 was part of the core CCR4-NOT complex, both CAF16 and CAF4 appeared to be present in the 1.9-MDa complex. CAF4 also displayed physical interactions with multiple CCR4-NOT components and with DBF2, a likely component of the 1.9-MDa complex. In addition, both CAF4 and CAF16 were found to interact in a CCR4-dependent manner with SRB9, a component of the SRB complex that is part of the yeast RNA polymerase II holoenzyme. The three related SRB proteins, SRB9, SRB10, and SRB11, were found to interact with and to coimmunoprecipitate DBF2, CAF4, CCR4, NOT2, and NOT1. Defects in SRB9 and SRB10 also affected processes at the ADH2 locus known to be controlled by components of the CCR4-NOT complex; an srb9 mutation was shown to reduce ADH2 derepression and either an srb9 or srb10 allele suppressed spt10-enhanced expression of ADH2. In addition, srb9 and srb10 alleles increased ADR1(c)-dependent ADH2 expression; not4 and not5 deletions are the only other known defects that elicit this phenotype. These results suggest a close physical and functional association between components of the CCR4-NOT complexes and the SRB9, -10, and -11 components of the holoenzyme.

Adenosine Triphosphatases↗