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PubMed1983

The effects of stimuli on the activity and functional connectivity of local neuronal groups in the cat auditory cortex.

Simultaneous extracellular recordings from one electrode of 'local' groups of 3-6 neurons were obtained from the auditory cortex of unanesthetized, paralyzed cats. The activity and functional connectivity of local microenvironments were examined under various auditory stimuli. Single cell response patterns were examined using peri-stimulus (PST) histograms and functional connectivity among neighboring cells by the cross renewal density (CRD) histograms. Analysis of the PST histograms suggested that a high percentage of single cells demonstrated different response patterns to different stimuli. Analysis of the CRD histograms suggested, on the one hand, that only small numbers of neighboring cells behaved as if there were direct connections from one cell to another, and that these direct connections appeared to be excitatory. On the other hand, many cell pairs shared input from shared sources which lay outside the local groups. The majority of functional connections were altered by at least one of the stimuli delivered, thus demonstrating the system's plasticity. It is suggested that long-term gates at the synaptic level are responsible for this phenomenon.

Action Potentials↗

PubMed2004

Measuring interregional functional connectivity using coherence and partial coherence analyses of fMRI data.

Understanding functional connectivity within the brain is crucial to understanding neural function; even the simplest cognitive operations are supported by highly distributed neural circuits. We developed a novel method to measure task-related functional interactions between neural regions by applying coherence and partial coherence analyses to functional magnetic resonance imaging (fMRI) data. Coherence and partial coherence are spectral measures that estimate the linear time-invariant (LTI) relationship between time series. They can be used to generate maps of task-specific connectivity associated with seed regions of interest (ROIs). These maps may then be compared across tasks, revealing nodes with task-related changes of connectivity to the seed ROI. To validate the method, we applied it to an event-related fMRI data set acquired while subjects performed two sequence tapping tasks, one of which required more bimanual coordination. Areas showing increased functional connectivity with both tasks were the same as those showing increased activity. Furthermore, though there were no significant differences in mean activity between the two tasks, significant increases in interhemispheric coherence were found between the primary motor (M1) and premotor (PM) regions for the task requiring more bimanual coordination. This increase in interhemispheric connectivity is supported by other brain imaging techniques as well as patient studies.

Adolescent↗

PubMed2000

Cocaine administration decreases functional connectivity in human primary visual and motor cortex as detected by functional MRI.

Functional magnetic resonance imaging (fMRI) was conducted to observe the effects of cocaine administration on the physiological fluctuations of fMRI signal in two brain regions. Seven long-term cocaine users with an average age of 32 years and 8 years of cocaine use history were recruited for the study. A T2*-weighted fast echo-planar imaging (EPI) pulse sequence was employed at 1.5 T to acquire three sets of brain images for each subject under three conditions (at rest, after saline injection, and after cocaine injection [0.57 mg/kg]). Cross-correlation maps were constructed using the synchronous, low frequency signal from voxel time courses after filtering respiratory, cardiac, and other physiological noise. A quantitative evaluation of the changes in functional connectivity was made using spatial correlation coefficient (SCC) analysis. A marked 50% reduction in SCC values in the region of primary visual cortex and 43% reduction in SCC values in the region of primary motor cortex were observed after cocaine administration. This significant reduction in SCC values in these cortical regions is a reflection of changes in neuronal activity. It is suggested that the observed changes in low frequency components after acute cocaine administration during a resting, no-task situation may be used as a baseline reference source when assessing the effects of cocaine on task-driven activation or on mesolimbic dopamine pathways.

Adolescent↗

PubMed2002

Abnormal functional connectivity in posttraumatic stress disorder.

This study investigated the efficacy of a combined multivariate/resampling procedure for the analysis of PET activation studies. The covariance-based multivariate analysis was used to investigate distributed brain systems in posttraumatic stress disorder (PTSD) patients and matched controls during performance of a working memory task. The results were compared to univariate results obtained in an earlier study. We also examined whether the PTSD patients demonstrated a breakdown in functional connectivity that may be associated with working memory difficulties often experienced by these patients. A resampling procedure was used specifically to test the reliability of measured between-group effects, to avoid mistaken inference on the basis of random intersubject differences. Significant and reproducible differences in network connectivity were obtained for the two groups. The functional connectivity pattern of the patient group was characterized by relatively more activation in the bilateral inferior parietal lobes and the left precentral gyrus than the control group, and less activation in the inferior medial frontal lobe, bilateral middle frontal gyri and right inferior temporal gyrus. The resampling procedure provided direct evidence that working memory updating was abnormal in PTSD patients relative to matched controls. This work focuses on the need to identify extended brain networks (in addition to regionally specific changes) for the full characterization of brain responses in neuroimaging experiments. Our multivariate analysis explicitly measures the reliability of the patterns of functional connectivity we obtain and demonstrates the potential of such analyses for the study of brain network dysfunction in psychopathology.

Adult↗

PubMed1993

Functional connectivity from CA3 to the ipsilateral and contralateral CA1 in the rat dorsal hippocampus.

Anatomical advances have led to a reappraisal of the organization of hippocampal circuitry. However, it is not clear whether the functional connectivity is fully determined by the anatomical connectivity or whether it is significantly modified by feed-forward inhibition and modulatory inputs. Therefore, we have mapped CA1 responses evoked by stimulation of ipsilateral and contralateral CA3 in vivo. Population spike amplitude and threshold were plotted to produce response maps. All CA3 subregions projected diffusely to ipsilateral CA1. However, a pattern of maximal response emerged. Caudal CA3 stimulation evoked the maximal responses septally, while rostral CA3 responses were maximal temporally. The ipsilateral CA3 response maps were compared with those produced by stimulation at the homotopic point in the contralateral CA3. The CA1 areas of maximal functional connectivity were the same implying that there is convergence of the input to CA1 from homotopic CA3 sites in the two hippocampi. Although a response in CA1 was evoked widely, our results suggest that the functional connectivity is ordered, within and between the dorsal hippocampi, and that it is consistent with the recent anatomical data. The present findings allow more precise study of the propagation of normal and abnormal neuronal activity, within and between the dorsal hippocampi. Information on the site and speed of propagation of neuronal activity would be necessary for the development of a physiologically realistic model of hippocampal computation.

Animals↗

PubMed2000

Mapping functionally related regions of brain with functional connectivity MR imaging.

BACKGROUND AND PURPOSE: In subjects who are performing no prescribed cognitive task, functional connectivity mapped with MR imaging (fcMRI) shows regions with synchronous fluctuations of cerebral blood flow. When specific tasks are performed, functional MR imaging (fMRI) can map locations in which regional cerebral blood flow increases synchronously with the performance of the task. We tested the hypothesis that fcMRI maps, based on the synchrony of low-frequency blood flow fluctuations, identify brain regions that show activation on fMRI maps of sensorimotor, visual, language, and auditory tasks. METHODS: In four volunteers, task-activation fMRI and functional connectivity (resting-state) fcMRI data were acquired. A small region of interest (in an area that showed maximal task activation) was chosen, and the correlation coefficient of the corresponding resting-state signal with the signal of all other voxels in the resting data set was calculated. The correlation coefficient was decomposed into frequency components and its distribution determined for each fcMRI map. The fcMRI maps were compared with the fMRI maps. RESULTS: For each task, fcMRI maps based on one to four seed voxel(s) produced clusters of voxels in regions of eloquent cortex. For each fMRI map a closely corresponding fcMRI map was obtained. The frequencies that predominated in the cross-correlation coefficients for the functionally related regions were below 0.1 Hz. CONCLUSION: Functionally related brain regions can be identified by means of their synchronous slow fluctuations in signal intensity. Such blood flow synchrony can be detected in sensorimotor areas, expressive and receptive language regions, and the visual cortex by fcMRI. Regions identified by the slow synchronous fluctuations are similar to those activated by motor, language, or visual tasks.

Adult↗

PubMedDate not supplied

[The manifestation of the functional connections between neurons depending on changes in the frequency of their pulsations during the performance by animals of conditioned-reflex food-acquisition reactions].

Multiunit activity in the motor cortex of cats was analysed in the process of food-procuring conditioning to time (interval of 2 min). Functional connections between pairs of neurons each of which changed its current firing frequency during performance of the food-procuring movement were analysed by crosscorrelation method. The same method was implemented for the analysis of functional connections between pairs of neurons which demonstrated no changes in their activity during conditioned movement. Total number of significant correlations in the phase of passive waiting was less between non-reactive neurons than between reactive ones. In the phase of active waiting this difference was eliminated. Relative increase in the number of correlations in the active waiting phase as compared with the passive one was higher in the pairs of non-reactive neurons. This finding is considered as intensification of information analysis and processing in the active phase. Lability of the functional connections was higher in the pairs of reactive neurons which might provide their capability for correction of the functional structure in the case of quick change in a situation or internal state of the animal.

Animals↗

PubMed1998

Elucidating dynamic brain interactions with across-subjects correlational analyses of positron emission tomographic data: the functional connectivity of the amygdala and orbitofrontal cortex during olfactory tasks.

Covariance analyses of positron emission tomography (PET) data are used increasingly to elucidate the functional connectivity between brain regions during different cognitive tasks. Functional connectivity may be estimated by examining the covariance between regions over time or across subjects. In functional brain-mapping studies, across-subjects covariance matrices derived from within-task (nonsubtracted) and between-task (subtracted) data characterize different, complementary aspects of functional interactions. The authors study amygdala-orbitofrontal interactions during three task conditions (aversive olfaction, odor detection, and resting with eyes closed) to illustrate the strengths and limitations of across-subjects covariance analyses based on subtracted and nonsubtracted data. This example underscores the dynamic nature of connectivity between the amygdalae and orbitofrontal cortices and highlights the importance of including data from resting conditions in covariance analyses.

Adult↗

PubMed2003

Functional connectivity analysis of the neural circuits of opiate craving: "more" rather than "different"?

We investigated the functional connectivity of brain regions activated during opiate craving. Previously we used recorded autobiographical scripts to induce opiate craving in 12 abstinent opiate-dependent subjects while they were undergoing positron emission tomography (PET) scanning using the regional cerebral blood flow (rCBF) tracer H2 15O. SPM99 was used to examine the connectivity patterns associated with the primary brain regions activated in response to drug-craving memories (anterior cingulate, AC) and correlated with opiate craving (orbitofrontal cortex, OFC). Two separate connectivity patterns were identified associated with the OFC and AC regions. The AC region was associated with activity in the left temporal region. The left OFC region activity correlated with activity in the right OFC, and left parietal and posterior insular regions. There was also a positive association with the hippocampus and brainstem. Both the AC and OFC regions showed a negative association with posterior visual areas. We suggest that the patterns of functional connectivity reflect the ability of drug-related stimuli to activate attentional and memory circuits to a greater degree than non-drug-related stimuli. This argues that neural circuits of dependence and craving are not specific "craving" or "addiction" brain regions but are "normal" circuits activated to a greater degree.

Brain Stem↗

PubMed2026

Comparison of the clinical efficacy, safety and EEG functional connectivity changes between 18-Hz rTMS and iTBS of accelerated dTMS treatment for major depressive disorder: a randomized controlled trial.

Although the antidepressant efficacy of 18-Hz deep transcranial magnetic stimulation (dTMS) has been validated, its prolonged treatment duration has considerable limitations for treatment capacity and patient adherence. Therefore, novel short-course protocols such as accelerated dTMS and intermittent theta burst stimulation (iTBS) present promising alternative options. Here we addressed the question of whether iTBS of accelerated dTMS achieves comparable therapeutic and electrophysiological effects to accelerated dTMS with the conventional 18-Hz rTMS protocol in patients with major depressive disorder (MDD). In a randomized controlled trial (n = 73), participants received either 18-Hz rTMS of accelerated dTMS (rTMS-dTMS group), iTBS of accelerated dTMS (iTBS-dTMS group), or pharmacotherapy alone (drug group). Both dTMS protocols were administered twice daily for 10 days targeting the left lateral prefrontal cortex including the dorsolateral region. Results showed that Hamilton Depression Rating Scale (HAMD) score of the iTBS-dTMS group decreased significantly from 22.5 ± 3.7 before treatment to 8.2 ± 4.1 after treatment (t = 15.900, p < 0.001). HAMD score of the rTMS-dTMS group decreased significantly from 21.3 ± 2.9 before treatment to 8.0 ± 3.8 after treatment (t = 17.232, p < 0.001). The drug group also exhibited significantly improved patients' mood symptoms, and the HAMD score decreased from 24.7 ± 6.8 to 14.0 ± 5.0 (t = 6.363, p < 0.001). The treatment response rate was 85.7% in the iTBS-dTMS group and 76.9% in the rTMS-dTMS group, which was much higher than that of the drug group (42.1%). The remission rate was 50.0% in the iTBS-dTMS group and 42.3% in the rTMS-dTMS group, which was significantly higher than 10.5% of the drug group. We demonstrate here that both accelerated dTMS protocols significantly reduced HAMD scores, improved the response rates, and remission rates, outperforming pharmacotherapy alone. Resting-state EEG analysis further revealed unique frequency-specific functional connectivity (FC) modulation effects: the rTMS-dTMS group primarily exhibited weakened alpha-band functional connectivity within the fronto-occipital, fronto-temporal and fronto-central networks after treatment, whereas the iTBS-dTMS group predominantly demonstrated reduced theta-band functional connectivity within the fronto-parietal, fronto-occipital and fronto-temporal pathways after treatment. These findings indicate that iTBS of accelerated dTMS demonstrates comparable efficacy and tolerability to 18-Hz rTMS of accelerated dTMS, whilst inducing treatment-specific network-level neurophysiological alterations. In the rTMS-dTMS group, relative changes in FC between the frontal and temporal/precentral regions showed significant negative correlation with HAMD score reduction rates, while relative changes in FC between the frontal lobe and parietal lobe showed a significant positive correlation with the rate of HAMD score reduction for the iTBS-dTMS group. This study revealed novel mechanisms by which accelerated dTMS protocols modulate brain networks, providing evidence for the clinical application of accelerated iTBS-dTMS as an efficient, evidence-based treatment for MDD.

Humans↗

PubMed2003

Functional connectivity: studying nonlinear, delayed interactions between BOLD signals.

Correlation analysis has been widely used in the study of functional connectivity based on fMRI data. It assumes that the relevant information about the interactions of brain regions is reflected by a linear relationship between the values of two signals at the same time. However, this hypothesis has not been thoroughly investigated yet. In this work, we study in depth the information shared by BOLD signals of pairs of brain regions. In particular, we assess the amount of nonlinear and/or nonsynchronous interactions present in data. This is achieved by testing models reflecting linear, synchronous interactions against more general models, encompassing nonlinear, nonsynchronous interactions. Many factors influencing measured BOLD signals are critical for the study of connectivity, such as paradigm-induced BOLD responses, preprocessing, motion artifacts, and geometrical distortions. Interactions are also influenced by the proximity of brain regions. The influence of all these factors is taken into account and the nature of the interactions is studied using various experimental conditions such that the conclusions reached are robust with respect to variation of these factors. After defining nonlinear and/or nonsynchronous interaction models in the framework of general linear models, statistical tests are performed on different fMRI data sets to infer the nature of the interactions. Finally, a new connectivity metric is proposed which takes these inferences into account. We find that BOLD signal interactions are statistically more significant when taking into account the history of the distant signal, i.e., the signal from the interacting region, than when using a model of linear instantaneous interaction. Moreover, about 75% of the interactions are symmetric, as assessed with the proposed connectivity metric. The history-dependent part of the coupling between brain regions can explain a high percentage of the variance in the data sets studied. As these results are robust with respect to various confounding factors, this work suggests that models used to study the functional connectivity between brain areas should in general take the BOLD signal history into account.

Algorithms↗

PubMed2025

Interrogating functional connectivity of in vitro neural glia tissue model modulated through integrative control of matrix stiffness and a neurotrophic factor.

Brain function emerges from intricate cellular communication within neural networks. Both In silico neuronal models and primary neuron cells have revealed that the branching architecture of individual neurons determines the bioelectrical signal propagation pattern and dynamics. However, whether stem cell-differentiated neurons can build functional connectivity regulated by neuronal morphology has yet to be determined. Here, we hypothesized that neurite length, branching, or both factors would regulate the functional connectivity of the stem cell-differentiated neural network. We examined this hypothesis by differentiating mouse cortical neural stem cells (NSCs) on Matrigel substrates with varying storage moduli, both with and without basic fibroblast growth factor (bFGF). Interestingly, with bFGF, Matrigel with a storage modulus (G') of 100 Pa drives NSCs to differentiate into neurons with more dendritic branches, while the gel with G' of 50 Pa led to the development of longer neurites with fewer branches. Notably, branch-rich neural networks exhibited an increased frequency of calcium transients. Using a MATLAB-based analysis pipeline incorporating graph theory, we constructed spatial and temporal calcium activity maps, revealing that branching complexity, more than neurite length, correlates with the density and strength of functional neural circuits. Overall, this study demonstrates that the dendritic branching of neurons, modulated with matrix stiffness and neurotrophic factors, is a key element in enhancing the electrophysiological functionality of the stem cell-differentiated neural network. This finding will have a significant impact on efforts to reconstruct functional neural tissue models, advancing both regenerative therapies and unexplored applications, including biological computing.

Animals↗

PubMed2007

Altered functional connectivity in early Alzheimer's disease: a resting-state fMRI study.

Previous studies have led to the proposal that patients with Alzheimer's disease (AD) may have disturbed functional connectivity between different brain regions. Furthermore, recent resting-state functional magnetic resonance imaging (fMRI) studies have also shown that low-frequency (<0.08 Hz) fluctuations (LFF) of the blood oxygenation level-dependent signals were abnormal in several brain areas of AD patients. However, few studies have investigated disturbed LFF connectivity in AD patients. By using resting-state fMRI, this study sought to investigate the abnormal functional connectivities throughout the entire brain of early AD patients, and analyze the global distribution of these abnormalities. For this purpose, the authors divided the whole brain into 116 regions and identified abnormal connectivities by comparing the correlation coefficients of each pair. Compared with healthy controls, AD patients had decreased positive correlations between the prefrontal and parietal lobes, but increased positive correlations within the prefrontal lobe, parietal lobe, and occipital lobe. The AD patients also had decreased negative correlations (closer to zero) between two intrinsically anti-correlated networks that had previously been found in the resting brain. By using resting-state fMRI, our results supported previous studies that have reported an anterior-posterior disconnection phenomenon and increased within-lobe functional connectivity in AD patients. In addition, the results also suggest that AD may disturb the correlation/anti-correlation effect in the two intrinsically anti-correlated networks.

Aged↗

PubMed2003

Detecting low-frequency functional connectivity in fMRI using a self-organizing map (SOM) algorithm.

Low-frequency oscillations (<0.08 Hz) have been detected in functional MRI studies, and appear to be synchronized between functionally related areas. A current challenge is to detect these patterns without using an external reference. Self-organizing maps (SOMs) offer a way to automatically group data without requiring a user-biased reference function or region of interest. Resting state functional MRI data was classified using a self-organizing map (SOM). Functional connectivity between the left and right motor cortices was detected in five subjects, and was comparable to results from a reference-based approach. SOMs are shown to be an attractive option in detecting functional connectivity using a model-free approach. Hum. Brain Mapping 20:220-226, 2003.

Algorithms↗

PubMedDate not supplied

[Changes in functional connections between adjacent and distant neurons of the motor cortex in the cat during elaboration of an electrodefensive reflexes].

Dynamic reorganization of functional connections between neurones was observed in the motor cortex of cats in the process of electrodefensive conditioning. At a stable conditioned reflex, an increase of number of functional connections was observed more expressed between the neurones of distant microareas (within the range of 450 mcm investigated). In the process of conditioning sometimes one and the same neurone did not change its network properties within its own microarea but became noticeably activated in relation to the neurones of other microareas. The results obtained confirm the suggestion about a multilevel structure of neuronal integration in the process of learning, the first level consisting of consolidation of neighbouring neurones in the microarea, the second one consisting in consolidation of neurones of neighbouring microareas.

Action Potentials↗

PubMed1984

Prenatal development of functional connections in the cat's retinogeniculate pathway.

The development of functional connections between the axons of retinal ganglion cells and the neurons of the dorsal lateral geniculate nucleus (LGNd) of fetal and neonatal cats was studied using an in vitro assay. Extracellular microelectrode recordings of single units were made from histologically identified sites in the LGNd of isolated diencephalon preparations between embryonic day 39 ( E39 ) and postnatal day 2 (P2). (Gestation is 65 days in the cat.) Postsynaptic units activated by electrical stimulation of one or both optic nerves were found at all ages tested from E39 onwards. Over 90% of the units studied in the fetal preparations received convergent excitation from both optic nerves, compared with roughly half of the units studied in the neonatal optic nerves, compared with roughly half of the units studied in the neonatal preparations. Inhibition was detected in the LGNd of the neonatal preparations, but in only the oldest of the fetal preparations ( E59 ). This physiological change from predominantly convergent excitation to an adult-like mixture of excitation and inhibition seen at birth coincides with the change from mixed to segregated afferent input from the two eyes seen anatomically ( Shatz , C. J. (1983) J. Neurosci . 3: 482-499). These results indicate that attainment of the adult pattern of retinogeniculate connectivity involves the elimination of already functional synapses.

Animals↗

PubMed2006

Small-world networks and functional connectivity in Alzheimer's disease.

We investigated whether functional brain networks are abnormally organized in Alzheimer's disease (AD). To this end, graph theoretical analysis was applied to matrices of functional connectivity of beta band-filtered electroencephalography (EEG) channels, in 15 Alzheimer patients and 13 control subjects. Correlations between all pairwise combinations of EEG channels were determined with the synchronization likelihood. The resulting synchronization matrices were converted to graphs by applying a threshold, and cluster coefficients and path lengths were computed as a function of threshold or as a function of degree K. For a wide range of thresholds, the characteristic path length L was significantly longer in the Alzheimer patients, whereas the cluster coefficient C showed no significant changes. This pattern was still present when L and C were computed as a function of K. A longer path length with a relatively preserved cluster coefficient suggests a loss of complexity and a less optimal organization. The present study provides further support for the presence of "small-world" features in functional brain networks and demonstrates that AD is characterized by a loss of small-world network characteristics. Graph theoretical analysis may be a useful approach to study the complexity of patterns of interrelations between EEG channels.

Aged↗

PubMed2002

Is the functional connectivity within temporal lobe influenced by saccadic eye movements?

Local evoked potentials (LEPs), recorded in response to electrical stimulation, were used to study functional connectivity between different sites of the temporal lobe. Permanent electrodes were implanted in anterior and posterior positions of both inferotemporal cortex (IT) and hippocampal formation (HF). In each experimental session, one of these four sites was stimulated and LEPs were recorded in the others. Clear LEPs were found in the anterior and posterior IT sites in response to stimulation of the anterior as well as posterior HF. Bidirectional connections (as judged by the potentials) were found between the anterior and posterior sites of the same structure (IT or HF). The timing of the LEPs indicates that much of the response was carried in multisynaptic circuits. Stimulation delivered just after the monkey made a saccade produced larger late components in the LEPs than the same stimulation delivered without a saccade. The influence was maximal when the delay between the end of the saccade and the electrical stimulation was in the range of 50-100 ms. This saccadic modulation of the functional connectivity was observed within IT (bidirectional) and between posterior HF and IT (unidirectional).

Animals↗