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PubMed2002

Functional connectivity of gamma EEG activity is modulated at low frequency during conscious recollection.

We examined two subjectively distinct memory states that are elicited during recognition memory in humans and compared them in terms of the gamma oscillations (20-60 Hz) in the electroencepahalogram (EEG) that they induced. These subjective states, 'recollection' and 'familiarity' both entail correct recognition but one involves a clear and conscious recollection of the event including memory for contextual detail whilst the other involves a sense of familiarity without clear recollection. Here we show that during a verbal recognition memory test, the subjective experience of 'recollection' induced higher amplitude gamma oscillations than the subjective experience of 'familiarity' in the time period 300-500 ms after stimulus presentation. Recollection, but not familiarity, was also associated with greater functional connectivity in the gamma frequency range between frontal and parietal sites. Furthermore, the magnitude of the gamma functional connectivity varied over time and was modulated at 3 Hz. Previous studies in animals have shown local theta frequency modulation (3-7 Hz) of gamma-oscillations but this is the first time that a similar effect has been reported in the human EEG.

Adult↗
PubMed2004

Enhancement of GABA-related signalling is associated with increase of functional connectivity in human cortex.

Structural or operational synchrony analysis with EEG was conducted in order to detect functional interaction between cortical areas during an enhanced inhibition induced by the GABAergic agonist lorazepam in a double-blind, randomized, placebo-controlled, cross-over study in eight healthy human subjects. Specifically, we investigated whether a neuronal inhibitory system in the brain mediates functional decoupling of cortical areas. Single-dose lorazepam administration resulted in a widespread increase in the inter-area functional connectivity and an increase in the strength of functional long-range and interhemispheric connections. These results suggest that inhibition can be an efficient mechanism for synchronization of large neuronal populations.

Adult↗
PubMed2004

Radial correlation contrast--a functional connectivity MRI contrast to map changes in local neuronal communication.

A functional connectivity MRI method that groups neighboring voxels in relation to their degree of temporal cross-correlation between their time courses is presented. This grouping generates a vector field, which is assumed to provide insights into the local organization of neuronal activity. Application with high spatial resolution fMRI rat data subjected to electric forepaw sensory stimulation (156 . 156 . 1000 micron1) shows a significant localized increase of the vector field amplitude in cortical layers 4 and 2/3 of the primary sensory cortex and in layer 2/3 of the primary motor cortex, suggesting a strong correlation with local neuronal communication. Vector field phases exhibit a transition with neuronal activation from random-like orientations during rest to clusters of common orientations. Cluster size is shown to be weakly dependent on the radii of the vector field calculation, and shuffling voxel position within clusters generates a random-like vector orientation instead. This suggests that changes in vector orientations upon activation represent changes in the internal correlation between voxels that is interpreted as a change in the internal neuronal communication.

Animals↗
PubMed2003

Transition metal-catalyzed/mediated reaction of allenes with a nucleophilic functionality connected to the alpha-carbon atom.

Allenes with a nucleophilic functionality connected to the alpha-carbon atom have been shown to be versatile building blocks for the syn-thesis of gamma-butenolides, gamma-lactams, gamma-iminolactones, vinylic epoxides, 4-amino-2-alkenols, 2-amino-3-alkenols, 2,5-dihydrofurans, furans, vinylic cyclopropanes, and cyclopentenes, depending on the nature of the nucleophilic centers. The reaction may proceed via the carbometalation-nucleophilic attack mechanism or nucleometallation-reductive elimination. The stereochemical outcomes by these two pathways are different.

Journal Article↗
PubMed2006

Oncostatin M expression is functionally connected to neutrophils in the early inflammatory phase of skin repair: implications for normal and diabetes-impaired wounds.

In this study, we investigated the role of the cytokine oncostatin M (OSM) for wound biology. OSM and its specific OSM receptor subunit beta (OSMRbeta) were induced upon injury. OSM induction paralleled the early influx of polymorphonuclear neutrophils (PMN) into the wound. OSM protein was localized in PMN in very early wounds, whereas OSMRbeta could be detected on macrophages, keratinocytes, and fibroblasts later in repair. To establish a functional connection between PMN and OSM expression in wounds, we depleted mice from circulating PMN by injecting an anti-PMN monoclonal antibody (Ly-6G). PMN-depleted wounds were characterized by a nearly complete loss of OSM but not OSMRbeta mRNA and protein expression within the initial 16-24 hours after injury. PMN-rich chronic wounds from diabetic ob/ob mice were characterized by a strongly elevated OSM mRNA and protein expression as compared to healthy animals. Moreover, a leptin-mediated improvement of chronic wounds in ob/ob mice was paralleled by a complete inhibition of PMN influx associated again with a dramatic loss of OSM expression at the wound site. These data constitute strong evidence that OSM expression during wound inflammation is functionally connected to PMN infiltration.

Animals↗
PubMed2005

Cingulate control of fronto-temporal integration reflects linguistic demands: a three-way interaction in functional connectivity.

In a recent fMRI language comprehension study, we asked participants to listen to word-pairs and to make same/different judgments for regularly and irregularly inflected word forms [Tyler, L.K., Stamatakis, E.A., Post, B., Randall, B., Marslen-Wilson, W.D., in press. Temporal and frontal systems in speech comprehension: an fMRI study of past tense processing. Neuropsychologia, available online.]. We found that a fronto-temporal network, including the anterior cingulate cortex (ACC), left inferior frontal gyrus (LIFG), bilateral superior temporal gyrus (STG) and middle temporal gyrus (MTG), is preferentially activated for regularly inflected words. We report a complementary re-analysis of the data seeking to understand the behavior of this network in terms of inter-regional covariances, which are taken as an index of functional connectivity. We identified regions in which activity was predicted by ACC and LIFG activity, and critically, by the interaction between these two regions. Furthermore, we determined the extent to which these inter-regional correlations were influenced differentially by the experimental context (i.e. regularly or irregularly inflected words). We found that functional connectivity between LIFG and left MTG is positively modulated by activity in the ACC and that this effect is significantly greater for regulars than irregulars. These findings suggest a monitoring role for the ACC which, in the context of processing regular inflected words, is associated with greater engagement of an integrated fronto-temporal language system.

Acoustic Stimulation↗
PubMed2003

Selective enhancement of functional connectivity in the left prefrontal cortex during sentence processing.

We present the results of correlation analyses for identifying temporally correlated activations between multiple regions of interest. We focused on functional connectivity for two regions in the prefrontal cortex: the left inferior frontal gyrus (L. F3t/F3O) and the left precentral sulcus (L. PrCS). Temporal correlations of functional magnetic resonance imaging signals were separately examined during a sentence comprehension task and a lexical decision task, thereby averaging data throughout all voxels within a region of interest used as a reference region. We found that the reciprocal connectivity between L. F3t/F3O and L. PrCS was significantly enhanced during sentence processing, but not during lexico-semantic processing, which was confirmed under both auditory and visual conditions. Furthermore, significantly correlated regions were mostly concentrated in the left prefrontal cortex during the sentence task. These results demonstrate that the functional connectivity within the left prefrontal cortex is selectively enhanced for processing sentences, which may subserve the use of syntactic information for integrating lexico-semantic information.

Adult↗
PubMed1997

Functional connectivity in the rodent trigeminal pathway grown in vitro.

In explant cocultures of the rat trigeminal pathway, embryonic trigeminal ganglion cells grow their axons into peripheral cutaneous and central nervous system targets (R.S. Erzurumlu, S. Jhaveri, Target influences on the morphology of trigeminal axons, Exp. Neurol, 135 (1995) 1-16; R.S. Erzurumlu, S. Jhaveri, H. Takahashi, R.D.G. McKay, Target-derived influences on axon growth modes in explant cocultures of trigeminal neurons, Proc. Natl. Acad. Sci. USA 90 (1993) 7235-7239). In heterochronic cocultures, composed of embryonic trigeminal ganglion, embryonic whisker pad and postnatal brainstem slice, trigeminal axons develop arbors and terminal boutons in the brainstem trigeminal nuclei. To determine whether these terminal arbors establish functional connections with the brainstem neurons, we examined the electrophysiological properties of brainstem neurons and their responsiveness to trigeminal ganglion stimulation. Intracellular recordings were done in vitro on cells of the trigeminal subnucleus interpolaris (SPI) in trigeminal pathway cocultures (E15 whisker pad, E15 trigeminal ganglion, and postnatal day (PND) 0-2 brainstem slice) or in the SPI of acutely prepared brainstem slices. Electrophysiological properties of SPI cells in both preparations were virtually identical. The voltage responses of SPI neurons to intracellular current injection were highly linear suggesting they lacked a number of voltage-dependent conductances. Depolarizing current injection produced trains of action potentials with a frequency that varied with stimulus intensity. In explant cocultures, electrical activation of the trigeminal ganglion evoked EPSPs, and EPSPs coupled with IPSPs in SPI cells. Bicuculline blockade of IPSP activity resulted in long lasting EPSPs whose duration increased with membrane depolarization. These results show that brainstem trigeminal neurons can retain their functional properties in culture and establish functional connections with primary sensory afferents.

Animals↗
PubMed2006

Lagged covariance structure models for studying functional connectivity in the brain.

Most cognitive processes are supported by large networks of brain regions. To describe the operation of these networks, it is critical to understand how individual areas are functionally connected. Here, we establish a statistical framework for studying effective and functional brain connectivity, using data obtained with a relatively new neuroimaging method, the event-related optical signal (EROS). The novelty of our approach is the use of timing information (in the form of lagged cross-correlations) in interpreting the connections between areas. Interpretation of lagged cross-correlations exploits the combination of spatial and temporal resolution provided by EROS. In this paper, we apply dynamic factor analysis as a method for testing various structural models on the lagged covariance matrices derived from the EROS data. We first illustrate the approach by testing a simple path model of neural activity propagation from area V1 to V3 in a visual stimulation task. We then build more complex structural equation models with latent variables, describing both within-hemisphere integrity, and interactions between the two hemispheres, to interpret data from a second task involving inter-hemispheric competition. The results demonstrate how the integrity of anatomical connections between the two hemispheres explains different patterns of cross-hemispheric interactions. This approach allows for fitting brain imaging data to complex models that capture dynamic cognitive processes as they rapidly evolve over time.

Adolescent↗
PubMed1996

Functional connections between the pineal gland and immune system.

Experimental findings which support a functional connection between the pineal gland and immune system in mammals and birds are summarized. Developmental and age-related changes in pineal gland function appear, at least partially, to be related with immune system efficiency. Mechanisms whereby melatonin influences immune system function are complex, but include participation of mediators (endogenous opioids, cytokines, hormones, zinc pool) as well as specific binding sites on the immune cells. Melatonin, as a highly lyophilic compound, may also penetrate immune cells without mediation of specific receptors and act within as a potent free radical scavenger and as an anti-aging and oncostatic factor. The immune system may, in turn, via synthesis and secretion of soluble factors, cytokines, influence pineal gland function, thereby closing the information loop to maintain homeostasis in order to face the harmful environment.

Animals↗
PubMed1991

Functional connections in the human temporal lobe. II. Evidence for a loss of functional linkage between contralateral limbic structures.

In a previous investigation of functional limbic pathways in the human mesial temporal lobe, we found evidence for strong connections between ipsilateral mesial temporal structures, but none for contralateral functional connections (Wilson et al. 1990). In the present study, we focused specifically upon the question of functional commissural linkages between these structures by systematic stimulation of a total of 390 electrode placements in 74 epileptic patients with temporal lobe depth electrodes implanted for surgical diagnosis. Eight standard electrode placement regions were targeted: amygdala, entorhinal cortex, anterior, middle and posterior hippocampus, subicular cortex, middle parahippocampal gyrus, and posterior parahippocampal gyrus. Three to six electrodes were implanted bilaterally in each patient, and each electrode was individually stimulated while recording from all the other sites. Out of the 390 electrodes stimulated, 78% were effective in evoking clear responses in adjacent ipsilateral structures, and 75% of 581 ipsilateral recording sites were responsive to stimulation. Only one of the stimulated electrode sites was effective in evoking responses in contralateral recording sites, and only two of 511 contralateral recording sites were responsive to that stimulation. The effective stimulation site was in presubicular cortex, and the responsive contralateral recording sites were in entorhinal and presubicular cortices. Response to this stimulation site was intermittent and variable in latency. The relative ease of obtaining functional verification of significant ipsilateral anatomical pathways in the human limbic system, and the sharply contrasting difficulty of functionally activating commissural pathways to contralateral limbic sites are discussed in the context of decreases in hippocampal contribution to commissural pathways in the primate brain compared to sub-primate mammals, and the significance of this change to normal limbic system function as well as to mechanisms of seizure spread in epilepsy.

Amygdala↗
PubMed2001

Altered brain functional connectivity and impaired short-term memory in Alzheimer's disease.

To examine functional interactions between prefrontal and medial temporal brain areas during face memory, blood flow was measured in patients with Alzheimer's disease and healthy controls using PET. We hypothesized that controls would show correlated activity between frontal and posterior brain areas, including the medial temporal cortex, whereas patients would not, although frontal activity per se might be spared or even increased compared with controls. We used a delayed match to sample paradigm with delays from 1 to 16 s. There was no change in recognition accuracy with increasing delay in controls, whereas patients showed impaired recognition over all delays that worsened as delay increased. Controls showed increased activity in the bilateral prefrontal and parietal cortex with increasing delay, whereas the patients had increased activity in the right prefrontal, anterior cingulate and left amygdala. Increased activity in the right prefrontal cortex was associated with better memory performance in both groups and activity in the left amygdala was correlated with better performance in the patients. Based on these task and behavioural effects, we examined functional connectivity of the right prefrontal cortex and left amygdala in both groups by determining those areas whose activity was correlated with activity in these regions. In controls, activity in the right prefrontal cortex was positively correlated with blood flow in the left prefrontal cortex, bilateral extrastriate and parietal areas and the right hippocampus. In patients, activity in the right prefrontal cortex was correlated mainly with other prefrontal regions. Areas where activity was correlated with the left amygdala in patients included the bilateral posterior parahippocampal gyri, a number of left prefrontal regions, anterior and posterior cingulate, thalamus, and insula. Controls had a relatively restricted set of regions where activity correlated with the left amygdala, mainly temporal and occipital areas. These results support the idea of a functional disconnection between the prefrontal cortex and the hippocampus in Alzheimer's disease and suggest that memory breakdown in early Alzheimer's disease is related to a reduction in the integrated activity within a distributed network that includes these two areas. The unexpected finding of increased involvement of the amygdala suggests that the patients may have processed the emotional content of the faces to a greater degree than did the controls. Furthermore, the positive association between amygdala activity and memory performance in the patients suggests a possible compensatory role for an emotion-related network of regions.

Aged↗
PubMed2006

Small-world network organization of functional connectivity of EEG slow-wave activity during sleep.

OBJECTIVE: To analyze the functional connectivity patterns of the EEG slow-wave activity during the different sleep stages and Cyclic Alternating Pattern (CAP) conditions, using concepts derived from Graph Theory. METHODS: We evaluated spatial patterns of EEG slow-wave synchronization between all possible pairs of electrodes (19) placed over the scalp of 10 sleeping healthy young normal subjects using two graph theoretical measures: the clustering coefficient (Cp) and the characteristic path length (Lp). The measures were obtained during the different sleep stages and CAP conditions from the real EEG connectivity networks and randomized control (surrogate) networks (Cp-s and Lp-s). RESULTS: Cp and Cp/Cp-s increased significantly from wakefulness to sleep while Lp and Lp/Lp-s did not show changes. Cp/Cp-s was higher for A1 phases, compared to B phases of CAP. CONCLUSIONS: The network organization of the EEG slow-wave synchronization during sleep shows features characteristic of small-world networks (high Cp combined with low Lp); this type of organization is slightly but significantly more evident during the CAP A1 subtypes. SIGNIFICANCE: Our results show feasibility of using graph theoretical measures to characterize the complexity of brain networks during sleep and might indicate sleep, and the A1 phases of CAP in particular, as a period during which slow-wave synchronization shows optimal network organization for information processing.

Adult↗
PubMed2004

Changes in functional connectivity of human MT/V5 with visual motion input.

The neural basis of human mental function is characterized by interactions between brain regions. Temporal correlations in MR signals between areas may provide one method for investigating these interactions. This approach was used to examine functional connectivity in the motion processing system of the human brain. Correlations between MT/V5 and other brain regions were examined in a resting state (without visual stimulation) and in an active state produced by viewing moving concentric circles. A network of regions consistent with the known functional anatomy of visual processing was correlated with MT/V5 during rest. When subjects were viewing motion, a more limited network was correlated with MT/V5, suggesting MT/V5 was acting in concert with a smaller network specific to the task.

Brain Mapping↗
PubMed2005

Functional connectivity: integrating behavioral, diffusion tensor imaging, and functional magnetic resonance imaging data sets.

In the present study, we combined 2 types of magnetic resonance technology to explore individual differences on a task that required the recognition of objects presented from unusual viewpoints. This task was chosen based on previous work that has established the necessity of information transfer from the right parietal cortex to the left inferior cortex for its successful completion. We used reaction times (RTs) to localize regions of cortical activity in the superior parietal and inferior frontal regions (blood oxygen level-dependent [BOLD] response) that were more active with longer response times. These regions were then sampled, and their signal change used to predict individual differences in structural integrity of white matter in the corpus callosum (using diffusion tensor imaging). Results show that shorter RTs (and associated increases in BOLD response) are associated with increased organization in the splenium of the corpus callosum, whereas longer RTs are associated with increased organization in the genu.

Adult↗
PubMed2006

A method to produce evolving functional connectivity maps during the course of an fMRI experiment using wavelet-based time-varying Granger causality.

Functional magnetic resonance imaging (fMRI) is widely used to identify neural correlates of cognitive tasks. However, the analysis of functional connectivity is crucial to understanding neural dynamics. Although many studies of cerebral circuitry have revealed adaptative behavior, which can change during the course of the experiment, most of contemporary connectivity studies are based on correlational analysis or structural equations analysis, assuming a time-invariant connectivity structure. In this paper, a novel method of continuous time-varying connectivity analysis is proposed, based on the wavelet expansion of functions and vector autoregressive model (wavelet dynamic vector autoregressive-DVAR). The model also allows identification of the direction of information flow between brain areas, extending the Granger causality concept to locally stationary processes. Simulation results show a good performance of this approach even using short time intervals. The application of this new approach is illustrated with fMRI data from a simple AB motor task experiment.

Adult↗
PubMed2004

BOLD response to direct thalamic stimulation reveals a functional connection between the medial thalamus and the anterior cingulate cortex in the rat.

Recent functional neuroimaging studies in humans and rodents have shown that the anterior cingulate cortex (ACC) is activated by painful stimuli, and plays an important role in the affective aspect of pain sensation. The aim of the present study was to develop a suitable stimulation method for direct activation of the brain in fMRI studies and to investigate the functional connectivity in the thalamo-cingulate pathway. In the first part of the study, tungsten, stainless steel, or glass-coated carbon fiber microelectrodes were implanted in the left medial thalamus (MT) of anesthetized rats, and T2*-weighted gradient-echo (GE) images were obtained in the sagittal plane on a 4.7 T system (Biospec BMT 47/40). Only the images obtained with the carbon fiber electrode were acceptable without a reduction of the signal-to-noise ratio (SNR) and image distortion. In the second part of the study, a series of two-slice GE images were acquired during electrical stimulation of the MT with the use of a carbon fiber electrode. A cross-correlation analysis showed that the signal intensities of activated areas in the ipsilateral ACC were significantly increased by about 4.5% during MT stimulation. Functional activation, as assessed by the distribution of c-Fos immunoreactivity, showed strong c-Fos expression in neurons in the ipsilateral ACC. The present study shows that glass-coated carbon fiber electrodes are suitable for fMRI studies and can be used to investigate functional thalamocortical activation.

Animals↗
PubMed1999

Effects of BDNF and NT-3 on development of Ia/motoneuron functional connectivity in neonatal rats.

Effects of BDNF and NT-3 on development of Ia/motoneuron functional connectivity in neonatal rats. The effects of neurotrophin administration and neurotrophin removal via administration of tyrosine kinase (trk) immunoadhesins (trk receptor extracellular domains fused with IgG heavy chain) on the development of segmental reflexes were studied in neonatal rats. Brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), trkB-IgG, and trkC-IgG were delivered via subcutaneous injection on days 0, 2, 4, and 6 of postnatal life. Electrophysiological analysis of EPSPs recorded intracellularly in L5 motoneurons in response to stimulation of dorsal root L5 was carried out on postnatal day 8 in the in vitro hemisected spinal cord. Treatment with BDNF resulted in smaller monosynaptic EPSPs with longer latency than those in controls. EPSP amplitude became significantly larger when BDNF was sequestered with trkB-IgG, suggesting that BDNF has a tonic action on the development of this synapse in neonates. Treatment with NT-3 resulted in larger EPSPs, but the decrease noted after administration of trkC-IgG was not significant. Neurotrophins had little effect on the response to high-frequency dorsal root stimulation or on motoneuron properties. Polysynaptic components were exaggerated in BDNF-treated rats and reduced after NT-3 compared with controls. As in control neonates the largest monosynaptic EPSPs in NT-3 and trkB-IgG-treated preparations were observed in motoneurons with relatively large values of rheobase, probably those that are growing the most rapidly. We conclude that supplementary NT-3 and BDNF administered to neonates can influence developing Ia/motoneuron synapses in the spinal cord but with opposite net effects.

Animals↗